Functional correlates of motor control impairments in multiple sclerosis: A 7 Tesla task functional MRI study.

Upper and lower limb impairments are common in people with multiple sclerosis (pwMS), yet difficult to clinically identify in early stages of disease progression. Tasks involving complex motor control can potentially reveal more subtle deficits in early stages, and can be performed during functional MRI (fMRI) acquisition, to investigate underlying neural mechanisms, providing markers for early motor progression. We investigated brain activation during visually guided force matching of hand or foot in 28 minimally disabled pwMS (Expanded Disability Status Scale (EDSS) < 4 and pyramidal and cerebellar Kurtzke Functional Systems Scores ≤ 2) and 17 healthy controls (HC) using ultra-high field 7-Tesla fMRI, allowing us to visualise sensorimotor network activity in high detail. Task activations and performance (tracking lag and error) were compared between groups, and correlations were performed. PwMS showed delayed (+124 s, p = .002) and more erroneous (+0.15 N, p = .001) lower limb tracking, together with lower cerebellar, occipital and superior parietal cortical activation compared to HC. Lower activity within these regions correlated with worse EDSS (p = .034), lower force error (p = .006) and higher lesion load (p < .05). Despite no differences in upper limb task performance, pwMS displayed lower inferior occipital cortical activation. These results demonstrate that ultra-high field fMRI during complex hand and foot tracking can identify subtle impairments in lower limb movements and upper and lower limb brain activity, and differentiates upper and lower limb impairments in minimally disabled pwMS.

Microstructural correlates of 23Na relaxation in human brain at 7 Tesla.

23Na provides the second strongest MR-observable signal in biological tissue and exhibits bi-exponential T2∗ relaxation in micro-environments such as the brain. There is significant interest in developing 23Na biomarkers for neurological diseases that are associated with sodium channel dysfunction such as multiple sclerosis and epilepsy. We have previously reported methods for acquisition of multi-echo sodium MRI and continuous distribution modelling of sodium relaxation properties as surrogate markers of brain microstructure. This study aimed to compare 23Na T2∗ relaxation times to more established measures of tissue microstructure derived from advanced diffusion MRI at 7 â€‹T. Six healthy volunteers were scanned using a 3D multi-echo radial ultra-short TE sequence using a dual-tuned 1H/23Na birdcage coil, and a high-resolution multi-shell, high angular resolution diffusion imaging sequence using a 32-channel 1H receive coil. 23Na T2∗ relaxation parameters [mean T2∗ (T2∗mean) and fast relaxation fraction (T2∗ff)] were calculated from a voxel-wise continuous gamma distribution signal model. White matter (restricted anisotropic diffusion) and grey matter (restricted isotropic diffusion) density were calculated from multi-shell multi-tissue constrained spherical deconvolution. Sodium parameters were compared with white and grey matter diffusion properties. Sodium T2∗mean and T2∗ff showed little variation across a range of white matter axonal fibre and grey matter densities. We conclude that sodium T2∗ relaxation parameters are not greatly influenced by relative differences in intra- and extracellular partial volumes. We suggest that care be taken when interpreting sodium relaxation changes in terms of tissue microstructure in healthy tissue.

Substantially thinner internal granular layer and reduced molecular layer surface in the cerebellar cortex of the Tc1 mouse model of down syndrome - a comprehensive morphometric analysis with active staining contrast-enhanced MRI.

Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this model of Down Syndrome resided in the inner granule cell layer, while a larger proportion of the surface area shrinkage was in the molecular layer.

Compressed sensing effects on quantitative analysis of undersampled human brain sodium MRI.

PURPOSE: The clinical application of sodium MRI is hampered due to relatively low image quality and associated long acquisition times. Compressed sensing (CS) aims at a reduction of measurement time, but has been found to encompass quantitative estimation bias when used in low SNR x-Nuclei imaging. This work analyses CS in quantitative human brain sodium MRI from undersampled acquisitions and provides recommendations for tissue sodium concentration (TSC) estimation. METHODS: CS reconstructions from 3D radial acquisitions of 5 healthy volunteers were investigated over varying undersampling factors (USFs) and CS penalty weights on different sparsity domains, Wavelet, Discrete Cosine Transform (DCT), and Identity. Resulting images were compared with highly sampled and undersampled NUFFT-based images and evaluated for image quality (i.e. structural similarity), image intensity bias, and its effect on TSC estimates in gray and white matter. RESULTS: Wavelet-based CS reconstructions show highest image quality with stable TSC estimates for most USFs. Up to an USF of 4, images showed good structural detail. DCT and Identity-based CS enable good image quality, however show a bias in TSC with a reduction in estimates across USFs. CONCLUSIONS: The image intensity bias is lowest in Wavelet-based reconstructions and enables an up to fourfold acquisition speed up while maintaining good structural detail. The associated acquisition time reduction can facilitate a translation of sodium MRI into clinical routine.

Extracting more for less: multi-echo MP2RAGE for simultaneous T1 -weighted imaging, T1 mapping, R2∗ mapping, SWI, and QSM from a single acquisition.

PURPOSE: To demonstrate simultaneous T1 -weighted imaging, T1 mapping, R2∗ mapping, SWI, and QSM from a single multi-echo (ME) MP2RAGE acquisition. METHODS: A single-echo (SE) MP2RAGE sequence at 7 tesla was extended to ME with 4 bipolar gradient echo readouts. T1 -weighted images and T1 maps calculated from individual echoes were combined using sum of squares and averaged, respectively. ME-combined SWI and associated minimum intensity projection images were generated with TE-adjusted homodyne filters. A QSM reconstruction pipeline was used, including a phase-offsets correction and coil combination method to properly combine the phase images from the 32 receiver channels. Measurements of susceptibility, R2∗ , and T1 of brain tissue from ME-MP2RAGE were compared with those from standard ME-gradient echo and SE-MP2RAGE. RESULTS: The ME combined T1 -weighted, T1 map, SWI, and minimum intensity projection images showed increased SNRs compared to the SE results. The proposed coil combination method led to QSM results free of phase-singularity artifacts, which were present in the standard adaptive combination method. T1 -weighted, T1 , and susceptibility maps from ME-MP2RAGE were comparable to those obtained from SE-MP2RAGE and ME-gradient echo, whereas R2∗ maps showed increased blurring and reduced SNR. T1 , R2∗ , and susceptibility values of brain tissue from ME-MP2RAGE were consistent with those from SE-MP2RAGE and ME-gradient echo. CONCLUSION: High-resolution structural T1 weighted imaging, T1 mapping, R2∗ mapping, SWI, and QSM can be extracted from a single 8.5-min ME-MP2RAGE acquisition using a customized reconstruction pipeline. This method can be applied to replace separate SE-MP2RAGE and ME-gradient echo acquisitions to significantly shorten total scan time.

A continuum of T2* components: Flexible fast fraction mapping in sodium MRI.

PURPOSE: Parameter mapping in sodium MRI data is challenging due to inherently low SNR and spatial resolution, prompting the need to employ robust models and estimation techniques. This work aims to develop a continuum model of sodium T2* -decay to overcome the limitations of the commonly employed bi-exponential models. Estimates of mean T2* -decay and fast component fraction in tissue are emergent from the inferred continuum model. METHODS: A closed-form continuum model was derived assuming a gamma distribution of T2* components. Sodium MRI was performed on four healthy human subjects and a phantom consisting of closely packed vials filled with an aqueous solution of varying sodium and agarose concentrations. The continuum model was applied to the phantom and in vivo human multi-echo 7T data. Parameter maps by voxelwise model-fitting were obtained. RESULTS: The continuum model demonstrated comparable estimation performance to the bi-exponential model. The parameter maps provided improved contrast between tissue structures. The fast component fraction, an indicator of the heterogeneity of localised sodium motion regimes in tissue, was zero in CSF and high in WM structures. CONCLUSIONS: The continuum distribution model provides high quality, high contrast parameter maps, and informative voxelwise estimates of the relative weighting between fast and slow decay components.

Zero-gradient-excitation ramped hybrid encoding (zGRF -RHE) sodium MRI.

PURPOSE: Fast bi-exponential transverse signal decay compounds sodium image quality. This work aims at enhancing image characteristics using a special case of ramped hybrid encoding (RHE). Zero-gradient-excitation (zGRF )-RHE provides (1) gradient-free excitation for high flip angle, artifact-free excitation profiles and (2) gradient ramping during dead-time for the optimization of encoding time (tenc ) to reduce T2* signal decay influence during acquisition. METHODS: Radial zGRF -RHE and standard radial UTE were investigated over a range of receiver bandwidths in simulations, phantom and in vivo brain experiments. Central k-space in zGRF -RHE was acquired through single point measurements at the minimum achievable TE. T2* blurring artifacts and image SNR and CNR were assessed. RESULTS: zGRF -RHE enabled 90° flip angle artifact-free excitation, whereas gradient pre-ramping provided greater tenc efficiency for any readout bandwidths. Experiments confirmed simulation results, revealing sharper edge characteristics particularly at short readout durations (TRO ). Significant SNR improvements of up to 4.8% were observed for longer TRO . CONCLUSION: zGRF -RHE allows for artifact-free high flip angle excitation with time-efficient encoding improving on image characteristics. This hybrid encoding concept with gradient pre-ramping is trajectory independent and can be introduced in any center-out UTE trajectory design.

7T-fMRI: Faster temporal resolution yields optimal BOLD sensitivity for functional network imaging specifically at high spatial resolution.

Recent developments in accelerated imaging methods allow faster acquisition of high spatial resolution images. This could improve the applications of functional magnetic resonance imaging at 7 Tesla (7T-fMRI), such as neurosurgical planning and Brain Computer Interfaces (BCIs). However, increasing the spatial and temporal resolution will both lead to signal-to-noise ratio (SNR) losses due to decreased net magnetization per voxel and T1-relaxation effect, respectively. This could potentially offset the SNR efficiency gains made with increasing temporal resolution. We investigated the effects of varying spatial and temporal resolution on fMRI sensitivity measures and their implications on fMRI-based BCI simulations. We compared temporal signal-to-noise ratio (tSNR), observed percent signal change (%∆S), volumes of significant activation, Z-scores and decoding performance of linear classifiers commonly used in BCIs across a range of spatial and temporal resolution images acquired during an ankle-tapping task. Our results revealed an average increase of 22% in %∆S (p=0.006) and 9% in decoding performance (p=0.015) with temporal resolution only at the highest spatial resolution of 1.5×1.5×1.5mm3, despite a 29% decrease in tSNR (p<0.001) and plateaued Z-scores. Further, the volume of significant activation was indifferent (p>0.05) across spatial resolution specifically at the highest temporal resolution of 500ms. These results demonstrate that the overall BOLD sensitivity can be increased significantly with temporal resolution, granted an adequately high spatial resolution with minimal physiological noise level. This shows the feasibility of diffuse motor-network imaging at high spatial and temporal resolution with robust BOLD sensitivity with 7T-fMRI. Importantly, we show that this sensitivity improvement could be extended to an fMRI application such as BCIs.

3D-multi-echo radial imaging of 23 Na (3D-MERINA) for time-efficient multi-parameter tissue compartment mapping.

PURPOSE: This work demonstrates a 3D radial multi-echo acquisition scheme for time-efficient sodium (23 Na) MR-signal acquisition and analysis. Echo reconstructions were used to produce signal-to-noise ratio (SNR)-enhanced 23 Na-images and parameter maps of the biexponential observed transverse relaxation time ( T2*) decay. METHODS: A custom-built sequence for radial multi-echo acquisition was proposed for acquisition of a series of 3D volumetric 23 Na-images. Measurements acquired in a phantom and in vivo human brains were analyzed for SNR enhancement and multi-component T2* estimation. RESULTS: Rapid gradient refocused imaging acquired 38 echoes within a repetition time of 160 ms. Signal averaging of multi-echo time (TE) measurements showed an average brain tissue SNR enhancement of 34% compared to single-TE images across subjects. Phantom and in vivo measurements detected distinguishable signal decay characteristics for fluid and solid media. Mapping results were investigated in phantom and in vivo experiments for sequence timing optimization and signal decay analysis. The T2* mapping results were consistent with previously reported values and facilitated fluid-signal discrimination. CONCLUSION: The proposed method offers an efficient 23 Na-imaging scheme that extends existing 23 Na-MRI sequences by acquiring signal decay information with no increase in time or specific absorption rate. The resultant SNR-enhanced 23 Na-images and estimated T2* signal decay characteristics offer great potential for detailed investigation of tissue compartment characterization and clinical application. Magn Reson Med 79:1950-1961, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Optimized partial-coverage functional analysis pipeline (OPFAP): a semi-automated pipeline for skull stripping and co-registration of partial-coverage, ultra-high-field functional images.

OBJECTIVE: Ultra-high-field functional MRI (UHF-fMRI) allows for higher spatiotemporal resolution imaging. However, higher-resolution imaging entails coverage limitations. Processing partial-coverage images using standard pipelines leads to sub-optimal results. We aimed to develop a simple, semi-automated pipeline for processing partial-coverage UHF-fMRI data using widely used image processing algorithms. MATERIALS AND METHODS: We developed automated pipelines for optimized skull stripping and co-registration of partial-coverage UHF functional images, using built-in functions of the Centre for Functional Magnetic Resonance Imaging of the Brain's (FMRIB's) Software library (FSL) and advanced normalization tools. We incorporated the pipelines into the FSL's functional analysis pipeline and provide a semi-automated optimized partial-coverage functional analysis pipeline (OPFAP). RESULTS: Compared to the standard pipeline, the OPFAP yielded images with 15 and 30% greater volume of non-zero voxels after skull stripping the functional and anatomical images, respectively (all p = 0.0004), which reflected the conservation of cortical voxels lost when the standard pipeline was used. The OPFAP yielded the greatest Dice and Jaccard coefficients (87 and 80%, respectively; all p < 0.0001) between the co-registered participant gyri maps and the template gyri maps, demonstrating the goodness of the co-registration results. Furthermore, the greatest volume of group-level activation in the most number of functionally relevant regions was observed when the OPFAP was used. Importantly, group-level activations were not observed when using the standard pipeline. CONCLUSION: These results suggest that the OPFAP should be used for processing partial-coverage UHF-fMRI data for detecting high-resolution macroscopic blood oxygenation level-dependent activations.

Diffusion microscopic MRI of the mouse embryo: Protocol and practical implementation in the splotch mouse model.

PURPOSE: Advanced methodologies for visualizing novel tissue contrast are essential for phenotyping the ever-increasing number of mutant mouse embryos being generated. Although diffusion microscopic MRI (µMRI) has been used to phenotype embryos, widespread routine use is limited by extended scanning times, and there is no established experimental procedure ensuring optimal data acquisition. METHODS: We developed two protocols for designing experimental procedures for diffusion µMRI of mouse embryos, which take into account the effect of embryo preparation and pulse sequence parameters on resulting data. We applied our protocols to an investigation of the splotch mouse model as an example implementation. RESULTS: The protocols provide DTI data in 24 min per direction at 75 µm isotropic using a three-dimensional fast spin-echo sequence, enabling preliminary imaging in 3 h (6 directions plus one unweighted measurement), or detailed imaging in 9 h (42 directions plus six unweighted measurements). Application to the splotch model enabled assessment of spinal cord pathology. CONCLUSION: We present guidelines for designing diffusion µMRI experiments, which may be adapted for different studies and research facilities. As they are suitable for routine use and may be readily implemented, we hope they will be adopted by the phenotyping community.

Segmentation propagation using a 3D embryo atlas for high-throughput MRI phenotyping: comparison and validation with manual segmentation.

Effective methods for high-throughput screening and morphometric analysis are crucial for phenotyping the increasing number of mouse mutants that are being generated. Automated segmentation propagation for embryo phenotyping is an emerging application that enables noninvasive and rapid quantification of substructure volumetric data for morphometric analysis. We present a study to assess and validate the accuracy of brain and kidney volumes generated via segmentation propagation in an ex vivo mouse embryo MRI atlas comprising three different groups against the current "gold standard"--manual segmentation. Morphometric assessment showed good agreement between automatically and manually segmented volumes, demonstrating that it is possible to assess volumes for phenotyping a population of embryos using segmentation propagation with the same variation as manual segmentation. As part of this study, we have made our average atlas and segmented volumes freely available to the community for use in mouse embryo phenotyping studies. These MRI datasets and automated methods of analyses will be essential for meeting the challenge of high-throughput, automated embryo phenotyping.

Enhanced tissue differentiation in the developing mouse brain using magnetic resonance micro-histology.

PURPOSE: Worldwide efforts to understand developmental processes demand new high-resolution 3D imaging methods to detect the consequences of gene function in embryo development and diseases. Encouragingly, recent studies have shown that MRI contrast agents can highlight specific tissue structures in ex vivo adult mouse brains. MR imaging of mouse embryos is currently limited by a lack of tissue staining capabilities that would provide the flexibility and specificity offered by histological stains conventionally used for mouse embryo phenotyping. METHODS: The MRI staining properties of two readily available contrast agents, Mn-DPDP and Gd-DTPA, were investigated in mid-gestation mouse embryos. RESULTS: Brain tissue substructures not normally visible using MRI were detected. Mn-DPDP and Gd-DTPA provided spatially distinct tissue staining patterns. An initial assessment indicated that these agents utilized independent contrast enhancement mechanisms. Mn-DPDP was identified as a potential MRI contrast agent for enhancement of mouse embryonic cellular density and enabled identification of regions containing populations of neural stem and progenitor cells within the intact embryo brain. CONCLUSIONS: Different contrast agents may be used to provide tissue-specific contrast enhancement, suggesting that a host of specialized MRI stains may be available for probing the developing mouse brain and investigating developmental and disease mechanisms.

Structural correlates of active-staining following magnetic resonance microscopy in the mouse brain.

Extensive worldwide efforts are underway to produce knockout mice for each of the ~25,000 mouse genes, which may give new insights into the underlying pathophysiology of neurological disease. Microscopic magnetic resonance imaging (µMRI) is a key method for non-invasive morphological phenotyping, capable of producing high-resolution 3D images of ex-vivo brains, after fixation with an MR contrast agent. These agents have been suggested to act as active-stains, enhancing structures not normally visible on MRI. In this study, we investigated the structural correlates of the MRI agent Gd-DTPA, together with the optimal preparation and scan parameters for contrast-enhanced gradient-echo imaging of the mouse brain. We observed that in-situ preparation was preferential to ex-situ due to the degree of extraction damage. In-situ brains scanned with optimised parameters, enabled images with a high signal-to-noise-ratio (SNR ~30) and comprehensive anatomical delineation. Direct correlation of the MR brain structures to histology, detailed fine histoarchitecture in the cortex, cerebellum, olfactory bulb and hippocampus. Neurofilament staining demonstrated that regions of negative MR contrast strongly correlated to myelinated white-matter structures, whilst structures of more positive MR contrast corresponded to areas with high grey matter content. We were able to identify many sub-regions, particularly within the hippocampus, such as the unmyelinated mossy fibres (stratum lucidum) and their region of synapse in the stratum pyramidale, together with the granular layer of the dentate gyrus, an area of densely packed cell bodies, which was clearly visible as a region of hyperintensity. This suggests that cellular structure influences the site-specific distribution of the MR contrast agent, resulting in local variations in T(2)*, which leads to enhanced tissue discrimination. Our findings provide insights not only into the cellular distribution and mechanism of MR active-staining, but also allow for three dimensional analysis, which enables interpretation of magnetic resonance microscopy brain data and highlights cellular structure for investigation of disease processes in development and disease.

Magnetic resonance virtual histology for embryos: 3D atlases for automated high-throughput phenotyping.

Ambitious international efforts are underway to produce gene-knockout mice for each of the 25,000 mouse genes, providing a new platform to study mammalian development and disease. Robust, large-scale methods for morphological assessment of prenatal mice will be essential to this work. Embryo phenotyping currently relies on histological techniques but these are not well suited to large volume screening. The qualitative nature of these approaches also limits the potential for detailed group analysis. Advances in non-invasive imaging techniques such as magnetic resonance imaging (MRI) may surmount these barriers. We present a high-throughput approach to generate detailed virtual histology of the whole embryo, combined with the novel use of a whole-embryo atlas for automated phenotypic assessment. Using individual 3D embryo MRI histology, we identified new pituitary phenotypes in Hesx1 mutant mice. Subsequently, we used advanced computational techniques to produce a whole-body embryo atlas from 6 CD-1 embryos, creating an average image with greatly enhanced anatomical detail, particularly in CNS structures. This methodology enabled unsupervised assessment of morphological differences between CD-1 embryos and Chd7 knockout mice (n=5 Chd7(+/+) and n=8 Chd7(+/-), C57BL/6 background). Using a new atlas generated from these three groups, quantitative organ volumes were automatically measured. We demonstrated a difference in mean brain volumes between Chd7(+/+) and Chd7(+/-) mice (42.0 vs. 39.1mm(3), p<0.05). Differences in whole-body, olfactory and normalised pituitary gland volumes were also found between CD-1 and Chd7(+/+) mice (C57BL/6 background). Our work demonstrates the feasibility of combining high-throughput embryo MRI with automated analysis techniques to distinguish novel mouse phenotypes.

Head and neck manifestations of granulomatosis with polyangiitis.

Granulomatosis with polyangiitis is a rare autoimmune condition which causes respiratory tract granulomas, small to medium vessel vasculitis and renal disease. Head and neck manifestations are some of the most common presentations of the condition, with a significant proportion of patients experiencing sinonasal disease alone. The recognition of suggestive imaging findings, in combination with clinical history and serology, aids the diagnosis and appropriate treatment. This pictorial review describes and illustrates the head and neck imaging features of granulomatosis with polyangiitis, highlighting the range of CT and MRI findings of upper aerodigestive tract, orbital and skull-base disease. Recognition of the radiological appearances is of importance, since clinical presentations may be non-specific and limited disease may have negative serology. Imaging features may overlap with other pathologies so important differential diagnoses will be considered, and these are particularly relevant in the context of treatment resistance.

Ultra-High Field Magnetic Resonance Imaging of the Retrobulbar Optic Nerve, Subarachnoid Space, and Optic Nerve Sheath in Emmetropic and Myopic Eyes.

Purpose: We aimed to image the optic nerve, subarachnoid space and optic nerve sheath in emmetropes and myopes ultra-high field (7-Tesla) magnetic resonance imaging (MRI). We targeted the retrobulbar distance of approximately 3 mm behind the eyeball, an area of clinical interest because of optic nerve sheath distensibility and pressure-related enlargement. Methods: Eleven emmetropes (+0.75 to -0.50D, aged 20-41 years) and 10 myopes (-4.5 to -12D, aged 21-37 years) participated. Cross-sectional area of the optic nerve, subarachnoid space and optic nerve sheath at approximately 3 mm behind the eye were measured from two-dimensional T2-weighted coronal oblique MRI images obtained through the left optic nerve. Axial length of the left eye was measured from T2-weighted axial MRI images. In nine emmetropes and seven myopes, the optic nerve head was imaged with optical coherence tomography to compare retrobulbar and intraocular measures. Results: Retrobulbar optic nerve, subarachnoid space and optic nerve sheath dimensions differed between myopes and emmetropes. Myopes tended to have smaller optic nerve and subarachnoid space. Longer MRI-derived axial length was associated with smaller optic nerve area (P = 0.03). Bruch's membrane opening area did not predict retrobulbar optic nerve area (P = 0.48). Conclusions: This study demonstrates the feasibility of using 7-Tesla MRI to measure optic nerve, subarachnoid space, and optic nerve sheath dimensions behind the eye. In healthy adults, the retrobulbar optic nerve and subarachnoid space size are influenced by the degree of myopia. Translational Relevance: ultra-high field MRI is a practical tool for assessing the morphometry of the optic nerve and surrounding anatomy behind the eye.

MR-EYE: High-Resolution MRI of the Human Eye and Orbit at Ultrahigh Field (7T).

Ultrahigh-field (7T) MRI provides improved contrast and a signal-to-noise gain compared with lower magnetic field strengths. Here, we demonstrate feasibility and optimization of anatomic imaging of the eye and orbit using a dedicated commercial multichannel transmit and receive eye coil. Optimization of participant setup techniques and MRI sequence parameters allowed for improvements in the image resolution and contrast, and the eye and orbit coverage with minimal susceptibility and motion artifacts in a clinically feasible protocol.

Axonal loss in major sensorimotor tracts is associated with impaired motor performance in minimally disabled multiple sclerosis patients.

Multiple sclerosis is a neuroinflammatory disease of the CNS that is associated with significant irreversible neuro-axonal loss, leading to permanent disability. There is thus an urgent need for in vivo markers of axonal loss for use in patient monitoring or as end-points for trials of neuroprotective agents. Advanced diffusion MRI can provide markers of diffuse loss of axonal fibre density or atrophy within specific white matter pathways. These markers can be interrogated in specific white matter tracts that underpin important functional domains such as sensorimotor function. This study aimed to evaluate advanced diffusion MRI markers of axonal loss within the major sensorimotor tracts of the brain, and to correlate the degree of axonal loss in these tracts to precise kinematic measures of hand and foot motor control and gait in minimally disabled people with multiple sclerosis. Twenty-eight patients (Expanded Disability Status Scale < 4, and Kurtzke Functional System Scores for pyramidal and cerebellar function ≤ 2) and 18 healthy subjects underwent ultra-high field 7 Tesla diffusion MRI for calculation of fibre-specific measures of axonal loss (fibre density, reflecting diffuse axonal loss and fibre cross-section reflecting tract atrophy) within three tracts: cortico-spinal tract, interhemispheric sensorimotor tract and cerebello-thalamic tracts. A visually guided force-matching task involving either the hand or foot was used to assess visuomotor control, and three-dimensional marker-based video tracking was used to assess gait. Fibre-specific axonal markers for each tract were compared between groups and correlated with visuomotor task performance (force error and lag) and gait parameters (stance, stride length, step width, single and double support) in patients. Patients displayed significant regional loss of fibre cross-section with minimal loss of fibre density in all tracts of interest compared to healthy subjects (family-wise error corrected p-value < 0.05), despite relatively few focal lesions within these tracts. In patients, reduced axonal fibre density and cross-section within the corticospinal tracts and interhemispheric sensorimotor tracts were associated with larger force tracking error and gait impairments (shorter stance, smaller step width and longer double support) (family-wise error corrected p-value < 0.05). In conclusion, significant gait and motor control impairments can be detected in minimally disabled people with multiple sclerosis that correlated with axonal loss in major sensorimotor pathways of the brain. Given that axonal loss is irreversible, the combined use of advanced imaging and kinematic markers could be used to identify patients at risk of more severe motor impairments as they emerge for more aggressive therapeutic interventions.

Post-mortem examination of human fetuses: a comparison of whole-body high-field MRI at 9.4 T with conventional MRI and invasive autopsy.

BACKGROUND: Conventional whole-body MRI at 1.5 T does not provide adequate image quality of small fetuses, thus reducing its potential for use as an alternative to invasive autopsy. High-field whole-body MRI at 9.4 T provides good images of small animals. We therefore compared the diagnostic usefulness of high-field MRI with conventional MRI for post-mortem examination of human fetuses. METHODS: We did whole-body MRI at 9.4 T and 1.5 T on 18 fetuses of less than 22 weeks' gestation, using three-dimensional T(2)-weighted fast-spin echo sequences, before doing invasive autopsy. Images obtained with MRI for each system were compared with the findings of invasive autopsy in a blinded manner. Tissue contrast of 14 different regions was compared on 1.5 T and 9.4 T images that were provided by paediatric radiologists separately and in a random order, and image quality was scored on a four-point scale. The primary endpoint was diagnostic accuracy. FINDINGS: Spatial resolution, tissue contrast, and image quality of all organ systems were much better with high-field MRI than with conventional MRI. All structural abnormalities that were detected with invasive autopsy and internal examination of visceral organs were also detected with high-field MRI, whereas conventional MRI was not diagnostically useful in 14 (78%) cases. INTERPRETATION: Whole-body high-field MRI is a feasible option for post-mortem examination of human fetuses, and can provide good tissue characterisation even in small fetuses (5 g). The use of MRI at 9.4 T might be helpful in the development of a minimally invasive perinatal autopsy system. FUNDING: Department of Health Policy Research Programme, British Heart Foundation, National Institute of Health Research, Higher Education Funding Council for England, Biotechnology and Biological Sciences Research Council, Engineering and Physical Sciences Research Council, Great Ormond Street Hospital, University College London (UCL) Institute of Child Health, UCL Hospital, and UCL.