Pdt Systems, LLC

Miravant Systems, Inc.

University of California

Laser Therapeutics, Inc.

Daniel R Doiron

Hugh L Narciso, Jr

John B Dunn

Paul M Paspa

Steven C Anderson

A Charles Lytle

Christine J Radasky

Richard A Hill

Gregory S Graham

Hugh L Narcisco, Jr

David H Crean

Leslie A Edwards

Brian K Dalton

David E Mai

Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

Method for photo-altering a biological system to improve biological

A method for intraoperatively administering Photodynamic Therapy (PDT) to a highly vascularized target tissue. The method of PDT begins with the introduction of an exogenous photosensitizing agent into the target tissue-associated vasculature. Upon entry of the photosensitizer into the vasculature, the target tissue is immediately exposed to phototherapeutic light having a wavelength suitable for photoactivating the photosensitizer within the target tissue-associated vasculature. Continued illumination of the target tissue affects destruction of the vasculature within the tissue without requiring the photosensitizer to accumulate within the nonvascular tissue cells prior to photoactivation. The destruction of the vasculature supplying the target tissue destroys the target tissue. The method eliminates the prior art procedural step of waiting for the photosensitive compound to accumulate within the target tissue cells prior to administering photoactivating light to the target tissue. The photodynamic treatment of Dysfunctional Uterine Bleeding is presented as an example of applying the method to treat highly vascularized target tissue. The intraoperative method may be adapted for treating other tissues by increasing the amount of photosensitizer laden blood in the tissue by adjunctive means such as inducing localized vasodilator.

Photodynamic Therapy of highly vascularized tissue

A light diffuser tip for use with an optical fiber. The diffuser tip is affixed to an optical fiber and comprises an optically transparent elastomer core positioned to receive light from the output terminus of the optical fiber. The concentration of scattering centers embedded in the transparent elastomer core varies along the length of the core to yield a particular light distribution pattern. For example, the scattering centers may be distributed within an optically transparent elastomeric core material such as silicone to provide a scatterer density gradient along the diffuser tip in the axial direction of the optical fiber. A diffuser tip which provides uniform cylindrical light output intensity in air will provide a different output intensity distribution in a medium with a different index of refraction such as human tissue. The distribution of scattering centers within the transparent core of the diffuser tip can be customized to provide a substantially uniform radiance along the length of the diffuser tip when the tip is embedded within a medium having an index of refraction different from air. Such a custom diffuser tip is particularly useful for laser radiation treatment of tumors. Similarly, the concentration gradient of scatterers within the transparent core of the diffuser tip can be adjusted to provide an output light intensity distribution which will uniformly illuminate the wall of an irregular cavity.

Custom cylindrical diffusion tips

A catheter and a method for using the catheter for the transluminal hyperthermic treatment of target tissue is presented. The catheter comprises an elongate tubular member having two coolant circulating lumens and an optical waveguide coextensive therewith, the proximal end of the optical waveguide being adapted to receive light from a light source and the distal end of the optical waveguide terminating in a diffuser tip. The diffuser tip provides a means for radially distributing treatment light from the light source to tissue adjacent to the distal tip of the catheter to heat the tissue. A transparent, inflatable balloon surrounds the diffuser tip. The inflatable balloon permits the flow of an optically transparent coolant around the diffuser tip to cool the tissue immediately adjacent to the diffuser tip to prevent overheating. A method of using the device for the transurethral treatment of benign prostate hypertrophy is presented as an example.

Transluminal hyperthermia catheter and method for use

A device for delivering phototherapeutic light to uniformly illuminate a tissue surface. The device is a bowl-shaped shell with a more-or-less parabolic profile and having an open end and an apex. The inner surface of the shell is adapted to diffusely reflect light with very low absorption by the shell material. A light output end of a fiber optic is introduced into the interior of the shell through a fiber optic port in the shell wall near the apex. The light output end of the fiber is positioned such that light emanating therefrom impinges upon the inner surface of the shell. The shape of the shell causes greater than 60 percent of the light emanating from the fiber to intercept the shell's surface and be diffusely reflected. The diffusely reflected light may then undergo further diffuse reflection within the shell prior to reaching the treatment surface adjacent to the open end of the shell to provide more uniform illumination of the treatment surface than the fiber could otherwise provide. A highly reflective coating is applied to the outer surface of the shell to prevent loss of treatment light from the device. In addition, treatment light which is reflected from the tissue surface and normally lost is captured by the interior surface of the shell and re-reflected to reenter the tissue surface. Thus, little or no treatment light is lost due to reflection or scattering from tissue providing improved efficiency. The shell preferably includes a laterally extending flange around a portion of the open end which can be affixed to the tissue surface thereby preventing relative motion between the illuminator and tissue surface during treatment enabling accurate dosimetry.

Surface illuminator for photodynamic therapy

A light delivery catheter having an elongate, flexible inner tube coaxially disposed within a lumen within a flexible outer tube, and axially movable with respect to the outer tube. An optical waveguide disposed within the inner tube conducts light from an external light source to a light diffuser element in optical communication with the distal end of the optical waveguide. A portion of the light conducted to the diffuser element is scattered radially into the surrounding volume. The outer diameter of the inner tube is less than the diameter of the outer tube lumen, the annular space therebetween forming a cylindrical lumen coextensive with the inner tube. One or more fiber optics disposed within the cylindrical lumen are attached to the outer surface of the inner tube and terminate distally in an isotropic tip. Fiber optic bending means, responsive to advancement of the inner tube within the outer tube, causes the distal tips of the fiber optics to bend radially outward, as the distal tip of the inner tube emerges from the confines of the outer tube lumen. In operation, the distal tip of the outer tube is positioned within a body cavity. The inner tube is advanced through the outer tube lumen until the element and the distal tips of the fiber optics project beyond distal end of the outer tube. Therapeutic light from an external source is conducted from the proximal end of the optical waveguide to the diffuser element. The diffuser element scatters a portion the light radially, a portion of the radially scattered light being picked up by the fiber optic tips which are in contact with the tissue on the inner surface of the body cavity. The portion of light entering the isotropic tips is conducted to the proximal end of the catheter via the respective fiber optics for light detection and measurement.

Light delivery catheter

A light delivery device including an interchangeable handpiece and a semiconductor light source module adapted to releasably attach to the handpiece. The light source module includes a two-dimensional array of light emitting diodes (LED's) disposed on a surface of a fluid-cooled electrically conductive support plate. The device is adapted for uniformly illuminating a tissue surface with phototherapeutic light. The phototherapeutic light is produced by an array of over-driven LED's mounted on the surface of the heat-sinked support. The semiconductor light source employs a multi-layer construction wherein electrically conductive layers are thermally isolated from each other. The device is rugged, inexpensive and can produce high optical power while operating at a temperature well below the temperature at which device failure occurs. The light source module is adapted to be releasably connected to an interchangeable LED handpiece which provides power to the LED's and conducts a coolant fluid. The light source includes an integral unitary reflector for directing the light output from the individual LED's in the LED array in a desired direction. The reflector is a thin perforated sheet having a top, tissue facing surface and bottom surface and an array of cup shaped openings therebetween, each such perforation in the sheet being disposed to overly a LED in the LED array. The inner surface of each cup-shaped opening has a parabolic vertical cross section and is reflectively coated to maximize red reflectivity.

Uniform illuminator for phototherapy

An apparatus for detecting the presence of cancerous tissue using fluorescence. The apparatus employs an external light source capable of delivering about 50 milliwatts of excitation power within the absorption spectrum of tumor-specific target fluorescent molecules. Excitation light enters the fluorescent probe where it is chopped and divided, a portion being transmitted through an optical fiber to endogenous or exogenous photosensitive molecules on the surface of the tumor. The photosensitive molecules, once excited, generate a fluorescence spectrum characteristic of the cell type. The fluorescence emitted from the excited photoactive molecules on the tumor enters the optical fiber and passes to the fluorescence probe where it is filtered and analyzed. The use of the single fiber for both excitation and detection of fluorescence light enables the probe to be inserted into extremely small openings. The fluorescence probe will measure the magnitude of excitation light delivered and reflected from the tissue thereby giving a quantitative measurement of the fiber tip-to-tissue distance and tissue optical characteristics. The apparatus also can distinguish variations in fluorescence due to differences in distance of the fiber tip from the tissue under investigation by measuring the ratio of fluorescence and/or reflectance at two different wavelengths.

Apparatus for detecting the presence of abnormal tissue within a target

This invention describes a method for the accurate and sensitive measurement of an exogenous fluorescence chromophore in vivo. The method provides a means for normalizing a typical endogenous fluorescence signal into a relatively narrow band of values for different tissue types. The method employs irradiation of a target tissue at a single excitation wavelength while measuring two narrow bands of emission wavelengths, one of which is principally associated with the endogenous autofluorescence of the tissue while the other is chosen to be characteristic of the exogenous chromophore of interest. An exogenous chromophore is administered to a target tissue in vivo. A fiber optic positioned near the target tissue delivers illuminating excitation light from a light source to the tissue and receives fluorescence light from both exogenous and endogenous chromophores in the tissue and conducts the fluorescence light to a detector. The ratio of the exogenous fluorescence intensity to the endogenous fluorescence intensity is used to calculate the exogenous chromophore concentration in tissue. The temporal change in the ratio provides a measure of the rate of uptake, retention and excretion of the exogenous chromophore by the target tissue.

In vivo pharmacokinetics of photosensitive drugs and method

A device for measuring the fluorescence generated by photoactivated molecules during photodynamic therapy (PDT) and a method of using the device for dosimetry. The device, which comprises an isotropic spherical probe and detector electronics, simultaneously measures the space irradiance and time-integrated fluorescence during PDT. It is shown that there is a correlation between the time-integrated fluorescence generated during PDT treatment of a tumor and the delay in the regrowth of the tumor. The device provides the simultaneous measurement of the space irradiance and integrated fluorescence which measurements enable real time dosimetry during PDT.

Vivo dosimeter for photodynamic therapy

A diffuser tip for a fiber optic or array of fibers having a proximal end which abuts against the tip of the fiber optic or array of fibers. The diffuser tip has a cylindrical center core of transparent elastomer which contains scattering centers embedded therein. The scattering centers are distributed within the core so that the concentration of scatterers increases continuously in a direction from the proximal end of the diffuser tip to the distal end of the diffuser tip.

Continuous gradient cylindrical diffusion tip for optical fibers and

A cylindrical diffuser tip for use with an optical fiber is described. The diffuser tip comprises a silicone core abutted to the terminus of the conventional optical core of an optical fiber, an outer layer of silicone plus a suitable scatterer, and a final cladding of plastic tubing to provide controlled stiffness or rigidity to the silicone diffuser tip while maintaining a flexibility comparable to the optical fiber. The tip provides a substantially uniform distribution of radiance along its length and is particularly useful for laser radiation treatment of tumors. The stiffness of the diffuser tip can be varied by choosing an outer tubing of varying wall thickness and durometer. The diffuser tip is useful for providing uniform cylindrical illumination of target tissue in remote areas of the body and is particularly useful in such areas as Photodynamic Therapy of tumors and atheromas and hyperthermia.

Diffusion tip for optical fibers

A flexible tip for a medical catheter suitable for the transmission of light and dimensioned to pass through extremely small tubular members is described. The flexible tip, preferably made of optically transparent silicone elastomer, is affixed to the terminal end of a conventional optical fiber. In a preferred embodiment, the flexible tip comprises a central silicone core surrounded by a cladding having an index of refraction less than that of the core, permitting internal reflection. The flexible tip is provided with an outer jacket which serves two purposes: a) it provides structural integrity for the tip, and b) it reinforces the union between the flexible tip and the optical fiber to which it is abutted. The tip enables the delivery of a comparable amount of light as a large glass fiber of equal core diameter but possesses much greater flexibility. The tip has the flexibility to be able to enter tortuous tubular members while retaining the light transmitting capabilities of relatively inflexible glass optical waveguides of the same diameter.

Optical waveguide with flexible tip

An improved power meter for measuring the energy and wavelength of light emanating from an optical fiber. The meter is an integrating sphere having a source aperture for receiving the tip of an optical fiber and coupling the light from the tip into the sphere's central cavity. The source aperture is modified to include a sterilizable, liquid-fillable insert which mimics the optical environment within tissue. The sphere also has improved baffling and the sensitivity of wavelength verification is improved by means of a rotatable interference filter placed between an exit aperture and a light detector.

Integrating sphere power meter

A microlens assembly for use with an optical fiber or fiber bundle that requires no crimping or mechanical distortion of the optical fiber. The microlens assembly has a front lens mounting portion and a rear portion. The rear portion is a cylindrical tube which is bonded to the sheath and cladding of the optical fiber or fiber bundle by means of suitable adhesive. The front lens mounting portion which houses the output lens is also tubular, having an inner diameter greater than the outer diameter of the rear portion. The front lens mounting portion is slid over the rear portion until the desired distribution of light emanating from the lens is achieved. The front lens mounting portion is then locked into position by bonding it to the rear portion by means of an appropriate adhesive. The adhesives are stable at high temperature and have an index of refractions suitable for preventing refractive loss of light from the lateral walls of the fiber core. In one embodiment, the cylindrical space in the microlens assembly between the output lens and the tip of the optical fiber or fiber bundle is filled with an optically transparent fluid or elastomer such as silicone. The filling excludes body fluids from entering the microlens assembly.

Growing community of inventors

Santa Ynez, CA, United States of America

Daniel R Doiron