Spatial frequency domain imaging to capture compression-induced hemodynamics in breast tissue with applications toward neoadjuvant chemotherapy monitoring

Neoadjuvant chemotherapy (NAC) for breast cancer is used to shrink a tumor prior to surgery, with complete pathologic response to NAC (assessed post-surgery) being predictive of patient survival. Methods for predicting this outcome early in therapy are lacking, with tumor size assessments such as structural imaging and clinical palpation not always corresponding to extent of residual disease. Diffuse optical near-infrared imaging methods have demonstrated sensitivity to vascular differences between tumors and healthy tissue, including both differences in hemoglobin concentrations and differential hemodynamic responses to perturbation, and longitudinal tracking of these properties has demonstrated predictive value for therapy response. This dissertation seeks to enable the use of spatial frequency domain imaging (SFDI) to predict therapy outcome based on hemodynamic response elicited by localized breast compression. SFDI is chosen for its low-cost and portability, being suitable for frequent monitoring and the potential for at-home imaging by the patient during the crucial time period following the beginning of NAC.

The work of this dissertation addresses a number of challenges relevant to the use of SFDI and tissue compression for therapy prediction. The depth sensitivity of SFDI is examined and the effect of compression on measured contrast is first established in breast tissue/tumor-mimicking phantoms. The ability of a handheld device to elicit a hemodynamic response recorded with SFDI is then established in healthy volunteers, and an optimization procedure is introduced to overcome the high sensitivity of SFDI to absorption by skin pigmentation, permitting improved recovery of subcutaneous optical properties. Finally, optical and mechanical simulations are used to demonstrate that the types of tumor changes associated with response to therapy (reduction in size, stiffness, and hemoglobin concentrations) produce reductions in SFDI contrast (and contrast change from compression) that could be used as a biomarker for therapy response.