An ultra-fast digital diffuse optical spectroscopic imaging system for neoadjuvant chemotherapy monitoring

Up to 20% of breast cancer patients who undergo presurgical (neoadjuvant) chemotherapy have no response to treatment. Standard-of-care imaging modalities, including MRI, CT, mammography, and ultrasound, measure anatomical features and tumor size that reveal response only after months of treatment. Recently, non-invasive, near-infrared optical markers have shown promise in indicating the efficacy of treatment at the outset of the chemotherapy treatment. For example, frequency domain Diffuse Optical Spectroscopic Imaging (DOSI) can be used to characterize the optical scattering and absorption properties of thick tissue, including breast tumors. These parameters can then be used to calculate tissue concentrations of chromophores, including oxyhemoglobin, deoxyhemoglobin, water, and lipids. Tumors differ in hemoglobin concentration, as compared with healthy background tissue, and changes in hemoglobin concentration during neoadjuvant chemotherapy have been shown to correlate with efficacy of treatment. Using DOSI early in treatment to measure chromophore concentrations may be a powerful tool for guiding neoadjuvant chemotherapy treatment. Previous frequency-domain DOSI systems have been limited by large device footprints, complex electronics, high costs, and slow acquisition speeds, all of which complicate access to patients in the clinical setting. In this work a new digital DOSI (dDOSI) system has been developed, which is relatively inexpensive and compact, allowing for use at the bedside, while providing unprecedented measurement speeds. The system builds on, and significantly advances, previous dDOSI setups developed by our group and, for the first time, utilizes hardware-integrated custom board-level direct digital synthesizers (DDS) and analog to digital converters (ADC) to generate and directly measure signals utilizing undersampling techniques. The dDOSI system takes high-speed optical measurements by utilizing wavelength multiplexing while sweeping through hundreds of modulation frequencies in tens of milliseconds. The new dDOSI system is fast, inexpensive, and compact without compromising accuracy and precision