U.S. patent application number 16/165583 was filed with the patent office on 2019-04-25 for medical probes and methods of use.
The applicant listed for this patent is Massachusetts Institute of Technology. Invention is credited to Michael J. Cima, Max Joseph Cotler, Khalil Basil Ramadi, Erin Byrne Rousseau.
Application Number | 20190117319 16/165583 |
Document ID | / |
Family ID | 64564957 |
Filed Date | 2019-04-25 |
United States Patent
Application |
20190117319 |
Kind Code |
A1 |
Cima; Michael J. ; et
al. |
April 25, 2019 |
MEDICAL PROBES AND METHODS OF USE
Abstract
A medical probe for guided insertion into soft tissue, such as
the brain, is disclosed. The medical probe may include a flexible,
elongated body having a proximal end portion and an opposed distal
end portion. The elongated body has a length of at least 1 cm and
an outer diameter of 80 .mu.m or less. The distal end portion may
comprise a beveled tip such that the distal end portion of the
medical probe can be steered independently to a target site in the
soft tissue.
Inventors: |
Cima; Michael J.;
(Winchester, MA) ; Ramadi; Khalil Basil;
(Brookline, MA) ; Rousseau; Erin Byrne; (Clifton,
NY) ; Cotler; Max Joseph; (Somerville, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Massachusetts Institute of Technology |
Cambridge |
MA |
US |
|
|
Family ID: |
64564957 |
Appl. No.: |
16/165583 |
Filed: |
October 19, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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62574821 |
Oct 20, 2017 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 90/10 20160201;
A61B 2017/3454 20130101; A61M 2025/0042 20130101; A61M 5/158
20130101; A61B 17/3417 20130101; A61B 34/20 20160201; A61B 17/3403
20130101; A61B 2034/107 20160201 |
International
Class: |
A61B 34/20 20060101
A61B034/20; A61B 90/10 20060101 A61B090/10 |
Goverment Interests
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] This invention was made with Government support under Grant
No. R01 EB016101 awarded by the National Institutes of Health. The
Government has certain rights in the invention.
Claims
1. A medical probe for insertion into soft tissue, the medical
probe comprising: a flexible, elongated body having a proximal end
portion and an opposed distal end portion, wherein the elongated
body has a length of at least 1 cm and an outer diameter of 80
.mu.m or less, and wherein the distal end portion comprises a
beveled tip such that the distal end portion of the medical probe
can be steered independently to a target site in the soft
tissue.
2. The medical probe of claim 1, wherein the elongated body is a
microcapillary.
3. The medical probe of claim 1, wherein the elongated body is
formed of a biocompatible glass or biocompatible metal.
4. The medical probe of claim 1, wherein the beveled tip has a
bevel angle between about 15 degrees and 85 degrees.
5. The medical probe of claim 1, wherein the outer diameter of the
elongated body is between 10 .mu.m and 80 .mu.m.
6. The medical probe of claim 1, wherein the outer diameter of the
elongated body is from about 60 .mu.m to about 80 .mu.m.
7. The medical probe of claim 1, wherein: the outer diameter of the
elongated body is between 20 and 80 .mu.m, the beveled tip has a
bevel angle between about 30 degrees and 80 degrees, the elongated
body has a length from 1 cm to 20 cm, and the elongated body has a
proximal end portion and a distal end portion which comprises the
beveled tip.
8. The medical probe of claim 7, wherein at least 1 cm of the
distal end portion including the beveled tip is unsupported.
9. The medical probe of claim 8, wherein the elongated body is a
metal or glass microcapillary.
10. A kit of parts, comprising: two or more medical probes of claim
1, wherein the angle of the bevel of the beveled tip of at least
one of the medical probes is different from the angle of the bevel
of the beveled tip of at least a second of the medical probes.
11. A system for guided insertion of a medical probe into soft
tissue, comprising: at least one medical probe of claim 1; and an
insertion system which is operable to steer the distal end portion
of the at least one medical probe a traverse distance of at least 1
cm into the soft tissue without the use of a guide tube or
shuttle.
12. The system of claim 11, wherein the insertion system includes a
motor, actuator, and controller configured to linearly displace and
axially rotate the at least one medical probe.
13. A method of inserting a medical probe into soft tissue, the
method comprising: identifying a target site in the soft tissue;
providing the medical probe of claim 1; and independently steering
the distal end portion of the medical probe into the soft tissue a
distance to insert the beveled tip to reach the target site.
14. The method of claim 13, wherein the steering comprises rotating
the beveled tip about the longitudinal axis of the elongated
bodying during insertion into the soft tissue.
15. The method of claim 13, wherein at least 1 cm of a distal end
portion of the medical probe including the beveled tip is
unsupported during the steering.
16. The method of claim 13, wherein at least 2 cm of a distal end
portion of the medical probe including the beveled tip is
unsupported during the steering.
17. The method of claim 13, wherein the step of providing the
medical probe comprise selecting the medical probe which has a
bevel angle of the beveled tip predetermined to produce a radius of
curvature of insertion trajectory desired to reach the target site
from an initial insertion point.
18. The method of claim 13, wherein the soft tissue is the brain of
a patient in need of treatment and/or diagnosis.
19. A method of treatment of a specific site in soft tissue in a
patient, comprising: identifying a target site in the soft tissue;
providing the medical probe of claim 1; independently steering the
distal end portion of the medical probe into the soft tissue a
distance to insert the beveled tip to reach the target site; and
delivering a treatment substance or energy through the elongated
body of the medical probe and out of the distal end portion to the
target site in the soft tissue.
20. The method of claim 19, wherein the step of identifying a
target site in the soft tissue comprises imaging the soft tissue
and identifying an initial insertion point and an insertion
trajectory desired to reach the target site from the initial
insertion point.
21. The method of claim 19, wherein the soft tissue is the brain of
the patient.
22. The method of claim 19, wherein the step of identifying a
target site in the soft tissue comprises imaging the soft tissue
and identifying an initial insertion point and an insertion
trajectory desired to reach the target site from the initial
insertion point.
23. The method of claim 19, wherein the medical probe is a
microcapillary, the soft tissue is the brain, and a
pharmaceutically active agent is delivered through a lumen of the
microcapillary to the target site.
24. A method of inserting a medical probe into soft tissue, the
method comprising: identifying a target site in the soft tissue;
providing an elongated medical probe having an outer diameter
between 10 and 80 .mu.m and comprising a distal end portion having
a beveled tip; and independently steering the distal end portion of
the medical probe into the soft tissue a distance of at least 1 cm
to reach the target site.
25. The method of claim 24, wherein the soft tissue is the brain of
a patient in need of treatment and/or diagnosis.
26. The method of claim 24, wherein the steering comprises rotating
the beveled tip about a longitudinal axis of the medical probe
during insertion into the soft tissue.
27. The method of claim 24, wherein the step of providing the
medical probe comprise selecting the medical probe which has a
bevel angle of the beveled tip predetermined to produce a radius of
curvature of insertion trajectory desired to reach the target site
from an initial insertion point.
28. A method of treatment of a specific site in soft tissue in a
patient, comprising: identifying a target site in the soft tissue;
providing a medical probe comprising a distal end portion having a
beveled tip, wherein providing the medical probe comprises
selecting the medical probe which has a bevel angle of the beveled
tip predetermined to produce a radius of curvature of insertion
trajectory desired to reach the target site from an initial
insertion point; independently steering the distal end portion of
the medical probe into the soft tissue a distance of at least 1 cm
to reach the target site; and delivering a treatment substance or
energy through the medical probe and out of the distal end portion
to the target site in the soft tissue.
29. The method of claim 28, wherein the soft tissue is the brain of
the patient.
30. The method of claim 28, wherein the step of identifying a
target site in the soft tissue comprises imaging the soft tissue
and identifying the initial insertion point and the insertion
trajectory desired to reach the target site from the initial
insertion point.
31. The method of claim 28, wherein the medical probe is a
microcapillary, the soft tissue is the brain, and a
pharmaceutically active agent is delivered through a lumen of the
microcapillary to the target site.
32. A method of diagnosis of a patient, comprising: identifying a
target site in a soft tissue in the patient; providing a medical
probe comprising a distal end portion having a beveled tip, wherein
providing the medical probe comprises selecting the medical probe
which has a bevel angle of the beveled tip predetermined to produce
a radius of curvature of insertion trajectory desired to reach the
target site from an initial insertion point; independently steering
the distal end portion of the medical probe into the soft tissue a
distance of at least 1 cm to reach the target site; and withdrawing
a fluid sample from the target site through a lumen in the medical
probe and then analyzing the fluid sample.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This disclosure claims priority to and the benefit of U.S.
provisional patent application No. 62/574,821, filed Oct. 20, 2017,
which is incorporated by reference herein in its entirety.
FIELD OF THE DISCLOSURE
[0003] The disclosure generally relates to medical devices and more
particularly relates to a medical probe for insertion into soft
tissue and methods of targeting specific sites within soft tissue
for treatment or diagnosis.
BACKGROUND
[0004] The insertion of thin probes through a variety of media is
important for a number of medical applications including infusion
and withdrawal of fluid, as well as electrical and
photo-stimulation. For example, neurological diseases have garnered
increased interest in new drug delivery strategies due to the
difficulty of targeting the brain through systemic drug
administration (intravenous or oral). Additionally, diseases
arising from specific malfunction of a brain region are ideal
candidates for targeted therapy through implanted devices. For
example, epilepsy affects over 4 million adults in the U.S. alone
with over $40B/yr in direct costs. Parkinson's disease affects over
10 million people worldwide and generates over $25B/yr in costs.
Deep brain stimulation probes have become increasingly common to
treat various neurological disorders. Over 100,000 procedures have
been performed, with each costing on average $50,000.
[0005] Biological implant dimensions are generally minimized to
reduce trauma of insertion as well as foreign body response. In a
clinical scenario, probe size is minimized to reduce trauma. For
the same reason, the number insertion points are minimized. Both
aspects are particularly important in the brain, where trauma needs
to be minimized. However, the size minimization is limited by
functional and mechanical requirements of the implant and by
conventional beliefs about the insertion/deployment process of such
implants into patients' soft tissues.
[0006] Microcapillaries (<100 .mu.m) have been inserted into the
brain to target specific regions. However, these conventional
probes have been inserted only with the use of a larger guide tube
or shuttle due to their small size and fragility, wherein the
microcapillary extends merely a few millimeters out of the guide
tube or shuttle. Accordingly, the large size of the shuttle
obviates the benefit of the small size of the microcapillary. In
addition, the small size of these probes presents a unique
challenge in handling and insertion to desired targets without
breakage while maintaining high precision. Such small-scale
capillaries, sometimes thinner than a human hair, have been
considered unsuitable for unsupported insertion due to their high
aspect ratio (length:diameter) making them susceptible to buckling
and breaking, limiting their applicability to uses requiring
precise guided insertion. Since the high aspect ratio of such
capillaries causes them to be highly flexible and prone to buckling
upon insertion into tissue, the microscale probes conventionally
used in neuroscience are always inserted with the help of a larger
guide shuttle or a dissolvable support material. However, these
relatively large auxiliary components negate the potential
advantages of the microcapillaries to reduce trauma and
scarring.
[0007] It therefore would be desirable to provide improved medical
probes and microcapillary devices and improved methods of
targeted/guided insertion of such medical probes to internal soft
tissue sites (e.g., the brain) for a variety of treatment and other
medical interventions.
SUMMARY
[0008] Some or all of the above needs and/or problems may be
addressed by certain embodiments of the medical probes and methods
disclosed herein. Medical probes for guided insertion into soft
tissue are provided, along with methods of inserting and using
those medical probes.
[0009] In one aspect, a medical probe for insertion into soft
tissue is provided. The medical probe includes: a flexible,
elongated body having a proximal end portion and an opposed distal
end portion, wherein the elongated body has a length of at least 1
cm and an outer diameter of 80 .mu.m or less (e.g., between 10 and
80 .mu.m), and wherein the distal end portion comprises a beveled
tip such that the distal end portion of the medical probe can be
steered independently to a target site in the soft tissue. The
beveled tip may have a bevel angle between about 15 degrees and 85
degrees. The elongated body may be a microcapillary and may be
formed of a biocompatible glass or metal.
[0010] In another aspect, a method of inserting a medical probe
into soft tissue is provided. In some embodiments, the method
includes: identifying a target site in the soft tissue; providing
an elongated medical probe having an outer diameter between 10 and
80 .mu.m and comprising a distal end portion having a beveled tip;
and independently steering the distal end portion of the medical
probe into the soft tissue a distance, e.g., at least 1 cm, to
reach the target site. In embodiments, the distal end portion of
the medical probe including the beveled tip, e.g., at least 1 cm of
the distal end portion, is unsupported during the steering and
insertion. The soft tissue may be the brain of a patient in need of
treatment and/or diagnosis. The steering may include rotating the
beveled tip about a longitudinal axis of the medical probe during
insertion into the soft tissue. The step of providing the medical
probe may include selecting the medical probe which has a bevel
angle of the beveled tip predetermined to produce a radius of
curvature of insertion trajectory desired to reach the target site
from an initial insertion point.
[0011] In still another aspect, a method of treatment of a specific
site in soft tissue in a patient is provided. In some embodiments,
the method includes: identifying a target site in the soft tissue;
providing a medical probe comprising a distal end portion having a
beveled tip, wherein providing the medical probe comprises
selecting the medical probe which has a bevel angle of the beveled
tip predetermined to produce a radius of curvature of insertion
trajectory desired to reach the target site from an initial
insertion point; independently steering the distal end portion of
the medical probe into the soft tissue a distance, e.g., of at
least 1 cm, to reach the target site; and then delivering a
treatment substance or energy through the medical probe and out of
the distal end portion to the target site in the soft tissue. The
soft tissue may be the brain of a patient in need of treatment. In
some embodiments, the medical probe is a microcapillary and a
pharmaceutically active agent is delivered through a lumen of the
microcapillary to the target site. In some other embodiments, the
medical probe is solid and electrical and photo-stimulation is
delivered through the probe to the target site.
[0012] In yet another aspect, a method of diagnosis of a patient is
provided. In some embodiments, the method includes: identifying a
target site in a soft tissue in the patient; providing a medical
probe comprising a distal end portion having a beveled tip, wherein
providing the medical probe comprises selecting the medical probe
which has a bevel angle of the beveled tip predetermined to produce
a radius of curvature of insertion trajectory desired to reach the
target site from an initial insertion point in the patient;
independently steering the distal end portion of the medical probe
into the soft tissue a distance of at least 1 cm to reach the
target site; and withdrawing a fluid sample from the target site
through a lumen in the medical probe and then analyzing the fluid
sample.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] The detailed description is set forth with reference to the
accompanying drawings. The use of the same reference numerals may
indicate similar or identical items. Various embodiments may
utilize elements and/or components other than those illustrated in
the drawings, and some elements and/or components may not be
present in various embodiments. Elements and/or components in the
figures are not necessarily drawn to scale. Throughout this
disclosure, depending on the context, singular and plural
terminology may be used interchangeably.
[0014] FIG. 1 is a perspective view of a beveled tip end of a
capillary medical probe in accordance with one or more embodiments
of the disclosure. The line drawing of this figure is a
reproduction for clarity of a scanning electron microscopy (SEM)
image of a bevel tipped borosilicate capillary that was
produced.
[0015] FIG. 2 is a side view of a beveled tip end of a medical
probe, depicting a beveled tip having an angle .theta. and a
theoretical force F, in accordance with one or more embodiments of
the disclosure. The line drawing of this figure is a reproduction
for clarity of an SEM image of a bevel tipped borosilicate
capillary that was produced.
[0016] FIG. 3 depicts an experimental set-up of a linear insertion
system for inserting and steering a medical probe into a soft
tissue model, in accordance with an embodiments of the
disclosure.
[0017] FIGS. 4A-4C depict curved trajectories of a medical probe
inserted into a soft tissue model, relative to a linear insertion
axis, in accordance with one or more embodiments of the disclosure.
The line drawings of these figures are reproductions for clarity of
photographic images of a bevel tipped borosilicate capillary that
was inserted into an agarose gel tissue model. FIG. 4A is taken
from an optical image, and FIGS. 4B and 4C are taken from
fluorescent images taken during testing.
[0018] FIGS. 5A-5B are graphs depicting the radius of curvature of
the insertion path (trajectory) of a medical probe inserted into
different agarose tissue models and into ex vivo cow brain, as it
relates to the bevel angle of the medical probe, in accordance with
one or more embodiments of the disclosure.
[0019] FIG. 6 is a graph which depicts the radius of curvature
versus the bevel angle, in accordance with one or more embodiments
of the disclosure.
[0020] FIG. 7A is a graph which depicts insertion distance from a
predetermined target for bevel tipped probes and unpolished probes
in experiment assessing targeting accuracy, in accordance with one
or more embodiments of the disclosure.
[0021] FIG. 7B is a photographic image which depicts a capillary
guided within 0.5 mm of a target in 0.6% agarose gel at 2 cm while
avoiding an obstacle, in accordance with one or more embodiments of
the disclosure.
[0022] FIGS. 8A-8C are graphs depicting three biomarkers for glial
scarring following 8 weeks of probe implantation in rat brain, in
accordance with one or more embodiments of the disclosure.
[0023] FIG. 9 shows two CT scans of 60 .mu.m medical probes,
flushed with iodine contrast agent, in rats, in accordance with one
or more embodiments of the disclosure.
DETAILED DESCRIPTION
[0024] Improved medical probes for insertion into soft tissue have
been developed and are disclosed herein. In certain embodiments,
the probe is a microscale, flexible elongate structure having a
large aspect ratio, yet advantageously can be inserted into and
steered in the soft tissue without the use of real-time imaging
guidance and without the use a larger guide tube or shuttle to
accurately and reproducibly reach a target site (e.g., an
anatomical structure) in the tissue.
[0025] It has been surprisingly discovered that--unlike larger
diameter probes--probes having an outer diameter of 80 microns, 60
microns, or less, are small enough that the lateral forces produced
by a beveled tip are large enough to produce a curved insertion
trajectory of the probe. That is, at this small size, a defined
relationship between bevel angle and trajectory curvature exists
and is reproducible. It also has been surprisingly discovered that
these medical probes can be inserted into soft tissue unsupported
and independently, e.g., without a guide tube, without breakage of
the probe.
[0026] An additional benefit of the small-scale of these medical
probes is that this size range greatly reduce glial scarring when
inserted into the brain as compared to conventional, larger
diameter medical probes.
[0027] The Medical Probe
[0028] The medical probe generally includes a flexible, elongated
body having a proximal end portion and an opposed distal end
portion, wherein the elongated body has a length of at least 1 cm
and an outer diameter of 80 .mu.m or less, and wherein the distal
end portion comprises a beveled tip such that the distal end
portion of the medical probe can be steered independently to a
target site in the soft tissue. As used herein, the term
"independently steering" means without mechanical support of at
least 1 cm of the distal end portion of the probe and without the
use of real-time imaging guidance.
[0029] As detailed in the examples, the geometry of at least the
distal portion of the medical probe are important to produce the
asymmetric force and deflection needed for non-linear steering of
the probe in biological tissue. In preferred embodiments, the
elongated body is cylindrical in shape, i.e., it has a circular
cross-sectional shape when viewed along the longitudinal axis
extending between the proximal and distal ends. In some
embodiments, the outer diameter of the elongated body of the probe
is from 5 .mu.m to 80 .mu.m, e.g., from 10 .mu.m to 80 .mu.m, 20
.mu.m to 80 .mu.m, from 25 .mu.m to 80 .mu.m, from 30 .mu.m to 80
.mu.m, or between 30 and 80 .mu.m. In some embodiments, the outer
diameter of the elongated body of the probe is from 5 .mu.m to 60
.mu.m, e.g., from 10 .mu.m to 60 .mu.m, 20 .mu.m to 60 .mu.m, from
25 .mu.m to 60 .mu.m, from 30 .mu.m to 60 .mu.m, or between 30 and
60 .mu.m. In some embodiments, the outer diameter of the elongated
body of the probe is from 40 .mu.m to 80 .mu.m, e.g., from 50 .mu.m
to 80 .mu.m, from 60 .mu.m to 80 .mu.m, or between 60 and 80 .mu.m.
It is possible that other diameters of the elongated body may be
used in some embodiments.
[0030] The angle of the beveled tip correlates to the radius of
curvature of the insertion path of the medical probe in biological
tissue. A bevel angle is defined by the intersection between a
longitudinal axis of the body and the beveled tip surface. In some
embodiments, the beveled tip has a bevel angle from about
15.degree. to about 85.degree., from about 30.degree. to about
70.degree., from about 25.degree. to about 60.degree., or from
about 35.degree. to about 45.degree.. In some embodiments, the
beveled tip has a bevel angle between about 30 degrees and 80
degrees. The angle may be selected based on the preferred radius of
curvature identified to reach a selected target tissue site from a
selected initial point of insertion into the tissue. The beveled
tip surface preferably is substantially planar.
[0031] The medical probe may have essentially any length suitable
for use. Typically, the length is at least 1 cm. In some
embodiments, the elongated body has a length from 1 cm to 20 cm. In
some embodiments, at least 1 cm, or at least 2 cm, of the distal
end portion including the beveled tip is unsupported, at least
during insertion to the target tissue site.
[0032] The elongated body may be formed of essentially any
biocompatible material which is manufacturable in the required
dimensions and possesses the desired flexibility and mechanical
strength for use without breaking. In particular embodiments, the
biocompatible material is a glass or metal known in the art. In
some embodiments, the elongated body is formed of a
borosilicate.
[0033] The elongated body of the medical probe may be a
microcapillary (i.e., includes a lumen extending between the
proximal and distal ends) or may be solid (i.e., includes no lumen
extending between the proximal and distal ends). In some preferred
embodiments, the elongated body of the microcapillary is annular in
shape. The description of microcapillaries in the examples below
also applies to solid medical probes except where the lumen is
essential (e.g., for the transport of substances therethrough).
[0034] In some embodiments, the medical probe has an elongated body
having a length from 1 cm to 20 cm and an outer diameter between 30
and 80 .mu.m, and the beveled tip has a bevel angle between about
15.degree. and 85.degree., e.g., from 30.degree. to 80.degree.. In
some of these embodiments, the outer diameter is between 30 .mu.m
and 60 .mu.m, or between 40 .mu.m and 75 .mu.m. In some of these
embodiments, the elongated body has a proximal end portion and a
distal end portion which comprises the beveled tip, and at least 1
cm of the distal end portion including the beveled tip is
unsupported. The proximal end of the elongated body may be
configured for attachment to (i) a fluid transfer device such as a
pump or syringe, and/or (ii) an electrical energy source or light
energy source. Such attachment may be with or adapted from
conventional means for operably connecting known pumps and
conventional larger medical probes. The elongated body may be a
metal or glass microcapillary, such a borosilicate
microcapillary.
[0035] In some embodiments, a kit is provided that includes two or
more medical probes having different predefined bevel angles. That
is, the angle of the bevel of the beveled tip of at least one of
the medical probes is different from the angle of the bevel of the
beveled tip of at least a second of the medical probes. For
example, a kit may include ten or more different bevel angles
(e.g., 20.degree., 25.degree., 30.degree., 35.degree., 40.degree.,
50.degree., 55.degree., 60.degree., 65.degree., 70.degree.), such
that a physician can select the appropriate one after determining a
desired radius of curvature for a particular insertion path to
reach a target tissue site in a patient.
[0036] FIG. 1 illustrates the distal end portion of one embodiment
of medical probe 100. The medical probe 100 includes a flexible,
elongated body 102 having a proximal end portion 104 and an opposed
distal end portion 106. The distal end portion 106 has a beveled
tip 108. The medical probe 100 is a microcapillary, and the
elongated body 102 includes a lumen 110 extending between the ends,
e.g., through the longitudinal axis of the medical probe. FIG. 2
shows the angle .theta. of the bevel of the beveled tip 108 of the
medical probe 100, and the net force F.sub.net as it related to the
bevel angle.
[0037] Insertion Systems
[0038] System also are provided for guiding insertion of the
medical probe into soft tissue. In embodiments, the system includes
at least of the medical probes described herein, and an insertion
system which is operable to steer the distal end portion of the at
least one medical probe a traverse distance, e.g., at least 1 cm,
into the soft tissue without the use of a guide tube or shuttle.
Suitable insertion and steering mechanisms for operable engaging
with the proximal end of the medical probe (or any portion between
the proximal end and the distal end) may be adapted from those
known in the art. For example, the insertion system may include a
motor, actuator, and controller configured to linearly displace and
axially rotate the at least one medical probe. For example, the
proximal end portion of the medical probe may be releasably fixed
to an actuator that is mechanically coupled to the motor.
Micromotors and step motors are known in the art for controlling
linear and rotation movements at micrometer scale distances.
[0039] Methods of Inserting the Medical Probe
[0040] Methods for guided insertion of a medical probe into soft
tissue are provided. The soft tissue may be essentially any
suitable biological tissue of a patient. The patient may be a human
or other mammal, for example. The soft tissue may be a neural
tissue, such as the brain or a nerve. In some embodiments, the soft
tissue is the brain of a patient in need of treatment and/or
diagnosis. In other instances, the soft tissue is one or more
abdominal organs (e.g. the liver and/or lungs) of a patient in need
of treatment and/or diagnosis. The soft tissue may be essentially
any suitable biological tissue of a patient that has a localized
disease (e.g., a tumor, abscess, etc.) in need of treatment and/or
diagnosis.
[0041] In some embodiments, the method of inserting a medical probe
into soft tissue includes: (i) identifying a target site in the
soft tissue; and then (ii) independently steering the distal end
portion of the medical probe into the soft tissue a distance to
insert the beveled tip to reach the target site. The distance may
be at least 1 cm, or at least 2 cm, wherein at least 1 cm, or at
least 2 cm, of a distal end portion of the medical probe including
the beveled tip is unsupported during the steering. The insertion
path is generally non-linear, e.g., arcuate.
[0042] In some embodiments, the steering comprises rotating the
beveled tip about the longitudinal axis of the elongated bodying
during insertion into the soft tissue. Rotational steering can be
useful for an insertion trajectory that includes two or more
different radii of curvature, e.g., to steer around and avoid
certain more sensitive anatomical structures. In another case, the
inclusion of rotation can be useful for reaching two or more
different target sites without or with only partial withdrawal of
the probe, which advantageously can help minimize collateral tissue
damage and scarring.
[0043] In some embodiments, the step of identifying a target site
in the soft tissue comprises imaging the soft tissue and
identifying an initial insertion point and an insertion trajectory
desired to reach the target site from the initial insertion point.
Any suitable imaging devices may be used, including CT or the like.
In some embodiments, the step of providing the medical probe
comprises selecting a medical probe which has a bevel angle of the
beveled tip predetermined to produce a radius of curvature of
insertion trajectory desired to reach the target site from the
initial insertion point.
[0044] For example, a surgeon may begin by imaging the brain or
other soft tissue site to be treated. Using the image data from the
treatment site, the surgeon can map a pathway to the treatment
site, from a specific insertion site, such as a burr hole. Through
the known and predictable relationship, disclosed herein, between
the bevel angle and the radius of curvature, the physician can
select an appropriate beveled tip probe from a kit containing
multiple probes (e.g., microcapillaries) with different bevel
angles. The probe may then be directly inserted without the need
for a guide tube or shuttle, including depths of 1 cm or more.
Alternatively, it would be possible for a surgeon, in real-time, to
polish the desired bevel angle on the probes prior to use. Due to
the flexibility of the probes a second treatment site may be
reached utilizing the original insertion hole, through guiding the
probes to a different anatomic site by varying the rotation during
insertion, or through the use of a different bevel angle on a new
probes.
[0045] In this way, the insertion method allows for the control of
the micron-scale probes during insertion through steering, allowing
them to precisely target an anatomically diverse set of targets
with no or minimal probe fracture. The method may include imaging a
soft tissue area that requires treatment, such as the brain. The
surgeon may then identify a targeted treatment area prior to the
insertion of the probe through a burr hole into the soft tissue
without the use of a guide, sheath, or shuttle. During insertion,
the surgeon may then steer the tip of the probe by rotating the
probe about its longitudinal axis during insertion, the resulting
force causing the tip of the probe to follow a predictable arc as
it is inserted.
[0046] When the probe is inserted, the resulting force causes the
tip to follow a predictable arc (if inserted linearly) or corkscrew
(if rotated during insertion). By rotating the probe during the
insertion, precise positioning of the tip in three dimensions can
be achieved allowing the device to be guided, or steered along
numerous different paths to multiple different anatomical locations
from a single insertion point. Various bevel angles may be utilized
to achieve different radii of curvature during
implantation/insertion. These configurations allow for
significantly deeper unsupported insertion of capillaries in this
size range than was previously assumed feasible.
[0047] With the ability to guide or steer the probe through the
soft tissue during insertion, non-linear pathways can be taken to
targeted treatment sites, which can allow for access to multiple
anatomical locations from a single insertion point, and allow the
insertion process to be guided around and away from sensitive
tissues. With predictable guidance, the need for real-time imaging
of the insertion process is obviated which is additionally
beneficial due to the difficulty of imaging such small-scale
probes. Implantation (insertion) of solid probes and
microcapillaries such as the ones described here may be
particularly useful for their ability to target different regions
of the brain, for example, through a single burr hole, decreasing
risk for surgical morbidity and mortality.
[0048] Methods of Using the Medical Probe
[0049] The medical probes disclosed herein may be used for
essentially any suitable purpose, This purpose typically includes
the transport of substances or energy to or from the target tissue
site. The target tissue site may be in healthy soft tissue or
diseased tissue, e.g., a tumor. In some embodiments, the probe is a
microcapillary effective for transport of fluid substances
therethrough, e.g., of the delivery of a pharmaceutical agent to
the target tissue site or the withdrawal of a biological fluid at
the site. In some other embodiments, the medical probe is solid or
a microcapillary and is used to deliver electrical energy or light
to stimulate certain cells or nerves at the tissue site, or to
sense electrical signals.
[0050] In some embodiments, a method is provided for treatment of a
specific site in soft tissue in a patient. The method includes (i)
identifying a target site in the soft tissue; (ii) independently
steering the distal end portion of the medical probe into the soft
tissue a distance to insert the beveled tip to reach the target
site; and then (iii) delivering a treatment substance or energy
through the elongated body of the medical probe and out of the
distal end portion to the target site in the soft tissue. The step
of identifying a target site in the soft tissue may include imaging
the soft tissue and identifying an initial insertion point and an
insertion trajectory desired to reach the target site from the
initial insertion point. The step of steering the distal end of the
medical probe may include inserting the tip a distance of at least
1 cm, or at least 2 cm, wherein the distal end portion of the probe
is unsupported. In some embodiments, the soft tissue is the brain
of the patient. In some particular embodiments, the medical probe
is a microcapillary, the soft tissue is the brain, and a
pharmaceutically active agent is delivered through a lumen of the
microcapillary to the target site.
[0051] In some particular embodiments, the treatment method
includes (i) identifying a target site in the soft tissue; (ii)
providing a medical probe comprising a distal end portion having a
beveled tip, wherein providing the medical probe comprises
selecting the medical probe which has a bevel angle of the beveled
tip predetermined to produce a radius of curvature of insertion
trajectory desired to reach the target site from an initial
insertion point; (iii) independently steering the distal end
portion of the medical probe into the soft tissue a distance to
reach the target site; and (iv) delivering a treatment substance or
energy through the medical probe and out of the distal end portion
to the target site in the soft tissue. The step of identifying a
target site in the soft tissue may include imaging the soft tissue
and identifying the initial insertion point and the insertion
trajectory desired to reach the target site from the initial
insertion point. The step of steering the distal end of the medical
probe may include inserting the tip a distance of at least 1 cm,
wherein the distal end portion of the probe is unsupported.
[0052] In some embodiments, the medical probe is a microcapillary
used to deliver drugs, of specific volumes and administration
timelines, to targeted regions of the body. In some particular
embodiments of the method, the medical probe is a microcapillary,
the soft tissue is the brain, and a drug is delivered through a
lumen of the microcapillary to the target site. The drug may be
essentially any prophylactic or therapeutic agents, or any active
pharmaceutical ingredient, known in the art. The drug typically is
in liquid excipient vehicle, such as water or saline. The drug may
include a neuromodulating agent. In some embodiments, the
neuromodulating agent comprises muscimol or another GABA agonist.
Other neuromodulating agents known in the art also may be used.
[0053] In some other particular embodiments, the medical probe
includes a solid tubular body (e.g., borosilicate) configured for
use in electrical and photo-stimulation, as known in the art.
[0054] In some embodiments, the medical probe is a microcapillary
used to take liquid biopsies from the body of a patient, which may
be used to identify disease type, state, and progression.
[0055] Once the medical probe is inserted at the desired location
in vivo, for example, in the brain of a patient, the small size of
the probes minimizes glial scarring, allowing for long-term fluid
infusion and withdrawal for a variety of therapeutic and diagnostic
applications.
EXAMPLES
[0056] As depicted in FIG. 3, a linear insertion system 112 was
used to insert and steer the medical probe 100 into a soft tissue
model 114. The experimental setup depicted in FIG. 3 was used to
linearly insert fibers (i.e., medical probes 100 comprising 60
micron or 80 micron OD microcapillaries having a 50.degree. beveled
tip made by polishing) into the soft tissue model 114, which in
this experiment comprises 0.6% agarose gel, to curved trajectories
of up to 10 cm depth. The soft tissue model 114 was disposed on an
adjustable table 116, and the medical probe 100 was attached to a
linear stage 118 via a fiber holder 120. The fiber holder 120 was
rotatable. As can be seen in FIGS. 4A-4C, the medical probe 100
includes curved trajectories of up to 10 cm depth in the soft
tissue model 114 relative to the linear insertion axis 122. The
test was repeated in different insertion media.
[0057] A beveled-tip cylindrical probe experienced a net lateral
force during insertion into a medium resulting in a predictable
curved trajectory. This force arises from the asymmetry of the tip,
and is dependent on the tip geometry. A theoretical illustration of
this net lateral force is shown in FIG. 2, which depicts an example
beveled-tip with bevel angle .theta. and theoretical force F. By
controlling rotation of the probe during lateral insertion, the
probe trajectory curvature can be guided to a multitude of
locations from a single insertion point, and can be done so without
the need for real-time imaging.
[0058] As depicted in FIGS. 5A, 5B, and 6, several relationships
has been identified between probe geometry and final trajectory
through the systematic insertion of bevel tipped probes into 0.6%
agarose gel tissue model and other media. FIGS. 5A and 5B
illustrate that the radius of curvature of the 60 micron OD medical
probe is predictable in multiple insertion media based upon bevel
angle, while FIG. 6 illustrates that the curvature, at several
bevel angles, is repeatable and statistically significant in 0.6%
Agarose. For example, increased bevel angles (increased surface
area) results in a lower radius of curvature (more deflection).
Similar results were also obtained when repeated with 80 micron OD
medical probes. This relationship can be utilized to create
predicted needle trajectories for precise of targeting of multiple
anatomical locations in the brain or other soft tissue sites.
[0059] For a comparison of targeting accuracy, microcapillaries
with no beveled tip (unpolished) were also inserted into a tissue
model (0.6% agarose gel). The results, as illustrated in FIG. 7A
show that the 50.degree. bevel-tipped probes reached the target
more accurately more often than the unpolished probes. FIG. 7B
depicts one of these bevel-tipped probes reaching a predicted
target along a curved trajectory around a hypothetical obstacle.
This shows that these probes enable insertion methods which can
obviate the need for any closed-loop feedback or real-time image
guidance.
[0060] The tests that were conducted show that the curvature of the
insertion trajectory is predictable in different insertion media
based upon the bevel angle and that the curvature of the insertion
trajectory is repeatable and statistically significant in the
tissue models, at insertion distances of 1 cm and 2 cm.
[0061] Previous investigators have proposed using bevel angle as a
means of controlling cannula deflection. However, a relationship
between bevel angle and deflection has not been observed. For
example, a recent publication has claimed that bevel angle had no
effect on curvature ex vivo or in vivo (Van de Berg et al.
IEEE/ASME Transactions on Mechatronics. 2015; 20 (5)) and thus, is
an ineffective means for controlling or guiding the tip during
insertion.
[0062] The importance of cannula dimensions to guidance has been
previously unrecognized. However, a defined relationship between
bevel angle and curvature in vitro and ex vivo for cannulas less
than or equal to 80 microns in diameter has now been discovered.
The relationship is also surprisingly reproducible, so much so,
that it enables placement of cannulas in the brain without imaging
guidance. In fact, the small diameter of the microcapillaries
actually pronounces the effectiveness and predictability of the
control.
[0063] The smallest beveled capillaries previously tested have a
diameter of 500 .mu.m. The large size of the tip limits the
feasibility of using them in practice due to additional trauma.
Recent publications on this have acknowledged this limitation, and
recommended that needle size be minimized. However, they also state
that "flexible needle navigation inside the tissue is very
complicated and requires implementing image processing abilities"
(Ramezanpour H., Yousefi H., Rezaei M., Rostami M., J Biomed Phys
Eng 2015; 5(4) 211).
[0064] Here, control of flexible thin probes in tissue phantoms
(models) has been achieved without image processing abilities.
Although certain applications have used small-scale capillaries in
the past, those applications have relied on the use of a larger
guide tube or shuttle, with only a small fraction of the capillary
exposed from the end of the guide tube or shuttle. As described
herein, the outer diameter of the beveled capillaries may range
between 10 .mu.m and 80 .mu.m.
[0065] Testing utilizing 60 .mu.m and 80 .mu.m glass fiber
microcapillaries produced surprisingly repeatable results, although
microcapillaries made from metals with a similar moduli of
elasticity may also be suitable. Through the use of different bevel
angles, different radii of curvature for the insertion path of the
microcapillary can be achieved.
[0066] Medical probes as described herein (60 .mu.m diameter) were
implanted in vivo in the brains of rats for eight weeks to assess
tissue response to the implant (e.g., scarring). Glial fibrillary
acidic protein (GFAP), neuronal nuclear protein (NeuN) antibodies,
and ionized calcium-binding adapter molecule 1 (Iba1) were measured
at and distal from the site of implantation as indicators for glial
scarring. FIGS. 8A-8C depict the integrated intensity versus
distance from implant in rats following 8 weeks of implantation.
The greater the distance from the implant, the lower the integrated
intensity in glial fibrillary acidic protein, ionized calcium
binding adaptor molecule 1, and NeuN antibodies.
[0067] FIG. 9 shows that the probes (microcapillaries) can be
detectable in vivo when filled with a contrast agent. The arrows in
FIG. 9 depict 60 .mu.m medical probes in rat brains were detected
by CT when flushed with an iodine contrast agent.
[0068] Although specific embodiments of the disclosure have been
described, numerous other modifications and alternative embodiments
are within the scope of the disclosure. For example, any of the
functionality described with respect to a particular device or
component may be performed by another device or component. Further,
while specific device characteristics have been described,
embodiments of the disclosure may relate to numerous other device
characteristics. Further, although embodiments have been described
in language specific to structural features and/or methodological
acts, it is to be understood that the disclosure is not necessarily
limited to the specific features or acts described. Rather, the
specific features and acts are disclosed as illustrative forms of
implementing the embodiments. Conditional language, such as, among
others, "can," "could," "might," or "may," unless specifically
stated otherwise, or otherwise understood within the context as
used, is generally intended to convey that certain embodiments
could include, while other embodiments may not include, certain
features, elements, and/or steps. Thus, such conditional language
is not generally intended to imply that features, elements, and/or
steps are in any way required for one or more embodiments.
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