A scalable, multi-wavelength, broad bandwidth frequency-domain near-infrared spectroscopy platform for real-time quantitative tissue optical imaging.

Frequency-domain near-infrared spectroscopy (FD-NIRS) provides quantitative noninvasive measurements of tissue optical absorption and scattering, as well as a safe and accurate method for characterizing tissue composition and metabolism. However, the poor scalability and high complexity of most FD-NIRS systems assembled to date have contributed to its limited clinical impact. To address these shortcomings, we present a scalable, digital-based FD-NIRS platform capable of measuring optical properties and tissue chromophore concentrations in real-time. The system provides single-channel FD-NIRS amplitude/phase, optical property, and chromophore data at a maximum display rate of 36.6 kHz, 17.9 kHz, and 10.2 kHz, respectively, and can be scaled to multiple channels as well as integrated into a handheld format. The entire system is enabled by several innovations including an ultra-high-speed k-nearest neighbor lookup table method (maximum of 250,000 inversions/s for a large 2500x700 table of absorption and reduced scattering coefficients), embedded FPGA and CPU high-speed co-processing, and high-speed data transfer (due to on-board processing). We show that our 6-wavelength, broad modulation bandwidth (1-400 MHz) system can be used to perform 2D high-density spatial mapping of optical properties and high speed quantification of hemodynamics.

Optimizing sensitivity and dynamic range of silicon photomultipliers for frequency-domain near infrared spectroscopy.

Diffuse optical imaging and tomography based upon frequency-domain near-infrared spectroscopy (fdNIRS) is used to noninvasively measure tissue structure and function through quantitative absolute measurements of tissue optical absorption and scattering. Here we describe how utilizing a silicon photomultiplier (SiPM) detector for fdNIRS improves performance. We discuss the operation of SiPMs, how they differ from other fdNIRS photodetectors, and show theoretically that SiPMs offer similar sensitivity to photomultiplier tube (PMT) detectors while having a higher dynamic range and lower cost, size, and operating voltage. With respect to avalanche photodiode (APD) detectors, theoretical and experimental data shows drastically increased signal to noise ratio performance, up to 25dB on human breast, head, and muscle tissue. Finally, we extend the dynamic range (∼10dB) of the SiPM through a nonlinear calibration technique which reduced absorption error by a mean 16 percentage points.

Next-generation frequency domain diffuse optical imaging systems using silicon photomultipliers.

Diffuse optical imaging of biological tissue is a well-established methodology used to measure functional information from intrinsic contrast due to hemoglobin, water, and lipid. This information is exploited in frequency domain diffuse optical spectroscopy (FD-DOS) systems, which have been used to investigate chemotherapy response, optical mammography, and brain imaging. FD-DOS depth sensitivity and dynamic range are typically constrained by photodetector sensitivity. Here we present FD-DOS utilizing a silicon photomultiplier (SiPM) detector that has a higher signal-to-noise ratio (SNR) compared to an avalanche photodiode (APD), and thus enables extended source-detector (S/D) separations and increased depth penetration. We find the SiPM to have 10-30 dB greater SNR than a comparably sized APD while detecting 1.5-2 orders of magnitude lower light levels, down to ∼4 pW at 50 MHz modulation. The SiPM and APD recover optical property values of tissue-simulating phantoms within 13% agreement and are stable with 1% coefficient of variation over one hour. Finally, the SiPM is used to accurately recover optical properties in a reflectance geometry at S/D separations up to 48 mm in phantoms mimicking human breast tissue.

Frequency domain diffuse optical spectroscopy with a near-infrared tunable vertical cavity surface emitting laser.

We present an approach for performing frequency domain diffuse optical spectroscopy (fd-DOS) utilizing a near-infrared tunable vertical cavity surface emitting laser (VCSEL) that enables high spectral resolution optical sensing in a miniature format. The tunable VCSEL, designed specifically for deep tissue imaging and sensing, utilizes an electrothermally tunable microelectromechanical systems topside mirror to tune the laser cavity resonance. At room temperature, the laser is tunable across 14nm from 769 to 782nm with single mode CW output and a peak output power of 1.3mW. We show that the tunable VCSEL is suitable for use in fd-DOS by measuring the optical properties of a tissue-simulating phantom over the tunable range. Optical properties were recovered within 0.0006mm-1 (absorption) and 0.09mm-1 (reduced scattering) compared to a broadband fd-DOS reference system. Our results indicate that tunable VCSELs may be an attractive choice to enable high spectral resolution optical sensing in a wearable format.