Ning Liu, Yang Yu, Angelo Sassaroli, and Sergio Fantini

1. Near-infrared Spectral Imaging Instrument for Oximetry of the Human Breast Ning Liu, Yang Yu, Angelo Sassaroli, and Sergio Fantini Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA AbstractWe present a spectral imaging system for 2-D projection mammography that acquires broadband spectra (650-850nm) with a tandem scan of illumination/detection fibers. The design of the system implements our recently developed methods to enhance the spectral and spatial information of optical mammograms. We present a second-derivative image of a human breast that enhances the detection of breast structures, and we apply the spectral approach to measure the oxygenation along blood vessels. Such enhanced spatial and functional information can help develop optical mammography into an imaging modality for detection and monitoring of breast cancer. Instrumentation design A band-pass filtered Xenon arc lamp (Oriel Instruments, Model No. 66984) is coupled to the source optical fiber (internal diameter: 3 mm). The light collected with the detector optical fiber (internal diameter: 4 mm) is sent to a spectrograph (Acton Research Corporation, SpectraPro-150) equipped with a 300 G/mm grating to achieve a spectral dispersion of 20nm/mm. A CCD camera detector (Andor Tech., DV-420-BR-DD) is placed at the exit port of the spectrograph for spectral collection. A planar array of illumination and collection fibers allows for depth-sensitive imaging. The system works in a transmission geometry through the slightly compressed breast, and acquires 2-dimensional projection images by tandem-scanning the illumination and collection optical fiber array over the breast area. Introduction Near-infrared optical mammography is a powerful tool to measure the hemoglobin concentration and oxygenation within the breast. It is known for its potential of non-invasiveness, safety, relatively compact instrumentation (suitable for doctor’s office use, bed-side use, and even home use), and cost-effectiveness. Since the 1990’s, the development of more quantitative approaches and novel experimental techniques led to the emergence of new optical mammography system. Our objective is to take full advantage of the potential of optical mammography to collect information on spectral and spatial features of optical inhomogeneities within the breast. The importance of spectral information has already been pointed out in the literature for diagnostic characterization of breast tumors [1,2], and for monitoring neoadjuvant therapy [3]. We have previously proposed a dual-wavelength spectral method for tumor oximetry that is designed to be insensitive to unknown geometrical features of breast tumors [4,5]. We have previously shown how a spatial second derivative operator can enhance the spatial information content of diffuse optical images [6]. Depth discrimination in 2-D projection imaging can be achieved with off-axis detection [7], and we have recently proposed using planar source/detector arrays to generate images that enhance the visibility of structures at various depth levels [8]. • Scanning speed: along X-axis was 3.5 cm/s; along Y-axis was 0.2 cm/s. • Optical data acquisition time over a 128 cm2 area: < 4 min; • Breast image pixel size: 2 mm2mm. • Temporal sampling: 57 ms (full spectrum) Feasibility tests on a healthy human We have proposed a paired-wavelength spectral approach to quantify the oxygen saturation of the hemoglobin in breast tumors [4]. The first step is to identify the set of paired wavelengths λ1 and λ2 for which the intensity perturbation is the same (three such wavelength pairs are shown in the bottom figure), then calculate the relative concentration of the two chromophores according to equations derived from first-order perturbation theory. The second step is to take the average value of the relative concentrations associated with wavelength pairs for which the error is smaller than a threshold. The breast image was collected on a 40 year old healthy subject. The left side images show (a) the intensity image at 800nm after edge-correction; (b) the second-derivative image based on the image after integration over the full spectral range; and (c) the oxygen-saturation image calculated based on paired-wavelength method. The color scaled data indicate the oxygen saturation of hemoglobin measured with the new spectral approach at the locations indicated by the second-derivative image. Different color indicate different oxygenation level along the area of interest within the breast. (a) Features implemented in the new instrumentSpatial informationWe have reported a spatial 2nd-derivative algorithm for enhanced spatial resolution and discrimination of embedded optical inhomogeneities [6], and a method based on a planar array of sources and detectors [8] to generate images that feature preferential sensitivity to different depths within the tissue. The depth discrimination is achieved by arranging multiple source and/or detector elements in a planar configuration, and then combine the normalized intensities (I/I0, with I the measured intensity and I0 reference intensity) measured by each source-detector pair to yield a source-array intensity that is preferentially sensitive to inhomogeneities over a specific range of depths in tissue .We performed a phantom study to demonstrate the potential of this approach to depth discrimination. A turbid medium contained three cylindrical inhomogeneities that were placed 2.0, 3.0, and 4.0 cm from a seven-element, two-dimensional source array. A single detector was placed at a distance of 6.0 cm from the source array. (b) For instance, the oxygenation measured at position (x, y) = (2cm, 9.2cm) is: SO2 = 76%  5% (c) The spectrum of negative relative intensity change (-ΔI/I0) at position (x, y) = (2cm, 9.2cm). Conclusions and future works References We have demonstrated the applicability of the proposed spectral oximetry approach to the human breasts of healthy volunteers, and we found that the oxygenation measurements of blood vessels yielded values in expected ranges. The further development of the system including the feasibility test of the phased-array system on human subject; the real-time display of the intensity data. [1] C. M. Carpenter, B. W. Pogue, S. D. Jiang, H. Dehghani, X. Wang, K. D. Paulsen, W. A. Wells, J. Forero, C. Kogel, J. B. Weaver, and S. P. Poplack, “Image-guided optical spectroscopy provides molecular-specific information in vivo: MRI-guided spectroscopy of breast cancer hemoglobin, water, and scatterer size,” Opt. Lett. 32, 933-935 (2007). [2] S. Kukreti, A. Cerussi, B. Tromberg, and E. Gratton, “Intrinsic tumor biomarkers revealed by novel double-differential spectroscopic analysis of near-infrared spectra,” J. Biomed. Opt. 12, 020509 (2007). [3] A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, and B. J. Tromberg, “Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy,” Proc. Acad. Natl. Acad. Sci. (USA) 104, 4014-4019 (2007). [4] E. L. Heffer and S. Fantini, “Quantitative oximetry of breast tumors: a near-infrared method that identifies two optimal wavelengths for each tumor,” Appl. Opt. 41, 3827-3839 (2002). [5] N.Liu, A.Sassaroli, and S.Fantini, “Paired-wavelength spectral approach to measuring the relative concentrations of two localized chromophores in turbid media: an experimental study,” J. Biomed. Opt. 12, 051602 (2007). [6] V. E. Pera, E.L. Heffer, H. Siebold, O. Schutz, S. Heywang-Kobrunner, L. Gotz, A. Heinig, and S. Fantini, “Spatial second-derivative image processing: an application to optical mammography to enhance the detection of breast tumors,” J. Biomed. Opt. 8, 517-524 (2003). [7] D. Grosenick, H. Wabnitz, K.T. Moesta, J. Mucke, M. Moller, C. Stroszczynski, J. Stossel, B. Wassermann, P.M. Schlag, H. Rinneberg, “Concentration and oxygen saturation of haemoglobin of 50 breast tumours determined by time-domain optical mammography,” Phys. Med. Biol. 49, 1165-81 (2004). [8] N. Liu, A. Sassaroli, and S. Fantini, “Two-dimensional phased-arrays of sources and detectors for depth discrimination in diffuse optical imaging,” J. Biomed. Opt. 10, 051801 (2005). Acknowledgments This research is supported by the National Institutes of Health (Grant CA95885), and by the National Science Foundation (Award BES-93840).