U.S. patent application number 13/506658 was filed with the patent office on 2012-12-20 for renovascular treatment device, system, and method for radiosurgically alleviating hypertension.
This patent application is currently assigned to CyberHeart, Inc.. Invention is credited to Edward Gardner, Patrick Maguire.
Application Number | 20120323233 13/506658 |
Document ID | / |
Family ID | 47139855 |
Filed Date | 2012-12-20 |
United States Patent
Application |
20120323233 |
Kind Code |
A1 |
Maguire; Patrick ; et
al. |
December 20, 2012 |
Renovascular treatment device, system, and method for
radiosurgically alleviating hypertension
Abstract
A radiosurgical method for treating cardiorenal disease of a
patient, the method including directing radiosurgery radiation from
outside the patient towards one or more target treatment regions
encompassing sympathetic ganglia of the patient so as to inhibit
the cardiorenal disease. In an exemplary embodiment, the method
further includes acquiring three dimensional planning image data
encompassing the first and second renal arteries, planning an
ionizing radiation treatment of first and second target regions
using the three dimensional planning image data so as to mitigate
the hypertension, the first and second target regions encompassing
neural tissue of or proximate to the first and second renal
arteries, respectively, and remodeling the target regions by
directing the planned radiation from outside the body toward the
target regions.
Inventors: |
Maguire; Patrick; (Foster
City, CA) ; Gardner; Edward; (San Jose, CA) |
Assignee: |
CyberHeart, Inc.
Sunnyvale
CA
|
Family ID: |
47139855 |
Appl. No.: |
13/506658 |
Filed: |
May 9, 2012 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
61483962 |
May 9, 2011 |
|
|
|
Current U.S.
Class: |
606/33 |
Current CPC
Class: |
A61N 5/1042 20130101;
A61B 2018/00404 20130101; A61N 5/1083 20130101; A61B 2018/00434
20130101; A61N 5/1039 20130101; A61N 5/1084 20130101; A61N
2005/1061 20130101; A61B 2018/00511 20130101; A61N 5/1065
20130101 |
Class at
Publication: |
606/33 |
International
Class: |
A61B 18/18 20060101
A61B018/18 |
Claims
1. A radiosurgical method for treating cardiorenal disease of a
patient, the method comprising: directing radiosurgery radiation
from outside the patient towards one or more target treatment
regions encompassing a periarterial space of the renal artery of
the patient so as to inhibit the cardiorenal disease.
2. The method of claim 1, wherein target treatment region
encompasses a sympathetic ganglia of the patient, and wherein the
action of directing the radiation is part of a renal denervation
procedure, the resulting renal denervation inhibiting
hypertension.
3. The method of claim 1, wherein the action of directing the
radiation towards the target treatment regions substantially
reduces the ability of a central nervous system of the patient to
communicate with at least one kidney of the patient.
4. The method of claim 1, wherein the action of directing the
radiation towards the target treatment regions at least one of
blocks or down-regulates sympathetic impulses between at least one
kidney of the patent and a central nervous system of the
patient.
5. The method of claim 1, wherein the target treatment region
envelops renal nerves of the patient, wherein the renal nerves are
located about a renal artery of the patient, and wherein an inner
diameter of the artery proximate the target treatment region is at
least substantially the same six months after the action of
directing the radiation as prior to directing the radiation.
6. The method of claim 1, wherein the action of directing the
radiation results in the destruction of substantially much, but not
all, of a segment of renal nerves surrounding a renal artery of the
patient.
7. The method of claim 1, wherein the action of directing the
radiation results in the destruction of renal nerves in a toroidal
arc-segment.
8. The method of claim 20, wherein the action of directing the
radiation results in the destruction of renal nerves in an area
having a cross-section, when taken normal to the longitudinal axis
of a renal artery about which the destroyed renal nerves are
arrayed, in the general shape of a "C".
9. The method of claim 1, further comprising, prior to the action
of directing the radiation: evaluating the state of a renovasucular
system of the patient; and determining that the renovasucular
system is not afflicted with a tumor.
10. The method of claim 1, further comprising: prior to the action
of directing the radiation, initially evaluating at least one of a
systolic or a diastolic blood pressure of the patient and
determining, as a result of the evaluation, that the respective
pressure correspond to a pressure indicative of hypertension;
wherein the radiation is directed in response to the initial
evaluation; after the action of directing the radiation,
reevaluating at least one of a systolic or a diastolic blood
pressure of the patient and determining, as a result of the
reevaluation, whether the respective reevaluated pressures
correspond to a pressure indicative of hypertension, wherein the
reevaluated at least one of the systolic or diastolic blood
pressure is lower than the respective initially evaluated systolic
or diastolic blood pressure.
11. A radiosurgical method for treating a patient body having a
renovascular system including a first and second renal arteries,
the patient having hypertension, the method comprising: acquiring
three dimensional planning image data encompassing the first and
second renal arteries; planning an ionizing radiation treatment of
first and second target regions using the three dimensional
planning image data so as to mitigate the hypertension, the first
and second target regions encompassing neural tissue of or
proximate to the first and second renal arteries, respectively; and
remodeling the target regions by directing the planned radiation
from outside the body toward the target regions.
12. The method of claim 11, further comprising: prior to the
planning of the treatment, implanting a position surrogate within
the body, wherein the action of remodeling the target regions of
the renovascular system includes directing the planned radiation
from outside the body toward the target regions with reference to
the implanted surrogate.
13. The method of claim 12, wherein the position surrogate remains
implanted in the body for at least a year or until dissolution.
14. The method of claim 11, wherein the treatment comprises a
bilateral treatment, the target regions comprising two spatially
separated non-contiguous regions, and wherein the remodeling of the
target regions inhibits the hypertension.
15. The method of claim 14, wherein the radiation is directed to
the two regions in a single treatment procedure on a single
day.
16. The method of claim 14, wherein the radiation is sequentially
directed to the two regions in separate treatment procedures on
separate days.
17. The method of claim 11, wherein the planning of the treatment
further comprises determining an estimated lesion of the
renovascular system based on the planned radiation, and reviewing a
graphical representation of the estimated lesion.
18. The method of claim 11, wherein the radiation is directed from
a radiation source, and wherein the action of remodeling the target
regions of the renovascular system includes moving the radiation
source about the body.
19. The method of claim 1, wherein the radiation is directed from a
plurality of fixed radiation sources arrayed about the body.
20. The method of claim 14, wherein the radiation is sequentially
directed to the two regions in separate treatment procedures on
separate days.
21. The method of claim 11, wherein the planning of the treatment
further comprises determining an estimated lesion of the
renovascular system based on the planned radiation, and reviewing a
graphical representation of the estimated lesion.
22. The method of claim 11, wherein the radiation is directed from
a radiation source, and wherein the action of remodeling the target
regions of the renovascular system includes moving the radiation
source about the body.
23. The method of claim 11, wherein the radiation is directed from
a plurality of fixed radiation sources arrayed about the body.
24. The method of claim 11, wherein the target regions includes a
distinct region that is generally cylindrical in shape.
25. The method of claim 11, wherein the target regions
substantially surrounds a majority of respective perimeters of the
first and second renal arteries of the patient, the target regions
having two sections separated by a space into which a therapeutic
level of radiation is not directed.
26. The method of claim 12, wherein the action of implanting a
position surrogate within the body includes locating a fiducial in
one or more of the renal artery, renal vein, aorta, inferior vena
cava, side branch of the aorta or side branch of the vena cava.
27. The method of claim 12, wherein the action of implanting a
position surrogate within the body includes implanting passive
fiducial seeds within the body.
28. The method of claim 12, wherein the fiducial seeds comprise
substantially non-toxic seeds, with respect to the dosages used in
the method, with an electron density visible on CT and/or guidance
imaging.
29. The method of claim 12, wherein the action of implanting a
position surrogate within the body includes inserting a needle tip
percutaneously to a position where the surrogate is to be
implanted, and implanting one or more surrogates by ejecting the
one or more surrogates out of the needle tip.
30. The method of claim 11, wherein the action of remodeling the
target regions by directing the planned radiation from outside the
body toward the target regions results in renal denervation,
wherein the renal denervation results in the reduction of a cardiac
infarct size expansion.
31. The method of claim 12, further comprising monitoring movement
of at least one of the first and second renal arteries due to a
heart beat cycle of the patient, wherein the remodeling of the
target region is performed by: monitoring the heart beat cycle of
the body, and tracking at least a portion of the movement of tissue
of the at least one first and second renal arteries due to the
heart beat cycle while directing the radiation to the target region
while compensating for the movement.
32. The method of claim 12, further comprising monitoring a heart
beat cycle from the body while acquiring the planning image data,
and acquiring a time series of three dimensional image data sets
distributed throughout the heart beat cycle so as to indicate
renovascular tissue movement with the heart beat cycle; wherein the
planning of the treatment comprises: identifying radiation
sensitive collateral tissue, and determining a series of radiation
beams suitable for providing a desired radiation dose in the target
region without excessively irradiating the collateral tissue; and
wherein the remodeling of the target region is performed by:
monitoring the heart beat cycle of the body, and tracking at least
a portion of the movement of the tissue in response to the
monitored heart beat cycle while directing the radiation to the
target region using a time series of datasets.
33. The method of claim 11, wherein the action of directing the
planned radiation from outside the body toward the targets regions
results in respective absorbed radiation dose distributions of the
target regions of at least one unit dose of absorbed radiation and
absorbed radiation dose distributions of respective first outer
regions outside of and proximate to the target regions of at least
2/3rds of the unit dose of absorbed radiation, the first outer
region having a volume of about 1.5 to 4.0 times the volume of a
corresponding target region.
34. The method of claim 11, wherein the first target region
surrounds a majority of a perimeter of the first renal artery of
the patient, wherein the first renal artery has a first lumen
adjacent the perimeter, the first lumen defined by a first wall of
the first renal artery, and wherein a collateral dose of the
radiation in the first wall adjacent the first lumen is
sufficiently less than a dose of the radiation in the target region
so as to inhibit tissue response-induced occlusion of the first
renal artery.
35. The method of claim 11, further comprising: implanting a
position surrogate from within an inferior vena cava of the body
prior to acquiring of the planning image data; monitoring a
breathing cycle from the body while acquiring the planning image
data; monitoring the breathing cycle from the body while directing
the planned radiation to the target regions; and controlling the
directing of the planned radiation in response to the monitored
breathing cycle; wherein no position surrogate is implanted within
at least the first renal artery; and wherein the directing of the
planned radiation is performed without tracking movement of at
least the first renal artery in response to a heartbeat cycle of
the body.
36. The method of claim 12, wherein the fiducial seeds comprise
gold seeds.
37. The method of claim 12, further comprising monitoring movement
of at least one of the first and second renal arteries due to a
blood pressure component and/or a displacement component of the
heart beat cycle of the patient, wherein the remodeling of the
target region is performed by: monitoring the heart beat cycle of
the body, and tracking at least a portion of the movement of tissue
of the at least one first and second renal arteries.
38. A radiosurgical system for treating a patient body with a renal
artery and hypertension and/or congestive heart failure, the system
comprising: an image capture device for acquiring three dimensional
planning image data from the renal artery and/or a location
proximate the renal artery; a radiation source for transmitting a
plurality of beams of ionizing radiation from outside the body; and
a processor system configured to direct the ionizing radiation
beams toward a target region of the renal artery and/or a target
region at the location proximate the renal artery such that the
radiation beams remodel the target region and the hypertension
and/or congestive heart failure is mitigated.
39. The system of claim 38, wherein the processor system is
configured to control the direction of the radiation to account for
heartbeat-induced movement of the renal artery and/or the location
proximate the renal artery.
40. The system of claim 38, wherein the processor system is
configured to control the direction of the radiation to account for
breathing-induced movement of the renal artery and/or the location
proximate the renal artery.
41. The system of claim 38, wherein the processor system is
configured to direct the ionizing radiation beams to impinge upon
renal nerves proximate the renal artery to deliver one or more
doses of radiation to the renal nerves, the collective delivered
doses being sufficient to destroy at least a portion of the renal
nerves upon which the radiation beams impinge.
42. The system of claim 38, wherein the processor system is
configured to direct the ionizing radiation beams such that the
beams do not impart a collective radiation dose to a wall of the
renal artery that destroys a substantial amount of tissue of the
wall.
43. They system of claim 38, wherein the processor system is
configured to direct the ionizing radiation beams to provide a
therapeutic dose of radiation to a periarterial space of a renal
artery of the patient.
44. The system of one of claim 38, wherein the processor is
configured to control the direction of the radiation to account for
breathing-induced movement of the renal artery and/or the location
proximate the renal artery, wherein the processor is configured to
control the direction of the radiation without tracking
heartbeat-induced movement of the renal artery and/or the location
proximate the renal artery.
45. The system of any one of claims 38-44, further comprising a
position surrogate configured for implantation within an inferior
vena cava of the body.
46. The system of claim 45, wherein the processor is configured to
control the direction of the radiation in response to the position
surrogate within the inferior vena cava and without a position
surrogate disposed within the renal artery.
47. The system of any one of claim 44, wherein the processor is
configured to provide a margin of less than 2 mm to account for
heartbeat-induced movement of the renal artery and/or the location
proximate the renal artery.
48. The system of claim 47, wherein the processor is configured to
provide a margin of less than 0.5 mm to account for
heartbeat-induced movement of the renal artery and/or the location
proximate the renal artery.
Description
CROSS REFERENCE TO RELATED APPLICATION DATA
[0001] The present application claims the benefit under 35 USC
119(e) of U.S. Provisional Application No. 61/483,962 filed May 9,
2011. The full disclosure of which is incorporated herein by
reference in its entirety for all purposes.
BACKGROUND OF THE INVENTION
[0002] The present invention generally provides improved devices,
systems, and methods for treatment of a patient. Exemplary
embodiments provide radiosurgical treatment of tissues, including
nerves, in a patient body, often to treat a renovascular disease
and/or to treat heart failure. Exemplary embodiments may deposit a
sufficient ionizing radiation dose at a target region of the
renovascular system in general, and renal nerves located proximate
to the renal arteries in particular, so as to treat hypertension of
the patient body. Along with allowing treatment of tissues which
may move at a relatively rapid pace, embodiments of the invention
may accommodate significant deformation or relative repositioning
of regions of the renovascular system without subjecting the
patient to unnecessary long-term trauma or inconvenience, and
without unnecessarily constraining the time available for
radiosurgical treatment planning.
[0003] Kidneys may play a role in the development and maintenance
of hypertension. In particular, there is a link between nerves
surrounding the renal arteries and hypertension. Particularly,
hyperactivity of these nerves is associated with hypertension and,
therefore, progression to chronic kidney disease and heart failure.
Nephrectomy in patients with end-stage renal disease indicate that
renal denervation may be a therapy to treat renovascular
hypertension. This may lead to a reduction in the blood pressure of
the patient and total systemic resistance. More particularly,
denervation may be an effective way to reduce sympathetic outflow
to the kidneys, increase urine output (naturiesis and diuresis) and
thereby reducing rennin disease without adversely affecting other
functions of the kidneys (e.g., glomerular filtration rate and/or
renal blood flow. The kidneys and/or the renal nerves may also play
a role in other disease states, including congestive heart failure
secondary to hypertension and the like, so that renal denervation
may be included in other therapies as well.
[0004] Ablating the origin of the renal nerves in the sympathetic
ganglia has historically been considered very difficult.
Pharmacologic assault on nerve functions is associated with
systemic complications. The sympathetic renal nerves arborize
throughout the walls of the renal arteries, and frustrate access
thereto.
[0005] Tumors and other targets in the head, spine, abdomen, and
lungs have been successfully treated using radiosurgery. During
radiosurgery, a series of beams of ionizing radiation are often
directed from outside a patient so as to converge at a target
region, with the radiation beams often comprising MeV X-ray beams
fired from different positions and orientations. The beams can be
directed through intermediate tissue toward the target tissue so as
to alter the biology of a tumor. The beam trajectories help limit
the radiation exposure to the intermediate and other collateral
tissues, while the cumulative radiation dose at the target can
treat the tumor. The CyberKnife.TM. radiosurgical system (Accuray
Inc.) and the Trilogy.TM. radiosurgical system (Varian Medical
Systems) are two known radiosurgical treatment systems.
[0006] Modern radiosurgical systems incorporate imaging into the
treatment system so as to verify the position of the target tissue
and adjust to minor patient movements. Some systems also have an
ability to treat tissues that move during respiration, and this has
significantly broadened the number of patients that can benefit
from radiosurgery. Unfortunately, some radiosurgical therapies, and
particularly those which seek to target and track moving tissues
using x-ray imaging, fluoroscopy, or other remote imaging
modalities, may subject collateral tissues to significant
imaging-related radiation and associated injury.
[0007] In light of the above, the present inventors have determined
that it is desirable to provide improved devices, systems, and
methods for treating hypertension utilizing radiotherapy.
[0008] It would be particularly beneficial if these improvements
were compatible with (and could be implemented by modification of)
existing radiosurgical systems, ideally without significantly
increasing the exposure of patients to incidental imaging
radiation, without increasing the system costs so much as to make
these treatments unavailable to many patients, without
unnecessarily degrading the accuracy of the treatments, and/or
without causing unnecessary collateral damage to the healthy
tissues of the patient.
BRIEF SUMMARY OF THE INVENTION
[0009] The present invention generally provides improved devices,
systems, and methods for treating cardiorenal disease. An exemplary
method of treating a cardiorenal disease according to the present
invention includes directing radiosurgery radiation from outside a
patient towards one or more target treatment regions encompassing
sympathetic ganglia of the patient so as to inhibit the cardiorenal
disease. More specifically, an exemplary method includes a method
for treating hypertension through renal denervation, including
directing ionizing radiation onto renal nerves to destroy at least
some of the renal nerves.
[0010] Embodiments detailed herein include deices, systems and
method for renal denervation of one or both renal arteries
(unilateral treatment and bilateral treatment, respectively, at one
session and/or sequentially). It shall be understood that reference
to the singular, as in a renal artery, renal nerves about a renal
artery, kidney, etc., encompasses both the singular and plural
(e.g., renal arteries, renal nerves about a plurality of renal
arteries, a plurality of kidneys), and visa-versa. It is further to
be understood that while embodiments may be described herein with
reference to renal nerves, the teachings herein and variations
thereof are also applicable to the renal ganglia and/or the
aortic-reanl ganglia in general. Indeed, the teachings herein and
variations thereof are applicable to a wide variety of devices,
systems and/or methods that utilize ionizing radiation to partially
or completely block neurological communication between one or both
kidneys of a patient and a patient's central nervous system,
thereby reducing hypertension or the like, including robotic
radiosurgical systems, gantry-type radiosurgical systems, and the
like.
[0011] The renal nerves, owing to their position vis-a-vis the
renal arteries, may correspond to moving tissue of a patient, both
as a result of respiration of the patient, the pulsation of the
aorta and renal artery, and the heartbeat of the patient. With
respect to the latter, the temporal rise and fall of blood pressure
of the heartbeat cycle may cause the outer diameter of the renal
arteries to expand and contract by an amount that is sufficient to
move the renal nerves by an amount which may affect the treatment.
Embodiments of the invention allow improved radiosurgical
treatments of tissues of the renovascular system, often enhancing
the capabilities of existing radiosurgical systems for targeting
what in at least some instances may be relatively rapidly moving
tissues (renal nerves) so as to mitigate hypertension. Treatment of
renal nerves may benefit from an implanted position surrogate for
identification of the location of the target tissue, with the
surrogate optionally comprising a fiducial marker positioned in or
near the renal arteries and/or the kidneys using catheterization
techniques or direct transcutaneous routes. Novel catheters and/or
delivery structures having active fiducials may limit the need for
X-rays (and thereby minimize collateral imaging radiation
exposure). Enhanced planning and tracking techniques may also be
employed, with the radiosurgical renovascular system treatments
described herein generally being compatible with many components of
existing radiosurgical treatment systems.
[0012] According to a first aspect of the present invention, there
is a radiosurgical method for treating a patient body having a
renovascular system including a first and second renal arteries,
the patient having hypertension and/or congestive heart failure.
The method comprises acquiring three dimensional planning image
data encompassing the first and second renal arteries, planning an
ionizing radiation treatment of first and second target regions
using the three dimensional planning image data so as to mitigate
the hypertension, the first and second target regions encompassing
neural tissue of or proximate to the first and second renal
arteries, respectively and
[0013] remodeling the target regions by directing the planned
radiation from outside the body toward the target regions. In some
embodiments, the ionizing radiation includes electromagnetic waves
that ionize atoms or molecules within the body of the patient.
Ionizing radiation may include x-rays, gamma rays, photons, protons
and/or high-frequency ultraviolet radiation. In other embodiments,
the ionizing radiation may include alpha particles, beta particles
and neutrons.
[0014] When treating hypertension, for example, an appropriate
lesion pattern may be identified with the help of a renovascular
specialist, who may work with a radiosurgical specialist (such as a
radiologist, a radiation or medical physicist, and/or the like) so
as to identify the target region in the renovascular system
suitable for alleviating the hypertension, the radiation dose
gradients so as to avoid collateral damage to sensitive structures,
and other details of the treatment plan. Other medical specialists
may be consulted for identifying target regions of the heart for
implanting of the surrogates, and the like. Typically, the planning
of the treatment will comprise defining an estimated lesion of the
renovascular system based on the planned radiation, ideally
allowing a graphical representation of the estimated lesion to be
reviewed as part of the process.
[0015] In many embodiments, implanting of the surrogates will
comprise advancing at least one elongate flexible body through a
blood vessel. The surrogate may be coupled to tissue so that the
surrogate exhibits heartbeat- and/or respiratory-induced movement.
The implanted surrogate may comprise a non-colinear set of discrete
fiducial markers so that a three-dimensional offset orientation
between the surrogate and the target area can be determined from an
image of the fiducial markers. In some embodiments, implanting of
the surrogate may comprise screwing a helical structure of the
elongate body into a soft, contractile tissue of the heart.
Implanting of the surrogate may also include expanding an
expandable body with a lumen or cavity bordered by the tissue, with
the expandable body optionally comprising an inflatable balloon, a
temporary stent-like structure, or the like, which can be safely
and reversibly expanded within a vessel so as to engage the
surrounding tissue. In exemplary embodiments, implanting the
surrogate may comprise fixing an active three-dimensional position
indicator to the tissue, with the position indicator transmitting a
position indicating signal that can be used to register a location
of the implanted surrogate with the planning image data. In many
embodiments, the fiducial(s) will be implanted prior to acquiring
planning image data. In other embodiments, an image taken after
implanting the surrogate may facilitate registration. For example,
when the position indicating signal indicates an offset between the
surrogate and a position sensor (or transmitter) disposed outside
the body, the position indicating signal can be calibrated using
post-implant image data that encompasses the position sensor. In
one exemplary embodiment, the image data used for calibrating the
position indicating signal comprises post-planning calibration
image data, and a calibration position sensing signal is generated
while a catheter tip engages a heart tissue. A positional
relationship between the sensor and the body is maintained during
acquisition of the calibration image data and the generation of the
position sensing signal. More generally, the position indicator
typically comprises a sensor or signal generator used within
ultrasound or electromagnetic position indicating systems. The
target region can be treated by directing the planned radiation
using a position indicating signal from the position indicator
between intermittent tracking verification images. Hence, position
surrogates employing such active fiducial systems may limit the
need for imaging X-rays (and thereby minimize collateral imaging
radiation exposure).
[0016] In some embodiments, a fiducial may be placed in soft tissue
or bone, optionally in or near the renal nerve. Such a fiducial may
be used with spinal tracking for target localization. This fiducial
may comprise a temporary wire placed under fluoroscopic guidance,
with the wire remaining in place only during CT scanning and the
ablation procedure, then being removed. Optional position surrogate
structures may also comprise one or more bioresorbable fiducial in
or around the vicinity of the renal nerve that could be used for
tracking and target localization. In some embodiments the fiducials
may be introduced and affixed via peptides, chemicals, proteins
(e.g. syaptophysin), antibodies, or even inert conjugates that can
carry or be bound to materials that present a high contrast
suitable for imaging. Such a fiducial material support structure
may bind to a target material, tissue, or moiety in or near the
target region, with the imagable material optionally comprising
gold particles or nanoparticles other heavy metal with a
sufficiently high z number, polymer beads including such materials,
and/or the like that can be used for tracking and localization.
[0017] The planning image data may comprise computed tomography
(CT) data, magnetic resonance imaging (MRI), ultrasound (US),
Positron Emission Tomography (PET), Single Positron Emmision
Computed Tomography (SPECT), or the like.
[0018] A variety of approaches may be used to align a radiation
treatment source with the implanted fiducials. For example,
alignment image data of the surrogate may be acquired, particularly
where the target region is not easily visible. The surrogate images
can then be brought into a desired position and orientation by
movement of a patient support. Alternative alignment approaches may
include providing appropriate offsets for a radiation source
supporting robot or the like.
[0019] In some embodiments, a heartbeat cycle from the body will be
monitored while acquiring the planning image. A time series of
three-dimensional image datasets may be acquired, with the datasets
distributed throughout the heartbeat cycle so as to indicate renal
artery movement with the heartbeat cycle. The planning of the
treatment may include identifying radiation sensitive collateral
tissues and determining a series of radiation beams suitable for
providing a desired radiation dose in the target region without
excessively irradiating the collateral tissue, such as the tissue
forming the walls of the renal arteries. The remodeling of the
target region may be performed by monitoring the heartbeat cycle of
the body, and tracking at least a portion of the movement of the
tissue in response to the monitored heartbeat cycle and while
directing the radiation to the target region. The tracking may use
the time series of datasets.
[0020] The implanting of the surrogate will often comprise
advancing at least one elongate flexible body through a blood
vessel and coupling the surrogate to the renal arteries so that the
surrogate moves with the heartbeat cycle and respiratory cycle. A
time average offset between the surrogate and the target region may
be determined using the time series of image datasets. Tracking of
the target region may be performed by determining a position of the
surrogate, monitoring the heartbeat cycle of the body, and
directing the radiation beam to the target region using the
monitored heartbeat and respiratory cycles, the determined position
of the surrogate, and the time average offset. Hence, deformation
of the renal arteries between the surrogate and the target region
need not necessarily be tracked by the system.
[0021] In exemplary embodiments, the time average offset may be
determined for the heart cycle (which is used to determine a renal
artery cycle, as is detailed below) by identifying a series of
three-dimensional offsets from the time series of image datasets.
The time average offset may be applied throughout the heart cycle
so that tissue deformation between the surrogate and the target
region during the heartbeat cycle is untracked. The time average
offset may be further determined by selecting an image dataset from
among the time series of datasets. The selected dataset may
correspond to a calculated average of the measured series of
offsets. The selected offset need not necessarily correspond to a
quiescent phase of the heart cycle, nor to the calculated time
average offset itself. In other embodiments, the calculated time
average of the identified series of offsets may be used
directly.
[0022] In another aspect, the invention provides a treatment kit
for use with a radiosurgical system to treat a patient body. The
body has a renovascular system, and the body is afflicted with
hypertension and/or cardiac failure. The radiosurgical system has a
radiation source for transmitting a plurality of beams of ionizing
radiation from outside the patient body per a plan so as to
mitigate the hypertension. The radiosurgical system also has a
plurality of tracking inputs for synchronizing the radiation beams
with movement of a target region of the renovascular system. The
kit comprises an electrode couple-able to the patient so as to
transmit a heart cycle signal of the patient to a first tracking
input of the radiosurgical system. An elongate flexible body of the
kit has a proximal end and a distal end insertable though a blood
vessel of the patient. Alternatively or in addition to this, the
kit may include a percutaneous needle configured to deliver
fiducials. A position surrogate may be supported by the distal end
of the flexible body so as to be insertable into operational
engagement with a renal artery or the renal vein such that the
surrogate moves with the renal artery suitably for generating a
second tracking input of the radiosurgical system. Optionally, the
distal end remains in operational engagement with the renal artery
so that the distal end moves with the renal artery during
treatment. Alternatively, the surrogate may be retrievable deployed
from the distal end and the flexible body may be removed during
application of the radiation beams.
[0023] The electrode, flexible body, and surrogate will typically
be contained in a package, the package often being hermetically
sealed and also containing instructions for use of the kit and the
like. Additional components of the kit will also typically be
included in the package.
[0024] The second input of the radiosurgical system may include a
remote imaging system. The surrogate may comprise a set of passive,
high-contrast fiducial markers having a sufficiently non-colinear
configuration when deployed for defining a three-dimensional offset
between the surrogate and the target region. The set of fiducials
may have a substantially linear insertion configuration, and the
surrogate may alternatively comprise an active ultrasound or
electromagnetic component. The active surrogate may be included
within an ultrasound or electromagnetic system that provides a
signal to the second input so as to facilitate tracking of a
position of the surrogate (and hence the target region). In many
embodiments, a fixation surface may be provided for affixing the
distal end of the elongate body to a tissue of the heart, renal
artery or vein. The fixation surface may be defined by a radially
expandable body, a vacuum seal body, or a helical fixation screw.
In an alternative embodiment, passive surrogates are used. Such
passive surrogates may be in the form of gold seeds or other
substantially non-toxic seeds or other configurations, with respect
to the dosages used in the methods herein, with an electron density
visible on CT and/or guidance imaging.
[0025] Many embodiments of the treatment kit may include a body
surface marker affixable to an exposed surface of the patient body
so as to facilitate imaging of a respiration movement of the body.
For example, light emitting diodes (LEDs) may be mounted to a torso
of the patient. The LEDs may be imaged by a standard video camera
so as to monitor respiration using standard image processing
techniques.
[0026] In many embodiments, the electrode may be included in a set
of electrocardiogram (EKG) electrodes. An adhesive patch suitable
for affixing an ultrasound imaging transducer to a skin of the
patient may also be included with the kit. Components for accessing
and implanting the surrogate may also be included. For example, an
introducer sheath having a proximal end affixable to skin of the
patient during the radiation treatments, a distal end insertable
into the patient and a lumen therebetween may be provided. The
lumen may sealingly receive the elongate body, typically with a
valve member of the introducer sheath providing the sealing.
Additional ports or channels can be provided so that multiple
surrogate-supporting catheters can be positioned simultaneously. In
exemplary embodiments, the kit may also include one or more
additional components, such as a guidewire, imaging contrast
deliverable through a lumen of the elongate body to lumens of the
renal arteries, anesthetic skin cleansing solution, a locater
needle, a guidewire, and/or the like.
[0027] According to another aspect of the present invention, there
is a radiosurgical system for treating a patient body with a renal
artery and hypertension. The system comprises an image capture
device for acquiring three dimensional planning image data from the
renal artery and/or a location proximate the renal artery, a
radiation source for transmitting a plurality of beams of ionizing
radiation from outside the body, and a processor system configured
to direct the ionizing radiation beams toward a target region of
the renal artery and/or a target region at the location proximate
the renal artery such that the radiation beams remodel the target
region and the hypertension is mitigated.
[0028] In some embodiments, a position surrogate may be positioned
and/or implanted from within an inferior vena cava (IVC) of the
body prior to acquiring of the planning image data. The IVC
position surrogate may be temporary, but will often remain
implanted at least throughout planning and radiation delivery
(optionally being permanent). Advantageously, an IVC surrogate may
comprise a bioresorbable or biodegradable structure. Any
inadvertent emboli associated with an IVC position surrogate may be
relatively safely directed to the pulmonary vasculature by the
bloodflow, and access to the IVC for implantation of prosthetic
structures is well established with good patient safety.
Surprisingly, in many of the embodiments described herein
(including those employing an IVC position surrogate), no position
surrogate may be implanted within at least the first renal artery,
often within either of the renal arteries. This lack of a surrogate
within the renal artery may help avoid challenges of accessing the
renal arteries, and perhaps more importantly, may completely avoid
potential implant induced-occlusive response of the tissues of the
renal arteries (which could otherwise induce associated increase in
blood pressure and thereby potential decrease or even overwhelm the
hypertension alleviation available via denervation).
[0029] In many embodiment, a breathing cycle from the body will be
monitored while acquiring the planning image data. The breathing
cycle may also be monitored while directing the planned radiation
to the target regions. The directing of the planned radiation may
be controlled in response to the monitored breathing cycle. For
example, the planned radiation may be gated to the breathing (so
that radiation is directed only during a portion of the breathing
cycle during which the target is in a desired area), and/or by
tracking the breathing-induced movement of the target(s)
(optionally using modified systems included on commercially
available radiosurgical systems for tracking tumor target movement
associated with breathing). Advantageously, the directing of the
planned radiation may be performed in many of the embodiments
described herein (and surprisingly, even including those that
employ tracking for breathing-induced motion) without tracking
movement of at least the first renal artery in response to a
heartbeat cycle of the body (particularly without tracking
heartbeat-induced movement of the left renal artery), and often
without tracking such movement of both arteries.
[0030] The processor of the systems described herein can be
configured to control the direction of the radiation to account for
breathing-induced movement of the renal artery and/or the location
proximate the renal artery. The processor may be configured to
control the direction of the radiation without tracking
heartbeat-induced movement of the renal artery and/or the location
proximate the renal artery. The processor can be configured to
control the direction of the radiation in response to the position
surrogate within the inferior vena cava and without a position
surrogate disposed within the renal artery. In such embodiments,
the processor may be configured to provide a margin of less than 2
mm to account for heartbeat-induced movement of the renal artery
and/or the location proximate the renal artery, and may optionally
be configured to provide a margin of less than 0.5 mm to account
for heartbeat-induced movement of the renal artery and/or the
location proximate the renal artery (for example, when treating the
left artery).
[0031] As will be understood, the teachings herein are applicable
to any device, system or method that utilizes ionizing radiation to
partially or completely block the renal nerve plexus.
BRIEF DESCRIPTION OF THE DRAWINGS
[0032] FIG. 1 is an exemplary CyberKnife.TM. stereotactic
radiosurgery system for use in embodiments of the invention;
[0033] FIG. 1A schematically illustrates a method for treating a
target tissue using a radiosurgical system;
[0034] FIGS. 1B and 1C depict an exemplary renovascular structure
to which embodiments of the present invention may be
applicable;
[0035] FIGS. 1D-1G depict exemplary target treatment regions with
reference to anatomical structure according to an exemplary
embodiment of the present invention;
[0036] FIGS. 1H-1I depict alternate exemplary target treatment
regions with reference to anatomical structure according to an
exemplary embodiment of the present invention;
[0037] FIG. 1J depict an exemplary target treatment region without
reference to anatomical structure according to an exemplary
embodiment of the present invention;
[0038] FIG. 1K schematically illustrates a method for treating a
target tissue using a radiosurgical system wherein the method may
utilize the method related to FIG. 1A;
[0039] FIG. 2 is a graph showing exemplary data from the
anterior/posterior motion of a point on the outer wall of a renal
artery, showing movement associated with both the heart beat cycle
and the respiration cycle;
[0040] FIG. 3 schematically illustrates a method for treating a
target tissue using a radiosurgical system that may utilize the
methods related to FIGS. 1A and/or 1K;
[0041] FIG. 4 is an illustration of an EKG waveform showing
exemplary phases where a time sequence of CT volumes are
acquired;
[0042] FIG. 5A depicts exemplary target treatment regions without
reference to anatomical structure according to an exemplary
embodiment of the present invention pertaining to a bilateral
treatment for hypertension;
[0043] FIG. 5B graphically shows portions of a user interface
display, including a planning input for a target region so as to
treat hypertension, along with a graphical representation of a
lesion of the renal nerves estimated by components of the treatment
system;
[0044] FIG. 5C depicts exemplary an isometric view of a conformal
target treatment region according to an embodiment of the present
invention;
[0045] FIG. 5D depicts an exemplary isometric view of radiation
dose regions resulting from a conformal treatment according to an
embodiment of the present invention;
[0046] FIGS. 5E-F depict exemplary radiation clouds resulting from
a conformal treatment according to an embodiment of the present
invention;
[0047] FIGS. 5G-K depict exemplary isodose lines resulting from a
conformal treatment according to an embodiment of the present
invention;
[0048] FIGS. 6A-6C show catheter-based fiducials deployed in a
lumens of the renal artery so as to provide a tracking
surrogate;
[0049] FIGS. 6D-6K show temporarily implantable surrogate systems,
including catheter-based intraluminal fixation structures and/or
non-tethered retrievable intraluminal fixation structures, as well
as their use when deployed in a renal artery so as to provide a
tracking surrogate;
[0050] FIG. 7 schematically illustrates a radiosurgical system and
method for treating a renovascular system in which fiducials are
implanted into the renal artery or adjacent structures after
planning of the target regions and the associated series of
radiation beams;
[0051] FIG. 7A schematically illustrates an alternative
radiosurgical system and method for treating a renovascular system
in which fiducials are temporarily implanted into the renal artery
or adjacent structures before planning of the target regions and
the associated series of radiation beams, and are explanted after
treatment;
[0052] FIGS. 8A-8F illustrate alternative catheter-based surrogate
systems having image-able and/or active fiducials to facilitate
tracking of moving heart tissues;
[0053] FIGS. 9A and 9B schematically illustrate a system and method
for registering a catheter tip with a CT dataset so as to calibrate
a position sensing system including an active fiducial or the
like;
[0054] FIG. 9C is a functional block diagram schematically
illustrating an exemplary active catheter calibration module;
[0055] FIG. 10 schematically illustrates registration of implanted
catheter-based active and/or passive fiducials with a treatment
plan;
[0056] FIG. 11 graphically illustrates a registered treatment plan
and passive fiducial system;
[0057] FIG. 12 graphically illustrates alignment of the treatment
plan with the treatment system;
[0058] FIG. 12A is a functional block diagram schematically
illustrating an embodiment of an active catheter tracking
module;
[0059] FIG. 13 schematically illustrates a method for treating a
target region according to a treatment plan;
[0060] FIGS. 14A-14E schematically illustrate relative motion
between a tracking surrogate and a target tissue as may be caused
by tissue deformation, along with a calculated average target
center; and
[0061] FIG. 15 schematically illustrates a kit for use with the
systems and methods described herein for treatment of non-tumerous
diseases of the heart.
[0062] FIGS. 16A and 16B illustrate 3D renderings of an exemplary
position surrogate disposed within the inferior vena cava of a
system, and also shows gold bead fiducials disposed on the right
renal artery and near the left renal artery.
DETAILED DESCRIPTION OF THE INVENTION
[0063] The present invention generally provides improved systems,
devices, and methods for treatment of tissue to alleviate
cardiorenal disease, including hypertension, using radiosurgical
systems. The embodiments of the present invention detailed herein
and variations thereof may have the therapeutic effect of slowing,
including halting, the progression of congestive heart failure via
a non-invasive or minimally invasive (in embodiments utilizing
catheters or percutaneous needles to implant surrogates, as
detailed below) surgical procedure. Some or all embodiments
detailed herein and variations thereof may be practiced to mitigate
the conjunctive heart failure that sometimes develops following a
myocardial infarction.
[0064] FIG. 1A provides an exemplary flowchart 1 of a method for
treating cardiorenal disease of a patient, such as hypertension. At
step 11, a patient diagnosed with cardiorenal disease, such as
hypertension, is positioned relative to a radiosurgery system such
as that detailed below with respect to FIG. 1 that emits ionizing
radiation. At step 12, radiosurgery radiation (ionizing radiation)
is directed from outside the patient by the radiosurgery system
towards one or more target treatment regions encompassing
sympathetic ganglia of the patient so as to inhibit the cardiorenal
disease. In an exemplary embodiment, step 12 is a renal denervation
procedure where the radiation deteriorates and/or destroys at least
some of the renal nerves surrounding one or both renal arteries of
the patient (depending on whether the procedure encompasses a
unilateral or bilateral denervation procedure), resulting in the
inhibition of hypertension of the patient. More particularly, the
radiation directed towards the renal nerves at least partially,
including substantially and entirely, reduces the ability of a
central nervous system of the patient to communicate with one or
both kidneys of the patient. This has the resulting effect of
reducing hypertension.
[0065] Step 12 may be considered to correspond to renal nerve
modulation via radiosurgical ablation of the renal nerves. Again,
as noted above, while this embodiment has been described with
respect to renal nerves, this embodiment also corresponds to the
radiosurgical ablation of the renal plexus and ganglion to reduce
hypertension. As will be understood, the result of step 12 (i.e.,
the direction of the radiation to the target treatment regions
encompassing the sympathetic ganglia) blocks or at least
down-regulates sympathetic impulses between one or both kidneys of
the patent and a central nervous system of the patient. That is,
renal nerve activity in the patient is blocked or at least
down-regulated. As detailed above, reducing communication between
the central nervous system and the kidneys via renal denervation
reduces (including eliminates) hypertension, in at least some
patients. More specific features the renal denervation procedures
according to some exemplary embodiments of the present invention
will now be described.
[0066] FIG. 1B provides a schematic of a portion of the
renovascular structure 300 of a patient. As may be seen in FIG. 1B,
the renovascular structure 300 includes kidney 310 (and, if
present, the second kidney, which is not shown), renal artery 320
and renal vein 330 (again, if present, the second renal artery and
second renal vein). Renal nerves 340, a portion of which are shown
in FIG. 1B, are located about the renal artery 320 (and the second
renal artery, if present) in the periarterial space 323 of the
renal artery 320. FIG. 1C depicts a conceptual unsealed
cross-sectional view of the renal artery 320 and renal nerves 340,
the renal nerves being surrounded by membrane 350 located in
periarterial space 323, the boundary of the membrane which is
depicted, again conceptually, as 352. In an exemplary embodiment of
the present invention, the target treatment regions of step 12
envelopes renal nerves 340. By envelopes renal nerves 340, it is
meant that at least a portion of the renal nerves 340 is enveloped
by the treatment region. Accordingly, the treatment region may be
limited longitudinally, diametrically and/or laterally with respect
to the renal artery 320 while enveloping renal nerves. For example,
FIGS. 1D and 1E depict an exemplary three-dimensional treatment
region 360 enveloping renal nerves 340. FIG. 1D is a side-view of a
renal artery 320, and FIG. 1E is a cross-sectional view of FIG. 1D.
FIGS. 1F and 1G depict enlarged views of portions of FIGS. 1D and
1E, respectively. In these views, any anatomical structure taken up
by the treatment region is not shown. For example, FIG. 1F depicts
renal nerves 340 on the right side of the figure, but the treatment
region 360 eclipses those renal nerves on the left side of the
figure.
[0067] As may be seen from FIGS. 1D-1G, the target treatment region
360 may be in the shape of a toroidal arc-segment, such as a
generally cylindrical shape, as may be seen in the Figures, bounded
in the longitudinal direction (see FIG. 1D) and the lateral
direction (see FIG. 1E). FIG. 1J depicts an isometric view of
target region 360 without any anatomical structure, detailing the
longitudinal boundary, the lateral boundaries, and other useful
dimensions. FIGS. 1E and 1G, in view of FIG. 1J, show that the
target treatment region is bounded in the lateral direction both
circumferentially in that it does not completely surround the renal
artery (instead forming a "C" shape, as may be seen in FIG. 1E,
which depicts a cross-sectional view of the target region 360 when
taken on a plane normal to the longitudinal direction 321 of the
renal artery 320) and in the radial direction in that it has an
inner diameter that lies at the outer diameter of the renal artery
wall 322 and has an outer diameter that lies just beyond the
membrane wall 352. Optionally, the target treatment region has an
opening extending down the longitudinal axis of the cylinder.
[0068] It is noted that in other embodiments, the target treatment
region 360 may have different longitudinal and/or lateral
boundaries. FIGS. 1H and 1I correspond to FIGS. 1F and 1G,
respectively, except show that the inner diameter of the treatment
region 360 is located beyond the outer diameter of the renal artery
wall 322. Thus, there is a space 370 separating the renal wall 322
and the treatment region 360. It is noted that in other
embodiments, the inner diameter of the target treatment region 360
may be located inside the renal artery wall 322. Also, in other
embodiments, the outer diameter of the target treatment region 360
may be located inside the membrane wall 352. In yet other
embodiments, the target treatment region 360 surrounds the entire
renal artery (i.e., it has a cross-section when taken normal to the
longitudinal direction of the renal artery that is "O" shaped). In
such an embodiment, the renal nerves are essentially uniformly
"thinned out" within the longitudinal boundaries of the target
treatment region. This is in contrast to the target treatment
regions of FIGS. 1F and 1G, having the "C" shaped cross-section,
where the renal nerves are destroyed within the cross-section of
the "C" shape, but are left substantially unharmed outside of the
cross-section of the "C" shape. Thus, the surviving renal nerves
are not uniformly distributed within the longitudinal boundaries of
the target treatment region. In some such embodiments where the
target treatment region has an "O" shaped cross-section, the inner
diameter and/or the outer diameter of the target treatment region
360 is located such that some renal nerves are not enveloped by the
target treatment region, such as is the case, by way of example,
with respect to the target treatment regions depicted in FIGS. 1H
and 1I above. That is, some renal nerves located within the
longitudinal boundaries of the target treatment region lie outside
the lateral boundaries of the target treatment region. However, in
other embodiments, all of the renal nerves located within the
longitudinal boundaries of the target treatment region lie inside
the lateral boundaries of the target treatment region.
[0069] By controlling the boundaries of the target treatment region
360 relative to the structures of the renovascular system (e.g.,
the renal arteries), the functionality and performance of the renal
artery can be substantially maintained after the treatment for the
cardiorenal disease. By way of example, the target treatment region
may be controlled, relative to the renovascular structures such
that the radiation directed to the renal nerves does not result in
significant blockage of the renal artery. That is, even though the
target treatment region envelops renal nerves, and those renal
nerves are located about a renal artery of the patient, the renal
artery proximate the target treatment region remains is
substantially unblocked after the radiation is directed towards the
target treatment regions. Alternatively or in addition to this, to
the extent that radiation is delivered to the walls of the renal
arteries, the dose of radiation is not sufficient to result in
narrowing or stenosis of the renal arteries. In some embodiments,
after completing the treatment (i.e., final completion of directing
radiation to the renal nerves, after which directed radiation is
sufficient to alleviate the hypertension such that no further
radiation treatments are needed within at least six months, one
year, eighteen months or 2 years) to maintain the alleviation of
the hypertension), the inner diameter of the artery proximate the
target treatment region is at least substantially the same six
months after the action of directing the radiation as it was just
prior to directing the radiation.
[0070] It is noted that in some embodiments of the present
invention, the shapes of the target regions generally or
substantially correspond to the shapes of the resulting
deteriorated/destroyed renal nerves. This is because the
radiosurgical system is configured to precisely control the dose
level of radiation delivered to the target region such that there
is a rapid and significant drop-off of the radiation dose delivered
at or proximate to the boundaries of the target regions, as will be
described in greater detail below.
[0071] FIG. 1K presents a flow-chart 400 of an expanded method
according to an exemplary embodiment of the present invention,
which includes the method steps of flowchart 1 detailed above.
Flow-chart 400 includes step 410, which entails evaluating the
state of a renovasucular system of the patient. In an exemplary
embodiment, step 410 entails determining that the patient suffers
from hypertension, and, optionally, also determining that the
patient's renovascular system is not affected with a
non-hypertension related disease in general, and a tumorous disease
in particular. The determination(s) of step 410 may also include
the action of evaluating at least one of a systolic or a diastolic
blood pressure of the patient and determining, as a result of the
evaluation, that the respective pressure correspond to a pressure
indicative of hypertension. Based on the determinations and/or
evaluations of step 410, a determination is made at step 420 to
proceed with a renal denervation procedure including the method of
delivering radiation according to the steps of flow-chart 1 and/or
other methods detailed herein and variations thereof.
[0072] After step 420, the method proceeds to step 430, which
entails performing steps 11 and 12 of flowchart 1 or delivering
radiation via another method detailed herein. In this exemplary
method, the radiation directed to the target regions in step 12 is
directed in response to the determination/evaluation of step 410.
After step 430, the method proceeds to step 440, which entails
determining that the patient no longer suffers from hypertension
and/or determining that the hypertension has been substantially
clinically reduced. Step 430 may include the action of reevaluating
at least one of the systolic or a diastolic blood pressure of the
patient and, based on that reevaluation, making the determination
about the patients hypertension depending on whether or not the
respective reevaluated pressures correspond to a pressure
indicative of hypertension. In an exemplary embodiment of step 440,
if the reevaluated systolic or diastolic blood pressure is
clinically substantially lower than the respective initially
evaluated systolic or diastolic blood pressure (e.g., a reevaluated
systolic blood pressure lower than the initially evaluated systolic
blood pressure by about 20 mm Hg or more), a determination is made
that the hypertension has been substantially sufficiently
clinically reduced. In another embodiment, should it be determined
that hypertension has not been sufficiently or desirably treated,
and maximal radiation tolerance doses have not yet been met, then a
re-ablation can be performed.
[0073] In some embodiments of the present invention, the renal
denervation processes disclosed herein results in a reduction of a
cardiac infarct size expansion and improvement in ventricular
ejection fraction. Optionally, the methods, devices, and systems
described may be used of treatment of congestive heart failure
secondary to hypertension, and/or for modulation of neurohumoral
chemicals that effect ion and peptide chemicals. Such treatments
may be used to modulate and improve heart failure, congestive heart
failure, and/or to reduce left ventricular size and/or mass.
[0074] Embodiments of the invention may be particularly well suited
for treatment of moving tissues, such as tissues adjacent the real
arteries, such as the renal nerves. Such embodiments may take
advantage of structures and methods which have been developed for
treating tumors, particularly those which are associated with
treatment of tissue structures that move with respiration cycles.
The cardiac cycle is typically considerably faster than the
respiration cycle, and overall treatment times can be fairly
lengthy for effective radiosurgical procedures on the renovascular
system (typically being up to 100 minutes, depending on the
treatment plan). Hence, it will often be advantageous to avoid
continuous imaging of the target and adjacent tissues using
fluoroscopy or the like so as to limit exposure to excessive
imaging radiation. Advantageously, the invention can provide
physicians and other medical professionals with adequate time for
planning a proper radiosurgical course of treatment once a planning
image dataset and other diagnostic measurements have been
obtained.
[0075] The present invention may take advantage of many components
included in or derived from known radiation delivery systems. An
exemplary modified CyberKnife.TM. stereotactic radiosurgery system
10 is illustrated in FIG. 1. Radiosurgery system 10 includes a
lightweight linear accelerator 12 mounted to a robotic arm 14. In
an exemplary embodiment, the robotic arm 14 moves the linear
accelerator 12 about a body of a patient during remodeling of the
target regions. An image guidance system 16 includes biplane
diagnostic X-ray sources 18 and image detectors 20 so as to enhance
registration between robot arm 14 and the target site. As the
tissues in the target region may not present a high-contrast image,
image guidance system 16 may use image processing techniques to
identify the location of one or more surrogate structures, with the
surrogates typically including a high-contrast natural tissue
structure (such as a bone or the like) or an artificial implanted
fiducial marker that moves in correlation with the target tissue.
Target tracking may also make use of one or more surface image
cameras 22, particularly for identifying movement of the chest wall
and/or the wall of the abdominal cavity corresponding to
respiration. Cameras 22 may monitor light emitting diodes (LEDs) or
other high-contrast fiducial markers visible on the patient's chest
and/or abdomen. A patient support 24 is movably supported by an
alignment arm 26 so as to facilitate bringing the patient (and
treatment site) into alignment with robot arm 14. As will be
understood, exemplary embodiments of the present invention include
practicing the methods detailed herein using the radiosurgical
system 10.
[0076] In other embodiments, the methods detailed herein may be
implemented using an alternate radiosurgical system where, instead
of a robotic arm 14 supporting a linear accelerator 12, a plurality
of radiation sources fixed relative to the radiosurgical system may
be arrayed about the body. Such an alternate radiosurgical system
may still include one or more or all of the features just detailed
with respect to radiosurgical system 10. In an exemplary
embodiment, a GammaKnife.TM. radiosurgical system may be used.
[0077] FIG. 2 graphically depicts hypothetical motion of a point on
a renal artery. As can be seen, the motion includes two components:
a slowly varying breathing component and a more rapid cardiac
component. As used herein, the cardiac component includes (i)
dilation of the artery due to the increase of blood pressure and
the subsequent contraction due to subsequent decrease in blood
pressure of the heart cycle and (ii) motion resulting from pressure
waves traveling from the outer surface of the heart and/or from
tissue contiguous therewith, as a result of expansion and/or
contraction of the outer surface of the heart during the heart
cycle, which travel through tissue and/or fluid of the body that
impinge on the artery (typically, the outside wall of the artery)
and/or tissue contiguous thereto, thus causing the artery to move.
Motion "i" is referred to as a "blood pressure component" of the
cardiac cycle/heart cycle and motion "ii" is referred to as a
"displacement component" of the cardiac cycle/heart cycle."
Embodiments of the present invention may address one, some or all
of these motion components. For example, robot arm 14 may move
linear accelerator 12 synchronously with a target site so as to
compensate both for the respiration component, and for the cardiac
component of overall motion. Alternatively, synchronous movement of
robot arm may track only the respiration component while
disregarding the cardiac component in at least one or more degrees
of freedom. In some embodiments, robot arm 14 may track the
respiration component of motion with gating of linear accelerator
12 applied so as to limit the radiation beam to portions of the
heartbeat cycle where the target tissues are sufficiently aligned
with the robot so as to mitigate or eliminate cardiac
motion-induced errors. As the significance of the different motion
components in different degrees of freedom may vary, differing
combinations of motion component tracking, motion component
disregarding, and radiation gating may be employed. Exemplary
tracking approaches are described in more detail in U.S. Patent
Publication 2008/0177280 in the name of Adler et al., as published
on Jul. 24, 2008 (the full disclosure of which is incorporated
herein by reference.)
[0078] Referring now to FIG. 3, a relatively simple treatment
flowchart 40 can represent steps used before and during
radiosurgical treatment according to embodiments of the present
invention. The internal tissues are imaged 42 for planning
purposes, typically using a remote imaging modality such as a
computed tomography (CT), magnetic resonance imaging (MRI),
ultrasound imaging, X-ray imaging, PET, SPECT, optical coherence
tomography, a combination of these, or other imaging modalities.
With respect to radiosurgical methods for treating a patient body
having a renovascular system, where the patient has hypertension, a
three dimensional planning image data encompassing one or both
renal arteries and/or the respective renal nerves is acquired. Note
that the tissue structure which will actually be targeted for
radiation remodeling (e.g., renal nerves) need not necessarily be
visible in the image, so long as sufficiently contrasting surrogate
structures are visible in the image data to identify the target
tissue location. In an exemplary embodiment, the location of the
tissue structure which will actually be targeted but not readily
imaged can be sufficiently estimated with reference to structures
that can be imaged and/or to the implanted surrogate. For example,
the renal nerves may not be readily imaged, but their position may
be estimated with reference to an imaged renal artery. The planning
imaging used in many embodiments may include a time sequence of
three-dimensional tissue volumes, with the time sequence typically
spanning one or more movement cycles (such as a cardiac or
heartbeat cycle, a respiration or breathing cycle, and/or the
like). In exemplary embodiments, the image data comprises a series
of CT slices through the heart so as to provide volumetric or
three-dimensional image data. The time series of three-dimensional
heart images may be acquired at times that are distributed
throughout the heartbeat cycle, so that the image planning data
effectively comprises a time series of three-dimensional image
datasets providing information regarding the motion of renovascular
tissues during the heartbeat. FIG. 4 shows a typical heartbeat
electrocardiogram (EKG) waveform from which ten phases have been
identified and for which ten associated CT volumes are acquired. In
some embodiments, the target tissue may be outlined in each of the
ten volumes, or the target outline may be identified in one CT
volume and automatically tracked over the other CT volumes. As will
be described in more detail hereinbelow, other alternatives include
selecting an appropriate one of the three-dimensional image
datasets from the time series, generating an average positional
dataset, or the like. Regardless, acquisition of the series of
three-dimensional datasets can be performed using any of a variety
of commercially available CT systems.
[0079] Referring still to FIG. 3, based on the imaging data
obtained from image step 42, a plan 44 can be prepared for
treatment of the tissue at the target site. The plan typically
comprises a target region or regions and a series of radiation
beams which intersect within the target region. The radiation dose
within the target tissue should be at least sufficient to provide
the desired remodeling effect. With respect to the methods of renal
denervation detailed herein, the plan may entail planning an
ionizing radiation treatment of a first region (in the case of a
unilateral treatment) or a first and second target region (in the
case of a bilateral treatment) using the three dimensional planning
image data detailed above. The first and, if applicable, second
target regions encompass neural tissue of or proximate to the first
and second renal arteries, respectively. In the case of a bilateral
treatment, the first and second target regions may comprise two
spatially separated non-contiguous regions, as is depicted by way
of example in FIG. 5A, which depicts a target region group 500
comprising a first target region 510 arrayed about the a first
renal artery and a second target region 520 arrayed about a second
renal artery. It is noted that the term target region as used
herein is not limited to a region surrounding a single artery. A
target region may be such that the region surrounds a majority of
respective perimeters of the first and second renal arteries of the
patient, the target region thus having two sections (510 and 520,
respectively) separated by a space into which a therapeutic level
of radiation is not directed.
[0080] Typically, the radiation dose delivered to the target
regions will be sufficient to ablate renal nerves to inhibitor
otherwise reduce neural communication between one or both kidneys
and the central nervous system, inhibit hypertension, and/or the
like. Radiation dosages outside the target tissue will in many
embodiments, decrease with a relatively steep gradient so as to
inhibit excessive damage to collateral tissues, with radiation
dosages in specified sensitive and/or critical tissue structures
often being maintained below a desired maximum threshold to avoid
deleterious side effects. It is noted that in some embodiments, the
target treatment regions have boundaries such that the outer
diameter of the treatment region is less than the outer diameter of
the renal nerves, the area between the two being an area where the
radiation dose gradient substantially decreases. That is, by
controlling the outer diameter of the treatment region, the
gradient may be maintained within the renal nerves. As will be
understood, renal denervation often entails avoiding the
destruction of all of the renal nerves. Accordingly, the renal
nerves located within the gradient region may be the renal nerves
which are permitted to survive the renal denervation process.
[0081] Referring now to FIGS. 3 and 5, an exemplary treatment
planning module and user interface allows the system user to input
a desired lesion pattern with reference to a surface of a tissue.
For treatment of moving tissues of the renovascular system (e.g.,
renal nerves arrayed about the renal arteries) so as to inhibit
hypertension, a reference surface of the renal nerves may comprise
the nerve/tissue interface of the renal nerves. Alternatively or in
addition to this, a reference may be an extrapolated surface
roughly equidistant between the membrane surrounding the renal
nerves. In other embodiments, renal artery surfaces may be used as
a reference surface. Such surfaces may comprise the blood/tissue
interface or the inner surface of the lumen of the renal artery.
Alternative embodiments may employ an outer surface of the renal
artery as the reference surface, although the surface may be more
easily identified from the three-dimensional planning image data by
introducing imaging contrast agent during the planning image
acquisition step 42.
[0082] The reference surfaces (e.g., boundary between the blood
(including the added contrast) and the renal nerves and/or the
arterial tissue) in each slice of the CT data can be segmented in
one, some, or all of the volumetric datasets associated with the
cardiac cycle phases. The segmented regions can be stacked or
assembled together, and smoothing techniques can be applied between
the boundaries of the slices. This allows the planning medical
professionals to input an appropriate lesion pattern as a series of
lines or curves relative to the renovascular tissue surface, with
the lines being expanded to volumes so as to provide the desired
therapeutic benefit. In such embodiments, the user may optionally
define the lesion with reference to the renal artery or aortic wall
surface. Once the target region has been identified, existing
radiosurgical planning approaches to identification of radiation
sensitive structures may be implemented. Similarly, existing
radiosurgical radiation beam calculating modules may be used to
determine the resulting radiation distribution.
[0083] FIG. 5B graphically shows portions of a user interface
display 50 including a planning input for a target region so as to
treat hypertension, along with a user interface display 54
including a graphical representation of a lesion of the renal
nerves estimated by components of the treatment system for a
conformal treatment plan. Along with inputting a desired lesion
pattern 51 (as schematically illustrated on the left side of FIG.
5B), the planning module and user interface may output an estimate
of the actual radiation exposure along the surface of a renal
artery, potentially in the form of an estimated renal nerves and
renal artery lesion 55 (as schematically illustrated on the right
side of FIG. 5B). Estimated lesion 55 may represent the portion of
renovascular tissue surface which receives a radiation dose above a
necrotic threshold, optionally based on radiation beams and
radiation dose output from an existing radiosurgical treatment
planner. Alternative patterns may represent an estimate of tissue
which will receive a sufficient dose of radiation for therapeutic
remodeling so as to inhibit the hypertension. The user may
interactively develop the plan based on iterative input into and
output from the planning treatment module. The exemplary display of
estimated lesion 55 shown on renovascular tissue surface seen in
FIG. 5B shows a highlighted (false color) area of surface that
receives a radiation dose higher than a first (lower) threshold and
less than a second (higher) threshold. Alternative displays may
indicate a tissue surface area which receives a sufficient dose to
eventually cause the tissue to scar, to necrose, to ablate, and/or
the like, with the indicated tissue optionally being highlighted
using a color or tissue surface image which corresponds to the
eventual tissue state (for example, so that scar tissue that is
typically whiter than a corresponding healthy tissue is indicated
by a whiter shade than the surrounding tissue, or the like).
[0084] Referring once again to FIG. 3 (along with reference to FIG.
1 and FIGS. 6A-6C) after completion of plan 44, radiosurgical
treatment 46 of the renovascular system may be initiated by
positioning the patient on patient support 24, bringing the patient
into alignment with robot arm 14, and directing the planned series
of radiation beams from the linear accelerator 12 to the target
region of the renovascular system. In an exemplary embodiment, this
entails remodeling the target region(s) by directing the planned
radiation from outside the body toward the target region(s). In the
case of a bilateral treatment, the radiation is directed to the
first and second target regions in a single treatment procedure on
a single day. In some embodiments, a full dose of radiation is
delivered to one of the first and second target regions, followed
by delivery of a full dose of radiation to the other of the first
and second target regions, during the single treatment procedure on
the single day. In other embodiments, partial doses are delivered
to the first and/or second target regions in an alternate pattern
until the full doses are delivered to the target regions. Note that
the partial doses may be of about the same magnitude or may be
different for the two target regions. For example, the first region
may receive a 60% dose, followed by delivery of the full 100% dose
to the second region, followed by delivery of the remaining 40% of
the dose to the first region. Note further that these staggered
doses may be delivered over a series of treatment procedures
spanning respective different days. In yet other embodiments, the
full dose of radiation is delivered to the first target region
during a treatment procedure on a first day, and the full dose of
radiation is delivered to the second target region during a
separate treatment procedure on a second day.
[0085] FIG. 5C depicts an exemplary conformal target treatment
region 530 of the renovascular system to be imparted on that system
during a radiosurgical method for treating a patient having
hypertension. It is noted that in other embodiments, the target
treatment regions may be isocentric. While the following details an
exemplary embodiment of a conformal treatment plan, other
embodiments include concentric treatment plans. With respect to
FIG. 5C, the size of the elements of FIG. 5C is scaled to the
anatomy of an average male adult. More particularly, by
implementing the methods detailed herein with respect to a
conformal treatment plan, a conformal target lesion corresponding
to region 530 will be imparted onto the patient's renovascular
system by directing ionizing radiation to the region 530. FIG. 5D
depicts an estimated three-dimensional radiation dose pattern
resulting at the completion of the conformal treatment (not
including later periodic treatments to address re-growth of renal
nerves, etc.). The red portions 540 indicate structure subjected to
about >30 Gy of radiation, the green portions 550 indicate
structure subjected to about 20 to about 30 GY of radiation, and
the blue portions (remainder) indicate structure subjected to about
<20 Gy of radiation. The sizes of elements of FIG. 5D are scaled
to the anatomy of an average male adult FIGS. 5E and 5F depict in a
quasi-three-dimensional manner the outer boundaries of a 20 Gy dose
cloud 560 and a 10 Gy dose cloud 562, respectively, again where
size of the elements of these figures is scaled to the anatomy of
an average male adult.
[0086] FIGS. 5G-K depict isodose lines in two-dimensional format
for various planar sections taken through a patient, where the
planar sections encompass structure of the renovascular system.
(The information of FIG. 5K is substantially duplicative of the
prior figures--FIG. 5K being presented because it presents the data
in a different contrast.) FIGS. 5G-K also depict the outline of the
target, which is the innermost contour, the innermost contour also
having a thickness greater than the isodose lines. Starting in
order from the innermost to the outermost isodose line, after the
contours corresponding to target 570, the points on the innermost
isodose 580 correspond to an absorbed dose of 30 Gy of radiation,
and the points inside of isodose 580 receive an absorbed dose of at
least 30 Gy of radiation. The points on the next innermost isodose
582 correspond to an absorbed dose of 20 Gy of radiation, and the
points inside of isodose 582 receive an absorbed dose of at least
20 Gy of radiation. The points on the next innermost isodose 584
correspond to an absorbed dose of 10 Gy of radiation, and the
points inside of isodose 584 receive an absorbed dose of at least
10 Gy of radiation. The points on outer isodose 586 correspond to
an absorbed dose of 5 Gy of radiation, and the points inside of
isodose 584 receive an absorbed dose of at least 5 Gy of radiation.
It is noted that points within box 588 receive less than 5 Gy of
radiation. However, it is noted that there may be areas outside a
given isodose/box 588 and/or inside a given isodose/box 588 where
the predicted absorbed dose is different than specified. By way of
example, there may be areas near the skin that experience a dose
flare and/or areas inside the isodose lines that experience a dose
deficiency. The size of the elements of these figures is scaled to
the anatomy of an average male adult. Along these lines, it can be
seen that embodiments of the present invention result in
inhomogeneous radiation delivery that delivers more than about 15
Gy within 4 mm of the outer wall of the renal arteries. It is noted
that while a unilateral treatment has been depicted with respect to
FIGS. 5C-5J, the data presented with respect to these figures is
applicable to a bilateral treatment as well, and the opposite
renovascular structure from that depicted in the Figures would
substantially correspond to that depicted in the Figures.
[0087] From FIGS. 5G-K, it can be seen that directing radiation
from outside the body toward a targets region in accordance with a
conformal treatment plan can result in a large fraction of the
target region 570 receiving at least the specified prescription
dose (the areas on and in isodose 580 receive the prescription
dose). This prescription dose can be expressed as a percentage of
the maximum dose delivered to any point in a given volume. In an
exemplary embodiment, the prescription dose is 65% of the maximum
dose in the field. The volume receiving 2/3.sup.rds of the
prescription dose (43% of the maximum dose, isodose 582 depicting a
cross-section of that volume) has a volume of approximately 3 times
the target volume (isodose 580 depicting a cross-section of that
volume--all isodoses depicted in a given frame are taken on the
same plane). In an exemplary embodiment, the target volume is 3.7
ml and the volume receiving 2/3.sup.rds of the prescription dose is
about 3 times that (11.1 ml).
[0088] In an exemplary embodiment, a target volume is 3.7 ml, and
the volume receiving at least the prescription dose is 4.3 ml, and
points within that latter volume receive at least 30 Gy of
radiation. Still further with respect to this exemplary embodiment,
a volume of 7.5 ml (about 2 times the target volume) receives at
least 24.92 Gy of radiation, a volume of 11.1 mm (about 3 times the
target volume) receives at least 20.77 Gy of radiation, a volume of
14.7 mm (about 4 times the target volume) receives at least 18.00
Gy of radiation (about 2/3rds the prescription dose), a volume of
18.7 mm (about 5 times the target volume) receives at least 15.69
Gy of radiation (about 1/2 the prescription dose) and a volume of
38.8 mm (about 10 times the target volume) receives at least 10.00
Gy of radiation (about 1/3.sup.rd the prescription dose). It is
noted that in an exemplary embodiments, the just recited volumes of
larger size envelop or substantially envelop the smaller volumes.
From these figures, it can further be seen that directing radiation
from outside the body toward a target region in accordance with a
conformal treatment plan results in respective radiation dose
distributions to most of the target region 570 of at least the
prescription dose and a dose distribution at a boundary (isodose
586) of a volume about seven to ten times the volume of the target
region 570, and approximately centered thereabout, of about
one-fifth of a unit of radiation. By directing radiation to a
target treatment region to obtain the exemplary isodoses FIGS. 5G-J
and/or directing the radiation according to other embodiments
detailed herein and variations thereof, where the target region
surrounds a majority of a perimeter of a renal artery, a collateral
dose of the directed radiation into the walls of the renal artery
is sufficiently less than a dose of the radiation in the target
region so as to inhibit tissue response-induced occlusion of the
renal artery.
[0089] As noted above, the target region of the renovascular system
(i.e., the renal nerves) may not be readily identified in the
images obtained by image guidance system 16. To enhance tracking of
the renal nerves, it will often be advantageous to advance a
catheter 60 through a blood vessel 62, such as the renal artery, so
as to couple one or more surrogate structures 64 to a tissue that
moves in correlation with the target region of the renovascular
system. In the embodiment of FIGS. 6A-6C, catheter 60 has a distal
end 66 with astent-like structure 68. The stent-like structure 68
can be expanded atraumatically within a lumen of a renal artery so
as to support fiducials 64 against the tissue surface of the
surrounding luminal wall. Stent-like structure 68 can also be
radially contracted and withdrawn proximally after radiosurgical
treatment of the target region. The exemplary method illustrated in
FIGS. 6A-6C shows a series of fiducials 64 being deployed in a
non-colinear configuration in the renal artery 62. Such a
non-colinear configuration facilitates defining a three-dimensional
offset based on image data of the fiducials, with the exemplary
offset extending between the fiducials and the target region, the
target regions here represented by element 63, as seen in FIGS. 6B
and 6C.
[0090] Referring now to FIGS. 3 and 7, the time associated with
acquiring images 42 and planning treatments 44 may, taken together,
represent at least a significant portion of a day. The
radiosurgical treatments themselves 46 may likewise take a
significant amount of time, while the surgical implantation and
explantation of fiducials 70, 72 also involve some time. As it is
sometimes desirable to avoid leaving structures implanted in or
adjacent the renovascular tissues for more time than is necessary,
it may be beneficial to perform the fiducial implantation 70 and
fiducial explantation 72 on a radiosurgical treatment day 74, while
the imaging 42 and planning 44 are performed prior to the treatment
day. However, a result of this post-planning implantation of
fiducials 70 is that the fiducial images and locations may not be
available in the planning image data prior to the treatment day.
Note that, for this reason, post-planning fiducial implantation may
be contrary to standard radiosurgical treatment practice. Should
the planning and treatment extend over two days or longer, then
systemic low to medium dose anticoagulation (blood thinners) of the
patient may be utilized with an indwelling catheter in the arterial
system.
[0091] In light of the above, an exemplary treatment methodology 76
generally includes obtaining a planning image in the form of CT
data 42 without any artificial or implanted tracking fiducials.
Contrast agent will typically be used during the image acquisition
to facilitate identification of the blood-heart tissue surface, and
the planning image data may include a time series of
three-dimensional datasets, with each three-dimensional dataset
typically including a series of offset planar scans through the
heart tissue.
[0092] As described above, planning may be performed using a
general radiosurgical treatment plan module 78, along with a
specialized renovascular treatment plan module 80. The general plan
module 78 may be used during treatment of tumors and/or the
treatment of arrhythmia (as is detailed, for example, in U.S.
patent application Ser. No. 12/838,113, entitled Heart Treatment
Kit, System, and Method for Radiosurgically Alleviating Arrhythmia,
the contents of which are incorporated by reference herein in its
entirety), for example, to identify isocentric or other irradiation
target profiles in some of the planar CT slices of the planning
image. Radiation-sensitive collateral tissues may also be
identified in the planar CT scans, and based on this input the
general treatment planning module may generate a series of
radiation beams and associate dose information in the planes of the
CT scans. So as to facilitate treatment of hypertension with
tissue-surface based lesion patterns, renovascular tissue plan
module 80 may interface with (and take advantage of) the
capabilities of general plan module 78.
[0093] Renovascular tissue plan module 80, as with other
data-processing modules described herein, will typically comprise
computer processing hardware and/or software, with the software
typically being in the form of tangible media embodying
computer-readable instructions or code for implementing one, some,
or all of the associated method steps described herein. Suitable
tangible media may comprise a random access memory (RAM), a
read-only memory (ROM), a volatile memory, a non-volatile memory, a
flash memory, a magnetic recording media (such as a hard disk, a
floppy disk, or the like), an optical recording media (such as a
compact disk (CD), a digital video disk (DVD), a read-only compact
disk, a memory stick, or the like). The various modules described
herein may be implemented in a single processor board of a single
general purpose computer, or any one or more of the modules may run
on several different processor boards of multiple proprietary or
commercially available computer structures, with the code, data,
and signals being transmitted between the processor boards using a
bus, a network (such as an Ethernet, an Intranet, or an Internet),
via tangible recording media, using wireless telemetry, or the
like. The code may be written as a monolithic software program, but
will typically comprise a variety of separate subroutines and/or
programs handling differing functions in any of a wide variety of
software architectures, data processing arrangements, and the like.
Nonetheless, breaking the functionality of the program or hardware
into separate functional modules is useful for understanding the
capabilities of the various aspects of the invention.
[0094] Renovascular tissue plan module 80, as with other
data-processing modules described herein, may comprise
"programming." The term programming, as used herein, includes
hardware, software and firmware.
[0095] The exemplary renovascular tissue plan module 80 interfaces
with the Multiplan.TM. planning module of the CyberKnife.TM.
radiosurgical system or other system capable of delivering the
prescribed plan. Rather than inputting shapes onto the planar CT
scans, the user interface of the heart plan module 80 can define
lines and/or curves on the tissue surface, with the renovascular
tissue plan module identifying the associated shapes on the CT scan
planes. The renovascular tissue plan module also graphically
displays an estimated lesion of the heart tissue on a display of
either heart plan module 80 or radiosurgical plan module 78 (as
generally described above regarding FIG. 5.) This allows the
medical professional or professionals planning the patient's
treatment to verify that the lesion pattern is appropriate and
capable of producing the desired therapeutic benefits. An exemplary
renovascular tissue plan module 80 also simulates the effects of
gross misalignment between the patient and/or heart and the
radiosurgery treatment system 10 (with associated output to the
planning medical professional(s)), and/or provides output to the
planning medical professionals regarding tracking errors (for
example, in 6 degrees of freedom) on the estimated lesion location
and shape.
[0096] On a calendar day after plan 44 has been completed, and such
as on a treatment day 74, the patient will undergo surgical
implantation of the tracking surrogate or fiducial 70. In some
embodiments, as will be detailed below, the fiducial or fiducials
may be implanted the day prior to treatment being initiated, and/or
treatment may take place on more than one day (with fiducials
optionally being explanted and new fiducials being implanted
between treatments). Fiducials may be implanted by advancing a
distal end of a catheter through a blood vessel to a renal artery
or vein, with the distal end of the elongate flexible catheter body
coupling a high-contrast fiducial set to the renal artery tissue so
that the fiducial moves in correlation with the target tissue.
Exemplary coupling mechanisms include radially expandable balloons
or stent-like structures (optionally including helical coils,
braids, or the like) as described above regarding FIGS. 6A-6C.
These expandable bodies may be biased to expand radially when
released from a surrounding catheter sheath (such as by pulling the
sheath proximally from over the expandable body) or may be expanded
by introducing a fluid (typically a liquid such as saline or a gas
such as air) into an anterior of a balloon, shortening a length
between a proximal end and a distal end of the expandable body, or
the like. The expandable body will typically be configured to
contract radially such as by advancing a sheath over the expandable
body, emptying inflation fluid, pulling a filament of a helical
coil into a sheath, or the like. A wide variety of alternative
reversibly expandable structures are known in the stent field, and
many of these can be modified for use to temporarily affix a
surrogate to a tissue of the heart.
[0097] FIG. 7A schematically illustrates an alternative workflow
that may employ many aspects of the inventions described herein. In
the alternative treatment workflow 76', the fiducial implantation
70 may take place prior to acquiring a planning CT 42 or other
planning image. Following acquisition of the planning image, the
patient may return home for treatment on another day (so as to
allow treatment planning 44 to take at least a significant portion
of a day, the planning often taking one or more days to complete).
Tethered intraluminal surrogate systems (in which fiducials remain
tethered to an intraluminal access site by an elongate catheter
body) might optionally be temporarily implanted for more than one
day. Alternatively, it may be beneficial to instead employ
non-tethered intraluminal surrogate systems (in which temporarily
implanted and released fixation structures support the fiducials
within a lumen of the renovascular system, while no catheter body
extends between the vascular access site and the surrogate system).
Such a non-tethered fixation structures may be configured to
facilitate subsequent coupling of a catheter thereto and
endoluminal recapture and retrieval of the surrogate system during
fiducial explantation 72. Still further alternative embodiments of
workflow 76' may employ an in-patient and/or same day treatment
approach. For example, fidicial implantation 70, planning image
acquisition 42, treatment planning 44, alignment of the patient
with the treatment system 136, and treatment 46', and optionally
even explantation 72 may be coordinated so as to be completed
within one day, often with the patient remaining at the hospital or
other treatment facility throughout the treatment period. In
embodiments entailing remodeling a target region of the
renovascular system, the directed radiation is directed to the
target region with reference to the implanted surrogate(s). Related
alternative embodiments may extend beyond a single day to two or
three days (though typically less than a week), with at least
explantation 72 (and optionally the treatment itself) occurring two
days, or three days after the treatment, or within one week after
the treatment), often while the patient remains at the hospital or
other treatment site. Fiducial explantation 72 again typically
occurs at the end of the procedure. In alternate embodiments, the
surrogate(s) may be permanent implants. In this regard, the
surrogate(s) may remain implanted in the body of the patient for at
least a year or until dissolution, in the case of dissolving
surrogates.
[0098] It is noted that at least portions of the therapeutic
methods detailed herein, such as those related to FIGS. 3, 7, and
7A, may be repeated in a pattern having a standard or non-standard
period of months or years, and the therapeutic methods may be
intermixed with other therapeutic methods during the repetitions.
Such methods may be used to destroy at least some of the renal
nerves that grow back after the initial therapy to achieve
intermittent periodic blocking or re-down-regulation of renal nerve
activity. Indeed, such methods may include implanting permanent
surrogates that may remain implanted in the patient, and remain
clinically usable to practice the treatments detailed herein, for
about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 and/or 30 years, etc.
Accordingly, embodiments of the present invention may include a
treatment corresponding to those of FIG. 7 or 7A without the step
of fiducial explantation, followed by a treatment 0.5, 1, 1.5, 2,
2.5, 3, 3.5, 4, 4.5 and/or 30 years later corresponding to those of
FIG. 7 or 7A, except the step of fiducial implantation is not
executed in the latter treatment because the fiducials remain in
the patent in a usable condition.
[0099] Referring now to FIGS. 6D and 6E, an exemplary non-tethered
surrogate system can be understood. FIG. 6D shows a temporarily
implantable fixation structure comprising two opposed helical wires
coupled together. This exemplary non-tethered fixation structure
can be deployed and retrieved intraluminally using catheter
structures, and which can temporarily support one or more fiducials
during imaging, planning, and/or treatment. The fixation structure
of FIG. 6D may employ (or may be derived or modified from) a
structure developed for use as a vena cava filter by Crux
Biomedical Inc. of Menlo Park, Calif., and the fixation components
and use of this embodiment may be further understood with reference
to US Patent Publication No. 2008/0147111, published on Jun. 19,
2008 and entitled "Endoluminal Filter with Fixation," in the name
of Johnson et al. (application Ser. No. 11/969,827, filed Jan. 4,
2008), the full disclosure of which is incorporated herein by
reference. The methods and catheter structures used for deployment
of the structure of FIG. 6D (as well as the methods and catheter
structures used for recapture and retrieval) may also be understood
with reference to the '111 publication. As can be seen in FIGS. 6D
and 6E, for use with the radiosurgical treatment systems and
methods described herein, one or more enhanced contrast passive
fiducials may be affixed (directly or indirectly) to two opposed
outer helical wires or other filaments coupled together at their
ends, with the crossings and couplings of the wires defining frames
therebetween. Alternative embodiments may employ an active fiducial
affixed to the outer helical wires, with the active fiducial
optionally having a tether or being self-powered. The filter
filament elements shown in FIG. 6D extending between the outer
helical wires may be removed or omitted, or may remain in place in
some embodiments. The crossing helical wires may define two, three,
or more frames (as shown in FIG. 6E).
[0100] One or more two-frame temporary intraluminal fixation
structuresmay be implanted in the renal arteries and/or adjacent
the renal nerves to support non-collinear fiducials so as to
facilitate tracking of a moving tissue of the renovascular system,
such as the renal artery and/or the renal nerves. Anatomical
structures of the body may be identified for orientation. Target
regions may be tracked with the aid of a surrogate system having
multiple loops or frames temporarily implanted within a
renovascular structure or a structure adjacent a renovascular
structure. Prior to deployment, the non-tethered surrogate system
can be pre-loaded inside a delivery and/or guiding catheter. An
elongate flexible body (optionally a dilator) inside the guiding
catheter acts as a plunger to push out the surrogate system to be
indwelling inside a vessel. A custom delivery system can also be
used. Once the treatment is complete, a retrieval catheter such as
a snare can recapture and retrieve the indwelling surrogate system,
for example, by grabbing onto a protrusion or hood disposed at a
proximal end of the fixation structure (see FIG. 6D). The fixation
structure may optionally have anchors protruding radially from an
outer surface of the helical wires, similar to those provided on
the Crux.TM. IVC filter to provide better fixation to the vessel
walls. To deliver a fiducial system to the renal arteries, a
flow-directed balloon catheter similar to a Swan-Ganz catheter may
be used. Following this, a guide-wire can be inserted to the
delivery site. The guide-wire may also be twisted while the
flow-directed balloon is inflated to select a right or left renal
artery. The Swan-Ganz is then withdrawn while the guide-wire is in
place, and a catheter pre-loaded with the surrogate system is
advanced to the target site over the wire. The surrogate system is
deployed at the target site. The guide-wire and the delivery
catheter may be withdrawn, leaving the surrogate system behind.
Alternatively, a flow-directed balloon can be integrated with the
fiducial delivery system. Hence, the surrogate system may be
tethered and/or non-tethered (indwelling).
[0101] Referring now to FIGS. 6F-6K, additional alternative
fixation structures are illustrated. In the embodiment of FIG. 6F,
a helical stent-like fixation structure supports fiducials abutting
the walls of the blood vessel in which the fixation structure is
expanded, typically be releasing a helical filament structure from
within an associated sheath. In the embodiment of FIG. 6G, a
helical stent-like fixation structure includes a flow-directed
balloon near a distal end of the surrogate system and/or deployment
catheter to help guide advancement of the deployment catheter
downstream within a blood vessel. Once again, the fiducials will
abut the walls of the surrounding blood vessel, and the fiducials
may be separated along the helical length of the fixation structure
at regular or varying distances, for example, at every 1 cm. In the
embodiment of FIG. 6H, an axially series of expandable basket-like
structures are each defined by a circumferential series of flexible
members. A pull-wire allows a length of the basket like structures
to shortened and their diameter expanded in situ from outside the
patient. A flow-directed balloon at the distal end of the baskets
helps guide the catheter downstream, and the fiducials may remain
at the center of the blood vessel when the baskets are expanded by
mounting the fiducials along to the pull-wire or to another
structure that remains along the center of the baskets. FIGS. 6I
and 6J schematically illustrate a series of spoke and wheel
balloons (optionally referred to as cartwheel balloons) with an
optional flow-directed distal balloon to help guide distal
advancement of the deployment catheter downstream along a blood
vessel. Fiducials may again be mounted along a central portion of
one or more of the balloons. FIG. 6K schematically illustrates an
alternative expandable support structure comprising a braided tube
with a fiducial-supporting pull wire disposed along a center of a
braided tube. Shortening of the tube by pulling the pull wire
relative to the proximal end of the tube results in radial
expansion of the tube, with the fiducials remaining substantially
along the center of the blood vessel.
[0102] In yet other embodiments of the present invention, the
fiducials are gold seeds or seeds of a sufficiently detectable
material that are implanted into the recipient. Implantation of
such seeds may be accomplished via a catheter snaked through a
blood vessel, or via a more direct method, such as through the use
of a percutaneous needle. In some embodiments, the seeds are
substantially non-toxic seeds, with respect to the dosages used in
the methods herein, with an electron density visible on CT and/or
guidance imaging.
[0103] It is noted at this time that in many embodiments, the
fiducials are implanted such that the tissue to which they are
attached moves in a direction and with a speed substantially the
same as the movement of the renal artery, both do to respiration
and due to the heart cycle (blood pressure component and/or
displacement component of the cardiac cycle), including the
expansive-contractive movement of the renal artery due to
increasing and decreasing blood pressure. By way of example, in an
embodiment utilizing a stent to carry the fiducials, such as the
embodiment detailed above with respect to FIG. 6A, the stent is
configured to permit the fiducials to expand and contract with the
expansion and contraction of the inner wall of the renal artery
resulting from the heart cycle (blood pressure component of the
cardiac cycle).
[0104] FIGS. 8A-8C and 8E schematically illustrate still further
alternative catheter structures for deploying fiducials and
temporarily affixing the fiducials 64 to renovascular tissue T.
Catheters 86, 88, 90, 91 affix fiducials 64 to tissue T using a
helical screw 92 that can be screwed into tissue T by rotating the
catheter about its axis, with the exemplary helical screw being
similar in structure to helical cardiac pacemaker leads. Fiducials
64 are supported by resiliently or plastically flexible members,
allowing the fiducials to expand from the substantially linear
configuration with the surrounding sheath to a non-colinear
deployed configuration in engagement with the tissue T. The
non-colinear deployed configuration of fiducials 64 enhances the
accuracy with which a three-to-six-dimensional offset (shown
schematically by offset 94 in FIG. 8C) can be determined relative
to three-dimensional or bi-plane images of the fiducials. As the
target tissue may be identified using a three-to-six-dimensional
offset 94 from the fiducials during treatment, this may enhance
tracking accuracy. The resilient structure of catheter 91 is biased
to form an arc or lasso engaging a tissue intersecting helical
screw at least partially around the helical screw. FIG. 8E shows an
alternative fiducial deployment catheter 89 in which a deployable
cone 89a disposed at a distal end of the catheter can be
temporarily affixed to an endocardial tissue surface T by applying
a vacuum within the catheter using a vacuum source such as a
syringe 89b coupled to a proximal end of the catheter. A fiducial
catheter 89c can then positioned adjacent the distal end of
deployment catheter 89 by advancing the fiducial catheter distally
through a port 89e at the proximal end of the deployment catheter.
Additional monitoring or ablation devices may also be advanced
distally through the port, and deployment of the cone may be
effected from the proximal end of the deployment catheter using an
actuator 89f. Fiducials 89d may be mounted to or near the distal
end of fiducial catheter 89d.
[0105] A still further alternative catheter-based fiducial
structure which may be adapted for use in the present invention is
shown in FIG. 8D, and is described in more detail in U.S. Patent
Application 2008/0292054, entitled "Device for Measuring
Administered Dose in a Target" (the full disclosure of which is
incorporated herein by reference). While the exemplary embodiment
described in that reference comprises a urethral catheter for
facilitating treatment of prostate cancer, a similar structure
might be modified by inclusion of a helical screw 92 or stent-like
structure 68 as described above regarding FIGS. 8A-8C, 8E, and
FIGS. 6A-6C. Some embodiments may include the dose measurement
components of catheter 140 shown in FIG. 8D, although many other
embodiments will omit dose measurement capabilities. Regarding
exemplary catheter 140, that structure includes an elongate
flexible catheter body 141 provided with an electrical guide 142
and an electrical marker 143. The marker comprises a transmitter
T.sub.x used to determine the position of a target area in a
patient and in identification ID of the patient. The implant
further comprises a combined dose and identification unit 144
having a dose sensor 145 used to detect the amount of administered
dose in the target area and a dose identification Dose/ID.
[0106] The combined dose and identification unit 144 is provided
with a connector 146 that is arranged to be connected to electrical
guide 142, and can ensure the correct unit 144 is connected by
comparing the dose identification Dose/ID and the ID of the patient
in the electrical marker 143. The transmitter T.sub.x may be
powered through the combined dose and identification unit 144 so as
to verify position of the catheter 140, since movement of the
catheter (and tissue to which the catheter is attached), determine
an offset between a transmitter signal-based position of the
catheter and an image-based location of the catheter, and the like.
The combined dose and identification unit 144 is connected to an
externally arranged integrated circuit 147 through wires 148, and
the integrated circuit 147 includes the functionality associated
with dose conversion as more fully described in U.S. Patent
Publication 2008/0292054. Suitable alternative active fiducials
often rely on electromagnetic or ultrasound transmission to or from
the fiducial so as to identify a location of the fiducial
(independent of any imaging system obtaining an image of the
implanted fiducial with or without the surrounding tissue).
Suitable electromagnetic position sensing structures may be
commercially available from a variety of suppliers, including the
Carto AccuNav.TM. catheter available from Biosense Webster, the
various three-dimensional guidance tracker structures commercially
available from Ascension Technology Corporation of Vermont, the
ultrasound sensor and systems commercially available from
Sonometrics Corporation of Canada, the EnSite.TM. cardiac mapping
system from St. Jude Medical of St. Paul, Minn. and variations
thereof applicable to renovascular mapping, and the like. These
active fiducials send and/or receive signals indicating a position
of the fiducial, movement of the fiducial, and the like, with this
signal being used as an input into the processor of the
radiosurgical treatment system for tracking of the target
tissue.
[0107] The fiducials, fixation structures, and/or surrogate systems
described herein may be attached in and/or to a renal artery, as
well as in and/or to other tissue structures proximate the renal
arteries and/or the renal nerves. In other embodiments, the
surrogates can be attached to the walls of the renal vein, aorta,
inferior vena cava and/or a side branch of the aorta or vena cava.
Still further alternative embodiments may be employed, including
deployable or fixed annular rings supporting fiducials.
[0108] As the treatment plan will often have been developed before
the fiducial implantation (although, as detailed herein, the
treatment plan may be developed after fiducal implantation),
tracking of the target tissue will be easier once the location of
the fiducial relative to the planned target has been identified. A
process for registration a treatment plan with implanted passive
and/or active fiducials can be understood with reference to FIGS.
7, 10, and 11. As a starting point, a treatment plan 104 may have a
known positional relationship 106 with planning image data 108
(these elements being shown schematically in FIG. 10). Relationship
106 can be established by inputting the desired lesion pattern
relative to an image generated using the planning image data, as
described above. So as to identify a location of fiducials 64
relative to the treatment plan 104, registration image data 110 may
be acquired after fiducial implantation 70. Registration image data
110 will typically comprise three-dimensional image data
encompassing both the renal artery tissue tissue and at least some
of the implanted fiducials, particularly the passive high-contrast
fiducial marker structures. Identification of tissue surfaces and
the like may again be facilitated by releasing contrast in the
bloodstream. This facilitates segmenting the renal artery tissue
tissue surface and the heart/blood interface. The tissue/blood
interface from registration image data 110 and planning image data
108 may be used to identify a relationship 112 between the plan
image data set and the registration image dataset. The exemplary
relationship 112 may comprise a mapping or transformation, ideally
comprising a transformation matrix, offset, or the like. Rather
than relying on the blood/tissue interface, alternative
image/registration relationships 112 may be determined by
identifying a series of discrete tissue landmarks. Note that the
renovascular tissue may move significantly between acquisition of
the planning image data set 108 and the acquisition of the
registration dataset 110 relative to anatomical landmarks outside
the renovascular system, and that the shape of the renal arteries
may be deformed (even at similar phases of the beat cycle). Hence,
while embodiments of the invention may employ a simple rigid
transformation as the plan/registration image relationship 112,
other embodiments may employ any of a variety of deformable
registration techniques.
[0109] So as to facilitate identification of the plan/registration
image relationship 112, registration image dataset 110 may be
acquired using an image modality which is the same as that used to
acquire planning image dataset 108. For example, where the planning
image dataset comprises CT data, registration image dataset 110 may
also comprise CT data. Alternatively, if MRI data has been used for
the planning image dataset 108, MRI acquisition after fiducial
implantation may be used for the registration image dataset 110.
Similarly, if the planning image dataset 108 comprises ultraound
data, the registration image dataset 110 may also comprise
ultrasound data. Nonetheless, other embodiments may employ a
different image modality to acquire the registration image dataset
than that used for acquisition of the planning image dataset. Any
of a wide variety of three-dimensional image data fusion,
three-dimensional rigid transformation, and/or three-dimensional
deformable transformation techniques may be used despite the
application of different imaging modalities.
[0110] In exemplary embodiments, the registration image data 110
may include at least one component of an active fiducial system.
For example, FIGS. 9A, 9B, and 10 illustrate a method and system
for registering a catheter tip with a three-dimensional image
dataset (such as CT data) with high absolute accuracy. Standard
active catheter navigation systems may suffer from geometric
distortion due to either magnetic field inhomogeneities or
assumptions in electrical impedance. Analogous errors may be
present in ultrasound or other navigation systems. While these
tracking technologies provide good relative position measurements
with respect to, for example, an image-able electrode in the
coronary sinus, their absolute accuracy may not be as good as is
desirable for radiosurgical treatments from outside the body.
[0111] FIGS. 9A and 9B schematically illustrate a transmitter 122
of an active fiducial catheter navigation system, with the
exemplary transmitter shaped as a cube. The active fiducial may
comprise a sensor disposed near the distal end of the catheter that
senses the location of the position fiducial. The reference
coordinate system of the active fiducial may be positioned at a
corner of the cube-shaped transmitter 122. Alternative systems may
replace this external transmitter with an external sensor, with the
active fiducial comprising an associated transmitter. Regardless,
the patient may lie on a patient support 124, and the patient
support may also support the external active fiducial sensor 122 or
transmitter. In some embodiments, the patient support 124 may
comprise a vacuum bag or other structure so as to inhibit movement
of the patient relative to the patient support, and the patient
support may be movable (with the patient and the component of the
navigation system mounted thereon).
[0112] The movable patient support 124, active fiducial transmitter
122, and patient are positioned for imaging, such as by being
placed on a couch of a CT scanner 126. As a result, the
registration image dataset (an image of which 128 is conceptually
shown in FIG. 9B, the image being different with respect to the
renovascular treatments detailed herein) contains the transmitter
cube 122, such that the transmitter cube is visible in the CT
dataset along with the patient's tissue and any other implanted
fiducials.
[0113] In some embodiments, the patient support 124 and patient may
be moved to a radiosurgery suite and placed on a platform, with the
vacuum bag of the patient support 124 inhibiting movement of the
patient relative to transmitter 122. A catheter having the active
fiducial position sensor may be introduced into the patient and
advanced to the desired location, allowing the active fiducial
navigation system to determine position data from the active
fiducial. As the position of the sensor 122 in the CT dataset is
known, and location and orientation of the active fiducial
navigation system is also known, and an active fiducial marker can
be superimposed on the CT image dataset location identified by the
navigation system of the active fiducial. Hence, a relationship
between the active fiducial 130 and the tissue, passive fiducials,
and treatment plan 104 may also be identified (see FIG. 10). By
correlating the active fiducial position information with the phase
of the heart, and by knowing a relationship of the target region to
the active fiducial location throughout the heartbeat cycle (as can
be determined from the time series of three-dimensional datasets in
the planning image data), the active fiducial data signal may
enhance tracking of the target region. This may be done for the
blood pressure component and/or the displacement component of the
cardiac cycle.
[0114] As a result of the registration step 102, the
three-dimensional position offset (or transformation matrix or
matrices) between the fiducials and the treatment plan may be
determined, so that the fiducials are effectively registered with
the treatment plan 132.
[0115] Referring now to FIG. 9C, a block diagram of an exemplary
calibration module 200 indicates an alternative system and approach
for helping to register the patient tissue with a treatment plan,
and/or for helping to align the patient with the radiosurgical
treatment system. Calibration can, for example, be performed prior
to delivering a treatment either before the patient is present on
the patient support 24 or once the patient is on the patient
support 24 of the radiosurgical system 10. Calibration can
determine the mapping function, .phi., between a coordinate system
of an active fiducial system (such as a tracking coordinate system
of an Ascension Technology Corp. 3D tracking system) and a
coordinate system of radiosurgical system 10 (such as a
CyberKnife.TM. radiosurgical robot coordinate system):
.sup.CKp=.PHI.(.sup.ASp) Eq. 1
where, .sup.CKp is a point in robot coordinate system and .sup.ASp
is the same point in the active fiducial tracking coordinate
system. The mapping function .phi. can be determined, for example,
by moving an active fiducial (typically in the form of one or more
position sensors) to a series of locations, ideally to a series of
grid points inside a volume of interest. The grid points and/or
volume of interest may be centered at or near an isocenter of the
planned treatment and/or of the robot 14 supporting the linear
accelerator 12 (or other radiation source). When using the
exemplary CyberKnife radiosurgical treatment system, the treatment
isocenter may be a point in the CyberKnife room where the axes of
the two ceiling-mounted tracking cameras intersect. This may also
be used as the origin of the CyberKnife coordinate system. The
movement of the active fiducial between the locations or grid
points may be performed using a motion platform .OMEGA. robot 202
(a separate robot manipulator for mechanically moving the active
fiducials in an near the treatment site), and locations of the
active fiducials may be sensed and recorded by the tracking module
206 based on both the active fiducial tracking system 204 and also
the image tracking system 16 (such as the CyberKnife.TM. X-ray
system). A least squares fit between the image tracking-based
positions and the active fiducial-based positions can be used by
the calibration module 206 to find the best-matching mapping
function, .phi..
[0116] A Calibrator 208 is a component of calibration module 206.
Calibrator 208 will interact with a server application running on
the radiosurgical system, called CHServer. CHServer will serve some
requests from Calibrator 208, by communicating via an Ethernet.
Calibrator 208 is also connected to the active fiducial motion
platform, .OMEGA.Robot 202, and the active fiducial tracking system
204, both via USB. Calibrator 208 may:
[0117] Instruct the .OMEGA. .quadrature.Robot to move the sensors
to a specified location
[0118] Instruct the image tracking system 16 of the radiosurgical
system to acquire a pair of X-rays.
[0119] Capture active fiducial sensor coordinates for the present
location
[0120] Download the X-rays via CHServer.
[0121] Repeat steps 1-4 until all grid points or otherwise desired
locations have been visited. Once the data from all grid points
have been captured, Calibrator 208 will compute the mapping
function, .phi., and store it in a file.
[0122] Referring now to FIGS. 7, 12, and 1, alignment 136 of the
target regions of the tissue with the robot 14 will generally be
performed by having the patient supported by patient support 24,
and by moving the patient support using the articulated patient
support system 26 so that the fiducials (as seen in the bi-plane
X-ray images of image guidance system 16) are disposed at the
desired location, such that the target regions of the treatment
plan are aligned with the planned trajectories from linear
accelerator 12. Hence, although the fiducials have in fact been
implanted after the treatment plan was completed, the alignment
process may proceed with reference to superimposed fiducial
locations on the planning treatment data, with the alignment
process, as it appears to the medical personnel performing the
radiosurgical treatment, being quite similar to that applied when a
pre-planning fiducial is used.
[0123] Referring now to FIGS. 7 and 13, the treatment 46 and
tracking of the target tissues by the robot and linear accelerator
can be generally understood. The aligned treatment plan 152
(including the planned trajectories and the superimposed fiducials,
once they have been appropriately aligned with the robot 14 as
described above with reference to FIG. 12) defines appropriate
trajectories and beams of radiation from linear accelerator 12. As
with known radiosurgical treatments, an offset is determined to
compensate for the breathing cycle 154, with the breathing offset
generally being determined from the respiration amplitude as
identified using surface images of the patient, and specifically
from external LEDs mounted on the patient's skin 156. Intermittent
bi-plane X-ray data 158 can be used to revise and correct the
breathing motion offset for any patient movement or the like.
[0124] A heart cycle offset 160 may also be applied to the
treatment plan 152, with the phase of the heart cycle offset being
identified by an EKG sensor 162 or other heart cycle monitor
coupled to the patient. The heart cycle may be used to determine a
renal artery movement cycle, due to the blood pressure component
and/or the displacement component of the cardiac cycle. That is,
the beating of the heart will result in a corresponding movement of
the renal artery, such as due to an expansion of the outer diameter
of the renal artery resulting from the increased pressure of the
blood within the renal artery, and/or displacement of the entire
renal artery. The heart cycle can be temporally correlated with the
renal artery movement cycle or used as a direct proxy for the renal
artery cycle. For example, movement of the renal artery may
temporally lag behind a heartbeat indicator on which the treatment
relies (movement due to the blood pressure component of the cardiac
cycle may lag the displacement component of the cardiac cycle, or
visa-versa, and one or both may lag the heartbeat indicator). This
temporal lag may be exact or estimated, and factored into the heart
cycle offset 160. Alternatively, in other embodiments, the heart
cycle may be used without factoring in such a temporal lag. That
is, the heart cycle may be used to directly determine the time of
movement of a renal artery. Data or signals from the active
fiducial 164 may also be used to identify the phase of renal artery
motion, as well as providing an appropriate renal artery motion
offset. The renal artery motion offset may, as explained above, be
identified from the time series of three-dimensional datasets
included in the treatment plan 152. Alternatively, the EKG sensor
signals 162 and/or active fiducial signals 164 may be used for
gating of the radiation beams, such that the radiation beams are
only directed toward the renovascular tissue at portions of the
renal artery motion cycle during which the target regions are
sufficiently aligned with the plan 152. Note that some portion of
the movement of the renovascular tissue located at the target
regions may be disregarded, for example, with internal deformation
of the tissue between the fiducials and the target regions being
disregarded in favor of a fixed offset, with motions in one or more
orientations having a sufficiently limited amplitude being
disregarded, or the like. Regardless, once the appropriate offsets
have been applied to the treatment plan, the robotic radiation beam
targeting 166 can then be applied.
[0125] Referring now to FIG. 12A, a tracking module 210 using
components and techniques related to those of FIG. 9C can now be
understood. For convenience, we can here assume that the alignment
center in the planning CT data is disposed at a center of gravity
of the fiducials. As this will often not be the case, offsets
between the planning data and fiducial centers will typically be
included. Tracking module 210 includes software run on a
renovascular tracking computer RVTS during treatment delivery. The
alignment module 206 may similarly run on the renovascular tracking
computer RVTS, with the tracking module and alignment module
comprising code running on a personal computer (PC) in the
exemplary embodiment. The tracking module 210 receives as input the
position data 212 from all the active fiducial sensors (such as the
Ascension sensors) of the implanted catheter system via USB.
Tracking module 210 applies the calibration map 214, .phi., to this
active fiducial data to compute the active fiducial locations in
the coordinate system of the radiosurgical system (such as in
CyberKnife.TM. coordinates). From this, the position data flows
into 3 different paths: an Aligner 216, a Tracker 218, and a
Visualizer 220.
[0126] Aligner 216 makes use of the data from the active fiducials
to alter alignment of the patient with the radiosurgical system.
More specifically, the active fiducial sensor data can be matched
in aligner module block [4] to the fiducial coordinates from the
planning CT data (specified in radiosurcial system coordinates) to
determine the couch corrections. The average couch correction over
a specified period can be computed and displayed to the user. The
user can then apply these couch corrections and observe how couch
corrections change in real-time. The block [5] may display the
couch corrections to the user in a graphical form, computed as
running averages.
[0127] Tracker 218 may include a tracker module block [6]
configured to compute the target location from the incoming active
fiducial locations. After alignment the alignment center of the
patient, as defined in the planning CT coordinate system, coincides
with the iso-center of the radiosurgical treatment system. If there
is no motion, the output of block [6] might be (0, 0, 0). If there
is motion, the output of block [6] might be the change in position
from the initial or ideal position. A tracker module block [7] may
remove the renovascular tissue motion from the target motion. The
resulting `respiration only` change-from-ideal motion waveform can
be sent to a position predictor of the radiosurgical treatment
system processor, which can apply this information per a standard
data path to drive the robot.
[0128] The active fiducial data may be provided to visualizer 220,
which may display the fiducial locations superimposed on CT data,
optionally using display module components of the planning module.
This may allow the system user to visualize the locations of the
active fiducials after they have been implanted, and the like. In
addition, the visualizer may display the treatment beams fired by
the robot in real time using the position data measured using the
active position sensor.
[0129] As can be understood from the above, patient movement may
complicate radiation treatment of the renovascular system. If
patient movement is not tracked, targeting can direct the beams
into a time average location of the target. If a surrogate and
target are rigidly coupled together and tracking of the surrogate
is accurately maintained, targeting is not compromised. However,
when the surrogate is offset from the target and the tissue in
which the target and surrogate are disposed deform, and if the
deformation between the surrogate and target are not tracked, a
single imaging phase can be used to calculate the relative location
of the surrogate and target. Selection of the appropriate imaging
phase (from among the time series of phases at which
three-dimensional imaging is acquired) can affect the accuracy of
targeting. For example, if a calculation of the relative locations
is performed for a phase where the surrogate to target offset is
not close to the average offset throughout the heartbeat cycle,
targeting based on an average surrogate location may result in dose
delivery being offset from the target.
[0130] One relatively simple approach to accommodate untracked
motion is to use an integration of the target volume so that the
target is expanded to include the target region location throughout
all phases of the target region motion (including throughout a
heartbeat cycle and/or respiration cycle). Such an integrated
target can ensure treatment of the target region but may increase
the total treatment volume receiving relatively high doses of
radiation. Alternative pursuit tracking approaches (similar to
those used in the Accuray Synchrony.TM. tracking system) where the
radiation beams move synchronously with the target tissue can be
used in order to deliver dose to the target region. These existing
approaches may not consider motion of radiation sensitive
collateral tissues, nor motion of the surrogate relative to the
target region. Gating of the radiation beam to untracked motion can
also be employed, but may increase the total time to provide a
sufficient dose to the target region.
[0131] In an exemplary alternative untracked treatment approach,
the tissue may be analyzed as being subjected to the dose that is
integrated across an untracked tissue motion. The peak dose may be
delivered to the average position with some alteration of the dose
distribution in areas where the dose gradient is changing in the
direction of motion. For motions which are relatively small
relative to the rate of change of the dose gradient, the dose
distribution may only be slightly altered by the untracked motion.
The more significant change between the intended dose and that
actually applied to tissue may be imposed by any shift of the peak
dose from its planned anatomical locations.
[0132] In this exemplary targeting approach in the presence of
untracked motion, imaging of the tracking surrogate may be used to
direct the radiation beams. If only a single image of the tracking
surrogate is obtained there will be targeting errors resulting from
the untracked motion, so that intermittent acquisition of images
allow the location data to be combined so as to determine future
beam directions, potentially by averaging so as to better locate
the tracking surrogate. This approach may result in the beams being
directed relative to the average location of the tracking surrogate
relative to the target region. If the plan has been created based
on this same average relative positioning, the peak dose location
should correspond to the planned target region.
[0133] In light of the above, and as can be understood with
reference to FIGS. 14A-14E, targeting accuracy can be enhanced in
the presence of untracked motion by analysis of a time average
location of the target relative to the tracking surrogate
throughout renovascular and/or respiratory motion. One relatively
simple method is to use this time average relative location during
planning by selecting the phase where the tracking surrogate is
nearest to its average relative location. Note that the precise
location of the surrogate may not be known during planning, but the
target structure adjacent or in the renovascular system
corresponding to the target locations for fiducial implantation may
be identified, so that the surrogate may be targeted for deployment
at or near a location appropriate for the planned average offset.
The planning phase can be chosen based on the average location of
the target surrogate location relative to the target structure
location.
[0134] Note that no discrete phase, as selected from the time
series of three-dimensional planning datasets, may correspond
exactly to the time average location. Some targeting error may
remain because of this difference. Additionally, the average
location of the tracking surrogate may not correspond to the
average configuration of the target relative to the tracking
surrogate. A somewhat more accurate solution may be to consider the
time average relationship between the surrogate and the target. As
shown in FIGS. 14A-D, this time average may not correspond to any
particular phase in the captured time series. Nonetheless, it may
be convenient and beneficial to select the closest phase to the
calculated time average.
[0135] Addressing FIGS. 14A-D an example of two-dimensional
relative motion between a tracking surrogate (represented by the
filled circle) and the target (represented by the open circle).
FIGS. 14A-D show the location of the target and circuit relative to
a reference frame in four phases of cyclical renovascular tissue
motion. Both the surrogate and the target move relative to the
reference frame, but the target also moves relative to the
surrogate.
[0136] In FIG. 14E, a calculated average target center may provide
accuracy advantages. The relationship between the average target
center and the tracking surrogate does not necessarily match any of
the discrete images of FIGS. 14A-D, but instead the configuration
corresponds to an average separation between the objects.
[0137] In many radiosurgical systems, a CT volume set is used to
create digitally reconstructed radiographs (DRRs). During
treatment, guidance images are matched to these DRRs in order to
align the patient. A DRR can conveniently be constructed from any
one of the datasets for a particular phase of the time series.
Hence, the target itself may be somewhat difficult to identify in
the DRR, which provides motivation for use of a tracking surrogate.
The offsets used to target the beams can, nonetheless, be based on
the average target location of a DRR generated from a selected
phase which most nearly matches the time average relationship.
Alternatively, the relative location of the target and offset may
use a calculated time average without relying on the DRR, so that
the target location of the target in the CT volume may not
correspond to a particular DRR. For example, if you have fiducial
coordinates f(k,t), then the distances linking the fiducials are: d
(k,m,t)=|f(k,t)-f(m-t)|. There will be
M = N 2 ( N - 1 ) ##EQU00001##
such link distances between fiducials, where N is the number of
fiducials. The link distances can be represented as: {d(k,m,t)},
which is a M dimensional vector. Then the time average distances
can be computed as: {{circumflex over (d)}(k,m)}. Then compute the
vector distance:
.DELTA. ( t ) = .A-inverted. N 2 ( N - 1 ) values ( d ( k , m , t )
- d ( k , m ) ) 2 . ##EQU00002##
Then pick the phase corresponding to the smallest .DELTA.(t)
[0138] Referring now to FIG. 15, a kit of components will
facilitate radiosurgical treatments using the systems and methods
described herein. These and/or other components may be included in
one or more hermetically sealed packages 170, along with
instructions for use 172 of the enclosed components and/or the
system in general. An exemplary embodiment of the kit will include
some or all disposable items used during insertion of a
percutaneous catheter into a recipient to treat hypertension as
detailed herein. The catheter 174 will generally have an elongate
flexible body 176 extending between a proximal end 178 and a distal
end 180. A sheath 182 may have a lumen receiving the catheter body
176, the sheath optionally restraining fiducials in a small profile
configuration suitable for insertion and positioning, and the
sheath optionally also enclosing a helical or radially expandable
fixation structure as described above. Proximal hubs 184, 186 of
the sheath and catheter may allow the sheath to be withdrawn
proximally from over the catheter body 176, optionally using a
rapid exchange approach. Similarly, the catheter may have a rapid
exchange guidewire lumen for receiving a guidewire 190, or may have
a through lumen for using the catheter in an over-the-wire
approach. Furthermore, the catheter may have a flow-directed
balloon at the distal end, which will facilitate rapid deployment
of the catheter downstream into a target site. While the catheter
may be inserted prior to the planning image acquisition and
throughout the radiation treatment, the catheter will typically be
deployed on a treatment day after image acquisition and treatment
planning is complete.
[0139] As described above, the catheter can include passive
fiducials which include high-contrast markers that can be readily
visualized during radiosurgical treatments so as to provide a
passive surrogate. Alternatively, catheter 174 may include an
active fiducial which transmits or receives signals electronically,
ultrasonically, electromagnetically, radioactively, or the like so
as to indicate a position of the catheter (and via a known
relationship between a position of the catheter and the target
region, thereby indicating a position of the target). Passive
fiducials may comprise, for example, small metallic structures
comprising gold, platinum, iridium, and/or tantallum, or the like.
The catheter may also include sensors for measuring the dose
received during treatment, blood pressure, and other biometric
signals.
[0140] Reviewing some exemplary components included within one or
more sterile packages 170, the kit may include an iodine or other
skin cleansing lotion 192, a vial of 1% xylocalne, or the like.
These materials may be used to create an anesthetic skin wheal at
the site of skin puncture. An introducer sheath 194 may include at
least one or possibly two side ports so as to allow for blood
withdrawal, infusion of multiple simultaneous drugs, and other
intravenous maintenance solution transmission. Exemplary introducer
sheath 194 has two ports or channels so as to allow two catheters
to be positioned simultaneously. A rubber diaphragm may be found at
the entrance of each port, with an exemplary introducer having a 3
mm cotton tubular cuff that is impregnated with a compound
comprising silver can be advanced to the site of skin puncture
along a sheath of the introducer for use as a bacteriostatic.
[0141] A needle 196 allows, when used in combination with guidewire
190 and sheath 194, venous cannulation and secure positioning of
catheter 174. A set of EKG electrodes 198 allows for tracking of
cardiac rhythms, while a set of LEDs or gold fiducials (or
fiducials of an alternatively acceptable material) may be mounted
to the chest wall for monitoring respiration. A conductor may
extend along catheter body 176 so as to couple a helical fixation
lead or other conductive distal structure to engage the
renovascular tissue with a proximal connector of proximal hub 186.
This may allow the fixation lead or other conductive structure at
the distal end of the catheter to be used as a heart signal
electrode for monitoring the heartbeat, alone or in addition to the
other EKG electrodes. The kit package 170 may also include a
patient mattress, which may be a mattress configured to limit
changes in patient position such as a vacuum bag mattress, with the
vacuum bag optionally having a vacuum port and/or containing
discrete pellets so as to reconfiguring and affixing of a shape of
the bag once the patient has been comfortably positioned on the
patient support.
[0142] In use or during deployment of the catheter-based fiducial
system, needle 196 (such as a 20-gauge locator needle) may be used
to identify an internal jugular vein, subclavian or brachial vein,
or other vein as necessary. Alternatively, and artery may be
identified. A 14-gauge needle (not shown) also to be included in
the kit and within package 170 may then be inserted and wire 190
placed through the inserted needle, with the needle then being
withdrawn. The skin may be incised with a roughly 2 mm incision at
the wire insertion site, and a dilator used (optionally at the
distal end of insertion sheath 194) to enlarge the tissue track. A
distal end 180 of catheter 174 may then be inserted over the
needle, with the position of the distal end of the catheter being
checked using X-ray or fluoroscopic guidance. The fixation
structure near the distal end 180 of catheter 174 may be exposed by
proximally withdrawing sheath 182 from over catheter body 176, and
the distal end affixed to a target tissue of the renovascular
system. Proximal hub 186 of catheter 174 may then be sutured or
otherwise affixed to the skin of the patient.
[0143] Using fluoroscopic or ultrasound guidance, an alternative
affixation approach may comprise deployment of a polyethylene cone
from a small profile configuration to a large profile configuration
at distal end 180 of catheter 184, as described above regarding
FIG. 8F. The cone may be deployed by sliding a switch on the side
of the proximal portion of the catheter. A vacuum may be applied to
an open end of the cone, optionally using a 10 or 20 cc syringe or
the like. A stopcock may be closed to maintain the vacuum, and the
syringe removed. In some embodiments, the cone may be affixed via
suction to an appropriate surface.
[0144] Optionally, a detecting, pacing, or ablating electrode can
be placed through a port of catheter hub 186 or through introducer
sheath 194. If an active fiducial or surrogate is used,
communication between the navigation system and robotic control
system may be confirmed.
[0145] Some or all embodiments detailed herein and variations
thereof may be practiced to achieve resolution of fluid overload
with respect to conjunctive heart failure by induction or
enhancement of diuresis, reduction of remodeling after a myocardial
infarct and slowing of the progression of chronic renal disease to
dialysis. Some or all of the therapeutic effects detailed herein
may be a result of one or more of the reduction of the systemic
sympathetic tone causing vasoconstriction of blood vessels,
reduction of the load on the heart and/or the direct effects of
denervation on the kidney(s).
Experiments
[0146] An animal experiment was conducted to record the motion of
the renal artery as a target for radiosurgery in order to affect
the sympathetic nerve and reduce hypertension. For this experiment,
an expanding helical structure with three fiducials was placed in
the inferior vena cava of a pig model through a femoral vein
sheath, with the expanding structure similar to that shown in FIGS.
6C and 6D, and modified from a vascular filter structure developed
by Crux Biomedical Inc of California. Separately, gold beads were
surgically attached to the right renal artery and to a location
near the left renal artery. Three cardiac gated CT's were acquired
with these fiducials implanted: at exhale; at inhale; and at exhale
where the blood pressure had been increased medically. An analysis
of the CT data was made based on these experiments.
[0147] The five targets (two surgical fiducials and three fiducials
on the Crux device) showed very little cardiac motion. The
amplitude of cardiac motion of all of the fiducials was less than
0.5 mm. This amount of motion may optionally be treated as
negligible during radiosurgical treatment--including for high-blood
pressure conditions.
[0148] Comparing the locations measured for inhale and exhale
showed movements of 5-7 mm with respiration. This motion may be
compensated for (for example, using the Synchrony.TM. tracking
system of the Cyberknife.TM. radiosurgical treatment system) for
desired accuracy in radiosurgical treatment. The use of spine
alignment may be an alternative but may involve margins of 3-7 mm
to achieve a therapeutic result, and such margins will often be
larger than is ideal.
[0149] The respiratory motion of the Crux fiducials were very
similar to the motion of the sutured fiducials. The relative motion
between the right renal artery fiducial and the average of the Crux
fiducials was 1.6 mm. The relative motion between the left fiducial
and the average of the Crux fiducials was much less--0.2 mm. A
margin of 2 mm may be considered if a Crux device were used for
targeting. This margin is likely manageable.
[0150] As shown in FIGS. 16A and 16B, the Crux fiducials were in
close proximity to the surgically placed fiducials. The right
surgically placed fiducial was placed on the right renal artery but
surgical placement of the left fiducial very near the left renal
artery was more challenging, so that the left surgically placed
fiducial was separated somewhat from the left renal artery as
shown.
[0151] The positions of the central Crux fiducial for ten cardiac
phases (5%, 15%, 25%, . . . 95%) at inhale are shown in Table 1.
More specifically, Table 1 provides the measured fiducial center of
gravity, showing the largest amount of cardiac motion (which was
the central Crux fiducial measured at inhale). These distances are
expressed in mm using CT coordinates.
[0152] This measurement showed more motion than any of the other
fiducials and any of the other CT sets. Although the variation in
location appears to be measureable, it is clearly negligible for
radiosurgery.
TABLE-US-00001 TABLE 1 Fiducial center of gravity: (phase, x, y, z)
0 -0.334879 33.0463 -448.703 1 -0.332905 33.0451 -448.706 2
-0.247289 33.0463 -449.25 3 -0.249885 32.9588 -448.707 4 -0.202549
33.0023 -448.586 5 -0.287425 33.0036 -448.661 6 -0.247289 33.0458
-448.91 7 -0.250808 33.046 -448.919 8 -0.292489 33.0015 -448.753 9
-0.292446 33.0012 -448.752 Mean center of gravity: -0.273796
33.0197 -448.795
[0153] The positions of each of the fiducials in phase 0 (5% R-R)
were compared between the inhale and exhale CT sets. Table 2 shows
respiratory motion of each fiducial (top) and the relative motion
between the sutured fiducials and the Crux fiducials (bottom). All
distances are presented in mm using standard CT coordinates. As
shown in Table 2, respiratory motion of 5-7 mm was measured for all
of the fiducials.
TABLE-US-00002 TABLE 1 Motion (Exhale-Inhale) Fiducial CT X CT Y C
T Z Mag(mm) Rt. Renal Artery 0.6487 0.5921 4.787 4.866905 Lt. Renal
Artery -0.577 0.811 6.322 6.39987 Superior Crux -0.3042 0.805 7.051
7.103321 Center Crux -0.029 0.352 6.12 6.130183 Inferior Crux -0.2
1.959 5.008 5.38124 Rt. Renal - mean(crux) 0.826 -0.446 -1.272
1.582 Left Renal - mean(crux) -0.399 -0.227 0.262 0.529
[0154] The motion of each of the surgically placed fiducials was
compared to the average of the Crux device fiducial motions. The
Crux device positions were averaged because it may be desirable,
when using commercially available systems such as the
CyberKnife.TM. radiosurgical system, to use multiple Crux fiducial
implants and/or multiple fiducials on a single Crux implant, and
because the CyberKnife and other systems may track the center of
mass of all fiducials that the system locates. The magnitude of the
difference in motion was 1.6 mm. This relative motion may degrade
the targeting accuracy slightly if the Crux were used for
targeting, so that 1.6 mm could be added to the margins (of either
the target contours or the critical structure contours) in order to
use the Crux device as a fiducial and provide the therapeutic
result that is desired.
[0155] Based on the motion measurements made in the abdomen,
radiosurgical treatment of the renal artery may use tracking to
compensate for respiratory motion, without tracking of
heartbeat-induced motion of the renal arteries. A temporary
fiducial in the inferior vena cava will be sufficient for targeting
the nerves near the renal arteries.
[0156] While the exemplary embodiments have been described in some
detail for clarity of understanding and by way of example, a number
of changes, modifications, and adaptations may be obvious to those
of skill in the art. Hence, the scope of the present invention is
limited solely by the appended claims.
* * * * *