Diffuse reflectance spectroscopy to monitor murine colorectal tumor progression and therapeutic response

Abstract

Diffuse reflectance spectroscopy to monitor murine colorectal tumor progression and therapeutic response," J. AbstractSignificance: Many studies in colorectal cancer (CRC) use murine ectopic tumor models to determine response to treatment. However, these models do not replicate the tumor microenvironment of CRC. Physiological information of treatment response derived via diffuse reflectance spectroscopy (DRS) from murine primary CRC tumors provide a better understanding for the development of new drugs and dosing strategies in CRC.Aim: Tumor response to chemotherapy in a primary CRC model was quantified via DRS to extract total hemoglobin content (tHb), oxygen saturation (StO 2 ), oxyhemoglobin, and deoxyhemoglobin in tissue.Approach: A multimodal DRS and imaging probe (0.78 mm outside diameter) was designed and validated to acquire diffuse spectra longitudinally-via endoscopic guidance-in developing colon tumors under 5-fluoruracil (5-FU) maximum-tolerated (MTD) and metronomic regimens. A filtering algorithm was developed to compensate for positional uncertainty in DRS measurements Results: A maximum increase in StO 2 was observed in both MTD and metronomic chemotherapy-treated murine primary CRC tumors at week 4 of neoadjuvant chemotherapy, with 21 AE 6% and 17 AE 6% fold changes, respectively. No significant changes were observed in tHb. Conclusion:Our study demonstrates the feasibility of DRS to quantify response to treatment in primary CRC models.

Longitudinal examination of perfusion and angiogenesis markers in primary colorectal tumors shows distinct signatures for metronomic and maximum-tolerated dose strategies

“…Additionally, because there was an endoscopically-visible reduction in tumor size between each therapy cycle in the MTD group (Figure 1C), the reduction in Vegf expression, and similar trends in the increase of StO 2 and HbO 2 would indicate a reduction in oxygen demand in surrounding tissue due to the number of tumor cells killed after each round of therapy driven by an anti-angiogenic effect in MTD NAC, consistent with results we have previously reported 27 . In other words, it appears that the magnitude of the decrease in Vegf expression that MTD NAC is able to achieve (and that is significantly lower than that achieved in the MET group) leads to significant blood vessel reduction/remodeling in the tumor when compared to the MET and CG groups (Figure 5C, D).…”

“…In this regard, one way that tumor response to therapy (chemotherapy, radiotherapy or their combination) has been extensively studied in the past involves the use of DRS as a low-cost, non-destructive approach that quantifies changes in perfusion parameters (StO 2 , HbO 2 , etc.) which are known to change after therapy 25,27,[53][54][55][56] . However, perfusion values that are quantifiable via DRS only represent 'high level' view of a preceding sequence of molecular shifts in the angiogenic program of tumors.…”

“…At 16 weeks after the last AOM injection the size of tumors was periodically assessed using a veterinary colonoscopy system (ColoVIEW, Karl Storz) as we have previously described 27 . Briefly, mice were anesthetized using 2% isoflurane using a precision vaporizer and placed on a heating pad set at 42 • C to maintain body temperature through the procedure.…”

“…All spectra were collected using an integration time of 75 ms. Spectra were post-processed to obtain perfusion values from tissue (StO 2 , HbO 2 , etc.) as we have described in detail elsewhere 27 . Briefly, we used an inverse lookup table (LUT) model 33 to extract absorption and scattering properties from tumors from spectra which were used to obtain perfusion values.…”

Non-invasive real-time assessment of hepatic macrovesicular steatosis in liver donors: Hypothesis, design and proof-of-concept study

“…The need for a quick, portable, efficacious and economical device to diagnose MS is evident by the number of proof-of-concept studies available in this regard[ 7 , 9 , 11 , 15 ]. DRS as a diagnostic modality has been used in endoluminal studies of upper and lower gastrointestinal endoscopies[ 16 , 17 ]. Using the absorption and scattering patterns of biological tissues, DRS allows for accurate differentiation of polyps and subendothelial pathology.…”