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US-12616373-B2 - Optical spectroscopy and treatment planning software for photodynamic therapy of hollow cavities

US12616373B2US 12616373 B2US12616373 B2US 12616373B2US-12616373-B2

Abstract

The present invention provides an optical probe system that allows for determination of optical properties at the wall of a hollow cavity and photosensitizer uptake at the time of photodynamic therapy (PDT). In one embodiment, this system provides for rigorous treatment planning to maximize efficacy and minimize risk to patients by optimizing the concentration of the scattering emulsion infused into the cavity and the delivered laser power.

Inventors

  • Timothy M. Baran

Assignees

  • UNIVERSITY OF ROCHESTER

Dates

Publication Date
20260505
Application Date
20220304

Claims (7)

  1. 1 . A method of delivering, detecting, and analyzing diffuse optical reflectance and fluorescence in a target tissue comprising the steps of: providing an optical probe system comprising at least one transmitting fiber having a proximal end and a distal end, at least one receiving fiber having a proximal end and a distal end, at least one light source, a spectrometer, and a controller; positioning the proximal end of the at least one transmitting fiber and the proximal end of the at least one receiving fiber at a surface of a target tissue; enabling and selecting the at least one light source for fluorescence or reflectance measurements; detecting a first spectra for the at least one receiving fiber by the spectrometer; detecting a second spectra without the at least one light source enabled to correct for dark background; correcting the first spectra for at least one of: dark background, system throughput and wavelength-dependent system response; analyzing the corrected first spectra by the controller to obtain optical property spectra for both absorption and scattering; performing an initial simulation of light propagation at a set scattering emulsion concentration and optical power; and determining the scattering emulsion concentration at which minimum laser power is required to achieve the fluence rate target in 95% of the target tissue; and treating a subject using the determined scattering emulsion concentration and laser power.
  2. 2 . The method of claim 1 , wherein the target tissue comprises a hollow cavity.
  3. 3 . A method of analyzing diffuse optical reflectance and fluorescence in a target tissue and treating a subject comprising the steps of: delivering light to a surface of a target tissue and detecting a first spectra at the surface of the target tissue; detecting a control spectra at the surface of the target tissue in the absence of delivering light to the target tissue; correcting the first spectra based in part on the control spectra for at least one of: dark background, system throughput, and wavelength-dependent system response; determining one or more optical properties of the target tissue based on the first spectra; performing a simulation of light propagation in the target tissue at a set scattering emulsion concentration and optical power; determining a scattering emulsion at which a minimum laser power is required to achieve a fluence rate target in 95% of the target tissue; and treating a subject using the determined scattering emulsion concentration and laser power.
  4. 4 . The method of claim 3 , wherein the target tissue comprises a hollow cavity.
  5. 5 . The method of claim 3 , wherein the one or more optical properties comprise optical property spectra for absorption or optical property spectra for scattering.
  6. 6 . The method of claim 3 , wherein the light is delivered via at least one transmitting fiber, and wherein the first spectra is detected via a first receiving fiber.
  7. 7 . The method of claim 6 , further comprising the step of detecting a second spectra at the surface of the target tissue via a second receiving fiber, and wherein the determination of one or more optical properties is further based on the second spectra.

Description

CROSS-REFERENCE TO THE RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63/157,177 filed Mar. 5, 2021, the contents of which are incorporated by reference herein in its entirety. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with government support under Grant No. EB029921 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND OF THE INVENTION Photodynamic therapy (PDT) is a promising treatment modality for oncology and antimicrobial applications that relies on the excitation of light-sensitive drugs known as photosensitizers by visible light in order to generate reactive oxygen species. The efficacy of PDT is largely determined by the combination of the absorbed light dose and the photosensitizer concentration. The absorbed light dose is determined by the optical properties, absorption and scattering of the target tissue. In the case of hollow cavities, this is further complicated by the integrating sphere effect, where light that is diffusely reflected at the boundary re-enters the cavity and can result in fluence rates much higher than those predicted purely by geometry or diffusion of light. In order to compensate for heterogeneity in cavity shape and light dose, a scattering emulsion including but not limited to Intralipid, Liposyn, dissolved polystyrene spheres, and etc. can be infused into the cavity to homogenize the light dose through efficient light scattering. These optical properties are currently unknown for many applications, precluding prediction of light dose and design of treatment plans for maximally efficacious treatment. Furthermore, photosensitizer uptake is unknown in most cases. In order to perform rigorous and efficacious PDT in hollow cavities, a means for determination of these quantities is required. Thus, there is a need in the art for the development of a system that allows for determination of optical properties at the wall of a hollow cavity and photosensitizer uptake at the time of PDT. The present invention meets this need. BRIEF DESCRIPTION OF THE DRAWINGS The following detailed description of invention will be better understood when read in conjunction with the appended drawings. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings. FIG. 1A and FIG. 1B depict a schematic of an exemplary custom fiber-optic probe and a corresponding optical system to deliver, detect and analyze diffuse optical reflectance and fluorescence in the target tissue. FIG. 1A depicts a cross sectional view of an optical probe of the present invention. FIG. 1B depicts the design of the optical system of the present invention. FIG. 2A and FIG. 2B depict an exemplary custom fiber-optic probe and a corresponding optical system of the present invention. FIG. 2A depicts a top view of an optical probe of the present invention. FIG. 2B depicts the spectroscopy system of the present invention. FIG. 3 is a flowchart depicting an exemplary method of delivering, detecting, and analyzing diffuse optical reflectance and fluorescence in a target tissue using the device of the present invention. FIG. 4 is a graph of the percentage of abscess cavity patients eligible for PDT as a function of the absorption coefficient (pa) at the abscess wall. Simulated conditions are, for case 1 the current clinical practice, partial treatment planning for case 2, allowing for control of the laser power, and full treatment planning for case 3, allowing for control of Intralipid (scattering emulsion) concentration and laser power. FIG. 5 is a graph of threshold optical power as a function of abscess wall absorption (μa,wall) and Intralipid concentration (μs,cavity). FIG. 6A and FIG. 6B, depict threshold optical power as a function of (FIG. 6A) abscess wall absorption and (FIG. 6B) Intralipid concentration. The horizontal dashed line indicates the maximum attainable optical power (2000 mW) with the disclosed clinical laser. Data points represent mean threshold power across simulations performed for all 60 abscesses, with error bars corresponding to standard deviation. FIG. 7 is a graph of optimal Intralipid concentration as a function of abscess wall absorption. FIG. 8 is a graph of abscess eligibility for MB-PDT as a function of abscess wall absorption (μa,wall) and Intralipid concentration (μs,cavity). FIG. 9 is a graph of percentage eligibility for MB-PDT as a function of abscess wall absorption for two treatment methods. Blue is optimized Intralipid concentration and power (patient-specific method). Red is fixed Intralipid concentration with optimized power (uniform dose). FIG. 10 depicts percentage eligibility for MB-PDT as a function of abscess wall absorption at different levels of absorption inside abscess cavity, corresponding to MB concentrations of 0 to 1 μM, after optimization