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Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six cases were malignant (infiltrating ductal carcinomas) and showed higher hemoglobin (34\u201386% increase), a reduction in oxygen saturation, an increase in water content as well as scatter changes relative to surrounding normal tissue. Three of six cases were benign, two of which were diagnosed with fibrocystic disease and showed a dominant contrast in water, consistent with fluid filled cysts. Scatter amplitude was the main source of contrast in the volunteer with the benign condition fibrosis, which typically contains denser collagen tissue. The changes monitored correspond to physiological changes associated with angiogenesis, hypoxia and cell proliferation anticipated in cancers. These changes represent potential diagnostic indicators, which can be assessed to characterize breast tumors.<\/jats:p>","DOI":"10.1177\/153303460500400505","type":"journal-article","created":{"date-parts":[[2014,10,3]],"date-time":"2014-10-03T14:55:00Z","timestamp":1412348100000},"page":"513-526","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":98,"title":["Near-Infrared Characterization of Breast Tumors\n                    <i>In Vivo<\/i>\n                    using Spectrally-Constrained Reconstruction"],"prefix":"10.1177","volume":"4","author":[{"given":"Subhadra","family":"Srinivasan","sequence":"first","affiliation":[{"name":"Dartmouth College Thayer School of Engineering Hanover, New Hampshire 03755, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian W.","family":"Pogue","sequence":"additional","affiliation":[{"name":"Dartmouth College Thayer School of Engineering Hanover, New Hampshire 03755, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Brooksby","sequence":"additional","affiliation":[{"name":"Dartmouth College Thayer School of Engineering Hanover, New Hampshire 03755, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shudong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Dartmouth College Thayer School of Engineering Hanover, New Hampshire 03755, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid","family":"Dehghani","sequence":"additional","affiliation":[{"name":"Dartmouth College Thayer School of Engineering Hanover, New Hampshire 03755, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Kogel","sequence":"additional","affiliation":[{"name":"Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center Lebanon, New Hampshire 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy A.","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Pathology Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center Lebanon, New Hampshire 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven P.","family":"Poplack","sequence":"additional","affiliation":[{"name":"Department of Radiology Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center Lebanon, New Hampshire 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith D.","family":"Paulsen","sequence":"additional","affiliation":[{"name":"Dartmouth College Thayer School of Engineering Hanover, New Hampshire 03755, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2005,10,1]]},"reference":[{"key":"bibr1-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1997.0053"},{"key":"bibr2-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.218.1.r01ja51261"},{"key":"bibr3-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1997.0047"},{"key":"bibr4-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1118\/1.1573791"},{"key":"bibr5-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.12.6468"},{"key":"bibr6-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1016\/S1076-6332(03)00562-2"},{"key":"bibr7-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1364\/OL.28.002339"},{"key":"bibr8-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1364\/OL.29.000256"},{"key":"bibr9-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1364\/AO.44.001858"},{"key":"bibr10-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1364\/AO.44.002082"},{"key":"bibr11-153303460500400505","first-page":"6449","volume":"49","author":"Vaupel P.","year":"1989","journal-title":"Cancer Research"},{"key":"bibr12-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.4.266"},{"key":"bibr13-153303460500400505","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(93)90280-9"},{"key":"bibr14-153303460500400505","first-page":"941","volume":"56","author":"Brizel D. 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