U.S. patent application number 15/382949 was filed with the patent office on 2017-04-20 for catheter device including flow sensing.
The applicant listed for this patent is MC10, Inc.. Invention is credited to Roozbeh Ghaffari, Yung-Yu Hsu, Lauren E. Klinker, Stephen P. Lee, Clifford Liu, Fernando Quivira, John Work.
Application Number | 20170105795 15/382949 |
Document ID | / |
Family ID | 49879081 |
Filed Date | 2017-04-20 |
United States Patent
Application |
20170105795 |
Kind Code |
A1 |
Lee; Stephen P. ; et
al. |
April 20, 2017 |
CATHETER DEVICE INCLUDING FLOW SENSING
Abstract
Devices and methods are provided for performing an ablation
procedure on tissue with flow monitoring using flow sensors. The
devices include a catheter, and at least one flow sensor disposed
on the catheter, and a component for applying the ablation
procedure. An assessment module provides an indication of the
efficacy of the ablation procedure based on the flow measurement
from the flow sensor.
Inventors: |
Lee; Stephen P.; (Ann Arbor,
MI) ; Liu; Clifford; (Randolph, MA) ;
Ghaffari; Roozbeh; (Cambridge, MA) ; Work; John;
(South Dennis, MA) ; Quivira; Fernando;
(Somerville, MA) ; Klinker; Lauren E.; (Cambridge,
MA) ; Hsu; Yung-Yu; (San Jose, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
MC10, Inc. |
Lexington |
MA |
US |
|
|
Family ID: |
49879081 |
Appl. No.: |
15/382949 |
Filed: |
December 19, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14874148 |
Oct 2, 2015 |
9554850 |
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15382949 |
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13844677 |
Mar 15, 2013 |
9168094 |
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14874148 |
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61668338 |
Jul 5, 2012 |
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61728653 |
Nov 20, 2012 |
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61733575 |
Dec 5, 2012 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 2018/0022 20130101;
A61B 2018/00541 20130101; A61B 2018/00577 20130101; A61B 2018/00821
20130101; A61B 2018/0212 20130101; A61B 18/02 20130101; A61B
2018/00678 20130101; A61B 2018/00815 20130101; A61B 2018/00404
20130101; A61B 2018/00386 20130101; A61B 2018/00708 20130101; A61B
18/20 20130101; A61B 18/06 20130101; A61B 2018/00863 20130101; A61B
2018/00434 20130101; A61N 7/02 20130101; A61B 18/1815 20130101;
A61B 2018/00375 20130101; A61B 18/1492 20130101; A61B 2018/00511
20130101; A61B 2018/00791 20130101; A61B 2018/2244 20130101; A61N
1/36117 20130101; A61B 2090/065 20160201; A61B 2018/206 20130101;
A61B 2018/00267 20130101; A61B 2018/00041 20130101; A61N 1/36017
20130101; A61B 2018/00666 20130101; A61B 2018/1861 20130101; A61B
2018/00178 20130101; A61N 1/0551 20130101; A61B 90/30 20160201;
A61B 2018/20361 20170501; A61B 2018/00273 20130101; A61B 2018/00702
20130101; A61B 2018/00839 20130101 |
International
Class: |
A61B 18/14 20060101
A61B018/14 |
Claims
1. A device, comprising: a catheter; at least one flow sensor
coupled to the catheter; at least one component coupled to the
catheter to perform an ablation procedure on a portion of a tissue
proximate to the catheter; and an assessment module coupled to the
flow sensor to receive data indicative of at least one flow
measurement from the at least one flow sensor and provide an
indication of the efficacy of the ablation procedure based on the
data indicative of at least one flow measurement.
2-46. (canceled)
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. provisional
application Ser. No. 61/668,338, filed on Jul. 5, 2012, entitled
"METHOD AND APPARATUS FOR DENERVATION," U.S. provisional
application Ser. No. 61/728,653, filed on Nov. 20, 2012, entitled
"RENAL DENERVATION," and U.S. provisional application Ser. No.
61/733,575, filed on Dec. 5, 2012, entitled "INCREASING THE
RESOLUTION OF TEMPERATURE MEASUREMENT FOR FLOW DETECTION IN THE
RENAL ARTERY," each of which is hereby incorporated herein by
reference in its entirety, including drawings.
BACKGROUND
[0002] Diseases such as heart disease, stroke and hypertension are
a global epidemics that affects billions of people worldwide
Hypertension underlies the progression of several debilitating
diseases, including heart disease and stroke. Despite widespread
use of anti-hypertension medication to counter high blood pressure,
the prevalence of hypertension is alarmingly high and constitutes a
severe economic burden on health care.
[0003] Blood pressure is controlled, in large part, by the
sympathetic nervous system. The sympathetic nervous system involves
several organs that are responsible for regulating blood pressure
such as the brain, heart and kidneys. The kidney is a key element
in long-term blood pressure regulation. Hypertension, or high blood
pressure, results from hyperactive renal nerves. This, in turn, can
cause heart, kidney, and blood vessel damage.
SUMMARY
[0004] The Inventors have recognized that an ability to monitor
procedures during treatment of tissue is advantageous. For example,
renal ablation represents a useful and potentially safe technique.
Its applicability may be limited due to a lack of sensing
capability following ablation.
[0005] In view of the foregoing, various examples described herein
are directed generally to systems, apparatus and methods for
facilitating the verification verifying the outcome of renal nerve
denervation, which can be used to determine a clinical endpoint of
a denervatin procedure. Systems and methods described herein also
facilitate establishing a credible endpoint in renal sympathetic
denervation procedures.
[0006] Systems and methods described herein provide novel devices,
including catheter devices, with diagnostic capabilities, to assess
the state of the renal arteries following each procedure, including
each ablation cycle of a series of ablation cycles.
[0007] Systems and methods described herein provide novel devices,
including catheter devices, with diagnostic capabilities, to assess
the state of the tissue in other systems, including in pulmonary
veins, coronary arteries, and peripheral blood vessels, following
each procedure in a series of procedures, such as each ablation
cycle of a series of ablation cycles.
[0008] In an example, a system, apparatus and method is provided
that is based on thin device islands, including integrated
circuitry (IC) chips and/or stretchable and/or flexible
interconnects that are encapsulated in an encapsulant.
[0009] In an example, a system, apparatus and method is provided
that includes a catheter, at least one flow sensor coupled to the
catheter; at least one component coupled to the catheter to perform
an ablation procedure on a portion of a tissue proximate to the
catheter, and an assessment module coupled to the flow sensor to
receive data indicative of at least one flow measurement from the
at least one flow sensor and provide an indication of the efficacy
of the ablation procedure based on the data indicative of at least
one flow measurement.
[0010] In an example, a system, apparatus and method can further
include an inflatable and/or expandable body coupled to the
catheter, and an electronic circuit disposed on the inflatable
and/or expandable body, the electronic circuit includes a plurality
of components that accommodate expanding of the inflatable and/or
expandable body, the plurality of components including a plurality
of electrodes, at least one electrode of the plurality of
electrodes is a radiofrequency electrode to deliver a
radiofrequency energy to a tissue proximate to the radiofrequency
electrode.
[0011] The tissue proximate the catheter can be a portion of a
renal artery and where the measurement of the flow sensor provides
an indication of a rate of renal blood flow.
[0012] The can further include an electronic circuit disposed on
the catheter, the electronic circuit includes a plurality of
electrodes, where at least one electrode of the plurality of
electrodes is a pacing electrode to deliver an electrical
stimulation to a portion of the renal artery proximate to the
pacing electrode.
[0013] The electrical stimulation can be applied to the portion of
the renal artery prior to performance of the ablation procedure on
the portion of the renal artery.
[0014] In an example, the electrical stimulation is applied to the
portion of the renal artery subsequent performance of the ablation
procedure on the portion of the renal artery.
[0015] In an example, the temperature sensor can be a thermistor, a
thermocouple, a resistance temperature detector, a junction
potential temperature sensor, an integrated-circuit temperature
sensor, or a semiconductor temperature sensor.
[0016] The ablation procedure can be a radiofrequency ablation, a
cryo-ablation, an ultrasound ablation, a laser-light-based
ablation, a drug-based ablation, an ultrasound energy ablation, an
alcohol injection-based ablation, or a microwave energy
ablation.
[0017] In an example, the device can further include an electronic
circuit disposed on the catheter, the electronic circuit includes
at least one radiofrequency electrode, where the at least one
radiofrequency electrode is a bipolar electrode or a unipolar
electrode.
[0018] In an example, the device can further include an electronic
circuit disposed on the catheter, the electronic circuit includes a
plurality of components, where the plurality of components further
comprises at least one of a light-emitting device, a contact
sensor, an image detector, a mapping electrode, a pressure sensor,
a biological activity sensors, and a temperature sensor.
[0019] The device can also include an inflatable and/or expandable
body coupled to the catheter, where the inflatable and/or
expandable body is a compliant balloon or a non-compliant
balloon.
[0020] The device can further includes an inflatable and/or
expandable body coupled to the catheter, where the inflatable
and/or expandable body is an expandable spiral coil, an expandable
mesh, or a deployable netting.
[0021] In an example, the device can further include an inflatable
and/or expandable body coupled to the catheter, an electronic
circuit disposed on the inflatable and/or expandable body, the
electronic circuit includes a plurality of components, and at least
four flow sensors disposed on the portion of the inflatable and/or
expandable body, and where the plurality of components comprises at
least four pacing electrodes and at least four radiofrequency
electrodes.
[0022] In an example, the tissue is a portion of a tissue
lumen.
[0023] The tissue can be a renal artery, a pulmonary vein, a
coronary artery, or a peripheral blood vessel.
[0024] In an example, a system, apparatus and method is provided
for performing a medical diagnosis and/or treatment on a tissue.
The method includes disposing in proximity to the tissue. The
apparatus includes a catheter, at least one flow sensor disposed on
a portion of the catheter, each of the at least one flow sensor
including a heating element, and a temperature sensor disposed
proximate to the heating element, and an assessment module coupled
to the flow sensor to receive data indicative of at least one flow
measurement from the at least one flow sensor and provide an
indication of the efficacy of the ablation procedure based on the
data indicative of at least one flow measurement. A flow
measurement of the flow sensor can be used to provide an indication
of a flow rate of a fluid proximate to the inflatable and/or
expandable body. At least one component coupled to the catheter to
perform an ablation procedure on a portion of a tissue proximate to
the catheter. The method can further include applying the ablation
procedure to the surface of the tissue proximate to the catheter,
and recording the flow measurement of the flow sensor, where the
assessment module provides the indication of the efficacy of the
ablation procedure.
[0025] In an example, a system, apparatus and method is provided
for recording the flow measurement prior to and subsequent to
performing the ablation procedure, where the ablation procedure is
a radiofrequency ablation, a cryo-ablation, an ultrasound ablation,
a laser-light-based ablation, a drug-based ablation, an ultrasound
energy ablation, an alcohol injection-based ablation, or a
microwave energy ablation of the tissue.
[0026] In an example, a system, apparatus and method is provided
for recording of the flow measurement of the flow sensor is
performed subsequent to the applying of the ablation procedure to
the surface of the tissue proximate to the catheter.
[0027] In an example, a system, apparatus and method is provided
for recording of the flow measurement of the flow sensor is
performed prior to the applying of the ablation procedure to the
surface of the tissue proximate to the catheter.
[0028] The example, a system, apparatus and method can further
include recording of the flow measurement of the flow sensor
subsequent to the applying of the ablation procedure to the surface
of the tissue proximate to the catheter, and comparing data
indicative of the flow measurement prior to the applying of the
ablation procedure to data indicative of the flow measurement
subsequent to the applying of the ablation procedure to provide the
indication of the efficacy of the ablation procedure.
[0029] In an example system, apparatus and method provided herein,
an indication of an increase in the flow rate of the fluid provides
an indication of the efficacy of the applying of the ablation
procedure to the surface of the tissue.
[0030] The catheter can further include a pacing electrode to
deliver an electrical stimulation to a portion of the tissue
proximate to the pacing electrode.
[0031] The method can further include delivering the electrical
stimulation to the portion of the tissue proximate to the pacing
electrode prior to the recording of the temperature measurement of
the temperature sensor.
[0032] The tissue can be a left renal artery, a right renal artery,
and/or a carotid body.
[0033] an example system, apparatus and method provided herein, an
indication of an increase in the flow rate of the fluid provides an
indication of the efficacy of the applying of the ablation
procedure to the surface of the left renal artery, the right renal
artery, and/or the carotid body.
[0034] An example system, apparatus and method herein provides a
catheter device for performing a procedure on tissue of a renal
artery. The catheter device includes an inflatable and/or
expandable body disposed near a distal end of the catheter, at
least one flow sensor disposed on the inflatable and/or expandable
body. At least one component coupled to the catheter to perform an
ablation procedure on a portion of the tissue of the renal artery.
Each of the at least one flow sensor includes a heating element to
heat an area proximate to the inflatable and/or expandable body,
and a temperature sensor disposed proximate to the heating element,
where measurement of the temperature sensor provides an indication
of a flow rate of blood in the renal artery proximate to the
inflatable and/or expandable body.
[0035] The following publications, patents, and patent applications
are hereby incorporated herein by reference in their entirety:
[0036] Kim et al., "Stretchable and Foldable Silicon Integrated
Circuits," Science Express, Mar. 27, 2008, 10.1126/science.1154367;
[0037] Ko et al., "A Hemispherical Electronic Eye Camera Based on
Compressible Silicon Optoelectronics," Nature, Aug. 7, 2008, vol.
454, pp. 748-753; [0038] Kim et al., "Complementary Metal Oxide
Silicon Integrated Circuits Incorporating Monolithically Integrated
Stretchable Wavy Interconnects," Applied Physics Letters, Jul. 31,
2008, vol. 93, 044102; [0039] Kim et al., "Materials and
Noncoplanar Mesh Designs for Integrated Circuits with Linear
Elastic Responses to Extreme Mechanical Deformations," PNAS, Dec.
2, 2008, vol. 105, no. 48, pp. 18675-18680; [0040] Meitl et al.,
"Transfer Printing by Kinetic Control of Adhesion to an Elastomeric
Stamp," Nature Materials, January, 2006, vol. 5, pp. 33-38; [0041]
U.S. Patent Application publication no. 2010 0002402-A1, published
Jan. 7, 2010, filed Mar. 5, 2009, and entitled "STRETCHABLE AND
FOLDABLE ELECTRONIC DEVICES;" [0042] U.S. Patent Application
publication no. 2010 0087782-A1, published Apr. 8, 2010, filed Oct.
7, 2009, and entitled "CATHETER BALLOON HAVING STRETCHABLE
INTEGRATED CIRCUITRY AND SENSOR ARRAY;" [0043] U.S. Patent
Application publication no. 2010 0116526-A1, published May 13,
2010, filed Nov. 12, 2009, and entitled "EXTREMELY STRETCHABLE
ELECTRONICS;" [0044] U.S. Patent Application publication no. 2010
0178722-A1, published Jul. 15, 2010, filed Jan. 12, 2010, and
entitled "METHODS AND APPLICATIONS OF NON-PLANAR IMAGING ARRAYS;"
and [0045] U.S. Patent Application publication no. 2010 027119-A1,
published Oct. 28, 2010, filed Nov. 24, 2009, and entitled
"SYSTEMS, DEVICES, AND METHODS UTILIZING STRETCHABLE ELECTRONICS TO
MEASURE TIRE OR ROAD SURFACE CONDITIONS." [0046] Kim, D. H. et al.
(2010). Dissolvable films of silk fibroin for ultrathin conformal
bio-integrated electronics. Nature Materials, 9, 511-517. [0047]
Omenetto, F. G. and D. L. Kaplan. (2008). A new route for silk.
Nature Photonics, 2, 641-643. [0048] Omenetto, F. G., Kaplan, D. L.
(2010). New opportunities for an ancient material. Science, 329,
528-531. [0049] Halsed, W. S. (1913). Ligature and suture material.
Journal of the American Medical Association, 60, 1119-1126. [0050]
Masuhiro, T., Yoko, G., Masaobu, N., et al. (1994). Structural
changes of silk fibroin membranes induced by immersion in methanol
aqueous solutions. Journal of Polymer Science, 5, 961-968. [0051]
Lawrence, B. D., Cronin-Golomb, M., Georgakoudi, I., et al. (2008).
Bioactive silk protein biomaterial systems for optical devices.
Biomacromolecules, 9, 1214-1220. [0052] Demura, M., Asakura, T.
(1989). Immobilization of glucose oxidase with Bombyx mori silk
fibroin by only stretching treatment and its application to glucose
sensor. Biotechnology and Bioengineering, 33, 598-603. [0053] Wang,
X., Zhang, X., Castellot, J. et al. (2008). Controlled release from
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application Ser. No. 12/723,475 entitled "SYSTEMS, METHODS, AND
DEVICES FOR SENSING AND TREATMENT HAVING STRETCHABLE INTEGRATED
CIRCUITRY," filed Mar. 12, 2010. [0055] U.S. patent application
Ser. No. 12/686,076 entitled "Methods and Applications of
Non-Planar Imaging Arrays," filed Jan. 12, 2010. [0056] U.S. patent
application Ser. No. 12/636,071 entitled "Systems, Methods, and
Devices Using Stretchable or Flexible Electronics for Medical
Applications," filed Dec. 11, 2009. [0057] U.S. Patent Application
publication no 2012-0065937-A1, published Mar. 15, 2012, and
entitled "METHODS AND APPARATUS FOR MEASURING TECHNICAL PARAMETERS
OF EQUIPMENT, TOOLS AND COMPONENTS VIA CONFORMAL ELECTRONICS."
[0058] U.S. patent application Ser. No. 12/616,922 entitled
"Extremely Stretchable Electronics," filed Nov. 12, 2009. [0059]
U.S. patent application Ser. No. 12/575,008 entitled "Catheter
Balloon Having Stretchable Integrated Circuitry and Sensor Array,"
filed on Oct. 7, 2009. [0060] U.S. patent application Ser. No.
13/336,518 entitled "Systems, Methods, and Devices Having
Stretchable Integrated Circuitry for Sensing and Delivering
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[0061] It should be appreciated that all combinations of the
foregoing concepts and additional concepts described in greater
detail below (provided such concepts are not mutually inconsistent)
are contemplated as being part of the inventive subject matter
disclosed herein. It also should be appreciated that terminology
explicitly employed herein that also may appear in any disclosure
incorporated by reference should be accorded a meaning most
consistent with the particular concepts disclosed herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0062] The skilled artisan will understand that the figures,
described herein, are for illustration purposes only, and that the
drawings are not intended to limit the scope of the disclosed
teachings in any way. In some instances, various aspects or
features may be shown exaggerated or enlarged to facilitate an
understanding of the inventive concepts disclosed herein (the
drawings are not necessarily to scale, emphasis instead being
placed upon illustrating the principles of the teachings). In the
drawings, like reference characters generally refer to like
features, functionally similar and/or structurally similar elements
throughout the various figures.
[0063] FIGS. 1A-1C show example voltage waveforms for stimulating
nerves, according to the principles described herein.
[0064] FIG. 2 shows a plot of percent changes of renal blood flow
as a function of integrated voltage being delivered during pacing,
according to the principles described herein.
[0065] FIG. 3A shows an example device that can be used to perform
a procedure, according to the principles described herein.
[0066] FIG. 3B shows an example flow sensor. according to the
principles described herein.
[0067] FIGS. 4A and 4B show example implementation of an example
device, according to the principles described herein.
[0068] FIG. 5 shows an example implementation of an electronic
circuit and flow sensor, according to the principles described
herein.
[0069] FIG. 6A shows another example device, according to the
principles described herein,
[0070] FIG. 6B shows another example device, according to the
principles described herein.
[0071] FIGS. 7A and 7B illustrate an operation of the flow sensors
of FIG. 6A-6B, according to the principles described herein.
[0072] FIG. 8 shows an example simplified schematic of a
differential pre-amplifier, according to the principles described
herein.
[0073] FIG. 9 shows an example operation of a 3-.omega. acquisition
system, according to the principles described herein.
[0074] FIGS. 10A-10C show cross-sectional layering structure of
various components of an example device, according to the
principles described herein.
[0075] FIG. 11 shows a flowchart of an example method for
performing an example assessment, according to the principles
described herein.
[0076] FIG. 12 shows a block diagram of an example system including
an assessment module according to the principles described
herein.
[0077] FIG. 13A shows an example flow sensor, according to the
principles described herein.
[0078] FIG. 13B shows example measurements using an example flow
sensor, according to the principles described herein.
[0079] FIG. 14 shows an example method for performing a procedure,
according to the principles described herein.
[0080] FIG. 15 shows an example architecture of an illustrative
computer system, according to the principles described herein
[0081] FIGS. 16A and 16B show the results of example measurement
using an example device, according to the principles described
herein.
[0082] FIGS. 17A and 17B show the results of example use of an
example device, according to the principles described herein
[0083] FIGS. 18A-18G illustrates examples of multi-electrode and
balloon catheter devices, according to the principles described
herein.
[0084] FIGS. 19A-19D shows examples of catheter devices.
[0085] FIGS. 19E and 19F shows example forms of sensing, according
to the principles described herein.
[0086] FIG. 20 shows a non-limiting example of flow sensors on
catheters, according to the principles described herein.
[0087] FIG. 21 shows an example of flow sensors on a spiral-shaped
catheter, according to the principles described herein.
[0088] FIG. 22 shows a catheter with bipolar electrodes and metal
interconnects, according to the principles described herein.
DETAILED DESCRIPTION
[0089] Following below are more detailed descriptions of various
concepts related to, and embodiments of, an apparatus and systems
for embedding thinned chips in a flexible polymer. It should be
appreciated that various concepts introduced above and described in
greater detail below may be implemented in any of numerous ways, as
the disclosed concepts are not limited to any particular manner of
implementation. Examples of specific implementations and
applications are provided primarily for illustrative purposes.
[0090] As used herein, the term "includes" means includes but is
not limited to, the term "including" means including but not
limited to. The term "based on" means based at least in part on. As
used herein, the term "disposed on" or "disposed above" is defined
to encompass "at least partially embedded in."
[0091] With respect to substrates or other surfaces described
herein in connection with various examples of the principles
herein, any references to "top" surface and "bottom" surface are
used primarily to indicate relative position, alignment and/or
orientation of various elements/components with respect to the
substrate and each other, and these terms do not necessarily
indicate any particular frame of reference (e.g., a gravitational
frame of reference). Thus, reference to a "bottom" of a substrate
or a layer does not necessarily require that the indicated surface
or layer be facing a ground surface. Similarly, terms such as
"over," "under," "above," "beneath" and the like do not necessarily
indicate any particular frame of reference, such as a gravitational
frame of reference, but rather are used primarily to indicate
relative position, alignment and/or orientation of various
elements/components with respect to the substrate (or other
surface) and each other. The terms "disposed on" "disposed in" and
"disposed over" encompass the meaning of "embedded in," including
"partially embedded in." In addition, reference to feature A being
"disposed on," "disposed between," or "disposed over" feature B
encompasses examples where feature A is in contact with feature B,
as well as examples where other layers and/or other components are
positioned between feature A and feature B.
[0092] Renal denervation therapy can be used to disrupt the renal
nerve through ablation, including through applying energy in the
form of RF energy, heating, or cryo (extreme cold) to the nerves.
This can be done by inserting a tube or catheter into the groin and
guiding the device into the renal artery. The renal denervation
procedure ordinarily is not configured to provide measurement of
the efficacy of the process.
[0093] Other non-limiting examples of ablation energy that can be
applied using a catheter with flow sensing: according to the
principles described herein include radiofrequency (RF), ultrasound
energy, cryoablation, drug-based ablation, alcohol injection,
microwave energy ablation, and light-based ablation (laser
energy).
[0094] While the description of the assessment is described
relative to a procedure on a renal artery, the assessment of the
efficacy of a procedure can be performed in other systems. For
example, an assessment described herein for determining the
efficacy of a procedure using flow measurements can be applied to
procedures being performed in other tissue lumen, such as pulmonary
veins, coronary arteries, peripheral blood vessels, cardiac lumen,
and any other lumen in which flow can be assessed.
[0095] An increase in blood flow in the renal artery can be used as
an indicator of the degree of efficacy of a renal sympathetic
denervation (RSDN) procedure. For example, an indication of an
increase in the rate of blood flow can be considered an indicator
that a RSDN procedure is effective in achieving the desired degree
and/or amount of denervation in the tissue being targeted. Such an
indication of the degree of efficacy can be extrapolated to signal
an endpoint to the procedure if the flow-rate of blood is
approaching the desired level. As another example, an indication of
little or no change in the rate of blood flow can be considered an
indicator that a RSDN procedure is ineffective or marginally
effective in achieving the desired degree and/or amount of
denervation in the tissue being targeted. Such an indication of the
degree of efficacy can be extrapolated used in a determination of
an expected number of additional procedures to be performed to
achieve the desired outcome, or potential changes that could be
made to make the RSDN procedure more effective.
[0096] According to the principles described herein, example
devices and methods are described for determining the efficacy of a
renal denervation procedure is disclosed that relates to monitoring
changes in blood flow rates before and after the procedure.
[0097] This disclosure relates to flow measurement systems that can
be implemented to determine the efficacy of interventional
procedures such as renal denervation. According to an example and
method described herein, a change in flow rate of blood through the
tissue lumen can be used to provide an indication of the
effectiveness of a procedure performed on the renal artery. The
procedure can be any procedure to disrupt the renal nerve, e.g.,
through ablation, including through applying energy in the form of
RF energy, heating, or cryo (extreme cold) to the nerves. An
example application of a flow measurement system, apparatus and
method described herein is to provide an indication to a physician
that the clinical procedure is successful.
[0098] According to the principles described herein, example
devices and methods are described for use in establishing a
clinical endpoint in a procedure in a renal artery. In an example
system and method, a measure of blood flow in a renal artery prior
to the procedure and/or subsequent to the procedure can be used to
provide an indication of an efficacy of a procedure. In another
example, blood flow measurements during a pre-procedure cycle
and/or during a post-procedure cycle can be used to establish a
clinical endpoint for the procedure being performed to disrupt the
renal nerve, e.g., through ablation, including through applying
energy in the form of RF energy, heating, or cryo (extreme cold) to
the nerves.
[0099] Sympathetic nerve activity controls blood pressure and flow
by virtue of vasoconstriction. Delivery of electrical stimulation
to renal sympathetic nerves can, in turn, be used to stimulate the
renal nerves and cause a modulation in renal blood flow. According
to the principles described herein, example devices and methods are
described for measuring changes in local blood flow and/or pressure
during a procedure, such as but not limited to a RSDN
procedure.
[0100] At present, most forms of high-performance electronics and
electrodes are rigid, bulky and have cylindrical cuff-like formats
that are inherently low density and incompatible with the soft,
complex topologies of arteries. In various example implementations,
novel multifunctional catheter devices are described that include
novel microfabrication technology to build arrays of soft and
flexible nanomembrane flow sensing and electrode elements that can
be used to provide feedback about renal blood flow, while
concurrently delivering pacing energy and ablation energy. In
various examples described herein, novel design strategies and
fabrication techniques are described that use inorganic
semiconductor processes to achieve high performance flexible flow
sensor and electrode arrays on catheter devices, such as but not
limited to, spiral shaped and balloon catheters that concurrently
measure flow and apply RF energy and pacing energy inside a renal
artery.
[0101] An example catheter device according to the principles
described herein can include at least one pacing electrode. In a
pacing procedure, a potential is applied to a portion of tissue
proximate to a nerve to stimulate blood flow. FIGS. 1A-1C show
example voltage waveforms that can be used to stimulate the nerves.
FIG. 2 shows a plot of percent changes of renal blood flow as a
function of integrated voltage being delivered during pacing. FIGS.
1A-1C and FIG. 2 demonstrate that blood flow can be changed in the
renal artery due to programmed nerve stimulation (during pacing).
In an example, such pacing can be performed during a procedure
performed according to the principles described herein. For
example, at least one pacing electrode can be disposed on an
example catheter device described herein to provide an electrical
stimulation to tissue, e.g., in a region of a nerve source, prior
to, during, and/or following a procedure. That procedure can be any
procedure that disrupts the renal nerve through ablation, including
through applying energy in the form of RF energy, heating, or cryo
(extreme cold) to the nerves.
[0102] Example devices and methods are described that combine, on a
single catheter device, components to perform a procedure on a
tissue and components to perform sensing of the flow rate of blood,
according to the principles described herein. Example devices and
methods are also described that combine on a single catheter
device, components to perform nerve stimulation (such as using
pacing electrodes) and components to perform sensing of the flow
rate of blood, according to the principles described herein. In an
example, an indication of \the flow rate of blood based on
measurements using the catheter device can be used to establish a
clinical endpoint during a procedure, including a RSDN
procedure.
[0103] FIG. 3A shows an example device 300 that can be used to
perform a procedure according to the principles described herein.
The example device 300 includes an inflatable and/or expandable
body 302, a flow sensor 304 disposed on a portion of the inflatable
and/or expandable body 302, and an electronic circuit 306 disposed
on the inflatable and/or expandable body 302. The electronic
circuit 306 includes a number of components that accommodate
expanding of the inflatable and/or expandable body 302. In FIG. 3A,
the flow sensor 304 is illustrated as being disposed on a distal
portion of the inflatable body. In another example, the flow sensor
can be disposed on or proximate to a proximal portion of the
inflatable and/or expandable body.
[0104] In an example implementation, the flow sensor can be a
formed as illustrated in FIG. 3B. FIG. 3B shows an example flow
sensor 306' that includes a heating element 307 disposed proximate
to a temperature sensor 308. In various examples, the heating
element 307 can be separated from the temperature sensor 308 by
about 1 mm, about 2 mm, about 3 mm, about 5 mm, about 8 mm, about
10 mm, about 12 mm, about 18 mm, about 24 mm, about 30 mm or more.
Temperature sensor 308 can be a thermocouple, a resistance
temperature detector (RTD) temperature sensor, a junction potential
temperature sensor (including sensors that use a voltage measure
across a junction as an indicator of temperature), a thermistor, an
integrated-circuit temperature sensor (including a LM35-series
temperature sensor), or a semiconductor temperature sensor. Example
flow sensor 306' can provide a measure of the flow rate of blood in
a tissue lumen based on temperature measurements of the temperature
sensor. In operation, the heating element is used to maintain the
temperature sensor at a specified temperature measurement value.
Any fluid flowing past the heating element and temperature sensor
can cause some change or fluctuation in the temperature measurement
of the temperature sensor. The heating element is configured such
that it tried to maintain the temperature sensor at the stable
specified temperature reading. A change in the fluid flow rate that
causes some fluctuation in the reading of the temperature sensor
causes the heating element to increase of decrease its heat output
to bring the temperature sensor to its specified reading. A faster
flow rate of the fluid (e.g., the blood) in the region of the flow
sensor can cause the heating element to increase its heat output. A
slower flow rate of the fluid (e.g., the blood) in the region of
the flow sensor can cause the heating element to decrease its heat
output. As a result, a change in the operating point of the heating
element can be used to provide an indication of the flow rate of
the fluid measurement of the temperature sensor can be used to
provide an indication of the flow rate of fluid proximate to the
inflatable and/or expandable body 302.
[0105] The example flow sensors according to the principles
described herein can include a temperature sensor proximate to a
thermal `radiation` source. According to any of the example
systems, methods and apparatus described herein, non-limiting
examples of heating elements that can provide the thermal radiation
include any form of heater that can be coupled with a catheter,
including a resistive heater or a thermoelectric heater.
[0106] In any example device according to the principles described
herein, the temperature sensor can include at least one of a
resistance temperature detector (RTD) temperature sensor, a
thermocouple, a junction potential temperature sensor (including
sensors that use a voltage measure across a junction as an
indicator of temperature), a thermistor, an integrated-circuit
temperature sensor (including a LM35-series temperature sensor),
and a semiconductor temperature sensor. In various examples, a
sensor of known impedance is used. Other non-limiting examples of
sensors that can be used according to any of the systems and
methods described herein include vapor deposited gold resistors and
ceramic thermistors. In another example, other materials such as
foils can be used.
[0107] In an example, a calibration standard can be developed for
the flow sensor 306', to correlate the operating point of the
heating element to a flow rate. For example, training samples can
be used to convert a flow measurement, each training sample being a
fluid caused to flow at a specific flow rate. For a given amount
and/or rate of change of operating point of the heating element by
the heating element, the operating point of the flow sensor is
obtained for each training sample. The flow rate of each training
sample is known (given that it is pre-set for the training
samples). The amount and/or rate of heating supplied by the heating
element is also known. The calibration standard can be developed to
correlate the known heating supplied to the known flow rate to
obtain calibration data. The example calibration standard can be
used to convert a flow sensor measurement to a flow rate for a
fluid having similar properties as the fluid used in the training
standard.
[0108] In an example implementation, the examples device of FIGS.
3A and 3B can further include a flow sensor that is disposed on a
portion of a catheter that is coupled to the proximal portion of
the inflatable and/or expandable body.
[0109] In an example, the electronic circuit 306 can include a
number of electrodes disposed on the inflatable and/or expandable
body 302. The electrodes can be used to perform a procedure
according to the principles described herein. For example, at least
one of the electrodes can be a radiofrequency (RF) electrode that
delivers RF energy to a portion of the tissue surface that is
proximate to the RF electrode. According to the principles
described herein, the delivered RF energy is used to modify the
tissue, including to disrupt a renal nerve.
[0110] In another example, the device 300 can include components to
perform a procedure using other modalities. For example, the device
300 can include components to disrupt the renal nerve, e.g.,
through ablation, including through applying energy in the form of
RF energy, heating, or cryo (extreme cold) to the nerves.
[0111] In another example, the electronic circuit 306 of device 300
can include at least one pacing electrode. The pacing electrode can
be implemented to deliver an electrical stimulation to a portion of
a tissue (such as but not limited to a renal artery) proximate to
the pacing electrode. As described above, the pacing electrode can
be used to stimulate nerve at different stages of a procedure. For
example, the electrical stimulation from the pacing electrode(s)
can be applied to the portion of the tissue to stimulate nerves
prior to delivery of an energy to disrupt the nerves, such as but
not limited to through ablation, including through applying energy
in the form of RF energy, heating, or cryo (extreme cold) to the
nerves. In another example, the electrical stimulation from the
pacing electrode(s) can be applied to the portion of the tissue to
stimulate nerves subsequent to delivery of an energy to disrupt the
nerves, such as but not limited to through ablation, including
through applying energy in the form of RF energy, heating, or cryo
(extreme cold) to the nerves.
[0112] In another example, the electronic circuit 306 can also
include temperature sensors, each temperature being disposed
proximate to an electrode of the electronic circuit 306.
[0113] In another example, the device 300 can include one or more
other components disposed on the inflatable and/or expandable body
such as, but not limited to, a pacing electrode, a light-emitting
device, a contact sensor, an image detector, a pressure sensor, a
biological activity sensors, a temperature sensor, or any
combination thereof.
[0114] FIGS. 4A and 4B show a non-limiting example implementation
of an example device example device 400. The example device 400
includes an inflatable and/or expandable body 402, a flow sensor
404 disposed on a portion of the inflatable and/or expandable body
402, and an electronic circuit 406 disposed on the inflatable
and/or expandable body 402. The electronic circuit 406 includes a
number of components that accommodate expanding of the inflatable
and/or expandable body 402. As shown in FIGS. 4A and 4B, the flow
sensor 404 can be being disposed on a distal portion of the
inflatable and/or expandable body 402. As a non-limiting example, a
portion of the distal region of the expandable and/or inflatable
structure can be extended to form a protrusion. The flow sensor 404
can be mounted on the protrusion. In another example, the flow
sensor 404 can be disposed on or proximate to a proximal portion of
the inflatable and/or expandable body.
[0115] In an example implementation, the flow sensor 404 can be a
formed as including a heating element 407 disposed proximate to a
temperature sensor 408. In various examples, the heating element
407 can be separated from the temperature sensor 408 by about 1 mm
or about 2 mm. As a non-limiting example, the heating element 407
can be a temperature-controlled heating element. As a non-limiting
example, the temperature sensor 408 can be a thermistor.
[0116] In the non-limiting example of FIGS. 4A and 4B, the
electronic circuit can include a number of electrodes 410 disposed
on the inflatable and/or expandable body 402. The electrodes can be
used to perform a procedure according to the principles described
herein. For example, at least one of the electrodes 410 can be a
radiofrequency (RF) electrode that delivers RF energy to a portion
of the tissue surface that is proximate to the RF electrode.
According to the principles described herein, the delivered RF
energy is used to modify the tissue, including to disrupt a renal
nerve.
[0117] As shown in the non-limiting example of FIGS. 4A and 4B, the
electronic circuit 406 of the example device 400 can include
stretchable interconnects 412 disposed on the surface of the
inflatable and/or expandable body 402. As shown in FIG. 4B, the
stretchable interconnects can be used to electrically couple at
least one of the plurality of electrodes 410 to an external
circuit.
[0118] As shown in the non-limiting example of FIGS. 4A and 4B, the
electronic circuit 406 of the example device 400 can also include a
main bus 414. As shown in FIG. 4B, the stretchable interconnects
412 electrically couple the electrodes 410 to the man bus 414. As
also shown in FIG. 4B, the main bus 414 can extend beyond the
inflatable and/or expandable body 402 to facilitate electrical
coupling of the electrodes 410 to an external circuit.
[0119] In another example, the at least one of the electrodes 410
of electronic circuit 406 of device 400 can be a pacing electrode.
The pacing electrode can be implemented to deliver an electrical
stimulation to a portion of a tissue (such as but not limited to a
renal artery) proximate to the pacing electrode. As described
above, the pacing electrode can be used to stimulate nerve at
different stages of a procedure. For example, the electrical
stimulation from the pacing electrode(s) can be applied to the
portion of the tissue to stimulate nerves prior to delivery of an
energy to disrupt the nerves, such as but not limited to through
ablation, including through applying energy in the form of RF
energy, heating, or cryo (extreme cold) to the nerves. In another
example, the electrical stimulation from the pacing electrode(s)
can be applied to the portion of the tissue to stimulate nerves
subsequent to delivery of an energy to disrupt the nerves, such as
but not limited to through ablation, including through applying
energy in the form of RF energy, heating, or cryo (extreme cold) to
the nerves.
[0120] In another example, the device 400 can include components to
perform a procedure using other modalities. For example, the device
400 can include components to disrupt the renal nerve, e.g.,
through ablation, including through applying energy in the form of
RF energy, heating, or cryo (extreme cold) to the nerves.
[0121] In another example, the device 400 can include one or more
other components disposed on the inflatable and/or expandable body
such as, but not limited to, a pacing electrode, a light-emitting
device, a contact sensor, an image detector, a pressure sensor, a
biological activity sensors, a temperature sensor, or any
combination thereof.
[0122] In another example, the device 400 can also include
temperature sensors, each temperature being disposed proximate to
an electrode 410 of the electronic circuit 406.
[0123] FIG. 5 shows a non-limiting example implementation of an
electronic circuit 506 and flow sensor 504 that can be disposed on
a catheter and extend to a shaft of an example device according to
the principles described herein. The electronic circuit 506
includes a number of electrodes 510. In various examples, the
electrodes 510 can be conformable electrodes that conform to the
surface of the inflatable and/or expandable body. As shown in FIG.
5, the flow sensor 404 includes a heating element 507 disposed
proximate to a temperature sensor 808. As a non-limiting example,
the heating element 507 can be a temperature-controlled heating
element. As a non-limiting example, the temperature sensor 508 can
be a thermistor.
[0124] In the non-limiting example of FIG. 5, at least one of the
electrodes 510 can be a radiofrequency (RF) electrode that delivers
RF energy to a portion of the tissue surface that is proximate to
the RF electrode. According to the principles described herein, the
delivered RF energy is used to modify the tissue, including to
disrupt a renal nerve. At least one of the electrodes 510 can be a
pacing electrode that delivers an electrical stimulation to a
nerve, as described herein.
[0125] As shown in the non-limiting example of FIG. 5, the
electronic circuit 506 includes stretchable interconnects 512
disposed on the surface of the inflatable and/or expandable body.
The stretchable interconnects 512 can be used to electrically
couple at least one of the plurality of electrodes 510 to an
external circuit.
[0126] As also shown in the non-limiting example of FIG. 5, the
electronic circuit 506 also includes a main bus 514. As shown in
FIG. 5, the stretchable interconnects 512 electrically couple the
electrodes 510 to the man bus 514. As also shown in FIG. 5, the
main bus 514 include connection pads 516 that facilitate electrical
coupling of the electrodes 510 to an external circuit.
[0127] FIG. 6A shows another example device 600 that can be used to
perform a procedure according to the principles described herein.
The example device 600 includes an inflatable and/or expandable
body 602, a pair of flow sensors 604-a and 604-b, and an electronic
circuit 606 disposed on the inflatable and/or expandable body 602.
The device 600 is coupled to a distal portion of a shaft 608. The
electronic circuit 606 includes a number of components that
accommodate expanding of the inflatable and/or expandable body 602.
In FIG. 6A, one of the flow sensor 604-a is shown to be disposed on
a proximal portion of the inflatable body. The other flow sensor
(reference flow sensor 604-b) is shown to be disposed on a portion
of shaft 608 at some distance away from the inflatable and/or
expandable body 602. In the example implementation of FIG. 6A, the
flow rate can be measured based on comparison of the measurement of
the pair of flow sensors 606-a and 606-b. For example, the flow
rate can be measured based on comparison of voltage measurements of
the pair of flow sensors 606-a and 606-b.
[0128] FIG. 6B shows another example device 600' that can be used
to perform a procedure according to the principles described
herein. Example device 600' includes an inflatable and/or
expandable body 602, a pair of flow sensors 604-a and 604-b, an
electronic circuit 606 disposed on the inflatable and/or expandable
body 602, and a shaft 608, the same components as example device
600, and they are not repeated. Example device 600' also includes a
shaft 610 that can be disposed over reference electrode 604-b
during a procedure or a flow measurement. The example device 610
also can be retracted to such an extent that reference flow sensor
604-b is exposed.
[0129] In the various examples described herein, the reference
sensor can be positioned on the shaft at a location that can be
covered by a sheath. FIG. 6B shows a non-limiting example of a
catheter device that includes a sheath member that can be
positioned to cover at least a portion of the reference sensor. In
an example implementation, this distance can be determined as
greater than or equal to about 10 cm away from the proximal end of
the balloon. In another example implementation, this distance can
be determined as less than about 10 cm away from the proximal end
of the balloon. For example, the reference flow sensor 604-b can be
positioned at a distance away on the shaft of the catheter that is
at least about 5 cm, at least about 8 cm, at least about 10 cm, at
least about 13 cm, at least about 15 cm or more. In an example
implementation, a sheath can be included and used to guide,
introduce and steer the catheter. The sheath can be a member that
surrounds at least a portion of the circumference of the shaft of
the catheter and/or can be co-axial with the shaft of the catheter.
During a procedure, the reference sensor can be maintained under
the sheath. The sheath can be configured to provide a stable known
environment and provide a chamber that can include blood in the
absence of flow. In this example, blood enters the sheath but flow
can be halted by the presence of a stopcock or flow switch. The
blood can be maintained at body temperature but does not flow,
thereby providing a useful comparison in proximity of the reference
sensors. The measurement performed using the reference sensor in
this environment of blood that is not flowing can serve as a
reference for comparison to the renal artery sensor.
[0130] The internal shaft near the reference sensor can include
surface features in the form of bumps or tracks that provide
channels for the blood. The blood forms an insulating layer on the
reference sensor, allowing a reference quiescent blood temperature
to be measured. The surface features can be designed and configured
to allow blood to circulate as freely and prevent the shaft from
making contact with the sheath in that area. For example, the shaft
may include one or more spacers (also referred to as protuberances)
to maintain the shaft spaced apart from a portion of the surface of
the sheath. The spacing apart of the shaft from the sheath helps to
maintain a static layer of blood static between the sheath and the
shaft.
[0131] FIGS. 7A and 7B illustrate an operation of the flow sensors
of FIG. 6A-6B. FIG. 7A shows an example device 700 that includes an
inflatable and/or expandable body 702, a pair of flow sensors 704-a
and 704-b, an electronic circuit 706 disposed on the inflatable
and/or expandable body 702, a shaft 708 and a sheath 710. Flow
sensor 704-b is coupled to the shaft and covered by the sheath 710.
In the example of FIG. 7B, blood flows in the aorta and renal
artery, yet blood remains static in the sheath due to a stopcock or
flow switch. This allows a differential measurement of flow in the
renal artery versus static flow in the sheath. It also allows for
better use of dynamic range since the measurement is limited
between the two sensors. As also shown in FIG. 7B, the inflatable
or expandable structure can be deflated or retracted at the time of
flow sensor measurement.
[0132] In an example implementation, the method in connection with
FIGS. 7A and 7B can be used to resolve small changes in temperature
in the body. An example system, apparatus and method according to
the principles described herein can be used to measure the signal
of interest in connection with a procedure and reject information
that does not relate to the signal of interest, thereby increasing
resolution and reducing the requirements for expensive signal
processing.
[0133] An example system, apparatus and method according to the
principles described herein can be used to measure differential
flow, such as described in connection with FIGS. 7A and 7B. In an
example implementation, two (or more) sensors are used to measure
flow via a change in flow sensor operating point. As shown in FIGS.
7A and 7B, at least one reference sensor can be placed on the shaft
of a catheter used to perform a measurement described herein. The
non-limiting example catheter can include one or more renal artery
flow sensors and/or one or more other sensors, including one or
more ablation components and/or one or more pacing electrodes. The
reference sensor can be disposed about the inflatable or expandable
member of the catheter, such as but not limited to a balloon, an
expandable mesh, or a deployable netting. The reference sensor can
be disposed at a sufficient separation distance away from the
proximal end of the balloon so that the reference sensor is covered
by the sheath of the catheter when it is proximate to the tissue of
the body. One or more renal artery sensors can be positioned at or
near the proximal end of the balloon. Each measurement taken can be
compared or displayed in reference to a measurement of the
reference sensor.
[0134] Systems, methods and apparatus are described herein that can
be used to increase the dynamic range of measurements by focusing
on the signal of interest. In an example implementation, each flow
sensor, including any reference sensor, can be excited using the
same controlled current source. In an example implementation, each
sensor can be measured using an instrumentation amplifier. FIG. 8
shows a non-limiting example simplified schematic of a differential
pre-amplifier that can be used to measure differences in voltages.
The example differential pre-amplifier circuitry can be implemented
to compare measurements of flow sensors according to the principles
of FIGS. 3A-7B. In this non-limiting example, the flow sensors can
include thermistors. In other examples, the flow sensors can
include at least one of a resistance temperature detector (RTD)
temperature sensor, a thermocouple, a junction potential
temperature sensor (including sensors that use a voltage measure
across a junction as an indicator of temperature), an
integrated-circuit temperature sensor (including a LM35-series
temperature sensor), and a semiconductor temperature sensor. In
various examples, a sensor of known impedance is used. Other
non-limiting examples of sensors that can be used according to any
of the systems and methods described herein include vapor deposited
gold resistors and ceramic thermistors. In another example, other
materials such as foils can be used.
[0135] In the example of FIG. 8, the difference in the voltage can
be measured between the flow sensors (such as but not limited to
the thermistor) that are driven by an excitation current. Signal C
is the difference between the signal from the flow sensor proximate
to the inflatable and/or expandable body (renal flow sensor
measurement--signal A) and the signal from the reference flow
sensor (reference flow sensor measurement--signal B).
[0136] The instrumentation amplifiers can be used to reject
common-mode signals, thereby providing a higher fidelity signal. In
a non-limiting example, an apparatus or system described herein can
include thermistors that are well matched (used as the flow sensors
in this example). The absolute values of the thermistor
measurements can be used. A benefit of measuring a reference
thermistor and renal artery thermistor can be improvement of the
dynamic range by measuring the difference of the values between the
sensors as compared to using the absolute values. Limiting the
measurements between the reference and the renal artery sensor can
facilitate improvement of the dynamic range of the
measurements.
[0137] An example implementation to perform a measurement is
described. In an example, the flow sensors are of known impedances,
and application of an excitation current using the flow sensors
creates a voltage that is measured using instrumentation
amplifiers. The amplifiers are used to measure a voltage
correlating to a flow rate. Changes in blood flow can result in a
change in operating set point in at least one of the flow sensors.
By comparing the value of voltage measured using the reference
sensor to the value of voltage measured using a flow sensor
disposed proximate to the expandable and/or inflatable body, the
flow rate can be quantified. Through this comparison, the
instrument voltage in the absence of flow also can be removed. In
an example, the value of voltage measured using the reference
sensor is subtracted from the renal artery sensor voltage to
provide an indication of the instrument voltage in the absence of
flow. In an example where a reference flow sensor is surrounded by
a sheath, blood in the sheath is physically static. That is, it is
not flowing and remains at body temperature. Blood in the renal
artery is also at body temperature but flows at some rate (desired
to be measured).
[0138] The differential voltage comparison can be computed based on
the flow sensor measurement data as follows:
Differential Measurement(C)=Renal Artery Sensor
Voltage(A)-Reference Sensor Voltage(B)
It also can be expressed as: C=A-B Effectively, in an example
implementation, the equation can be expressed as:
Differential
Measurement=(Voltage.sub.BodyTemp+Voltage.sub.RenalFlow)-(Voltage.sub.Bod-
yTemp+0)
where V.sub.SheathFlow=0.
Differential Measurement=Voltage.sub.RenalFlow
[0139] A gain can be added at any of the instrumentation amplifiers
to increase the amplitude of the signal.
[0140] In an example implementation, one or more flow sensors can
be calibrated. An offset value between the flow sensors disposed
proximate to the inflatable and/or expandable body and the
reference flow sensor(s) can be eliminated by placing the catheter
in a known temperature and flow rate, and measuring the difference
between the two sets of sensors. The measurement can be performed
and/or the offset value can be derived at the time of manufacture
of the catheter and/or time of assembly of the flow sensors with
the inflatable and/or expandable body of the catheter. The offset
value can be stored and/or indicated as a written value, or a
barcode or other form of identification (ID). In an example, an
integrated circuit or memory device or other means can be used to
provide this value and ID to a console that is in communication
with the catheter (including with the flow sensors disposed on or
proximate to the inflatable and/or expandable body). This offset
value can be programmed into the catheter. When the catheter is
coupled with the console, the console can use the offset value to
compensate for an offset in the measurements when calculating
flow.
[0141] Detecting a change in reading of a thermistor, such as in an
example of the implementation described in connection with FIGS.
6A-7B and 8, can provide an indication of the rate of fluid flow.
Detecting flow rate change in the renal artery can require
high-resolution measurement.
[0142] For example, the differential measurement described in
connection with FIGS. 6A-7B and 8 can be used in conjunction with
other methods, such as peak-to-peak measurements,
synchronous-demodulation (lock-in), and three omega (3.omega.)
methods. In different example implementations, the differential
measurement can be used to measure peak-to-peak output, or it can
be input into a lock-in amplifier or 3.omega. acquisition system as
shown in FIG. 9. The 3.omega. method can be implemented using a
micro-fabricated metal pattern acting as a resistive heater. An
alternating current (AC) voltage signal energizes the resistive
element at a frequency .omega.. The periodic heating generates
oscillations in the electrical resistance of the metal line at a
frequency of 2.omega.. In turn, this leads to a third harmonic
(3.omega.) in the voltage signal. The third harmonic is used
according to an example implementation to determine the magnitude
of the temperature oscillations. The temperature oscillations can
be used to provide an indication of the flow rate of a fluid. For
example, the frequency dependence of these temperature oscillations
can be used to derive the thermal properties of the specimen (e.g.,
the fluid). The data indicative of the thermal properties of the
specimen can be used to derive data indicative of the flow rate of
the fluid.
[0143] In any of the examples described herein, the flow sensor
(including the 3-omega sensor) can be disposed on the example
device such that the flow sensor is disposed within a mid-point of
a tissue lumen when the example device is disposed within the
lumen. The mid-point of the lumen in tissue (including the renal
artery lumen) can be the location of maximum flow velocity). The
central positioning of the flow sensor can facilitate more accurate
measured of fluid flow rate by sampling the area of maximum
flow.
[0144] In an example, any system or device according to the
principles described herein may be entirely or at least partially
encapsulated by an encapsulating material, such as a polymer
material (including any of the polymer materials described herein).
An encapsulating material can be any material that can be used to
laminate, planarize, or encase at least one component of a system
or device described herein, including any electronic or other type
of component. For example, a method of fabricating any system or
device according to the principles described herein can further
include encapsulating the system or device. In an example, an
encapsulating material can be disposed over, or otherwise applied
to, an device that includes an inflatable and/or expandable body
and the electronic circuit or a plurality of electrodes. In an
example, a polyurethane can be used as the encapsulating material.
In another example, the encapsulating material can be the same
material as the material for the inflatable and/or expandable body.
Encapsulating any portion of the systems or device described herein
can be useful to enhance the mechanical stability and robustness of
the system or device, or to maintain electronic performance of the
electronic components of the system or device against a stress or
strain applied to the system or device during use.
[0145] In any of the example devices according to the principles
described herein, the encapsulating material can be formed from any
material having elastic properties. For example, the encapsulating
can be formed from a polymer or polymeric material. Non-limiting
examples of applicable polymers or polymeric materials include, but
are not limited to, a polyimide, a polyethylene terephthalate
(PET), a silicone, or a polyeurethane. Other non-limiting examples
of applicable polymers or polymeric materials include plastics,
elastomers, thermoplastic elastomers, elastoplastics, thermostats,
thermoplastics, acrylates, acetal polymers, biodegradable polymers,
cellulosic polymers, fluoropolymers, nylons, polyacrylonitrile
polymers, polyamide-imide polymers, polyarylates,
polybenzimidazole, polybutylene, polycarbonate, polyesters,
polyetherimide, polyethylene, polyethylene copolymers and modified
polyethylenes, polyketones, poly(methyl methacrylate,
polymethylpentene, polyphenylene oxides and polyphenylene sulfides,
polyphthalamide, polypropylene, polyurethanes, styrenic resins,
sulphone based resins, vinyl-based resins, or any combinations of
these materials. In an example, a polymer or polymeric material
herein can be a DYMAX.RTM. polymer (Dymax Corporation, Torrington,
Conn.). or other UV curable polymer, or a silicone such as but not
limited to ECOFLEX.RTM. (BASF, Florham Park, N.J.).
[0146] For applications in biomedical devices, the encapsulant
should be biocompatible. The stretchable interconnects can be
embedded in a polyimide that also acts as a mechanical
reinforcement.
[0147] In an example, any of the systems or device according to the
principles herein can be disposed on the inflatable and/or
expandable body such that a functional layer of the system or
device lies at a neutral mechanical plane (NMP) or neutral
mechanical surface (NMS) of the system or device. The NMP or NMS
lies at the position through the thickness of the device layers for
the system or device where any applied strains are minimized or
substantially zero. In an example, the functional layer of a system
or device according to the principles described herein includes the
plurality of sensing elements, the coupling bus, and/or the
stretchable electronic system that includes the flexible annular
interconnect and the plurality of electrodes.
[0148] The location of the NMP or NMS can be changed relative to
the layer structure of the system or device through introduction of
materials that aid in strain isolation in various layers of the
system or device. In various examples, polymer materials described
herein can be introduced to serve as strain isolation materials.
For example, the encapsulating material described hereinabove can
be used to position the NMP or NMS, e.g., by varying the
encapsulating material type and/or layer thickness. For example,
the thickness of encapsulating material disposed over the
functional layers described herein may be modified (i.e., decreased
or increased) to depress the functional layer relative to the
overall system or device thickness, which can vary the position of
the NMP or NMS relative to the functional layer. In another
example, the type of encapsulating, including any differences in
the elastic (Young's) modulus of the encapsulating material.
[0149] In another example, at least a partial intermediate layer of
a material capable of providing strain isolation can be disposed
between the functional layer and the inflatable and/or expandable
body to position the NMP or NMS relative to the functional layer.
In an example, the intermediate layer can be formed from any of the
polymer materials described herein, aerogel materials or any other
material with applicable elastic mechanical properties.
[0150] Based on the principles described herein, the NMP or NMS can
be positioned proximate to, coincident with or adjacent to a layer
of the system or device that includes the strain-sensitive
component, such as but not limited to the functional layer. The
layer can be considered "strain-sensitive" if it is prone to
fractures or its performance can be otherwise impaired in response
to a level of applied strain. In an example where the NMP or NMS is
proximate to a strain-sensitive component rather than coincident
with it, the position of the NMP or NMS may still provide a
mechanical benefit to the strain-sensitive component, such as
substantially lowering the strain that would otherwise be exerted
on the strain-sensitive component in the absence of strain
isolation layers. In various examples, the NMS or NMP layer is
considered proximate to the strain-sensitive component that
provides at least 10%, 20%, 50% or 75% reduction in strain in the
strain-sensitive component for a given applied strain, e.g., where
the inflatable body is inflated.
[0151] In various examples, the encapsulating material and/or the
intermediate layer material may be disposed at positions coincident
with the strain-sensitive component, including in the functional
layer. For example, portions of the encapsulating material and/or
the intermediate layer material may be interspersed with the
strain-sensitive component, including at positions within the
functional layer.
[0152] In any of the example devices according to the principles
described herein, portions of the stretchable interconnects, the
electrodes and portions of the main bus can be formed from a
conductive material. In any of the examples described herein, the
conductive material can be but is not limited to a metal, a metal
alloy, a conductive polymer, or other conductive material. In an
example, the metal or metal alloy of the coating may include but is
not limited to aluminum, stainless steel, or a transition metal
(including copper, silver, gold, platinum, zinc, nickel, titanium,
chromium, or palladium, or any combination thereof) and any
applicable metal alloy, including alloys with carbon. In other
non-limiting example, suitable conductive materials may include a
semiconductor-based conductive material, including a silicon-based
conductive material, indium tin oxide or other transparent
conductive oxide, or Group III-IV conductor (including GaAs). The
semiconductor-based conductive material can be doped.
[0153] In any of the example structures described herein, the
stretchable interconnects can have a thickness of about 0.1 .mu.m,
about 0.3 .mu.m, about 0.5 .mu.m, about 0.8 .mu.m, about 1 .mu.m,
about 1.5 .mu.m, about 2 .mu.m or greater. The buffer structure
and/or flexible base can have a thickness of about 5 .mu.m, about
7.5 .mu.m, about 9 .mu.m, about 12 .mu.m or greater. In any example
herein, the encapsulant can have a thickness of about 100 .mu.m,
about 125 .mu.m, about 150 .mu.m, about 175 .mu.m, about 200 .mu.m,
about 225 .mu.m, about 250 .mu.m, about 300 .mu.m or greater.
[0154] FIGS. 10A and 10B show cross-sectional layering structure of
various components of the example devices described herein, which
can be microfabricated. FIG. 10A shows the layering structure of an
electrode, which includes a polymer layer 1002, a layer of
conductive material 1004, and an annular structure of a polymer
1006 about a perimeter of the electrode. FIG. 10B shows the
layering structure of a stretchable interconnect, which includes a
polymer layer 1002, a layer of conductive material 1004, and a
layer of a polymer 1006. FIG. 10C shows the layering structure of a
flow sensor disposed on the inflatable and/or expandable body,
which includes a polymer layer 1002, a layer of conductive material
1004, a layer of a polymer 1006, a flow sensor 1008, and an
encapsulating layer 1010. In an example, the components can be
fabricated on a carrier substrate, released from the carrier
substrate, and disposed on the inflatable and/or expandable
body.
[0155] A non-limiting example fabrication process for the example
device of FIGS. 10A and 10B is as follows. The electrode can be
fabricated using a microfabrication and transfer printing process
to be between about 1 micron and about 5 microns thick. The sensors
can be 3-omega sensors (described below) and the surface mount
components (including the flow sensors) can be fabricated using use
pure gold or Cu--Au--Ni fabrication techniques. The fabricated
electronic structure are integrated on the surface of an inflatable
and/or expandable body (such as but not limited to a balloon of a
catheter). In the example device structures of FIGS. 10A and 10B,
the polyimide can be about 25 microns in thickness. A polyurethane,
formed of a resin and a solvent, can be used as an encapsulant to
planarize the array of electrodes and other components on the
surface of the inflatable and/or expandable body. The encapsulant
helps to provide durability during sheath insertion of the example
device into a tissue lumen.
[0156] In an example, the micro-fabricated flow sensors, electrode
arrays (including ablation RF electrodes), electronics and other
components of the example device are ultrathin, and have mechanical
properties substantially similar or matched with the mechanical
properties of the inflatable or expandable surface.
[0157] Systems and methods are described for performing a procedure
on a tissue, including a renal artery, using any example device
described herein. The example method includes disposing an example
device in proximity to the tissue, applying the treatment to be
applied to the tissue, and recording the flow measurement of the
flow sensor as described herein to provide an indication of the
flow rate of a fluid in proximity to the example device.
[0158] In an example, the treatment can include applying an
ablation or applying energy in the form of RF energy, heating, or
cryo (extreme cold) to the tissue. In an example, the treatment is
performed to disrupt nerves in proximity to the tissue.
[0159] In an example, the method can be performed with an example
device that includes a flow sensor element configured as a heating
element in proximity to a temperature sensor. In this example, the
operating point of the heating element can be monitored to provide
an indication of flow rate. In an example, the recording of the
flow measurement of the flow sensor can be performed subsequent to
applying the RF energy to the surface of the tissue proximate to
the RF electrode. In another example, the recording of the flow
measurement of the flow sensor can be performed prior to the
applying of the RF energy to the surface of the tissue proximate to
the RF electrode.
[0160] In an example, the temperature measurement may be performed
before and after application of the RF energy, to obtain an
indication of the flow rate of the fluid (such a blood) prior to
and subsequent to the treatment procedure being performed.
[0161] In an example, systems, methods and devices for monitoring
an efficacy of, determining a clinical endpoint for, a procedure.
According to the principles described herein, the procedure can be
any procedure to disrupt the renal nerves, such as but not limited
to an ablation, including through applying energy in the form of RF
energy, heating, or cryo (extreme cold) to the nerves. The
procedure is not performed completed blindly with no feedback on
the success of the procedure, with potential risk of damage to
tissue. The example systems, methods and devices described herein
provide an assessment of a renal denervation procedure based on
renal hemodynamics (including based on the measures of fluid flow
rate).
[0162] In any example described herein, an assessment module is
provided according to the systems and methods described herein,
where the assessment module includes a processor and a memory
storing processor executable instructions. Execution of the
processor executable instructions causes the assessment module to
perform the activities associated with any method described herein,
including using the data indicative of flow rate to provide an
indication of the efficacy of a clinical procedure.
[0163] In an example, the example method can include using an
indication of an increase in the flow rate of the fluid subsequent
to the performance of the treatment as an indicator of the efficacy
of the treatment procedure to disrupt the nerves (including the
efficacy of applying the RF energy to the tissue). For example, a
pre-set value of fluid flow rate or clinically desired percentage
increase in flow rate can be used as an indicator of the efficacy
of the procedure, including being used as an indication of an
end-point of performance of the procedure. As a non-limiting
example, a baseline flow rate can be measured using the flow
sensors described herein prior to performing the procedure to
disrupt the nerves. A desired pre-set value of fluid flow rate or
clinically desired percentage increase in flow rate can be
determined based on the baseline flow rate. For example, the
pre-set value of fluid flow rate or clinically desired percentage
increase in flow rate can be set as the amount needed to return the
flow rate to an average, mean or median range of values for renal
blood flow rate. In a feedback assessment, the procedure can be
performed, the flow rate subsequently re-measured/re-determined
based on flow sensor measurement data according to the principles
described herein, and the re-measured flow rate compared to the
pre-set value of fluid flow rate or clinically desired percentage
increase in flow rate. If the desired pre-set value of fluid flow
rate or clinically desired percentage increase in flow rate is not
attained, the procedure can be repeated and the flow rate
re-measured. If the desired pre-set value of fluid flow rate or
clinically desired percentage increase in flow rate is attained, it
signals the endpoint, and the procedure can be discontinued. In an
example, the example method can include using an indication of
little or no increase in the flow rate of the fluid subsequent to
the performance of the treatment as an indicator of a lack of the
efficacy of the treatment (including the efficacy of applying the
RF energy to the tissue), or as an indication that the treatment
procedure should be repeated, discontinued or modified. If the
desired pre-set value of fluid flow rate or clinically desired
percentage increase in flow rate is not attained, the procedure can
be modified to achieve the desired outcome. In an example, the
feedback of performing the procedure, re-measuring the flow rate
and comparing to the pre-set value of fluid flow rate or clinically
desired percentage increase in flow rate can be repeated until the
endpoint is signaled.
[0164] While the assessment is described relative to a procedure on
a renal artery, the assessment of the efficacy of a procedure can
be performed in other systems. For example, an assessment described
herein for determining the efficacy of a procedure using flow
measurements can be applied to procedures being performed in other
tissue lumen, such as pulmonary veins, coronary arteries,
peripheral blood vessels, cardiac lumen, and any other lumen in
which flow can be assessed.
[0165] In an example, the method can include activating at least
one pacing electrode of the example device to deliver an electrical
stimulation to a portion of the tissue proximate to the pacing
electrode. For example, the method can include delivering the
electrical stimulation to the portion of the tissue proximate to
the pacing electrode prior to recording a flow measurement
(including recording a flow measurement of a flow sensor).
[0166] A non-limiting example process sequence, for performance of
a procedure on renal artery tissue using an example device that is
configured as a balloon catheter, is as follows: [0167] Perform
initial measurement (e.g., obtain a baseline flow) [0168] Inflate
catheter balloon to block blood flow [0169] Measure renal flow
using any of the example devices or methods described herein [0170]
Pace the renal artery (e.g., apply electrical signals to tissue
using electrodes of the system) [0171] Deflate catheter balloon
[0172] Measure "pre-ablation" flow using any of the example devices
or methods described herein [0173] Inflate catheter balloon [0174]
Perform ablation of the renal artery (e.g., apply energy to tissue
to induce lesions and necrosis, including RF energy, heating, and
cryoablation) [0175] Deflate catheter balloon [0176] Measure
"post-ablation" flow using any of the example devices or methods
described herein
[0177] A non-limiting example process sequence, for renal
denervation on renal artery tissue using an example device that is
configured as a balloon catheter, is as follows: [0178] Pace the
renal artery (e.g., apply electrical signals to tissue using
electrodes of the system) [0179] Measure "pre-ablation" flow rate
using any of the example devices or methods described herein [0180]
Perform ablation of the renal artery (e.g., apply energy to tissue
to induce lesions and necrosis, including RF energy, heating, and
cryoablation) [0181] Pace the renal artery (e.g., apply electrical
signals to tissue using electrodes of the system) [0182] Measure
"post-ablation" flow rate using any of the example devices or
methods described herein
[0183] The flowchart of FIG. 11 shows another non-limiting example
method for performing an assessment during performance of a
procedure, including an ablation procedure. In this example, a
two-fold or three-fold increase in blood flow rate in the renal
artery is the pre-set condition used as an indicator of an endpoint
of applying the procedure in a feedback assessment. In block 1102,
a baseline flow rate is measured. In block 1104, a procedure is
performed on the tissue, such as but not limited to, a procedure
performed using an example device described herein. In block 1106,
the flow rate subsequently re-measured/re-determined based on flow
sensor measurement data according to the principles described
herein. In block 1108, in a feedback assessment, the re-measured
flow rate is compared to the pre-set value of fluid flow rate or
clinically desired percentage increase in flow rate. If the desired
pre-set value of fluid flow rate or clinically desired percentage
increase in flow rate is attained (block 1110), it signals the
endpoint (1112), and the procedure can be discontinued. If the
desired pre-set value of fluid flow rate or clinically desired
percentage increase in flow rate is not attained (block 1114), the
procedure can be repeated (block 1116) and the flow rate
re-measured and compared to the pre-set value of fluid flow rate or
clinically desired percentage increase in flow rate (1118). If the
desired pre-set value of fluid flow rate or clinically desired
percentage increase in flow rate is attained (block 1120), it
signals the endpoint (1112), and the procedure can be discontinued.
If the desired pre-set value of fluid flow rate or clinically
desired percentage increase in flow rate is not attained (block
1122), the procedure can be modified to achieve the desired
outcome. For example, as shown in block 1124, the position of the
instrument can be changed to some other region of the tissue and
the treatment procedure repeated. In an example, the feedback of
performing the procedure, re-measuring the flow rate and comparing
to the pre-set value of fluid flow rate or clinically desired
percentage increase in flow rate can be repeated until the endpoint
is signaled.
[0184] In an example, an assessment module is provided according to
the systems and methods described herein, where the assessment
module includes a processor and a memory storing processor
executable instructions. Execution of the processor executable
instructions causes the assessment module to perform any of the
example methods described herein, including in connection with FIG.
11.
[0185] FIG. 12 shows a block diagram of an example system including
an assessment module, according to the systems and methods
described herein. A non-limiting example of the system 1200
according to the principles described herein is illustrated in FIG.
12. The system 1200 includes at least one communication interface
1211, at least one memory 1212, and at least one processing unit
1213. The at least one processing unit 1213 is communicatively
coupled to the at least one communication interface 1211 and the at
least one memory 1212. The at least one memory 1212 is configured
to store processor-executable instructions 1214 and an assessment
module 1215. As described in greater detail herein, the assessment
module 1215 can be applied to determine, based on the flow sensor
measurement data 1216, the indication of the flow rate of fluid in
the tissue lumen, including to perform a differential comparison of
flow sensor measurements or using the measures of flow rate to
provide an indication of the efficacy of a procedure being
performed on the tissue (such as but not limited to a procedure to
disrupt nerves). In a non-limiting example, the at least one
processing unit 1213 executes the processor-executable instructions
1214 stored in the memory 1212 at least to provide the feedback
described herein during performance of a procedure. The at least
one processing unit 1213 also executes processor-executable
instructions 1214 to control the memory 1212 to store, or to
control the communication interface 1211 to transmit 1217 to, e.g.,
a user interface or to a controller for any of the example devices
described herein, at least one of an indication of the flow rate,
an indication of an endpoint for the procedure, an indication of an
efficacy of the procedure, and a suggested modification of the
procedure.
[0186] In any example implementation according to the principles
described herein, readings of 3-omega sensors can be used as the
flow sensor on any of the devices described herein to provide an
indication of the rate of flow of the fluid. The 3-omega sensors
have similar fabrication processing steps as the pacing electrodes
or the ablation electrodes. FIG. 13A shows a non-limiting example
of a 3-omega sensor. The 3-omega sensors have intricate filamentary
patterns, which can survive extreme mechanical bending and twisting
and yet maintain performance. The 3-omega sensors measure blood
flow by assessing minute changes in local temperature. Example
results collected in a perfusion chamber with preset flow rates are
shown in FIG. 13B. The 3-omega sensors can be disposed proximate to
the inflatable and/or expandable body (including at the distal
portion of the catheter). The 3-omega sensor can be disposed on the
example device such that the 3-omega sensor is disposed within a
mid-point of a tissue lumen (location of maximum flow velocity) and
three other locations near the wall of the tissue lumen. Data
collected across multiple 3-omega sensors in this configuration can
facilitate flow rate measurements at multiple positions inside the
tissue lumen. The sensitivity of the 3-omega sensors (such as the
example of FIG. 13A) is in the range compatible with blood flow
rates that exist in vivo (.about.5-50 cm/s flow rates).
[0187] In any example implementation according to the principles
described herein, the flow sensing can be performed using other
techniques. For example, an ultrasound measurement can be performed
to provide an indication of the rate of flow of fluid pre-renal
denervation procedure and/or post-renal denervation procedure to
provide the feedback for determining the end-point or a procedure
or to determine whether the procedure should be modified. As
another example, an optical measurement can be used to provide the
indication of the rate of flow of fluid pre-renal denervation
procedure and/or post-renal denervation procedure to provide the
feedback for determining the end-point or a procedure or to
determine whether the procedure should be modified. Other
applicable flow sensing technology is a time-of-flight measurement,
where the flow behavior of a tracker fluid introduced into the
renal artery is measured to used to provide the indication of the
rate of flow of fluid pre-renal denervation procedure and/or
post-renal denervation procedure.
[0188] Fluid flow monitoring before, during and after delivery of
nerve pacing and delivery of a treatment according to the
principles described herein (including ablation energy) are
powerful capability sets, that when offered in a single spiral
catheter, can enhance the efficacy of a treatment procedure
(including a renal denervation procedure). Variations in blood flow
change the local steady-state temperature, which is measured with
the 3-omega sensors. Absence of modulation in renal blood flow
during pacing can indicate that ablation was successful and enable
physicians to determine the end point of the renal denervation
procedure.
[0189] In an example implementation, flow in a perfusion chamber
can be systematically measured that provides programmable fluid
volume velocity to test the sensitivity of a measurement system.
Fluid flow rates can be systematically characterized at various
ambient temperatures, ionic strengths, and viscosities to test how
heat flux, electro-osmosis (during electrical stimulation) and
fluid boundary layer thickness affect flow. The perfusion chamber
can be equipped with electrical sensors that allow concomitant
testing of pacing and ablation.
[0190] An example method for performing a procedure is described in
connection with FIG. 14. The example method includes disposing 1402
an example device according to the principles described herein in
proximity to a tissue, the device including a catheter, at least
one flow sensor disposed on a portion of the catheter, at least one
component coupled to the catheter to perform an ablation procedure
on a portion of a tissue proximate to the catheter, and an
assessment module coupled to the flow sensor to receive data
indicative of at least one flow measurement from the at least one
flow sensor and provide an indication of the efficacy of the
ablation procedure based on the data indicative of at least one
flow measurement. The example method also includes applying 1404
the ablation procedure to the surface of the tissue proximate to
the catheter and recording 1406 a measurement of the flow sensor to
provide an indication of the efficacy of the ablation
procedure.
[0191] FIG. 15 shows an example architecture of an illustrative
computer system 1500 that can be employed to implement any of the
systems and methods described herein. The computer system 1500 of
FIG. 15 comprises one or more processors 1520 communicatively
coupled to memory 1525, one or more communications interfaces 1505,
and one or more output devices 1510 (e.g., one or more display
units) and one or more input devices 1515.
[0192] In the computer system 1500 of FIG. 15, the memory 1525 may
comprise any computer-readable storage media, and may store
computer instructions such as processor-executable instructions for
implementing the various functionalities described herein for
respective systems, as well as any data relating thereto, generated
thereby, or received via the communications interface(s) or input
device(s). The processor(s) 1520 shown in FIG. 15 may be used to
execute instructions stored in the memory 1525 and, in so doing,
also may read from or write to the memory various information
processed and or generated pursuant to execution of the
instructions.
[0193] The example computer system 1500 also includes an assessment
module 1530. Assessment module comprises processor-executable
instructions for performing any of the methods described herein to,
for example, provide an indication of a flow rate, or to provide an
indication of the efficacy of a procedure to disrupt nerves based
on the measured values of flow rate. Processor 1520 can be used to
execute the processor-executable instructions in connection with
assessment module 1530.
[0194] The processor 1520 of the computer system 1500 shown in FIG.
15 also may be communicatively coupled to or control the
communications interface(s) 1505 to transmit or receive various
information pursuant to execution of instructions. For example, the
communications interface(s) 1505 may be coupled to a wired or
wireless network, bus, or other communication means and may
therefore allow the computer system 1500 to transmit information to
and/or receive information from other devices (e.g., other computer
systems). Communication interface(s) 1505 also may be in
communication with an external network 1535. In some
implementations, the communications interface(s) may be configured
(e.g., via various hardware components or software components) to
provide a website or applications program (an App) on a handheld
device as an access portal to at least some aspects of the computer
system 1500. Non-limiting examples of such hand-held devices are
tablets, slates, smartphones, electronic readers, or other similar
hand-held electronic devices.
[0195] The output devices 1510 of the computer system 1500 shown in
FIG. 15 may be provided, for example, to allow various information
to be viewed or otherwise perceived in connection with execution of
the instructions. The input device(s) 1515 may be provided, for
example, to allow a user to make manual adjustments, make
selections, enter data or various other information, or interact in
any of a variety of manners with the processor during execution of
the instructions.
[0196] FIGS. 16A and 16B show the results of example measurement
using an example device according to the principles described
herein. FIGS. 16A and 16B show data from flow sensor measurements
over a dynamic range of flow rates (from about 100 mL/min to about
600 mL/min) for a flow sensor strategically tuned for renal
hemodynamic. FIG. 16A shows measurements made for a 50 microAmps
sensor. FIG. 16A shows measurements made for a 20 microAmps
sensor.
[0197] FIGS. 17A and 17B show the results of example use of an
example device according to the principles described herein for use
in performing an ablative procedure at about 0.2 W to about 0.3 W
of power using electrodes for different exposure times (5 sec, 10
sec, 15 sec, 30 sec, 60 sec). The ablation electrodes are shown to
generate lesions within about 5 seconds of contact with tissue,
without charring. It is observed that a lesion is generated once
the electrodes are in contact with the tissue, soft contact was
sufficient to generate lesions, without excess pressure being
exerted.
[0198] An non-limiting example measurement implementation is
described. A system according to the principles described herein
can be used to process differential measurement. If one sensor is
used, the body temperature of the subject would be taken into
account as well as static flow of the subject. This may require
calibrations that may differ from patient to patient, leading to
less accurate results or may require the physician to slow the
procedure to take separate body temperature static blood flow
measurements in addition to the renal artery flow measurement.
[0199] Non-limiting examples of the innovations described in this
disclosure include:
[0200] a) Expediting up the clinical procedure;
[0201] b) Providing more accurate results to the end point in
therapy; and
[0202] c) Reducing the amount of computation required.
[0203] In a non-limiting example, temperature sensing devices can
be used in combination with a catheter to provide flow
measurements. Electrical circuits can be used to provide
differential measurements. Thin, stretchable, flexible and/or
conformal electronics can be used to provide thin and conformal
means to deploy the sensors described herein on the balloon of the
catheter. The flow sensing systems, device, and methods described
herein can be used for blood flow quantification and for other
types of fluid flows.
[0204] In different example implementations, the change in flow can
be reported to the clinician via direct values. The changes in flow
can be used to show the stage, the progress, or the degree of
success, of a procedure being performed, such as but not limited to
an ablation procedure, for example, by indicating on a console or
display device the procedure status. For example, a change in the
flow rate above a defined value or threshold, can be used to signal
or trigger an action. In an example, the action can be the turning
on of an indicator on the catheter device, or the display of an
icon, numeric value or chart on a display. In an example, the
signal or trigger of the action can be used to provide the
indication of the stage, the progress, or the degree of success of
a procedure.
[0205] According to the example systems, methods and devices
herein, sensing technology onboard catheters are described that
employ thin, conformal arrays of sensors that can deform with the
curvilinear structure of various balloon and spiral-shaped
catheters. The ability to integrate conformal sensors along with
silicon-based electronics on spiral-shaped extrusions and balloons
facilitates, for the first time, ways to integrate multimodal
sensory elements, micro-light emitting diodes (.mu.LEDs) and
integrated circuit building blocks (i.e. amplifiers and logic
gates) onboard catheters, thereby optimizing sensing while at the
same time, not impacting the mechanical properties.
[0206] FIGS. 18A-18G illustrates examples of multi-electrode and
balloon catheter devices, according to the principles described
herein. FIGS. 18A-18G illustrates examples of multi-sensing element
(including multielectrode) devices and catheter devices. The
devices in FIGS. 18A-18D include passive wires with polyimide-based
encapsulation. The wires are exposed in select areas, thus forming
electrode contacts. The electrode array can include, for example,
64 electrodes. FIGS. 18E-18G show the balloon-based ablation
catheters that can be used to apply cryo-, laser-, and high
intensity ultrasound-forms of therapy, respectively, when deployed
proximate to tissue. Any system according to the principles
described herein can be implemented using any of the catheters
shown in FIGS. 18A-18G.
[0207] Other non-limiting examples of catheters that are applicable
to the systems, methods, and apparatus described herein include
Mallecot catheters, spiral coil catheter, mesh catheters,
single-Rod catheters, compliant balloon-based catheters,
non-compliant balloon-based catheters, lasso-shaped catheters,
multispline catheters, dilatation balloon catheters, and
angioplasty balloon catheters.
[0208] Examples of this kind of device are shown in FIGS. 19A-19D.
Electrodes, flow sensors and .mu.LEDs are able to withstand the
significant mechanical strains caused by repetitive inflation and
deflation cycles of the balloon by virtue of their nanomembrane
form factor and the serpentine interconnect geometries, which help
to absorb mechanical strains. FIGS. 19E and 19F highlight
alternative forms of sensing--temperature sensors, electrodes and
flow sensors on conformal substrates. The flow sensing and
electrode elements are useful for RSDN catheters, because
assessment of blood flow can be achieved quickly, without the need
for separate diagnostic devices.
[0209] In an example, 3-omega sensor arrays are used to measure
thermal conductivity and other related thermal, mechanical and
material properties that relate to thermal conductivity. To measure
flow, the sensors are each positioned perpendicularly to the flow
direction. Such a configuration can be compatible with the design
of a spiral shaped catheter system. AC current is applied across
each sensor and the resulting AC voltage is measured. This measured
voltage decreases monotonically as flow rate increases and
increases if the blood is stagnant or slows down. Computations of
measured voltages according to any of the example devices herein
can be calibrated using a perfusion chamber and the flow is assumed
to follow the Hagen-Poiseuille equation and its respective
assumptions. Measurements using 3-omega sensor technology are
versatile because they can be used to extract several other
physical parameters that may be relevant to clinicians. This
sensing modality can be used to serve as a viable platform for RSDN
catheters.
[0210] In an example, mechanical modeling of flow sensors and
electrodes during mechanical stress can be performed. Using
modeling simulations, the dynamic material and mechanical
properties can be characterized for conformal sensor arrays on
balloon and spiral-shaped catheters that experience significant
bending and twisting during operation. This includes analytical and
finite element modeling of the mechanics of flex electronics
affixed to balloon catheters. The strain distributions obtained
through analytical and computational modeling capture,
quantitatively, the nature of deformations in the electronics
layers. Characterization of the effective strain and displacement
distributions in the sensor islands and serpentine interconnects
provide important insights into critical fracture strains and
buckling phenomena. Such characterization of conformal sensors can
dramatically improve the way nanomembrane flow sensors and
electrodes are designed and implemented on highly deformable
substrates (i.e. deflectable catheters). Furthermore, the approach
holds promise for increasing the understanding of the mechanical
stresses involved during catheter deployment in vivo.
[0211] FIG. 20 shows non-limiting examples of flow sensors on
rod-shaped catheters that include "clover-shaped" flow sensors. The
metal rectangles are electrodes on the catheter. In some of the
example catheters of FIG. 20, the flow sensors include angioplasty
balloons with ablation electrodes (the circular pads). In the novel
example systems herein, the clover flow sensors are combined with
the balloon electrodes on a single device.
[0212] According to the systems and methods described herein,
ablation electrodes can be embedded on angioplasty balloon along
with the clover-shaped flow sensors on the proximal and distal
sides of the balloon on the catheter extrusion. According to the
novel systems and methods herein, a multifunctional balloon
catheter that has (i) array of electrodes is coupled with (ii) flow
sensors embedded on the catheter's shaft proximate to the balloon.
In some examples, the balloon catheter may include other sensors on
the balloon, such as but not limited to LEDs, contact sensors,
pressure sensors, biological activity sensors, and temperature
sensors.
[0213] In an example implementation, the catheter with balloon is
deployed proximate to the renal tissue (or other portion of the
renal system) in a deflated state. For example, once the catheter
is in the renal artery, fluid flow can be measured (including blood
flow). Once captured, the balloon can be inflated and the ablation
can be performed. Once the ablation is completed, or at selected
points during performance of the ablation, the balloon can be
deflated and flow is sensed again to see what changes are measured.
In this example, an increase in flow can be used to serve as an
indicator of a successful ablation procedure.
[0214] In another example implementation, the nerve can be paced
and the flow can be measured pre-ablation. The ablation cycle can
be performed. Once the ablation is completed, or at selected points
during performance of the ablation, the nerve can be paced and the
flow can be measured again (including a post-ablation measurement).
If the pacing is determined to causes a change in flow, that can be
used as an indicator that the nerves are still active. If the
pacing does not cause a shift in flow, this can be used as an
indicator that the nerves have been successfully denervated. The
flow sensors coupled with ablation electrodes according to the
systems and methods described herein facilitate this novel analysis
and determination of clinical endpoint.
[0215] FIG. 21 shows a non-limiting example of flow sensors on a
spiral-shaped catheters. FIG. 22 shows a catheter with bipolar
electrodes and metal interconnects disposed on its surface.
[0216] Example design and fabrication are described for examples of
4 flow sensors, 4 pacing electrodes and 4 ablation electrodes all
co-located on spiral-shaped catheters. A custom data acquisition
system is implemented, and the initial functionality of the flow
sensors and electrodes is tested by deploying them in flow
perfusion chambers. Example combined functionalities of the flow
sensors, pacing electrodes and ablation electrodes in the renal
arteries of live porcine models are also described. Spiral
catheters containing the sensors and electrodes are used to measure
blood flow during nerve stimulation immediately pre- and post renal
ablation event. A comparative analysis is conducted of a catheter
system's performance, ease of use, and procedure time relative to
other renal ablation devices being used in the clinical setting to
gain insight into how having a clinical endpoint in RSDN helps to
improve the overall procedure efficacy and safety.
[0217] Non-limiting examples of flow sensors, pacing and ablation
electrodes on multifunctional spiral catheter in perfusion
apparatus is described. Constrained spaces in the renal artery can
reduce the number of devices that can be positioned inside. As a
result, it can be challenging to deploy multiple devices in such as
a confined space as in the renal arteries. Multifunctional RSDN
catheters are constructed with electrodes on spiral-shaped
extrusions that are small enough to conform to the renal artery to
enable electrical stimuli delivery without affecting measurements.
Mechanically optimized nanomembrane electrodes are incorporated
with 3-omega flow sensors that interface with the limited space of
the renal artery. In an example, up to 8 electrodes
(0.25.times.0.25 mm.sup.2) and 4 (1.times.1 mm.sup.2) sensors are
fabricated to measure renal blood flow pre- and post-ablation
events. A data acquisition system (National Instruments Inc.) is
implemented, coupled with an Electrical stimulator console
(Medtronic Inc.) to deliver the 5-10 W of energy to pace and ablate
the renal nerves. This power supply can be used to apply pacing
energy. Using this new system, fundamental limits of the ablation
and pacing electrodes with in vitro tissue can be characterized. In
addition, a custom perfusion chamber can be built to test the flow
sensing capabilities. Taken together, these new designs,
microfabrication approaches and measurements using in-vitro models
can provide insight into the optimal configuration of electrodes
and flow sensors necessary determine changes in flow rate following
renal denervation.
[0218] Non-limiting example pacing and ablation electrodes on
spiral catheter and test performance in vitro are described.
Ultrathin geometries impart flexibility to otherwise rigid and
brittle materials. Ultrathin conformal nanomembrane sensors
(.about.250 nm) embedded in thin polyimide and elastomeric
substrates (.about.50-100 .mu.m) in neutral mechanical plane
layouts accommodate significant mechanical durability with radii of
curvature less than about 1 mm. To achieve conformal sensors with
such designs, arrays of electrodes can be formed on silicon.
Lithographic processing and vertical trench wet-etching techniques
yield isolated chiplets (.about.0.25.times.0.25 mm.sup.2, and
.about.1-5 .mu.m thick) that remain tethered to the underlying
wafer through `anchor` structures. This process can be used to
yield electrodes that are referred to as `printable`, due to their
ability to be removed and placed onto a target substrate with a
soft, elastomeric stamp and transferred onto a spiral catheter. The
attractive features of this approach include: (1) ultrathin circuit
layouts for mechanical flexibility to conform to limited space in
the renal artery, and (2) compatibility with other elements such as
contact or flow sensors.
[0219] The utility of nanomembrane electrodes are tested be perform
ablation measurements by driving RF energy (5-10 W) to show that
renal nerves fibers can be ablated through arterial vessel.
Histological assessment is performed of the nerves pre- and post
ablation cycles to test nanomembrane electrode array performance
and to see if the surface properties of the electrodes change over
time (as a result of protein coating and/or electromosis
phenomena). Measurements performed in the heart and on excised
muscle tissue yield promising results on both pacing and ablation
with this new class of nanomembrane electrodes.
[0220] A non-limiting example data acquisition system is described.
Stimulation waveforms in the form of rectified triangular pulses
with fixed amplitude of 10-20 V and 100-150 ms durations can be
delivered through the pacing electrodes using instructions
programmed into machine readable instructions. The waveform
patterns are chosen strategically to induce renal nerve activity
and to give rise to vasoconstriction or changes in local blood
flow. The data acquisition system includes three modules to measure
blood flow, induce nerve stimulation, and deliver ablation energy.
The data from any of these modules can be transmitted to the
assessment module to perform an assessment of efficacy as described
in connection with any of the examples described herein. A National
Instruments Inc. PXI-6289 (a multifunction M Series data
acquisition (DAQ) system), controlled with custom machine readable
instructions (including in LABVIEW.TM. software), controls voltages
across the sensors.
[0221] Non-limiting example flow sensing, pacing and ablation using
multifunctional spiral catheters in live animal models are
described. Multifunctional balloon and spiral shaped catheter
described in section 1 above are applied to flow sensing and
ablation measurements in live animal models. Balloon catheters can
be used. In an example, balloon catheters may have larger profiles
that can affect flow. In a non-limiting example, to minimize
effects of the catheter on blood flow, spiral-shaped catheters can
be used instead of balloons. Flow can be measured upon initial
deployment in the renal arteries over the course of a few minutes
to determine the initial average flow rate. Once established,
pacing can ensue and flow can be monitored concurrently. A 20-30%
reduction in flow can be expected during this step if the renal
nerves are functioning properly. Once this initial calibration is
completed, the same set of procedures can be run following renal
ablation cycles. It is possible that the renal blood flow may shift
to a different baseline than in the initial measurement. In an
example, this is not used as an indicator of successful ablation.
If ablation is successful, there can be an interpretable effect
that can be apparent during pacing. That is, there may be little
shift in flow during pacing because the vasoconstriction properties
of the nerves can be dysfunctional, which can serve as the clinical
endpoint of the procedure.
[0222] In an example, an example method for determining renal
denervation endpoint when blood pressure and flow are modulated
with nitroglycerine is described. To determine how changes in flow
can be assessed with the sensors described herein, variations in
blood flow caused by nitroglycerine lead to changes in blood
pressure and renal blood flow rates before and after ablation can
be monitored. Systemic injections of nitroglycerine can cause
shifts in blood pressure that can give rise to changes in renal
blood flow. Injections of nitroglycerine also can be monitored to
determine an affect on blood flow pre-pacing and again following
pacing.
[0223] In an example, leakage currents and encapsulation are
described. Conformal flow sensor arrays can be fabricated using a
multi-layer process, which has a thin layer polyimide as the
encapsulating layer. Horizontal and vertical interconnect layers
are insulated using this thin layer of polyimide. In an example
system, leakage currents may escape and lead to noisy recordings,
bubble formation in the fluid, or sensor deterioration over time.
In an example, to prevent leakage currents in these systems,
additional polymeric encapsulation (UV curable polyurethanes or
parylenes) can be coated over the sensors, creating an additional
.about.10 m encapsulating layer to withstand current leakage
effects. Over the course of a few hours (the extent of RSDN
procedures), leakage currents may be manageable with polyurethane,
parylene and UV curable encapsulation strategies.
[0224] Data visualization and signal fidelity is described. Data
acquisition systems developed for recording flow, pacing and
ablation may not be provided in a single module. The visualization
of the measurements recordings and stimuli application may require
feedback from multiple physicians. Interpretation of the flow data
in real time can be challenging. A first generation data
acquisition system is described for measuring and displaying flow.
In an example, the user interface can be configured to be presented
on the same LABVIEW.TM. display as the controls for pacing and
ablation, thereby providing all of the catheter control features on
a single console. This system architecture may be well suited for a
product development implementation.
[0225] Renal nerve stimulation is described. In some examples, the
nerve pacing electrodes may lose contact with the arterial vessel
wall. This variability in good contact may cause poor denervation
results. To counter this effect, x-ray imaging and electrode
impedance recordings can be monitored to restore proper contact
with the vessel wall.
[0226] While various inventive embodiments have been described and
illustrated herein, those of ordinary skill in the art will readily
envision a variety of other means and/or structures for performing
the function and/or obtaining the results and/or one or more of the
advantages described herein, and each of such variations and/or
modifications is deemed to be within the scope of the inventive
embodiments described herein. More generally, those skilled in the
art will readily appreciate that all parameters, dimensions,
materials, and configurations described herein are meant to be
examples and that the actual parameters, dimensions, materials,
and/or configurations will depend upon the specific application or
applications for which the inventive teachings is/are used. Those
skilled in the art will recognize, or be able to ascertain using no
more than routine experimentation, many equivalents to the specific
inventive embodiments described herein. It is, therefore, to be
understood that the foregoing embodiments are presented by way of
example only and that inventive embodiments may be practiced
otherwise than as specifically described. Inventive embodiments of
the present disclosure are directed to each individual feature,
system, article, material, kit, and/or method described herein. In
addition, any combination of two or more such features, systems,
articles, materials, kits, and/or methods, if such features,
systems, articles, materials, kits, and/or methods are not mutually
inconsistent, is included within the inventive scope of the present
disclosure.
[0227] The above-described embodiments of the invention may be
implemented in any of numerous ways. For example, some embodiments
may be implemented using hardware, software or a combination
thereof. When any aspect of an embodiment is implemented at least
in part in software, the software code may be executed on any
suitable processor or collection of processors, whether provided in
a single device or computer or distributed among multiple
devices/computers.
[0228] Also, the technology described herein may be embodied as a
method, of which at least one example has been provided. The acts
performed as part of the method may be ordered in any suitable way.
Accordingly, embodiments may be constructed in which acts are
performed in an order different than illustrated, which may include
performing some acts simultaneously, even though shown as
sequential acts in illustrative embodiments.
[0229] All definitions, as defined and used herein, should be
understood to control over dictionary definitions, definitions in
documents incorporated by reference, and/or ordinary meanings of
the defined terms.
[0230] The indefinite articles "a" and "an," as used herein in the
specification, unless clearly indicated to the contrary, should be
understood to mean "at least one."
[0231] The phrase "and/or," as used herein in the specification,
should be understood to mean "either or both" of the elements so
conjoined, i.e., elements that are conjunctively present in some
cases and disjunctively present in other cases. Multiple elements
listed with "and/or" should be construed in the same fashion, i.e.,
"one or more" of the elements so conjoined. Other elements may
optionally be present other than the elements specifically
identified by the "and/or" clause, whether related or unrelated to
those elements specifically identified. Thus, as a non-limiting
example, a reference to "A and/or B", when used in conjunction with
open-ended language such as "comprising" can refer, in one
embodiment, to A only (optionally including elements other than B);
in another embodiment, to B only (optionally including elements
other than A); in yet another embodiment, to both A and B
(optionally including other elements); etc.
[0232] As used herein in the specification, "or" should be
understood to have the same meaning as "and/or" as defined above.
For example, when separating items in a list, "or" or "and/or"
shall be interpreted as being inclusive, i.e., the inclusion of at
least one, but also including more than one, of a number or list of
elements, and, optionally, additional unlisted items. Only terms
clearly indicated to the contrary, such as "only one of" or
"exactly one of," or "consisting of," will refer to the inclusion
of exactly one element of a number or list of elements. In general,
the term "or" as used herein shall only be interpreted as
indicating exclusive alternatives (i.e. "one or the other but not
both") when preceded by terms of exclusivity, such as "either,"
"one of," "only one of," or "exactly one of."
[0233] As used herein in the specification, the phrase "at least
one," in reference to a list of one or more elements, should be
understood to mean at least one element selected from any one or
more of the elements in the list of elements, but not necessarily
including at least one of each and every element specifically
listed within the list of elements and not excluding any
combinations of elements in the list of elements. This definition
also allows that elements may optionally be present other than the
elements specifically identified within the list of elements to
which the phrase "at least one" refers, whether related or
unrelated to those elements specifically identified. Thus, as a
non-limiting example, "at least one of A and B" (or, equivalently,
"at least one of A or B," or, equivalently "at least one of A
and/or B") can refer, in one embodiment, to at least one,
optionally including more than one, A, with no B present (and
optionally including elements other than B); in another embodiment,
to at least one, optionally including more than one, B, with no A
present (and optionally including elements other than A); in yet
another embodiment, to at least one, optionally including more than
one, A, and at least one, optionally including more than one, B
(and optionally including other elements); etc
* * * * *