Joelle E. Sarlls

Effects of image distortions originating from susceptibility variations and concomitant fields on diffusion MRI tractography results.

In this work we investigate the effects of echo planar imaging (EPI) distortions on diffusion tensor imaging (DTI) based fiber tractography results. We propose a simple experimental framework that would enable assessing the effects of EPI distortions on the accuracy and reproducibility of fiber tractography from a pilot study on a few subjects. We compare trajectories computed from two diffusion datasets collected on each subject that are identical except for the orientation of phase encode direction, either right-left (RL) or anterior-posterior (AP). We define metrics to assess potential discrepancies between RL and AP trajectories in association, commissural, and projection pathways. Results from measurements on a 3 Tesla clinical scanner indicated that the effects of EPI distortions on computed fiber trajectories are statistically significant and large in magnitude, potentially leading to erroneous inferences about brain connectivity. The correction of EPI distortion using an image-based registration approach showed a significant improvement in tract consistency and accuracy. Although obtained in the context of a DTI experiment, our findings are generally applicable to all EPI-based diffusion MRI tractography investigations, including high angular resolution (HARDI) methods. On the basis of our findings, we recommend adding an EPI distortion correction step to the diffusion MRI processing pipeline if the output is to be used for fiber tractography.

Three-dimensional analytical magnetic resonance imaging phantom in the Fourier domain.

This work presents a basic framework for constructing a 3D analytical MRI phantom in the Fourier domain. In the image domain the phantom is modeled after the work of Kak and Roberts on a 3D version of the famous Shepp‐Logan head phantom. This phantom consists of several ellipsoids of different sizes, orientations, locations, and signal intensities (or gray levels). It will be shown that the k‐space signal derived from the phantom can be analytically expressed. As a consequence, it enables one to bypass the need for interpolation in the Fourier domain when testing image‐reconstruction algorithms. More importantly, the proposed framework can serve as a benchmark for contrasting and comparing different image‐reconstruction techniques in 3D MRI with a non‐Cartesian k‐space trajectory. The proposed framework can also be adapted for 3D MRI simulation studies in which the MRI parameters of interest may be introduced to the signal intensity from the ellipsoid. Magn Reson Med, 2007. Published 2007 Wiley‐Liss, Inc.

In vivo detection of microscopic anisotropy using quadruple pulsed-field gradient (qPFG) diffusion MRI on a clinical scanner

We report our design and implementation of a quadruple pulsed-field gradient (qPFG) diffusion MRI pulse sequence on a whole-body clinical scanner and demonstrate its ability to non-invasively detect restriction-induced microscopic anisotropy in human brain tissue. The microstructural information measured using qPFG diffusion MRI in white matter complements that provided by diffusion tensor imaging (DTI) and exclusively characterizes diffusion of water trapped in microscopic compartments with unique measures of average cell geometry. We describe the effect of white matter fiber orientation on the expected MR signal and highlight the importance of incorporating such information in the axon diameter measurement using a suitable mathematical framework. Integration of qPFG diffusion-weighted images (DWI) with fiber orientations measured using high-resolution DTI allows the estimation of average axon diameters in the corpus callosum of healthy human volunteers. Maps of inter-hemispheric average axon diameters reveal an anterior-posterior variation in good topographical agreement with anatomical measurements reported in previous post-mortem studies. With further technical refinements and additional clinical validation, qPFG diffusion MRI could provide a quantitative whole-brain histological assessment of white and gray matter, enabling a wide range of neuroimaging applications for improved diagnosis of neurodegenerative pathologies, monitoring neurodevelopmental processes, and mapping brain connectivity.

Clinical feasibility of using mean apparent propagator (MAP) MRI to characterize brain tissue microstructure.

Diffusion tensor imaging (DTI) is the most widely used method for characterizing noninvasively structural and architectural features of brain tissues. However, the assumption of a Gaussian spin displacement distribution intrinsic to DTI weakens its ability to describe intricate tissue microanatomy. Consequently, the biological interpretation of microstructural parameters, such as fractional anisotropy or mean diffusivity, is often equivocal. We evaluate the clinical feasibility of assessing brain tissue microstructure with mean apparent propagator (MAP) MRI, a powerful analytical framework that efficiently measures the probability density function (PDF) of spin displacements and quantifies useful metrics of this PDF indicative of diffusion in complex microstructure (e.g., restrictions, multiple compartments). Rotation invariant and scalar parameters computed from the MAP show consistent variation across neuroanatomical brain regions and increased ability to differentiate tissues with distinct structural and architectural features compared with DTI-derived parameters. The return-to-origin probability (RTOP) appears to reflect cellularity and restrictions better than MD, while the non-Gaussianity (NG) measures diffusion heterogeneity by comprehensively quantifying the deviation between the spin displacement PDF and its Gaussian approximation. Both RTOP and NG can be decomposed in the local anatomical frame for reference determined by the orientation of the diffusion tensor and reveal additional information complementary to DTI. The propagator anisotropy (PA) shows high tissue contrast even in deep brain nuclei and cortical gray matter and is more uniform in white matter than the FA, which drops significantly in regions containing crossing fibers. Orientational profiles of the propagator computed analytically from the MAP MRI series coefficients allow separation of different fiber populations in regions of crossing white matter pathways, which in turn improves our ability to perform whole-brain fiber tractography. Reconstructions from subsampled data sets suggest that MAP MRI parameters can be computed from a relatively small number of DWIs acquired with high b-value and good signal-to-noise ratio in clinically achievable scan durations of less than 10min. The neuroanatomical consistency across healthy subjects and reproducibility in test-retest experiments of MAP MRI microstructural parameters further substantiate the robustness and clinical feasibility of this technique. The MAP MRI metrics could potentially provide more sensitive clinical biomarkers with increased pathophysiological specificity compared to microstructural measures derived using conventional diffusion MRI techniques.

Diffusion tensor and volumetric magnetic resonance measures as biomarkers of brain damage in a small animal model of HIV.

Background There are currently no widely accepted neuro-HIV small animal models. We wanted to validate the HIV-1 Transgenic rat (Tg) as an appropriate neuro-HIV model and then establish in vivo imaging biomarkers of neuropathology, within this model, using MR structural and diffusion tensor imaging (DTI). Methods Young and middle-aged Tg and control rats were imaged using MRI. A subset of middle-aged animals underwent longitudinal repeat imaging six months later. Total brain volume (TBV), ventricular volume (VV) and parenchymal volume (PV = TBV–VV) were measured. Fractional anisotropy (FA) and mean diffusivity (MD) values of the corpus callosum (CC) were calculated from DTI data. Results TBV and PV were smaller in Tg compared to control rats in young and middle-aged cohorts (p<0.0001). VV increased significantly (p = 0.005) over time in the longitudinal Tg cohort. There were lower FA (p<0.002) and higher MD (p<0.003) values in the CC of middle-aged Tg rats compared to age-matched controls. Longitudinally, MD significantly decreased over time in Tg rats (p<0.03) while it did not change significantly in the control cohort over the same period of time (p>0.05). Conclusions We detected brain volume loss in the Tg rat, probably due to astrocytic dysfunction/loss, loss of structural/axonal matrix and striatal neuronal loss as suggested by immunofluorescence. Increased MD and decreased FA in the CC probably reflect microstructural differences between the Tg and Control rats which could include increased extracellular space between white matter tracts, demyelination and axonal degeneration, among other pathologies. We believe that the Tg rat is an adequate model of neuropathology in HIV and that volumetric MR and DTI measures can be potentially used as biomarkers of disease progression.

Robust fat suppression at 3T in high-resolution diffusion-weighted single-shot echo-planar imaging of human brain.

Single‐shot echo‐planar imaging is the most common acquisition technique for whole‐brain diffusion tensor imaging (DTI) studies in vivo. Higher field MRI systems are readily available and advantageous for acquiring DTI due to increased signal. One of the practical issues for DTI with single‐shot echo‐planar imaging at high‐field is incomplete fat suppression resulting in a chemically shifted fat artifact within the brain image. Unsuppressed fat is especially detrimental in DTI because the diffusion coefficient of fat is two orders of magnitude lower than that of parenchyma, producing brighter appearing fat artifacts with greater diffusion weighting. In this work, several fat suppression techniques were tested alone and in combination with the goal of finding a method that provides robust fat suppression and can be used in high‐resolution single‐shot echo‐planar imaging DTI studies. Combination of chemical shift saturation with slice‐select gradient reversal within a dual‐spin‐echo diffusion preparation period was found to provide robust fat suppression at 3 T. Magn Reson Med, 2011.

Diffusion‐weighted radial fast spin‐echo for high‐resolution diffusion tensor imaging at 3T

There is a need for an imaging sequence that can provide high‐resolution diffusion tensor images at 3T near air–tissue interfaces. By employing a radial fast spin‐echo (FSE) collection in conjunction with magnitude filtered back‐projection reconstruction, high‐resolution diffusion‐weighted images can be produced without susceptibility artifacts. However, violation of the Carr‐Purcell‐Meiboom‐Gill (CPMG) condition of diffusion prepared magnetization is a prominent problem for FSE trains that is magnified at higher fields. The unique aspect of violating the CPMG condition in trajectories that oversample the center of k‐space and the implications for choosing the solution are examined. For collecting diffusion‐weighted radial‐FSE data at 3T we propose mixed‐CPMG phase cycling of RF refocusing pulses combined with a 300% wider refocusing than excitation slice. It is shown that this approach produces accurate diffusion values in a phantom, and can be used to collect undistorted, high‐resolution diffusion tensor images of the human brain. Magn Reson Med 60:270–276, 2008.

A system and mathematical framework to model shear flow effects in biomedical DW‐imaging and spectroscopy

The pulsed‐field gradient (PFG) MR experiment enables one to measure particle displacements, velocities, and even higher moments of complex fluid motions. In diffusion‐weighted MRI (DWI) in living tissue, where the PFG MRI experiment is used to measure diffusion, Brownian motion is assumed to dominate the displacements causing the observed signal loss. However, motions of water molecules caused by various active biological processes occurring at different length and time scales may also cause additional dephasing of magnetization and signal loss. To help understand their relative effects on the DWI signal attenuation, we used an integrated experimental and theoretical framework: a Rheo‐NMR, which served as an experimental model system to precisely prescribe a microscopic velocity distribution; and a mathematical model that relates the DW signal intensity in the Rheo‐NMR to experimental parameters that characterize the impressed velocity field. A technical innovation reported here is our use of ‘natural’ (in this case, polar) coordinates both to simplify the description the fluid motion within the Couette cell of the Rheo‐NMR, as well as to acquire and reconstruct magnitude and phase MR images obtained within it. We use this integrated model system to demonstrate how shear flows appears as pseudo‐diffusion in magnitude DW MR signals obtained using PFG spin‐echo (PGSE) NMR and MRI sequences. Our results lead us to reinterpret the possible causes of signal loss in DWI in vivo, in particular to revise and generalize the previous notion of intra‐voxel incoherent motion (IVIM) in order to describe activity driven flows that appear as pseudo‐diffusion over multiple length and time scales in living tissues. Copyright

Improvement of temporal signal-to-noise ratio of GRAPPA accelerated echo planar imaging using a FLASH based calibration scan

To demonstrate that the temporal signal‐to‐noise ratio (SNR) of generalized autocalibrating partially parallel acquisitions (GRAPPA) accelerated echo planar imaging (EPI) can be enhanced and made more spatially uniform by using a fast low angle shot (FLASH) based calibration scan.

White Matter Microstructure Alterations: A Study of Alcoholics with and without Post-Traumatic Stress Disorder

Many brain imaging studies have demonstrated reductions in gray and white matter volumes in alcoholism, with fewer investigators using diffusion tensor imaging (DTI) to examine the integrity of white matter pathways. Among various medical conditions, alcoholism and post-traumatic stress disorder (PTSD) are two comorbid diseases that have similar degenerative effects on the white matter integrity. Therefore, understanding and differentiating these effects would be very important in characterizing alcoholism and PTSD. Alcoholics are known to have neurocognitive deficits in decision-making, particularly in decisions related to emotionally-motivated behavior, while individuals with PTSD have deficits in emotional regulation and enhanced fear response. It is widely believed that these types of abnormalities in both alcoholism and PTSD are related to fronto-limbic dysfunction. In addition, previous studies have shown cortico-limbic fiber degradation through fiber tracking in alcoholism. DTI was used to measure white matter fractional anisotropy (FA), which provides information about tissue microstructure, possibly indicating white matter integrity. We quantitatively investigated the microstructure of white matter through whole brain DTI analysis in healthy volunteers (HV) and alcohol dependent subjects without PTSD (ALC) and with PTSD (ALC+PTSD). These data show significant differences in FA between alcoholics and non-alcoholic HVs, with no significant differences in FA between ALC and ALC+PTSD in any white matter structure. We performed a post-hoc region of interest analysis that allowed us to incorporate multiple covariates into the analysis and found similar results. HV had higher FA in several areas implicated in the reward circuit, emotion, and executive functioning, suggesting that there may be microstructural abnormalities in white matter pathways that contribute to neurocognitive and executive functioning deficits observed in alcoholics. Furthermore, our data do not reveal any differences between ALC and ALC+PTSD, suggesting that the effect of alcohol on white matter microstructure may be more significant than any effect caused by PTSD.