A wide field-of-view, modular, high-density diffuse optical tomography system for minimally constrained three-dimensional functional neuroimaging.

The ability to produce high-quality images of human brain function in any environment and during unconstrained movement of the subject has long been a goal of neuroimaging research. Diffuse optical tomography, which uses the intensity of back-scattered near-infrared light from multiple source-detector pairs to image changes in haemoglobin concentrations in the brain, is uniquely placed to achieve this goal. Here, we describe a new generation of modular, fibre-less, high-density diffuse optical tomography technology that provides exceptional sensitivity, a large dynamic range, a field-of-view sufficient to cover approximately one-third of the adult scalp, and also incorporates dedicated motion sensing into each module. Using in-vivo measures, we demonstrate a noise-equivalent power of 318 fW, and an effective dynamic range of 142 dB. We describe the application of this system to a novel somatomotor neuroimaging paradigm that involves subjects walking and texting on a smartphone. Our results demonstrate that wearable high-density diffuse optical tomography permits three-dimensional imaging of the human brain function during overt movement of the subject; images of somatomotor cortical activation can be obtained while subjects move in a relatively unconstrained manner, and these images are in good agreement with those obtained while the subjects remain stationary. The scalable nature of the technology we described here paves the way for the routine acquisition of high-quality, three-dimensional, whole-cortex diffuse optical tomography images of cerebral haemodynamics, both inside and outside of the laboratory environment, which has profound implications for neuroscience.

Geometrically complex 3D-printed phantoms for diffuse optical imaging.

Tissue-equivalent phantoms that mimic the optical properties of human and animal tissues are commonly used in diffuse optical imaging research to characterize instrumentation or evaluate an image reconstruction method. Although many recipes have been produced for generating solid phantoms with specified absorption and transport scattering coefficients at visible and near-infrared wavelengths, the construction methods are generally time-consuming and are unable to create complex geometries. We present a method of generating phantoms using a standard 3D printer. A simple recipe was devised which enables printed phantoms to be produced with precisely known optical properties. To illustrate the capability of the method, we describe the creation of an anatomically accurate, tissue-equivalent premature infant head optical phantom with a hollow brain space based on MRI atlas data. A diffuse optical image of the phantom is acquired when a high contrast target is inserted into the hollow space filled with an aqueous scattering solution.

Probe for evaluating the absorbing and transport scattering properties of turbid fluids using low-cost time-of-flight technology.

A probe is described that when immersed into a highly scattering fluid provides a measurement of its scattering and absorbing properties at a single optical wavelength. It uses recently available low-cost proximity sensor modules to estimate the mean flight times of photons diffusely transmitted between near-infrared sources and detectors at two different separations. The probe has been designed with a specific application for enabling the rapid and efficient production of fluids, which mimic the optical properties of biological tissues. The potential of the device is demonstrated using precalibrated solutions of intralipid, an intravenous nutrient, and absorbing dye. It is shown that a combination of time-of-flight measurements at two source­detector separations can uniquely specify the absorption coefficient and the transport scattering coefficient.

Functional imaging of the human brain using a modular, fibre-less, high-density diffuse optical tomography system.

We present the first three-dimensional, functional images of the human brain to be obtained using a fibre-less, high-density diffuse optical tomography system. Our technology consists of independent, miniaturized, silicone-encapsulated DOT modules that can be placed directly on the scalp. Four of these modules were arranged to provide up to 128, dual-wavelength measurement channels over a scalp area of approximately 60 × 65 mm2. Using a series of motor-cortex stimulation experiments, we demonstrate that this system can obtain high-quality, continuous-wave measurements at source-detector separations ranging from 14 to 55 mm in adults, in the presence of hair. We identify robust haemodynamic response functions in 5 out of 5 subjects, and present diffuse optical tomography images that depict functional haemodynamic responses that are well-localized in all three dimensions at both the individual and group levels. This prototype modular system paves the way for a new generation of wearable, wireless, high-density optical neuroimaging technologies.

Towards a wearable near infrared spectroscopic probe for monitoring concentrations of multiple chromophores in biological tissue in vivo.

The first wearable multi-wavelength technology for functional near-infrared spectroscopy has been developed, based on a custom-built 8-wavelength light emitting diode (LED) source. A lightweight fibreless probe is designed to monitor changes in the concentrations of multiple absorbers (chromophores) in biological tissue, the most dominant of which at near-infrared wavelengths are oxyhemoglobin and deoxyhemoglobin. The use of multiple wavelengths enables signals due to the less dominant chromophores to be more easily distinguished from those due to hemoglobin and thus provides more complete and accurate information about tissue oxygenation, hemodynamics, and metabolism. The spectroscopic probe employs four photodiode detectors coupled to a four-channel charge-to-digital converter which includes a charge integration amplifier and an analogue-to-digital converter (ADC). Use of two parallel charge integrators per detector enables one to accumulate charge while the other is being read out by the ADC, thus facilitating continuous operation without dead time. The detector system has a dynamic range of about 80 dB. The customized source consists of eight LED dies attached to a 2 mm × 2 mm substrate and encapsulated in UV-cured epoxy resin. Switching between dies is performed every 20 ms, synchronized to the detector integration period to within 100 ns. The spectroscopic probe has been designed to be fully compatible with simultaneous electroencephalography measurements. Results are presented from measurements on a phantom and a functional brain activation study on an adult volunteer, and the performance of the spectroscopic probe is shown to be very similar to that of a benchtop broadband spectroscopy system. The multi-wavelength capabilities and portability of this spectroscopic probe will create significant opportunities for in vivo studies in a range of clinical and life science applications.

Design and implementation of a wireless capsule suitable for autofluorescence intensity detection in biological tissues.

We report on the design, fabrication, testing, and packaging of a miniaturized system capable of detecting autofluorescence (AF) from mammalian intestinal tissue. The system comprises an application-specific integrated circuit (ASIC), light-emitting diode, optical filters, control unit, and radio transmitter. The ASIC contains a high-voltage charge pump and single-photon avalanche diode detector (SPAD). The charge pump biases the SPAD above its breakdown voltage to operate in Geiger mode. The SPAD offers a photon detection efficiency of 37% at 520 nm, which corresponds to the AF emission peak of the principle human intestinal fluorophore, flavin adenine dinucleotide. The ASIC was fabricated using a commercial triple-well high-voltage CMOS process. The complete device operates at 3 V and draws an average of 7.1 mA, enabling up to 23 h of continuous operation from two 165-mAh SR44 batteries.