Dr. Diana C. Hsiung Stripp Profile

Dr. Diana C. Hsiung Stripp

at Univ of Pennsylvania Health System

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Publications (4)

Proceedings Article | 6 March 2006 Paper

In vivo light dosimetry of interstitial PDT of human prostate

Timothy Zhu, Jun Li, Jarod Finlay, Andreea Dimofte, Diana Stripp, Bruce Malkowicz, Stephen Hahn

Proceedings Volume 6139, 61390L (2006) https://doi.org/10.1117/12.646220

KEYWORDS: Prostate, Optical properties, Photodynamic therapy, Sensors, Light, In vivo imaging, Optical testing, Optical fibers, Light sources, Ultrasonography

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Proceedings Article | 8 April 2005 Paper

In vivo measurement of fluorescence emission in the human prostate during photodynamic therapy

Jarod Finlay, Timothy Zhu, Andreea Dimofte, Diana Stripp, S. Malkowicz, Richard Whittington, Jeremy Miles, Eli Glatstein, Stephen Hahn

Proceedings Volume 5689, (2005) https://doi.org/10.1117/12.590709

KEYWORDS: Luminescence, Photodynamic therapy, Prostate, Absorption, Optical fibers, In vivo imaging, Sensors, Optical properties, Fluorescence spectroscopy, Tissue optics

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Among the challenges to the clinical implementation of photodynamic therapy (PDT) is the delivery of a uniform photodynamic dose to induce uniform damage to the target tissue. As the photodynamic dose depends on both the local sensitizer concentration and the local fluence rate of treatment light, knowledge of both of these factors is essential to the delivery of uniform dose. In this paper, we investigate the distribution and kinetics of the photosensitizer motexafin lutetium (MLu, Lutrin) as revealed by its fluorescence emission. Our current prostate treatment protocol involves interstitial illumination of the organ via cylindrical diffusing fibers (CDF’s) inserted into the prostate though clear catheters. For planning and treatment purposes, the prostate is divided into 4 quadrants. We use one catheter in each quadrant to place an optical fiber-based fluorescence probe into the prostate. This fiber is terminated in a beveled tip, allowing it to deliver and collect light perpendicular to the fiber axis. Excitation light is provided by a 465 nm light emitting diode (LED) source coupled to a dichroic beamsplitter, which passes the collected fluorescence emission to a CCD spectrograph. Spectra are obtained before and after PDT treatment in each quadrant of the prostate and are analyzed via a linear fitting algorithm to separate the MLu fluorescence from the background fluorescence originating in the plastic catheter. A computer-controlled step motor allows the excitation/detection fiber to be moved along the catheter, building up a linear profile of the fluorescence emission spectrum of the tissue as a function of position. We have analyzed spectral fluorescence profiles obtained in 4 patients before and after MLu-mediated PDT. We find significant variation both within individual prostates and among patients. Within a single quadrant, we have observed the fluorescence signal to change by as much as a factor of 3 over a distance of 2 cm. Comparisons of pre- and post-PDT spectra allow a quantification treatment-induced photobleaching. Like the drug distribution, the extent of photobleaching varies widely among patients. In two cases, we observed bleaching of approximately 50% of the drug, while others exhibited negligible photobleaching.

Proceedings Article | 14 June 2004 Paper

Phase I trial of motexafin-lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer

Diana Stripp, Rosemarie Mick, Timothy Zhu, Richard Whittington, Debbie Smith, Andreea Dimofte, Jarod Finlay, Jeremy Miles, Theresa Busch, Daniel Shin, Alex Kachur, Zelig Tochner, S. Bruce Malkowicz, Eli Glatstein, Stephen Hahn

Proceedings Volume 5315, (2004) https://doi.org/10.1117/12.529181

KEYWORDS: Photodynamic therapy, Prostate, Toxicity, Prostate cancer, Tissues, Biopsy, Radiotherapy, Sensors, Cancer, Tumors

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Therapeutic options for patients with locally recurrent prostate cancer after treatment with radiation therapy are limited. An ongoing Phase I trial of interstitial photodynamic therapy (PDT) with the photosensitizer motexafin lutetium (MLu) was initiated in year 2000 for men with locally recurrent prostate cancer. The primary objective of this trial is to determine the maximally tolerated dose of motexafin lutetium-mediated PDT. Twelve men with biopsy-proven recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled. Pre-treatment evaluation included an MRI of the prostate, bone scan, laboratory studies, cystoscopy, and transrectal ultrasound. Treatment plans were generated based upon the ultrasound findings. PDT dose was escalated by increasing the motexafin lutetium dose, increasing the 732 nm light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 3, 6, or 24 hours prior to 732 nm light delivery. The light dose measured in real time with in situ spherical detectors was 25-100 J/cm2 for all patients. Light was delivered through optical fibers inserted through a transperineal brachytherapy template in the operating room and optical property measurements were made before and after light therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake. Twelve patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I PDT-related genitourinary symptoms were observed. One patient had Grade II urinary urgency that was urinary catheter-related. No rectal or other GI PDT-related toxicities were observed. Measurements of motexafin lutetium in prostate tissue demonstrated the presence of photosensitizer at all dose levels. Conclusions: Motexafin lutetium-mediated PDT designed to treat comprehensively the entired prostate gland has been well-tolerated at the doses studied to date.

Proceedings Article | 14 June 2004 Paper

In vivo determination of the absorption and scattering spectra of the human prostate during photodynamic therapy

Jarod Finlay, Timothy Zhu, Andreea Dimofte, Diana Stripp, S. Malkowicz, Richard Whittington, Jeremy Miles, Eli Glatstein, Stephen Hahn

Proceedings Volume 5315, (2004) https://doi.org/10.1117/12.528968

KEYWORDS: Absorption, Photodynamic therapy, Scattering, Prostate, Tissue optics, Magnesium, In vivo imaging, Tissues, Sensors, Optical properties

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A continuing challenge in photodynamic therapy is the accurate in vivo determination of the optical properties of the tissue being treated. We have developed a method for characterizing the absorption and scattering spectra of prostate tissue undergoing PDT treatment. Our current prostate treatment protocol involves interstitial illumination of the organ via cylindrical diffusing optical fibers (CDFs) inserted into the prostate through clear catheters. We employ one of these catheters to insert an isotropic white light point source into the prostate. An isotropic detection fiber connected to a spectrograph is inserted into a second catheter a known distance away. The detector is moved along the catheter by a computer-controlled step motor, acquiring diffuse light spectra at 2 mm intervals along its path. We model the fluence rate as a function of wavelength and distance along the detector’s path using an infinite medium diffusion theory model whose free parameters are the absorption coefficient μ_a at each wavelength and two variables A and b which characterize the reduced scattering spectrum of the form μ’_s = Aλ^-b. We analyze our spectroscopic data using a nonlinear fitting algorithm to determine A, b, and μ_a at each wavelength independently; no prior knowledge of the absorption spectrum or of the sample’s constituent absorbers is required. We have tested this method in tissue simulating phantoms composed of intralipid and the photosensitizer motexafin lutetium (MLu). The MLu absorption spectrum recovered from the phantoms agrees with that measured in clear solution, and μ_a at the MLu absorption peak varies linearly with concentration. The µ’_s spectrum reported by the fit is in agreement with the known scattering coefficient of intralipid. We have applied this algorithm to spectroscopic data from human patients sensitized with MLu (2 mg kg^-1) acquired before and after PDT. Before PDT, the absorption spectra we measure include the characteristic MLu absorption peak. Using our phantom data as a calibration, we have determined the pre-treatment MLu concentration to be approximately 2 to 8 mg kg^-1. After PDT, the concentration is reduced to 1 to 2.5 mg kg^-1, an indication of photobleaching induced by irradiation. In addition, absorption features corresponding to the oxygenated and deoxygenated forms of hemoglobin indicate a reduction in tissue oxygenation during treatment.

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