Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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Improved Method For Targeted Topical Treatment Of Disease
BACKGROUND OF THE INVENTION
The present invention is related to a method and apparatus for topical
treatment of
tissue, particularly diseased tissue, using photodynamic therapy (PDT) and a
PDT agent.
More specifically, the present invention is directed to a method and apparatus
for topical
or systemic application of the PDT agent to the diseased tissue and then
topical
application of light to the diseased tissue.
PDT was developed to treat cancer and other diseases with the promise of
limiting
the invasiveness of the therapeutic intervention and lessening potential
collateral damage
to normal, non-diseased tissue. Key elements ofPDT include either selective
application
or selective uptake of a photosensitive agent into the diseased tissue and
site-directable
application of an activating light. PDT agents are typically applied
systemically (for
example, via intravenous injection or oral administration) or via localized
topical
application directly to diseased tissues (for example, via topical creams,
ointments, or
sprays). Subsequent to administration of the agent (typically 30 minutes to 72
hours
later), an activating light is applied to the disease site, locally activating
the agent, and
destroying the diseased tissue. Light is typically applied by direct
illumination of the site,
or by delivery of light energy to internal locations using a fiberoptic
catheter or similar
means.
Most current PDT regimens are based on systemic appiication of porphyrin-based
agents or topical or systemic application of psoralen-based agents. Examples
of
porphyrin-based agents include porfimer sodium (PHOTOFRIN ), hematoporphyrin-
derivative (HPD), or SnET2. PHOTOFRIN is one of the few agents currently
licensed
by the FDA. Porphyrin-based agents generally are derived from complex mixtures
of
natural or synthetically prepared materials. Many components of porphyrin-
based agents
are lipophilic. As a result of this lipophilicity, porphyrin-based agents have
shown a slight
tendency to preferentially accumulate in some tumors. However, the targeting
of such
agents to diseased tissue is still unacceptably low when compared to uptake in
normal
tissue, (i.e., 2-lOx greater uptake in diseased tissue relative to normal
tissue).
Further, porphyrin-based agents were developed primarily as a result of a
desire to
have agents that are compatible with highly-penetrating activating light so as
to enable
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treatment of deep-seated cancerous tumors. For example, porphyrin-based agents
are
typically activated using light at wavelengths from 600-750 nm, which may
penetrate
tissue to a depth of 1 cm or more. In contrast, light at wavelengths below 600
nm will
penetrate tissue only to a depth much less than 1 cm.
However, the dark toxicity of most porphyrin-based agents is high. Dark
toxicity
is the cellular toxicity in the absence of activating light. Only a small
increase in
cytotoxicity is achieved upon illumination which necessitates high dosages of
agent in
order to effect treatment in specific tissues. Moreover, the systemic
clearance time, which
is the duration subsequent to agent administration wherein significant agent
concentrations
are present in skin and other external tissues, can extend from weeks to
months, forcing
patients to avoid exposure to bright light or sunlight for extensive periods
in order to
avoid serious skin irritation and other complications. Systemic administration
also
necessitates a delay of between 30 min to 72 hours between agent
administration and light
activation, essentially precluding the possibility of immediate treatment of
diseased tissue
upon detection of such diseased tissue. Further, detection and treatment of
gastrointestinal diseases, such as Barrett's esophagus) requires at least two
endoscopic
procedures: one procedure to diagnose, and a subsequent procedure to treat the
diseased
tissue with light following administration of a PDT agent.
The absence of a significant difference between light and dark cytotoxicity
and the
low preferential concentration ratio of most common PDT agents necessitates
use of high
agent dosages. For example, the dosage for treatment of an adult male 'with
PHOTOFRIN may require greater than 100 mg of agent at a cost of more than
$5,000
for the agent alone. This large dose also gives rise to a significant
potential for
development of adverse side effects in healthy tissue (such as skin
phototoxicity) that may
remain for several weeks. Also, since porphyrin-based agents are activated
with light at
wavelengths greater than 600 nm (i.e., near infrared light (NIR)), procedures
based on
porphyrins + NIR can subject the patient to significant risk of serious
complications due
to the tissue penetration potential of such NIR light. Complications can
include
perforation of internal structures, such as the esophagus during treatment of
esophageal
disease, due to undesirable activation of the agent present in healthy tissue
layers which
are beyond the topical treatment site.
Additionally, porphyrin-based PDT agents achieve light-activated cytotoxicity
via
type-II mechanisms, typically the conversion of cellular OZ into cytotoxic
singlet oxygen.
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Because cellular O, levels can be readily depleted during activation of a type-
Il PDT
agent, use of such agents mandates relatively low intensity illumination and
thus relatively
long illumination durations in order to allow 02 levels to remain sufficient
throughout the
duration of light activation. For example, in the treatment of Barrett's
esophagus with
PHOTOFRIN , light intensities typically must be held well below 100-150 mW/cmZ
during treatment, necessitating illumination periods of 10-20 minutes or more.
Numerous
practitioners have also found with type-II agents that it is equally important
to avoid any
tissue manipulation that might compromise blood circulation at the treatment
site during
illumination, again in order to avoid potential depletion of available O2.
Thus, careful
control of the illumination apparatus and procedure is critical in order to
assure that
proper light intensities are delivered without affecting tissue in a manner
that might affect
blood circulation.
Barrett's esophagus is a perfect example of a superficial disease that is an
attractive
candidate for PDT as it occurs in a location that is difficult to access via
conventional
surgical means but is readily accessible using endoscopic catheters. It is a
condition in
which chronic acid reflux from the stomach irritates the esophagus at the
gastro-
esophageal junction, causing epithelial tissue in the esophagus to
proliferate. Patients with
Barrett's esophagus have a significantly increased risk of developing
esophageal cancer.
The FDA has approved PDT (PHOTOFRIN with light at 630 nm) to destroy the
proliferating tissue in Barrett's patients. Similar regimens can also be used
to remove
esophageal stricture caused by esophageal cancer.
A common method for treatment of Barrett's esophagus using PDT is shown in
cross-sectional form in Fig. 1(a). The esophagus 10 has a proximal tissue
surface 12 and
a distal tissue surface 14. In the example shown in Fig. 1(a), a portion of
esophagus 10
is healthy tissue 16 while another portion is diseased tissue 18. Typically, a
non-compliant
balloon 20 inserted into the esophagus 10 is used to stabilize the tissue to
be treated. The
balloon is filled with gas or liquid so that it will expand to a known radius
(nearly filling
the esophagus) while avoiding dilation of the esophagus. Such dilation could
cause
restriction of blood flow to the treatment site which could compromise the 02
supply
during light activation. An optical fiber inserted into the center of the
balloon 20 serves
as a light source 22 to provide a uniform light intensity at the surface of
the balloon. The
outer structure of this balloon 20 may be composed of a material that scatters
activating
light 24 or may be transparent to the activating light.
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PDT agent present in tissue located proximal to the balloon (on the proximal
tissue
surface 12) is thereby activated by light emitted from the surface of the
balloon 20.
Because the balloon 20 is non-compliant, it is possible to estimate the light
intensity at the
surface of the balloon based on geometrical properties of the balloon and
knowledge of
the light emitting properties of the light source 22. A fiberoptic diffuser
tip is an example
of such a light source. However, since the external surface of the balloon 20
generally will
not conform exactly to the shape of the esophagus, it is not possible to
accurately estimate
light intensity at all points along the circumference of the proximal tissue
surface 12.
Moreover, should the light field present at the proximal tissue surface 12 be
uneven, for
example due to non-uniform light emitting properties of the light source 22 or
incorrect
location of the light source 22 in the esophagus 10, uneven treatment may
result. In
extreme cases, such uneven treatment can compromise tissue sufficiently to
result in tissue
perforation and patient death.
As shown in Fig. 1(b), activation of the PDT agent in the esophageal tissue
upon
illumination will produce a treatment zone 26 which will generally include the
entire zone
of diseased tissue 18 in Fig.1(a) and may extend radially and
circumferentially a significant
distance beyond the margins of the zone of diseased tissue 18. In fact, use of
NIR light
for agent activation can result in formation of a treatment zone that extends
a significant
distance from the proximal tissue surface 12 to the distal tissue surface 14
of the
esophagus 10. This is a consequence of the large penetration depths
characteristic ofNIR
light and the presence of a significant systemic concentration of agent in
healthy tissue.
In extreme cases, this enlargement of the treatment zone can compromise
healthy tissue
sufficiently enough to result in tissue perforation and patient death.
This example of the use of PDT for treatment of superficial lesions
illustrates a
number of disadvantages of current methods and apparatus. For example:
(1) Systemic agent application is costly due to high agent dosage
requirements;
(2) Systemic agent application results in sensitization of healthy tissue
outside of the
desired treatment zone;
(3) Systemic agent application results in prolonged skin photosensitization;
(4) Systemic agent application requires significant delay between disease
diagnosis and
disease treatment in order for the agent to reach the diseased tissue while
clearing
out of the surrounding healthy tissue;
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(5) Systemic agent application provides PDT practitioners with limited control
over the
site of agent delivery and concentration;
(6) Systemic agent application results in uneven treatment due to uneven
partitioning
of the agent into the diseased tissues;
(7) Use of type-II agents requires slow and lengthy agent activation to avoid
02
depletion;
(8) Use of type-II agents requires careful tissue handling to avoid
restriction of blood
flow and the resultant O2 depletion during tissue illumination; and
(9) Use oftype-II agents, when commonly combined with NIR activating light,
results
in excessive treatment depths in most topical applications, adversely
affecting
surrounding healthy tissue.
Therefore, it is an object of the present invention to provide new methods and
apparatus for an improved application of PDT while increasing the efficacy and
safety of
the procedure and reducing the cost of treatment.
SUMMARY OF THE PRESENT INVENTION
The present invention is directed to a method and apparatus for topical
treatment
of diseased tissue, including topical or systemic application of a PDT agent
to diseased
tissue, followed by topical application of light. In general, the method
involves the steps
of applying a PDT agent to diseased tissue to form a treatment zone; purging
excess
agent; and applying light to the treatment zone to activate agent associated
with the
diseased tissue. The light penetrates the treatment zone while minimizing
activation of the
agent outside the treatment zone.
In a preferred embodiment, Rose Bengal is the PDT agent.
In a further embodiment, the PDT agent is directly applied only to the
treatment
zone. Alternatively, the PDT agent can be applied systemically.
In a still further embodiment, the depth of activation of the PDT agent is
controlled
by proper selection of wavelength of activating light so as to avoid
activation of agent that
may be present in underlying healthy tissues.
In yet a further embodiment, the diseased tissue is diagnosed before applying
the
PDT agent.
In another embodiment, detection and treatment of a lesion may be effected in
a
short time period using a single procedure (such as endoscopy) instead of by
separate
diagnostic and therapeutic procedures.
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In another embodiment, treatment rate is not limited by oxygen-dependent
mechanisms.
In another embodiment, heat is also applied to the treatment zone to increase
efficacy of activation of the agent.
In still another embodiment, activating light is delivered through a "balloon"
or
other delivery apparatus located at the disease site.
In another embodiment, the method of the present invention can be used for
treatment of disease in the gastrointestinal tract.
The method of the present invention can also be used for treatment of disease
in
vessels of the circulatory system.
The present invention is also directed to an apparatus for topical treatment
of
diseased tissue.
Accordingly, the present invention is directed to a method and apparatus to
improve the evenness of light delivery, and to improve the safety and efficacy
and reduce
the cost of PDT, for treatment of Barrett's esophagus and other conditions.
The invention in a broad aspect seeks to provide an endoscopic apparatus for
topical treatment of diseased tissue located within a body comprising
applicator means for
applying a PDT agent to the diseased tissue so as to form a treatment zone,
and means
for purging excess agent from the treatment zone prior to photoactivation of
residual PDT
agent. There is a source of light to activate the PDT agent in the, wherein
the light , is
able to penetrate the diseased tissue while minimizing activation of the agent
outside the
diseased tissue, the light having a wavelength between approximately 400-600
nm.
The invention also pertains to the use of such apparatus for the treatment of
diseased tissue located within a body.
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BRIEF DESCRIPTION OF THE DRAWINGS
In describing the preferred embodiments, reference is made to the accompanying
drawings wherein:
FIGURE 1(a) shows a cross-sectional view ofan esophagus illustrating a common
method for treatment of Barrett's esophagus using PDT;
FIGURE 1(b) iltustrates the treatment zone of the method of Figure 1(a);
FIGURE 2(a) illustrates an example of an embodiment of the present invention
for
treatment of diseased esophageal tissue;
FIGURE 2(b) illustrates an alternate example of the embodiment of Figure 2(a);
FIGURE 2(c) illustrates an additional alternate example of the embodiment of
Figure 2(a);
FIGURE 3(a) illustrates an example of another embodiment for the treatment of
disease in vessels of the circulatory system; and
FIGURE 3(b) illustrates an alternate example of the embodiment of Figure 3(a)
wherein the PDT agent is directly applied to the diseased tissue.
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DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED
EMBODIMENTS
The method and apparatus of the present invention is applicable to improved
treatment of various dermatologic afflictions, such as psoriasis or skin
cancer, and to
diseased tissues at sites within the body, such as disease of the digestive or
respiratory
tracts. The present invention can also be used for the treatment of other
anatomical sites,
including intra-abdominal, intra-thoracic, intra-cardial, intra-circulatory,
intra-cranial, and
the reproductive tract.
In general, the method of the present invention involves one or more of the
following steps. Initially, disease is diagnosed using, for example,
histologic examination,
or by measurement of the autofluorescence properties of diseased tissue or by
detecting
selective uptake of an indicator agent, such as a fluorescent dye or a PDT
agent, into such
diseased tissue. Thereafter, a sufficient quantity of a topical or systemic
formulation of
a desired PDT agent is applied to the disease site so as to cover, perfuse, or
saturate the
diseased tissue. After a brief accumulation period to allow the agent to coat,
perfuse, or
otherwise become active within the diseased tissue, excess agent is purged or
flushed from
the disease site, and a substantially uniform light field is applied to the
disease site in order
to activate the agent associated with the diseased tissue.
For treatment of superficial diseased tissue, the wavelength of the light is
preferably
chosen so as to allow optical penetration into the diseased tissue but to
minimize further
optical penetration beyond the diseased tissue into underlying healthy tissue.
For example,
visible light in the spectral region between 400-600 nm may be used to afford
shallow
penetration depths on the order of several millimeters or less. Use of such
light affords
efficacy in agent activation in superficial diseased tissues while
simultaneously minimizing
potential for deleterious photosensitization of underlying tissue. Preferably,
laser light is
used. It can be delivered by fiberoptic catheters. Alternatively, light can be
delivered by
direct illumination. Other alternate light source configurations and delivery
apparatus
include fiberoptic bundles, hollow-core optical waveguides, and liquid-filled
waveguides.
Alternate light sources, including light emitting diodes, micro-lasers,
monochromatic or
continuum lasers or lamps for production of activating light, and continuous
wave or
pulsed lasers or lamps. Either single-photon or two-photon excitation methods
can be
used for agent activation. A more detailed explanation of such excitation
methods is given
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in commonly assigned Canadian Patent File No. 2.252,783 filed October 28. 1997
which may be referred to for fiirther details.
Furthermore, the time and order of the applications of the agent and light can
also
be varied. For example, application of the agent and the light treatment
regimen can be
repeated one or more times to eliminate residual diseased tissue. Further, for
some
applications, an increased delay between agent application and light treatment
can be
beneficial. Additionally, the step of diagnosing can almost immediately be
followed by
the steps of applying a PDT agent, purging excess agent and applying light so
that said
method of diagnosis and treatment is done in a single procedure. If PDT agent
uptake is
used to diagnose or detect diseased tissue, the step of diagnosing can be
immediately
followed by the step of applying activating light. Alternatively, there may be
an indefinite.
delay between diagnosis and PDT treatment.
Preferably Rose Bengal is used as the PDT or photosensitizing agent as it is
inexpensive, non-toxic, has a proven safety record in human use, has
significant intrinsic
lipophilic properties, exhibits both type-I and type-II PDT response and
therefore can be
activated by type-I, oxygen-independent mechanism and is strongly phototoxic
upon
activation with light between 500 nm and 600 nm. Because of its 02-independent
response, Rose Bengal is compatible with high intensity light activation,
which reduces
treatment time relative to porphyrin-based agents. More specifically, Rose
Bengal is
optimally activated using light between 500 nm and 600 nm, which is sufficient
for
activation of superficial diseased tissue and substantially avoids the
potential for activation
of underlying healthy tissues. An example of such a PDT agent is a solution of
Rose
Bengal formulated with a suitable lipophilic delivery vehicle, such as I-
octanol or
liposomes.
Alternatively, other PDT agents, including type-I or type-II agents can be
used.
Examples of such standard PDT agents include psoralen derivatives; porphyrin
and
hematoporphyrin derivatives; chlorin derivatives; phthalocyanine derivatives;
rhodamine
derivatives; coumarin derivatives; benzophenoxazine derivatives;
chlorpromazine and
chlorpromazine derivatives; chlorophyll and bacteriochlorophyll derivatives;
pheophorbide
a (Pheo a); merocyanine 540 (MC 540); Vitamin D; 5-amino-laevulinic acid
(ALA);
photosan; pheophorbide-a (Ph-a); phenoxazine Nile blue derivatives including
various
phenoxazine dyes; PHOTOFRIN; benzoporphyrin derivative mono-acid; SnET,; and
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LutexT'. The inventors of the present invention believe that all present and
futiire
PDT agents will work in the method and apparatus of the present invention.
Additionally, the present invention is not limited to the use of one PDT
agent.
Instead, more than one PDT agent can be used during a treatment regimen.
In a further embodiment, the PDT agent used in the present invention can
include
at least one targeting moiety. Examples of such targeting moieties include
DNA, RNA,
amino acids, proteins, antibodies, ligands, haptens, carbohydrate receptors or
complexing
agents, lipid receptors or complexing agents, protein receptors or complexing
agents,
chelators, and encapsulating vehicles. Such targeting moieties may be used to
improve
the selectivity of agent delivery to diseased tissue, and can function either
by association
with the photosensitizing PDT agent (for exampie where the PDT agent is
encapsulated
in a vehicle composed of the targeting moiety) or by attachment to the
photosensitizing
PDT agent (for example where the PDT agent is covalently attached to the
targeting
moiety).
In a further preferred embodiment, the PDT agent is applied directly to the
diseased
tissue. Employment of direct topical application provides a number of
advantages. In
particular, it affords improved targeting of the agent specifically to the
diseased tissue,
reduces the required latency period between agent administration and light
activation and
thereby shortens the treatment cycle, substantially eliminates the potential
for systemic
photosensitization, reduces agent consumption, and reduces the overall
potential for side
effects from exposure to the agent. Preferably, the agent is applied as a
topical spray or
wash. After a brief accumulation period (generally not to exceed 30 minutes),
the excess
agent is removed from the tissue surface by flushing with liquid, such as with
water or
saline. Following this flushing, it is preferred that the residual agent
associated with the
diseased tissue be activated by illumination of the diseased site with visible
light between
400 nm and 600 nm. Optically, the light can be applied as discussed supra.
Alternatively, the PDT agent can be applied systemically. For example, this
application may be via intravenous injection or parenteral administration
(such as by
consumption of a tablet or liquid formulation of the PDT agent).
In a further embodiment, heat can be applied to the treatment zone to increase
PDT
effectiveness via hyperthermia. Heat can be applied, for example, through the
use of a.
heated liquid in an illumination balloon, a transparent heating pad positioned
between the
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illumination source and the tissue, or simultaneous illumination of the
treatment site with
infrared energy.
Examples of some of these embodiments of the present application are shown in
cross-sectional form in Figs. 2(a), 2(b), and 2(c).
Fig. 2(a) illustrates an example of a treatment of diseased esophageal tissue
using
a non-compliant balloon 20 illumination apparatus. Initially, a treatment zone
30 is
identified. This can be done for example via endoscopic examination of the
esophagus and
visual or spectroscopic identification of zones of diseased tissue. Such
identification can
include detection of histologic changes or other visual indicators of disease,
detection of
changes in autofluorescence, or detection of uptake of PDT or other agents
into diseased
tissue. Following identification of the treatment zone 30, PDT agent is
applied to the
identified diseased tissue. This agent can be applied, for example, via
systemic application
or more preferably, by direct spray application using a nozzle or other means
provided at
the distal end of an endoscope. Excess agent is subsequently purged from the
site by, for
example, natural systemic clearance or by flushing with liquid.
A transparent, non-compliant balloon apparatus 20 is then inserted into the
esophagus so as to span the treatment zone 30. The non-compliant balloon 20 is
filled
with gas or liquid to a pre-determined pressure so as to establish a desired
pre-determined
radius. Visible light 24 is then uniformly delivered radially to the treatment
site through
the walls of the balloon 20 using a light source 22, such as for example a
fiberoptic
diffuser, located along the central axis of the balloon.
Additionally, the balloon 20 can be filled with a scattering medium, such as a
dilute
solution of intralipid, so as to improve the uniformity of light intensity
delivered at the
surface of the balloon. Further, the balloon 20 can be composed of or include
a material
that scatters the light 24 delivered at the surface of the balloon so as to
further improve
the uniformity of light intensity delivered at the surface of the balloon.
Examples of such
a material include a material that is naturally translucent, such as latex; a
polymer that
includes particulate scattering materials; or a polymer with a roughened
surface.
In the example illustrated in Fig. 2(a), the intensity of the light source 22
is operated
at a pre-determined level for a pre-determined duration based on the filled
radius of the
non-compliant balloon 20 and the desired light intensity and light dose at the
surface of
the balloon.
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An alternate example of this embodiment is shown in cross-sectional form in
Fig.
2(b), where diseased esophageal tissue is treated using an enlarged non-
compliant balloon
40. In this example, following identification of diseased tissue, PDT agent is
applied to
the identified diseased tissue. Excess agent is subsequently purged from the
site.
A transparent, non-compliant balloon apparatus 40 is then inserted into the
esophagus so as to span the treatment zone 30. The non-compliant balloon 40 is
filled
with gas or liquid so as to substantially distend or slightly dilate the
esophagus, eliminating
folding of the esophageal surface and thereby presenting a more uniform tissue
surface 12
for illumination. Fill pressure is measured to establish the radius of the
filled balloon.
Visible light 24 is then uniformly delivered radially to the treatment site
through the walls
of the balloon using a light source 22, such as for example a fiberoptic
diffuser, located
along the central axis of the balloon.
Additionally, the balloon 40 can be filled with a scattering medium, such as a
dilute
solution of intralipid, so as to improve the uniformity of light intensity
delivered at the
surface of the balloon. Further, the balloon 40 can be composed of or include
a material
that scatters the light 24 delivered at the surface of the balloon. Examples
of such
materials include material that is naturally translucent, such as latex; a
polymer that
includes particulate scattering materials; or a polymer with a roughened
surface.
The pressure used to fill the balloon is measured and used to establish the
operational radius of the filled balloon, and the intensity of the light
source 22 is operated
at a level that is selected based on the operational radius of the filled non-
compliant
balloon 40 so as to deliver a desired light intensity and light dose at the
surface of the
balloon. It is preferred in this alternate embodiment that sufficient pressure
be used so as
to minimize folding of the treated esophageal region without significantly
dilating the
esophagus so as to avoid potential stenosis or other non-specific irritation
of esophageal
tissue.
An additional alternate example of this embodiment is shown in cross-sectional
form in Fig. 2(c), where diseased esophageal tissue is treated using a
compliant balloon
50. In this example, following identification of diseased tissue, PDT agent is
applied to
the identified diseased tissue. Excess agent is subsequently purged from the
site.
A transparent, compliant balloon apparatus 50 is then inserted into the
esophagus
so as to span the treatment zone 30. The compliant balloon 50 is filled with
gas or liquid
so as to fill, distend or slightly dilate the esophagus, substantially
eliminating non-uniform
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contact between the esophageal surface and the balloon and thereby presenting
a uniform
tissue surface for illumination. Fill pressure is measured to establish the
approximate
radius of the filled balloon. Visible light 24 is then uniformly delivered
radially to the
treatment site through the walls of the balloon 50 using a light source 22,
such as for
example a fiberoptic diffuser, located along the central axis of the balloon.
Additionally, the balloon 50 can be filled with a scattering medium, such as a
dilute
solution of intralipid, so as to improve uniformity of light intensity
delivered at the surface
of the balloon. Further, the balloon 50 can be composed of or include a
material that
scatters the light 24 delivered at the surface of the balloon. Examples of
such materials
include material that is naturally translucent, such as latex; a polymer that
includes
particulate scattering materials; or a polymer with a roughened surface.
The pressure used to fill the balloon is measured to establish the operational
radius
of the filled balloon. Thus, in this example, the intensity of the light
source 22 is operated
at a level that is selected based on the operational radius of the filled
compliant balloon
50 so as to deliver a desired light intensity and light dose at the surface of
the balloon.
Preferably, in this alternate embodiment, sufficient pressure is used so as to
minimize
folding of the treated esophageal region without significantly dilating the
esophagus (to
avoid potential stenosis or other non-specific irritation of esophageal
tissue).
For the treatment of disease in vessels of the circulatory system (such as
arterial or
venous plaque), Figs. 3(a) and 3(b) illustrate an alternate preferred
embodiment of the
present invention
In the specific example of Fig. 3(a), a photosensitive agent is applied
parenterally
or via intravenous injection. The agent accumulates in diseased tissue of the
vessel wall
60 to form a treatment zone 62. This agent is chosen based on preferential
concentration
in diseased material present at the desired treatment zone. After a brief
accumulation
period, a light 64 is applied to the disease site in order to activate the
agent associated
with the diseased material. This application may be effected by using a
fiberoptic catheter
66 or similar means having a focusing, collimating, or diffi.csing terminus
for spatial control
of light delivery. The fiberoptic catheter 66 is able to deliver the light 64
directly to the
treatment zone 62 so that the light can be applied topically. To minimize
potential optical
penetration into underlying healthy tissue, it is preferred that visible light
in the spectral
region between 400-600 nm be used so as to effect shallow penetration depths
on the
order of several millimeters or less. Use of such light affords efficacy in
agent activation
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in superficial diseased material while simultaneously minimizing potential for
deleterious
photosensitization of the underiying tissue.
Alternatively, the photosensitive agent administration can be effected via
localized,
direct application of an agent to diseased material in the treatment zone 62,
as illustrated
in Fig. 3(b). Agent administration may be readily effected via an agent
delivery device 68,
such as a capillary tube, attached to and terminating near the end of the
fiberoptic catheter
66, that is used to deliver a small quantity of agent, as a stream 70 or other
flow, directly
to or in the vicinity of the treatment zone 62. Alternately, this delivery
device 68 may be
separate from the fiberoptic catheter 66, thereby facilitating independent
position of the
respective termini of the light delivery fiberoptic catheter 66 and the agent
delivery device
68. In either embodiment, delivery of a small quantity of photosensitive agent
to diseased
material in the treatment zone 62 is followed, after a short accumulation
period, with
application of light 64 to the disease site in order to activate agent
associated with
diseased material.
Preferably, in these example embodiments, Rose Bengal is used as the
photosensitizing agent. Rose Bengal is optimally activated using light between
500 nm and
600 nm, which is sufficient for activation of superficial diseased material
and substantially
avoids potential for activation of underlying healthy tissues. Further, this
agent is
compatible with high intensity activating light, which may thereby be used to
substantially
reduce treatment times over that required with other agents, such as Type-II
PDT agents.
This description has been offered for illustrative purposes only and is not
intended
to limit the invention of this application, which is defined in the claims
below.
What is claimed as new and desired to be protected by Letters Patent is set
forth
in the appended claims.
SUBSTITUTE SHEET (RULE 26)
