A multimodal spectroscopy system for real-time disease diagnosis

Abstract

The combination of reflectance, fluorescence, and Raman spectroscopy-termed multimodal spectroscopy ͑MMS͒-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 nm͒, a nitrogen laser ͑337 nm͒, and a diode laser ͑830 nm͒, 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 fluorescence͒ and the other for the near-infrared ͑Raman͒, 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.

Design and characterization of a novel multimodal fiber-optic probe and spectroscopy system for skin cancer applications

“…34 Briefly, combination LIFS-DRS probes have been demonstrated by past studies, 35,36 as well as a probe combining all three techniques. 32 There are several important, and challenging, design and functional considerations for a probe that combines reflectance, fluorescence, and Raman signals. First, due to the very low probability of Raman scattering (one inelastically scattered photon for every 10 9 elastically scattered photons), the optical design must be fine-tuned to maximize RS signalto-noise ratios.…”

“…31 Furthermore, MMS has been successfully applied for the early detection of atherosclerotic plaque. 32,33 The successful application of MMS in non-cancer related pathologies indicates that it has considerable potential and its efficacy would be further tested by applying it to skin cancer.…”

Multimodal spectroscopy detects features of vulnerable atherosclerotic plaque

“…For a full description of the system, please refer to the related publication. 14 In brief, the MMS instrument utilized a xenon flash lamp (370 to 740 nm) to obtain reflectance spectra, a nitrogen laser (337 nm) to excite fluorescence, and a diode laser (830 nm) for Raman scattering. MMS spectra were collected by means of a unitary spectral probe previously sterilized overnight by either cold gas ethylene oxide or Sterrad R (Advanced Sterilization Products, Irvine, California).…”

Depth-resolved measurements with elliptically polarized reflectance spectroscopy

“…Recently, a number of approaches have been proposed to address this challenge including the use of spherical lenses [24][25][26], differential path length spectroscopy [27], or the use of fibers in an oblique orientation in order to favorably collect either superficial or deep penetrating photons from predetermined depths [28][29][30][31][32][33]. A major shortcoming of these systems is that they require multiple fibers with different fibers collecting signals from various depths.…”