Resolution Diffusion Tensor Imaging Research Articles

Rate of abnormalities in quantitative MR neuroimaging of persons with chronic traumatic brain injury

BackgroundMild traumatic brain injury (mTBI) can result in lasting brain damage that is often too subtle to detect by qualitative visual inspection on conventional MR imaging. Although a number of FDA-cleared MR neuroimaging tools have demonstrated changes associated with mTBI, they are still under-utilized in clinical practice.MethodsWe investigated a group of 65 individuals with predominantly mTBI (60 mTBI, 48 due to motor-vehicle collision, mean age 47 ± 13 years, 27 men and 38 women) with MR neuroimaging performed in a median of 37 months post-injury. We evaluated abnormalities in brain volumetry including analysis of left-right asymmetry by quantitative volumetric analysis, cerebral perfusion by pseudo-continuous arterial spin labeling (PCASL), white matter microstructure by diffusion tensor imaging (DTI), and neurometabolites via magnetic resonance spectroscopy (MRS).ResultsAll participants demonstrated atrophy in at least one lobar structure or increased lateral ventricular volume. The globus pallidi and cerebellar grey matter were most likely to demonstrate atrophy and asymmetry. Perfusion imaging revealed significant reductions of cerebral blood flow in both occipital and right frontoparietal regions. Diffusion abnormalities were relatively less common though a subset analysis of participants with higher resolution DTI demonstrated additional abnormalities. All participants showed abnormal levels on at least one brain metabolite, most commonly in choline and N-acetylaspartate.ConclusionWe demonstrate the presence of coup-contrecoup perfusion injury patterns, widespread atrophy, regional brain volume asymmetry, and metabolic aberrations as sensitive markers of chronic mTBI sequelae. Our findings expand the historic focus on quantitative imaging of mTBI with DTI by highlighting the complementary importance of volumetry, arterial spin labeling perfusion and magnetic resonance spectroscopy neurometabolite analyses in the evaluation of chronic mTBI.

Interhemispheric Connectivity of the Human Temporal Lobes.

Interhemispheric connections of the human temporal lobes were visualized using high angular resolution diffusion tensor imaging tractography.Results are displayed on serial orthogonal sections to reveal detailed spatial relationships.Corpus callosum projections through the splenium form distinct dorsal and ventral bundles and are absent from the caudal splenium.The transcallosal pathway consists of distinct medial and lateral divisions.The results reveal projections to the external capsule and claustrum not previously described.Transcallosal and anterior commissural pathways show complex patterns of overlap and interdigitation.Surface mapping revealed areas with relatively high density of projections to the cortical surface.

High resolution 0.5mm isotropic T1-weighted and diffusion tensor templates of the brain of non-demented older adults in a common space for the MIITRA atlas

High quality, high resolution T1-weighted (T1w) and diffusion tensor imaging (DTI) brain templates located in a common space can enhance the sensitivity and precision of template-based neuroimaging studies. However, such multimodal templates have not been constructed for the older adult brain. The purpose of this work which is part of the MIITRA atlas project was twofold: (A) to develop 0.5 mm isotropic resolution T1w and DTI templates that are representative of the brain of non-demented older adults and are located in the same space, using advanced multimodal template construction techniques and principles of super resolution on data from a large, diverse, community cohort of 400 non-demented older adults, and (B) to systematically compare the new templates to other standardized templates. It was demonstrated that the new MIITRA-0.5mm T1w and DTI templates are well-matched in space, exhibit good definition of brain structures, including fine structures, exhibit higher image sharpness than other standardized templates, and are free of artifacts. The MIITRA-0.5mm T1w and DTI templates allowed higher intra-modality inter-subject spatial normalization precision as well as higher inter-modality intra-subject spatial matching of older adult T1w and DTI data compared to other available templates. Consequently, MIITRA-0.5mm templates allowed detection of smaller inter-group differences for older adult data compared to other templates. The MIITRA-0.5mm templates were also shown to be most representative of the brain of non-demented older adults compared to other templates with submillimeter resolution. The new templates constructed in this work constitute two of the final products of the MIITRA atlas project and are anticipated to have important implications for the sensitivity and precision of studies on older adults.

Identifying and Re-Planning Challenging Retrospective SRS Patients to Evaluate the Potential for a White Matter Tract Sparing Knowledge-Based Planning Model

Diffusion tensor imaging (DTI) with automated tractography, along with auto-parcellation of volumetric MRI (vMRI), allows for reliable parcellation of critical white matter (WM) and hippocampal structures in the brain. Knowledge-based planning (KBP) may facilitate the optimization of new brain SRS plans that highly prioritize WM tracts and hippocampal sparing, allowing for cognitive preservation. However, building a high-performing model is challenging as the geometry of WM tracts and their proximity to planning target volumes (PTVs) can vary substantially. In this work we propose an iterative step for creating a KBP model where we used a preliminary model to identify challenging plans and worked on improving their dosimetry to refine the model predictions. Tractography of eloquent deep WM was obtained from high resolution DTI, along with auto-segmentation of bilateral hippocampi from vMRI and an open-source software for processing and analyzing brain MRI images. These ROIs were imported to the treatment planning system as organs-at-risk (OARsDTI). A preliminary KBP model was built from an IRB-approved cohort of 30 consecutive patients (75 plans total) treated for brain metastasis with non-coplanar SRS with total dose from 20 to 30 Gy in one to five fractions using a LINAC. This preliminary model was used to identify the 7 plans with the highest doses to the OARsDTI. These plans were re-optimized with new objectives on the OARsDTI that were partially or totally overlapped with the isodose line representing 30% of the prescription dose (as a surrogate for proximity to the PTV). The OARsDTI that were overlapping with the PTV were excluded from this analysis. We evaluated the re-optimized plans (PlanNew) by comparing maximum and mean dose (Dmax and Dmean, respectively) of OARsDTI to the initial values from the preliminary plans (PlanPre). In order to verify that the PlanNew were not compromising other structures or treatment goals, we also evaluated conformity index (CI), PTV coverage and the dosimetry of OARs included in the PlanPre. Additionally, the PlanNew were normalized to our clinical standard used for the PlanPre (100% of prescription dose to 98% of the PTV). In the 7 plans, there were 30 OARsDTI overlapping with the 30% isodose line. Refining the dosimetric objectives for the OARsDTI decreased the Dmean on average 31% when comparing PlanNew to Planpre (p<0.05, Wilcoxon rank-sum test). The CI of the PlanNew were not statistically different from the PlanPre. Although Dmax of PlanNew was 12% lower than Dmax of Planpre, the difference was not statistically different. The addition of a plan refinement step was shown to improve dose to the OARsDTI in 7 challenging SRS plans. The generation of these plans are a necessary step to creating a refined KBP model capable of accounting for the high variability in WM tracts geometry and their proximity with PTV.

Construction of the MIITRA T1‐weighted and DTI templates of the older adult brain in a common space at 0.5mm resolution

AbstractBackgroundHigh resolution multimodal MRI templates of the older adult brain have the potential to facilitate template‐based studies of aging. As part of the Multichannel Illinois Institute of Technology &amp; Rush university Aging (MIITRA) atlas, the present work developed high quality 0.5mm isotropic resolution T1‐weighted (T1w) and diffusion tensor imaging (DTI) templates in common space using data from a large, diverse, community cohort of non‐demented older adults.Method Data T1w and DTI data were collected using two 3T MRI scanners on 400 non‐demented older adults (50% male;64.9‐98.9 yrs;54% white,43% black) (Bennett et al.,2018; Barnes et al.,2012). Template construction Step1: An unbiased initial T1w template was created by pairwise affine registration (Ridwan et al.,2021).Step2: Spatial normalization was driven by T1w and DTI data alternatively (Wu et al., 2019). All transformations were combined to minimize interpolations and applied to both modalities. A patch‐based tissue‐guided sparse‐representation approach was employed to compute the template (Ridwan et al.,2021).Step3: High spatial resolution templates were created based on principles of super‐resolution (Niaz et al.,2022)The resulting templates are referred to as MIITRA_0.5mm templates. Evaluation T1w and DTI data from 202 ADNI3 non‐demented older adults were used for evaluation.The MIITRA_0.5mm templates were compared to other high resolution templates and the templates including older adults in terms of image sharpness and spatial normalization accuracy of ADNI3 data when each template was used as a reference for normalization.ResultMIITRA_0.5mm templates exhibited higher image sharpness (Fig.1,2). MIITRA_0.5mm templates allowed the highest inter‐subject spatial normalization accuracy across spatially normalized ADNI3 data and required less deformation than other high‐resolution templates (Fig.3,4). It should be noted that 1mm templates require on average less deformation than high‐resolution templates because larger voxels limit local deformations. Finally, the MIITRA_0.5mm templates allowed higher inter‐modality spatial matching of normalized older adult data (Fig.5).ConclusionThis work developed high resolution T1w and DTI multimodal templates of the older adult brain for the MIITRA atlas. The new templates exhibited higher image quality, were more representative of the older adult brain, and allowed higher spatial normalization accuracy compared to other templates. The new templates will be available for download at www.nitrc.org/projects/miitra.

Diffusion MRI alterations coincide with memory deficits in a novel hAβKI mouse model of Alzheimer’s Disease

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium is developing the next generation of Alzheimer’s disease (AD) models based on human genomic and imaging data. Recently, MODEL‐AD has generated a new human Aβ Knock‐In (hAβKI) mouse. These mice exhibit age‐dependent cognitive and synaptic impairments. Preclinical neuroimaging was performed, specifically diffusion MRI (dMRI) to investigate brain‐wide structural alterations in conjunction with connectomic analyses across the hAβKI mouse lifespan.MethodhAβKI and WT mice were compared at 4, 12, and 18 months (mo) of age. Two cohorts were generated for: 1) behavior and long‐term potentiation (LTP), and 2) high resolution diffusion tensor imaging at 9.4T (30 directions b=3000 mm2/sec) to assess regional white and gray matter changes. Regional tissue features based on the AMBMC atlas were extracted from fractional anisotropy (FA), radial (RD), axial (AxD) and mean diffusivity (MD) parametric maps.ResultSignificant impairments in hippocampal LTP were observed in male hAβKI mice at 4mo of age relative to WT but not at 12 or 18mo. In contrast, in female hAβKI mice, LTP impairments were observed only at 12 and 18mo relative to WT. dMRI heatmaps of MD highlighted regional differences between sexes across time and genotype, with MD progressively decreasing with time. Male hAβKI mice had progressive changes within the brain with advancing age whereas the largest changes in females was at 12mo of age. AxD in 18mo male hAβKI mice was increased in 4 of 7 white matter regions but not in female hAβKI mice compared to WT.ConclusionIn summary, using the newly developed hAβKI mouse model of AD, we identified progressive altered regional dMRI tissue metrics. The hippocampal CA1 region appeared to be particularly vulnerable, findings consistent with observed impairments in LTP and behavior. MRI of new mouse models is a powerful tool to investigate tissue level modifications to brain structure and function to inform human disease.

Lifespan diffusion MRI reveals structural abnormalities in the 5xFAD model of Alzheimer’s Disease

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium has been established to develop the next generation of Alzheimer’s disease (AD) models based on human genomic findings. As new models are developed, phenotypic data are compared to established models, including the 5xFAD mouse model. We undertook measurements of diffusion metrics to characterize the temporal alterations in brain structure in male and female 5xFAD mice, including connectivity analysis between the hippocampus and infralimbic prefrontal cortex (PFC).Method5xFAD mice were compared to age‐matched littermates (C57BL/6J, WT) at 4, 8, and 12 months (mo). Mice underwent high resolution diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) at 9.4T (5 B0, 30 directions b=3000 mm2/sec) to assess regional white and gray matter. Regional tissue features were extracted from fractional anisotropy (FA), radial (RD), axial (AxD) and mean diffusivity (MD) parametric maps. Tractography was performed based on the AMBMC mouse atlas. 18F‐AV45 PET was performed in a separate cohort at 4, 6, and 12mo to quantitate amyloid β (Aβ) load.ResultElevated FA within hippocampal CA1 was first observed in 5xFAD males at 8mo, but at 12mo 5xFAD females had increased FA in bilateral CA1 compared to WT mice. Connectivity between CA1 and PFC found 12mo 5xFAD females had significantly increased RD along the tract with concomitant increases in MD and AxD. AV45‐PET uptake was increased at 6mo (∼20%) and remained elevated at 12mo (∼25%) in the PFC in male and female 5xFAD compared to WT. In the hippocampus there was a ∼20% increase in AV45 binding at 6mo, that then declines by 12mo in 5xFAD mice.ConclusionPhenotyping of mouse models using DTI identifies altered brain connectivity and regional tissue modifications that may be indicative of increasing Aβ deposition. These data support that increasing Aβ deposition results in altered DTI metrics and connectivity using clinically relevant imaging modalities.

Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.

The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 μm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence. This work expands our understanding of the risks associated with opioid misuse during pregnancy and identifies biomarkers that may facilitate diagnosis and treatment.

Brain structural plasticity in rats subjected to early binocular enucleation characterized by high resolution anatomical magnetic resonance imaging and diffusion tensor imaging

Visual deprivation leads to structural neuroplasticity in the blind subjects, including gray matter (GM) and white matter (WM) atrophy and alterations in structural connectivity. The rat model of binocular enucleation (BE) is a frequently used animal model for studying brain plasticity induced by early blindness. Yet few neuroimaging studies have been performed on this model to investigate whether or not the BE rats have image phenotypes similar to or comparable to, those observed in the early blind subjects. The current study aimed to assess brain structural plasticity in BE rats using anatomical magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). The results demonstrated that early BE at postnatal day 4 (P4) caused almost complete degeneration of optic nerve (ON) and optic chiasma (OCH), atrophy in a number of visual and non-visual structures, including optic tract (OT), dorsal lateral geniculate nucleus (DLG) and corpus callosum (CC). The BE rats also exhibited impairments of WM microstructural integrity in the OT, and reduction of structural connectivity between the normal-appearing visual cortex (VC) and somatosensory/motor cortices at 4 months of age, likely as manifestations of deafferentation-induced maldevelopment. The structural neuroplasticity in BE rats observable to structural MRI parallels largely with what has been reported in blind subjects, suggesting that longitudinal neuroimaging studies on animal models of sensory deprivation can provide insights into how the brain changes its wiring and function during development/adaption in response to the lack of sensory stimuli.

Persistent myelin abnormalities in a third trimester-equivalent mouse model of fetal alcohol spectrum disorder.

Abnormal diffusion within white matter (WM) tracts has been linked to cognitive impairment in children with fetal alcohol spectrum disorder. Whether changes to myelin organization and structure underlie the observed abnormal diffusion patterns remains unknown. Using a third trimester-equivalent mouse model of alcohol exposure, we previously demonstrated acute loss of oligodendrocyte lineage cells with persistent loss of myelin basic protein and lower fractional anisotropy (FA) in the corpus callosum (CC). Here, we tested whether these WM deficits are accompanied by changes in: (i) axial diffusion (AD) and radial diffusion (RD), (ii) myelin ultrastructure, or (iii) structural components of the node of Ranvier. Mouse pups were exposed to alcohol or air vapor for 4h daily from postnatal day (P)3 to P15 (BEC: 160.4±12.0mg/dl; range=128.2 to 185.6mg/dl). Diffusion tensor imaging (DTI) and histological analyses were performed on brain tissue isolated at P50. Diffusion parameters were measured with Paravision™ 5.1 software (Bruker) following ex vivo scanning in a 7.0T MRI. Nodes of Ranvier were identified using high-resolution confocal imaging of immunofluorescence for Nav 1.6 (nodes) and Caspr (paranodes) and measured using Imaris™ imaging software (Bitplane). Myelin ultrastructure was evaluated by calculating the G-ratio (axonal diameter/myelinated fiber diameter) on images acquired using transmission electron microscopy. Consistent with our previous study, high resolution DTI at P50 showed lower FA in the CC of alcohol-exposed mice (p=0.0014). Here, we show that while AD (diffusion parallel to CC axons) was similar between treatment groups (p=0.30), RD (diffusion perpendicular to CC axons) in alcohol-exposed subjects was significantly higher than in controls (p=0.0087). In the posterior CC, where we identified the highest degree of abnormal diffusion, node of Ranvier length did not differ between treatment groups (p=0.41); however, the G-ratio of myelinated axons was significantly higher in alcohol-exposed animals than controls (p=0.023). High resolution DTI revealed higher RD at P50 in the CC of alcohol-exposed animals, suggesting less myelination of axons, particularly in the posterior regions. In agreement with these findings, ultrastructural analysis of myelinated axons in the posterior CC showed reduced myelin thickness in alcohol-exposed animals, evidenced by a higher G-ratio.

Development and evaluation of MIITRA T1w and DTI brain templates at 0.5 mm resolution

AbstractBackgroundAn MRI multimodal older adult brain atlas with high spatial resolution is in high demand. As part of the Multichannel Illinois Institute of Technology &amp; Rush university Aging (MIITRA) atlas project, this work aimed to develop high quality 0.5mm resolution T1‐weighted (T1w) and diffusion tensor imaging (DTI) multimodal templates using data from a large, diverse, community cohort of non‐demented older adults and quantitatively evaluate the new templates.MethodTemplate construction: T1w and DTI data were collected on 400 non‐demented older adults (50% male;64.9‐98.9 yrs;54% white,43% black) participating in longitudinal cohort studies of aging (Bennett et al.,2018; Barnes et al.,2012) with two 3T MRI scanners.First, a recently introduced approach for the development of high quality multimodal templates (Wu et al., 2019) was conducted in a 0.5mm isotropic resolution space to maximize the quality and anatomical consistency of the templates. Then an approach for the development of high spatial resolution templates based on principles of super‐resolution (Niaz et al., 2019) was used to eliminate interpolations in conventional template building methods. The resulting templates are named MIITRA templates. Evaluation: T1w and DTI data on 202 non‐demented older adults from ADNI3 were used for evaluation. The MIITRA templates were compared to other standardized templates in terms of the accuracy of inter‐subject spatial normalization and inter‐modality spatial matching of ADNI3 data achieved when each template was used as a reference for normalization.ResultVisual inspection shows that the MIITRA T1w and DTI templates with 0.5mm isotropic voxels exhibit high sharpness and are free of artifacts (Fig. 1, 2). Figures 3 and 4 demonstrate that the MIITRA templates provided higher inter‐subject spatial normalization accuracy of older adult data and required less deformation than other templates. Finally, the MIITRA T1w and DTI templates exhibited high spatial matching to each other and allowed higher inter‐modality spatial matching of normalized older adult data (Fig. 5).ConclusionThis work developed high quality 0.5mm resolution T1w and DTI templates for the MIITRA atlas using data from a large, diverse, community cohort of non‐demented older adults. The new templates allowed higher inter‐subject and inter‐modality spatial normalization of older adult data compared to other templates.

Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated

BackgroundThe corpus callosum (CC) deficits have been well documented in chronic schizophrenia. However, the long-term impacts of antipsychotic monotherapies on callosal anatomy remain unclear. This cross-sectional study sought to explore micro- and macro-structural characteristics of the CC in never-treated patients and those with long-term mono-antipsychotic treatment.MethodsThe study included 23 clozapine-treated schizophrenia patients (CT-SCZ), 19 risperidone-treated schizophrenia patients (RT-SCZ), 23 never-treated schizophrenia patients (NT-SCZ), and 35 healthy controls (HCs). High resolution structural images and diffusion tensor imaging (DTI) data for each participant were obtained via a 3.0 T MR scanner. FreeSurfer was used to examine the volumes and fractional anisotropy (FA) values of the CC for each participant.ResultsThere were significant deficits in the total and sub-regional CC volume and white matter integrity in NT-SCZ in comparison with healthy subjects. Compared with NT-SCZ, both CT-SCZ and RT-SCZ showed significantly increased FA values in the anterior CC region, while only RT-SCZ showed significantly increased volume in the mid-anterior CC region. Moreover, the volume of the mid-anterior CC region was significantly smaller in CT-SCZ compared to HCs. No correlations of clinical symptoms with callosal metrics were observed in schizophrenia patients.ConclusionsOur findings provide insight into micro- and macro-structural characteristics of the CC in chronic schizophrenia patients with or without antipsychotics. These results suggest that the pathology itself is responsible for cerebral abnormalities in schizophrenia and that chronic exposure to antipsychotics may have an impact on white matter structure of schizophrenia patients, especially in those with risperidone treatment.

High resolution diffusion tensor imaging of the hippocampus across the healthy lifespan.

The human hippocampus is difficult to image given its small size, location, shape, and complex internal architecture. Structural magnetic resonance imaging (MRI) has shown age-related hippocampal volume changes that vary along the anterior-posterior axis. Diffusion tensor imaging (DTI) provides complementary measures related to microstructure, but there are few hippocampus DTI studies investigating change with age in healthy participants, and all have been limited by low spatial resolution. The current study uses high resolution 1 mm isotropic DTI of 153 healthy volunteers aged 5-74 years to investigate diffusion and volume trajectories of the hippocampus (whole, head, body, and tail) and correlations with memory. Hippocampal volume showed age-related changes that differed between head (peaking at midlife), body (no changes), and tail (decreasing across the age span). Fractional anisotropy (FA) and mean, axial, and radial diffusivities (MD, AD, RD) yielded peaks or minima, respectively, at ~30-35 years in all three subregions of the hippocampus. Greater magnitude changes were observed during development than in aging. Age trajectories for both volume and DTI were similar between males and females. Correlations between tests of memory and FA and/or volume were significant in younger subjects (5-17 years), but not in 18-49 year olds or 50-74 year olds. MD was significantly correlated with memory performance in 18-49 year olds, but not in other age groups. Given the diffusion-weighted image contrast and resolution, head digitations could be examined revealing that the majority of subjects had 3-4 (48%) or 2 (32%) bilaterally with no effect of age. One millimeter isotropic DTI yielded high quality diffusion-weighted maps of the human hippocampus that showed regionally specific age effects and cognitive correlations along the anterior-posterior axis from 5 to 74 years.

Inflammatory reaction in the retina after focal non-convulsive status epilepticus in mice investigated with high resolution magnetic resonance and diffusion tensor imaging

Pathophysiological consequences of focal non-convulsive status epilepticus (fNCSE) have been difficult to demonstrate in humans. In rats fNCSE pathology has been identified in the eyes. Here we evaluated the use of high-resolution 7 T structural T1-weighted magnetic resonance imaging (MRI) and 9.4 T diffusion tensor imaging (DTI) for detecting hippocampal fNCSE-induced retinal pathology ex vivo in mice. Seven weeks post-fNCSE, increased number of Iba1+ microglia were evident in the retina ipsilateral to the hemisphere with fNCSE, and morphologically more activated microglia were found in both ipsi- and contralateral retina compared to non-stimulated control mice. T1-weighted intensity measurements of the contralateral retina showed a minor increase within the outer nuclear and plexiform layers of the lateral retina. T1-weighted measurements were not performed in the ipsilateral retina due to technical difficulties. DTI fractional anisotropy(FA) values were discretely altered in the lateral part of the ipsilateral retina and unaltered in the contralateral retina. No changes were observed in the distal part of the optic nerve. The sensitivity of both imaging techniques for identifying larger retinal alteration was confirmed ex vivo in retinitis pigmentosa mice where a substantial neurodegeneration of the outer retinal layers is evident. With MR imaging a 50 % decrease in DTI FA values and significantly thinner retina in T1-weighted images were detected. We conclude that retinal pathology after fNCSE in mice is subtle and present bilaterally. High-resolution T1-weighted MRI and DTI independently did not detect the entire pathological retinal changes after fNCSE, but the combination of the two techniques indicated minor patchy structural changes.

High-Resolution 3D in vivo Brain Diffusion Tensor Imaging at Ultrahigh Fields: Following Maturation on Juvenile and Adult Mice.

Diffusion tensor imaging (DTI) is a well-established technique for mapping brain microstructure and white matter tracts in vivo. High resolution DTI, however, is usually associated with low intrinsic sensitivity and therefore long acquisition times. By increasing sensitivity, high magnetic fields can alleviate these demands, yet high fields are also typically associated with significant susceptibility-induced image distortions. This study explores the potential arising from employing new pulse sequences and emerging hardware at ultrahigh fields, to overcome these limitations. To this end, a 15.2 T MRI instrument equipped with a cryocooled surface transceiver coil was employed, and DTI experiments were compared between SPatiotemporal ENcoding (SPEN), a technique that tolerates well susceptibility-induced image distortions, and double-sampled Spin-Echo Echo-Planar Imaging (SE-EPI) methods. Following optimization, SE-EPI afforded whole brain DTI maps at 135 μm isotropic resolution that possessed higher signal-to-noise ratios (SNRs) than SPEN counterparts. SPEN, however, was a better alternative to SE-EPI when focusing on challenging regions of the mouse brain –including the olfactory bulb and the cerebellum. In these instances, the higher robustness of fully refocused SPEN acquisitions coupled to its built-in zooming abilities, provided in vivo DTI maps with 75 μm nominal isotropic spatial resolution. These DTI maps, and in particular the mean diffusion direction (MDD) details, exhibited variations that matched very well the anatomical features known from histological brain Atlases. Using these capabilities, the development of the olfactory bulb (OB) in live mice was followed from week 1 post-partum, until adulthood. The diffusivity of this organ showed a systematic decrease in its overall isotropic value and increase in its fractional anisotropy with age; this maturation was observed for all regions used in the OB's segmentation but was most evident for the lobules' centers, in particular for the granular cell layer. The complexity of the OB neuronal connections also increased during maturation, as evidenced by the growth in directionalities arising in the mean diffusivity direction maps.

High spatial resolution nerve-specific DTI protocol outperforms whole-brain DTI protocol for imaging the trigeminal nerve in healthy individuals.

Diffusion tensor imaging (DTI) can provide markers of axonal micro-structure of the trigeminal nerve (cranial nerve five [CNV]), which may be affected in trigeminal neuralgia (TN) and other disorders. Previous attempts to image CNV have used low spatial resolution DTI protocols designed for whole-brain acquisition that are susceptible to errors from partial volume effects, particularly with adjacent cerebrospinal fluid (CSF). The purpose of this study was to develop a nerve-specific DTI protocol in healthy subjects that provides more accurate CNV tractography and diffusion quantification than whole-brain protocols. Four DTI protocols were compared in five healthy individuals (age 22-45 years, three males) on a 3 T Siemens Prisma MRI scanner: two newly developed nerve-specific high resolution (1.2 x 1.2 x 1.2 = 1.7 mm3 ) DTI protocols without (3.5 minutes) and with CSF suppression (fluid-attenuated inversion recovery [FLAIR]; 7.5 minutes) with limited slice-coverage, and two typical whole-brain protocols with either isotropic (2 x 2 x 2 = 8 mm3 ) or thicker slice anisotropic (1.9 x 1.9 x 3 = 10.8 mm3 ) voxels. Deterministic tractography was used to identify the CNV and quantify bilateral fractional anisotropy (FA), and mean (MD), axial (AD) and radial diffusivity (RD). CNV volume was determined by manual tracing on T1-weighted images. High spatial resolution nerve-specific protocols yielded better delineation of CNV, with less distortions and blurring, and markedly different diffusion parameters (42% higher FA, 35% lower MD, 27% lower RD and 43% lower AD) compared with the two lower resolution whole-brain protocols. The anisotropic whole-brain protocol showed a positive correlation between CNV FA and volume. The high resolution nerve-specific protocol with FLAIR yielded additional reductions in CNV AD and MD with a value of 1.0 x 10-3 mm2 /s, approaching that expected for healthy young adult white matter. In conclusion, high resolution nerve-specific DTI with FLAIR enhances the identification of CNV and provides more accurate quantification of diffusion compared with lower resolution whole-brain approaches.

Simultaneous Diffusion and T1 Weighted Contrast Imaging for Human Brain Mapping

Introduction: Diffusion tensor imaging (DTI) is conventionally performed using echo planar imaging (EPI) for human brain mapping. However, EPI suffers from susceptibility distortion, requiring elaborate image post processing. Besides, DTI alone is limited in assessing gray and white matter boundaries of the brain, which is important for accurately imaging brain atrophy. The goal of this study was to design and evaluate simultaneous diffusion and T1 weighting high resolution imaging for human brain mapping. Materials and Methods: Three dimensional Magnetization-prepared rapid gradient-echo (3D MPRAGE) with T1 weighting, which is generally the method of choice for mapping gray and white matter structures in the brain, was extended to incorporate diffusion encoding using simulation and experiment to develop high resolution DTI and T1-weighted human brain data. Results: It is shown that the incorporation of DTI contrast (i.e. fractional anisotropy (FA) and mean diffusivity (MD)) into T1 weighted 3D MPRAGE using simulations as well as experimental results from in-vivo human brain studies at 4 Tesla magnetic field strength improves the contrast between gray and white matter sub-structural boundaries. Moreover, incorporating diffusion encoding into 3D MPRAGE avoids the inherent image distortions typically seen in EPI based DTI.Conclusion: This study suggests DTI weighted 3D MPRAGE combined with T1w is feasible for human brain imaging and expected to benefit improved assessment of gray/white matter boundaries.

Ascending Axonal Degeneration of the Corticospinal Tract in Pure Hereditary Spastic Paraplegia: A Cross-Sectional DTI Study.

Objective: To identify structural white matter alterations in patients with pure hereditary spastic paraplegia (HSP) using high angular resolution diffusion tensor imaging (DTI). Methods: We examined 37 individuals with high resolution DTI, 20 patients with pure forms of hereditary spastic paraplegia and 17 age and gender matched healthy controls. DTI was performed using a 3 T clinical scanner with whole brain tract-based spatial statistical (TBSS) analysis of the obtained fractional anisotropy (FA) data as well as a region-of-interest (ROI)-based analysis of affected tracts including the cervical spinal cord. We further conducted correlation analyses between DTI data and clinical characteristics. Results: TBSS analysis in HSP patients showed significantly decreased fractional anisotropy of the corpus callosum and the corticospinal tract compared to healthy controls. ROI-based analysis confirmed significantly lower FA in HSP compared to controls in the internal capsule (0.77 vs. 0.80, p = 0.048), the corpus callosum (0.84 vs. 0.87, p = 0.048) and the cervical spinal cord (0.72 vs. 0.79, p = 0.003). FA values of the cervical spinal cord significantly correlated with disease duration. Conclusion: DTI metrics of the corticospinal tract from the internal capsule to the cervical spine suggest microstructural damage and axonal degeneration of motor neurons. The CST at the level of the cervical spinal cord is thereby more severely affected than the intracranial part of the CST, suggesting an ascending axonal degeneration of the CST. Since there is a significant correlation with disease duration, FA may serve as a future progression marker for assessment of the disease course in HSP.

Regional hippocampal diffusion abnormalities associated with subfield-specific pathology in temporal lobe epilepsy.

ObjectiveHippocampal sclerosis (HS) is the most common pathology and best predictor of surgical outcome for medically refractory patients with temporal lobe epilepsy (TLE). Current clinical MRI methods can detect HS, but subfield pathology is poorly characterized, limiting accurate prediction of seizure‐free outcomes after surgery. Diffusion tensor imaging (DTI) can probe regional microstructural changes associated with focal hippocampal pathology, but is typically limited by low‐resolution whole‐brain acquisitions.MethodsHigh‐resolution (1 × 1 × 1 mm3) DTI, T1, and quantitative T2 of the hippocampus was acquired in 18 preoperative TLE patients and 19 healthy controls. Diffusion images were qualitatively assessed for loss of internal architecture, and whole‐hippocampus diffusion, volume, and quantitative T2 were compared across groups. Regional hippocampal diffusion abnormalities were examined in all subjects and compared to histology in four subjects who underwent anterior temporal lobectomy.ResultsHigh‐resolution mean diffusion‐weighted images enabled visualization of internal hippocampal architecture, used to visually identify HS with 86% specificity and 93% sensitivity. Mean diffusivity (MD) elevations were regionally heterogenous within the hippocampus and varied across TLE patients. The spatial location of diffusion abnormalities corresponded with the location of focal subfield neuron loss, gliosis, and reduced myelin staining abnormalities identified with postsurgical histology in four subjects who underwent anterior temporal lobectomy. Whole‐hippocampus MD and T2 relaxation times were higher, and fractional anisotropy (FA) and volumes were lower in TLE patients relative to controls. Left hippocampus MD correlated with verbal memory in the TLE group.SignificanceVisualization of internal architecture and focal diffusion abnormalities on high‐resolution diffusion imaging suggests potential clinical utility of diffusion imaging in TLE and may have significant implications for surgical planning and prediction of seizure‐free outcomes in individual patients.

HARDI Segmentation via Fourth-Order Tensors and Anisotropy Preserving Similarity Measures

In this work, we discuss the higher-order tensors appearing in high angular resolution diffusion tensor imaging, and we have tested two segmentation methods, the Riemannian spectral clustering and the deformable models, using several projections of the fourth-order tensors to the second-order ones, and diverse similarity measures on them. High angular resolution diffusion imaging has proved its effectiveness in modeling white matter brain structures along with the fiber intersection regions, which is of high importance in brain research. Along with other known projections, we observe that the diagonal components of the flattened fourth-order tensors also live in the well-known Riemannian symmetric space of symmetric positive-definite matrices. We discuss and compare several natural approximations of the distance on the latter space to be used in clustering and segmentation algorithms. The results show that some of the projections unfold the geometry of the higher-order tensors very well, and we also propose the exploitation of the spherical linear interpolation spectral quaternion metric, which proves to be very effective. The latter claims are supported by experimental comparison of the effectiveness of our algorithms with the more usual logarithmic Euclidean and spectral quaternionic metrics, in particular in the presence of noise. Our methods allow to distinguish individual objects in complex structures with high curvatures and crossings.