A multimodal spectroscopy system for real-time disease diagnosis

The combination of reflectance, fluorescence, and Raman spectroscopy—termed multimodal spectroscopy (MMS)—provides complementary and depth-sensitive information about tissue composition. As such, MMS is a promising tool for disease diagnosis, particularly in atherosclerosis and breast cancer. We have developed an integrated MMS instrument and optical fiber spectral probe for simultaneous collection of all three modalities in a clinical setting. The MMS instrument multiplexes three excitation sources, a xenon flash lamp (370–740 nm), a nitrogen laser (337 nm), and a diode laser (830 nm), through the MMS probe to excite tissue and collect the spectra. The spectra are recorded on two spectrograph/charge-coupled device modules, one optimized for visible wavelengths (reflectance and fluorescence) and the other for the near-infrared (Raman), and processed to provide diagnostic parameters. We also describe the design and calibration of a unitary MMS optical fiber probe 2 mm in outer diameter, containing a single appropriately filtered excitation fiber and a ring of 15 collection fibers, with separate groups of appropriately filtered fibers for efficiently collecting reflectance, fluorescence, and Raman spectra from the same tissue location. A probe with this excitation/collection geometry has not been used previously to collect reflectance and fluorescence spectra, and thus physical tissue models (“phantoms”) are used to characterize the probe’s spectroscopic response. This calibration provides probe-specific modeling parameters that enable accurate extraction of spectral parameters. This clinical MMS system has been used recently to analyze artery and breast tissue in vivo and ex vivo.National Institutes of Health (U.S) ( Grant No. P41-RR-02594

Development of MMS for the detection of vulnerable atherosclerotic plaques

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2008.Includes bibliographical references (p. 205-228).The combination of reflectance, fluorescence, and Raman spectroscopy - which is termed multimodal spectroscopy (MMS) - provides complementary and depth-sensitive information about tissue composition. As such, MMS can provide biochemical and morphological information useful in detecting vulnerable atherosclerotic plaques, that is, plaques most prone to rupture and causing sudden death. Early detection of these vulnerable plaques is critical to reducing patient mortality associated with cardiovascular disease. In developing MMS into a clinical diagnostic modality, several scientific and engineering directions are explored in this work: the physical motivation for MMS, the framework of quantitative extraction of spectral parameters, the spectral probes that enable the efficient collection of data, a clinical instrument able to provide real-time diagnosis, and, finally, a clinical implementation of the entire methodology. The motivation for MMS is shown through a pilot in vitro study using carotid artery specimens, which shows the promise for MMS to detect features of vulnerable plaque. Having established the motivation, the next step describes the mathematical tools used to extract quantitative spectral parameters and, moreover, to assess the uncertainty and confidence of the spectral information. In order to implement MMS, the development of an efficient, specialized MMS probe for data acquisition and a compact and practical clinical MMS instrument are described. Lastly, in vivo and ex vivo results from a relatively large clinical study of vulnerable plaque in humans show excellent agreement between MMS and histopathology. Specifically, MMS is shown to have the ability to detect a thin fibrous cap, necrotic core or superficial foam cells, and thrombus.(cont.) In addition, these studies show that vulnerable plaques could be detected with a cross validated sensitivity of 89-96%, specificity of 72-78%, and a negative predictive value of 89-97%. These very encouraging results serve as an important step in bringing MMS into the clinical arena as a powerful diagnostic technique.by Obrad R. Šćepanović.Ph.D

Light scattering spectroscopy clinical imaging device implementation

Thesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.Includes bibliographical references.by Obrad R. Šćepanović.M.Eng