Search PubMed⌕ Search

Biomedical subjects

R M Leahy

Publications and source records attributed to R M Leahy.

At least 19 recordsLinked to original sources

Model-based normalization for iterative 3D PET image reconstruction.

We describe a method for normalization in 3D PET for use with maximum a posteriori (MAP) or other iterative model-based image reconstruction methods. This approach is an extension of previous factored normalization methods in which we include separate factors for detector sensitivity, geometric response, block effects and deadtime. Since our MAP reconstruction approach already models some of the geometric factors in the forward projection, the normalization factors must be modified to account only for effects not already included in the model. We describe a maximum likelihood approach to joint estimation of the count-rate independent normalization factors, which we apply to data from a uniform cylindrical source. We then compute block-wise and block-profile deadtime correction factors using singles and coincidence data, respectively, from a multiframe cylindrical source. We have applied this method for reconstruction of data from the Concorde microPET P4 scanner. Quantitative evaluation of this method using well-counter measurements of activity in a multicompartment phantom compares favourably with normalization based directly on cylindrical source measurements.

Algorithms↗

Internet2-based 3D PET image reconstruction using a PC cluster.

We describe an approach to fast iterative reconstruction from fully three-dimensional (3D) PET data using a network of PentiumIII PCs configured as a Beowulf cluster. To facilitate the use of this system, we have developed a browser-based interface using Java. The system compresses PET data on the user's machine, sends these data over a network, and instructs the PC cluster to reconstruct the image. The cluster implements a parallelized version of our preconditioned conjugate gradient method for fully 3D MAP image reconstruction. We report on the speed-up factors using the Beowulf approach and the impacts of communication latencies in the local cluster network and the network connection between the user's machine and our PC cluster.

Algorithms↗

On MEG forward modelling using multipolar expansions.

Magnetoencephalography (MEG) is a non-invasive functional imaging modality based on the measurement of the external magnetic field produced by neural current sources within the brain. The reconstruction of the underlying sources is a severely ill-posed inverse problem typically tackled using either low-dimensional parametric source models, such as an equivalent current dipole (ECD), or high-dimensional minimum-norm imaging techniques. The inability of the ECD to properly represent non-focal sources and the over-smoothed solutions obtained by minimum-norm methods underline the need for an alternative approach. Multipole expansion methods have the advantages of the parametric approach while at the same time adequately describing sources with significant spatial extent and arbitrary activation patterns. In this paper we first present a comparative review of spherical harmonic and Cartesian multipole expansion methods that can be used in MEG. The equations are given for the general case of arbitrary conductors and realistic sensor configurations and also for the special cases of spherically symmetric conductors and radially oriented sensors. We then report the results of computer simulations used to investigate the ability of a first-order multipole model (dipole and quadrupole) to represent spatially extended sources, which are simulated by 2D and 3D clusters of elemental dipoles. The overall field of a cluster is analysed using singular value decomposition and compared to the unit fields of a multipole, centred in the middle of the cluster, using subspace correlation metrics. Our results demonstrate the superior utility of the multipolar source model over ECD models in providing source representations of extended regions of activity.

Biophysical Phenomena↗

Magnetic resonance image tissue classification using a partial volume model.

We describe a sequence of low-level operations to isolate and classify brain tissue within T1-weighted magnetic resonance images (MRI). Our method first removes nonbrain tissue using a combination of anisotropic diffusion filtering, edge detection, and mathematical morphology. We compensate for image nonuniformities due to magnetic field inhomogeneities by fitting a tricubic B-spline gain field to local estimates of the image nonuniformity spaced throughout the MRI volume. The local estimates are computed by fitting a partial volume tissue measurement model to histograms of neighborhoods about each estimate point. The measurement model uses mean tissue intensity and noise variance values computed from the global image and a multiplicative bias parameter that is estimated for each region during the histogram fit. Voxels in the intensity-normalized image are then classified into six tissue types using a maximum a posteriori classifier. This classifier combines the partial volume tissue measurement model with a Gibbs prior that models the spatial properties of the brain. We validate each stage of our algorithm on real and phantom data. Using data from the 20 normal MRI brain data sets of the Internet Brain Segmentation Repository, our method achieved average kappa indices of kappa = 0.746 +/- 0.114 for gray matter (GM) and kappa = 0.798 +/- 0.089 for white matter (WM) compared to expert labeled data. Our method achieved average kappa indices kappa = 0.893 +/- 0.041 for GM and kappa = 0.928 +/- 0.039 for WM compared to the ground truth labeling on 12 volumes from the Montreal Neurological Institute's BrainWeb phantom.

Adult↗

Qualitative and quantitative evaluation of six algorithms for correcting intensity nonuniformity effects.

The desire to correct intensity nonuniformity in magnetic resonance images has led to the proliferation of nonuniformity-correction (NUC) algorithms with different theoretical underpinnings. In order to provide end users with a rational basis for selecting a given algorithm for a specific neuroscientific application, we evaluated the performance of six NUC algorithms. We used simulated and real MRI data volumes, including six repeat scans of the same subject, in order to rank the accuracy, precision, and stability of the nonuniformity corrections. We also compared algorithms using data volumes from different subjects and different (1.5T and 3.0T) MRI scanners in order to relate differences in algorithmic performance to intersubject variability and/or differences in scanner performance. In phantom studies, the correlation of the extracted with the applied nonuniformity was highest in the transaxial (left-to-right) direction and lowest in the axial (top-to-bottom) direction. Two of the six algorithms demonstrated a high degree of stability, as measured by the iterative application of the algorithm to its corrected output. While none of the algorithms performed ideally under all circumstances, locally adaptive methods generally outperformed nonadaptive methods.

Algorithms↗

Automated graph-based analysis and correction of cortical volume topology.

The human cerebral cortex is topologically equivalent to a sheet and can be considered topologically spherical if it is closed at the brain stem. Low-level segmentation of magnetic resonance (MR) imagery typically produces cerebral volumes whose tessellations are not topologically spherical. We present a novel algorithm that analyzes and constrains the topology of a volumetric object. Graphs are formed that represent the connectivity of voxel segments in the foreground and background of the image. These graphs are analyzed and minimal corrections to the volume are made prior to tessellation. We apply the algorithm to a simple test object and to cerebral white matter masks generated by a low-level tissue identification sequence. We tessellate the resulting objects using the marching cubes algorithm and verify their topology by computing their Euler characteristics. A key benefit of the algorithm is that it localizes the change to a volume to the specific areas of its topological defects.

Algorithms↗

Paired MEG data set source localization using recursively applied and projected (RAP) MUSIC.

An important class of experiments in functional brain mapping involves collecting pairs of data corresponding to separate "Task" and "Control" conditions. The data are then analyzed to determine what activity occurs during the Task experiment but not in the Control. Here we describe a new method for processing paired magnetoencephalographic (MEG) data sets using our recursively applied and projected multiple signal classification (RAP-MUSIC) algorithm. In this method the signal subspace of the Task data is projected against the orthogonal complement of the Control data signal subspace to obtain a subspace which describes spatial activity unique to the Task. A RAP-MUSIC localization search is then performed on this projected data to localize the sources which are active in the Task but not in the Control data. In addition to dipolar sources, effective blocking of more complex sources, e.g., multiple synchronously activated dipoles or synchronously activated distributed source activity, is possible since these topographies are well-described by the Control data signal subspace. Unlike previously published methods, the proposed method is shown to be effective in situations where the time series associated with Control and Task activity possess significant cross correlation. The method also allows for straightforward determination of the estimated time series of the localized target sources. A multiepoch MEG simulation and a phantom experiment are presented to demonstrate the ability of this method to successfully identify sources and their time series in the Task data.

Algorithms↗

Resolution and noise properties of MAP reconstruction for fully 3-D PET.

We derive approximate analytical expressions for the local impulse response and covariance of images reconstructed from fully three-dimensional (3-D) positron emission tomography (PET) data using maximum a posteriori (MAP) estimation. These expressions explicitly account for the spatially variant detector response and sensitivity of a 3-D tomograph. The resulting spatially variant impulse response and covariance are computed using 3-D Fourier transforms. A truncated Gaussian distribution is used to account for the effect on the variance of the nonnegativity constraint used in MAP reconstruction. Using Monte Carlo simulations and phantom data from the microPET small animal scanner, we show that the approximations provide reasonably accurate estimates of contrast recovery and covariance of MAP reconstruction for priors with quadratic energy functions. We also describe how these analytical results can be used to achieve near-uniform contrast recovery throughout the reconstructed volume.

Algorithms↗

A sensor-weighted overlapping-sphere head model and exhaustive head model comparison for MEG.

The spherical head model has been used in magnetoencephalography (MEG) as a simple forward model for calculating the external magnetic fields resulting from neural activity. For more realistic head shapes, the boundary element method (BEM) or similar numerical methods are used, but at greatly increased computational cost. We introduce a sensor-weighted overlapping-sphere (OS) head model for rapid calculation of more realistic head shapes. The volume currents associated with primary neural activity are used to fit spherical head models for each individual MEG sensor such that the head is more realistically modelled as a set of overlapping spheres, rather than a single sphere. To assist in the evaluation of this OS model with BEM and other head models, we also introduce a novel comparison technique that is based on a generalized eigenvalue decomposition and accounts for the presence of noise in the MEG data. With this technique we can examine the worst possible errors for thousands of dipole locations in a realistic brain volume. We test the traditional single-sphere model, three-shell and single-shell BEM, and the new OS model. The results show that the OS model has accuracy similar to the BEM but is orders of magnitude faster to compute.

Brain↗

EEG source localization and imaging using multiple signal classification approaches.

Equivalent current dipoles are a powerful tool for modeling focal sources. The dipole is often sufficient to adequately represent sources of measured scalp potentials, even when the area of activation exceeds 1 cm2 of cortex. Traditional least-squares fitting techniques involve minimization of an error function with respect to the location and orientation of the dipoles. The existence of multiple local minima in this error function can result in gross errors in the computed source locations. The problem is further compounded by the requirement that the model order, i.e. the number of dipoles, be determined before error minimization can be performed. An incorrect model order can produce additional errors in the estimated source parameters. Both of these problems can be avoided using alternative search strategies based on the MUSIC (multiple signal classification) algorithm. Here the authors review the MUSIC approach and demonstrate its application to the localization of multiple current dipoles from EEG data. The authors also show that the number of detectable sources can be determined in a recursive manner from the data. Also, in contrast to least-squares, the method can find dipolar sources in the presence of additional non-dipolar sources. Finally, extensions of the MUSIC approach to allow the modeling of distributed sources are discussed.

Action Potentials↗

EEG and MEG: forward solutions for inverse methods.

A solution of the forward problem is an important component of any method for computing the spatio-temporal activity of the neural sources of magnetoencephalography (MEG) and electroencephalography (EEG) data. The forward problem involves computing the scalp potentials or external magnetic field at a finite set of sensor locations for a putative source configuration. We present a unified treatment of analytical and numerical solutions of the forward problem in a form suitable for use in inverse methods. This formulation is achieved through factorization of the lead field into the product of the moment of the elemental current dipole source with a "kernel matrix" that depends on the head geometry and source and sensor locations, and a "sensor matrix" that models sensor orientation and gradiometer effects in MEG and differential measurements in EEG. Using this formulation and a recently developed approximation formula for EEG, based on the "Berg parameters," we present novel reformulations of the basic EEG and MEG kernels that dispel the myth that EEG is inherently more complicated to calculate than MEG. We also present novel investigations of different boundary element methods (BEM's) and present evidence that improvements over currently published BEM methods can be realized using alternative error-weighting methods. Explicit expressions for the matrix kernels for MEG and EEG for spherical and realistic head geometries are included.

Electric Conductivity↗

A theoretical study of the contrast recovery and variance of MAP reconstructions from PET data.

We examine the spatial resolution and variance properties of PET images reconstructed using maximum a posteriori (MAP) or penalized-likelihood methods. Resolution is characterized by the contrast recovery coefficient (CRC) of the local impulse response. Simplified approximate expressions are derived for the local impulse response CRC's and variances for each voxel. Using these results we propose a practical scheme for selecting spatially variant smoothing parameters to optimize lesion detectability through maximization of the local CRC-to-noise ratio in the reconstructed image.

Analysis of Variance↗

A study of dipole localization accuracy for MEG and EEG using a human skull phantom.

OBJECTIVE: To investigate the accuracy of forward and inverse techniques for EEG and MEG dipole localization. DESIGN AND METHODS: A human skull phantom was constructed with brain, skull and scalp layers and realistic relative conductivities. Thirty two independent current dipoles were distributed within the 'brain' region and EEG and MEG data collected separately for each dipole. The true dipole locations and orientations and the morphology of the brain, skull and scalp layers were extracted from X-ray CT data. The location of each dipole was estimated from the EEG and MEG data using the R-MUSIC inverse method and forward models based on spherical and realistic head geometries. Additional computer simulations were performed to investigate the factors affecting localization accuracy. RESULTS: Localization errors using the relatively simpler locally fitted sphere approach are only slightly greater than those using a BEM approach. The average localization error over the 32 dipoles was 7-8 mm for EEG and 3 mm for MEG. CONCLUSION: The superior performance of MEG over EEG appears to be because the latter is more sensitive to errors in the forward model arising from simplifying assumptions concerning the conductivity of the skull, scalp and brain.

Computer Simulation↗

High-resolution 3D Bayesian image reconstruction using the microPET small-animal scanner.

A Bayesian method is described for reconstruction of high-resolution 3D images from the microPET small-animal scanner. Resolution recovery is achieved by explicitly modelling the depth dependent geometric sensitivity for each voxel in combination with an accurate detector response model that includes factors due to photon pair non-collinearity and inter-crystal scatter and penetration. To reduce storage and computational costs we use a factored matrix in which the detector response is modelled using a sinogram blurring kernel. Maximum a posteriori (MAP) images are reconstructed using this model in combination with a Poisson likelihood function and a Gibbs prior on the image. Reconstructions obtained from point source data using the accurate system model demonstrate a potential for near-isotropic FWHM resolution of approximately 1.2 mm at the center of the field of view compared with approximately 2 mm when using an analytic 3D reprojection (3DRP) method with a ramp filter. These results also show the ability of the accurate system model to compensate for resolution loss due to crystal penetration producing nearly constant radial FWHM resolution of 1 mm out to a 4 mm radius. Studies with a point source in a uniform cylinder indicate that as the resolution of the image is reduced to control noise propagation the resolution obtained using the accurate system model is superior to that obtained using 3DRP at matched background noise levels. Additional studies using pie phantoms with hot and cold cylinders of diameter 1-2.5 mm and 18FDG animal studies appear to confirm this observation.

Animals↗

Recursive MUSIC: a framework for EEG and MEG source localization.

The multiple signal classification (MUSIC) algorithm can be used to locate multiple asynchronous dipolar sources from electroencephalography (EEG) and magnetoencephalography (MEG) data. The algorithm scans a single-dipole model through a three-dimensional (3-D) head volume and computes projections onto an estimated signal subspace. To locate the sources, the user must search the head volume for multiple local peaks in the projection metric. This task is time consuming and subjective. Here, we describe an extension of this approach which we refer to as recursive MUSIC (R-MUSIC). This new procedure automatically extracts the locations of the sources through a recursive use of subspace projections. The new method is also able to locate synchronous sources through the use of a spatio-temporal independent topographies (IT) model. This model defines a source as one or more nonrotating dipoles with a single time course. Within this framework, we are able to locate fixed, rotating, and synchronous dipoles. The recursive subspace projection procedure that we introduce here uses the metric of canonical or subspace correlations as a multidimensional form of correlation analysis between the model subspace and the data subspace. By recursively computing subspace correlations, we build up a model for the sources which account for a given set of data. We demonstrate here how R-MUSIC can easily extract multiple asynchronous dipolar sources that are difficult to find using the original MUSIC scan. We then demonstrate R-MUSIC applied to the more general IT model and show results for combinations of fixed, rotating, and synchronous dipoles.

Algorithms↗

MEG-based imaging of focal neuronal current sources.

We describe a new approach to imaging neural current sources from measurements of the magnetoencephalogram (MEG) associated with sensory, motor, or cognitive brain activation. Many previous approaches to this problem have concentrated on the use of weighted minimum norm (WMN) inverse methods. While these methods ensure a unique solution, they do not introduce information specific to the MEG inverse problem, often producing overly smoothed solutions and exhibiting severe sensitivity to noise. We describe a Bayesian formulation of the inverse problem in which a Gibbs prior is constructed to reflect the sparse focal nature of neural current sources associated with evoked response data. We demonstrate the method with simulated and experimental phantom data, comparing its performance with several WMN methods.

Bayes Theorem↗

Bayesian reconstruction of PET images: methodology and performance analysis.

We describe a practical statistical methodology for the reconstruction of PET images. Our approach is based on a Bayesian formulation of the imaging problem. The data are modelled as independent Poisson random variables and the image is modelled using a Markov random field smoothing prior. We describe a sequence of calibration procedures which are performed before reconstruction: (i) calculation of accurate attenuation correction factors from re-projected Bayesian reconstructions of the transmission image; (ii) estimation of the mean of the randoms component in the data; and (iii) computation of the scatter component in the data using a Klein-Nishina-based scatter estimation method. The Bayesian estimate of the PET image is then reconstructed using a pre-conditioned conjugate gradient method. We performed a quantitation study with a multi-compartment chest phantom in a Siemens/CTI ECAT931 system. Using 40 1 min frames, we computed the ensemble mean and variance over several regions of interest from images reconstructed using the Bayesian and a standard filtered backprojection (FBP) protocol. The values for the region of interest were compared with well counter data for each compartment. These results show that the Bayesian protocol can produce substantial improvements in relative quantitation over the standard FBP protocol, particularly when short transmission scans are used. An example showing the application of the method to a clinical chest study is also given.

Algorithms↗

Error bounds for EEG and MEG dipole source localization.

General formulas are presented for computing a lower bound on localization and moment error for electroencephalographic (EEG) or magnetoencephalographic (MEG) current source dipole models with arbitrary sensor array geometry. Specific EEG and MEG formulas are presented for multiple dipoles in a head model with 4 spherical shells. Localization error bounds are presented for both EEG and MEG for several different sensor configurations. Graphical error contours are presented for 127 sensors covering the upper hemisphere, for both 37 sensors and 127 sensors covering a smaller region, and for the standard 10-20 EEG sensor arrangement. Both 1- and 2-dipole cases were examined for all possible dipole orientations and locations within a head quadrant. The results show a strong dependence on absolute dipole location and orientation. The results also show that fusion of the EEG and MEG measurements into a combined model reduces the lower bound. A Monte Carlo simulation was performed to check the tightness of the bounds for a selected case. The simple head model, the low power noise and the few strong dipoles were all selected in this study as optimistic conditions to establish possibly fundamental resolution limits for any localization effort. Results, under these favorable assumptions, show comparable resolutions between the EEG and the MEG models, but accuracy for a single dipole, in either case, appears limited to several millimeters for a single time slice. The lower bounds increase markedly with just 2 dipoles. Observations are given to support the need for full spatiotemporal modeling to improve these lower bounds. All of the simulation results presented can easily be scaled to other instances of noise power and dipole intensity.

Brain↗