Multiband accelerated 2D EPI for multi-echo brain QSM at 3 T.

PURPOSE: Data for QSM are typically acquired using multi-echo 3D gradient echo (GRE), but EPI can be used to accelerate QSM and provide shorter acquisition times. So far, EPI-QSM has been limited to single-echo acquisitions, which, for 3D GRE, are known to be less accurate than multi-echo sequences. Therefore, we compared single-echo and multi-echo EPI-QSM reconstructions across a range of parallel imaging and multiband acceleration factors. METHODS: Using 2D single-shot EPI in the brain, we compared QSM from single-echo and multi-echo acquisitions across combined parallel-imaging and multiband acceleration factors ranging from 2 to 16, with volume pulse TRs from 21.7 to 3.2 s, respectively. For single-echo versus multi-echo reconstructions, we investigated the effect of acceleration factors on regional susceptibility values, temporal noise, and image quality. We introduce a novel masking method based on thresholding the magnitude of the local field gradients to improve brain masking in challenging regions. RESULTS: At 1.6-mm isotropic resolution, high-quality QSM was achieved using multi-echo 2D EPI with a combined acceleration factor of 16 and a TR of 3.2 s, which enables functional applications. With these high acceleration factors, single-echo reconstructions are inaccurate and artefacted, rendering them unusable. Multi-echo acquisitions greatly improve QSM quality, particularly at higher acceleration factors, provide more consistent regional susceptibility values across acceleration factors, and decrease temporal noise compared with single-echo QSM reconstructions. CONCLUSION: Multi-echo acquisition is more robust for EPI-QSM across parallel imaging and multiband acceleration factors than single-echo acquisition. Multi-echo EPI can be used for highly accelerated acquisition while preserving QSM accuracy and quality relative to gold-standard 3D-GRE QSM.

Initial findings using high-resolution magnetic resonance imaging for visualisation of the sural nerve and surrounding anatomy in healthy volunteers at 7 Tesla.

BACKGROUND AND AIMS: Histopathological diagnosis is the gold standard in many acquired inflammatory, infiltrative and amyloid based peripheral nerve diseases and a sensory nerve biopsy of sural or superficial peroneal nerve is favoured where a biopsy is deemed necessary. The ability to determine nerve pathology by high-resolution imaging techniques resolving anatomy and imaging characteristics might improve diagnosis and obviate the need for biopsy in some. The sural nerve is anatomically variable and occasionally adjacent vessels can be sent for analysis in error. Knowing the exact position and relationships of the nerve prior to surgery could be clinically useful and thus reliably resolving nerve position has some utility. METHODS: 7T images of eight healthy volunteers' (HV) right ankle were acquired in a pilot study using a double-echo in steady-state sequence for high-resolution anatomy images. Magnetic Transfer Ratio images were acquired of the same area. Systematic scoring of the sural, tibial and deep peroneal nerve around the surgical landmark 7 cm from the lateral malleolus was performed (number of fascicles, area in voxels and mm2, diameter and location relative to nearby vessels and muscles). RESULTS: The sural and tibial nerves were visualised in the high-resolution double-echo in steady-state (DESS) image in all HV. The deep peroneal nerve was not always visualised at level of interest. The MTR values were tightly grouped except in the sural nerve where the nerve was not visualised in two HV. The sural nerve location was found to be variable (e.g., lateral or medial to, or crossing behind, or found positioned directly posterior to the saphenous vein). INTERPRETATION: High-resolution high-field images have excellent visualisation of the sural nerve and would give surgeons prior knowledge of the position before surgery. Basic imaging characteristics of the sural nerve can be acquired, but more detailed imaging characteristics are not easily evaluable in the very small sural and further developments and specific studies are required for any diagnostic utility at 7T.

Quantitative susceptibility mapping identifies hippocampal and other subcortical grey matter tissue composition changes in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is associated with widespread brain alterations. Using quantitative susceptibility mapping (QSM) alongside transverse relaxation rate ( R 2 * ), we investigated regional brain susceptibility changes in 36 patients with left-sided (LTLE) or right-sided TLE (RTLE) secondary to hippocampal sclerosis, and 27 healthy controls (HC). We compared three susceptibility calculation methods to ensure image quality. Correlations of susceptibility and R 2 * with age of epilepsy onset, frequency of focal-to-bilateral tonic-clonic seizures (FBTCS), and neuropsychological test scores were examined. Weak-harmonic QSM (WH-QSM) successfully reduced noise and removed residual background field artefacts. Significant susceptibility increases were identified in the left putamen in the RTLE group compared to the LTLE group, the right putamen and right thalamus in the RTLE group compared to HC, and a significant susceptibility decrease in the left hippocampus in LTLE versus HC. LTLE patients who underwent epilepsy surgery showed significantly lower left-versus-right hippocampal susceptibility. Significant R 2 * changes were found between TLE and HC groups in the amygdala, putamen, thalamus, and in the hippocampus. Specifically, decreased R2 * was found in the left and right hippocampus in LTLE and RTLE, respectively, compared to HC. Susceptibility and R 2 * were significantly correlated with cognitive test scores in the hippocampus, globus pallidus, and thalamus. FBTCS frequency correlated positively with ipsilateral thalamic and contralateral putamen susceptibility and with R 2 * in bilateral globi pallidi. Age of onset was correlated with susceptibility in the hippocampus and putamen, and with R 2 * in the caudate. Susceptibility and R 2 * changes observed in TLE groups suggest selective loss of low-myelinated neurons alongside iron redistribution in the hippocampi, predominantly ipsilaterally, indicating QSM's sensitivity to local pathology. Increased susceptibility and R 2 * in the thalamus and putamen suggest increased iron content and reflect disease severity.

Investigating the effect of oblique image acquisition on the accuracy of QSM and a robust tilt correction method.

PURPOSE: Quantitative susceptibility mapping (QSM) is used increasingly for clinical research where oblique image acquisition is commonplace, but its effects on QSM accuracy are not well understood. THEORY AND METHODS: The QSM processing pipeline involves defining the unit magnetic dipole kernel, which requires knowledge of the direction of the main magnetic field B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ with respect to the acquired image volume axes. The direction of B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ is dependent on the axis and angle of rotation in oblique acquisition. Using both a numerical brain phantom and in vivo acquisitions in 5 healthy volunteers, we analyzed the effects of oblique acquisition on magnetic susceptibility maps. We compared three tilt-correction schemes at each step in the QSM pipeline: phase unwrapping, background field removal and susceptibility calculation, using the RMS error and QSM-tuned structural similarity index. RESULTS: Rotation of wrapped phase images gave severe artifacts. Background field removal with projection onto dipole fields gave the most accurate susceptibilities when the field map was first rotated into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ . Laplacian boundary value and variable-kernel sophisticated harmonic artifact reduction for phase data background field removal methods gave accurate results without tilt correction. For susceptibility calculation, thresholded k-space division, iterative Tikhonov regularization, and weighted linear total variation regularization, all performed most accurately when local field maps were rotated into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ before susceptibility calculation. CONCLUSION: For accurate QSM, oblique acquisition must be taken into account. Rotation of images into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ should be carried out after phase unwrapping and before background-field removal. We provide open-source tilt-correction code to incorporate easily into existing pipelines: https://github.com/o-snow/QSM_TiltCorrection.git.

Quantitative MRI outcome measures in CMT1A using automated lower limb muscle segmentation.

BACKGROUND: Lower limb muscle magnetic resonance imaging (MRI) obtained fat fraction (FF) can detect disease progression in patients with Charcot-Marie-Tooth disease 1A (CMT1A). However, analysis is time-consuming and requires manual segmentation of lower limb muscles. We aimed to assess the responsiveness, efficiency and accuracy of acquiring FF MRI using an artificial intelligence-enabled automated segmentation technique. METHODS: We recruited 20 CMT1A patients and 7 controls for assessment at baseline and 12 months. The three-point-Dixon fat water separation technique was used to determine thigh-level and calf-level muscle FF at a single slice using regions of interest defined using Musclesense, a trained artificial neural network for lower limb muscle image segmentation. A quality control (QC) check and correction of the automated segmentations was undertaken by a trained observer. RESULTS: The QC check took on average 30 seconds per slice to complete. Using QC checked segmentations, the mean calf-level FF increased significantly in CMT1A patients from baseline over an average follow-up of 12.5 months (1.15%±1.77%, paired t-test p=0.016). Standardised response mean (SRM) in patients was 0.65. Without QC checks, the mean FF change between baseline and follow-up, at 1.15%±1.68% (paired t-test p=0.01), was almost identical to that seen in the corrected data, with a similar overall SRM at 0.69. CONCLUSIONS: Using automated image segmentation for the first time in a longitudinal study in CMT, we have demonstrated that calf FF has similar responsiveness to previously published data, is efficient with minimal time needed for QC checks and is accurate with minimal corrections needed.

Diffusion MRI of the facial-vestibulocochlear nerve complex: a prospective clinical validation study.

OBJECTIVES: Surgical planning of vestibular schwannoma surgery would benefit greatly from a robust method of delineating the facial-vestibulocochlear nerve complex with respect to the tumour. This study aimed to optimise a multi-shell readout-segmented diffusion-weighted imaging (rs-DWI) protocol and develop a novel post-processing pipeline to delineate the facial-vestibulocochlear complex within the skull base region, evaluating its accuracy intraoperatively using neuronavigation and tracked electrophysiological recordings. METHODS: In a prospective study of five healthy volunteers and five patients who underwent vestibular schwannoma surgery, rs-DWI was performed and colour tissue maps (CTM) and probabilistic tractography of the cranial nerves were generated. In patients, the average symmetric surface distance (ASSD) and 95% Hausdorff distance (HD-95) were calculated with reference to the neuroradiologist-approved facial nerve segmentation. The accuracy of patient results was assessed intraoperatively using neuronavigation and tracked electrophysiological recordings. RESULTS: Using CTM alone, the facial-vestibulocochlear complex of healthy volunteer subjects was visualised on 9/10 sides. CTM were generated in all 5 patients with vestibular schwannoma enabling the facial nerve to be accurately identified preoperatively. The mean ASSD between the annotators' two segmentations was 1.11 mm (SD 0.40) and the mean HD-95 was 4.62 mm (SD 1.78). The median distance from the nerve segmentation to a positive stimulation point was 1.21 mm (IQR 0.81-3.27 mm) and 2.03 mm (IQR 0.99-3.84 mm) for the two annotators, respectively. CONCLUSIONS: rs-DWI may be used to acquire dMRI data of the cranial nerves within the posterior fossa. CLINICAL RELEVANCE STATEMENT: Readout-segmented diffusion-weighted imaging and colour tissue mapping provide 1-2 mm spatially accurate imaging of the facial-vestibulocochlear nerve complex, enabling accurate preoperative localisation of the facial nerve. This study evaluated the technique in 5 healthy volunteers and 5 patients with vestibular schwannoma. KEY POINTS: • Readout-segmented diffusion-weighted imaging (rs-DWI) with colour tissue mapping (CTM) visualised the facial-vestibulocochlear nerve complex on 9/10 sides in 5 healthy volunteer subjects. • Using rs-DWI and CTM, the facial nerve was visualised in all 5 patients with vestibular schwannoma and within 1.21-2.03 mm of the nerve's true intraoperative location. • Reproducible results were obtained on different scanners.

Evidence of nerve hypertrophy in patients with inclusion body myositis on lower limb MRI.

INTRODUCTION/AIMS: Inclusion body myositis (IBM) is a myopathic condition but in some patients has been associated with an axonal length-dependent polyneuropathy. In this study, we quantified the cross-sectional area of the sciatic and tibial nerves in patients with IBM comparing with Charcot-Marie-Tooth disease type 1A (CMT1A) and healthy controls using magnetic resonance neurography (MRN). METHODS: MRN of the sciatic and tibial nerves was performed at 3T using MPRAGE and Dixon acquisitions. Nerve cross-sectional area (CSA) was measured at the mid-thigh and upper third calf regions by an observer blinded to the diagnosis. Correlations were performed between these measurements and clinical data. RESULTS: A total of 20 patients with IBM, 20 CMT1A and 29 healthy controls (age- and sex-matched) were studied. Sciatic nerve CSA was significantly enlarged in patients with IBM and CMT1A compared to controls (sciatic nerve mean CSA 62.3 ± 22.9 mm2 (IBM) vs. 35.5 ± 9.9 mm2 (controls), p < 0.001; and 96.9 ± 35.5 mm2 (CMT1A) vs. 35.5 ± 9.9 mm2 (controls); p < 0.001). Tibial nerve CSA was also enlarged in IBM and CMT1 patients compared to controls. DISCUSSION: MRN reveals significant hypertrophy of the sciatic and tibial nerves in patients with IBM and CMT1A compared to controls. Further studies are needed to correlate with neurophysiological measures and assess whether this finding is useful diagnostically.

Clinical evaluation of automated quantitative MRI reports for assessment of hippocampal sclerosis.

OBJECTIVES: Hippocampal sclerosis (HS) is a common cause of temporal lobe epilepsy. Neuroradiological practice relies on visual assessment, but quantification of HS imaging biomarkers-hippocampal volume loss and T2 elevation-could improve detection. We tested whether quantitative measures, contextualised with normative data, improve rater accuracy and confidence. METHODS: Quantitative reports (QReports) were generated for 43 individuals with epilepsy (mean age ± SD 40.0 ± 14.8 years, 22 men; 15 histologically unilateral HS; 5 bilateral; 23 MR-negative). Normative data was generated from 111 healthy individuals (age 40.0 ± 12.8 years, 52 men). Nine raters with different experience (neuroradiologists, trainees, and image analysts) assessed subjects' imaging with and without QReports. Raters assigned imaging normal, right, left, or bilateral HS. Confidence was rated on a 5-point scale. RESULTS: Correct designation (normal/abnormal) was high and showed further trend-level improvement with QReports, from 87.5 to 92.5% (p = 0.07, effect size d = 0.69). Largest magnitude improvement (84.5 to 93.8%) was for image analysts (d = 0.87). For bilateral HS, QReports significantly improved overall accuracy, from 74.4 to 91.1% (p = 0.042, d = 0.7). Agreement with the correct diagnosis (kappa) tended to increase from 0.74 ('fair') to 0.86 ('excellent') with the report (p = 0.06, d = 0.81). Confidence increased when correctly assessing scans with the QReport (p < 0.001, η2p = 0.945). CONCLUSIONS: QReports of HS imaging biomarkers can improve rater accuracy and confidence, particularly in challenging bilateral cases. Improvements were seen across all raters, with large effect sizes, greatest for image analysts. These findings may have positive implications for clinical radiology services and justify further validation in larger groups. KEY POINTS: • Quantification of imaging biomarkers for hippocampal sclerosis-volume loss and raised T2 signal-could improve clinical radiological detection in challenging cases. • Quantitative reports for individual patients, contextualised with normative reference data, improved diagnostic accuracy and confidence in a group of nine raters, in particular for bilateral HS cases. • We present a pre-use clinical validation of an automated imaging assessment tool to assist clinical radiology reporting of hippocampal sclerosis, which improves detection accuracy.

Automated quantitative MRI volumetry reports support diagnostic interpretation in dementia: a multi-rater, clinical accuracy study.

OBJECTIVES: We examined whether providing a quantitative report (QReport) of regional brain volumes improves radiologists' accuracy and confidence in detecting volume loss, and in differentiating Alzheimer's disease (AD) and frontotemporal dementia (FTD), compared with visual assessment alone. METHODS: Our forced-choice multi-rater clinical accuracy study used MRI from 16 AD patients, 14 FTD patients, and 15 healthy controls; age range 52-81. Our QReport was presented to raters with regional grey matter volumes plotted as percentiles against data from a normative population (n = 461). Nine raters with varying radiological experience (3 each: consultants, registrars, 'non-clinical image analysts') assessed each case twice (with and without the QReport). Raters were blinded to clinical and demographic information; they classified scans as 'normal' or 'abnormal' and if 'abnormal' as 'AD' or 'FTD'. RESULTS: The QReport improved sensitivity for detecting volume loss and AD across all raters combined (p = 0.015* and p = 0.002*, respectively). Only the consultant group's accuracy increased significantly when using the QReport (p = 0.02*). Overall, raters' agreement (Cohen's κ) with the 'gold standard' was not significantly affected by the QReport; only the consultant group improved significantly (κs 0.41➔0.55, p = 0.04*). Cronbach's alpha for interrater agreement improved from 0.886 to 0.925, corresponding to an improvement from 'good' to 'excellent'. CONCLUSION: Our QReport referencing single-subject results to normative data alongside visual assessment improved sensitivity, accuracy, and interrater agreement for detecting volume loss. The QReport was most effective in the consultants, suggesting that experience is needed to fully benefit from the additional information provided by quantitative analyses. KEY POINTS: • The use of quantitative report alongside routine visual MRI assessment improves sensitivity and accuracy for detecting volume loss and AD vs visual assessment alone. • Consultant neuroradiologists' assessment accuracy and agreement (kappa scores) significantly improved with the use of quantitative atrophy reports. • First multi-rater radiological clinical evaluation of visual quantitative MRI atrophy report for use as a diagnostic aid in dementia.

Cerebrospinal fluid flow dynamics in Huntington's disease evaluated by phase contrast MRI.

Multiple targeted therapeutics for Huntington's disease are now in clinical trials, including intrathecally delivered compounds. Previous research suggests that CSF dynamics may be altered in Huntington's disease, which could be of paramount relevance to intrathecal drug delivery to the brain. To test this hypothesis, we conducted a prospective cross-sectional study comparing people with early stage Huntington's disease with age- and gender-matched healthy controls. CSF peak velocity, mean velocity and mean flow at the level of the cerebral aqueduct, and sub-arachnoid space in the upper and lower spine, were quantified using phase contrast MRI. We calculated Spearman's rank correlations, and tested inter-group differences with Wilcoxon rank-sum test. Ten people with early Huntington's disease, and 10 controls were included. None of the quantified measures was associated with potential modifiers of CSF dynamics (demographics, osmolality, and brain volumes), or by known modifiers of Huntington's disease (age and HTTCAG repeat length); and no significant differences were found between the two studied groups. While external validation is required, the attained results are sufficient to conclude tentatively that a clinically relevant alteration of CSF dynamics - that is, one that would justify dose-adjustments of intrathecal drugs - is unlikely to exist in Huntington's disease.

Development of MRC Centre MRI calf muscle fat fraction protocol as a sensitive outcome measure in Hereditary Sensory Neuropathy Type 1.

OBJECTIVES: Hereditary sensory neuropathy type 1 (HSN1) is a rare, slowly progressive neuropathy causing profound sensory deficits and often severe motor loss. L-serine supplementation is a possible candidate therapy but the lack of responsive outcome measures is a barrier for undertaking clinical trials in HSN1. We performed a 12-month natural history study to characterise the phenotype of HSN1 and to identify responsive outcome measures. METHODS: Assessments included Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), CMTNSv2-Rasch modified, nerve conduction studies, quantitative sensory testing, intraepidermal nerve fibre density (thigh), computerised myometry (lower limbs), plasma 1-deoxysphingolipid levels, calf-level intramuscular fat accumulation by MRI and patient-based questionnaires (Neuropathic Pain Symptom Inventory and 36-Short Form Health Survey version 2 [SF-36v2]). RESULTS: 35 patients with HSN1 were recruited. There was marked heterogeneity in the phenotype mainly due to differences between the sexes: males generally more severely affected. The outcome measures that significantly changed over 1 year and correlated with CMTNSv2, SF-36v2-physical component and disease duration were MRI determined calf intramuscular fat accumulation (mean change in overall calf fat fraction 2.36%, 95% CI 1.16 to 3.55, p=0.0004), pressure pain threshold on the hand (mean change 40 kPa, 95% CI 0.7 to 80, p=0.046) and myometric measurements of ankle plantar flexion (median change -0.5 Nm, IQR -9.5 to 0, p=0.0007), ankle inversion (mean change -0.89 Nm, 95% CI -1.66 to -0.12, p=0.03) and eversion (mean change -1.61 Nm, 95% CI -2.72 to -0.51, p=0.006). Intramuscular calf fat fraction was the most responsive outcome measure. CONCLUSION: MRI determined calf muscle fat fraction shows validity and high responsiveness over 12 months and will be useful in HSN1 clinical trials.

Stability and sensitivity of water T2 obtained with IDEAL-CPMG in healthy and fat-infiltrated skeletal muscle.

Quantifying muscle water T2 (T2 -water) independently of intramuscular fat content is essential in establishing T2 -water as an outcome measure for imminent new therapy trials in neuromuscular diseases. IDEAL-CPMG combines chemical shift fat-water separation with T2 relaxometry to obtain such a measure. Here we evaluate the reproducibility and B1 sensitivity of IDEAL-CPMG T2 -water and fat fraction (f.f.) values in healthy subjects, and demonstrate the potential of the method to quantify T2 -water variation in diseased muscle displaying varying degrees of fatty infiltration. The calf muscles of 11 healthy individuals (40.5 ± 10.2 years) were scanned twice at 3 T with an inter-scan interval of 4 weeks using IDEAL-CPMG, and 12 patients with hypokalemic periodic paralysis (HypoPP) (42.3 ± 11.5 years) were also imaged. An exponential was fitted to the signal decay of the separated water and fat components to determine T2 -water and the fat signal amplitude muscle regions manually segmented. Overall mean calf-level muscle T2 -water in healthy subjects was 31.2 ± 2.0 ms, without significant inter-muscle differences (p = 0.37). Inter-subject and inter-scan coefficients of variation were 5.7% and 3.2% respectively for T2 -water and 41.1% and 15.4% for f.f. Bland-Altman mean bias and ±95% coefficients of repeatability were for T2 -water (0.15, -2.65, 2.95) ms and f.f. (-0.02, -1.99, 2.03)%. There was no relationship between T2 -water (ρ = 0.16, p = 0.07) or f.f. (ρ = 0.03, p = 0.7761) and B1 error or any correlation between T2 -water and f.f. in the healthy subjects (ρ = 0.07, p = 0.40). In HypoPP there was a measurable relationship between T2 -water and f.f. (ρ = 0.59, p < 0.001). IDEAL-CPMG provides a feasible way to quantify T2 -water in muscle that is reproducible and sensitive to meaningful physiological changes without post hoc modeling of the fat contribution. In patients, IDEAL-CPMG measured elevations in T2 -water and f.f. while showing a weak relationship between these parameters, thus showing promise as a practical means of quantifying muscle water in patient populations.

Muscle magnetic resonance imaging in congenital myasthenic syndromes.

INTRODUCTION: In this study we investigated muscle magnetic resonance imaging in congenital myasthenic syndromes (CMS). METHODS: Twenty-six patients with 9 CMS subtypes and 10 controls were imaged. T1-weighted (T1w) and short-tau inversion recovery (STIR) 3-Tesla MRI images obtained at thigh and calf levels were scored for severity. RESULTS: Overall mean the T1w score was increased in GFPT1 and DPAGT1 CMS. T1w scans of the AChR-deficiency, COLQ, and CHAT subjects were indistinguishable from controls. STIR images from CMS patients did not differ significantly from those of controls. Mean T1w score correlated with age in the CMS cohort. CONCLUSIONS: MRI appearances ranged from normal to marked abnormality. T1w images seem to be especially abnormal in some CMS caused by mutations of proteins involved in the glycosylation pathway. A non-selective pattern of fat infiltration or a normal-appearing scan in the setting of significant clinical weakness should suggest CMS as a potential diagnosis. Muscle MRI could play a role in differentiating CMS subtypes. Muscle Nerve 54: 211-219, 2016.

Extra-ocular muscle MRI in genetically-defined mitochondrial disease.

OBJECTIVES: Conventional and quantitative MRI was performed in patients with chronic progressive external ophthalmoplegia (CPEO), a common manifestation of mitochondrial disease, to characterise MRI findings in the extra-ocular muscles (EOMs) and investigate whether quantitative MRI provides clinically relevant measures of disease. METHODS: Patients with CPEO due to single mitochondrial DNA deletions were compared with controls. Range of eye movement (ROEM) measurements, peri-orbital 3 T MRI T1-weighted (T1w) and short-tau-inversion-recovery (STIR) images, and T2 relaxation time maps were obtained. Blinded observers graded muscle atrophy and T1w/STIR hyperintensity. Cross-sectional areas and EOM mean T2s were recorded and correlated with clinical parameters. RESULTS: Nine patients and nine healthy controls were examined. Patients had reduced ROEM (patients 13.3°, controls 49.3°, p < 0.001), greater mean atrophy score and increased T1w hyperintensities. EOM mean cross-sectional area was 43 % of controls and mean T2s were prolonged (patients 75.6 ± 7.0 ms, controls 55.2 ± 4.1 ms, p < 0.001). ROEM correlated negatively with EOM T2 (rho = -0.89, p < 0.01), whilst cross-sectional area failed to correlate with any clinical measures. CONCLUSIONS: MRI demonstrates EOM atrophy, characteristic signal changes and prolonged T2 in CPEO. Correlation between elevated EOM T2 and ROEM impairment represents a potential measure of disease severity that warrants further evaluation. KEY POINTS: Chronic progressive external ophthalmoplegia is a common clinical manifestation of mitochondrial disease. • Existing extra-ocular muscle MRI data in CPEO reports variable radiological findings. MRI confirmed EOM atrophy and characteristic signal changes in CPEO. EOM T2 was significantly elevated in CPEO and correlated negatively with ocular movements. EOM T2 represents a potential quantitative measure of disease severity in CPEO.

Design, operation, and safety of single-room interventional MRI suites: practical experience from two centers.

The design and operation of a facility in which a magnetic resonance imaging (MRI) scanner is incorporated into a room used for surgical or endovascular cardiac interventions presents several challenges. MR safety must be maintained in the presence of a much wider variety of equipment than is found in a diagnostic unit, and of staff unfamiliar with the MRI environment, without compromising the safety and practicality of the interventional procedure. Both the MR-guided cardiac interventional unit at Kings College London and the intraoperative imaging suite at the National Hospital for Neurology and Neurosurgery are single-room interventional facilities incorporating 1.5 T cylindrical-bore MRI scanners. The two units employ similar strategies to maintain MR safety, both in original design and day-to-day operational workflows, and between them over a decade of incident-free practice has been accumulated. This article outlines these strategies, highlighting both similarities and differences between the units, as well as some lessons learned and resulting procedural changes made in both units since installation.

Auditory tracts identified with combined fMRI and diffusion tractography.

The auditory tracts in the human brain connect the inferior colliculus (IC) and medial geniculate body (MGB) to various components of the auditory cortex (AC). While in non-human primates and in humans, the auditory system is differentiated in core, belt and parabelt areas, the correspondence between these areas and anatomical landmarks on the human superior temporal gyri is not straightforward, and at present not completely understood. However it is not controversial that there is a hierarchical organization of auditory stimuli processing in the auditory system. The aims of this study were to demonstrate that it is possible to non-invasively and robustly identify auditory projections between the auditory thalamus/brainstem and different functional levels of auditory analysis in the cortex of human subjects in vivo combining functional magnetic resonance imaging (fMRI) with diffusion MRI, and to investigate the possibility of differentiating between different components of the auditory pathways (e.g. projections to areas responsible for sound, pitch and melody processing). We hypothesized that the major limitation in the identification of the auditory pathways is the known problem of crossing fibres and addressed this issue acquiring DTI with b-values higher than commonly used and adopting a multi-fibre ball-and-stick analysis model combined with probabilistic tractography. Fourteen healthy subjects were studied. Auditory areas were localized functionally using an established hierarchical pitch processing fMRI paradigm. Together fMRI and diffusion MRI allowed the successful identification of tracts connecting IC with AC in 64 to 86% of hemispheres and left sound areas with homologous areas in the right hemisphere in 86% of hemispheres. The identified tracts corresponded closely with a three-dimensional stereotaxic atlas based on postmortem data. The findings have both neuroscientific and clinical implications for delineation of the human auditory system in vivo.

Cerebral venous system and anatomical predisposition to high-altitude headache.

OBJECTIVE: As inspired oxygen availability falls with ascent to altitude, some individuals develop high-altitude headache (HAH). We postulated that HAH results when hypoxia-associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies. METHODS: In high-altitude studies, retinal venous distension (RVD) was ophthalmoscopically assessed in 24 subjects (6 female) and sea-level cranial magnetic resonance imaging was performed in 12 subjects ascending to 5,300m. Correlation of headache burden (summed severity scores [0-4]≤24 hours from arrival at each altitude) with RVD, and with cerebral/cerebrospinal fluid (CSF)/venous compartment volumes, was sought. In a sea-level hypoxic study, 11 subjects underwent gadolinium-enhanced magnetic resonance venography before and during hypoxic challenge (fraction of inspired oxygen=0.11, 1 hour). RESULTS: In the high-altitude studies, headache burden correlated with both RVD (Spearman rho=0.55, p=0.005) and with the degree of narrowing of 1 or both transverse venous sinuses (r=-0.56, p=0.03). It also related inversely to both the lateral+third ventricle summed volumes (Spearman rho=-0.5, p=0.05) and pericerebellar CSF volume (r=-0.56, p=0.03). In the hypoxic study, cerebral and retinal vein engorgement were correlated, and rose as the combined conduit score fell (a measure of venous outflow restriction; r=-0.66, p<0.05 and r=-0.75, p<0.05, respectively). INTERPRETATION: Arterial hypoxemia is associated with cerebral and retinal venous distension, whose magnitude correlates with HAH burden. Restriction in cerebral venous outflow is associated with retinal distension and HAH. Limitations in cerebral venous efferent flow may predispose to headache when hypoxia-related increases in cerebral arterial flow occur.

Improved anatomical reproducibility in quantitative lower-limb muscle MRI.

PURPOSE: To compare the influence of two limb positions and slice prescription using scout-image-based and surface-anatomy-based methods on the reproducibility of quantitative MRI of lower-limb muscles. MATERIALS AND METHODS: Ten healthy subjects were scanned at 3 Tesla with a two-dimensional turbo spin-echo T1-weighted acquisition. Imaging was performed at thigh and calf level in two subject limb positions and independently repeated by a second operator. Regions-of-interest (ROI) were drawn on three muscles at thigh and calf levels on axial slices at fixed distance from the knee joint and at a level determined by surface anatomy. RESULTS: Test-retest reliability of muscle cross-sectional area and ROI area overlap were similar for both limb positioning methods. Changing limb position between scans reduced ROI overlap (P < 0.01). Scout-image-based slice prescription resulted in narrower limits of agreement and higher intraclass correlation coefficients compared with surface-anatomy-based slice prescription. CONCLUSION: Slice prescription based on fixed distance from the knee joint provided superior reproducibility of slice location than a surface anatomy-based method and should be used for longitudinal quantitative MRI studies. Exact subject positioning will depend on scanner and coil configuration, but should be consistent through a longitudinal study.

Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers.

OBJECTIVES: Quantitative magnetic resonance imaging (MRI) can potentially meet the pressing need for objective, sensitive, reproducible outcome measures in neuromuscular disease trials. We tested, in healthy volunteers, the consistency, reliability and sensitivity to normal inter-subject variation of MRI methods targeted to lower limb muscle pathology to inform the design of practical but comprehensive MRI outcome measure protocols for use in imminent patient studies. METHODS: Forty-seven healthy volunteers, age 21-81 years, were subject at 3T to three-point Dixon fat-fraction measurement, T1-relaxometry, T2-relaxometry and magnetisation transfer ratio (MTR) imaging at mid-thigh and mid-calf level bilaterally. Fifteen subjects underwent repeat imaging at 2 weeks. RESULTS: Mean between-muscle fat fraction and T2 differences were small, but significant (p < 0.001). Fat fraction and T 2 correlated positively, and MTR negatively with subject age in both the thigh and calf, with similar significant correlations with weight at thigh level only (p < 0.001 to p < 0.05). Scan-rescan and inter-observer intra-class correlation coefficients ranged between 0.62-0.84 and 0.79-0.99 respectively. CONCLUSIONS: Quantitative lower-limb muscle MRI using readily implementable methods was sensitive enough to demonstrate inter-muscle differences (small in health), and correlations with subject age and weight. In combination with high reliability, this strongly supports the suitability of these methods to provide longitudinal outcome measures in neuromuscular disease treatment trials. KEY POINTS: • Quantitative lower limb muscle MRI provides potential outcome measures in neuromuscular diseases • Bilateral thigh/calf coverage using sequences sensitive to acute and chronic pathology • Measurements have excellent scan-rescan and interobserver reliability • Measurements show small but significant inter-subject age and weight dependency • Readily implementable sequences suitable for further assessment in patient studies.