Medium-adaptive compressive diffuse optical tomography.

The low spatial resolution of diffuse optical tomography (DOT) has motivated the development of high-density DOT systems utilizing spatially-encoded illumination and detection strategies. Data compression methods, through the application of Fourier or Hadamard patterns, have been commonly explored for both illumination and detection but were largely limited to pre-determined patterns regardless of imaging targets. Here, we show that target-optimized detection patterns can yield significantly improved DOT reconstructions in both in silico and experimental tests. Applying reciprocity, we can further iteratively optimize both illumination and detection patterns and show that these simultaneously optimized source/detection patterns outperform predetermined patterns in simulation settings. In addition, we show media-adaptive measurement data compression methods enable wide-field DOT systems to recover highly complex inclusions inside optically-thick media with reduced background artifacts. Furthermore, using truncated optimized patterns shows an improvement of 2-4× in increased speed of data acquisition and reconstruction without significantly losing image quality. The proposed method can be readily extended for additional data dimensions such as spectrum and time.

Flexible circuit-based spatially aware modular optical brain imaging system for high-density measurements in natural settings.

Significance: Functional near-infrared spectroscopy (fNIRS) presents an opportunity to study human brains in everyday activities and environments. However, achieving robust measurements under such dynamic conditions remains a significant challenge. Aim: The modular optical brain imaging (MOBI) system is designed to enhance optode-to-scalp coupling and provide a real-time probe three-dimensional (3D) shape estimation to improve the use of fNIRS in everyday conditions. Approach: The MOBI system utilizes a bendable and lightweight modular circuit-board design to enhance probe conformity to head surfaces and comfort for long-term wearability. Combined with automatic module connection recognition, the built-in orientation sensors on each module can be used to estimate optode 3D positions in real time to enable advanced tomographic data analysis and motion tracking. Results: Optical characterization of the MOBI detector reports a noise equivalence power of 8.9 and 7.3 pW / Hz at 735 and 850 nm, respectively, with a dynamic range of 88 dB. The 3D optode shape acquisition yields an average error of 4.2 mm across 25 optodes in a phantom test compared with positions acquired from a digitizer. Results for initial in vivo validations, including a cuff occlusion and a finger-tapping test, are also provided. Conclusions: To the best of our knowledge, the MOBI system is the first modular fNIRS system featuring fully flexible circuit boards. The self-organizing module sensor network and automatic 3D optode position acquisition, combined with lightweight modules ( 18 g / module ) and ergonomic designs, would greatly aid emerging explorations of brain function in naturalistic settings.

Flexible-circuit-based 3-D aware modular optical brain imaging system for high-density measurements in natural settings.

Significance: Functional near-infrared spectroscopy (fNIRS) presents an opportunity to study human brains in everyday activities and environments. However, achieving robust measurements under such dynamic condition remains a significant challenge. Aim: The modular optical brain imaging (MOBI) system is designed to enhance optode-to-scalp coupling and provide real-time probe 3-D shape estimation to improve the use of fNIRS in everyday conditions. Approach: The MOBI system utilizes a bendable and lightweight modular circuit-board design to enhance probe conformity to head surfaces and comfort for long-term wearability. Combined with automatic module connection recognition, the built-in orientation sensors on each module can be used to estimate optode 3-D positions in real-time to enable advanced tomographic data analysis and motion tracking. Results: Optical characterization of the MOBI detector reports a noise equivalence power (NEP) of 8.9 and 7.3 pW / H z at 735 nm and 850 nm, respectively, with a dynamic range of 88 dB. The 3-D optode shape acquisition yields an average error of 4.2 mm across 25 optodes in a phantom test compared to positions acquired from a digitizer. Results for initial in vivo validations, including a cuff occlusion and a finger-tapping test, are also provided. Conclusions: To the best of our knowledge, the MOBI system is the first modular fNIRS system featuring fully flexible circuit boards. The self-organizing module sensor network and automatic 3-D optode position acquisition, combined with lightweight modules (18 g/module) and ergonomic designs, would greatly aid emerging explorations of brain function in naturalistic settings.

Compact breast shape acquisition system for improving diffuse optical tomography image reconstructions.

Diffuse optical tomography (DOT) has been investigated for diagnosing malignant breast lesions, but its accuracy relies on model-based image reconstructions, which in turn depends on the accuracy of breast shape acquisition. In this work, we have developed a dual-camera structured light imaging (SLI) breast shape acquisition system tailored for a mammography-like compression setting. Illumination pattern intensity is dynamically adjusted to account for skin tone differences, while thickness-informed pattern masking reduces artifacts due to specular reflections. This compact system is affixed to a rigid mount that can be installed into existing mammography or parallel-plate DOT systems without the need for camera-projector re-calibration. Our SLI system produces sub-millimeter resolution with a mean surface error of 0.26 mm. This breast shape acquisition system results in more accurate surface recovery, with an average 1.6-fold reduction in surface estimation errors over a reference method via contour extrusion. Such improvement translates to 25% to 50% reduction in mean squared error in the recovered absorption coefficient for a series of simulated tumors 1-2 cm below the skin.

MOCA: a systematic toolbox for designing and assessing modular functional near-infrared brain imaging probes.

Significance: The expansion of functional near-infrared spectroscopy (fNIRS) systems toward broader utilities has led to the emergence of modular fNIRS systems composed of repeating optical source/detector modules. Compared to conventional fNIRS systems, modular fNIRS systems are more compact and flexible, making wearable and long-term monitoring possible. However, the large number of design parameters makes understanding their impact on a probe's performance a daunting task. Aim: We aim to create a systematic software platform to facilitate the design, characterization, and comparison of modular fNIRS probes. Approach: Our software-modular optode configuration analyzer (MOCA)-implements semi-automatic algorithms that assist in tessellating user-specified regions-of-interest, in interconnecting modules of various shapes, and in quantitatively comparing probe performance using metrics, such as spatial channel distributions and average brain sensitivity of the resulting probes. There is also support for limited parameter sweeping capabilities. Results: Through several examples, we show that users can use MOCA to design and optimize modular fNIRS probes, study trade-offs between several module shapes, improve brain sensitivity in probes via module re-orientation, and enhance probe performance via adjusting module spatial layouts. Conclusion: Despite its simplicity, our modular probe design platform offers a framework to describe and quantitatively assess probes made by modules, opening a new door for the growing fNIRS user community to approach the challenging problem of module- and probe-parameter selection and fine-tuning.

Non-invasive and quantitative in vivo monitoring of gold nanoparticle concentration and tissue hemodynamics by hybrid optical spectroscopies.

Owing to their unique combination of chemical and physical properties, inorganic nanoparticles show a great deal of potential as suitable agents for early diagnostics and less invasive therapies. Yet, their translation to the clinic has been hindered, in part, by the lack of non-invasive methods to quantify their concentration in vivo while also assessing their effect on the tissue physiology. In this work, we demonstrate that diffuse optical techniques, employing near-infrared light, have the potential to address this need in the case of gold nanoparticles which support localized surface plasmons. An orthoxenograft mouse model of clear cell renal cell carcinoma was non-invasively assessed by diffuse reflectance and correlation spectroscopies before and over several days following a single intravenous tail vein injection of polyethylene glycol-coated gold nanorods (AuNRs-PEG). Our platform enables to resolve the kinetics of the AuNR-PEG uptake by the tumor in quantitative agreement with ex vivo inductively coupled plasma mass spectroscopy. Furthermore, it allows for the simultaneous monitoring of local tissue hemodynamics, enabling us to conclude that AuNRs-PEG do not significantly alter the animal physiology. We note that the penetration depth of this current probe was a few millimeters but can readily be extended to centimeters, hence gaining clinical relevance. This study and the methodology presented here complement the nanomedicine toolbox by providing a flexible platform, extendable to other absorbing agents that can potentially be translated to human trials.

Pre-clinical longitudinal monitoring of hemodynamic response to anti-vascular chemotherapy by hybrid diffuse optics.

The longitudinal effect of an anti-vascular endothelial growth factor receptor 2 (VEGFR-2) antibody (DC 101) therapy on a xenografted renal cell carcinoma (RCC) mouse model was monitored using hybrid diffuse optics. Two groups of immunosuppressed male nude mice (seven treated, seven controls) were measured. Tumor microvascular blood flow, total hemoglobin concentration and blood oxygenation were investigated as potential biomarkers for the monitoring of the therapy effect twice a week and were related to the final treatment outcome. These hemodynamic biomarkers have shown a clear differentiation between two groups by day four. Moreover, we have observed that pre-treatment values and early changes in hemodynamics are highly correlated with the therapeutic outcome demonstrating the potential of diffuse optics to predict the therapy response at an early time point.

Scanning, non-contact, hybrid broadband diffuse optical spectroscopy and diffuse correlation spectroscopy system.

A scanning system for small animal imaging using non-contact, hybrid broadband diffuse optical spectroscopy (ncDOS) and diffuse correlation spectroscopy (ncDCS) is presented. The ncDOS uses a two-dimensional spectrophotometer retrieving broadband (610-900 nm) spectral information from up to fifty-seven source-detector distances between 2 and 5 mm. The ncDCS data is simultaneously acquired from four source-detector pairs. The sample is scanned in two dimensions while tracking variations in height. The system has been validated with liquid phantoms, demonstrated in vivo on a human fingertip during an arm cuff occlusion and on a group of mice with xenoimplanted renal cell carcinoma.

Non-contact scanning diffuse correlation tomography system for three-dimensional blood flow imaging in a murine bone graft model.

A non-contact galvanometer-based optical scanning system for diffuse correlation tomography was developed for monitoring bone graft healing in a murine femur model. A linear image reconstruction algorithm for diffuse correlation tomography was tested using finite-element method based simulated data and experimental data from a femur or a tube suspended in a homogeneous liquid phantom. Finally, the non-contact system was utilized to monitor in vivo blood flow changes prior to and one week after bone graft transplantation within murine femurs. Localized blood flow changes were observed in three mice, demonstrating a potential for quantification of longitudinal blood flow associated with bone graft healing.