Huijuan Zhao

Maps of optical differential pathlength factor of human adult forehead, somatosensory motor and occipital regions at multi-wavelengths in NIR

The optical differential pathlength factor (DPF) is an important parameter for physiological measurement using near infrared spectroscopy, but for the human adult head it has been available only for the forehead. Here we report measured DPF results for the forehead, somatosensory motor and occipital regions from measurements on 11 adult volunteers using a time-resolved optical imaging system. The optode separation was about 30 mm and the wavelengths used were 759 nm, 799 nm and 834 nm. Measured DPFs were 7.25 for the central forehead and 6.25 for the temple region at 799 nm. For the central somatosensory and occipital areas (10 mm above the inion), DPFs at 799 nm are 7.5 and 8.75, respectively. Less than 10% decreases of DPF for all these regions were observed when the wavelength increased from 759 nm to 834 nm. To compare these DPF maps with the anatomical structure of the head, a Monte Carlo simulation was carried out to calculate DPF for these regions by using a two-layered semi-infinite model and assuming the thickness of the upper layer to be the sum of the thicknesses of scalp and skull, which was measured from MRI images of a subjects head. The DPF data will be useful for quantitative monitoring of the haemodynamic changes occurring in adult heads.

Improvement of image quality in diffuse optical tomography by use of full time-resolved data

In the field of diffuse optical tomography (DOT), it is widely accepted that time-resolved (TR) measurement can provide the richest information on photon migration in a turbid medium, such as biological tissue. However, the currently available image reconstruction algorithms for TR DOT are based mostly on the cw component or some featured data types of original temporal profiles, which are related to the solution of a time-independent diffusion equation. Although this methodology can greatly simplify the reconstruction process, it suffers from low spatial resolution and poor quantitativeness owing to the limitation of effectively applicable data types. To improve image quality, it has been argued that exploiting the full TR data is essential. We propose implementation of a DOT algorithm by using full TR data and furthermore a variant algorithm with time slices of TR data to alleviate the computational complexity and enhance noise robustness. Compared with those algorithms where the featured data types are used, our evaluations on the spatial resolution and quantitativeness show that a significant improvement in imaging quality can be achieved when full TR data are used, which convinces the DOT community of the potential advantage of the TR domain over cw and frequency domains.

A linear, featured-data scheme for image reconstruction in time-domain fluorescence molecular tomography

Fluorescence diffuse optical tomography (DOT) has attracted many attentions from the community of biomedical imaging, since it provides effective enhancement in imaging contrast. This modality is now rapidly evolving as a potential means of monitoring molecular events in small living organisms with help of molecule-specific contrast agents, referred to as fluorescence molecular tomography (FMT). FMT could greatly promote pathogenesis research, drug development, and therapeutic intervention. Although FMT in steady-state and frequency-domain modes have been heavily investigated, the extension to time-domain scheme is imminent for its several unique advantages over the others. By extending the previously developed generalized pulse spectrum technique for time-domain DOT, we propose a linear, featured-data image reconstruction algorithm for time-domain FMT that can simultaneously reconstruct both fluorescent yield and lifetime images of multiple fluorophores, and validate the methodology with simulated data.

Time-resolved diffuse optical tomographic imaging for the provision of both anatomical and functional information about biological tissue

We present in vivo images of near-infrared (NIR) diffuse optical tomography (DOT) of human lower legs and forearm to validate the dual functions of a time-resolved (TR) NIR DOT in clinical diagnosis, i.e., to provide anatomical and functional information simultaneously. The NIR DOT system is composed of time-correlated single-photon-counting channels, and the image reconstruction algorithm is based on the modified generalized pulsed spectral technique, which effectively incorporates the TR data with reasonable computation time. The reconstructed scattering images of both the lower legs and the forearm revealed their anatomies, in which the bones were clearly distinguished from the muscles. In the absorption images, some of the blood vessels were observable. In the functional imaging, a subject was requested to do handgripping exercise to stimulate physiological changes in the forearm tissue. The images of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentration changes in the forearm were obtained from the differential images of the absorption at three wavelengths between the exercise and the rest states, which were reconstructed with a differential imaging scheme. These images showed increases in both blood volume and oxyhemoglobin concentration in the arteries and simultaneously showed hypoxia in the corresponding muscles. All the results have demonstrated the capability of TR NIR DOT by reconstruction of the absolute images of the scattering and the absorption with a high spatial resolution that finally provided both the anatomical and functional information inside bulky biological tissues.

Time-resolved diffuse optical tomography and its application to in vitro and in vivo imaging

This work reviews our research during the past several years on time-resolved (TR) near-infrared diffuse optical tomography (DOT). Following an introduction of the measuring modes, two proposed schemes of image reconstruction in TR-DOT are described: one utilizes the full TR data, and the other, referred to as the modified generalized pulse spectrum technique (GPST), uses the featured data extracted from the TR measurement. The performances of the two algorithms in quantitativeness and spatial resolution are comparatively investigated with 2-D simulated data. TR-DOT images are then presented for phantom experiments, which are obtained by using a 16-channel time-correlated single photon counting system, and the factors affecting the quantification of the reconstruction are discussed. Finally, in vitro and in vivo imaging examples are illustrated for validating the capibility of TR-DOT to provide not only the anatomical but also the physiological information of the objects.

A self-normalized, full time-resolved method for fluorescence diffuse optical tomography

A full time-resolved scheme that has been previously applied in diffuse optical tomography is extended to time-domain fluorescence diffuse optical tomography regime, based on a finite-element-finite-time-difference photon diffusion modeling and a Newton-Raphson inversion framework. The merits of using full time-resolved data are twofold: it helps evaluate the intrinsic performance of time-domain mode for improvement of image quality and set up a valuable reference to the assessment of computationally efficient featured-data-based algorithms, and provides a self-normalized implementation to preclude the necessity of the scaling-factor calibration and spectroscopic-feature assessments of the system as well as to overcome the adversity of system instability. We validate the proposed methodology using simulated data, and evaluate its performances of simultaneous recovery of the fluorescent yield and lifetime as well as its superiority to the featured-data one in the fidelity of image reconstruction.

Simultaneous fluorescence yield and lifetime tomography from time-resolved transmittances of small-animal-sized phantom

There has been recently a considerable interest in simultaneously reconstructing yield and lifetime distributions of fluorescent imaging agents inside a bulky tissue, since combined monitoring of these two parameters provides a potential means of in vivo interrogating quantitative and environmental information of specific molecules, as well as accessing interactions among them. It is widely accepted that an advantageous way of accomplishing the task in the context of small-animal imaging is to use a time-domain (TD) modality. In this paper, we present a full three-dimensional, featured-data algorithm for TD diffuse fluorescence tomography, which inverts the Laplace-transformed TD coupled photon diffusion equations and employs a pair of real-domain transform-factors to effectively separate the fluorescent yield and lifetime parameters. By use of a specifically designed 16x16 channel time-correlated single photon counting system and a normalized Born formulation for the inversion, the proposed scheme in a transmission mode is experimentally validated to achieve simultaneous reconstruction of the fluorescent yield and lifetime distributions with reasonable accuracy.

Three-dimensional scheme for time-domain fluorescence molecular tomography based on Laplace transforms with noise-robust factors.

As a visualizing and quantitative method, Fluorescence Molecular Tomography (FMT) has many potential applications in biomedical field and its three-dimensional (3D) implementation is needed in both theory and practice. In this paper, we propose a 3D scheme for time-domain FMT within the normalized Born-ratio formulation. A finite element method solution to the Laplace transformed time-domain coupled diffusion equations is employed as the forward model, and the resultant linear inversions at two distinct transform-factors are solved with an algebraic reconstruction technique to separate fluorescent yield and lifetime images. The algorithm is validated using simulated data for 3D cylinder phantoms, and the spatial resolution and quantitativeness of the reconstruction assessed. We demonstrate that the proposed approach can accurately retrieve the positions and shapes of the targets with high spatial resolution and quantitative accuracy, and tolerate a signal-to-noise ratio down to 25dB by appropriately choosing the transform factors.

Semi-three-dimensional algorithm for time-resolved diffuse optical tomography by use of the generalized pulse spectrum technique

Although a foil three-dimensional (3-D) reconstruction with both 3-D forward and inverse models provide, the optimal solution for diffuse optical tomography (DOT), because of the 3-D nature of photon diffusion in tissue, it is computationally costly for both memory requirement and execution time in a conventional computing environment. Thus in practice there is motivation to develop an image reconstruction algorithm with dimensional reduction based on some modeling approximations. Here we have implemented a semi-3-D modified generalized pulse spectrum technique for time-resolved DOT, where a two-dimensional (2-D) distribution of optical properties is approximately assumed, while we retain 3-D distribution of photon migration in tissue. We have validated the proposed algorithm by reconstructing 3-D structural test objects from both numerically simulated and experimental date. We demonstrate our algorithm by comparing it with the calibrated 2-D reconstruction that is in widespread use as a shortcut to 3-D imaging and proving that the semi-3-D algorithm outperforms the calibrated 2-D algorithm.

Imaging of in vitro chicken leg using time-resolved near-infrared optical tomography

Near-infrared optical imaging gains much attention because of its noninvasiveness and deep penetration depths into tissue. Here, we report near-infrared optical tomographic imaging of an in vitro chicken leg from time-resolved measurements. The in vitro chicken leg, dipped in a cylindrical container filled with diluted Intralipid-10% solution, was imaged with a multichannel time-resolved imaging system. A two-dimensional reconstruction algorithm based on a modified generalized pulse spectrum technique has been developed to reconstruct the images of both the absorption and reduced scattering coefficients simultaneously and quickly. The results demonstrate that a simultaneous reconstruction of absorption and reduced scattering coefficients from time-resolved measurement has a potential to reveal the changes in the optical properties associated with not only the physiological information but also the anatomical structure of the organ.