Interstitial Doppler Optical Coherence Tomography as a Local Tumor Necrosis Predictor in Photodynamic Therapy of Prostatic Carcinoma: AnIn vivoStudy

Abstract

We have tested the feasibility of real-time localized blood flow measurements, obtained with interstitial (IS) Doppler optical coherence tomography (DOCT), to predict photodynamic therapy (PDT)-induced tumor necrosis deep within solid Dunning rat prostate tumors. IS-DOCT was used to quantify the PDT-induced microvascular shutdown rate in s.c. Dunning prostate tumors (n = 28). Photofrin (12.5 mg/kg) was administered 20 to 24 hours before tumor irradiation, with 635 nm surface irradiance of 8 to 133 mWcm À2 for 25 minutes.High frequency ultrasound and calipers were used to measure the thickness of the skin covering the tumor and the location of the echogenic IS probe within it. A two-layer Monte Carlo model was used to calculate subsurface fluence rates within the IS-DOCT region of interest (ROI). Treatment efficacy was estimated by percent tumor necrosis within the ROI, as quantified by H&E staining, and correlated to the measured microvascular shutdown rate during PDT treatment. IS-DOCT measured significant PDT-induced vascular shutdown within the ROI in all tumors. A strong relationship (R 2 = 0.723) exists between the percent tumor necrosis at 24 hours posttreatment and the vascular shutdown rate: slower shutdown corresponded to higher treatment efficacy, i.e., more necrosis. Controls (needle + light, no drug, n = 3) showed minimal microvascular changes or necrosis (4% F 1%). This study has correlated a biological end point with a direct and localized measurement of PDT-induced microvascular changes, suggesting a potential clinical role of on-line, real-time microvascular monitoring for optimizing treatment efficacy in individual patients. [Cancer Res 2008;68(23):9987-95]

Imaging of Human Lymph Nodes Using Optical Coherence Tomography: Potential for Staging Cancer

“…However, several groups have shown that an OCT probe may be miniaturized and encased in a medical needle (19,20). Such an imaging probe could be used interstitially to image lymph nodes in vivo.…”

Real-time monitoring of hemodynamic changes in tumor vessels during photoimmunotherapy using optical coherence tomography

“…6 For instance, Doppler OCT (DOCT) has been used to monitor vascular changes caused by photodynamic therapy. 7 However, it remains challenging to obtain in situ information without resorting to window chamber-implanted tumors due to motion artifacts. In this study, we overcome this challenge with realtime motion gating using speckle variance (SV) imaging.…”

Blood flow dynamics during local photoreaction in a head and neck tumor model

“…For technical reasons, the microvessel density could only be determined for post-PDT tumor tissue because removing a portion of the tumor before PDT would cause bleeding, interfering with the blood flow measurements. As previously already demonstrated, an accurate measure for vasculature shutdown is the change in microvessel density [10,17,19,[54][55][56][57][58][59][60][61][62].…”