Spatial Frequency Domain Imaging (SFDI) can provide longitudinal label-free, wide field hemodynamic and scattering information of murine tumors. Here we present a longitudinal study utilizing SFDI to monitor a paired immune responsive-resistant model for up to 30 days of treatment. Mice receiving the immunomodulatory treatment had a large increase in the reduced optical scattering throughout treatment compared to the mice receiving an immune-blocking antibody. These results indicate that scattering is sensitive to the immune-mediated apoptosis of tumor cells and capable of discriminating between responsive and resistant tumor models.
Optical scattering parameters were correlated with markers of apoptosis and proliferation in preclinical tumor models, and outperformed tumor volume and functional parameters in treatment response prediction.
Significance: Diffuse optical spectroscopic imaging (DOSI) measures quantitative functional and molecular information in thick tissue in a noninvasive manner using near-infrared light. DOSI may be useful for diagnosis and prognosis of bone pathologies including osteosarcoma and Ewing’s sarcoma, but little is currently known about DOSI-derived parameters in bony anatomic locations where this disease occurs.
Aim: Our goal is to quantify the optical characteristics and chromophore content of bony anatomic locations of healthy volunteers and assess differences due to anatomic region, age, sex, ethnicity, race, and body fat.
Approach: Fifty-five healthy volunteers aged 4 to 72 were enrolled in the study. The optical properties and quantitative tissue concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipids were assessed at the distal humerus, distal femur, and proximal tibia. Body fat was assessed using skinfold calipers. One volunteer underwent a more comprehensive body scan from neck to foot to explore chromophore distributions within an individual. Regression analysis was used to identify the most important sources of variation in the measured data set.
Results: Statistical differences between bony locations were found for scattering, water, and lipids, but not for hemoglobin. All chromophores had statistical differences with sex, but there were no significant age-related correlations. Regression analysis revealed that body fat measured with skinfold calipers was the most important predictor of oxy-, deoxy-, total hemoglobin, and lipids. Hemoglobin and lipid levels were highly correlated (ρ ≥ 0.7) over the subject population and within the single-subject body scan.
Conclusions: DOSI can successfully measure bony anatomic sites where osteosarcomas and Ewing’s sarcomas commonly occur. Future studies of bone pathology using DOSI should account for the variation caused by anatomic region, sex, race and ethnicity, and body fat as these cause substantial variations in DOSI-derived metrics.
Alterations in tumor microvascular architecture are associated with resistance to several breast cancer therapies, and may be important markers for in vivo detection of resistance. Our goal is to map how micro-scale alterations in tumor vasculature manifest at the tissue level. To this end, we developed a multiscale preclinical imaging technique called Diffuse and Nonlinear Imaging (DNI) that integrates Spatial Frequency Domain Imaging (SFDI) for tissue-level mapping of tumor optical properties and hemodynamics, with Multiphoton Microscopy (MPM) to image tumor microvascular architecture with cellular resolution. Importantly, SFDI measures the same parameters as clinical Diffuse Optical Spectroscopy, providing a pathway to the clinic for microvascular imaging biomarkers. We demonstrated that the dual modality system can be spatially co-registered with high accuracy and precision (≤ 50 µm), and can be matched in optical sampling depth based on wavelength and spatial frequency selection. We also conducted an in vivo DNI study of untreated murine mammary tumors (Py230) in female C57BL/6 mice, and found strong multiscale relationships between tumor oxygen saturation and micro-vessel diameter, as well as deoxyhemoglobin concentrations and micro-vessel length (|Pearson’s ρ| > 0.5, p < 0.05).
We carried out in vivo DNI monitoring in two mammary tumor xenograft models grown in BALB/c athymic nude female mice; one model was responsive to Trastuzumab (Herceptin®) (BT474) and the other was resistant (HR6). This presentation will report on characterizing the vascular structure-function relationships with DNI across length scales within each model, and differences in the multiscale vascular relationships between the models.
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