Frequency domain optical spectroscopy in the diffusive regime is currently being investigated for biomedical applications including tumor detection, therapy monitoring, exercise metabolism, and others. Analog homodyne or heterodyne detection of sinusoidally modulated signals have been the predominant method for measuring phase and amplitude of photon density waves that have traversed through tissue. Here we demonstrate the feasibility of utilizing direct digital sampling of modulated signals using a 3.6 Gigasample/second 12 bit Analog to Digital Converter. Digitally synthesized modulated signals between 50MHz and 400MHz were measured on tissue simulating phantoms at six near-infrared wavelengths. An amplitude and phase precision of 1% and 0.6 degrees were achieved during drift tests. Amplitude, phase, scattering and absorption values were compared with a well-characterized network analyzer based diffuse optical device. Measured optical properties measured with both systems were within 3.6% for absorption and 2.8% for scattering over a range of biologically relevant values. Direct digital sampling represents a viable method for frequency domain diffuse optical spectroscopy and has the potential to reduce system complexity, size, and cost.

Frequency-domain photon migration (FDPM) uses modulated laser light to measure the bulk optical properties of turbid media and is increasingly applied for noninvasive functional medical imaging in the near-infrared. Although semiconductor edge-emitting laser diodes have been traditionally used as miniature light sources for this application, we show that vertical-cavity surface-emitting lasers (VCSELs) exhibit output power and modulation performance characteristics suitable for FDPM measurements of tissue optical properties at modulation frequencies exceeding 1 GHz. We also show that an array of multiple VCSEL devices can be coherently modulated at frequencies suitable for FDPM and can improve optical power. In addition, their small size and simple packaging make them an attractive choice as components in wearable sensors and clinical FDPM-based optical spectroscopy systems. We demonstrate the benefits of VCSEL technology by fabricating and testing a unique, compact VCSEL-based optical probe with an integrated avalanche photodiode. We demonstrate sensitivity of the VCSEL-based probe to subcutaneous tissue hemodynamics that was induced during an arterial cuff occlusion of the upper arm in a human subject.

A quantitative and dynamic analysis of skeletal muscle structure and function can guide training protocols and optimize interventions for rehabilitation and disease. While technologies exist to measure body composition, techniques are still needed for quantitative, long-term functional imaging of muscle at the bedside. We evaluate whether diffuse optical spectroscopic imaging (DOSI) can be used for long-term assessment of resistance training (RT). DOSI measures of tissue composition were obtained from 12 adults before and after 5 weeks of training and compared to lean mass fraction (LMF) from dual-energy X-ray absorptiometry (DXA). Significant correlations were detected between DXA LMF and DOSI-measured oxy-hemo/myoglobin, deoxy-hemo/myoglobin, total-hemo/myoglobin, water, and lipid. RT-induced increases of ∼6% in oxy-hemo/myoglobin (3.4±1.0  μM, p=0.00314) and total-hemo/myoglobin (4.9±1.1  μM, p=0.00024) from the medial gastrocnemius were detected with DOSI and accompanied by ∼2% increases in lean soft tissue mass (36.4±12.4  g, p=0.01641) and ∼60% increases in 1 rep-max strength (41.5±6.2  kg, p=1.9E-05). DOSI measures of vascular and/or muscle changes combined with correlations between DOSI and DXA suggest that quantitative diffuse optical methods can be used to evaluate body composition, provide feedback on long-term interventions, and generate new insight into training-induced muscle adaptations.

Significance

Growing levels of obesity and metabolic syndrome have driven demand for more advanced forms of body composition assessment. While various techniques exist to measure body composition, devices are typically expensive and not portable, involve radiation [in the case of dual-energy x-ray absorptiometry (DXA)], and are limited to analysis of adiposity while metabolic information from blood supply and oxygenation are not considered.

Aim

We evaluate whether diffuse optical spectroscopic imaging (DOSI) can be used to predict site-specific adiposity and percent fat (whole body) while simultaneously providing information about local tissue hemoglobin levels and oxygenation.

Approach

DOSI measures of tissue composition in gastrocnemius, quadriceps, abdomen, and biceps, DXA whole-body composition, and ultrasound-derived skin and adipose tissue thickness (SATT) in the quadriceps were obtained from 99 individuals aged 7 to 34 years old.

Results

Various DOSI-derived parameters were correlated with SATT and an optical method is proposed for estimating SATT using a newly defined parameter, the optical fat fraction (OFF), which considers all parameters that correlate with SATT. Broadband absorption and scattering spectra from study participants with the thinnest (SATT  ≈  0.25  ±  0.02  cm) and thickest SATT (SATT  ≈  1.55  ±  0.14  cm), representing best estimates for pure in vivo lean and fatty tissue, respectively, are reported. Finally, a trained prediction model is developed which allows DOSI assessment of OFF to predict DXA body-fat percentage, demonstrating that DOSI can be used to quantify body composition.

Conclusions

This study shows that DOSI can be used to assess the adiposity of specific tissues or the entire human body, and the OFF parameter is defined for corroboration and further evaluation in future research.

Diffuse optical spectroscopic imaging (DOSI) is a versatile technology sensitive to changes in tissue composition and hemodynamics and has been used for a wide variety of clinical applications. Specific applications have prompted the development of versions of the DOSI technology to fit specific clinical needs. This work describes the development and characterization of a multi-modal DOSI (MM-DOSI) system that can acquire metabolic, compositional, and pulsatile information at multiple penetration depths in a single hardware platform. Additionally, a 3D tracking system is integrated with MM-DOSI, which enables registration of the acquired data to the physical imaging area. We demonstrate imaging, layered compositional analysis, and metabolism tracking capabilities using a single MM-DOSI system on optical phantoms as well as in vivo human tissue. We characterize system performance with a silicone phantom containing an embedded object. To demonstrate multi-layer sensitivity, we imaged human calf tissue with a 4.8-mm skin-adipose thickness. Human thenar tissue was also measured using a combined broadband DOSI and continuous-wave near-infrared spectroscopy method (∼15  Hz acquisition rate). High-resolution optical property maps of absorption (μa) and reduced scattering (μs  '  ) were recovered on the phantom by capturing over 1000 measurement points in under 5 minutes. On human calf tissue, we show two probing depth layers have significantly different (p  <  0.001) total-hemo/myoglobin and μs  '   composition. On thenar tissue, we calculate tissue arterial oxygen saturation, venous oxygen saturation, and tissue metabolic rate of oxygen consumption during baseline and after release of an arterial occlusion. The MM-DOSI can switch between collection of broadband spectra, high-resolution images, or multi-depth hemodynamics without any hardware reconfiguration. We conclude that MM-DOSI enables acquisition of high resolution, multi-modal data consolidated in a single platform, which can provide a more comprehensive understanding of tissue hemodynamics and composition for a wide range of clinical applications.

Instrument equivalence and quality control are critical elements of multi-center clinical trials. We currently have five identical Diffuse Optical Spectroscopic Imaging (DOSI) instruments enrolled in the American College of Radiology Imaging Network (ACRIN, #6691) trial located at five academic clinical research sites in the US. The goal of the study is to predict the response of breast tumors to neoadjuvant chemotherapy in 60 patients. In order to reliably compare DOSI measurements across different instruments, operators and sites, we must be confident that the data quality is comparable. We require objective and reliable methods for identifying, correcting, and rejecting low quality data. To achieve this goal, we developed and tested an automated quality control algorithm that rejects data points below the instrument noise floor, improves tissue optical property recovery, and outputs a detailed data quality report. Using a new protocol for obtaining dark-noise data, we applied the algorithm to ACRIN patient data and successfully improved the quality of recovered physiological data in some cases. © 2013 Copyright SPIE.

Objective

To quantitatively measure tissue composition and hemodynamics during resuscitative endovascular balloon occlusion of the aorta (REBOA) in two tissue compartments using non-invasive two-channel broadband diffuse optical spectroscopy (DOS).

Methods

Tissue concentrations of oxy- and deoxyhemoglobin (HbO2 and HbR), water, and lipid were measured in a porcine model (n = 10) of massive hemorrhage (65% total blood volume over 1 h) and 30-min REBOA superior and inferior to the aortic balloon.

Results

After hemorrhage, hemoglobin oxygen saturation (StO2 = HbO2/[HbO2 + HbR]) at both sites decreased significantly (-29.9% and -42.3%, respectively). The DOS measurements correlated with mean arterial pressure (MAP) (R2 = 0.79, R2 = 0.88), stroke volume (SV) (R2 = 0.68, R2 = 0.88), and heart rate (HR) (R2 = 0.72, R2 = 0.88). During REBOA, inferior StO2 continued to decline while superior StO2 peaked 12 min after REBOA before decreasing again. Inferior DOS parameters did not associate with MAP, SV, or HR during REBOA.

Conclusions

Dual-channel regional tissue DOS measurements can be used to non-invasively track the formation of hemodynamically distinct tissue compartments during hemorrhage and REBOA. Conventional systemic measures MAP, HR, and SV are uncorrelated with tissue status in inferior (downstream) sites. Multi-compartment DOS may provide a more complete picture of the efficacy of REBOA and similar resuscitation procedures.