U.S. patent number 6,013,053 [Application Number 08/649,439] was granted by the patent office on 2000-01-11 for balloon catheter for photodynamic therapy.
This patent grant is currently assigned to QLT Photo Therapeutics Inc.. Invention is credited to Bob Bower, Mike Stonefield, Joseph Yan.
United States Patent |
6,013,053 |
Bower , et al. |
January 11, 2000 |
Balloon catheter for photodynamic therapy
Abstract
The present invention provides improved balloon catheter
apparatuses for use in therapies requiring delivery of uniform
light to a treatment area. The improved apparatus comprises a
balloon having a defined treatment window where the window is
delineated using a reflective material. The apparatus may further
include a fiber optic cable that terminates in a diffusion tip
where the diffusion tip is longer than the treatment window. The
present invention further provides improved therapeutic methods
that use the improved balloon catheters of the present
invention.
Inventors: |
Bower; Bob (Richmond,
CA), Stonefield; Mike (Vancouver, CA), Yan;
Joseph (Vancouver, CA) |
Assignee: |
QLT Photo Therapeutics Inc.
(CA)
|
Family
ID: |
24604792 |
Appl.
No.: |
08/649,439 |
Filed: |
May 17, 1996 |
Current U.S.
Class: |
604/96.01;
606/192 |
Current CPC
Class: |
A61N
5/062 (20130101); A61B 18/24 (20130101); A61N
5/0601 (20130101); A61B 2017/22059 (20130101); A61B
2017/22058 (20130101); A61B 2017/00057 (20130101); A61B
2018/2261 (20130101) |
Current International
Class: |
A61B
18/20 (20060101); A61B 18/24 (20060101); A61N
5/06 (20060101); A61B 17/22 (20060101); A61B
17/00 (20060101); A61B 18/22 (20060101); A61M
029/00 () |
Field of
Search: |
;606/7,8,13-17
;604/19-21,49,96 ;607/80,88,89 ;128/633,634 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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0 311 458 |
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Apr 1989 |
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EP |
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0 411 132 |
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Feb 1991 |
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EP |
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0 448 004 |
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Sep 1991 |
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EP |
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WO 90/00420 |
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Jan 1990 |
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WO |
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WO 90/00914 |
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Feb 1990 |
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WO |
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9000914 |
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Feb 1990 |
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WO |
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Other References
Allardice, J.T. et al., "A new light delivery system for the
treatment of obstructing gastrointestinal cancers by photodynamic
therapy," Gastrointestinal Endoscopy 35(6) :548-551 (Nov./Dec.
1989). .
Marcus, S.L., "Photodynamic Therapy of Human Cancer: Clinical
Status, Potential, and Needs," Future Directions and Applications
in Photodynamic Therapy/SPIE Institute Series vol. IS 6:5-56
(1990). .
Nseyo, U.O. et al., "Whole Bladder Photodynamic Therapy: Critical
Review of Present-Day Technology and Rationale for Development of
Intravesical Laser Catheter and Monitoring System," Urology
36(5):398-402 (Nov. 1990). .
Overholt, B.F. et al., "Photodynamic Therapy in Barrett's
Esophagus: Reduction of Specialized Mucosa, Ablation of Dysplasia,
and Treatment of Superficial Esophageal Cancer," Seminars in
Surgical Oncology 11(5):372-376 (Sep./Oct. 1995). .
Overholt, B.F. et al., "Photodynamic Therapy for Esophageal Cancer
Using a 180.degree. Windowed Esophageal Balloon," Lasers in Surgery
and Medicine 14(1):27-33 (1994). .
Panjehpour, M. et al., "Centering Balloon to Improve Esophageal
Photodynamic Therapy," Lasers in Surgery and Medicine 12(6):631-638
(1992) ..
|
Primary Examiner: Yasko; John D.
Assistant Examiner: Mendez; Manuel
Attorney, Agent or Firm: Morrison & Foerster
Claims
We claim:
1. A balloon catheter apparatus for providing irradiation to a
defined treatment area, said apparatus comprising:
i) a clear central channel into which a fiber optic cable can be
inserted; and
ii) an outer sleeve, for use in inflating a balloon, both the
sleeve and balloon have a proximal end and a distal end, said
sleeve is positioned within the inflatable balloon proximate to
said distal end; wherein the surface of said balloon is coated on
both ends with a coated reflective material so as to define a
treatment window therebetween and the coated reflective material,
which defines the treatment window, collects and reflects light
through the treatment window, thereby enhancing uniformity of light
distribution in the treatment area.
2. The apparatus of claim 1, wherein said treatment window is from
about 1 cm to 20 cm in length.
3. The apparatus of claim 1 wherein the treatment window in said
balloon is cylindrical in shape.
4. The apparatus of claim 3 wherein said cylindrical treatment
window is from about 3 mm to about 200 mm in length and from about
1 mm to 100 mm in diameter when inflated.
5. The apparatus of claim 1 wherein said reflective coating is
selected from the group consisting of TiO.sub.2, aluminum, silver
and gold.
6. The apparatus of claim 1 further comprising a fiber optic cable
that terminates in a diffuser, said diffuser being positioned
within the treatment window so that it extends beyond each side of
said treatment window and results in light being more uniformly
distributed on the treatment area and wherein said fiber optic
cable is adapted so as to be provided with light from a light
source.
7. The apparatus of claim 6, wherein said diffuser is a cylindrical
diffuser.
8. The apparatus of claim 7 wherein said diffuser extends about 0.3
cm to about 5 cm beyond each side of said treatment window.
9. The apparatus of claim 1 wherein said balloon is made of high
density polyurethane.
10. The apparatus of claim 1 wherein said treatment window is
transparent.
11. The apparatus of claim 1 wherein said treatment window is
translucent.
12. The apparatus of claim 1 further comprising one or more optical
sensors attached to the wall of said balloon.
13. The apparatus of claim 1 further comprising in said central
channel a fiber optic cable that terminates in a diffuser disposed
within said treatment window, wherein said fiber optic cable is
adapted to be provided with light from a light source.
14. The apparatus of claim 13, wherein a laser diode of less than
about 1.5W is used as a light source.
15. A method for administering light to a defined target area in a
subject, which method comprises inserting into said subject the
balloon catheter as defined in claim 13, and introducing light from
a light source into said fiber optic cable.
16. The apparatus of claim 1 wherein the reflective or scattering
material is coated on the outside of the balloon.
17. The apparatus of claim 1 wherein the reflective or scattering
material is coated on the inside of the balloon.
18. A balloon catheter apparatus for providing irradiation to a
defined area, said apparatus comprising
(i) a clear central channel into which a fiber optic cable can be
inserted; and
(ii) an outer sleeve for use in inflating a balloon, the sleeve and
balloon have a proximal end and a distal end, said sleeve
containing the inflatable balloon proximal to said distal end;
and
wherein said balloon contains a treatment window between the ends
defined by a coating on the interior walls of said balloon; and
(iii) inserted into said clear central channel, a fiber optic cable
terminating in a diffuser positioned within said treatment window,
which cable is adapted to be provided with light from a light
source,
wherein said diffuser extends sufficiently beyond each side of the
treatment window to enhance the efficiency and uniformity of light
distribution in the treatment area.
19. The apparatus of claim 18, wherein a laser diode of less than
about 1.5W is used as a light source.
20. An improved method for administering light to a defined target
area wherein a balloon catheter coupled to a light source is
inserted into a subject and light is emitted from said light source
into said catheter said improvement comprising the use of a balloon
catheter as defined in claim 18.
21. A method for administering light to a defined target area in a
subject, which method comprises inserting into said subject the
balloon catheter as defined in claim 18, and introducing light from
a light source into said fiber optic cable.
22. An improved balloon catheter apparatus containing a defined
treatment window for providing irradiation to a defined area, said
improvement comprising using a reflective material to define the
treatment window.
23. An improved method for administering light to a defined target
area wherein a balloon catheter coupled to a light source is
inserted into a subject and light is emitted from said light source
into said catheter said improvement comprising the use of a balloon
catheter as defined in claim 13.
24. A balloon catheter apparatus for providing irradiation to a
defined treatment area, said apparatus comprising:
a multi-channel sleeve with a first clear central lumen into which
a fiber optic cable can be inserted; and
one or more second lumens for use in inflating a balloon, both the
tubing and balloon having a proximal end and a distal end, said
tubing being attached to the inflatable balloon proximate to said
distal end of said balloon;
wherein 1) the ends of the balloon contain a reflective or a
scattering material, which defines the treatment window, collects
and reflects and/or scatters light through the treatment window,
thereby enhancing uniformity of light distribution in the treatment
area and 2) wherein said multi-channel sleeve comprises:
i) a sleeve, having a clear central channel into which a fiber
optic cable can be inserted; and
ii) at least one additional channel, for use in inflating a
balloon.
25. The apparatus of claim 24 wherein the reflective or scattering
material is coated on the outside of the balloon.
Description
TECHNICAL FIELD
The present invention is in the field of medical devices used in
administering light to a location within the body of a patient,
such as in photodynamic therapy (PDT). The present invention
provides improved balloon catheter devices that more evenly
distribute light throughout the area of a treatment window.
BACKGROUND ART
There is a variety of medical procedures that require light or
irradiated energy to be administered to a patient within the body.
One example is that of therapeutic methods that use a light
activated compound to selectively kill target cells in a patient,
termed photoactivated chemotherapy. Other examples include optical
diagnostic methods, hypothermia treatment and biostimulation. In
photoactivated chemotherapeutic methods, a light-sensitive drug is
injected into a patient and a targeted light source is used to
selectively activate the light-sensitive drug. When activated by
light of a proper wavelength, the light-sensitive drug produces a
cytotoxic agent that mediates the destruction of the surrounding
cells or tissue.
The main application of photoactivated therapy, such as PDT, is for
the destruction of malignant cell masses. Photoactivated therapy
has been used effectively in the treatment of a variety of human
tumors and precancerous conditions including basal and squamous
cells, skin cancers, breast cancer, metastatic to skin, brain
tumors, head and neck, stomach, and female genital tract
malignancy, cancers and precancerous conditions of the esophagus
such as Barrett's esophagus. A review of the history and progress
of photoactivated therapy is provided by Marcus, S. Photodynamic
Therapy of Human Cancer: Clinical Status, Potential, and Needs. In
Gomer, C. J. (ed.); "Future Directions and Applications in
Photodynamic Therapy." Bellingham, W. A. SPIE Optical Engineering
Press (1990) pp 5-56 and specific applications of PDT are provided
by Overholt et al., Sem. Surg. Oncol. 11:1-5 (1995).
One area of focus in the development of phototherapeutic methods
and apparatus is the development of targeted light sources that
provide uniform illumination to a given treatment area.
Allardice et al. Gastrointestinal Endoscopy 35:548-551 (1989) and
Rowland et al. PCT application WO 90/00914, disclose one type of
light delivery system designed for use with PDT. The disclosed
system involves a flexible tube comprising a dilator and a
transparent treatment window that defines a treatment area by using
opaque end-caps made of stainless steel. A fiber optic element that
is connected to a laser and ends in a diffusing tip is used in
combination with the dilator to deliver light to a tissue source.
Allardice et al. discloses that the advantages of this apparatus
over the use of balloon-type catheter reside in providing a more
uniform distribution of light.
Nseyo et al. Urology 36:398-402 (1990) and Lundahl, U.S. Pat. Nos.
4,998,930 and 5,125,925, disclose a balloon catheter device for
providing uniform irradiation to the inner walls of hollow organs.
The device is based on a balloon catheter design and includes a
balloon at one end of the apparatus and an optical fiber ending in
a diffusion tip that is inserted into the lumen of the balloon
through the catheter. The use of the catheter's centering tube was
disclosed as providing a more uniform distribution of the laser
light by centering the optical fiber in the inflated balloon. The
catheter devices disclosed in these references further incorporate
optical sensing fibers in the balloon wall to provide means for
measuring illumination. However, there is no disclosure about the
use of specific coating materials on the balloon to improve light
uniformity or the use of a long diffusion tip that is longer than a
delineated treatment window.
Panjehpour et al. Lasers and Surgery in Medicine 12:631-638 (1992)
discloses the use of a centering balloon catheter to improve
esophageal photodynamic therapy. Panjehpour discloses a cylindrical
balloon catheter into which a fiber optic probe ending in a light
diffuser is inserted. The cylindrical balloon containing the
catheter is transparent and is not modified with a reflective
coating to improve the diffusion of light within the balloon or to
define a treatment window
Overholt et al. Lasers and Surgery in Medicine 14:27-33 (1994)
discloses modified forms of the balloon catheter device described
by Panjehpour. The cylindrical balloon catheter was modified by
coating both ends of the balloon with a black opaque coating to
define a 360 degree treatment window. Overholt additionally
describes a modified balloon in which one-half of the circumference
of the treatment window is rendered opaque to light using the black
coating material. This configuration provides a 180.degree.
treatment window. The black color guard used in the balloon to
define the target window was not a reflective material and did not
increase the uniformity of the light passing through the treatment
window.
Rowland et al. PCT application WO 90/00420, discloses a
light-delivery system for irradiating a surface. The device
comprises a hemispherical shell whose inside is entirely coated
with a diffuse reflector and a light source that is mounted within
the shell. The light source may contain a diffusing source at the
tip allowing diffusion of light within the reflective shell.
Spears, U.S. Pat. No. 5,344,419, discloses apparatuses and methods
for making laser-balloon catheters. Spears utilizes a process that
etches an end of a fiber optic cable to provide a diffusion tip on
the optical cable. The optical cable containing the etched tip is
secured within a central channel of a balloon catheter using a
coating of adhesive containing microballoons. The position of the
tip within the central channel and the microballoons contained in
the adhesive provide increased efficiency in diffusing the laser
radiation in a cylindrical pattern, providing a more uniform
illumination at the target site.
Beyer, et al. U.S. Pat. No. 5,354,293 discloses a balloon catheter
apparatus for delivering light for use in PDT. The balloon catheter
device disclosed employs a conical tipped fiber optic cable to
provide means of deflecting a light beam radially outward through a
transparent portion of an inflated catheter.
In summary, there have been numerous devices that have been
developed for use in PDT that employ a balloon catheter to support
a light source in an ideal central point within a target area that
is to be illuminated (Spears, Overholt, Beyer, Lundahl and
Allardice). The main benefits of using a centering type balloon are
that 1) the clinician does not have to hold the fiber optic in the
central location, this is done automatically by the balloon
catheter, 2) the light dose is more uniform across the entire
treatment are than would be the case of light delivered by a fiber
optic that is held central to the treatment volume without the aid
of a balloon (while this is true with existing designs of balloon
catheters, it is herein demonstrated that the uniformity can be
significantly improved), 3) the treatment field is kept clean of
contaminants e.g. blood, urine that might absorb the light and so
effect the final PDT result, and 4) the overall treatment procedure
can be considerably shortened as it is simpler setting up the fiber
optic and getting the light dose correct. However, the disadvantage
of using current cylindrical centering balloons with existing fiber
optic diffusers is the inability to obtain uniform light being
transmitted through the balloon to the target site.
Although each of the above disclosures provides means for providing
light to a target site, there is no suggestion to use a reflective
coating at the ends of a balloon catheter as a means of increasing
uniformity in the distribution of the transmitted light. In
addition, none of the devices employs a diffusing tip at the end of
the fiber optic cable that is longer than the treatment window.
These two features are present, alone or in combination, in the
apparatus of the present invention and provides improved balloon
catheter devices that more uniformly and efficiently distribute
light over a treatment area.
SUMMARY OF THE INVENTION
The present invention provides improved balloon catheter
apparatuses for use in therapeutic methods that require light
illumination to a specific site. The improved apparatus comprises a
balloon having a defined treatment window where the window is
delineated using material that reflects and/or scatters light back
towards the lumen of the balloon and zone defined as the treatment
window. The apparatus may further comprise a fiber optic cable that
terminates in a diffusion tip where the diffusion tip is longer
than the treatment window.
The present invention further provides improved phototherapeutic
methods that use the improved balloon catheters of the present
invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 provides a diagrammatic representation of the balloon
components of the apparatus of the present invention. Panel A shows
a balloon that provides a 360 degree treatment window. Panel B
shows a balloon that provides a treatment window that is not 360
degrees.
FIG. 2 shows scans of non-reflective, black-end coated catheters
(Overholt catheter) having a 30 mm window using a fiber optic cable
ending in a 25 mm diffuser, with and without white paper to
simulate the effect of tissue scattering.
FIG. 3 shows scans of non-reflective, black-end coated catheters
(Overholt catheter) having a 30 mm window using a fiber optic cable
ending in a 30 mm diffuser, with and without white paper to
simulate the effect of tissue scattering.
FIG. 4 shows scans of non-reflective, black-end coated catheters
(Overholt catheter) having a 30 mm window using a fiber optic cable
ending in a 50 mm diffuser, with and without white paper to
simulate the effect of tissue scattering.
FIG. 5 shows scans of reflective, white-end coated catheters having
a 30 mm window using a fiber optic cable ending in a 25 mm
diffuser, with and without white paper to simulate the effect of
tissue scattering.
FIG. 6 shows scans of reflective, white-end coated catheters having
a 30 mm window using a fiber optic cable ending in a 30 mm
diffuser, with and without white paper to simulate the effect of
tissue scattering.
FIG. 7 shows scans of reflective, white-end coated catheters having
a 30 mm window using a fiber optic cable ending in a 50 mm
diffuser, with and without white paper to simulate the effect of
tissue scattering.
FIG. 8 shows scans of non-reflective, black-end coated catheters
having a 50 mm window using a fiber optic cable ending in a 50 mm
diffuser, with and without various colored paper to simulate the
effect of tissue scattering.
FIG. 9 shows scans of non-reflective, black-end coated catheters
having a 50 mm window using a fiber optic cable ending in a 70 mm
diffuser, with and without various colored paper to simulate the
effect of tissue scattering.
FIG. 10 shows scans of reflective, white-end coated catheters
having a 50 mm window using a fiber optic cable ending in a 50 mm
diffuser, with and without various colored paper to simulate the
effect of tissue scattering.
FIG. 11 shows scans of reflective, white-end coated catheters
having a 50 mm window using a fiber optic cable ending in a 70 mm
diffuser, with and without various colored paper to simulate the
effect of tissue scattering.
FIG. 12 shows scans of non-reflective, black-end coated catheters
having a 70 mm window using a fiber optic cable ending in a 50 mm
diffuser, with and without white colored paper to simulate the
effect of tissue scattering.
FIG. 13 shows scans of non-reflective, black-end coated catheters
having a 70 mm window using a fiber optic cable ending in a 70 mm
diffuser, with and without white colored paper to simulate the
effect of tissue scattering.
FIG. 14 shows scans of reflective, white-end coated catheters
having a 70 mm window using a fiber optic cable ending in a 50 mm
diffuser, with and without white colored paper to simulate the
effect of tissue scattering.
FIG. 15 shows scans of reflective, white-end coated catheters
having a 70 mm window using a fiber optic cable ending in a 70 mm
diffuser, with and without white colored paper to simulate the
effect of tissue scattering.
FIG. 16 shows scans of reflective coated catheters in which the
length of the fiber active region and the balloon window are
equivalent.
FIG. 17 shows scans of reflective coated catheters in which the
length of the fiber active region is 2 cm longer than the balloon
window.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides improved balloon catheter devices
for providing light irradiation to a defined area. Previous
art-known balloon catheters, such as those disclosed by Overholt et
al. Lasers and Surgery in Medicine 14:27-33 (1994), utilize an
absorbing coating, such as black Color Guard supplied by Permatex
Industrial Corp. Avon, Conn., on portions of the balloon to prevent
the light from being transmitted through portions of the balloon.
The non-blacked-out portions of the balloon thus define a treatment
window that can be 360 degrees or can be segmented to be less than
the entire circumference of the balloon, for example a 180 degree
treatment window. It has been found that the intensity and overall
uniformity of the light transmitted through the treatment window
can be dramatically increased by using a coating that reflects
and/or scatters light into the lumen of the balloon rather than the
black absorbing coating used in the Overholt catheter.
Additionally, previously disclosed balloon catheter devices used in
phototherapeutic methods employ a fiber optic cable ending in a
diffusion tip that is centered in the balloon to provide even
radial distribution of the light transmitted through the cable. The
present invention improves on this configuration by disclosing that
the intensity and overall uniformity of light transmitted through
the treatment window can be increased by employing a diffusion tip
that is longer than the treatment window.
Utilizing these observations, the present invention provides
improved balloon catheters for use in providing light irradiation
to a defined area. As used herein, light irradiation, light or
irradiation, refers to light of wavelengths from about 300 nm to
about 1200 nm. This includes UV, visible and infrared light. The
choice of wavelength will be based on the intended use, namely
being selected to match the activation wavelength of the
photoactivated drug or the wavelength used for irradiation when a
photoactivated compound is not employed. Examples of photoactivated
compounds include, but are not limited to ALA, SnET2,
phthalocyanines, BPD, PHOTOFRIN, MACE, psoralen, and derivatives
thereof.
In one embodiment, the apparatus comprises an optically clear
central channel into which a fiber optic probe can be inserted and
an outer sleeve having a proximal end and a distal end and
containing an inflatable balloon proximal to the distal end.
The balloon portion of the apparatus of the present invention can
be manufactured to be any of a variety of shapes when inflated.
Such shapes include, but are not limited to, spherical and
cylindrical shapes with tapering ends. The preferred shape will
depend on the shape and nature of the area of treatment. For
example, when treating the esophageal tract, e.g., when treating
Barrett's esophagus, a cylindrical shape with tapering ends is
preferred.
The size and shape of the balloon and treatment will depend on the
intended use. For example, when the device of the present:
invention is used to treat Barrett's esophagus, the preferred shape
is cylindrical and will be from about 10 mm to about 200 mm in
length and from about 10 mm to 35 mm in diameter when inflated. The
diameter being selected to flatten the folds in the esophagus.
Any semi-resilient material that can form a balloon that can be
inflated using either air or fluid can be used in making the
balloon component of the present apparatus. The material can be
either transparent or translucent. The preferred material will be
transparent and non-distendable. The preferred material is a
polyurethane membrane of a thickness of about 0.11 mm. However, any
material that is used in the construction of other art known
inflatable balloon catheters can readily be used in the devices of
the present invention.
The balloon used in this embodiment of the apparatus of the present
invention contains a reflective material that reflects and
preferably also scatters light into the lumen and treatment window
of the balloon. The material is contained on the ends of the
balloon and the area that is not coated with the reflecting
material defines a treatment area or window.
As used herein, a material is said to be reflective if the material
prevents the transmission of light through the material by
deflecting the light striking the material. The preferred material
will also be able to scatter the deflected light, providing a
diffuse reflection of the light hitting the material. The function
of the reflective material is to provide increased uniformity and
efficiency in the light transmitted through the treatment window
and to prevent light from exposing non-target areas outside the
treatment window.
FIG. 1 provides a diagrammatic representation of a balloon catheter
that contain a reflective coating at both ends (panel a), or a
reflective coating at both ends and a reflective coating over a
portion of the circumference of the treatment window of the balloon
(panel b).
Any coating material that is reflective, and in addition, can
preferably scatter the reflected light, can be used as the
reflective coating for the balloon component of this embodiment of
the apparatus of the present invention. Examples of coating
material include, but are not limited to, titanium dioxide,
aluminum, gold, silver, and dielectric films. The choice of
reflective material used will depend, in a large part, on the
material used in the balloon, the method used to manufacture the
balloon and the wavelength of light used in the phototherapy. A
skilled artisan can readily adapt known reflective materials for
incorporation into the balloon component of the apparatus of the
present invention.
The preferred reflective material will reflect and scatter light
and prevent from about 20% to 100% of light striking the material
from passing through the material. The most preferred will reflect
and scatter from about 70% to about 100% of the light.
The reflective material can be incorporated in the balloon
component of the apparatus of the present invention in a variety of
ways. For example, the reflective material can be applied to the
surface of the balloon after the balloon is formed, for example by
using a dipping process. Alternatively, the reflective material can
be directly incorporated into the material used to form the balloon
during the manufacturing of the balloon. The method used to
incorporate the reflective material into the balloon will be based
primarily on the reflective material used, the material the balloon
is made of, and the method used to manufacture the balloon
component. A skilled artisan can readily employ art-known
procedures for incorporating a reflective material within or onto a
surface of a balloon.
In addition to a reflective coating, the balloon component may
further have an additional opaque coating over the reflective
coating. An opaque coating is used to further prevent light from
exiting the balloon outside the defined treatment window.
The balloon component may further contain optical sensors. Optical
sensors that are integral to the balloon component can be used to
measure the intensity of illumination when the catheter is used
therapeutically. Optical sensors, such as a fiber optic probe or a
photodiode as part of a balloon catheter, have been described in
U.S. Pat. No. 5,125,925.
The apparatus of the present invention may further comprise a fiber
optic cable, a fiber optic bundle or liquid light guide, for
convenience, hereinafter referred collectively as a fiber optic
cable. The fiber optic cable will contain one end that is readily
attachable to a laser or non-laser light source and a second end
onto which a diffuser is attached.
The light carrying section of the fiber optic cable, hereinafter
the fiber optic core, can be of any diameter so long as the fiber
optic cable can be inserted into the central channel of the balloon
catheter. The preferred fiber optic core will be from about 50 to
about 1000 microns in diameter, preferably about 400 microns. The
choice of the core diameter will depend on the brightness of the
light source and the optical power output required from the fiber
optic diffuser tip.
As stated above, the fiber optic cable will terminate in a
diffusion tip or diffuser. As used herein, a diffuser or diffusion
tip, is defined as an element that can be attached to the end of a
fiber optic cable, or a structure that can be formed at the end of
the fiber optic cable, that provides a means for diffusing
(scattering) the light being transmitted through the fiber optic
cable so that it radiates outward from the fiber. Fiber optic
diffusers are readily available and can be created by a variety of
methods including, but not limited to, surrounding a central core
with a scattering media or a scattering film, tapering the tip of
the fiber optic cable to form a conical tip, or by inserting a
tapered fiber optic tip into a cylindrical body containing optical
scattering media. A variety of diffusion tips for using in PDT
apparatus are described in U.S. Pat. Nos. 5,431,647, 5,269,777,
4,660,925, 5,074,632, and 5,303,324. The preferred diffusing tip
for the fiber optic cable contained in the apparatus of the present
invention is the cylindrical diffusion tip described in SBIR
application grant 2R44CA60225/02 and are available from Laserscope
(CA).
The length of the diffusion tip can be varied relative to the size
of the treatment window defined by the reflective material at the
ends of the balloon component. It has been found that the intensity
and uniformity of light being transmitted through the treatment
window can be optimized by selecting a diffusion tip that is longer
than the treatment window. Additionally, the longer diffusion tip
eliminates the need for precise positioning of the fiber optic in
the center of the treatment window. In the Examples that follow, it
was found that a diffusion tip that is longer than the treatment
window provided an increase in the uniformity of light being
transmitted through the treatment window. Preferably, the diffusion
tip will extend from about 0.3 cm to about 5 cm on either side of
the treatment window.
Recent developments in producing small efficient light emitting
diodes (LEDs) permits the use of a probe having multiple LEDs
mounted on an end to form a distributed array. Such a probe can
replace the fiber optic cable and diffuser by being inserted, LED
end first, into the central channel. The LEDs emit a diverging beam
of light without the need for a diffuser, although a diffuser can
be incorporated into such a probe to increase diffusion. In such a
configuration, the LEDs cover the probe to a length equivalent to
the diffuser tip and is equivalent to, and referred to as the fiber
optic cable or probe.
In an alternative configuration, the balloon component can be
provided without the optically clear central channel. In such a
configuration, a fiber optic cable containing the diffusion tip is
connected to the distal end of the balloon and is pulled to a
central location when the balloon is inflated.
The catheters of the present invention can be used with any
wavelength of light. The choice of the wavelength will be
determined by the intended use. In the examples that follows, 633
nm wavelength light, supplied using a helium neon laser, was used.
This is the activation wavelength for a variety of photoactivated
compounds used in PDT. The choice of materials used in each of the
components of the catheters of the present invention, and in
particular the reflective coating and the overall geometry of the
finished assembly, can be specifically tailored to provide the
desired properties for a given treatment wavelength and indication
being treated.
Each component of the improved balloon catheters of the present
invention, namely the reflective coating and a diffusion tip that
is longer than the treatment window, provides increased uniformity
and efficiency in transmitting light to a defined treatment area.
Each component can be used independently with presently available
catheters, for example a longer tip can be used with an Overholt
style catheter, or both components can be used in combination.
The present invention further provides improved methods for
irradiating a surface with light. Specifically, the improved
methods rely on the use of the balloon catheters of the present
invention. The balloon catheters of the present invention are
particularly useful in PDT for the treatment of malignancies of the
esophagus, particularly Barrett's esophagus, for biostimulation and
the treatment of hypothermia. The devices of the present invention
can readily be used by a skilled artisan in all known
phototherapeutic and illumination applications for which a balloon
illumination catheter can be used.
The following examples are intended to illustrate but not to limit
the invention. All of the cited references are herein incorporated
by reference.
EXAMPLE 1
The following data provides a comparison of the present disclosed
balloon catheters and balloon catheters essentially as described by
Overholt et al. Lasers and Surgery in Medicine 14:27-33 (1994). The
data summarizes studies performed using balloons with black ends
(B) or reflective white ends (W) under condition with and without a
simulated tissue reflector at the wall of the balloon (referred to
either paper:none or paper:white). Additionally, a comparison of
different balloon window length/fiber optic diffuser lengths is
provided.
Data were collected using an automated scanning system that
utilizes a modified UDT photodiode (Grasaby Optronics (FL)) as a
detector essentially as described by Kozodoy, et al., "New system
for Characterising the Light Distribution of Optical Fiber
Diffusers for PDT Application" Proc. SPIE OE/LASE 2131A-16 (January
1994) and modified to collect linear scans for the purposes of
these tests. Light of 633 nm wavelength was provided to the fiber
optic probe using a helium neon laser (Aerotech, PA). The balloon
catheters were supplied by Polymer Technology Group (CA). The
optical diffuser tips were supplied by Laserscope (CA).
The data in this example were obtained by simulating a reflective
end capped balloon by painting white liquid paper (Gillette (MA))
on the ends of a transparent PTG balloon. The data presented in
Examples 2 and 3 used balloon catheters containing a reflective
TiO.sub.2 coating that were specifically manufactured by PTG.
FIGS. 2-15 summarizes the data collected. Each figure shows one or
more scans along the length of the balloon window for a variety of
different parameters. The figures show the normalized light
intensity/fluence rate (y-axis) plotted against the position along
the balloon window (x-axis). All of the figures are plotted so that
the y-axis from one figure to the other can be directly compared.
The x-axis matches the balloon catheter window length (X=0 is the
center of the treatment window).
As can be seen, the light intensity drops off as the detector
starts to intersect the edges of the window ("window edge effect"
zone). The point at which the intensity drops off in this zone is
determined by the finite diameter of the detector (2 mm in this
case). The 2 mm diameter factors in the averaging of light in
tissue that results from scattering. For the purpose of analyzing
the data and comparing it from one geometry to another, the section
of the scan beyond the areas labeled as the "window edge effect"
was ignored and only the central section of the scans were
utilized. Each scan also has shown alongside it the average
intensity, and the caption at the bottom identifies the parameters
being investigated.
The figures can be split into 3 broad groups: FIGS. 2-7 show all
the 30 mm balloon window data; FIGS. 8-11 show all the 50 mm
balloon window data; FIGS. 12-15 show all the 70 mm balloon window
data.
Tables 1 and 2 summarize the numbers that have been compiled from
the data presented in FIGS. 2-15. Table 1 provides the data
obtained with a fiber optic diffuser that matches the length of the
balloon window while Table 2 provides the data obtained with a
fiber optic diffuser that is 2 cm longer than the balloon
window.
In addition to the basic description of the parameters being used
and the average and standard deviation, both tables provide
calculated values for the "goodness of uniformity". This is defined
as the percentage of the scan length within a defined plus/minus
band from the mean. A number of plus/minus tolerances (+10%, +20%,
+30%) were deliberately chosen to see what impact this would have
on the values calculated. The region that were of particular
interest is the "Properly Treated Region" (PTR), and values
approaching 1.0 were considered as being excellent (all power
within tolerance limits), and numbers less than this having some
power outside of the tolerances. PTR is meant to refer to whether
the light with a local intensity within this tolerance will produce
the desired PDT response in tissue.
One of the difficulties facing the development of effective PDT for
treating disorders of the esophagus is that there is little
information of how critical the light uniformity needs to be in
phototherapeutic methods such as PDT treatment of Barrett's
esophagus. However, it is reasonable to conclude that increased
uniformity of transmitted light should yield a more even response
in the treated area, potentially avoiding the need to retreat an
given region. Based on the above, using the .+-.10% data in Tables
1 and 2 as the data that is used to determine the ideal balloon
catheter and fiber optic geometry, with a nominal acceptance
criteria of >0.70 as being a good value for the PTR, then the
fiber optic balloon catheter configurations that meet typical
clinical needs will 1) have a fiber optic diffusion tip that is
approximately 2 cm longer than the treatment window and 2) will
have reflecting end material that defines the limits of the
treatment window.
An additional important characteristic relates to the average value
of the intensity (I.sub.av) for each balloon catheter/fiber optic
combination measured at the balloon window. With reflective coated,
white-end catheters and white paper around the balloon to simulate
tissue scattering: a 3 cm window and 5 cm diffuser had a I.sub.av
=3.6; a 5 cm window and 5 cm diffuser had a I.sub.av =3.5; a 7 cm
window and 7 cm diffuser had a I.sub.av =3.5; a 3 cm window and 5
cm diffuser had a I.sub.av =3.6; and a 5 cm window and 7 cm
diffuser had a I.sub.av =4.0.
With no paper around the balloon to simulate tissue scattering: a 3
cm window and 5 cm diffuser had a I.sub.av =1.8; a 5 cm window and
5 cm diffuser had a I.sub.av =1.3; a 7 cm window and 7 cm diffuser
had a I.sub.av =1.3; a 3 cm window and 5 cm diffuser had a I.sub.av
=1.8; and a 5 cm window and 7 cm diffuser had a I.sub.av =1.3.
For all the data given above, the power output from each length of
fiber optic diffuser was normalized to a single power/cm output
from the diffuser tip P, (mW/cm) so the I.sub.av data from the
various combinations given above can be directly compared.
Within each data set (white paper vs. no white paper) the average
values of I.sub.av are reasonably similar (to within .+-.10-20% of
their mean). This implies that a single J/cm value can be set for
each fiber optic, i.e., the clinician measures the power required
according to a known mW/cm for each fiber optic.
The I.sub.av obtained for non-reflective, black-end coated
catheters, using white paper to simulate tissue scattering: a 3 cm
window and 2.5 cm diffuser had a I.sub.av =1.1; and a 5 cm window
and 5 cm diffuser had a I.sub.av =2.1. With no paper to simulate
tissue reflection: a 3 cm window and 2.5 cm diffuser had a I.sub.av
=0.7; and a 5 cm window and 5 cm diffuser had a I.sub.av =1.0. (See
Table 2).
Clinically, Overholt has found it necessary to use 250-300 J/cm for
the 3 cm balloon and 125-150 J/cm for the 5 cm balloon. Overholt's
light doses define a ratio of 1.67-2.4:1 (average of 2:1) for the
different balloon catheters combinations he used. This is
comparable to the values measured above by looking at ration
calculated with and without white scattering paper, i.e.,
1.4-2.0:1.
Another key point to note is that the average intensity measure
above with the various geometry's are higher than those obtained
using an Overholt catheter. This means, quite significantly, that
where Overholt is using a light dose of about 275 J/cm with his 3
cm balloon, the present catheter would use only
to get the same clinical result and the same light dose
(J/cm.sup.2) at the tissue with any of the disclosed balloon
lengths. This can be used as a benefit in two ways. With existing
balloon catheters (black ended) 400 mW/cm is typically used,
resulting in a treatment time of 11.5 minutes for 275 J/cm. With
the reflective end balloon and diffuser tip that is longer than the
treatment window, either the treatment time can be reduced (for
example to 7 minutes at 200 mW/cm) or the mW/cm can be reduced to
84 mW/cm. The latter is extremely important since it would allow
the use of inexpensive laser diodes, even when using a 9 cm
diffuser (1.1 W laser diode needed assuming a 30% loss in the fiber
optic).
Based on the above results, a balloon with white ends provides a
more uniform light dose at tissue, and this together with an
appropriate cylindrical diffuser length fiber optic will permit a
single Pl (mW/cm) and El (J/cm) to be used for PDT treatment with
all such balloon catheter/fiber optic combinations. An additional
benefit is that the integration effect produced by the reflecting
balloon ends allows for the reduction in the treatment time or the
ability to use less expensive, lower power lasers.
In summary, extensive testing has shown that quite unexpectedly, by
changing the ends of the Overholt Barrett's style balloon catheter
from a black absorbing material to reflecting/scattering material,
together with the use of fiber optics that overlap the treatment
window, the uniformity of the light at the balloon surface is
significantly improved. Prior to the present investigation of the
optical characteristics of balloon catheters, it was assumed that
opaque balloon catheter ends should be used simply to prevent the
light from passing beyond the ideal treatment zone and it was
believed that the light dosimetry would be similar for each balloon
catheter irrespective of length. Recently Overholt and Panjehpour
have collected clinical data that confirms the assumption that with
a black ended balloon catheter, a single light dose EL cannot be
used.
When the light field out of the balloon catheter with black ends
was measured, it was observed that the light was decaying as the
edges of the windows were approached, and so the black balloon ends
were changed to a reflecting material. An improvement in the
uniformity profile was observed, although the uniformity still
dropped off at the ends. When the fiber optic diffuser was extended
beyond the window length, a further improvement in the uniformity
profile was observed. Using this configuration, it was possible to
define a balloon catheter/fiber optic geometry that allows a single
value of EL to be defined.
An additional surprising benefit was that the integration effect
obtained with the catheters of the present invention is
sufficiently great that low power lasers may now be usable in areas
that were previously impossible. This opens up many opportunities
for PDT as the need for costly high power lasers has been a
significant limitation. In particular it is likely that laser
diodes with a 1.5W output and operating at 630 nm will now be
usable to treat Barrett's esophagus, even though the currently
planned treatment lengths are up to 7 cm long. Previously this
would have been unthinkable as a means for delivering the light
dose required for typical PDT methods since the treatment time
would need to be about 1 hour using 3 to 4 treatment segments to
cover the entire 7 cm length.
EXAMPLE 2
The following data were generated using reflective coated,
TiO.sub.2, white-ended balloons (provided by the Polymer Technology
Group).
The results are presented in Table 3. The data have been normalized
in such a way that it can be directly compared with the data
provided in the previous examples.
Focusing on the scans generating using white paper to simulate
tissue scattering of the administered light, the key factors to
notice are:
1. The result confirm the results obtained in Example 1 using a
balloon that incorporates a clinically viable scatter in the wall,
namely TiO.sub.2.
2. The mean average is roughly constant (4.34 to 4.44; a difference
of only a few percent). Previously, the uncertainty about the
variability in the integration factor was a cause for concern. The
integration constant is also higher than for previous measurements
(the ends have higher reflectivity).
3. The properly treated region (PTR) remains high--no less than
88.7%.
4. The coefficient of variation is low and roughly constant: (the
standard deviation is no greater than 7% of the mean).
This demonstrates that with a well thought out design, matching the
reflectivity of the white ended balloons to the lengths, the mean
average can be held constant irrespective of the balloon window
length. The higher integration factor will help reduce the
requirements of the light system used to deliver light to the fiber
optic.
EXAMPLE 3
FIGS. 16 and 17 provide graphical scans that can be used to compare
the uniformity of light through the treatment window obtained with
different window size/diffuser size combinations. FIG. 16 shows the
scans for cases in which the lengths of the diffuser and the
balloon window are equivalent. FIG. 17 shows the scans for cases in
which the length of the diffuser is 2 cm longer than the balloon
window. Both scans were performed in the presence of a white
scatter paper to simulate tissue scattering effects.
The data presented in FIGS. 15 and 16 are summarized in Table 3.
Table 3 further contains a summary of results obtained when a white
scatter paper was not used.
These results confirm and further support the conclusions provided
in Example 3, namely the advantages of using the longer fiber
optics and a reflective coating.
TABLE 1
__________________________________________________________________________
T1 T2 T9 T10 T21 T22 T33 T34 T41 T42 T45 T46
__________________________________________________________________________
Paper None White None White None White None White None White None
White Ends B W W B B B W W B B W W Diffuser 5 5 5 3 5 3 3 3 7 7 7 7
Balloon 5 5 5 3 3 3 3 7 7 7 7 Mean Average 2.149 1.000 1.295 3.494
0.839 1.290 1.121 2.161 1.116 2.272 1.347 3.463 Standard Deviation
0.362147 0.133 0.291 0.099 0.187 0.146 0.279 0.146 0.391 0.098
0.314 Coefficient of Variation 0.147 0.169 0.103 0.083 0.118 0.145
0.130 0.129 0.130 0.172 0.073 0.091 Max (as Prcnt of Mean) 1.160
1.227 1.107 1.117 1.136 1.179 1.128 1.137 1.134 1.204 1.082 1.112
Min (as Prcnt of Mean) 0.635 0.536 0.674 0.640 0.712 0.637 0.649
0.610 0.634 0.536 0.670 0.668 ** +/- 30% ** Undertreated Region
0.07341 0.007 0.011 0.000 0.042 0.032 0.032 0.022 0.072 0.004 0.007
Overtreated Region 0.000000 0.000 0.000 0.000 0.000 0.000 0.000
0.000 0.000 0.000 0.000 Properly Treated Region 0.959 0.927 0.993
0.989 1.000 0.958 0.968 0.968 0.978 0.928 0.996 0.993 ** +/- 20% **
Undertreated Region 0.17036 0.057 0.045 0.085 0.132 0.111 0.106
0.112 0.162 0.022 0.039 Overtreated Region 0.050000 0.000 0.000
0.000 0.000 0.000 0.000 0.000 0.011 0.000 0.000 Properly Treated
Region 0.864 0.780 0.943 0.955 0.915 0.868 0.889 0.894 0.888 0.827
0.978 0.961 ** +/- 10% ** Undertreated Region 0.24761 0.181 0.109
0.222 0.238 0.222 0.206 0.235 0.283 0.077 0.173 Overtreated Region
0.429367 0.073 0.043 0.270 0.291 0.317 0.323 0.325 0.364 0.000
0.042 Properly Treated Region 0.372 0.324 0.746 0.848 0.508 0.471
0.460 0.471 0.441 0.353 0.923 0.785
__________________________________________________________________________
TABLE 2
__________________________________________________________________________
T5 T6 T13 T14 T17 T18 T25 T26 T29 T30 T37 T38
__________________________________________________________________________
Paper None White None White None White None White None White None
White Ends B W W B B B B B W W W W Diffuser 7 7 7 2.5 2.5 5 5 2.5
2.5 5 5 Balloon 5 5 5 3 3 3 3 3 3 3 3 Mean Average 2.26 0.98 1.30
3.98 0.69 1.08 1.15 1.75 0.91 1.81 1.84 3.61 Standard Deviation
0.25.05 0.09 0.16 0.10 0.18 0.10 0.21 0.13 0.25 0.16 0.29
Coefficient of Variation 0.05 0.11 0.07 0.04 0.15 0.17 0.09 0.12
0.14 0.14 0.08 0.08 Max (as Prcnt of Mean) 1.05 1.15 1.14 1.07 1.17
1.21 1.09 1.12 1.14 1.15 1.09 1.09 Min (as Prcnt of Mean) 0.82 0.66
0.71 0.83 0.62 0.58 0.73 0.65 0.61 0.59 0.67 0.70 ** +/- 30% **
Undertreated Region 0.02.00 0.00 0.00 0.05 0.07 0.00 0.03 0.05 0.04
0.01 0.01 0vertreated Region 0.000.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 Properly Treated Region 1.00 0.98 1.00 1.00
0.95 0.93 1.00 0.97 0.95 0.96 0.99 0.99 ** +/- 20% ** Undertreated
Region 0.08.00 0.01 0.00 0.12 0.16 0.04 0.10 0.12 0.12 0.05 0.04
0vertreated Region 0.000.00 0.00 0.00 0.00 0.07 0.00 0.00 0.00 0.00
0.00 0.00 Properly Treated Region 1.00 0.92 0.99 1.00 0.88 0.76
0.96 0.90 0.88 0.88 0.95 0.96 ** +/-10% ** Undertreated Region
0.18.06 0.02 0.02 0.26 0.28 0.16 0.21 0.23 0.22 0.12 0.12
0vertreated Region 0.160.00 0.09 0.00 0.36 0.38 0.00 0.19 0.35 0.29
0.00 0.00 Properly Treated Region 0.94 0.66 0.89 0.98 0.38 0.35
0.84 0.60 0.41 0.49 0.88 0.88
__________________________________________________________________________
TABLE 3
__________________________________________________________________________
New Data Using PTG Double-Thickness White-Ended Balloons (25% TiO2
Loading) File Name 53WE 75WE 97WE 53NE 75NE 97NE 33WE 55WE 77WE
33NE 55NE 77NE
__________________________________________________________________________
Fiber Length (cm) 5 7 9 5 7 9 3 5 7 3 5 7 Balloon Length (cm) 3 5 7
3 5 7 3 5 7 3 5 7 Scattering Paper White White White None None None
White White White None None None Mean Average 4.44 4.34 4.37 1.74
1.50 1.35 2.99 3.70 3.85 1.17 1.26 1.20 Standard Deviation 0.16
0.31 0.23 0.11 0.21 0.17 0.27 0.33 0.26 0.09 0.11 0.19 Coefficient
of Variation 0.04 0.07 0.05 0.06 0.14 0.13 0.09 0.09 0.07 0.07 0.09
0.16 Max (as Prcnt of Mean) 107.9% 113.1% 109.9% 111.3% 130.3%
132.8% 113.8% 113.7% 113.1% 106.4% 110.7% 136.1% Min (as Prcnt of
Mean) 93.0% 70.6% 78.4% 73.9% 53.0% 52.3% 72.2% 66.6% 68.8% 67.5%
58.7% 63.8% ** +/- 10% ** Undertreated Region 0.0% 6.2% 3.6% 3.5%
23.7% 3.6% 10.5% 13.4% 5.8% 8.8% 7.2% 33.6% Overtreated Region 0.0%
5.2% 0.0% 7.0% 23.7% 16.8% 15.8% 8.2% 4.4% 0.0% 3.1% 24.1% Properly
Treated Region 100.0% 88.7% 96.4% 89.5% 52.6% 79.6% 73.7% 78.4%
89.8% 91.2% 89.7% 42.3%
__________________________________________________________________________
* * * * *