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Cubital tunnel syndrome (CuTS) is the 2nd most common compressive neuropathy. To improve both diagnosis and the selection of patients for surgery, there is a pressing need to develop a reliable and objective test of ulnar nerve ‘health’. Diffusion tensor imaging (DTI) characterises tissue microstructure and may identify differences in the normal ulnar from those affected by CuTS. The aim of this study was to compare the DTI metrics from the ulnar nerves of healthy (asymptomatic) adults and patients with CuTS awaiting surgery. DTI was acquired at 3.0 T using single-shot echo-planar imaging (55 axial slices, 3 mm thick, 1.5 mm 2 in-plane) with 30 diffusion sensitising gradient directions, a b-value of 800 s/mm 2 and 4 signal averages. The sequence was repeated with the phase-encoding direction reversed. Data were combined and corrected using the FMRIB Software Library (FSL) and reconstructed using generalized q-sampling imaging in DSI Studio. Throughout the length of the ulnar nerve, the fractional anisotropy (FA), quantitative anisotropy (QA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were extracted, then compared using mixed-effects linear regression. Thirteen healthy controls (8 males, 5 females) and 8 patients with CuTS (6 males, 2 females) completed the study. Throughout the length of the ulnar nerve, diffusion was more isotropic in patients with CuTS. Overall, patients with CuTS had a 6% lower FA than controls, with the largest difference observed proximal to the cubital tunnel (mean difference 0.087 [95% CI 0.035, 0.141]). Patients with CuTS also had a higher RD than controls, with the largest disparity observed within the forearm (mean difference 0.252 × 10 –4  mm 2 /s [95% CI 0.085 × 10 –4 , 0.419 × 10 –4 ]). There were no significant differences between patients and controls in QA, MD or AD. Throughout the length of the ulnar nerve, the fractional anisotropy and radial diffusivity in patients with CuTS are different to healthy controls. These findings suggest that DTI may provide an objective assessment of the ulnar nerve and potentially, improve the management of CuTS.

Diffusion tensor imaging (DTI) metrics, such as the fractional anisotropy (FA) and estimates of diffusivity are sensitive to the microstructure of peripheral nerves and may be displayed as tractograms. However, the ideal conditions for tractography of the roots of the brachial plexus are unclear, which represents the rationale for this study. Ten healthy adults were scanned using a Siemens Prisma (3T) and single-shot echo-planar imaging (b-value 0/1000 s/mm 2 , 64 directions, 2.5 mm 3 with 4 averages; repeated in opposing phase encoding directions). Susceptibility correction and tractography were performed in DSI Studio by two independent raters. The effect of FA thresholding at increments of 0.01 (from 0.04 to 0.10) were tested. The mean FA varied between subjects by 2% (95% CI 1%, 3%). FA thresholds of 0.04, 0.05 and 0.06 all propagated 96% of tracts representing the roots; thresholding at 0.07 yielded 4% fewer tracts ( p  = 0.2), 0.08 yielded 11% fewer tracts ( p  = 0.008), 0.09 yielded 15% fewer tracts ( p  = 0.001) and 0.1 yielded 20% fewer tracts ( p  < 0.001). There was < 0.1% inter-rater variability in the measured FA and 99% agreement for tractography (κ = 0.92, p  < 0.001). The fractional anisotropy thresholds required to generate tractograms of the roots of the brachial plexus appears to be lower than those used in the brain. We provide estimates of the probability of generating true tracts for each spinal nerve root of the brachial plexus, at different fractional anisotropy thresholds.

Peripheral neuropathy affects 1 in 10 adults over the age of 40 years. Given the absence of a reliable diagnostic test for peripheral neuropathy, there has been a surge of research into diffusion tensor imaging (DTI) because it characterises nerve microstructure and provides reproducible proxy measures of myelination, axon diameter, fibre density and organisation. Before researchers and clinicians can reliably use diffusion tensor imaging to assess the ‘health’ of the major nerves of the upper limb, we must understand the “normal” range of values and how they vary with experimental conditions. We searched PubMed, Embase, medRxiv and bioRxiv for studies which reported the findings of DTI of the upper limb in healthy adults. Four review authors independently triple extracted data. Using the meta suite of Stata 17, we estimated the normal fractional anisotropy (FA) and diffusivity (mean, MD; radial, RD; axial AD) values of the median, radial and ulnar nerve in the arm, elbow and forearm. Using meta-regression, we explored how DTI metrics varied with age and experimental conditions. We included 20 studies reporting data from 391 limbs, belonging to 346 adults (189 males and 154 females, ~ 1.2 M:1F) of mean age 34 years (median 31, range 20–80). In the arm, there was no difference in the FA (pooled mean 0.59 mm 2 /s [95% CI 0.57, 0.62]; I 2 98%) or MD (pooled mean 1.13 × 10 –3 mm 2 /s [95% CI 1.08, 1.18]; I 2 99%) of the median, radial and ulnar nerves. Around the elbow, the ulnar nerve had a 12% lower FA than the median and radial nerves (95% CI − 0.25, 0.00) and significantly higher MD, RD and AD. In the forearm, the FA (pooled mean 0.55 [95% CI 0.59, 0.64]; I 2 96%) and MD (pooled mean 1.03 × 10 –3 mm 2 /s [95% CI 0.94, 1.12]; I 2 99%) of the three nerves were similar. Multivariable meta regression showed that the b-value, TE, TR, spatial resolution and age of the subject were clinically important moderators of DTI parameters in peripheral nerves. We show that subject age, as well as the b-value, TE, TR and spatial resolution are important moderators of DTI metrics from healthy nerves in the adult upper limb. The normal ranges shown here may inform future clinical and research studies.

Brain-computer interface-assisted motor imagery (MI-BCI) or transcranial direct current stimulation (tDCS) has been used in stroke rehabilitation, though their combinatory effect is unknown. We investigated brain plasticity following a combined MI-BCI and tDCS intervention in chronic subcortical stroke patients with unilateral upper limb disability. Nineteen patients were randomized into tDCS and sham-tDCS groups. Diffusion and perfusion MRI, and transcranial magnetic stimulation were used to study structural connectivity, cerebral blood flow (CBF), and corticospinal excitability, respectively, before and 4 weeks after the 2-week intervention. After quality control, thirteen subjects were included in the CBF analysis. Eleven healthy controls underwent 2 sessions of MRI for reproducibility study. Whereas motor performance showed comparable improvement, long-lasting neuroplasticity can only be detected in the tDCS group, where white matter integrity in the ipsilesional corticospinal tract and bilateral corpus callosum was increased but sensorimotor CBF was decreased, particularly in the ipsilesional side. CBF change in the bilateral parietal cortices also correlated with motor function improvement, consistent with the increased white matter integrity in the corpus callosum connecting these regions, suggesting an involvement of interhemispheric interaction. The preliminary results indicate that tDCS may facilitate neuroplasticity and suggest the potential for refining rehabilitation strategies for stroke patients.

Background Early and accurate clinical diagnosis of the extent of obstetric brachial plexus injury (OBPI) is challenging. The current gold standard for delineating the nerve injury is surgical exploration, and synchronous reconstruction is performed if indicated. Magnetic resonance imaging (MRI) is a non-invasive method of assessing the anatomy and severity of nerve injury in OBPI but the diagnostic accuracy is unclear. The primary objective of this review is to determine the diagnostic accuracy of MRI in comparison to surgical brachial plexus exploration for detecting root avulsion in children under 5 with OBPI. The secondary objectives are to determine its’ diagnostic accuracy for detecting nerve abnormality and detecting pseudomeningocele(s) in this group. Methods This review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).We will include studies reporting the accuracy of MRI (index test) compared to surgical exploration (reference standard) in detecting any of the three target conditions (root avulsion, any nerve abnormality and pseudomeningocele) in children under five with OBPI. Case reports and studies where the number of true positives, false positives, true negatives and false negatives cannot be derived will be excluded. We plan to search PubMed, Embase and CENTRAL for relevant studies from database inception to 15 June 2022. We will also search grey literature (medRxiv, bioRxiv and Google Scholar) and perform forward and backward citation chasing. Screening and full-text assessment of eligibility will be conducted by two independent reviewers, who will then both extract the relevant data. The QUADAS-2 tool will be used to assess methodological quality and risk of bias of included studies by two reviewers independently. The following test characteristics for the target conditions will be extracted: true positives, false positives, true negatives and false negatives. Estimates of sensitivity and specificity with 95% confidence intervals will be shown in forest plots for each study. If appropriate, summary sensitivities and specificities for target conditions will be obtained via meta-analyses using a bivariate model. Discussion This study will aim to clarify the diagnostic accuracy of MRI for detecting nerve injury in OBPI and define its clinical role. Systematic review registration PROSPERO CRD42021267629.

Cardiac diffusion tensor imaging (DTI) is limited by scan time and signal-to-noise (SNR) restrictions. This invariably leads to a trade-off between the number of averages, diffusion-weighted directions (ND), and image resolution. Systematic evaluation of these parameters is therefore important for adoption of cardiac DTI in clinical routine where time is a key constraint. High quality reference DTI data were acquired in five ex-vivo rat hearts. We then retrospectively set 2 ≤ SNR ≤ 97, 7 ≤ ND ≤ 61, varied the voxel volume by up to 192-fold and investigated the impact on the accuracy and precision of commonly derived parameters. For maximal scan efficiency, the accuracy and precision of the mean diffusivity is optimised when SNR is maximised at the expense of ND. With typical parameter settings used clinically, we estimate that fractional anisotropy may be overestimated by up to 13% with an uncertainty of ±30%, while the precision of the sheetlet angles may be as poor as ±31°. Although the helix angle has better precision of ±14°, the transmural range of helix angles may be under-estimated by up to 30° in apical and basal slices, due to partial volume and tapering myocardial geometry. These findings inform a baseline of understanding upon which further issues inherent to in-vivo cardiac DTI, such as motion, strain and perfusion, can be considered. Furthermore, the reported bias and reproducibility provides a context in which to assess cardiac DTI biomarkers.

Background Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages. The iBEAt study of the BEAt-DKD project aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim) and whether they have potential as prognostic biomarkers in DKD (secondary aim). Methods iBEAt is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR ≥30 ml/min/1.73m 2 . At baseline, blood and urine will be collected, clinical examinations will be performed, and medical history will be obtained. These assessments will be repeated annually for 3 years. At baseline each participant will also undergo quantitative renal MRI and US with central processing of MRI images. Biological samples will be stored in a central laboratory for biomarker and validation studies, and data in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers improve the prediction of DKD progression. Ancillary substudies will: (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow measurements against H 2 O 15 positron-emission tomography (PET); (3) validate methods for (semi-)automated processing of renal MRI; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether glycocalyx and microvascular measures are associated with imaging biomarkers and eGFR decline; (6) explore whether the findings in T2D can be extrapolated to type 1 diabetes. Discussion iBEAt is the largest DKD imaging study to date and will provide valuable insights into the progression and heterogeneity of DKD. The results may contribute to a more personalised approach to DKD management in patients with T2D. Trial registration Clinicaltrials.gov ( NCT03716401 ).

Background Pressure overload left ventricular (LV) hypertrophy is characterized by increased cardiomyocyte width and ventricle wall thickness, however the regional variation of this remodeling is unclear. Cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) may provide a non-invasive, comprehensive, and geometrically accurate method to detect regional differences in structural remodeling in hypertrophy. We hypothesized that DTI parameters, such as fractional and planar anisotropy, would reflect myocyte remodeling due to pressure overload in a regionally-dependent manner. Methods We investigated the regional distributions of myocyte remodeling in rats with or without transverse aortic constriction (TAC) via direct measurement of myocyte dimensions with confocal imaging of thick tissue sections, and correlated myocyte cross-sectional area and other geometric features with parameters of diffusivity from ex-vivo DTI in the same regions of the same hearts. Results We observed regional differences in several parameters from DTI between TAC hearts and SHAM controls. Consistent with previous studies, helix angles from DTI correlated strongly with those measured directly from histological sections ( p  < 0.001, R 2  = 0.71). There was a transmural gradient in myocyte cross-sectional area in SHAM hearts that was diminished in the TAC group. We also found several regions of significantly altered DTI parameters in TAC LV compared to SHAM, especially in myocyte sheet angle dispersion and planar anisotropy. Among others, these parameters correlated significantly with directly measured myocyte aspect ratios. Conclusions These results show that structural remodeling in pressure overload LV hypertrophy is regionally heterogeneous, especially transmurally, with a greater degree of remodeling in the sub-endocardium compared to the sub-epicardium. Additionally, several parameters derived from DTI correlated significantly with measurements of myocyte geometry from direct measurement in histological sections. We suggest that DTI may provide a non-invasive, comprehensive method to detect regional structural myocyte LV remodeling during disease.

IntroductionAdverse remodelling of the left ventricle (LV) after ST-elevation myocardial infarction (STEMI) is associated with poor prognosis, yet the underlying mechanism is still unclear. There is contradicting evidence about the timing of LV changes over 12 months post-reperfusion. Diffusion tensor cardiac magnetic resonance (cDTI) allows in vivo characterisation of myocardial microarchitecture and provides mechanistic insight into pathophysiologic changes following MI. We sought to investigate early remodelling (ER) (3 months) versus late remodelling (LR) (12 months) post-MI using cDTI.MethodsProspectively recruited STEMI patients post primary percutaneous coronary intervention (PPCI) underwent 3T MRI at different time points: 5 days, 3 months, and 12 months with the following protocol: functional imaging, T1 mapping pre and post-contrast, second-order motion compensated (M2), free-breathing spin-echo DTI (3 slices, 18 diffusion directions at b-values 100s/mm2, 200s/mm2 and 500s/mm2, acquired resolution was 2.20*2.27*8 mm3 and late gadolinium enhancement (LGE). Global and segmental analysis was undertaken to derive the mean diffusivity (MD) (a measure of oedema and/or interstitial fibrosis), fractional anisotropy (FA) (a measure of collagen infiltration and cardiomyocyte disorganisation), LGE%, ECV and volumes. Segments positive for LGE were classed as infarcted segments, and the remote myocardium was opposite the infarct myocardium. LV remodelling was defined as a 20% increase in LV end-diastolic volume (EDV) at 3 months and/or 12 months compared to baseline.ResultsOut of 132 patients, 13 remodelled early (ER) and 24 remodelled late (LR). Of the 13 ER, 3 were excluded as they had improved at 12 months, leaving 10 patients in the ER group. Between ER and LR, there was a significant difference in infarct size (IS) acutely but not at the remaining time points (p=0.05, 0.53 and 0.58, respectively); ejection fraction (EF) at 12 months (ER 35.75 ± 6.90 vs LR 42.92 ± 8.04, p=0.03); no difference was found in ECV at any time point nor in the remote or the infarcted myocardium. Furthermore, compared to the LR group, remote FA was lower in the ER group, both acutely (0.33± 0.03 vs 0.36 ± 0.03, p=0.02) and at 3 months (0.31± 0.03 vs 0.34± 0.03, p=0.005). At 12 months, remote MD was higher in ER patients than in the LR group (1.56± 0.04 vs 1.49±0.05, p=0.005).ConclusionContrary to previous studies, we demonstrated that the majority of post-MI patients remodel late. Furthermore, compared to the LR groups, the ER patients showed more disorganisation of cardiac myocytes in remote myocardium (as assessed by FA) both acutely and 3 months and a higher remote MD at 12 months possibly in keeping with increased interstitial fibrosis.Abstract 184 Figure 1Significant changes in DTI biomarkers between early remodelled (ER) and late remodelled (LR) groups. Panel A. FA in remote myocardium in the acute stage. Panel B. FA in remote myocardium in 3-months. Panel C. MD in remote myocardium in 12- monthsAbstract 184 Figure 2Conflict of InterestNo

BackgroundHypertrophic cardiomyopathy (HCM) is a genetic disease with a prevalence of 1 in 500, characterised by left ventricle hypertrophy (LVH). Identifying subclinical HCM, defined as genotype positive phenotype negative (G+LVH-), is clinically important for patient risk stratification and management. We previously demonstrated the role of cardiac diffusion tensor imaging (cDTI) cardiac magnetic resonance (CMR), in identifying microstructural changes in HCM (G+LVH-) patients. Myocardial strain with CMR feature-tracking (FT) has prognostic value in overt HCM, defined as HCM (G+LVH+). We sought to determine whether cDTI is a more sensitive marker than 3D-FT strain in the risk stratification of HCM (G+LVH-) patients.MethodsThis multi-centre collaboration included 127 subjects: 23 healthy volunteers (HV), 67 HCM (G+LVH-) and 37 HCM (G+LVH+) participants. All patients underwent 3T CMR imaging with the following protocol: cine imaging; second order motion compensated, free-breathing spin echo cDTI (b-values of 100 s/mm2 (3 DW directions, 12 repetitions), and 450 s/mm2 (30 DW directions, 6 repetitions); pre and post contrast T1 mapping and late gadolinium enhancement (LGE). Global cDTI analysis was undertaken to derive: mean diffusivity (MD) (a measure of the magnitude of diffusion, high values thought to reflect interstitial fibrosis), fractional anisotropy (FA) (directional variability of water diffusion with low levels thought to be related to collagen infiltration and cardiomyocyte disorganisation), secondary eigenvector angle (E2A) (a marker of sheetlet orientation). cDTI postprocessing was performed using an inhouse Matlab based software with automatic registration. Using Circle Cvi42 software, 3D feature tracking (FT) was derived for global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS).ResultsWhilst the HCM G+LVH- patients showed significantly different LVEF, mass and ECV compared to HCM G+LVH+, no difference in mass and ECV was found between HV and HCM G+LVH- (see table 1). GLS was significantly different only between HCM G+LVH- and HCM G+LVH+, while no other strain parameters differed significantly between groups.All cDTI biomarkers were significantly different between HV, HCM G+LVH- and HCM G+LVH+ [See table 1]. ROC curves showed a better diagnostic performance for cDTI biomarkers compared to strain in identifying subclinical HCM with AUC values of: MD 0.769, FA 0.828, E2A 0.731, GLS 0.579, GCS 0.547 and GRS 0.568. ROC curves analysis showed stronger diagnostic performance for cDTI biomarkers compared to strain in identifying overt HCM (G+LVH+) with AUC values of: MD 0.878, FA 0.939, E2A 0.971, GLS 0.805, GCS 0.595 and GRS 0.582.Abstract 6-003 Table 1Results [mean (SD)] HV(N=23) HCM (G+LVH-) (N=67) HCM (G+LVH+) (N=37) p-values HV vsHCM (G+LVH-) HCM (G+LVH-) vsHCM (G+LVH+) Age (yrs) 35 (9) 33 (11) 51 (14) 0.523 <0.001 LVEF (%) 66 (4) 71 (6) 77 (6) <0.001 <0.001 LV mass indexed (g/m2) 55 (15) 54 (22) 84 (22) 0.560 <0.001 Global ECV (%) 26 (3) 27 (3) 29 (3) 0.319 0.003 Septal ECV (%) 26 (3) 27 (3) 31 (5) 0.190 <0.001 MD (x 10–3mm2/s) 1.46 (0.04) 1.51 (0.05) 1.56 (0.08) <0.001 <0.001 FA 0.33 (0.02) 0.31 (0.02) 0.28 (0.04) <0.001 <0.001 |E2A|° 40.8 (8.6) 48.9 (8.5) 58.8 (5.6) <0.001 <0.001 GRS 39.9 (7.9) 42.4 (10.9) 44.1 (13.2) 0.334 0.752 GCS -21.6 (1.8) -21.1 (2.7) -20.8 (3.2) 0.505 0.417 GLS -16.4 (1.6) -15.9 (1.9) -13.5 (2.8) 0.263 <0.001 ConclusioncDTI has better diagnostic performance to detect adverse myocardial change associated with subclinical HCM than 3D-FT strain. Especially in the HCM G+LVH- population, where ECV showed no significant difference compared to HVs, cDTI may provide further utility in detecting subclinical HCM.