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 (rctHHbT/N=69±21%), oxyhemoglobin (rctO2HbT/N=73±25%), total hemoglobin (rctTHbT/N=72±17%), and lipid concentration (rctLipidT/N=116±13%). Similarly, DCS found significant changes in tumor/normal blood flow contrast (rBFT/N=75±7% on day 7 with respect to day 0). 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.
The sensitivity to collagen may be useful for diagnostic purposes in mammography, as collagen seems to be involved in
the development of breast cancer. Moreover, collagen content is expected to be related to breast density (i.e. breast
parenchymal pattern) and its quantification could allow the classification of breast type. Thus we have measured the
absorption properties of collagen from 610 to 1040 nm. Absorption spectra of breast from healthy volunteers were then
interpreted adding collagen to the other absorbers previously considered (i.e. oxy- and deoxyhemoglobin, water, and
lipids). A significant amount of collagen, depending on breast type, is estimated to be present and seems to correlate with
breast type. Moreover, adding collagen to the fitting procedure affects remarkably the estimated values of blood content
and oxygenation. We have also upgraded our time-resolved multi-wavelength optical mammograph, adding a long
wavelength (1060 nm) to improve the spectral information and, in particular, the sensitivity to collagen. Breast
measurements on volunteers have recently started.
Diffuse optical imaging (DOI) may be a beneficial diagnostic method for women with mammographically dense breast tissue. In order to evaluate the utility of DOI, we are developing broadband diffuse optical spectroscopy (DOS) to characterize the functional origins of optical signals in breast cancer patients. Broadband DOS combines multifrequency intensity-modulated and continuous-wave near-infrared light to quantify tissue absorption and scattering spectra from 650 to 1000 nm. Values of intrinsic physiological properties (oxy- and deoxy-hemoglobin, water, lipid, and scatter power) derived from absorption and scattering spectra provide detailed information on breast physiology. We present the results of clinical studies of 58 stage II/III malignant breast tumors using a noninvasive, handheld, broadband DOS probe. On average, eight positions were scanned over tumor and contralateral normal breast for each subject. Intrinsic physiological properties were statistically significantly different for malignant vs. normal tissues for all subjects, without patient age or tumor size/type stratification. Breast tissues containing malignant tumors displayed reduced lipid content (~20%) and increased water, deoxy-, and oxy-hemoglobin (>50% each) compared to normal breast tissues. Functional perturbations by the tumor were significantly larger than functional variations in normal tissues. A tissue optical index (TOI) derived from intrinsic physiological properties yielded an average two-fold contrast difference between malignant tumors and intrinsic tissue properties. Our results demonstrate that intrinsic optical signals can be influenced by functional perturbations characteristic of malignant transformation; cellular metabolism, extracellular matrix composition, and angiogenesis. Our findings further underscore the importance of broadband measurements and patient age stratification in breast cancer DOI.
KEYWORDS: Tumors, Magnetic resonance imaging, Breast, Tissues, Tissue optics, Diffuse optical spectroscopy, Scattering, In vivo imaging, Breast cancer, Skin
Monitoring tumor response to therapy can enable assessment of treatment efficacy, maximizing patient outcome and survival. We employ a noninvasive, handheld laser breast scanner (LBS) based on broadband diffuse optical spectroscopy (DOS) in conjunction with contrast-enhanced magnetic resonance imaging (cMRI) to assess tumor response to presurgical neoadjuvant chemotherapy. DOS and cMRI scans are performed after the first and fourth cycles of a doxorubicin/cyclophosphamide regimen in a patient with invasive ductal carcinoma. DOS measurements are used to quantify bulk tissue optical and physiological parameters, which are mapped to T2- and T1-weighted cMRI images. Initial DOS measurements show high tumor/normal contrast in total hemoglobin concentration (THC, 56±7 versus 27±4 µM) and water fraction (81.4±1% versus 24±3%) colocalized with regions of strongly enhancing T2-wieghted and cMRI signals. After the fourth cycle of chemotherapy, we observe decreases in peak MRI contrast-enhancement values (37.6%) and apparent lesion volume (21.9 versus 13.7 cm3), which corresponds to physiological changes measured by DOS, including a 20 to 25% reduction in the spatial extent of the tumor and a 38.7% drop in mean total hemoglobin content (THC, 41.6 versus 23.4 µM). These data provide in vivo validation of the accuracy of broadband DOS and the sensitivity of optical methods to changes in tumor physiology.
Near-infrared (NIR) diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) show promise as noninvasive clinical techniques for breast cancer screening and diagnosis. Since NIR methods are based on optical contrast between healthy and diseased tissue, it is essential to characterize the sources of endogenous contrast in normal subjects. We report intra- and inter-subject variation and bilateral asymmetry of the optical and physiological parameters of 31 women using a seven-wavelength NIR frequency-domain photon migration (FDPM) instrument. Wavelength-dependent absorption and reduced scattering parameters (µa and µs, respectively) were measured in four major quadrants and the areolar regions of left and right breasts. These values were used to determine tissue concentrations of oxy-(HbO2) and deoxy-(Hb-R) hemoglobin, lipid content, water concentration, and tissue "scatter power." Mean total hemoglobin for premenopausal (PRE) women (20 to 30 µM) is approximately two-fold higher than for postmenopausal (POST) subjects at all positions. POST women have approximately 50% higher lipid content (50 to 60%) than PRE at all positions. Water concentration on average is 1.8-fold higher for PRE subjects (30 to 40%) than POST. These differences are most pronounced when comparing the areolar complex to the other regions of the breast. In premenopausal women, the areolar regions have 40 to 45% increased total hemoglobin concentration (THC), 20 to 25% lower lipid content, and 30 to 60% higher scatter power versus the quadrants. Small-scale (3 cm) changes in optical properties are negligible compared to large-scale variations over all quadrants, where the intrinsic spatial heterogeneity of healthy breast tissue is 20 to 40% for µa and 5 to 12% for µs. Although no consistent right-left differences are observed in the study population, relative differences between symmetric positions ranged from 18 to 30% for THC, 10 to 40% for adipose, 10 to 25% for water, and 4 to 9% for scattering (674 nm) within an individual.
Near infrared diffuse optical spectroscopy and imaging may enhance existing technologies for breast cancer screening, diagnosis, and treatment. NIR spectroscopy yields quantitative functional information that cannot be obtained with other non-invasive radiological techniques. In this study we focused upon the origins of this contrast in healthy breast, especially from water and lipids.
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