Apparatus and method for multiwavelength photodynamic therapy
Inventors
Mandel, Arkady • Dumoulin-White, Roger • Embree, Wayne
Assignees
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Publication Number
US-10525279-B2
Publication Date
2020-01-07
Expiration Date
Abstract
A method for treating a condition in a tissue, includes the steps: (1) providing a PS within the tissue; (2) irradiating the tissue containing the PS with a first light of a first wavelength; and (3) irradiating the tissue containing the PS with a second light of a second wavelength so as to treat the condition in the tissue, wherein: (a) the PS absorbs light at the first wavelength and the second wavelength; and (b) the second light is more strongly absorbed by the tissue than the first light or vice versa, so as to achieve a predetermined absorbed photon density gradient. An apparatus for conducting the method includes first and second light sources, a power supply, a focusing device, and a controller which adjusts light emission such that I(d)=I(λ1 at d=0)×exp (μeff (λ1)×d)+I(λ2 at d=0)×exp (μeff(λ2)χd).
Core Innovation
The invention provides a method for treating a condition in tissue using a photosensitizer provided within the tissue and irradiating the tissue with first and second lights having first and second wavelengths so as to treat the condition in the tissue. The photosensitizer absorbs light at the first wavelength and/or the second wavelength, and the first light and second light are selected relative to tissue absorption so that one wavelength is more strongly absorbed by the tissue than the other wavelength.
To achieve a predetermined absorbed photon density gradient, the method detects reflected light reflected from the tissue and adjusts emissions of the first light and the second light based on the reflected light detected. The adjustment uses an intensity-vs-depth equation in which intensity at a depth d is expressed as a sum of contributions from the first and second wavelengths, each decaying exponentially with depth according to a population average tissue optical attenuation coefficient, and wavelength selection is constrained by the hemoglobin absorption band and the lowest effective attenuation coefficient of the tissue.
The invention also includes irradiation of a common focal point simultaneously or with overlap, with spatial and temporal modulation of overlapping illumination spots. In addition, the photosensitizer is an exogenous Ru(II), Os(II) or Rh(II) dyad that is activated with the first light or the second light at a depth corresponding to a depth of a target tumor in the tissue, delivering a cytotoxically effective treatment to the target tumor.
Claims Coverage
The independent claim set describes one method for treating a condition in tissue using two-wavelength photodynamic therapy with reflected-light based control of emissions to create a predetermined absorbed photon density gradient. It includes five inventive features covering wavelength selection, depth-dependent intensity control, common focal point irradiation with spatial/temporal modulation, and activation of an exogenous metal dyad PS at a target tumor depth.
Two-wavelength PS activation for depth gradient treatment
A method providing a photosensitizer within the tissue and irradiating the tissue containing the PS with a first light of a first wavelength and irradiating the tissue containing the PS with a second light of a second wavelength so as to treat the condition in the tissue, where the PS absorbs light at the first wavelength and/or the second wavelength and one wavelength is more strongly absorbed by the tissue than the other to achieve a predetermined absorbed photon density gradient.
Reflected-light based emission adjustment using intensity-depth equation
Detecting reflected light reflected from the tissue and adjusting emissions of the first light and the second light based on the reflected light detected and the equation I(d)=I(λ1 at d=0)×exp(μeff(λ1)×d)+I(λ2 at d=0)×exp(μeff(λ2)×d), where I is intensity, λ1 is the first wavelength, λ2 is the second wavelength, d is a depth of the photosensitizer, and μeff is population average tissue optical attenuation coefficient.
Wavelength selection using hemoglobin absorption and lowest effective attenuation
Selecting the first wavelength within a hemoglobin absorption band and the second wavelength at a lowest effective attenuation coefficient of the tissue, or selecting the second wavelength within the hemoglobin absorption band and the first wavelength at the lowest effective attenuation coefficient of the tissue.
Simultaneous or overlapping common focal point irradiation with spatial and temporal modulation
Irradiating the first light and the second light to irradiate a common focal point simultaneously or with some overlap, and conducting spatial and temporal modulation of overlapping illumination spots.
Exogenous metal dyad PS activated at target tumor depth
Using a PS that is a Ru(II), Os(II) or Rh dyad which is exogenous and activated with the first light or the second light at a depth corresponding to a depth of a target tumor in the tissue so as to deliver a cytotoxically effective treatment to the target tumor in the tissue.
The claims center on two-wavelength PDT using a PS whose excitation is controlled to create a predetermined absorbed photon density gradient, with emission adjustment based on detected reflected light using a depth-dependent exponential equation. The claims further specify wavelength selection using hemoglobin absorption band and tissue lowest effective attenuation, require common focal point simultaneous or overlapping irradiation with spatial and temporal modulation, and require an exogenous Ru(II), Os(II), or Rh dyad PS activated at a depth corresponding to a target tumor to deliver cytotoxically effective treatment.
Stated Advantages
Achieve a predetermined absorbed photon density gradient.
Deliver cytotoxically effective treatment to a target tumor in tissue by activating an exogenous Ru(II), Os(II) or Rh dyad PS at a depth corresponding to the target tumor.
Documented Applications
Treating a condition in tissue, including delivering cytotoxically effective treatment to a target tumor in the tissue.
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