Note: Descriptions are shown in the official language in which they were submitted.
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
ANATOMICAL PHANTOM FOR SIMULATED LASER ABLATION
PROCEDURES
FIELD
The present disclosure relates to medical phantoms, imaging
phantoms and surgical training phantoms. More particularly the present
disclosure relates to life like anatomical phantoms in which some portions
of the phantoms are responsive to laser light for simulating laser ablation
procedures.
BACKGROUND
In the field of medicine, imaging and image guidance are a
significant component of clinical care. From diagnosis and monitoring of
disease, to planning of the surgical approach, to guidance during
procedures and follow-up after the procedure is complete, imaging and
image guidance provides effective and multifaceted treatment approaches,
for a variety of procedures, including surgery and radiation therapy.
Targeted stem cell delivery, adaptive chemotherapy regimes, thermal
ablation, and radiation therapy are only a few examples of procedures
utilizing imaging guidance in the medical field.
Advanced imaging modalities such as Magnetic Resonance
Imaging ("MRI") have led to improved rates and accuracy of detection,
diagnosis and staging in several fields of medicine including neurology,
where imaging of diseases such as brain cancer, stroke, Intra-Cerebral
Hemorrhage ("ICH"), and neurodegenerative diseases, such as
Parkinson's and Alzheimer's, are performed. As an imaging modality, MRI
1
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
enables three-dimensional visualization of tissue with high contrast in soft
tissue without the use of ionizing radiation. This modality is often used in
conjunction with other modalities such as Ultrasound ("US"), Positron
Emission Tomography ("PET") and Computed X-ray Tomography ("CT"),
by examining the same tissue using the different physical principals
available with each modality. CT is often used to visualize boney
structures, and blood vessels when used in conjunction with an intra-
venous agent such as an iodinated contrast agent. MRI may also be
performed using a similar contrast agent, such as an intra-venous
gadolinium based contrast agent which has pharmaco-kinetic properties
that enable visualization of tumors, and break-down of the blood brain
barrier. These multi-modality solutions can provide varying degrees of
contrast between different tissue types, tissue function, and disease
states. Imaging modalities can be used in isolation, or in combination with
surgical techniques to provide previously unavailable options for the
treatment of disease. An example of this would be laser ablation
thermotherapy (referred to as laser ablation) where targeted tissue is
destroyed by exposing it to an elevated temperature with laser energy.
An example of this technique in the neurosurgical field would be the
guidance of a laser ablation apparatus to a brain tumor using a
preoperative scan of the patient in combination with a surgical navigation
system followed by imaging the laser ablation procedure using MR
thermometry to assure that optimal ablation margins are adhered to. The
data collected during these procedures typically consists of CT scans with
an associated contrast agent, such as iodinated contrast agent, as well as
2
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
MRI scans with an associated contrast agent, such as gadolinium contrast
agent. Also during similar procedures, MR imaging (such as a 12, Ti,
ADC, DWI, or etc.) may be used to differentiate the boundaries of the
tumor from healthy tissue, known as the peripheral zone. Tracking of
instruments relative to the patient and the associated imaging data is also
often achieved by way of external hardware systems such as mechanical
arms, radiofrequency, EM, or optical tracking devices. As a set, these
devices are commonly referred to as surgical navigation systems.
Brain simulators or brain phantoms can be used as training aids for
MRI guided laser ablation. Current methods used for training surgeons in
the stereotactic placement of a laser applicator, and subsequent simulation
of a laser ablation, are performed either using a cadaver for stereotactic
placement training, or a gel phantom for MRI guided thermography.
In the second case of MRI guided thermography, the gel phantom
used are either a bottle or a skull filled with a homogeneous gel. This gel
does not show thermography changes (i.e., changes in temperature and
rate of change in temperature) similar to brain tissue. Further, the skull
filled with homogeneous gel do not show any anatomical context to the
actual brain.
Thus, it is desirable to have a brain phantom or brain simulator with
anatomical structures suitable for laser ablation simulation.
SUMMARY
3
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
The present disclosure discloses physiological phantoms
incorporating for use during simulated medical procedures.
Disclosed herein is a tissue phantom for performing a simulated
laser ablation surgical procedure on an anatomical structure of an
organism, comprising:
a tissue phantom made of a material similar to the anatomical
structure of the organism; and
a laser responsive material embedded in at least a portion of said
tissue phantom, wherein said laser responsive material exhibits a
preselected response when irradiated by a laser beam during the
simulated laser ablation surgical procedure.
A further understanding of the functional and advantageous aspects
of the invention can be realized by reference to the following detailed
description and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
Embodiments disclosed herein will be more fully understood from
the following detailed description thereof taken in connection with the
accompanying drawings, which form a part of this application, and in
which:
FIGURE 1 is an illustration of an example laser ablation based
approach in whichan ablation needle is inserted into the brain to approach
a tumor.
4
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
FIGURE 2 is an illustration of an example training model head/brain
phantom in an exploded view, illustrating parts of the base component and
the training component.
FIGURE 3 is an illustration showing a brain phantom in a skull.
FIGURE 4 is a flow chart describing a typical laser ablation
procedure.
FIGURE 5 is an illustration where the left most image is showing an
MR scan used to locate a target in an actual patient's brain and the
rightmost image is showing an MR scan used to locate a target in a brain
shaped laser ablation tissue phantom.
FIGURE 6 is an illustration showing a stereo tactic frame and a
tissue phantom having a skull.
FIGURE 7 is an illustration of two exemplary tissue phantoms
having ablation targets.
FIGURE 8 is an illustration showing a typical laser ablation
approach with the laser ablation probe prior to being inserted shown on the
left hand side of FIGURE 8 and the laser ablation probe inserted into the
target being shown on the right hand side of FIGURE 8.
FIGURE 9 is an illustration showing a typical ablation sequence.
FIGURE 10 is an illustration showing laser ablative properties of
substances that comprise tissue.
FIGURE 11 is an illustration showing a cross section of the two
exemplary tissue phantoms having different ablation targets.
FIGURE 12 is an illustration showing a typical laser ablation
process on a brain phantom with the upper left section showing the laser
5
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
aligned with the target, the upper right showing the laser inserted to the
target area and the bottom center showing the ablation procedure
complete.
FIGURE 13 is an illustration showing a typical laser ablation with a
laser ablation brain phantom having an asymmetrical target.
FIGURE 14 is an illustration showing side by side intraoperative MR
thermometry scans derived from the thermography phase portion of the
MRI sequence and their corresponding magnitude portion of the sequence
with a real time overlayed Arrhenius modeled 'irreversible damage
estimate'.
FIGURE 15 is an illustration showing an intraoperative MR
thermometry scan on a laser ablation tissue phantom.
FIGURE 16 is an illustration showing various laser ablation
responsive materials.
FIGURE 17 is an illustration showing a cross-sectional view of a
Facet nerve ablation procedure on a laser ablation tissue phantom.
FIGURE 18 is an illustration showing a side view of a Facet nerve
ablation procedure on a laser ablation tissue phantom.
DETAILED DESCRIPTION
Various embodiments and aspects of the disclosure will be
described with reference to details discussed below. The following
description and drawings are illustrative of the disclosure and are not to be
construed as limiting the disclosure. Numerous specific details are
described to provide a thorough understanding of various embodiments of
6
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
the present disclosure. However, in certain instances, well-known or
conventional details are not described in order to provide a concise
discussion of embodiments of the present disclosure.
Disclosed herein are physiological phantoms incorporating
properties of tissue that respond to laser ablation to replicate a real laser
ablation procedure. The materials include waxes, polymers,
thermochromic polymer blends or hydrogels, temperature sensitive
hydrogels, and photodegradable hydrogels. The materials may mimic
tissue as part of the tissue phantom not only in their feel and movement
but also in any one or combination of their chemical, physical, mechanical,
optical response to a laser ablation application. They may mimic the
directionality, density, optical absorption, heat transmittance, heat
conductance properties, electrochemical properties, thermochemical
properties, and elasticity of the anatomical tissues they may be replicating.
The laser ablation responsive materials may change properties such that
they provide a measure of the success of a medical procedure.
As used herein, the terms "comprises" and "comprising" are to be
construed as being inclusive and open ended, and not exclusive.
Specifically, when used in the specification and claims, the terms
"comprises" and "comprising" and variations thereof mean the specified
features, steps or components are included. These terms are not to be
interpreted to exclude the presence of other features, steps or
components.
7
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
As used herein, the term "exemplary" means "serving as an
example, instance, or illustration," and should not be construed as
preferred or advantageous over other configurations disclosed herein.
As used herein, the terms "about" and "approximately" are meant to
cover variations that may exist in the upper and lower limits of the ranges
of values, such as variations in properties, parameters, and dimensions.
As used herein, the term "patient" is not limited to human patients
and may mean any organism to be treated using the planning and
navigation system disclosed herein.
As used herein the phrase "surgical tool" or "surgical instrument" or
"medical instrument" refers to any item that may be directed to a site along
a path in the patient's body. Examples of surgical tools may include (but
are not necessarily limited to) scalpels, resecting devices, imaging probes,
sampling probes, catheters, or any other device that may access a target
location within the patient's body (or aid another surgical tool in accessing
a location within a patient's body), whether diagnostic or therapeutic in
nature.
As used herein the term "tensides" refers to agents that modify
interfacial tension of water; usually substances that have one lipophilic and
one hydrophilic group in the molecule; includes soaps, detergents,
emulsifiers, dispersing and wetting agents, and several groups of
antiseptics.
Broadly, tissue phantoms for performing a simulated laser ablation
surgical procedure are disclosed herein. The tissue phantom is made of a
material designed to mimic an anatomical part of an animal and a laser
8
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
responsive material embedded in at least a portion of the tissue phantom.
The laser responsive material exhibits a preselected response when
being irradiated by a laser beam during the simulated laser ablation
surgical procedure.
As used herein, the phrase "preselected response" means the
material exhibits a predicable change in any one or combination of
physical, chemical, physico-chemical, optical, mechanical and structural
properties upon being irradiated by the laser light. This predicable change
allows a clinician practicing a laser ablation procedure to detect a
difference in the laser ablation responsive material due to it being
illuminated.
The change in one or more of the above-noted properties may be
induced by one of several mechanisms including an increase in
temperature under illumination, a photochemistry induced reaction due to
illumination of the laser ablation responsive material by a laser of a
specific
wavelength which causes a photochemical reaction. An example of this
may be light induced cross linking in the material.
The materials include waxes, polymers, thermochromic polymer
blends or hydrogels, temperature sensitive hydrogels, and
photodegradable hydrogels. The materials may mimic tissue as part of the
tissue phantom not only in their feel and movement but also in their
chemical response to a laser ablation application. They may mimic the
directionality, density, optical absorption, heat transmittance, heat
conductance properties, electrochemical properties, thermochemical
properties, and elasticity of the anatomical tissues they may be replicating.
9
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
The laser ablation responsive materials may change properties such that
they provide a measure of the success of a medical procedure.
Since image-guided medical procedures are complex in nature and
the risk associated with use of such procedures in the brain or any other
anatomical part is very high, the surgical staff must often resort to
performing a simulated rehearsal of the entire procedure. Unfortunately,
the tools and models that are currently available for such simulated
rehearsal and training exercises typically fail to provide a sufficiently
accurate simulation of the procedure.
Understanding and modeling tissue deformations and tissue
response to interventional medical instruments is important for surgeons
practicing invasive medical procedures on patients. Being able to
accurately model how various types of tissue deform and respond to
medical instruments may improve a surgeon's ability to approach and
apply therapeutic interventions to targets in the patient's body with minimal
damage and maximum effectiveness. Being able to produce tissue
phantoms which exhibit biomechanical, imaging, and therapeutic response
characteristics resembling those of patients is a necessary step in
providing a viable life-like tissue phantom on which to practice medical
procedures.
When performing surgical and/or diagnostic procedures that involve
ablation, neurosurgical techniques such as removing a small section of the
superficial tissue to provide access to internal anatomical structures may
be executed. In such procedures, as indicated, the medical procedure is
invasive of the mammalian body. For example, in the ablation based
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
surgical method illustrated in FIGURE 1, a generally elongated probe 100
is inserted along a planned trajectory into the brain 120 to access a tumor
(not shown) or other structures located deep in the brain to undergo laser
ablation. The elongated probe 100 provides the surgeon with the ability to
ablate the interior portion of the patients brain being operated on, without
significant negative repercussions resultant of more invasive procedures
such as those involving sizeable craniotomies.
According to embodiments provided herein, the simulation of such
procedures may be achieved by providing an anatomical model that is
suitable for simulating the medical procedure through one or more layers
of the head. Such a procedure may involve perforating, drilling, boring,
punching, piercing, stimulating, ablating, resecting, or any other suitable
methods, as necessary for a laser ablation based procedure. For example,
some embodiments of the present disclosure such as that shown in
FIGURE 2 provide brain models comprising an artificial skull layer 220 that
is suitable for simulating the process of penetrating a mammalian skull. As
described in further detail below, once the skull layer is penetrated, the
medical procedure to be simulated using the training model may include
further steps in the diagnosis and/or treatment of various medical
conditions. Such conditions may involve normally occurring structures,
aberrant or anomalous structures, and/or anatomical features underlying
the skull and possibly embedded within the brain material.
In some example embodiments, the anatomical model is suitable for
simulating a medical procedure involving a brain tumor that has been
selected for ablation. In such an example embodiment, the brain model
11
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
such as that shown in FIGURE 2 is comprised of a brain material 210
having a simulated brain tumor provided therein. This brain material
simulates, mimics, or imitates at least a portion of the brain at which the
medical procedure is directed or focused.
The simulation of the above described laser ablation medical
procedure is achieved through simulation of both the medical procedure
and the associated imaging steps that are performed prior to surgery (pre-
operative imaging) and during surgery (intra-operative imaging). Pre-
operative imaging simulation is used to train surgical teams on co-
registration of images obtained through more than one imaging
methodology such as magnetic resonance (MR), computed tomography
(CT) and positron emission tomography (PET). Appropriate co-registration
geometrically aligns images from different modalities and, hence, aids in
surgical planning step where affected regions in the human body are
identified and a suitable route to access the affected region is selected.
Intraoperative imaging assists the surgical team in guiding and confirming
a medical instruments position in the patient's body and allows them to
better estimate the progression of the procedure.
Referring to FIGURE 2, an exploded view of an example model or
phantom shown generally at 250 is provided that is suitable for use in
training or simulation of a medical procedure which is invasive of a
mammalian head. The training model 250 may be adapted or designed to
simulate any anatomical structure. It is to be understood that the person to
be trained on the phantom may be selected from a wide variety of roles,
including, but not limited to, a medical doctor, resident, student,
12
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
researcher, equipment technician, or other practitioner, professionals, or
personnel. In other embodiments, the models provided herein may be
employed in simulations involving the use of automated equipment, such
as robotic surgical and/or diagnostic systems. The present disclosure
relates to parts or all of a phantom being designed to mimic the response
of patient tissue during any of the steps involved of an ablation procedure.
Furthermore the present disclosure also relates to parts or all of a phantom
designed to provide a mechanism for obtaining a measure success of a
mock ablation procedure during or after it has been performed.
FIGURE 3 shows an exemplary embodiment of a tissue phantom
that may be used for a brain tissue ablation procedure as will be described
in further detail below. The tissue phantom as shown includes a skull
portion 310 and an additional brain portion 300 positioned inside the skull
portion 310. The brain portion 300 may contain further portions such as
other anatomical parts or sensors, or sensing materials that may be
desirable during a mock brain tissue ablation procedure.
FIGURE 4 depicts a flow chart describing a common brain tissue
laser ablation workflow as it is performed on a target tissue of interest in
the brain. The following sections will describe a laser ablation tissue
phantom with features in accordance with the steps of the generic brain
tissue laser ablation procedure workflow as shown in the flow chart in
FIGURE 4. The features of the exemplary laser ablation tissue phantom
may be designed to provide a training surgeon using the phantom with a
similar response to patient tissue during an actual laser ablation procedure
consonant with said workflow.
13
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
The exemplary brain tissue laser ablation workflow shown in
FIGURE 4 will be described with respect to its implementations in two
procedures that employ brain tissue laser ablation. It should be noted that
these procedures and workflow are provided as non-limiting examples only
and that the laser ablation tissue phantom as disclosed herein may be
used for any applicable medical procedure such as a prostate tumor laser
ablation or a Facet (Spinal) Laser Ablation which will be described in
further detail below. It should also be noted that any of the features of the
laser ablation tissue phantom as described herein may be produced in the
laser ablation tissue phantom individually or in combination with one or
more alternate features also described herein.
The two exemplary procedures that will be implemented using the
exemplary workflow provide in FIGURE 4 are an
amagydalohippocampotomy as described in the paper [Willie, Jon T., et
al. "Real-time magnetic resonance-guided stereotactic laser
amygdalohippocampotomy for mesial temporal lobe epilepsy."
Neurosurgery74.6 (2014): 569-585.] and a Glioblastoma thermal laser
ablation. Both of these procedures involve inserting a laser ablation probe
into the brain of a patient to ablate a volume of brain tissue and follow the
workflow as outlined by the flow chart in FIGURE 4. An
amydalohippocampotomy is generally performed on patients with epileptic
foci found to be within the boundaries of the two adjacently located
amygdala and hippocampus brain structures wherein, the ablation of the
structures tends to remove the source of the seizure (the epileptic foci).
Generally only segments of the adjacent structures showing epileptic
14
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
characteristics as determined by cortical mapping may be targeted
however in some cases such as the one that will be described as follows
dependent on the specific patient, the entire amygdala and hippocampus
structures may be targeted.
Referring to FIGURE 4 the first stage 400 of these procedures is to
image the patient using an imaging technique such as but not limited to
MRI, CT, PET, or any other applicable technique and identify the target of
interest. In the case of an amygdalohippocampotomy this would be the
hippocampus and amygdala structures located within the brain while for
the glioblastoma tumor ablation this would be the tumor of interest. A
trajectory corresponding to a path from an entry point to the target
structure (tumor, or Hippocampus/Amydala) is also chosen at this stage.
To employ the laser ablation tissue phantom as disclosed herein in the
replication of this step requires that the phantom have features such that:
a) the laser ablation tissue phantom may be scanned using an
applicable imaging technique such as MRI or those listed above
and;
b) the laser ablation tissue phantom have one or more identifiable
target or other volumes that can be used to define a trajectory
consonant with the procedure being performed.
c) the one or more volumes be differentiable in the scanning
modality used at this stage in the procedure.
FIGURE 5 shows a side by side comparison of an actual scan of a
patient 500 during such a workflow step 400, having a target and entry
point, with an actual scan of an exemplary laser ablation tissue phantom
WO 2016/119040
PCT/CA2015/050066
510 containing two targets (replicating two Glioblastomas) as is apparent
from the image. The laser ablation tissue phantom in the scan 510 was
produced using methods and apparatus as described in the International
PCT patent application Serial No. POT/ 0A2014050659 entitled
"SURGICAL IMAGING AND TRAINING BRAIN PHANTOM" which shows
two artificial Glioblastomas 515 that may be used to replicate the steps in
the stage 400 of the laser ablation workflow as shown in FIGURE 4 (i.e. by
allowing a training surgeon to identify an entry point and target).
However, in the case of the amygdalohippocampotomy the
structures shown in the scan 510 would have to be replaced by structures
mimicking the hippocampi and amygdalae as opposed to the
Glioblastomas 515 as shown to allow for a replication of an actual
amygdalohippocampotorny employing a thermal ablation probe. In addition
whereas Glioblastomas are arbitrarily located in the brain, the hippocampi
and amygdalae have specific anatomical locations (shown in FIGURE 7)
and it would be beneficial to provide the mimicking structures in locations
consonant with an anatomical atlas or if desired with an actual patient
anatomy.
Referring again to FIGURE 4 the next stage 410 in both procedures
is to align the laser ablation probe guide along a trajectory to be traversed
by the probe to access the target. FIGURE 6 shows an exemplary
stereotactic frame 600 that may be used to align the guide. As is apparent
from the stereotactic frame 600 in the figure the frame is typically attached
to a skull 605 and oriented accordingly. The frame 600 is typically aligned
16
CA 2974846 2018-12-27
WO 24116/1191)3()
PCT/CA2015/050066
in accordance with the trajectory defined by the target and entry point as
per the previous stage 400 where the trajectory was chosen. Commonly
the alignment of the frame 600 is assisted by a tracking system registered
with the patient and having tracked tools such as that described in the
International PCT patent application Serial No. PCTICA20141050270,
entitled "SYSTEMS AND METHODS FOR NAVIGATION AND
SIMULATION OF INVASIVE THERAPY", which is WO Publication
20141139022, An alternate option often used is to align the frame 600 in
relation to the patients' skull 605 by setting the frame 600 to frame
coordinates provided by the planning software, using the graduation
marks 610 on the frame 600. Once the trajectory is set a small entry hole
for the laser ablation probe 100 (FIGURE 1) is burred into the patients'
skull 605 coaxially with the trajectory. In typical procedures an MRI
compatible probe guide is then anchored into this hole to form a linear
channel to allow a laser ablation probe 100 to pass through along the
trajectory into the brain towards the target.
To employ the laser ablation tissue phantom as disclosed in this
embodiment the replication of this step requires that the phantom have
features such that:
a) a stereotactic frame may be mounted on the phantom or part of
the phantom as it would be on a patient (it should be noted that
various other types of frames such as a miniframe may be used
(Monteris Axiiis, http:fiwww.monteris.comtour-technology/axiiis-
stereotactic-miniframei), or a frameless mount may also be
17
CA 2974846 2018-12-27
=
WO 2016/119040
PCT/CA2015/050066
used in which frameless navigation occurs with a patient
secured to the table and a referenced attached to the securing
device;
b) the superficial part of the phantom have a layer with similar
properties of skull and;
C) an MRI compatible probe guide is able to be anchored into the
superficial part of the phantom at the location of the burr hole.
FIGURE 6 shows an exemplary embodiment of a skull part 615 of a
head/brain phantom potentially having the required properties of a
patients' skull for replicating the burr and probe guide anchoring steps of
the stage 410 of FIGURE 4. It should be noted that this skull part 615 may
also be registered with a tracking system for aligning the frame as
described above. The embodiment of the skull shown may be produced as
per the International PCT patent application Serial No.
PCT/0A2014/050272, entitled 'PLANNING, NAVIGATION AND
SIMULATION SYSTEMS AND METHODS FOR MINIMALLY INVASIVE
THERAPY", which is published as WO Publication 2014/139024.
Referring again to FIGURE 4 the next stage 425 in both procedures
is for the surgeon to advance the laser ablation probe through the MR1
compatible guide along the defined trajectory to access the target.
FIGURE 7 shows exemplary embodiments, at 700 and at 705, of the laser
ablation tissue phantom as disclosed herein that may be used for the
amygdalohippocampotomy and the Glioblastoma tumor laser ablation
procedures respectively. The embodiments of the laser ablation tissue
18
CA 2974846 2018-12-27
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
phantom for the amygdalohippocampotomy procedure 700 and the
Glioblastoma tumor laser ablation procedure 705 may be referred to as
Phantom A 700 and Phantom G 705 respectively henceforth. When
advancing an ablation probe 100 towards the targets along the trajectory in
medical procedures it is common for surgeons to analyze the tactile feel of
the probe 100 at various stages of advancement for trying to detect
inconsistencies with respect to the chosen trajectory and what they
"should" be feeling like at a certain point. For example if a trajectory is
chosen such that the probe 100 should pass through a ventricle at a
particular depth (or within a range of depths) within the brain then the
surgeon may expect to feel a reduction in opposing force against the probe
100 when that region is accessed (i.e. they will expect to feel the boundary
of the ventricle where the opposing force changes). If this reduction is not
felt through the surgeons' tactile perception it may indicate to the surgeon
that perhaps the trajectory is off or some other error has occurred for
example a shifting of the ventricular area after the scan.
In addition increased pressure against the probe 100 (FIGURE 1)
may be indicative of a ruptured vessel releasing blood into the brain
thereby increasing the overall pressure. Thus it may be advantageous to
produce a laser ablation tissue phantom with boundaries or structures
representative of the actual anatomy of a patient and the corresponding
tactile properties.
The laser ablation anatomical phantoms disclosed herein may be
generic phantoms used simply for training purposes. In addition, the
phantoms may be patient specific phantoms, produced based on
19
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
preoperative imaging of the anatomical part of the patient undergoing the
medical procedure. Thus if a patient has a brain tumor, preoperative
imaging of the patient's brain may be used to construct a lifelike brain
phantom (or other anatomical structure) including the tumor, with the brain
structures and tumor being made of responsive materials selected to
mimic selected properties of the brain, and tumor, including but not limited
to, mechanical, optical and biomechanical properties of the brain
structures and tumor. This phantom will give the clinician an opportunity to
practice the medical procedure in a very realistic manner.
In the case when surgeons perform an amygdalohippocampotomy
they target the same structure every time for each patient. Therefore
producing a phantom with target volume structures of the amygdala and
hippocampus having similar tactile properties to actual amygdalae and
hippocampi may assist in improving a surgeons training in providing them
not only directional familiarity but tactile familiarity with the structure
volumes to be ablated.
In the case when surgeons perform a Glioblastoma tumor laser
ablation they target a different volume every time for each patient.
However eloquent structures for example the optic tract are to be avoided
almost always to preserve important functionality in the patient. In this
example avoiding the optic tract would preserve the patient's vision. Thus,
producing a phantom with structures in addition to the target volumes may
assist in improving a surgeons training in providing them not only
directional familiarity but anatomical experience as to which areas to avoid.
In yet another case targeted Glioblastomas to be ablated at times may be
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
very dense compared to their surrounding tissue. Thus once again
producing a target structure with a similar tactile properties to a dense
Glioblastoma may assist in improving a surgeons training in providing
them not only directional familiarity but tactile familiarity with the
structure
volumes to be ablated.
In order to produce the changes in tactile feel between brain
structures various attributes of the structures may be altered. One example
factor that may be changed is the density of the materials used to produce
the structures. Table 1 as shown below, provides some densities of actual
brain structures that may be used to choose or produce artificial brain
structures materials to be used in the laser ablation tissue phantom as
disclosed herein with tactile properties similar to that of their
corresponding
actual brain structures. Other non-limiting properties that may be used to
produce artificial brain structure materials include, elasticity and,
hardness.
Human Brain Density (q/cm^3)
Frontal White 1.073
Frontal Gray 1.090
Parietal White 1.026
Parietal Gray 1.109
Occipital White 1.073
Occipital Gray 1.103
Corpus-callosum 1.093
Thalamus 1.052
Caudate Nucleus 1.075
Putamen 1.081
Global Pallidus 1.084
Brachium Pontis 1.116
Medulla 1.057
Pons 1.069
Cerebellum 1.058
21
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
Phantom A 700 shown in FIGURE 7 on the left hand side of the
FIGURE 7 shows the amygdala 715 and hippocampus 710 structures with
differing densities with respect to the surrounding brain tissue 300.
Therefore when employing this phantom (i.e. Phantom A) for a mock
amygdalohippocampotomy, a surgeon may feel a change in density
moving from the surrounding brain tissue 300 of the phantom into the
hippocampus 710 and again through the hippocampus into the amygdala
715.
Phantom G 705, shown on the right hand side in FIGURE 7 shows
a Glioblastoma 720 structure with differing density with respect to the
surrounding brain tissue 300. Therefore when employing this phantom (i.e.
Phantom G) for a mock Glioblastoma tumor laser ablation a surgeon may
feel a change in density moving from the surrounding brain tissue 300 of
the phantom into the tumor 720.
Referring again to FIGURE 4, the next stage 430 in both
procedures is to move the patient into an MRI machine. Again referring to
FIGURE 4 the following stage 435 in both procedures is to begin MRI
imaging and confirm that the ablation is properly placed in the target of
interest as described above for both procedures being described herein
with respect to the workflow. If the laser ablation probe 800 (seen in
FIGURE 8) is not found to be in the correct position the procedures may
be started over. If the laser ablation probe 800 is in the correct position,
then the laser ablation process can begin.
To employ the laser ablation tissue phantom as disclosed herein in
the replication of this stage requires that the phantom have all of the
22
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
features as required in the initial stage 400 of the workflow (i.e. it must
have properties such that it may be imaged with the particular imaging
modality used in the procedure etc.).
Once the probe 800 is correctly placed the ablation of the tumor
may begin. At this stage both MR thermometry imaging (step 470) and
ablation (step 475) may occur simultaneously such that the MR
thermometry is used to monitor the extent of the ablated region created by
the laser thermal ablation probe as it is applied within the target. FIGURE
8, left hand side of the Figure, shows a diagram of a simulated commonly
performed amygdalohippocampotomy on Phantom A prior to step 425 in
the workflow. The trajectory 810 shown in the left hand diagram 820 of this
figure is a typical trajectory chosen in most procedures of this kind. The
trajectory 810 attempts to avoid the lateral ventricles and enter the
hippocampus 710 posteriorly along the long axis of the hippocampus body
into the amygdala shown in the image at 715. The reason this trajectory
810 is commonly chosen is to allow the laser ablation probe 800 to ablate
as much of the hippocam pus as possible through one pass (achieved by
maneuvering the probe along a linear path coincident with the long axis of
the hippocampus). The laser ablation probe may have multiple laser light
emitters 805 on its distal end or a mechanical assembly to allow for
customizable ablative laser emission.
The right hand side of Figure 8 shows a simulated commonly
performed amygdalohippocampotomy on Phantom A, shown generally as
area/volume 825, wherein the laser ablation probe 800 has been
advanced to the target(s) of interest prior to step 465 in the workflow. The
23
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
highlighted area 815 of the right side 825 of FIGURE 8 can be seen in
FIGURE 9 which depicts further progression of the simulated commonly
performed amygdalohippocampotomy. Referring again to FIGURE 9, the
left hand side of the figure at900 shows a general starting location
between the hippocampus and amygdala (not to scale) for ablation during
a commonly performed amygdalohippocampotomy procedure. In this
frame ablation has begun on the most-distal end of the ablation probe as
can be seen as the region 915 shown in a darker elliptical shape. The
middle frame of the figure 905 shows a further progression where ablation
has begun in the body of the hippocampus, the ablation volume of this
stage in the progression shown as a second dark elliptical shape 920. The
right frame of the figure 910 shows an even further progression where
ablation has reached the posterior portion of the hippocampus, the
ablation volume at this stage is shown as a third dark elliptical shape.
As described above the specific trajectory chosen to reach the
target area is an important factor in determining the effectiveness of the
amygdalohippocampotomy. From the progression of the procedure shown
in Figure 9, it is apparent that the more the trajectory is aligned axially
with
the long axis of the hippocampus towards the amygdala the more access
the laser ablation probe will have to the volume to be ablated (i.e. the
hippocampus and amygdala). This is important in that the more of these
two structures that are ablated the better the chances are of the procedure
being a success (i.e. ablating the epileptic region of the patient's brain).
Thus it is vital that when producing a laser ablation tissue phantom that
structures be aligned in accordance with actual anatomy.
24
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
The ablation step 475 as shown in Figure 9 and described above
will be elaborated on in greater detail as follows to outline further features
of the laser ablation tissue phantom as disclosed herein. Referring again to
Figure 9, the laser 805 as shown in the figure is activated to ablate the
target tissue. To perform ablation the laser emits a light beam at a
particular wavelength in order to induce thermal heating in the target
tissue. The rate of tissue ablation and temperature gradient are important
factors when performing laser ablation. Specifically for the case of the rate
of tissue ablation, the faster the target tissue may be ablated the better the
more beneficial the ablation is to the outcome of the procedure. This result
follows from general medical procedural knowledge such as the less time
the patient is under general anesthesia the less likely complications are to
occur. In addition the less time the doctors spend performing the surgery
the more money is saved by the hospital. For the case of the temperature
gradient the steeper the gradient is over penetration distance the better, as
this allows the application of thermal ablation in focused areas while
affecting non-target areas minimally. A method of effectively achieving
such a result may be implemented by taking advantage of the
phenomenon of thermal confinement as described in further detail below.
Examples of wavelengths commonly used in laser ablation procedures to
optimally meet the important factors mentioned above are 980nm and
1064nm. The mechanisms through which laser thermal ablation acts on
tissue is important in determining how to best produce a laser ablation
tissue phantom that may mimic this ablation step 475 of the workflow
shown in FIGURE 4. Thus a description of the basic mechanisms through
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
which laser ablation acts on patient tissue and its interaction will be
elaborated on below in further detail.
FIGURE 10 (a) taken from [Chu, Katrina F., and Damian E.
Dupuy. "Thermal ablation of tumours: biological mechanisms and
advances in therapy." Nature Reviews Cancer 14.3 (2014): 199-208.]
shows a diagram of a tissue undergoing thermal ablation. The following
passage gives a summary of cell death caused by ablation and was
retrieved from [Chu, Katrina F., and Damian E. Dupuy. "Thermal
ablation of tumours: biological mechanisms and advances in
therapy." Nature Reviews Cancer 14.3 (2014): 199-208.]
"Hyperthermic injury.
RFA and MWA, as well as laser ablation and HIFU, cause focal
hyperthermic injury to ablated cells, which affects the tumour
microenvironment and damages cells at the membrane and subcellular
levels. The process of tumour destruction occurs in at least two phases,
through direct and indirect mechanisms.
Heat-ablated lesions can be thought of as having three zones: the
central zone, which is immediately beyond the application tip and which
undergoes ablation-induced coagulative necrosis; a peripheral or transi-
tional zone of sublethal hyperthermia, which mostly occurs from thermal
conduction of the central area that is either undergoing apoptosis or
recovering from reversible injury; and the surrounding tissue that is
unaffected by ablation. Direct cellular damage occurs at several levels,
from the subcellular level to the tissue level, and it depends on the thermal
26
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
energy that is applied, the rate of application and the thermal sensitivity of
the target tissue."
From the passage it is apparent that there are two zones of ablation
created during a thermal ablation therapy. The first zone (labelled as:
Coagulation necrosis in FIGURE 10 (a)) is the area where immediate cell
death occurs through coagulation necrosis, while the second zone
(labelled as: Sublethal damage in FIGURE 10 (a)) is the zone undergoing
reversible damage. It should be noted that the first zone occurring
"immediately beyond the application tip"is equivalent to the targeted area
by the laser beam of the laser ablation probe in a thermal laser ablation
application as described herein. Thus, the mentioned thermal zones are
also induced during laser ablation procedures as shown in the figure
similar to the induction of thermal zones that occur using an ablation
applicator with the difference being that the thermal energy transferred to
the tissue occurs through light absorption during laser ablation thermal
therapy as opposed direct thermal conduction which occurs when
employing a thermal applicator. Thus, the light absorption properties of the
tissue being ablated are essential in determining the effectiveness of the
ablation procedure.
Generally the optical absorption properties of tissue are dominated
by five biomolecules as described in the paper [Vogel, Alfred, and Vasan
Venugopalan. "Mechanisms of pulsed laser ablation of biological tissues."
Chemical reviews 103.2 (2003): 577-644.]. These molecules are protein,
DNA, melanin, hemoglobin, and water. FIGURE 10 (b) shows the
dependence of the light absorption coefficient of these five molecules on
27
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
the wavelength of applied laser light. It is apparent from Figure 10 (b) that
absorption of laser light in the near-infrared range is primarily due to water
and hemoglobin (and deoxyhemoglobin). However hemoglobin is
predominantly located in vasculature (also partially in tissue) and thus this
must be taken into consideration during ablation.
Given the provided information in order to employ the laser ablation
tissue phantom as disclosed herein in the replication of this step (475)
requires that the phantom have features such that:
a) generally the replicated tissue in the laser ablation tissue
phantom should respond as similarly as possible to how the
tissue it's replicating would respond to the same optical (light)
stimulus,
b) specified further for clarity;
i. the material should convert absorbed light energy into
heat at a similar rate to the target tissue it's replicating,
ii. the material should diffuse and absorb light at a similar
rate to the target tissue it's replicating,
iii. the material should change chemical properties similarly
to the tissue being replicated.
The first criteria b)-(i) regarding the conversion of light into heat by
the tissue can occur in two specific modalities such that in the first
modality heat absorption occurs under normal conditions and in the
second modality heat absorption as dictated by thermal confinement.
The first phenomenon is general heat diffusion through conduction
within a tissue. As will be described further below, the process of laser
28
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
ablation transfers energy in the form of photons to molecules in the tissue
to be ablated where the energy is then converted into heat causing thermal
damage to the tissue around it. Most tissues contain dominant light
absorbing molecules for specific wavelengths of light as for example
shown by FIGURE 10 (b) mentioned above and discussed further below.
These dominant light absorbing molecules absorb the bulk of the photons
of the applied laser light and convert them into thermal energy which is
then conducted by the surrounding molecules and/or remains with the
dominant light absorbing molecules. The absorption of the thermal energy
by the surrounding molecules is dictated by their respective thermal
conductivities. And the increase in temperature of the dominant light
absorbing molecules is dictated by their (as a whole) specific heat capacity
(individually this would be represented as mechanical energy such as an
increased atomic vibrational energy).
Referring to FIGURE 10 (c) the temperature (thermal energy) profile
of absorbed laser energy (in water) is shown with the dashed line
representing the absorption length of the wavelength of laser light. The
absorption length is the average penetrating distance photons of specific
wavelength will travel in a medium until 63% (1/e) of their initial intensity
is
absorbed by the medium. The temperature (thermal energy) profiles for
durations of laser pulses of 10ps or more effectively show the temperature
profiles for the first phenomenon, heat absorption under normal conditions.
In this absorption regime the thermal energy is dissipated to the
surrounding molecules as the thermal diffusion time (td) is less than the
29
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
pulse duration (tp). The thermal diffusion time for tissues enduring laser
ablation may be defined as:
1
td = ________________________________ 2
Kidd
Where K is defined as
P Cs
K =
Where K is the thermal conductivity, p is the density, and c, is the
specific heat capacity.
The second phenomenon termed thermal confinement refers to
specific scenarios where the pulse duration (t5) of the laser is less than
that
of the thermal diffusion time (td). This is shown in FIGURE 10 (c) [Vogel,
Alfred, and Vasan Venugopalan. "Mechanisms of pulsed laser ablation of
biological tissues." Chemical reviews 103.2 (2003): 577-644.] for when the
pulse durations are equal to or less than 3ps. During this phenomenon as
the light energy is absorbed and converted into thermal energy it
substantially remains in the area (with the molecules) it was initially
absorbed, effectively confining the heat energy to be diffused in that
region. This is apparent from the normalized temperatures of the curves
for pulse durations in the thermal confinement regime shown in FIGURE
10 (c) such as the curve for the 100ns pulse duration. This curve shows
that nearly all of the thermal energy (temperature) is absorbed at the
surface of the substance where the thermal laser ablation is applied. This
results from the short duration of the pulse resulting in their not being
enough time for the thermal energy to diffuse into the rest of the tissue as
is apparent from the figure. Employing this phenomenon allows laser
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
ablation to be done in more accurate and confined regions providing
greater accuracy with respect to the tissue to be ablated. Although
FIGURE 10 (c) is provided for explanatory purposes a material with the
thermal profile response shown may be chosen to replicate a tissue to be
ablated with a similar thermal profile response during step 475 of the
workflow shown in FIGURE 4. However it should be noted that this profile
response property may be adjusted accordingly for tissues with lower
water content such as grey matter in the brain which is typically composed
of 80% water. It should further be noted that temperature response profiles
such as the one shown in FIGURE 10 (c) (or with different axis providing
similar information on characteristic thermal properties as outlined
immediately below) may be acquired for tissues on which ablation is
commonly performed. These responses may then be used to produce a
laser ablation tissue phantom material with a similar temperature response
profile to the tissues on which ablation is commonly performed that the
laser ablation tissue phantom material is to replicate.
Thus to produce a laser ablation tissue phantom for use in step
(475) of the workflow depicted in FIGURE 4 the material should be ideally
chosen such that it has a similar net thermal conductivity, net specific heat
capacity and net thermal diffusivity to the tissue being replicated. The term
"net" as used above refers to the thermal characteristics (such as
conductivity and diffusivity) of the material as whole as opposed to its
constituent molecule concentrations although this would also be a viable,
albeit time consuming option.
31
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
The two commonly used wavelengths of typical laser ablation
probes mentioned above (i.e. 980nm and 1064nm) are in the near-infrared
range. Thus a material having a similar net light absorption coefficient to
the tissue being replicated at these wavelengths would suffice in
substantially meeting the criteria regarding b)-(ii). The net light absorption
may or may not refer to the light absorption (coefficient) of the tissue in
its
entirety as opposed to the light absorption (coefficient) of its constituent
individual biomolecules (for example water or hemoglobin).
Referring to Figure 10 (b) the two typically used wavelengths are
depicted on the wavelength axis as 1000 and 1100 for the 980nm and
1064nm wavelengths respectively. Thus a material replicating a tissue
comprising principally of water would have an absorption coefficient in
accordance with the line 1200 when being used in a simulated procedure
employing a 980nm laser ablation probe and in accordance with 1300
when being used in a simulated procedure employing a 1064nm laser
ablation probe. Although the mentioned absorption coefficients may suffice
for some embodiments, generally they may or may not be altered as per
the percentage of water content in a particular tissue. For example when a
laser ablation tissue phantom material is used to replicate a tissue with
40% water content the light absorption coefficient of the material at the
specific wavelength may be ideally chosen to be 40% of the light
absorption coefficient 1200. In other embodiments a proportionality
constant may be applied to the scaling of the water content to provide the
same net light absorption coefficient of the tissue being replicated (for
example for tissues with non-linear water content to light absorption
32
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
coefficient scaling) for example (P)X% where P is the proportionality
constant and X is the water content of the tissue being replicated.
Furthermore although the water content of a tissue may be a dominant
factor in determining the light absorption coefficient of the tissue in the
infrared wavelength range other biomolecular factors must also be taken
into consideration.
For example if the tissue being replicated is highly vascularized
than the light absorption coefficient of hemoglobin / deoxyhemoglobin (for
example as shown by the light absorption coefficient of the line 1400 at
980nm 1000) in addition to the light absorption coefficient of water must be
taken into consideration in determining the optimal light absorption
coefficient for the material being used to replicate the tissue. For example
if a 980nm wavelength laser ablation probe is applied to a tissue
comprising of 50% vasculature and 50% water than the optimal light
absorption coefficient of the material may be 50% of both the light
absorption coefficients indicated by lines 1400 and 1200 as these are the
intersection points of the 980nm line 1000 with the light absorption
coefficient curves of water and hemoglobin as shown in
FIGURE 12 and FIGURE 13 are provided to illustrate additional
scenarios that commonly occur in laser ablation procedures that may be
replicated through the addition of features of the laser ablation tissue
phantom as disclosed herein. FIGURE 11 shows the cross-sections about
the plane 1105 of both Phantom G 1115 and Phantom A 1120. The cross-
section of Phantom G 1115 is used in FIGURE 12 to describe the ablation
step 475 of the workflow as it pertains to a simulated Glioblastoma tumor
33
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
laser ablation procedure executed on Phantom G. The trajectory 1200 to
reach the target structure 720 shown in the left diagram 1225 of the figure
is an arbitrary trajectory that may or may not be chosen in such a
procedure depending on the specific anatomical orientation of the
(simulated) patients eloquent structures as per Phantom G. This diagram
1225 shows the state of the simulated Glioblastoma tumor laser ablation
procedure prior to step 425 shown in the workflow of FIGURE 4.
The laser ablation probe may have multiple laser light emitters 805
on its distal end or a mechanical, pneumatic, electormechanical, electrical,
or any other type of assembly to allow for customizable ablative laser
emission. The right diagram 1230 of FIGURE 12 shows a simulated
commonly performed Glioblastoma tumor laser ablation procedure on
Phantom G wherein the laser ablation probe has been advanced to the
target(s) of interest prior to step 465 in the workflow shown in FIGURE 4.
In the diagram 1230 the ablation of the Glioblastoma tumor 720 has begun
and the ablated area of the tumor at this stage is highlighted by the
segment 1205.
As the simulated procedure progresses this ablated region 1205
increases in size until it reaches the boundary 1210 of the tumor as shown
in the bottom diagram 1235. As is common with Glioblastomas this
boundary 1210 may be highly vascularized or an edema having different
optical properties resulting in a different response to the thermal laser
ablation application in comparison to the main body of the Glioblastoma
720. As per the description of light absorption properties illustrated above
in FIGURE 10 (b) the absorption properties of this boundary region 1210
34
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
may highly depend on the dominant light absorption biomolecule for the
particular wavelength(s) of light being applied by the laser ablation probe
to the area.
Typically the tumor volume has a much higher ratio of water to
hemoglobin (and deoxyhemoglobin) than does the boundary area which is
highly vascularized and thus has a higher ratio of hemoglobin (and
deoxyhemglobin) to water. Thus from the intersection of the 980nm line
1000 with the curves of water and hemoglobin in FIGURE 10 (b) it is
apparent that the light absorption at the boundary 1210 would greatly
increase relative to the light absorption within the body of the Glioblastoma
720 (i.e. because the intersections of the line 1400 has a greater light
absorption coefficient than the intersection of the line 1200). During
typically performed surgeries this is a common occurrence and the
vasculature tends to form a pseudo heat boundary at which the ablation
intensity must increase in intensity to surpass.
The consequence of this occurrence is a desirable one as it
increases the steepness of the gradient at the boundary where the tumor
ends. Thus when performing such a Glioblastoma tumor laser ablation
procedure this occurrence is commonly leveraged by the surgeon to
improve the results of the procedure by reducing the left over margins at
the boundary. Therefore when producing a laser ablation tissue phantom
as disclosed herein in an embodiment it may be advantageous to provide
an additional structure in the form of a boundary partially or entirely
encompassing a tissue replicating structure. This boundary having
different light absorption properties than the structure it's encompassing.
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
By providing this feature in the laser ablation tissue phantom as disclosed
herein a simulated Glioblastoma tumor laser ablation procedure may more
closely replicate such an occurrence for a training surgeon and/or a user of
the laser ablation tissue phantom.
It should be noted that the boundary region being highly
vascularized as described above was given as an example only and other
boundary regions being replicated such as regions plagued with edema
may also be benefitted from such an additional replicating structure. In
addition if an edema is replicated it may suffice to provide a liquid barrier
as opposed to a solid one by filling the area around the replicated
Glioblastoma with a liquid with similar properties to edema. Such a liquid
could be injected into a cavity built into the laser ablation tissue phantom
as disclosed herein for example such as the cavities 515 surrounding the
Glioblastomas built into the main body of the tissue laser ablation phantom
300 shown in diagram 510 of FIGURE 5. Other boundary regions to be
replicated may be the ventricles of the brain formed with artificial CSF.
FIGURE 13 shows the same ablation step 475 of the workflow
described above as it pertains to a simulated Glioblastoma tumor laser
ablation procedure executed on Phantom G as shown in FIGURE 12. The
difference being in this scenario the Glioblastoma tumor being ablated is
asymmetrical. To ablate such an asymmetrical tumor when performing a
Glioblastoma tumor laser ablation procedure a surgeon must then use
specific features provided by their laser ablation probe or other medical
instrument. In these scenarios it is common to use a laser ablation probe
which can be aimed to ablate the tumor in the chosen direction of the laser
36
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
ablation probe. Diagram 1320 of FIGURE 13 illustrates such a scenario,
where an asymmetrical tumor 1320 is to be ablated by the surgeon. The
portion outlined by the dashed area 1300 is highlighted in the two
diagrams below (1325 and 1330) showing the progression of such a
procedure. The first diagram 1325 shows the ablation as it is being
performed in one arm of the asymmetrical tumor wherein the probe is
being directionally aimed 1302 in the direction of the bulk of the tumor at
that arm leaving an ablated area 1315 as the procedure progresses. The
second diagram 1330 shows a further progression of the procedure where
an alternate laser is employed to ablate the bulk of the other arm of the
asymmetrical tumor. Given that surgeons may be required to perform
ablation procedures on asymmetrical tumors in some scenarios it would
thus be advantageous to produce the laser ablation tissue phantom as
disclosed herein with Glioblastoma replicating structures being of
asymmetrical shape. As a result such a feature may improve a surgeons
training in performing the Glioblastoma tumor laser ablation procedure as
described herein.
Referring again to FIGURE 4 the next stage 470 occurs in a loop
with the previous step 475 in the workflow. This stage 470 in both
procedures is to monitor a thermometry map of the patient as the ablation
probe is applying the laser to the target tissue and to progressively
estimate the boundary of the ablated lesion to assure it does not surpass
the boundary of the target tissue. FIGURE 14 shows an exemplary
progression of an ablation procedure and the corresponding MR
thermometry images of the patient as the procedure progresses. The
37
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
figure is provided by the paper [Willie, Jon T., et al. "Real-time magnetic
resonance-guided stereotactic laser amygdalohippocampotomy for
mesial temporal lobe epilepsy." Neurosurgery74.6 (2014): 569-585].
In general MR thermometry works by measuring the proton
resonance frequency shift in protons of water molecules of a tissue to
determine their temperature. The proton resonance frequency of the
protons in water molecules is dependent upon the water molecules
temperature. As a result the temperature of the water molecule may be
inferred from its proton resonance frequency that may be detected by an
MR scan of the patient. The MR images provided in FIGURE 14 are time
stamped at 25s, 75s, and 135s during the laser ablation procedure being
performed providing a visual cue of the temperature of the tissue about the
region being ablated. The figure also contains a diagram showing the
temperature of the thermal ablation area over the elapsed time of the
procedure. This diagram also provides information regarding the
temperatures of the ablated area in accordance with the time stamped
images. Using this technique of simultaneously imaging with MR
thermometry and performing laser ablation on the patient intraoperatively
allows for the surgeon to obtain real time feedback as per the progression
of their surgery and allows them to adjust their plan accordingly if any
unforeseen circumstances arise.
To employ the laser ablation tissue phantom as disclosed herein in
the replication of this MR thermometry monitoring step 470 requires that
the phantom have features such that:
38
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
a) the laser ablations tissue phantom may be imaged using MR
thermometry, and
b) the laser ablation tissue phantom has a water content high
enough such that it may be imaged using MR thermometry
during a simulated laser ablation procedure.
The exemplary laser ablation tissue phantom shown in the right
frame 510 of FIGURE 5 is provided again in FIGURE 15 depicting it in use
during step 470 of the workflow shown in FIGURE 4. The right frame of
FIGURE 15 depicts an embodiment of the phantom under MR
thermometry imaging at the ablation location(s) provided as an example
embodiment only where the red area 1505 is indicative of temperatures
over 60 C outlining the area of immediate thermal necrosis of tissue. The
yellow area 1515 is indicative of temperatures between 43 C and 59 C
where thermal damage is time dependent and the beige area 1520 is
indicative of temperatures lower than 43 C but higher than body
temperature where thermal exposure to the cells wouldn't cause them to
sustain any permanent damage. Using this MR thermometry temperature
profile an ablation zone estimate may be made by either a computer (as
shown as section 1500 in the left side of FIGURE 15) and/or a user on the
MR thermometry image set. This zone may then be transferred to an
alternate image set of the patient using a different protocol or modality.
The transfer may be done directly given that the alternate image set is
registered with the MR thermometry image set. The transfer may allow for
an overlaid area to be outlined on the alternate image identifying on that
image the estimated extent of the ablation. This may allow the surgeon to
39
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
use the information available in the alternate image to judge if the extent of
the ablated area are sufficient for the procedure.
During a laser ablation procedure, in addition to estimating the
extent of the ablation and assuring it does not cross the target regions
boundary, it is common to set markers at anatomical positions on a
patient's scan such that their temperature may be monitored to avoid
unintended thermal damage. For example, when performing an
amygdalohippocampotomy it is typical for the surgeon to place a virtual
position marker on the optic nerve such as 725 shown in the right hand
side of FIGURE 7 to track its temperature using MR thermometry or
thermography. If during the ablation procedure the position markers
temperature rises above a certain threshold for example 43 C when
potential damage may be incurred by the optic nerve the ablation probe
will automatically turn off. This safety feature allows the surgeon to protect
vital eloquent brain structures while maximizing the extent of the desired
ablation.
In order to employ the laser ablation tissue phantom as disclosed
herein in replicating this feature the phantom may be designed with not
only MR visible ablation target anatomical structures such as a
Glioblastoma, amygdala, and a hippocampus but also with important
anatomical structures to be avoided such as the optic tract, motor cortex,
or language centers.
Referring to the workflow depicted in FIGURE 4 the final stages 450
and 445 in both procedures is to remove the laser ablation probe and scan
the patient to verify how successful the ablation was.
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
Thus in order to employ the laser ablation tissue phantom as
disclosed herein in the replication of this step requires that the phantom
have features such that the success of the surgical ablation may be
measured post ablation. Some features that may provide a measure of the
relative progression or success of a simulated surgical procedure such as
that depicted in FIGURE 4 will be further described as follows.
One way to produce such a measure of the relative progress of
success is to fabricate the target structures or surrounding structures of a
laser ablation responsive material. This material being designed such that
a measurable/detectable change in properties of the material would result
from exposure to an application of laser ablation. The resulting changes in
the laser ablation responsive materials could then be interrogated and a
measure of success of the procedure derived from the results.
Following a simulated laser ablation medical procedure the laser
ablation tissue phantom having ablation responsive materials may be
interrogated in one or more ways, two of which will be provided as follows
for examples to determine the efficacy of the mock laser ablation
procedure. The first manner in which the laser ablation tissue phantom
may be interrogated is by scanning the patient using an imaging modality
that would allow the user to see the subsurface structures of the laser
ablation tissue phantom. In an embodiment, these structures would be the
target structures or the surrounding structures at least one of which may
be formed from a laser ablation responsive material. A second manner in
which the laser ablation tissue phantom may be interrogated is by
dissecting the laser ablation tissue phantom and observing or removing
41
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
the section of mimic tissue which were targeted by the laser ablation
procedure. Some exemplary descriptions of laser ablation responsive
materials and their use in concordance with the interrogation methods
described will be provided as follows.
FIGURE 16 illustrates some exemplary laser ablation tissue
phantom structures that have undergone property changes due to
exposure to laser ablation during a simulated laser ablation procedure.
The scan 1620 on the right hand side of FIGURE 16 shows an
embodiment of a tissue ablation phantom wherein two artificial
Glioblastoma tumor structures 1624 and 1622 made of laser ablation
responsive materials have been ablated in a simulated laser ablation
procedure. For illustrative purposes this exemplary scan includes two
separate laser ablation responsive materials for each of the artificial
tumors 1624 and 1622.
In this embodiment the first laser ablated artificial tumor 1624
formed of a laser ablation responsive material has properties such that on
exposure to an applied ablation laser the artificial tumor melts leaving a
cavity in the laser ablation tissue phantom where the artificial tumor had
been ablated. This may be seen at the area 1624 of the post-procedure
scan 1620 indicative of a cavity because of its signal (or lack thereof)
being characteristic of air, such as the area 1625 outside the laser ablation
tissue phantom body in the scan 1620. Thus a comparison of the artificial
tumor 1624 area on the post-procedure scan 1620 with the artificial tumor
area on the pre-procedure scan should be reflective of the success of the
procedure based on the size and location of a cavity. An example of laser
42
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
ablation responsive material that melts on exposure to laser ablation would
be a paraffin wax (melting point from 50 to ab0ut75 C) or a polymer such
as poly(c-caprolactone), poly(ethylene oxide), or polyvinyl acetate with
literature melting point ranges of between about 60 to ab0ut65 C.
In this embodiment the second laser ablated artificial tumor 1622
formed of a laser ablation responsive material has properties such that on
exposure to an applied ablation laser the artificial tumor density decreases.
In general a decrease in density of material in an MR, ultrasound, or any
type of imaging with a characteristic signal strength dependence on
density may result in a reduction of signal acquired from that material.
Thus if the artificial ablated tumor 1622 formed of the laser ablation
responsive material has a lower density and corresponding reduction in
signal strength than its original density and signal strength before a
simulated laser ablation procedure this should be reflective of the success
of the procedure based on the size and location of the area with a reduced
signal strength (such as 1622 shown in Figure 16). An example
embodiment of a laser ablation responsive material that reduces density
on exposure to laser ablation as described above may be a hydrogel
containing a temperature sensitive cross-linker such as PVA cross-linked
with borax or Poly(2-acrylamido-2-methyl-1-propanesulfonic acid) cross-
linked with NN'-methylenebisacrylamidexx (E. A. Karpushkin, "Anionic
Polymer Hydrogel Degradation by Ascorbic Acid" Russian Journal of
General Chemistry, 2013, 83, 1515-1518) where at higher temperatures
the hydrogel will convert back to a solution irreversibly.
43
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
Referring to FIGURE 16 the diagram 1600 shows a dissected laser
ablation tissue phantom embodied in the form of a brain after a simulated
laser ablation procedure. Where the simulated laser ablation procedure
performed, targeted the artificial hippocam pus 1604 and amygdala 1606
structures in the laser ablation tissue phantom. In this embodiment the
targeted structures (hippocampus 1604 and amygdala 1606) are formed of
a laser ablation responsive material that changes chromaticity (colour) on
exposure to a laser ablation application. The area that was ablated by the
laser ablation procedure in this embodiment can be seen as the area 1602
in the diagram and is characterized by a change in chromaticity (colour) in
comparison to its surrounding structures (i.e. the amygdala 1606 and the
hippocampus 1604). Thus by analytically observing the dissected laser
ablation tissue phantom 1600 the success of the laser ablation procedure
may be inferred from the volume of pre-procedure target areas that
remained at their original chromaticity (i.e. were not ablated and thus did
not change chromaticity). It should be noted that not only target structures
but surrounding structures such as the main body of the brain mimic
material 300 may also be fabricated with a laser ablation sensitive
material, such as a material that changes chromaticity as described, in
order to allow the training surgeon to infer the amount of peripheral
damage that has been potentially done. A nonlimiting example
embodiment of a laser ablation responsive material that changes
chromaticity on exposure to laser ablation as described above would be a
material containing an irreversible thermochromic pigment (i.e. OliKrom
smart pigments) that is typically used for thermal mapping that will change
44
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
colour as the temperature increases reaching a maximum colour change
at the desired temperature (50-80 C).xx (A Seeboth, et al. "Thermotropic
and Thermochromic Polymer Based Materials for Adaptive Solar Control".
Materials, 2010, 3, 5143-5168.) The material incorporating the pigment
may be a hydrogel of various densities, or a viscous solution. Another
example is the use of hydrogels that can achieve reversible color change
by adding suitable pH sensitive indicator dyes in combination with
tensides. This therm ochromic behavior is based on the interaction
between the dye's molecules and the hydrogel's micro-environment.
Another example is a polymer blend containing dyes that have an
irreversible colour change once the melt temperature of the blend has
been reached.xx (A Seeboth, et al. "Thermochromic Polymers- Function by
Design" Chem Reviews, 2014, 114, 3037-3068) (Page 3055 explains
polymer melt blends).
Referring to FIGURE 16, element 1610 shows a dissected laser
ablation tissue phantom embodiment where the target structure has been
removed from the surrounding structures of the phantom. In this
embodiment the targeted structure (artificial Glioblastoma) is formed of a
laser ablation responsive material that changes chemical properties such
that it becomes dissolvable by a particular solution after exposure to a
laser ablation application. The volume of the target structure that was
ablated by the simulated procedure in this embodiment of the laser
ablation tissue phantom can be seen as the area 1614 in the diagram and
is characterized by a change in dissolvability in comparison to the
unexposed segment of the remaining target structure 1612. Given the
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
change in chemical properties of the exposed area the target structure
may be bathed in a solution to dissolve away any area that had been
exposed to the ablation laser leaving behind the mass of target structure
that had not been exposed. Thus by comparing this remaining mass of
target structure with the original mass of the target structure the success of
the simulated ablation procedure may be determined quantitatively. An
example embodiment of a laser ablation responsive material that changes
its chemical properties such that it becomes dissolvable upon illumination
from a laser ablation application would be a polymer hydrogel with a
photosensitive cross-linker that will produce a water-soluble polymer after
it has been exposed to light at the desired wavelength.xx (R. P. Narayanan
"Photodegradable Iron(III) Cross-Linked Alginate Gels"
Biomacromolecules, 2012, 13, 2465-2471).
In general any material changing properties after exposure to laser
ablation application may suffice for use as a target or surrounding structure
in an embodiment of the laser ablation tissue phantom as disclosed herein
given the phantom may be fabricated with the material. Furthermore the
success of a laser ablation procedure may be determined quantitatively in
the case where measurable metrics are provided. Such as when
determining the success of the procedure by comparing a pre-procedure
and post-procedure weight in the case of the dissolvability changing laser
ablation responsive material target or surrounding structure. Or a volume
in the case of the melting or density changing laser ablation material target
or surrounding structure. For example if 80% of the desired volume of the
artificial tumor was ablated they may conclude that the simulated laser
46
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
ablation procedure was 80% successful or if 80% of the desired volume
was ablated but 10% of undesired volume was ablated they may conclude
the simulated laser ablation procedure was 70% successful.
It should be noted that these measures of success of a surgery are
being provided as examples only and should not be construed as limiting
and may be defined arbitrarily by any user of the laser ablation tissue
phantom disclosed herein. The success of a laser ablation procedure may
also be determined qualitatively in the case where qualitative metrics are
measured such as when determining the success of the procedure by
comparing a pre-procedure and post-procedure amount of tumor that has
changed colour in the case of the chromaticity changing laser ablation
responsive material target or surrounding structure.
In addition to embodiments where the laser ablation tissue phantom
takes the form of a brain, in some embodiments the laser ablation tissue
phantom as disclosed herein may take the form of other anatomical parts
for other anatomical procedures. For example when performing a Facet
nerve laser ablation as shown in FIGURE 17, the phantom may replicate
spinal bone surrounded by the soft and nervous tissue relating to the
spine. FIGURE 17 shows a cross section of such a laser ablation phantom
during a Facet nerve laser ablation. In the figure a laser ablation probe 800
is inserted through the ligaments of the spine and has gained access to
the Facet 1702 on which the Facet nerve 1700 lies. In order to complete
the procedure the Facet nerve must be ablated such that it no longer
functions. Once in place the laser 800 may be activated forming an
47
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
ablation region 1706 around the tip 805 of laser 800 encompassing the
peripheral Facet nerve 1700.
FIGURE 18 illustrates a side view of the phantom in FIGURE 17 for
further clarification. In addition to the embodiment of the laser ablation
tissue phantoms provided in FIGURES 17 and 18, other anatomical laser
ablation tissue phantoms may include a prostate phantom. It should be
noted that all of the features of the laser ablation tissue phantom
mentioned above may be applied to any of the laser ablation tissue
phantoms described herein. In doing so it should also be noted that all of
the requirements of the features given above such as tissue density or
light absorption coefficients are given as examples only for the tissues
described herein and are not to be construed as limiting. Furthermore
when applying these features or equivalent features individually or in any
combination thereof to laser ablation tissue phantoms of alternate
anatomical parts, correct information regarding those anatomical parts with
respect to the mentioned features may be acquired and used to provide
applicable requirements to produce a laser ablation tissue phantom of that
alternate anatomical part. Some examples of correct information may be
the bone densities of the spine for the spinal phantom as shown in
FIGURE 18. Another example may be the optical absorption spectra, of
bone and nerves located in the spine, or tumor tissue formed on a
prostate.
While the Applicant's teachings described herein are in conjunction
with various embodiments for illustrative purposes, it is not intended that
the applicant's teachings be limited to such embodiments. On the
48
CA 02974846 2017-07-25
WO 2016/119040
PCT/CA2015/050066
contrary, the applicants teachings described and illustrated herein
encompass various alternatives, modifications, and equivalents, without
departing from the embodiments, the general scope of which is defined in
the appended claims.
Except to the extent necessary or inherent in the processes
themselves, no particular order to steps or stages of methods or processes
described in this disclosure is intended or implied. In many cases the
order of process steps may be varied without changing the purpose, effect,
or import of the methods described.
49
