Mapping breast cancer blood flow index, composition, and metabolism in a human subject using combined diffuse optical spectroscopic imaging and diffuse correlation spectroscopy

Abstract. Diffuse optical spectroscopic imaging (DOSI) and diffuse correlation spectroscopy (DCS) are model-based near-infrared (NIR) methods that measure tissue optical properties (broadband absorption, μa, and reduced scattering, μs′) and blood flow (blood flow index, BFI), respectively. DOSI-derived μa values are used to determine composition by calculating the tissue concentration of oxy- and deoxyhemoglobin (HbO2, HbR), water, and lipid. We developed and evaluated a combined, coregistered DOSI/DCS handheld probe for mapping and imaging these parameters. We show that uncertainties of 0.3  mm−1 (37%) in μs′ and 0.003  mm−1 (33%) in μa lead to ∼53% and 9% errors in BFI, respectively. DOSI/DCS imaging of a solid tissue-simulating flow phantom and a breast cancer patient reveals well-defined spatial distributions of BFI and composition that clearly delineates both the flow channel and the tumor. BFI reconstructed with DOSI-corrected μa and μs′ values had a tumor/normal contrast of 2.7, 50% higher than the contrast using commonly assumed fixed optical properties. In conclusion, spatially coregistered imaging of DOSI and DCS enhances intrinsic tumor contrast and information content. This is particularly important for imaging diseased tissues where there are significant spatial variations in μa and μs′ as well as potential uncoupling between flow and metabolism.

[1]  Guoqiang Yu,et al.  Portable optical tissue flow oximeter based on diffuse correlation spectroscopy. , 2009, Optics letters.

[2]  Yu Shang,et al.  Intraoperative evaluation of revascularization effect on ischemic muscle hemodynamics using near-infrared diffuse optical spectroscopies. , 2011, Journal of biomedical optics.

[3]  B. Chance,et al.  Spectroscopy and Imaging with Diffusing Light , 1995 .

[4]  B. Chance,et al.  Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies. , 2005, Journal of biomedical optics.

[5]  Yu Shang,et al.  Noninvasive optical evaluation of spontaneous low frequency oscillations in cerebral hemodynamics , 2012, NeuroImage.

[6]  D. Boas,et al.  Noninvasive optical measures of CBV, StO2, CBF index, and rCMRO2 in human premature neonates' brains in the first six weeks of life , 2010, Human brain mapping.

[7]  A. Yodh,et al.  In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies. , 2001, Physics in medicine and biology.

[8]  Turgut Durduran,et al.  Noninvasive measurements of tissue hemodynamics with hybrid diffuse optical methods , 2004 .

[9]  Bruce J. Tromberg,et al.  Quantitative Absorption and Scattering Spectra in Thick Tissues Using Broadband Diffuse Optical Spectroscopy , 2008 .

[10]  Enrico Gratton,et al.  Assessing tumor contrast in radiographically dense breast tissue using Diffuse Optical Spectroscopic Imaging (DOSI) , 2013, Breast Cancer Research.

[11]  David Hsiang,et al.  Frequent optical imaging during breast cancer neoadjuvant chemotherapy reveals dynamic tumor physiology in an individual patient. , 2010, Academic radiology.

[12]  A. Yodh,et al.  Near-infrared Diffuse Correlation Spectroscopy for Assessment of Tissue Blood Flow Single Scattering @bullet Multiple Scattering Limit (dws) @bullet Correlation Diffusion Equation (dcs) Dcs System @bullet Fiber-optic Probes Cancer Therapy Monitoring @bullet Cerebral Physiology and Disease @bullet Sk , 2022 .

[13]  A. Yodh,et al.  Diffuse optical measurement of blood flow in breast tumors. , 2006, Optics letters.

[14]  D. Boas Diffuse photon probes of structural and dynamical properties of turbid media: Theory and biomedical applications , 1996 .

[15]  Louis Gagnon,et al.  Investigation of diffuse correlation spectroscopy in multi-layered media including the human head. , 2008, Optics express.

[16]  T. Floyd,et al.  Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI. , 2007, Optics express.

[17]  David A Boas,et al.  Sensitivity of near-infrared spectroscopy and diffuse correlation spectroscopy to brain hemodynamics: simulations and experimental findings during hypercapnia , 2014, Neurophotonics.

[18]  Scott D. Stevens,et al.  Influences of tissue absorption and scattering on diffuse correlation spectroscopy blood flow measurements , 2011, Biomedical optics express.

[19]  Guoqiang Yu,et al.  Diffuse optical monitoring of repeated cerebral ischemia in mice , 2011, Optics express.

[20]  Albert Cerussi,et al.  Design and testing of a miniature broadband frequency domain photon migration instrument. , 2008, Journal of biomedical optics.

[21]  Yu Shang,et al.  Extraction of diffuse correlation spectroscopy flow index by integration of Nth-order linear model with Monte Carlo simulation. , 2014, Applied physics letters.

[22]  Bruce J Tromberg,et al.  Diffuse optical imaging using spatially and temporally modulated light. , 2012, Journal of biomedical optics.

[23]  Mitchell D. Schnall,et al.  Optically Measured Microvascular Blood Flow Contrast of Malignant Breast Tumors , 2014, PloS one.

[24]  Shoko Nioka,et al.  Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study. , 2006, Journal of biomedical optics.

[25]  Campbell,et al.  Scattering and Imaging with Diffusing Temporal Field Correlations. , 1995, Physical review letters.

[26]  David Hsiang,et al.  Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy. , 2010, Radiology.

[27]  Laura B. Morrison,et al.  Assessment of a multi-layered diffuse correlation spectroscopy method for monitoring cerebral blood flow in adults. , 2016, Biomedical optics express.

[28]  Scott D. Stevens,et al.  Noninvasive diffuse optical monitoring of head and neck tumor blood flow and oxygenation during radiation delivery , 2012, Biomedical optics express.

[29]  Sergio Fantini,et al.  Effect of index of refraction mismatch on the recovery of optical properties of cylindrical inhomogeneities in an infinite turbid medium , 1997, Photonics West - Biomedical Optics.

[30]  Min-Ying Su,et al.  Optical imaging correlates with magnetic resonance imaging breast density and reveals composition changes during neoadjuvant chemotherapy , 2013, Breast Cancer Research.

[31]  B. Tromberg,et al.  Diffuse optical spectroscopic imaging correlates with final pathological response in breast cancer neoadjuvant chemotherapy , 2011, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[32]  B. Tromberg,et al.  Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy. , 2007, Journal of biomedical optics.

[33]  Yu Shang,et al.  A Nth-order linear algorithm for extracting diffuse correlation spectroscopy blood flow indices in heterogeneous tissues. , 2014, Applied physics letters.

[34]  Xingde Li Fluorescence and diffusive wave diffraction tomographic probes in turbid media , 1998 .

[35]  D. Boas,et al.  Spatially varying dynamical properties of turbid media probed with diffusing temporal light correlation , 1997 .

[36]  B. Tromberg,et al.  Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment , 2011, Proceedings of the National Academy of Sciences.

[37]  K. Verdecchia,et al.  Characterization of a hybrid diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy system for real-time monitoring of cerebral blood flow and oxygenation , 2015, Photonics West - Biomedical Optics.

[38]  J. Detre,et al.  Noninvasive Measurement of Cerebral Blood Flow and Blood Oxygenation Using Near-Infrared and Diffuse Correlation Spectroscopies in Critically Brain-Injured Adults , 2010, Neurocritical care.

[39]  G. Maret,et al.  Multiple light scattering from disordered media. The effect of brownian motion of scatterers , 1987 .

[40]  G. Maret Diffusing-Wave Spectroscopy , 1997 .

[41]  Susan M. Schultz,et al.  Cerebral hemodynamics in preterm infants during positional intervention measured with diffuse correlation spectroscopy and transcranial Doppler ultrasound. , 2009, Optics express.

[42]  Chao Zhou In-vivo optical imaging and spectroscopy of cerebral hemodynamics , 2007 .