PROJECT SUMMARY
In this Bioengineering Research project, we propose to develop a novel technique for frequency-domain near-
infrared spectroscopy (FD-NIRS) that aims to achieve selective sensitivity to deeper tissue in non-invasive
diffuse optical spectroscopy and imaging. A technique that features a stronger sensitivity to deeper tissue
relative to superficial tissue can have a broad impact on non-invasive optical diagnostics and monitoring and is
especially important in cerebral oximetry and functional brain imaging. The proposed technique is based on the
new concept of phase dual-slopes (this is the phase of the modulated optical signal measured in FD-NIRS),
which requires a minimum of two light sources and two optical detectors placed on the tissue according to a
special arrangement. In addition to achieving selective sensitivity to deeper tissue, phase dual slopes are
weakly sensitive to instrumental drifts and motion artifacts (except spikes), which is a highly desirable property
for robust measurements. First, we will use diffusion theory and Monte Carlo simulations to identify
source/detector geometrical arrangements and intensity modulation frequencies that optimize performance of
the phase dual-slope for a variety of heterogeneous layered media. Second, we will implement optimal phase
dual-slope conditions with a commercial FD-NIRS instrument to demonstrate effectiveness on tissue-like
phantoms, and we will design special source-detector arrays for imaging based on the Moore-Penrose
pseudoinverse of the Jacobian matrix for phase dual-slope measurements. Third, we will design and build a
dedicated compact, wearable, fiber-less, and cost-effective FD-NIRS device for further broadening the
applicability of the phase dual-slope method to freely moving subjects in everyday conditions, and for point-of-
care applications. Fourth, we will perform human studies for technical performance tests (in skeletal muscle
during vascular occlusions) and to demonstrate the effectiveness of the phase dual-slope method for functional
brain imaging (in the prefrontal cortex during cognitive activation). In particular, the latter study will elucidate
the relative blood flow/blood volume contributions to cortical hemodynamics and will allow for dual-task
measurements in subjects performing cognitive tasks while walking. The broad objective of this project is to
advance the field of diffuse optical measurements of biological tissue by developing special techniques for
collection and analysis of FD-NIRS data to enhance the quality, reliability, and information content of non-
invasive NIRS in research and clinical applications.
