Early assessment of tumor response to photodynamic therapy using combined diffuse optical and diffuse correlation spectroscopy to predict treatment outcome

Abstract

Photodynamic therapy (PDT) of cancer involves the use of a photosensitizer that can be light-activated to eradicate tumors via direct cytotoxicity, damage to tumor vasculature and stimulating the body's immune system. Treatment outcome may vary between individuals even under the same regime; therefore a non-invasive tumor response monitoring system will be useful for personalization of the treatment protocol. We present the combined use of diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) to provide early assessment of tumor response. The relative tissue oxygen saturation (rStO2) and relative blood flow (rBF) in tumors were measured using DOS and DCS respectively before and after PDT with reference to baseline values in a mouse model. In complete responders, PDT-induced decreases in both rStO2 and rBF levels were observed at 3 h post-PDT and the rBF remained low until 48 h post-PDT. Recovery of these parameters to baseline values was observed around 2 weeks after PDT. In partial responders, the rStO2 and rBF levels also decreased at 3 h post PDT, however the rBF values returned toward baseline values earlier at 24 h post-PDT. In contrast, the rStO2 and rBF readings in control tumors showed fluctuations above the baseline values within the first 48 h. Therefore tumor response can be predicted at 3 to 48 h post-PDT. Recovery or sustained decreases in the rBF at 48 h post-PDT corresponded to long-term tumor control. Diffuse optical measurements can thus facilitate early assessment of tumor response. This approach can enable physicians to personalize PDT treatment regimens for best outcomes.

Light Fluence Rate and Tissue Oxygenation (StO2) Distributions Within the Thoracic Cavity of Patients Receiving Intraoperative Photodynamic Therapy for Malignant Pleural Mesothelioma

“…We note here that clinical measurement of tissue S t O 2 after PDT is over a period of tens of minutes after the conclusion of light delivery and rarely coincides immediately with the termination of light, as is done in preclinical studies (13). Thus, clinical measurements are likely to be affected by PDT‐induced ischemia that develops after light delivery due to vascular damage and positively contributes to treatment outcomes (30–32) with less contribution from ischemia during illumination (33) that negatively impacts treatment outcomes by limiting production of reactive oxygen species. Photochemical oxygen consumption is another cause of hypoxia during PDT, although it is unlikely to be a factor in these measurements because oxygenation was measured after, and not during, light delivery.…”

Blood Flow Measurements Enable Optimization of Light Delivery for Personalized Photodynamic Therapy

“…In photodynamic therapy (PDT), light, photosensitizer and oxygen interact to produce tissue-damaging reactive oxygen species (ROS). PDT is directly cytotoxic to treated cells; moreover, it can promote antitumor immunity and damage tumor vasculature [1,2]. Vascular damage is often beneficial to achieving a complete response, but the timing of vascular damage relative to the period of light delivery is critical [3,4].…”

“…(29.0) (p = 0.0021 ) All p-values for pairwise comparisons are adjusted using Tukey's Honest Significant Difference in determinations 1 for comparison to 150 mWcm −2 -continuous; 2 for comparison to 25 mWcm −2 -continuous;3 for comparison to 150 mWcm −2 -fractionated. RIF: radiation-induced fibrosarcoma; PDT: photodynamic therapy; rBF: relative blood flow; BFI-Irrad: blood-flow-informed irradiance; BFI-Frac: blood-flow-informed fractionated; IQR: interquartile range; SD: standard deviation.…”

Diffuse Correlation Spectroscopy at Short Source-Detector Separations: Simulations, Experiments and Theoretical Modeling

“…Diffuse correlation spectroscopy (DCS) is a well-established optical technique capable of sensing blood flow in biological tissue using multiply scattered light and has widely been applied to quantify tissue perfusion in vivo [1][2][3][4][5][6][7][8][9][10][11][12][13]. The light source used in DCS is a long coherence length laser, which is delivered to a medium of interest through a large-core optical fiber while the back-scattered (reflected) intensity is collected using a small-core (single mode) fiber, placed at a fixed distance (the source-detector separation SDS) from the center of the source fiber.…”