Enhanced diffuse optical tomographic reconstruction using concurrent ultrasound information.

Multimodal imaging is an active branch of research as it has the potential to improve common medical imaging techniques. Diffuse optical tomography (DOT) is an example of a low resolution, functional imaging modality that typically has very low resolution due to the ill-posedness of its underlying inverse problem. Combining the functional information of DOT with a high resolution structural imaging modality has been studied widely. In particular, the combination of DOT with ultrasound (US) could serve as a useful tool for clinicians for the formulation of accurate diagnosis of breast lesions. In this paper, we propose a novel method for US-guided DOT reconstruction using a portable time-domain measurement system. B-mode US imaging is used to retrieve morphological information on the probed tissues by means of a semi-automatical segmentation procedure based on active contour fitting. A two-dimensional to three-dimensional extrapolation procedure, based on the concept of distance transform, is then applied to generate a three-dimensional edge-weighting prior for the regularization of DOT. The reconstruction procedure has been tested on experimental data obtained on specifically designed dual-modality silicon phantoms. Results show a substantial quantification improvement upon the application of the implemented technique. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

Heterodyne frequency-domain multispectral diffuse optical tomography of breast cancer in the parallel-plane transmission geometry.

PURPOSE: The authors introduce a state-of-the-art all-optical clinical diffuse optical tomography (DOT) imaging instrument which collects spatially dense, multispectral, frequency-domain breast data in the parallel-plate geometry. METHODS: The instrument utilizes a CCD-based heterodyne detection scheme that permits massively parallel detection of diffuse photon density wave amplitude and phase for a large number of source-detector pairs (10(6)). The stand-alone clinical DOT instrument thus offers high spatial resolution with reduced crosstalk between absorption and scattering. Other novel features include a fringe profilometry system for breast boundary segmentation, real-time data normalization, and a patient bed design which permits both axial and sagittal breast measurements. RESULTS: The authors validated the instrument using tissue simulating phantoms with two different chromophore-containing targets and one scattering target. The authors also demonstrated the instrument in a case study breast cancer patient; the reconstructed 3D image of endogenous chromophores and scattering gave tumor localization in agreement with MRI. CONCLUSIONS: Imaging with a novel parallel-plate DOT breast imager that employs highly parallel, high-resolution CCD detection in the frequency-domain was demonstrated.

Rapid processing of PET list-mode data for efficient uncertainty estimation and data analysis.

In this technical note we propose a rapid and scalable software solution for the processing of PET list-mode data, which allows the efficient integration of list mode data processing into the workflow of image reconstruction and analysis. All processing is performed on the graphics processing unit (GPU), making use of streamed and concurrent kernel execution together with data transfers between disk and CPU memory as well as CPU and GPU memory. This approach leads to fast generation of multiple bootstrap realisations, and when combined with fast image reconstruction and analysis, it enables assessment of uncertainties of any image statistic and of any component of the image generation process (e.g. random correction, image processing) within reasonable time frames (e.g. within five minutes per realisation). This is of particular value when handling complex chains of image generation and processing. The software outputs the following: (1) estimate of expected random event data for noise reduction; (2) dynamic prompt and random sinograms of span-1 and span-11 and (3) variance estimates based on multiple bootstrap realisations of (1) and (2) assuming reasonable count levels for acceptable accuracy. In addition, the software produces statistics and visualisations for immediate quality control and crude motion detection, such as: (1) count rate curves; (2) centre of mass plots of the radiodistribution for motion detection; (3) video of dynamic projection views for fast visual list-mode skimming and inspection; (4) full normalisation factor sinograms. To demonstrate the software, we present an example of the above processing for fast uncertainty estimation of regional SUVR (standard uptake value ratio) calculation for a single PET scan of (18)F-florbetapir using the Siemens Biograph mMR scanner.

3D level set reconstruction of model and experimental data in Diffuse Optical Tomography.

The level set technique is an implicit shape-based image reconstruction method that allows the recovery of the location, size and shape of objects of distinct contrast with well-defined boundaries embedded in a medium of homogeneous or moderately varying background parameters. In the case of diffuse optical tomography, level sets can be employed to simultaneously recover inclusions that differ in their absorption or scattering parameters from the background medium. This paper applies the level set method to the three-dimensional reconstruction of objects from simulated model data and from experimental frequency-domain data of light transmission obtained from a cylindrical phantom with tissue-like parameters. The shape and contrast of two inclusions, differing in absorption and diffusion parameters from the background, respectively, are reconstructed simultaneously. We compare the performance of level set recons uction with results from an image-based method using a Gauss-Newton iterative approach, and show that the level set technique can improve the detection and localisation of small, high-contrast targets.

Estimating chromophore distributions from multiwavelength photoacoustic images.

Biomedical photoacoustic tomography (PAT) can provide qualitative images of biomedical soft tissue with high spatial resolution. However, whether it is possible to give accurate quantitative estimates of the spatially varying concentrations of the sources of photoacoustic contrast-endogenous or exogenous chromophores-remains an open question. Even if the chromophores' absorption spectra are known, the problem is nonlinear and ill-posed. We describe a framework for obtaining such quantitative estimates. When the optical scattering distribution is known, adjoint and gradient-based optimization techniques can be used to recover the concentration distributions of the individual chromophores that contribute to the overall tissue absorption. When the scattering distribution is unknown, prior knowledge of the wavelength dependence of the scattering is shown to be sufficient to overcome the absorption-scattering nonuniqueness and allow both distributions of chromophore concentrations and scattering to be recovered from multiwavelength photoacoustic images.

k-space propagation models for acoustically heterogeneous media: application to biomedical photoacoustics.

Biomedical applications of photoacoustics, in particular photoacoustic tomography, require efficient models of photoacoustic propagation that can incorporate realistic properties of soft tissue, such as acoustic inhomogeneities both for purposes of simulation and for use in model-based image reconstruction methods. k-space methods are well suited to modeling high-frequency acoustics applications as they require fewer mesh points per wavelength than conventional finite element and finite difference models, and larger time steps can be taken without a loss of stability or accuracy. They are also straightforward to encode numerically, making them appealing as a general tool. The rationale behind k-space methods and the k-space approach to the numerical modeling of photoacoustic waves in fluids are covered in this paper. Three existing k-space models are applied to photoacoustics and demonstrated with examples: an exact model for homogeneous media, a second-order model that can take into account heterogeneous media, and a first-order model that can incorporate absorbing boundary conditions.

Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain.

Optical methods provide a means of monitoring cerebral oxygenation in newborn infants at risk of brain injury. A 32-channel optical imaging system has been developed with the aim of reconstructing three-dimensional images of regional blood volume and oxygenation. Full image data sets were acquired from 14 out of 24 infants studied; successful images have been reconstructed in 8 of these infants. Regional variations in cerebral blood volume and tissue oxygen saturation are present in healthy preterm infants. In an infant with a large unilateral intraventricular haemorrhage, a corresponding region of low oxygen saturation was detected. These results suggest that optical tomography may provide an appropriate technique for investigating regional cerebral haemodynamics and oxygenation at the cotside.

Reconstructing absorption and diffusion shape profiles in optical tomography by a level set technique.

A shape reconstruction algorithm for optical tomography is introduced that uses a level-set formulation for the shapes. Evolution laws based on gradient directions for a cost functional are derived for two different level-set functions, one describing the absorption and one the diffusion parameter, as well as for the parameter values inside these shapes. Numerical experiments are presented in 2D that show that the new method is able to simultaneously recover shapes and contrast values of absorbing and scattering objects embedded in a moderately heterogeneous background medium from simulated noisy data.

Three-dimensional whole-head optical tomography of passive motor evoked responses in the neonate.

Optical tomography has been used to reconstruct three-dimensional images of the entire neonatal head during motor evoked responses. Data were successfully acquired during passive movement of each arm on four out of six infants examined, from which eight sets of bilateral images of hemodynamic parameters were reconstructed. Six out of the eight images showed the largest change in total hemoglobin in the region of the contralateral motor cortex. The mean distance between the peak response in the image and the estimated position of the contralateral motor cortex was 10.8 mm. These results suggest that optical tomography may provide an appropriate technique for non-invasive cot-side imaging of brain function.

Approximation errors and model reduction in optical tomography.

Model reduction is often required in optical diffusion tomography (ODT), typically due to limited available computation time or computer memory. In practice, this often means that we are bound to use sparse meshes in the model for the forward problem. Conversely, if we are given more and more accurate measurements, we have to employ increasingly accurate forward problem solvers in order to exploit the information in the measurements. In this paper we apply the approximation error theory to ODT. We show that if the approximation errors are estimated and employed, it is possible to use mesh densities that would be unacceptable with a conventional measurement model.

Recent advances in diffuse optical imaging.

We review the current state-of-the-art of diffuse optical imaging, which is an emerging technique for functional imaging of biological tissue. It involves generating images using measurements of visible or near-infrared light scattered across large (greater than several centimetres) thicknesses of tissue. We discuss recent advances in experimental methods and instrumentation, and examine new theoretical techniques applied to modelling and image reconstruction. We review recent work on in vivo applications including imaging the breast and brain, and examine future challenges.

A method for generating patient-specific finite element meshes for head modelling.

Finite element modelling of fields within the body, whether electrical or optical, requires knowledge of the geometry of the object being examined. It can be clinically impractical to obtain accurate surface information for individual patients, although a limited set of measurements such as the locations of sensors attached to the body, can be acquired more readily. In this paper, we describe how a generic surface taken from an adult head is warped to fit points measured on a neonatal head surface to provide a new, individual surface from which a finite element mesh was generated. Simulations show that data generated from this mesh and from the original neonatal head surface are similar to within experimental errors. However, data generated from a mesh of the best fit sphere were significantly different from data generated from the original neonatal head surface.

Detection and modeling of non-Gaussian apparent diffusion coefficient profiles in human brain data.

This work details the observation of non-Gaussian apparent diffusion coefficient (ADC) profiles in multi-direction, diffusion-weighted MR data acquired with easily achievable imaging parameters (b approximately 1000 s/mm(2)). A technique is described for modeling the profile of the ADC over the sphere, which can capture non-Gaussian effects that can occur at, for example, intersections of different tissue types or white matter fiber tracts. When these effects are significant, the common diffusion tensor model is inappropriate, since it is based on the assumption of a simple underlying diffusion process, which can be described by a Gaussian probability density function. A sequence of models of increasing complexity is obtained by truncating the spherical harmonic (SH) expansion of the ADC measurements at several orders. Further, a method is described for selection of the most appropriate of these models, in order to describe the data adequately but without overfitting. The combined procedure is used to classify the profile at each voxel as isotropic, anisotropic Gaussian, or non-Gaussian, each with reference to the underlying probability density function of displacement of water molecules. We use it to show that non-Gaussian profiles arise consistently in various regions of the human brain where complex tissue structure is known to exist, and can be observed in data typical of clinical scanners. The performance of the procedure developed is characterized using synthetic data in order to demonstrate that the observed effects are genuine. This characterization validates the use of our method as an indicator of pathology that affects tissue structure, which will tend to reduce the complexity of the selected model.

Quantification of spinal cord atrophy from magnetic resonance images via a B-spline active surface model.

A method is presented that aims at segmenting and measuring the surface of the spinal cord from MR images in order to detect and quantify atrophy. A semiautomatic segmentation with very little intervention from an operator is proposed. It is based on the optimization of a B-spline active surface. The method allows for the computation of orthogonal cross-sections at any level along the cord, from which measurements are derived, such as cross-sectional area or curvature. An evaluation of the accuracy and reproducibility of the method is presented.

Time resolved optical tomography of the human forearm.

A 32-channel time-resolved optical imaging instrument has been developed principally to study functional parameters of the new-born infant brain. As a prelude to studies on infants, the device and image reconstruction methodology have been evaluated on the adult human forearm. Cross-sectional images were generated using time-resolved measurements of transmitted light at two wavelengths. All data were acquired using a fully automated computer-controlled protocol. Images representing the internal scattering and absorbing properties of the arm are presented, as well as images that reveal physiological changes during a simple finger flexion exercise. The results presented in this paper represent the first simultaneous tomographic reconstruction of the internal scattering and absorbing properties of a clinical subject using purely temporal data, with additional co-registered difference images showing repeatable absorption changes at two wavelengths in response to exercise.

Three-dimensional time-resolved optical tomography of a conical breast phantom.

A 32-channel time-resolved imaging device for medical optical tomography has been employed to evaluate a scheme for imaging the human female breast. The fully automated instrument and the reconstruction procedure have been tested on a conical phantom with tissue-equivalent optical properties. The imaging protocol has been designed to obviate compression of the breast and the need for coupling fluids. Images are generated from experimental data with an iterative reconstruction algorithm that employs a three-dimensional (3D) finite-element diffusion-based forward model. Embedded regions with twice the background optical properties are revealed in separate 3D absorption and scattering images of the phantom. The implications for 3D time-resolved optical tomography of the breast are discussed.

Simultaneous reconstruction of internal tissue region boundaries and coefficients in optical diffusion tomography.

In this paper we propose a new numerical method to the inverse problem in optical diffusion tomography. We consider the reconstruction of the diffusion and absorption coefficients (kappa, mu(a)) within a domain omega which is known to consist of a set of disjoint regions of distinct tissue types. The assumption is that the regions of different tissues are bounded by smooth boundary curves and have constant absorption and diffusion coefficients. The goal in the proposed method is to reconstruct simultaneously the boundaries of the tissue regions together with the absorption and diffusion coefficients within these regions. The solution of the problem is based on the finite element method and subdivision of the elements. The performance of the proposed method is evaluated by simulations in which the optical parameters (kappa, mu(a)) are relevant in medical applications of optical tomography. It is shown that the proposed method is able to recover both the boundaries and the coefficients with good accuracy.

The finite element model for the propagation of light in scattering media: a direct method for domains with nonscattering regions.

We present a method for handling nonscattering regions within diffusing domains. The method develops from an iterative radiosity-diffusion approach using Green's functions that was computationally slow. Here we present an improved implementation using a finite element method (FEM) that is direct. The fundamental idea is to introduce extra equations into the standard diffusion FEM to represent nondiffusive light propagation across a nonscattering region. By appropriate mesh node ordering the computational time is not much greater than for diffusion alone. We compare results from this method with those from a discrete ordinate transport code, and with Monte Carlo calculations. The agreement is very good, and, in addition, our scheme allows us to easily model time-dependent and frequency domain problems.

Multiple-slice imaging of a tissue-equivalent phantom by use of time-resolved optical tomography.

Following several years of development the construction of a multichannel time-resolved imaging device for medical optical tomography has been completed. Images are reconstructed from time-resolved measurements by use of a scheme that employs a finite-element diffusion-based forward model and an iterative reconstruction solver. Prior to testing on clinical subjects the fully automated instrument and the reconstruction software are evaluated with tissue-equivalent phantoms. We describe our first attempt to generate multiple-slice images of a phantom without uniform properties along the axial direction, while still using a computationally fast two-dimensional reconstruction algorithm. The image quality is improved by the employment of an approximate correction method that uses scaling factors derived from the ratios of finite-element forward simulations in two and three spatial dimensions. The 32-channel system was employed to generate maps of the internal scattering and the absorption properties at 14 different transverse planes across the phantom. The images clearly reveal the locations of small inhomogeneous regions embedded within the phantom. These results were obtained by use of purely temporal data and without resource to reference measurements.

Optical tomographic reconstruction in a complex head model using a priori region boundary information.

In this paper we investigate the application of anatomical prior information to image reconstruction in optical tomography. We propose a two-stage reconstruction scheme. The first stage is a reconstruction into a low-dimensional region basis, obtained by segmentation of an image obtained by an independent imaging modality, into areas of distinct tissue types. The reconstruction into this basis recovers global averages of the optical tissue parameters of each region. The recovered distribution of region values provides the starting point for the second stage of the reconstruction into the spatially resolved final image basis. This second step recovers localized perturbations within the regions. The benefit of this method is the improved stability and faster convergence of the imaging process compared with a direct reconstruction into a spatially resolved basis. This is particularly important for the simultaneous reconstruction of absorption and scattering images, where ambiguities between the two parameters and the resulting problems of crosstalk require a good initial parameter distribution to ensure convergence of the reconstruction. We use a segmented brain model obtained from a magnetic resonance image as a test case to compare the performance of the two-stage reconstruction and the direct reconstruction from a flat prior, and show that the former achieves superior results in the recovery of localized absorption and scattering hot spots embedded in the background tissue.