Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy

Abstract

We combine diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) to noninvasively monitor early hemodynamic response to neoadjuvant chemotherapy in a breast cancer patient. The potential for early treatment monitoring is demonstrated. Within the first week of treatment (day 7) DOS revealed significant changes in tumor/normal contrast compared to pretreatment (day 0) tissue concentrations of deoxyhemoglobin (rctHHb T/N =69±21%), oxyhemoglobin (rctO 2 Hb T/N =73±25%), total hemoglobin (rctTHb T/N =72±17%), and lipid concentration (rctLipid T/N =116±13%). Similarly, DCS found significant changes in tumor/normal blood flow contrast (rBF T/N =75±7% on day 7 with respect to day 0). Our observation suggest the combination of DCS and DOS enhances treatment monitoring compared to either technique alone. The hybrid approach also enables construction of indices reflecting tissue metabolic rate of oxygen, which may provide new insights about therapy mechanisms. Abstract. We combine diffuse optical spectroscopy ͑DOS͒ and diffuse correlation spectroscopy ͑DCS͒ to noninvasively monitor early hemodynamic response to neoadjuvant chemotherapy in a breast cancer patient. The potential for early treatment monitoring is demonstrated. Within the first week of treatment ͑day 7͒ DOS revealed significant changes in tumor/normal contrast compared to pretreatment ͑day 0͒ tissue concentrations of deoxyhemoglobin ͑rctHHb T/N = 69± 21% ͒, oxyhemoglobin ͑rctO 2 Hb T/N = 73± 25% ͒, total hemoglobin ͑rctTHb T/N = 72± 17% ͒, and lipid concentration ͑rctLipid T/N = 116± 13% ͒. Similarly, DCS found significant changes in tumor/ normal blood flow contrast ͑rBF T/N =75±7% on day 7 with respect to day 0͒. Our observations suggest the combination of DCS and DOS enhances treatment monitoring compared to either technique alone. The hybrid approach also enables construction of indices reflecting tissue metabolic rate of oxygen, which may provide new insights about therapy mechanisms. © 2007 Society of Photo-Optical Instrumentation Engineers.

Near-infrared diffuse correlation spectroscopy in cancer diagnosis and therapy monitoring

“…[25][26][27] DCS can be easily and continually applied at the bedside in clinical rooms. [28][29][30][31][32][33][34] 35 and has been used less in the "cancer" context than in other scenarios such as brain and muscle. Therefore, a review of potential for cancer applications of DCS is valuable at this time for both optical and cancer communities.…”

“…This review is not intended to discuss every detail about DCS; rather it provides a flavor for the DCS method and a snapshot of its recent progress in cancer research. For example, DCS has been utilized in the monitoring of tumor-to-normal flow contrasts 25,30 and early hemodynamic/metabolic responses to chemotherapy 30 in human breast cancers, physiological effects of chemoradiation therapy on human head and neck cancers, 29,53 hemodynamic responses to photodynamic therapy (PDT) in human prostate cancers, 28,51 and efficacies of PDT in murine tumor models. 5,35,[55][56][57] In some of these studies, DCS was combined with NIRS in hybrid instruments for accurately extracting tumor blood flow 21 and for calculating tumor metabolic rate of oxygen consumption (TMRO 2 ) from the measured flow and oxygenation data.…”

“…5,35,[55][56][57] In some of these studies, DCS was combined with NIRS in hybrid instruments for accurately extracting tumor blood flow 21 and for calculating tumor metabolic rate of oxygen consumption (TMRO 2 ) from the measured flow and oxygenation data. 30 It is expected that measurements with multiple hemodynamic and metabolic parameters have the potential to enhance sensitivity and specificity in detection of cancers and monitoring of therapies.…”

“…In practice, however, the diffusion model, i.e., hΔr 2 ðτÞi ¼ 6D B τ, fits the autocorrelation curves rather well over a broad range of tissue types, ranging from rat brain, 43,45 and mouse tumor, 5,35 to piglet brain, 39 adult human skeletal muscle, 23,26 premature brain, 34,38 adult brain, 20,27,33,41 and adult tumors. 21,29,30 Here D B is the effective Brownian diffusion coefficient. Therefore the combined term, αD B , has been referred to as the blood flow index in biological tissues and has been commonly used to calculate relative blood flow (rBF) compared to the baseline flow index before physiological changes.…”

“…1(b)) with straight or 90-deg bent fibers is used in studies of tumors close to the body surface (e.g., breast tumor, head and neck tumor). 21,25,29,30 The second probe [see Fig. 1(c)] is a noncontact probe mounted on the imaging plane of a mechanical camera which is fixed at a certain distance (e.g., 15 cm) from the tumor surface.…”