Time-resolved Diffuse Optical Tomography Research Articles

Ultrafast and Ultrahigh-Resolution Diffuse Optical Tomography for Brain Imaging with Sensitivity Equation based Noniterative Sparse Optical Reconstruction (SENSOR)

We introduce a novel image reconstruction method for time-resolved diffuse optical tomography (DOT) that yields submillimeter resolution in less than a second. This opens the door to high-resolution real-time DOT in imaging of the brain activity. We call this approach the sensitivity equation based noniterative sparse optical reconstruction (SENSOR) method. The high spatial resolution is achieved by implementing an asymptotic l0-norm operator that guarantees to obtain sparsest representation of reconstructed targets. The high computational speed is achieved by employing the nontruncated sensitivity equation based noniterative inverse formulation combined with reduced sensing matrix and parallel computing. We tested the new method with numerical and experimental data. The results demonstrate that the SENSOR algorithm can achieve 1 mm3 spatial-resolution optical tomographic imaging at depth of ∼60 mean free paths (MFPs) in 20∼30 milliseconds on an Intel Core i9 processor.

Chromophore reconstruction at depth in bilayered media: a method for quantification.

We report a method for deriving the absolute value of absorption coefficients at depth in bilayered media. The method was simplified from that of time-resolved diffuse optical tomography (TR-DOT) into one dimension to validate and set up the main parameters with the help of simulations, and to test it in an easy preclinical model. The method was applied to buried flaps as used in reconstructive surgery, and absolute chromophore concentrations in the flap and in the upper (skin and fat) layer were derived. The encouraging results obtained lay a foundation for developing more complex multidimensional models.

Real-Time Dual-Wavelength Time-Resolved Diffuse Optical Tomography System for Functional Brain Imaging Based on Probe-Hosted Silicon Photomultipliers.

Near-infrared diffuse optical tomography is a non-invasive photonics-based imaging technology suited to functional brain imaging applications. Recent developments have proved that it is possible to build a compact time-domain diffuse optical tomography system based on silicon photomultipliers (SiPM) detectors. The system presented in this paper was equipped with the same eight SiPM probe-hosted detectors, but was upgraded with six injection fibers to shine the sample at several points. Moreover, an automatic switch was included enabling a complete measurement to be performed in less than one second. Further, the system was provided with a dual-wavelength (670 and 820 ) light source to quantify the oxy- and deoxy-hemoglobin concentration evolution in the tissue. This novel system was challenged against a solid phantom experiment, and two in-vivo tests, namely arm occlusion and motor cortex brain activation. The results show that the tomographic system makes it possible to follow the evolution of brain activation over time with a 1-resolution.

Time-domain diffuse optical tomography utilizing truncated Fourier series approximation.

Diffuse optical tomography (DOT) uses near infrared light for in vivo imaging of spatially varying optical parameters in biological tissues. It is known that time-resolved measurements provide the richest information on soft tissues, among other measurement types in DOT such as steady-state and intensity-modulated measurements. Therefore, several integral-transform-based moments of the time-resolved DOT measurements have been considered to estimate spatially distributed optical parameters. However, the use of such moments can result in low-contrast images and cross-talks between the reconstructed optical parameters, limiting their accuracy. In this work, we propose to utilize a truncated Fourier series approximation in time-resolved DOT. Using this approximation, we obtained optical parameter estimates with accuracy comparable to using whole time-resolved data that uses low computational time and resources. The truncated Fourier series approximation based estimates also displayed good contrast and minimal parameter cross-talk, and the estimates further improved in accuracy when multiple Fourier frequencies were used.

Improving Localization of Deep Inclusions in Time-Resolved Diffuse Optical Tomography

Time-resolved diffuse optical tomography is a technique used to recover the optical properties of an unknown diffusive medium by solving an ill-posed inverse problem. In time-domain, reconstructions based on datatypes are used for their computational efficiency. In practice, most used datatypes are temporal windows and Fourier transform. Nevertheless, neither theoretical nor numerical studies assessing different datatypes have been clearly expressed. In this paper, we propose an overview and a new process to compute efficiently a long set of temporal windows in order to perform diffuse optical tomography. We did a theoretical comparison of these large set of temporal windows. We also did simulations in a reflectance geometry with a spherical inclusion at different depths. The results are presented in terms of inclusion localization and its absorption coefficient recovery. We show that (1) the new windows computed with the developed method improve inclusion localization for inclusions at deep layers, (2) inclusion absorption quantification is improved at all depths and, (3) in some cases these windows can be equivalent to frequency based reconstruction at GHz order.

The Direct Robin Boundary Value Parabolic System of Time-Resolved Diffuse Optical Tomography with Fluorescence

The Direct Robin Boundary Value Parabolic System of Time-Resolved Diffuse Optical Tomography with Fluorescence

Time Resolved Diffuse Optical Tomography model

Time Resolved Diffuse Optical Tomography (TRDOT) modality is presented. Images were reconstructed for four different scenarios. 64-source and 64-detector bifurcated positions were used for simulation model. Inclusion was buried in different coordinate locations. Time-dependent diffusion equation for photon-tissue interactions were used to create the forward model. Mostly used TRDOT devices have pulsed-laser source and photo-multiplier tube (PMT) photodetectors. In addition to pulsed laser source, continuous wave (CW) sources would be used for TRDOT imaging. In general usage, solid-state diode pumped pulsed-lasers and driving units constitute source module. Solid-state lasers are made of Titanium Sapphire (TiSa). These laser sources are difficult to use, modify, maintain, and they are also expensive. Instead of using expensive pulsed laser sources, cheap electronic-based pulsed-laser driving circuit will be implemented. Pseudomorphic high electron mobility transistors (pHEMTs) as switching elements will be used at both pulsed-laser and photodiode current readout sides. Hence, this work is taking its motivation from the next-generation electronic-based device instrument, creating the time dependent forward model as its focus. In this work, it was seen that selection of time intervals are important parameters to reconstruct the hidden images inside the homogeneous tissue. Inclusion was buried inside the homogeneous tissue model, and corresponding time modes have been selected to extract the hidden inclusion. In this work, time modes were analyzed for the TRDOT device. It has been realized that different time mode forward model weight functions should be used for different depth layers to reconstruct the hidden inclusion correctly. Hence, different time mode forward model weight matrix functions were generated from time 20 ps to 400 ps by 20 ps steps, and from time 2 ps to 40 ps by 2 ps steps. In the mathematical inverse problem solution algorithm, these time clusters were used to create two different weight matrixes.

Time-resolved diffuse optical tomography system using an accelerated inverse problem solver

A computationally efficient time-resolved diffuse optical tomography (TR-DOT) prototype was demonstrated using an accelerated inverse problem solver to reconstruct high quality 3D images of highly scattering media such as tissues. The inverse problem solver utilizes seven well-defined points on each experimentally recorded histogram of the distribution time-of-flight (DToF). In this work, the accuracy of the recovered optical properties, and the computational load and time of TR-DOT prototype were investigated using cylindrical turbid phantoms. These phantoms were measured using transmittance geometry under different conditions in multiple experiments to evaluate the performance of this prototype. Overall, the results of evaluation are important in the realization of a real-time and highly accurate TR-DOT system for diffuse optical imaging applications.

Chromophore decomposition in multispectral time-resolved diffuse optical tomography.

Multicomponent phantom measurements are carried out to evaluate the ability of multispectral time domain diffuse optical tomography in reflectance geometry to quantify the position and the composition of small heterogeneities at depths of 1-1.5 cm in turbid media. Time-resolved data were analyzed with the Mellin-Laplace transform. Results show good localization and correct composition gradation of objects but still a lack of absolute material composition accuracy when no a priori geometry information is known.

Multiple-view diffuse optical tomography system based on time-domain compressive measurements.

Compressive sensing is a powerful tool to efficiently acquire and reconstruct an image even in diffuse optical tomography (DOT) applications. In this work, a time-resolved DOT system based on structured light illumination, compressive detection, and multiple view acquisition has been proposed and experimentally validated on a biological tissue-mimicking phantom. The experimental scheme is based on two digital micromirror devices for illumination and detection modulation, in combination with a time-resolved single element detector. We fully validated the method and demonstrated both the imaging and tomographic capabilities of the system, providing state-of-the-art reconstruction quality.

Diffuse optical tomography to investigate the newborn brain.

Over the past 15 years, functional near-infrared spectroscopy (fNIRS) has emerged as a powerful technology for studying the developing brain. Diffuse optical tomography (DOT) is an extension of fNIRS that combines hemodynamic information from dense optical sensor arrays over a wide field of view. Using image reconstruction techniques, DOT can provide images of the hemodynamic correlates to neural function that are comparable to those produced by functional magnetic resonance imaging. This review article explains the principles of DOT, and highlights the growing literature on the use of DOT in the study of healthy development of the infant brain, and the study of novel pathophysiology in infants with brain injury. Current challenges, particularly around instrumentation and image reconstruction, will be discussed, as will the future of this growing field, with particular focus on whole-brain, time-resolved DOT.

Toward noninvasive assessment of flap viability with time-resolved diffuse optical tomography: a preclinical test on rats.

The noninvasive assessment of flap viability in autologous reconstruction surgery is still an unmet clinical need. To cope with this problem, we developed a proof-of-principle fully automatized setup for fast time-gated diffuse optical tomography exploiting Mellin-Laplace transform to obtain three-dimensional tomographic reconstructions of oxy- and deoxy-hemoglobin concentrations. We applied this method to perform preclinical tests on rats inducing total venous occlusion in the cutaneous abdominal flaps. Notwithstanding the use of just four source-detector couples, we could detect a spatially localized increase of deoxyhemoglobin following the occlusion (up to 550 μM in 54 min). Such capability to image spatio-temporal evolution of blood perfusion is a key issue for the noninvasive monitoring of flap viability.

Fast single photon avalanche photodiode-based time-resolved diffuse optical tomography scanner.

Resolution in diffuse optical tomography (DOT) is a persistent problem and is primarily limited by high degree of light scatter in biological tissue. We showed previously that the reduction in photon scatter between a source and detector pair at early time points following a laser pulse in time-resolved DOT is highly dependent on the temporal response of the instrument. To this end, we developed a new single-photon avalanche photodiode (SPAD) based time-resolved DOT scanner. This instrument uses an array of fast SPADs, a femto-second Titanium Sapphire laser and single photon counting electronics. In combination, the overall instrument temporal impulse response function width was 59 ps. In this paper, we report the design of this instrument and validate its operation in symmetrical and irregularly shaped optical phantoms of approximately small animal size. We were able to accurately reconstruct the size and position of up to 4 absorbing inclusions, with increasing image quality at earlier time windows. We attribute these results primarily to the rapid response time of our instrument. These data illustrate the potential utility of fast SPAD detectors in time-resolved DOT.

Hyperspectral time-resolved wide-field fluorescence molecular tomography based on structured light and single-pixel detection.

We present a time-resolved fluorescence diffuse optical tomography platform that is based on wide-field structured illumination, single-pixel detection, and hyperspectral acquisition. Two spatial light modulators (digital micro-mirror devices) are employed to generate independently wide-field illumination and detection patterns, coupled with a 16-channel spectrophotometer detection module to capture hyperspectral time-resolved tomographic data sets. The main system characteristics are reported, and we demonstrate the feasibility of acquiring dense 4D tomographic data sets (space, time, spectra) for time domain 3D quantitative multiplexed fluorophore concentration mapping in turbid media.

Spatial resolution in depth for time-resolved diffuse optical tomography using short source-detector separations.

Diffuse optical tomography for medical applications can require probes with small dimensions involving short source-detector separations. Even though this configuration is seen at first as a constraint due to the challenge of depth sensitivity, we show here that it can potentially be an asset for spatial resolution in depth. By comparing two fiber optic probes on a test object, we first show with simulations that short source-detector separations improve the spatial resolution down to a limit depth. We then confirm these results in an experimental study with a state-of-the-art setup involving a fast-gated single-photon avalanche diode allowing maximum depth sensitivity. We conclude that short source-detector separations are an option to consider for the design of probes so as to improve image quality for diffuse optical tomography in reflectance.

Optical Property of Indocyanine Green in a Tissue Model

The fluorescence temporal profile has been studied at the symmetrical point of the target in tissue phantom by a time-resolved fluorescence diffuse optical tomography method. Indocyanine green served as the fluorescence target. The results showed that the geometrical symmetry of the fluorescence peak intensity ratio was broken due to target position. By using this parameter, an unknown target location could be identified for fluorescence targeting and further reconstruction of the fluorescence image in a tissue model.

A fast SPAD-based small animal imager for early-photon diffuse optical tomography.

Photon scatter is the dominant light transport process in biological tissue and is well understood to degrade imaging performance in near-infrared diffuse optical tomography. Measurement of photons arriving at early times following a short laser pulse is considered to be an effective method to improve this limitation, i.e. by systematically selecting photons that have experienced fewer scattering events. Previously, we tested the performance of single photon avalanche photodiode (SPAD) in measurement of early transmitted photons through diffusive media and showed that it outperformed photo-multiplier tube (PMT) systems in similar configurations, principally due to its faster temporal response. In this paper, we extended this work and developed a fast SPAD-based time-resolved diffuse optical tomography system. As a first validation of the instrument, we scanned an optical phantom with multiple absorbing inclusions and measured full time-resolved data at 3240 scan points per axial slice. We performed image reconstruction with very early-arriving photon data and showed significant improvements compared to time-integrated data. Extension of this work to mice in vivo and measurement of time-resolved fluorescence data is the subject of ongoing research.

Time-resolved diffuse optical tomography using fast-gated single-photon avalanche diodes

We present the first experimental results of reflectance Diffuse Optical Tomography (DOT) performed with a fast-gated single-photon avalanche diode (SPAD) coupled to a time-correlated single-photon counting system. The Mellin-Laplace transform was employed to process time-resolved data. We compare the performances of the SPAD operated in the gated mode vs. the non-gated mode for the detection and localization of an absorbing inclusion deeply embedded in a turbid medium for 5 and 15 mm interfiber distances. We demonstrate that, for a given acquisition time, the gated mode enables the detection and better localization of deeper absorbing inclusions than the non-gated mode. These results obtained on phantoms demonstrate the efficacy of time-resolved DOT at small interfiber distances. By achieving depth sensitivity with limited acquisition times, the gated mode increases the relevance of reflectance DOT at small interfiber distance for clinical applications.

S8-3. Attempts to selectively and quantitatively measure cerebral hemoglobin with TRS

Near-infrared spectroscopy (NIRS), which was originally designed for clinical monitoring of tissue oxygenation, has been developing into a useful tool for neuroimaging studies, whereas the central issue of NIRS, difficulty in selective and quantitative measurement of cerebral hemoglobin (Hb), remains to be solved. In continuous wave measurements, multi-distance probe arrangement and mathematical approaches, such as principal component analysis (PCA) and independent component analysis (ICA), are effective for selective detection of cerebral Hb changes, but are insufficient for quantitative measurements. By using time-resolved spectroscopy (TRS), we have been developing some approaches to these issues: (1) the method with analytical solutions of the diffusion equation, (2) the method with spatially resolved and time-resolved reflectances, (3) time-segmented analysis of time-resolved reflectances and (4) diffuse optical tomography (DOT). Among them, DOT, which allows 3-D quantitative imaging of optical properties, is thought to be the most promising for solving the central issue. However, the image quality of DOT is still low, because the inverse problems are usually nonlinear, ill-posed, and underdetermined due to the diffusive nature of the photon migration. In this symposium, I first summarize our approaches, and then describe the current status and future prospects of DOT.

The effect of temporal impulse response on experimental reduction of photon scatter in time-resolved diffuse optical tomography

New fast detector technology has driven significant renewed interest in time-resolved measurement of early photons in improving imaging resolution in diffuse optical tomography and fluorescence mediated tomography in recent years. In practice, selection of early photons results in significantly narrower instrument photon density sensitivity functions (PDSFs) than the continuous wave case, resulting in a better conditioned reconstruction problem. In this work, we studied the quantitative impact of the instrument temporal impulse response function (TIRF) on experimental PDSFs in tissue mimicking optical phantoms. We used a multimode fiber dispersion method to vary the system TIRF over a range of representative literature values. Substantial disagreement in PDSF width-–by up to 40%–-was observed between experimental measurements and Monte Carlo (MC) models of photon propagation over the range of TIRFs studied. On average, PDSFs were broadened by about 0.3 mm at the center plane of the 2 cm wide imaging chamber per 100 ps of the instrument TIRF at early times. Further, this broadening was comparable on both the source and detector sides. Results were confirmed by convolution of instrument TIRFs with MC simulations. These data also underscore the importance of correcting imaging PDSFs for the instrument TIRF when performing tomographic image reconstruction to ensure accurate data–model agreement.