Abstract
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
, 64 directions, 2.5 mm
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.
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.
Delineating the normal development of brain white matter (WM) over the human lifespan is crucial to improved understanding of underlying WM pathology in neuropsychiatric and neurological conditions. ...We review the extant literature concerning diffusion tensor imaging studies of brain WM development in healthy individuals available until October 2012, summarise trends of normal development of human brain WM and suggest possible future research directions. Temporally, brain WM maturation follows a curvilinear pattern with an increase in fractional anisotropy (FA) from newborn to adolescence, decelerating in adulthood till a plateau around mid-adulthood, and a more rapid decrease of FA from old age onwards. Spatially, brain WM tracts develop from central to peripheral regions, with evidence of anterior-to-posterior maturation in commissural and projection fibres. The corpus callosum and fornix develop first and decline earlier, whilst fronto-temporal WM tracts like cingulum and uncinate fasciculus have protracted maturation and decline later. Prefrontal WM is most vulnerable with greater age-related FA reduction compared with posterior WM. Future large scale studies adopting longitudinal design will better clarify human brain WM changes over time.
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
/s 95% CI 0.57, 0.62; I
98%) or MD (pooled mean 1.13 × 10
mm
/s 95% CI 1.08, 1.18; I
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
96%) and MD (pooled mean 1.03 × 10
mm
/s 95% CI 0.94, 1.12; I
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.
Abstract
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 electrical excitation-propagation is influenced by myocyte orientations (cellular organization). Quantitatively understanding this relationship presents a significant research challenge, ...especially during arrhythmias in which excitation patterns become complex. Tissue-scale simulations of cardiac electrophysiology, incorporating both dynamic action potential behavior and image-based myocardial architecture, provide an approach to investigate three-dimensional (3D) propagation of excitation waves in the heart. In this study, we aimed to assess the importance of natural variation in myocyte orientations on cardiac arrhythmogenesis using 3D tissue electrophysiology simulations. Three anatomical models (i.e., describing myocyte orientations) of healthy rat ventricles—obtained using diffusion tensor imaging at 100 μm resolution—were registered to a single biventricular geometry (i.e., a single cardiac shape), in which the myocyte orientations could be represented by each of the diffusion tensor imaging data sets or by an idealized rule-based description. The Fenton-Karma cellular excitation model was modified to reproduce rat ventricular action potential duration restitution to create reaction-diffusion cardiac electrophysiology models. Over 250 3D simulations were performed to investigate the effects of myocyte orientations on the following: 1) ventricular activation, 2) location-dependent arrhythmia induction via rapid pacing, and 3) dynamics of re-entry averaged over multiple episodes. It was shown that 1) myocyte orientation differences manifested themselves in local activation times, but the influence on total activation time was small; 2) differences in myocyte orientations could critically affect the inducibility and persistence of arrhythmias for specific stimulus-location/cycle-length combinations; and 3) myocyte orientations alone could be an important determinant of scroll wave break, although no significant differences were observed in averaged arrhythmia dynamics between the four myocyte orientation scenarios considered. Our results show that myocyte orientations are an important determinant of arrhythmia inducibility, persistence, and scroll wave break. These findings suggest that where specificity is desired (for example, when predicting location-dependent, patient-specific arrhythmia inducibility), subject-specific myocyte orientations may be important.
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.
Diffusion tensor magnetic resonance imaging (DTI) can be used to reconstruct the brachial plexus in 3D via tracts connecting contiguous diffusion tensors with similar primary eigenvector ...orientations. When creating DTI tractograms, the turning angle of connecting lines (step angle) must be prescribed by the user; however, the literature is lacking detailed geometry of brachial plexus to inform such decisions. Therefore, the spinal cord and brachial plexus of 10 embalmed adult cadavers were exposed bilaterally by posterior dissection. Photographs were taken under standardised conditions and spatially calibrated in MATLAB. The roots of the brachial plexus were traced from the dorsal root entry zone for 5 cm laterally using a 2.5‐mm2 Cartesian grid overlay. The trace was composed of points connected by lines, and the turning angle between line segments (the step angle) was resolved. Our data show that the geometry of the roots increased in tortuosity from C5 to T1, with no significant differences between sides. The 1st thoracic root had the most tortuous course, turning through a maximum angle of 56° per 2.5 mm (99% CI 44° to 70°). Significantly higher step angles and greater variability were observed in the medial 2 cm of the roots of the brachial plexus, where the dorsal and ventral rootlets coalesce to form the spinal root. Throughout the brachial plexus, the majority of step angles (>50%) were smaller than 20° and <1% of step angles exceeded 70°. The geometry of the brachial plexus increases in tortuosity from C5 to T1. To reconstruct 99% of tracts representing the roots of the brachial plexus by DTI tractography, users can either customise the step angle per root based on our findings or select a universal threshold of 70°.
To create 3D reconstructions of the brachial plexus by diffusion tensor magnetic resonance imaging, the geometry of the brachial plexus must be defined at high resolution and throughout its course. Our study traces the brachial plexus in ten cadavers to resolve the step/turning angles at a resolution of 2.5 mm2. We show that the tortuosity of the roots increases in the caudal direction and show that a step/turning angle of 70° is optimal.
Transcranial direct current stimulation (tDCS) has been shown to modulate cortical plasticity, enhance motor learning and post-stroke upper extremity motor recovery. It has also been demonstrated to ...facilitate activation of brain-computer interface (BCI) in stroke patients. We had previously demonstrated that BCI-assisted motor imagery (MI-BCI) can improve upper extremity impairment in chronic stroke participants. This study was carried out to investigate the effects of priming with tDCS prior to MI-BCI training in chronic stroke patients with moderate to severe upper extremity paresis and to investigate the cortical activity changes associated with training.
This is a double-blinded randomized clinical trial. Participants were randomized to receive 10 sessions of 20-min 1 mA tDCS or sham-tDCS before MI-BCI, with the anode applied to the ipsilesional, and the cathode to the contralesional primary motor cortex (M1). Upper extremity sub-scale of the Fugl-Meyer Assessment (UE-FM) and corticospinal excitability measured by transcranial magnetic stimulation (TMS) were assessed before, after and 4 weeks after intervention.
Ten participants received real tDCS and nine received sham tDCS. UE-FM improved significantly in both groups after intervention. Of those with unrecordable motor evoked potential (MEP-) to the ipsilesional M1, significant improvement in UE-FM was found in the real-tDCS group, but not in the sham group. Resting motor threshold (RMT) of ipsilesional M1 decreased significantly after intervention in the real-tDCS group. Short intra-cortical inhibition (SICI) in the contralesional M1 was reduced significantly following intervention in the sham group. Correlation was found between baseline UE-FM score and changes in the contralesional SICI for all, as well as between changes in UE-FM and changes in contralesional RMT in the MEP- group.
MI-BCI improved the motor function of the stroke-affected arm in chronic stroke patients with moderate to severe impairment. tDCS did not confer overall additional benefit although there was a trend toward greater benefit. Cortical activity changes in the contralesional M1 associated with functional improvement suggests a possible role for the contralesional M1 in stroke recovery in more severely affected patients. This has important implications in designing neuromodulatory interventions for future studies and tailoring treatment.
The study was registered at https://clinicaltrials.gov (NCT01897025).
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