Tumor Hypoxia Targeted Fluorescence Imaging and Chest-wall-effect Reducing in Ultrasound-guided Diffuse Optical Tomography

Targeting tumor hypoxia has a profound impact in assessing anti-cancer treatments. Previously we reported the use of 2-nitroimidazole and indocyanine green conjugate (2-nitroimidazole-ICG) to target tumor hypoxia in in vivo tumor models. In this study, we evaluated a new generation hypoxia-targeted rigid dye that has a higher fluorescence yield. Results show that it has ~100 nm absorption/emission wavelengths shift and 3-4 times fluorescence quantum yield comparing with 2-nitroimidazole-ICG, as well as more than twice in vivo tumor fluorescence intensity. These initial results suggest that the targeted rigid dye may significantly improve in vivo tumor hypoxia targeting. We have developed ultrasound (US)-guided diffuse optical tomography (DOT) technique to assist US diagnosis of breast cancer and to predict neo-adjuvant chemotherapy response of breast cancer patients. With the US guidance, diffused light measurements were made at the breast lesion site and the normal contralateral reference site with a handheld hybrid probe, and the data was used to estimate the background tissue optical properties for imaging reconstruction. However, background optical properties were affected by the chest wall underneath the breast tissue. Results have shown statistical significant correlation between fitted optical properties (µa and µs’) and the chest wall depth. After subtracting background µa at each wavelength, the difference of computed total hemoglobin (tHb) between malignant and benign lesion groups has improved. Receiver operating characteristic (ROC) curve analysis shows significant improvement for diagnosing early stage malignant lesions after subtraction. For early stage malignant lesions, the area-under-the ROC curve (AUC) has improved from 88.5% to 91.5%.