A novel framework for in-vivo diffusion tensor distribution MRI of the human brain.

Neural tissue microstructure plays an important role in developmental, physiological and pathophysiological processes. Diffusion tensor distribution (DTD) MRI helps probe subvoxel heterogeneity by describing water diffusion within a voxel using an ensemble of non-exchanging compartments characterized by a probability density function of diffusion tensors. In this study, we provide a new framework for acquiring multiple diffusion encoding (MDE) images and estimating DTD from them in the human brain in vivo. We interfused pulsed field gradients (iPFG) in a single spin echo to generate arbitrary b-tensors of rank one, two, or three without introducing concomitant gradient artifacts. Employing well-defined diffusion encoding parameters we show that iPFG retains salient features of a traditional multiple-PFG (mPFG/MDE) sequence while reducing the echo time and coherence pathway artifacts thereby extending its applications beyond DTD MRI. Our DTD is a maximum entropy tensor-variate normal distribution whose tensor random variables are constrained to be positive definite to ensure their physicality. In each voxel, the second-order mean and fourth-order covariance tensors of the DTD are estimated using a Monte Carlo method that synthesizes micro-diffusion tensors with corresponding size, shape, and orientation distributions to best fit the measured MDE images. From these tensors we obtain the spectrum of diffusion tensor ellipsoid sizes and shapes, and the microscopic orientation distribution function (µODF) and microscopic fractional anisotropy (µFA) that disentangle the underlying heterogeneity within a voxel. Using the DTD-derived µODF, we introduce a new method to perform fiber tractography capable of resolving complex fiber configurations. The results revealed microscopic anisotropy in various gray and white matter regions and skewed MD distributions in cerebellar gray matter not observed previously. DTD MRI tractography captured complex white matter fiber organization consistent with known anatomy. DTD MRI also resolved some degeneracies associated with diffusion tensor imaging (DTI) and elucidated the source of diffusion heterogeneity which may help improve the diagnosis of various neurological diseases and disorders.

Evaluating effects of sex and age on white matter microstructural alterations in alcohol use disorder: A diffusion tensor imaging study.

BACKGROUND: Alterations in white matter microstructure associated with chronic alcohol use have been demonstrated in previous diffusion tensor imaging (DTI) research. However, there is conflicting evidence as to whether such differences are influenced by an individual's biological sex. The purpose of the present study was to investigate the prevalence of sex differences in the white matter microstructure of the brains of individuals with alcohol use disorder (AUD) and healthy controls. METHODS: One hundred participants with AUD (38 female, aged 21 to 68) participating in the National Institute on Alcohol Abuse and Alcoholism's inpatient treatment program and 98 healthy control participants (52 female) underwent a diffusion-weighted scan. Images collected were processed for each subject individually, and voxelwise, tract-based spatial statistics analysis was conducted to test for differences in the DTI measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: A 2-way, between-subjects ANCOVA that tested for differences by group and sex revealed widespread differences between AUD and control subjects, but no interaction between group and sex. Additional analyses exploring demographic and alcohol use variables showed significant impacts of age on white matter microstructure that were more pronounced in individuals with AUD. Plots of FA by age, sex, and group in major white matter tracts suggest a need to explore higher order interactions in larger samples. CONCLUSIONS: These results bolster recent findings of similar microstructural properties in men and women with AUD but provide a rationale for the consideration of age when investigating the impacts of chronic alcohol use on the brain's white matter.

Whole-Brain Imaging of Subvoxel T1-Diffusion Correlation Spectra in Human Subjects.

T1 relaxation and water mobility generate eloquent MRI tissue contrasts with great diagnostic value in many neuroradiological applications. However, conventional methods do not adequately quantify the microscopic heterogeneity of these important biophysical properties within a voxel, and therefore have limited biological specificity. We describe a new correlation spectroscopic (CS) MRI method for measuring how T1 and mean diffusivity (MD) co-vary in microscopic tissue environments. We develop a clinical pulse sequence that combines inversion recovery (IR) with single-shot isotropic diffusion encoding (IDE) to efficiently acquire whole-brain MRIs with a wide range of joint T1-MD weightings. Unlike conventional diffusion encoding, the IDE preparation ensures that all subvoxel water pools are weighted by their MDs regardless of the sizes, shapes, and orientations of their corresponding microscopic diffusion tensors. Accordingly, IR-IDE measurements are well-suited for model-free, quantitative spectroscopic analysis of microscopic water pools. Using numerical simulations, phantom experiments, and data from healthy volunteers we demonstrate how IR-IDE MRIs can be processed to reconstruct maps of two-dimensional joint probability density functions, i.e., correlation spectra, of subvoxel T1-MD values. In vivo T1-MD spectra show distinct cerebrospinal fluid and parenchymal tissue components specific to white matter, cortical gray matter, basal ganglia, and myelinated fiber pathways, suggesting the potential for improved biological specificity. The one-dimensional marginal distributions derived from the T1-MD correlation spectra agree well with results from other relaxation spectroscopic and quantitative MRI studies, validating the T1-MD contrast encoding and the spectral reconstruction. Mapping subvoxel T1-diffusion correlations in patient populations may provide a more nuanced, comprehensive, sensitive, and specific neuroradiological assessment of the non-specific changes seen on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted MRIs (DWIs) in cancer, ischemic stroke, or brain injury.

Multiple parietal pathways are associated with rTMS-induced hippocampal network enhancement and episodic memory changes.

Repetitive transcranial magnetic stimulation (rTMS) of the inferior parietal cortex (IPC) increases resting-state functional connectivity (rsFC) of the hippocampus with the precuneus and other posterior cortical areas and causes proportional improvement of episodic memory. The anatomical pathway(s) responsible for the propagation of these effects from the IPC is unknown and may not be direct. In order to assess the relative contributions of candidate pathways from the IPC to the MTL via the parahippocampal cortex and precuneus, to the effects of rTMS on rsFC and memory improvement, we used diffusion tensor imaging to measure the extent to which individual differences in fractional anisotropy (FA) in these pathways accounted for individual differences in response. FA in the IPC-parahippocampal pathway and several MTL pathways predicted changes in rsFC. FA in both parahippocampal and hippocampal pathways was related to changes in episodic, but not procedural, memory. These results implicate pathways to the MTL in the enhancing effect of parietal rTMS on hippocampal rsFC and memory.

Measuring non-parametric distributions of intravoxel mean diffusivities using a clinical MRI scanner.

We measure spectra of water mobilities (i.e., mean diffusivities) from intravoxel pools in brain tissues of healthy subjects with a non-parametric approach. Using a single-shot isotropic diffusion encoding (IDE) preparation, we eliminate signal confounds caused by anisotropic diffusion, including microscopic anisotropy, and acquire in vivo diffusion-weighted images (DWIs) over a wide range of diffusion sensitizations. We analyze the measured IDE signal decays using a regularized inverse laplace transform (ILT) to derive a probability distribution of mean diffusivities of tissue water in each voxel. Based on numerical simulations we assess the sensitivity and accuracy of our ILT analysis and optimize an experimental protocol for use with clinical MRI scanners. In vivo spectra of intravoxel mean diffusivities measured in healthy subjects generally show single-peak distributions throughout the brain parenchyma, with small differences in peak location and shape among white matter, cortical and subcortical gray matter, and cerebrospinal fluid. Mean diffusivity distributions (MDDs) with multiple peaks are observed primarily in voxels at tissue interfaces and are likely due to partial volume contributions. To quantify tissue-specific MDDs with improved statistical power, we average voxel-wise normalized MDDs in corresponding regions-of-interest (ROIs). This non-parametric, rotation-invariant assessment of isotropic diffusivities of tissue water may reflect important microstructural information, such as cell packing and cell size, and active physiological processes, such as water transport and exchange, which may enhance biological specificity in the clinical diagnosis and characterization of ischemic stroke, cancer, neuroinflammation, and neurodegenerative disorders and diseases.

Effectiveness of navigator-based prospective motion correction in MPRAGE data acquired at 3T.

In MRI, subject motion results in image artifacts. High-resolution 3D scans, like MPRAGE, are particularly susceptible to motion because of long scan times and acquisition of data over multiple-shots. Such motion related artifacts have been shown to cause a bias in cortical measures extracted from segmentation of high-resolution MPRAGE images. Prospective motion correction (PMC) techniques have been developed to help mitigate artifacts due to subject motion. In this work, high-resolution MPRAGE images are acquired during intentional head motion to evaluate the effectiveness of navigator-based PMC techniques to improve both the accuracy and reproducibility of cortical morphometry measures obtained from image segmentation. The contribution of reacquiring segments of k-space affected by motion to the overall performance of PMC is assessed. Additionally, the effect of subject motion on subcortical structure volumes is investigated. In the presence of head motion, navigator-based PMC is shown to improve both the accuracy and reproducibility of cortical and subcortical measures. It is shown that reacquiring segments of k-space data that are corrupted by motion is an essential part of navigator-based PMC performance. Subcortical structure volumes are not affected by motion in the same way as cortical measures; there is not a consistent underestimation.

Efficient experimental designs for isotropic generalized diffusion tensor MRI (IGDTI).

PURPOSE: We propose a new generalized diffusion tensor imaging (GDTI) experimental design and analysis framework for efficiently measuring orientationally averaged diffusion-weighted images (DWIs), which remove bulk signal modulations attributed to diffusion anisotropy and quantify isotropic higher-order diffusion tensors (HOT). We illustrate how this framework accelerates the clinical measurement of rotation-invariant tissue microstructural parameters derived from HOT, such as the HOT-Trace and the mean t-kurtosis. THEORY AND METHODS: For a large range of b-values, we compare orientationally averaged DWIs measured with high angular resolution diffusion imaging to those obtained with the proposed isotropic GDTI (IGDTI) experimental design. We compare rotation-invariant microstructural parameters measured with IGDTI to those derived from HOTs measured explicitly with GDTI. RESULTS: In both fixed-brain microimaging and in vivo clinical experiments, IGDTI accurately quantifies mean apparent diffusion coefficient (mADC)-weighted DWIs over a wide range of b-values and allows efficient computation of HOT-derived scalar tissue parameters from a small number of DWIs. CONCLUSIONS: IGDTI provides direct and accurate estimates of orientationally averaged tissue water mobilities over a wide range of b-values. This efficient method may enable new, sensitive, and quantitative assessments for clinical applications in which changes in mADC can be observe,d such as detecting and characterizing stroke, cancers, and neurodegenerative diseases. Magn Reson Med 79:180-194, 2018. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Pathology of callosal damage in ALS: An ex-vivo, 7 T diffusion tensor MRI study.

OBJECTIVES: The goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients. METHODS: Diffusion tensor imaging was carried out in postmortem brains of 4 ALS patients and two subjects without neurological disease on a 7 T MRI scanner using steady-state free precession sequences. Fractional anisotropy (FA) was measured in the genu, body, and splenium of the corpus callosum in formalin-fixed hemispheres. FA of the body and genu was expressed as ratio to FA of the splenium, a region unaffected in ALS. After imaging, tissue sections of the same segments of the callosum were stained for markers of different tissue components. Coded image fields were rated for pathological changes by blinded raters. RESULTS: The FA body/FA splenium ratio was reduced in ALS patients compared to controls. Patchy areas of myelin pallor and cells immunostained for CD68, a microglial-macrophage marker, were only observed in the body of the callosum of ALS patients. Blinded ratings showed increased CD68 + microglial cells in the body of the corpus callosum in ALS patients, especially those with C9orf72 mutations, and increased reactive astrocytes throughout the callosum. CONCLUSION: Reduced FA of the corpus callosum in ALS results from complex changes in tissue microstructure. Callosal segments with reduced FA had large numbers of microglia-macrophages in addition to loss of myelinated axons and astrogliosis. Microglial inflammation contributed to reduced FA in ALS, and may contribute to a pro-inflammatory state, but further work is needed to determine their role.

PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency.

Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right presupplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. Hum Brain Mapp 37:3236-3249, 2016. © 2016 Wiley Periodicals, Inc.

Endosphenoidal coil for intraoperative magnetic resonance imaging of the pituitary gland during transsphenoidal surgery.

OBJECTIVE Pituitary MR imaging fails to detect over 50% of microadenomas in Cushing's disease and nearly 80% of cases of dural microinvasion. Surface coils can generate exceptionally high-resolution images of the immediately adjacent tissues. To improve imaging of the pituitary gland, a receive-only surface coil that can be placed within the sphenoid sinus (the endosphenoidal coil [ESC]) during transsphenoidal surgery (TSS) was developed and assessed. METHODS Five cadaver heads were used for preclinical testing of the ESC. The ESC (a double-turn, 12-mm-diameter surface coil made from 1-mm-diameter copper wire) was developed to obtain images in a 1.5-T MR scanner. The ESC was placed (via a standard sublabial TSS approach) on the anterior sella face. Clinical MR scans were obtained using the 8-channel head coil and ESC as the receiver coils. Using the ESC, ultra-high-resolution, 3D, balanced fast field echo (BFFE) and T1-weighted imaging were performed at resolutions of 0.25 × 0.25 × 0.50 mm3 and 0.15 × 0.15 × 0.30 mm3, respectively. RESULTS Region-of-interest analysis indicated a 10-fold increase in the signal-to-noise ratio (SNR) of the pituitary when using the ESC compared with the 8-channel head coil. ESC-related improvements (p < 0.01) in the SNR were inversely proportional to the distance from the ESC tip to the anterior pituitary gland surface. High-resolution BFFE MR imaging obtained using ESC revealed a number of anatomical features critical to pituitary surgery that were not visible on 8-channel MR imaging, including the pituitary capsule, the intercavernous sinus, and microcalcifications in the pars intermedia. These ESC imaging findings were confirmed by the pathological correlation with whole-mount pituitary sections. CONCLUSIONS ESC can significantly improve SNR in the sellar region intraoperatively using current 1.5-T MR imaging platforms. Improvement in SNR can provide images of the sella and surrounding structures with unprecedented resolution. Clinical use of this ESC may allow for MR imaging detection of previously occult pituitary adenomas and identify microscopic invasion of the dura or cavernous sinus.

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.

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

PURPOSE: 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. METHODS: EPI of a phantom and human brains were acquired at 3 Tesla without and with GRAPPA acceleration factor of 2. The GRAPPA accelerated data were reconstructed using calibration scans acquired with EPI and FLASH acquisition schemes. The increase in temporal signal fluctuation due to GRAPPA reconstruction was quantified and compared. Simulated g-factor maps were also created for different calibration scans. RESULTS: GRAPPA accelerated phantom data exhibited areas with high g values when using the EPI based calibration for reconstruction. The g-factor maps were uniform when using the FLASH calibration scan. g was greater than 1.1 in 74% of pixels in 64 × 64 data reconstructed with the EPI calibration compared with only 15% when using the FLASH calibration scan. Human data also showed abnormally high g regions when using the EPI calibration but not when using the FLASH calibration scan. Use of the FLASH calibration scan increased the whole brain temporal SNR by ∼12% without affecting the image quality. Experimental observations were confirmed by simulations. CONCLUSION: A calibration scan based on a FLASH acquisition scheme can be used to improve the temporal SNR of GRAPPA accelerated EPI time series. Magn Reson Med 75:2362-2371, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Investigation of vibration-induced artifact in clinical diffusion-weighted imaging of pediatric subjects.

It has been reported that mechanical vibrations of the magnetic resonance imaging scanner could produce spurious signal dropouts in diffusion-weighted images resulting in artifactual anisotropy in certain regions of the brain with red appearance in the Directionally Encoded Color maps. We performed a review of the frequency of this artifact across pediatric studies, noting differences by scanner manufacturer, acquisition protocol, as well as weight and position of the subject. We also evaluated the ability of automated and quantitative methods to detect this artifact. We found that the artifact may be present in over 50% of data in certain protocols and is not limited to one scanner manufacturer. While a specific scanner had the highest incidence, low body weight and positioning were also associated with appearance of the artifact for both scanner types evaluated, making children potentially more susceptible than adults. Visual inspection remains the best method for artifact identification. Software for automated detection showed very low sensitivity (10%). The artifact may present inconsistently in longitudinal studies. We discuss a published case report that has been widely cited and used as evidence to set policy about diagnostic criteria for determining vegetative state. That report attributed longitudinal changes in anisotropy to white matter plasticity without considering the possibility that the changes were caused by this artifact. Our study underscores the need to check for the presence of this artifact in clinical studies, analyzes circumstances for when it may be more likely to occur, and suggests simple strategies to identify and potentially avoid its effects.

Diffusion tensor histogram analysis of pediatric diffuse intrinsic pontine glioma.

PURPOSE: To evaluate tumor structure in children with diffuse intrinsic pontine glioma (DIPG) using histogram analyses of mean diffusivity (MD), determine potential treatment and corticosteroid-related effects on MD, and monitor changes in MD distributions over time. MATERIALS AND METHODS: DTI was performed on a 1.5T GE scanner. Regions of interest included the entire FLAIR-defined tumor. MD data were used to calculate histograms. Patterns in MD distributions were evaluated and fitted using a two-normal mixture model. Treatment-related effects were evaluated using the R (2) statistic for linear mixed models and Cox proportional hazards models. RESULTS: 12 patients with DIPG underwent one or more DTI exams. MD histogram distributions varied among patients. Over time, histogram peaks became shorter and broader (P = 0.0443). Two-normal mixture fitting revealed large lower curve proportions that were not associated with treatment response or outcome. Corticosteroid use affected MD histograms and was strongly associated with larger, sharper peaks (R(2) = 0.51, P = 0.0028). CONCLUSIONS: MD histograms of pediatric DIPG show significant interpatient and intratumoral differences and quantifiable changes in tumor structure over time. Corticosteroids greatly affected MD and must be considered a confounding factor when interpreting MD results in the context of treatment response.

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.

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.

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.

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.

In vivo diffusion tensor imaging of the human optic chiasm at sub-millimeter resolution.

In this work we report findings from an in vivo diffusion tensor imaging (DTI) study of the human optic chiasm at sub-millimeter voxel resolution. Data were collected at 3 T using a diffusion-weighted radial-FSE sequence, which provides images free from typical magnetic susceptibility artifacts. The general DTI features observed in the optic chiasm region were consistent across subjects. They included a central area with high anisotropy and highest diffusivity in a predominately right/left direction corresponding to the decussation of nasal hemiretinae fibers, surrounded by a band of low anisotropy reflecting heterogeneous orientation of fibers within the voxel, and a lateral area with high anisotropy and highest diffusivity in a predominately anterior/posterior direction corresponding to temporal hemiretinae fibers that do not cross. Animal studies indicate that there is a significant dorsal-ventral reorganization of the retinotopic distribution of fibers along the optic pathways. We found that diffusion ellipsoids in the central portion of the optic chiasm show considerable planar anisotropy in the coronal plane indicating fiber crossings in the superior/inferior direction, rather than strictly right/left. This architectural feature of the chiasm suggests that dorso-ventral reorganization of fibers in the optic pathways also occurs in humans. We have shown that by collecting sub-millimeter resolution data, DTI can be used to investigate fine details of small and complex white matter structures, in vivo, with a clinical scanner. High spatial resolution, however, is necessary in the slice direction as well as in-plane to reduce the CSF contribution to the signal and to increase fiber coherence within voxels.

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.