Diffuse optical spectroscopy imaging (DOSI) has shown great potential for the early detection of non-responding
tumors during neoadjuvant chemotherapy in breast cancer, already one day after therapy starts. Patients with rectal
cancer receive similar chemotherapy treatment. The rectum geometry and tissue properties of healthy and tumor
tissue in the rectum and the requirement of surface contact impose constraints on the probe design.
In this work we present the design of a DOSI probe with the aim of early chemotherapy/radiotherapy
effectiveness detection in rectal tumors. We show using Monte Carlo simulations and phantom measurements that
the colon tissue can be characterized reliably using a source-detector separation in the order of 10 mm. We present a
design and rapid prototype of a probe for DOSI measurements that can be mounted on a standard laparoscope and
that fits through a standard rectoscope. Using predominantly clinically approved components we aim at fast clinical
translation.
Near-infrared (NIR) (650 to 1000 nm) optical properties of turbid media can be quantified accurately and noninvasively using methods based on diffuse reflectance or transmittance, such as frequency-domain photon migration (FDPM). Conventional FDPM techniques based on white-light steady-state (SS) spectral measurements in conjunction with the acquisition of frequency-domain (FD) data at selected wavelengths using laser diodes are used to measure broadband NIR scattering-corrected absorption spectra of turbid media. These techniques are limited by the number of wavelength points used to obtain FD data and by the sweeping technique used to collect FD data over a relatively large range. We have developed a method that introduces several improvements in the acquisition of optical parameters, based on the digital parallel acquisition of a comb of frequencies and on the use of a white laser as a single light source for both FD and SS measurements. The source, due to the high brightness, allows a higher penetration depth with an extremely low power on the sample. The parallel acquisition decreases the time required by standard serial systems that scan through a range of modulation frequencies. Furthermore, all-digital acquisition removes analog noise, avoids the analog mixer, and does not create radiofrequency interference or emission.
We describe an algorithm to calculate an index that characterizes spatial differences in broadband near-infrared [(NIR), 650-1000 nm] absorption spectra of tumor-containing breast tissue. Patient-specific tumor spatial heterogeneities are visualized through a heterogeneity spectrum function (HS). HS is a biomarker that can be attributed to different molecular distributions within the tumor. To classify lesion heterogeneities, we built a heterogeneity index (HI) derived from the HS by weighing the HS in specific NIR absorption bands. It is shown that neoadjuvant chemotherapy (NAC) response is potentially related to the tumor heterogeneity. Therefore, we correlate the heterogeneity index obtained prior to treatment with the final response to NAC. From a pilot study of 15 cancer patients treated with NAC, pathological complete responders (pCR) were separated from non-pCR according to their HI (-44 ± 12 and 43 ± 17, p = 3 × 10−8, respectively). We conclude that the HS function is a biomarker that can be used to visualize spatial heterogeneities in lesions, and the baseline HI prior to therapy correlates with chemotherapy pathological response.
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