Quantitative Optical Spectroscopy: A Robust Tool for Direct Measurement of Breast Cancer Vascular Oxygenation and Total Hemoglobin Content In vivo

Abstract

We propose the use of a robust, biopsy needle-based, fiberoptic tool for routine clinical quantification of tumor oxygenation at the time of diagnostic biopsy for breast cancer. The purpose of this study was to show diffuse reflectance spectroscopy as a quantitative tool to measure oxygenation levels in the vascular compartment of breast cancers in vivo via an optical biopsy technique. Thirty-five patients undergoing surgical treatment for breast cancer were recruited for the study at Duke University Medical Center. Diffuse reflectance spectroscopy was performed on the tumors in situ before surgical resection, followed by needle-core biopsy of the optically measured tissue. Hemoglobin saturation and total hemoglobin content were quantified from 76 optical spectratissue biopsy pairs, consisting of 20 malignant, 23 benign, and 33 adipose tissues. Hemoglobin saturation in malignant tissues was significantly lower than nonmalignant tissues (P < 0.002) and was negatively correlated with tumor size and pathologic tumor category (P < 0.05). Hemoglobin saturation was positively correlated with total hemoglobin content in malignant tissues (P < 0.02). HER2/neu-amplified tumors exhibited significantly higher total hemoglobin content (P < 0.05) and significantly higher hemoglobin saturation (P < 0.02), which is consistent with a model of increased angiogenesis and tumor perfusion promoted by HER2/neu amplification. Diffuse reflectance spectroscopy could aid in prognosis and prediction in breast cancer via quantitative assessment of tumor physiology at the time of diagnostic biopsy.

A low-cost, portable, and quantitative spectral imaging system for application to biological tissues

“…Diffuse reflectance spectroscopy (DRS) is one such technique which, when coupled with appropriate light transport models, is capable of extracting quantitative information about tissue absorption and scattering, both of which reflect underlying tissue composition [17][18][19][20][21][22]. Zhu et al characterized the underlying sources of optical contrast in malignant and non-malignant breast tissues that can be exploited for intra-operative margin assessment and her results are very consistent with other similar studies reported in the literature [21,[23][24][25].…”

“…The core instrumentation has been previously documented in detail [17,24,25]. To briefly summarize, the system consists of a Xenon arc lamp, spectrograph, and a 2D CCD camera.…”

Real-time In Vivo Tissue Characterization with Diffuse Reflectance Spectroscopy during Transthoracic Lung Biopsy: A Clinical Feasibility Study

“…We anticipate that DRS-based biopsy guidance, as described in this study, is not limited to lung cancer, but may also be used for breast (9)(10)(11)(12), liver (13), and other cancer types. Larger multicenter studies are needed to confirm our data and further elucidate the diagnostic value (sensitivity and specificity) of the reported method for lung cancer and other tumors.…”

“…Subsequent analysis of the tissue's spectral response provides specific quantitative morphologic, biochemical, and functional information, thereby enabling tissue discrimination and potentially improving diagnostic capability. Several preclinical and clinical studies have demonstrated the potential use of DRS for cancer detection and diagnosis for a variety of tissue sites (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Despite the proven potential of DRS (19,20), clinical translation involves a variety of major challenges, many of which are unique to this stage of technology development.…”

Diffuse reflectance spectroscopy of human liver tumor specimens - towards a tissue differentiating optical biopsy needle using light emitting diodes

“…Several studies demonstrate the feasibility of DRS to differentiate tumors from unaffected parenchyma in different organ systems such as breast [3][4][5][6], lung [7][8][9][10] and brain [11][12][13] both ex vivo and in vivo. The non-invasive optical measurement technique utilizes light absorption and scattering after its interaction with cells and molecules.…”