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The most common indications for magnetic resonance imaging (MRI) of the brachial plexus (BP) are traumatic injuries. The role of MRI of the BP has increased because of recent trends favoring earlier surgery. Determining preganglionic vs. postganglionic injury is essential, as different treatment strategies are required. Thus, MRI of the BP should be supplemented with cervical spine MRI to assess the intradural part of the spinal nerves, including highly T2-weighted techniques. Acute preganglionic injuries usually manifest as various combinations of post-traumatic pseudomeningocele, the absence of roots, deformity of nerve root sleeves, displacement of the spinal cord, hemorrhage in the spinal canal, presence of scars in the spinal canal, denervation of the back muscles, and syrinx. Spinal nerve root absence is more specific than pseudomeningocele on MRI. Acute postganglionic injuries can present as lesions in continuity or tears. The following signs indicate injury to the BP: side-to-side difference, swelling, partial, or total BP rupture. Injury patterns and localization are associated with the mechanism of trauma, which implies a significant role for MRI in the work-up of patients. The identification and description of traumatic lesions involving the brachial plexus need to be systematic and detailed. Using an appropriate MRI protocol, obtaining details about the injury, applying a systematic anatomical approach, and correlating imaging findings to relevant clinical data to make a correct diagnosis. Information about the presence or suspicion of root avulsion should always be provided., Highlights • Trauma is the most common indication for MRI of the brachial plexus. • MRI of the brachial plexus should include cervical spine MRI. • Spinal nerve root absence is seen in preganglionic injuries. • Determining preganglionic vs. postganglionic injury is essential for treatment planning. • Appropriate MRI rapport is crucial in communication with the clinician. more...

Compartmental diffusion MRI models that account for intravoxel incoherent motion (IVIM) of blood perfusion allow for estimation of the fractional volume of the microvascular compartment. Conventional IVIM models are known to be biased by not accounting for partial volume effects caused by free water and cerebrospinal fluid (CSF), or for tissue-dependent relaxation effects. In this work, a three-compartment model (tissue, free water and blood) that includes relaxation terms is introduced. To estimate the model parameters, in vivo human data were collected with multiple echo times (TE), inversion times (TI) and b-values, which allowed a direct relaxation estimate alongside estimation of perfusion, diffusion and fractional volume parameters. Compared to conventional two-compartment models (with and without relaxation compensation), the three-compartment model showed less effects of CSF contamination. The proposed model yielded significantly different volume fractions of blood and tissue compared to the non-relaxation-compensated model, as well as to the conventional two-compartment model, suggesting that previously reported parameter ranges, using models that do not account for relaxation, should be reconsidered. Keywords: Intravoxel incoherent motion, Perfusion fraction, Pseudo-diffusion, Relaxation, Diffusion more...

International audience; PURPOSE: High-resolution free-breathing late gadolinium enhancement (HR-LGE) was shown valuable for the diagnosis of acute coronary syndromes with non-obstructed coronary arteries. The method may be useful to detect COVID-related myocardial injuries but is hampered by prolonged acquisition times. We aimed to introduce an accelerated HR-LGE technique for the diagnosis of COVID-related myocardial injuries. METHOD: An undersampled navigator-gated HR-LGE (acquired resolution of 1.25 mm(3)) sequence combined with advanced patch-based low-rank reconstruction was developed and validated in a phantom and in 23 patients with structural heart disease (test cohort; 15 men; 55 ± 16 years). Twenty patients with laboratory-confirmed COVID-19 infection associated with troponin rise (COVID cohort; 15 men; 46 ± 24 years) prospectively underwent cardiovascular magnetic resonance (CMR) with the proposed sequence in our center. Image sharpness, quality, signal intensity differences and diagnostic value of free-breathing HR-LGE were compared against conventional breath-held low-resolution LGE (LR-LGE, voxel size 1.8x1.4x6mm). RESULTS: Structures sharpness in the phantom showed no differences with the fully sampled image up to an undersampling factor of x3.8 (P > 0.5). In patients (N = 43), this acceleration allowed for acquisition times of 7min21s ± 1min12s at 1.25 mm(3) resolution. Compared with LR-LGE, HR-LGE showed higher image quality (P = 0.03) and comparable signal intensity differences (P > 0.5). In patients with structural heart disease, all LGE-positive segments on LR-LGE were also detected on HR-LGE (80/391) with 21 additional enhanced segments visible only on HR-LGE (101/391, P more...

Atrophy of the brain grey matter (GM) is an accepted and important feature of multiple sclerosis (MS). However, its accurate measurement is hampered by various technical, pathological and physiological factors. As a consequence, it is challenging to investigate the role of GM atrophy in the disease process as well as the effect of treatments that aim to reduce neurodegeneration. In this paper we discuss the most important challenges currently hampering the measurement and interpretation of GM atrophy in MS. The focus is on measurements that are obtained in individual patients rather than on group analysis methods, because of their importance in clinical trials and ultimately in clinical care. We discuss the sources and possible solutions of the current challenges, and provide recommendations to achieve reliable measurement and interpretation of brain GM atrophy in MS., Highlights • Accurate measurement of brain GM atrophy in MS is hampered by various physiological, pathological and technical factors. • Challenges to achieve accuracy in quantification and interpretation of atrophy in MS are discussed. • Recommendations on how to achieve reliable measurement and interpretation of GM atrophy in MS are suggested. more...

The cardinal movement abnormalities of Parkinson's disease (PD), including tremor, muscle rigidity, and reduced speed and frequency of movements, are caused by degeneration of dopaminergic neurons in the substantia nigra that project to the putamen, compromising information flow through frontal-subcortical circuits. Typically, the nigrostriatal pathway is more severely affected on the side of the brain opposite (contralateral) to the side of the body that manifests initial symptoms. Several studies have suggested that PD is also associated with changes in white matter microstructural integrity. The goal of the present study was to further develop methods for measuring striatonigral connectivity differences between PD patients and age-matched controls using diffusion weighted magnetic resonance imaging (MRI). In this cross-sectional study, 40 PD patients and 44 controls underwent diffusion weighted imaging (DWI) using a 40-direction MRI sequence as well as an optimized 60-direction sequence with overlapping slices. Regions of interest (ROIs) encompassing the putamen and substantia nigra were hand drawn in the space of the 40-direction data using high-contrast structural images and then coregistered to the 60-direction data. Probabilistic tractography was performed in the native space of each dataset by seeding the putamen ROI with an ipsilateral substantia nigra classification target. The effect of disease group (PD versus control) on mean putamen-SN connection probability and streamline density were then analyzed using generalized linear models controlling for age, gender, education, as well as seed and target region characteristics. Mean putamen-SN streamline density was lower in PD on both sides of the brain and in both 40- and 60-direction data. The optimized sequence provided a greater separation between PD and control means; however, individual values overlapped between groups. The 60-direction data also yielded mean connection probability values either trending (ipsilateral) or significantly (contralateral) lower in the PD group. There were minor between-group differences in average diffusion measures within the substantia nigra ROIs that did not affect the results of the GLM analyses when included as covariates. Based on these results, we conclude that mean striatonigral structural connectivity differs between PD and control groups and that use of an optimized 60-direction DWI sequence with overlapping slices increases the sensitivity of the technique to putative disease-related differences. However, overlap in individual values between disease groups limits its use as a classifier., Highlights • The nigrostriatal pathway degenerates in Parkinson's disease. • Two diffusion tensor imaging (DTI) sequences were acquired in 84 participants. • Structural connectivity between putamen and substantia nigra was quantified. • Parkinson's patients had lower connection probability and streamline density. • A 60-direction DTI sequence with overlapping slices was most sensitive. more...

Delayed brain development in perinatally HIV-infected children may affect the functional brain activity and subsequently cognitive function. The current study evaluated the functional brain activity in HIV-infected children by quantifying the amplitude of low frequency fluctuations (ALFF) and functional connectivity (FC). Additionally, correlation of ALFF and FC with cognitive measures was performed. Twenty-six HIV-infected children and 20 control children underwent neuropsychological (NP) assessment and resting-state functional magnetic resonance imaging (rs-fMRI). ALFF and FC maps were generated and group differences were analyzed using two-sample t-test. Furthermore, ALFF and FC showing significant group differences were correlated with NP scores using Pearson's correlation. Significantly lower ALFF in the left middle temporal gyrus, precentral and post central gyrus was observed in HIV-infected children compared to controls. FC was significantly reduced in the right inferior parietal, vermis, middle temporal and left postcentral regions, and significantly increased in the right precuneus, superior parietal and left middle frontal regions in HIV-infected children as compared to control. HIV-infected children showed significantly lower NP scores in various domains including closure, exclusion, memory, verbal meaning, quantity and hidden figure than controls. These waning cognitive functions were significantly associated with changes in ALFF and FC in HIV-infected children. The findings suggest that abnormal ALFF and FC may responsible for cognitive deficits in HIV-infected children. ALFF and FC in association with cognitive evaluation may provide a clinical biomarker to evaluate functional brain activity and to plan neurocognitive intervention in HIV-infected children undergoing standard treatment., Highlights • Resting-state fMRI and cognitive assessment were performed in HIV-infected children. • HIV-infected children showed abnormal spontaneous neural activity (SNA) and functional connectivity (FC). • Lower cognitive scores were significantly associated with SNA and FC in HIV-infected children. • HIV infection may have significant impact on neurodevelopment and cognitive performance. more...

Background Cortical, thalamic and hippocampal gray matter atrophy in relapsing–remitting MS (RRMS) is associated cognitive deficits. However, the role of interconnecting white matter pathways including the fornix, cingulum, and uncinate fasciculus (UF) is less well studied. Objective To assess MS damage to a hippocampal–thalamic–prefrontal network and the relative contributions of its components to specific cognitive domains. Methods We calculated diffusion tensor fractional anisotropy (FA) in the fornix, cingulum and UF as well as thalamic and hippocampal volumes in 27 RRMS patients and 20 healthy controls. A neuropsychological battery was administered and 4 core tests known to be sensitive to MS changes were used to assess cognitive impairment. To determine the relationships between structure and cognition, all tests were grouped into 4 domains: attention/executive function, processing speed, verbal memory, and spatial memory. Univariate correlations with structural measures and depressive symptoms identified potential contributors to cognitive performance and subsequent linear regression determined their relative effects on performance in each domain. For significant predictors, we also explored the effects of laterality and axial versus radial diffusivity. Results RRMS patients had worse performance on the Symbol Digit Modalities Test, but no significant impairment in the 4 cognitive domains. RRMS had reduced mean FA of all 3 pathways and reduced thalamic and hippocampal volumes compared to controls. In RRMS we found that thalamic volume and BDI predicted attention/executive function, UF FA predicted processing speed, thalamic volume predicted verbal memory, and UF FA and BDI predicted spatial memory. Conclusions Hippocampal–thalamic–prefrontal disruption affects cognitive performance in early RRMS with mild to minimal cognitive impairment, confirming both white and gray matter involvement in MS and demonstrating utility in assessing functional networks to monitor cognition., Highlights • We detect limbic white matter and gray matter insult in early RRMS patients with mild to minimal cognitive impairment. • Thalamic atrophy and uncinate fasciculus microstructural changes are associated with cognitive performance in early RRMS. • Depressive symptomatology also independently predicts cognitive performance more...

In the current study, we have evaluated the performance of magnetic resonance (MR) T1rho (T1ρ) imaging and CSF biomarkers (T-tau, P-tau and Aβ-42) in characterization of Alzheimer's disease (AD) patients from mild cognitive impairment (MCI) and control subjects. With informed consent, AD (n = 27), MCI (n = 17) and control (n = 17) subjects underwent a standardized clinical assessment and brain MRI on a 1.5-T clinical-scanner. T1ρ images were obtained at four different spin-lock pulse duration (10, 20, 30 and 40 ms). T1ρ maps were generated by pixel-wise fitting of signal intensity as a function of the spin-lock pulse duration. T1ρ values from gray matter (GM) and white matter (WM) of medial temporal lobe were calculated. The binary logistic regression using T1ρ and CSF biomarkers as variables was performed to classify each group. T1ρ was able to predict 77.3% controls and 40.0% MCI while CSF biomarkers predicted 81.8% controls and 46.7% MCI. T1ρ and CSF biomarkers in combination predicted 86.4% controls and 66.7% MCI. When comparing controls with AD, T1ρ predicted 68.2% controls and 73.9% AD, while CSF biomarkers predicted 77.3% controls and 78.3% for AD. Combination of T1ρ and CSF biomarkers improved the prediction rate to 81.8% for controls and 82.6% for AD. Similarly, on comparing MCI with AD, T1ρ predicted 35.3% MCI and 81.9% AD, whereas CSF biomarkers predicted 53.3% MCI and 83.0% AD. Collectively CSF biomarkers and T1ρ were able to predict 59.3% MCI and 84.6% AD. On receiver operating characteristic analysis T1ρ showed higher sensitivity while CSF biomarkers showed greater specificity in delineating MCI and AD from controls. No significant correlation between T1ρ and CSF biomarkers, between T1ρ and age, and between CSF biomarkers and age was observed. The combined use of T1ρ and CSF biomarkers have promise to improve the early and specific diagnosis of AD. Furthermore, disease progression form MCI to AD might be easily tracked using these two parameters in combination., Highlights • Increased T1rho was observed in MCI and AD compared to controls. • Increased T-tau and P-tau and decreased Aβ1-42 were observed in MCI and AD. • Combined biomarkers have promise to improve early and specific diagnosis of AD. • MCI to AD progression might be tracked using these two biomarkers in combination. more...

In clinical practice signal hyperintensity in the cortex and/or in the striatum on magnetic resonance (MR) diffusion-weighted images (DWIs) is a marker of sporadic Creutzfeldt–Jakob Disease (sCJD). MR diagnostic accuracy is greater than 90%, but the biophysical mechanisms underpinning the signal abnormality are unknown. The aim of this prospective study is to combine an advanced DWI protocol with new mathematical models of the microstructural changes occurring in prion disease patients to investigate the cause of MR signal alterations. This underpins the later development of more sensitive and specific image-based biomarkers. DWI data with a wide a range of echo times and diffusion weightings were acquired in 15 patients with suspected diagnosis of prion disease and in 4 healthy age-matched subjects. Clinical diagnosis of sCJD was made in nine patients, genetic CJD in one, rapidly progressive encephalopathy in three, and Gerstmann–Sträussler–Scheinker syndrome in two. Data were analysed with two bi-compartment models that represent different hypotheses about the histopathological alterations responsible for the DWI signal hyperintensity. A ROI-based analysis was performed in 13 grey matter areas located in affected and apparently unaffected regions from patients and healthy subjects. We provide for the first time non-invasive estimate of the restricted compartment radius, designed to reflect vacuole size, which is a key discriminator of sCJD subtypes. The estimated vacuole size in DWI hyperintense cortex was in the range between 3 and 10 µm that is compatible with neuropathology measurements. In DWI hyperintense grey matter of sCJD patients the two bi-compartment models outperform the classic mono-exponential ADC model. Both new models show that T2 relaxation times significantly increase, fast and slow diffusivities reduce, and the fraction of the compartment with slow/restricted diffusion increases compared to unaffected grey matter of patients and healthy subjects. Analysis of the raw DWI signal allows us to suggest the following acquisition parameters for optimized detection of CJD lesions: b = 3000 s/mm2 and TE = 103 ms. In conclusion, these results provide the first in vivo estimate of mean vacuole size, new insight on the mechanisms of DWI signal changes in prionopathies and open the way to designing an optimized acquisition protocol to improve early clinical diagnosis and subtyping of sCJD., Highlights • An advanced DWI acquisition scheme was applied to 15 patients with suspected sCJD. • Data fitting with two bi-compartment models outperformed the classic ADC model. • In affected GM T2 values were increased, diffusion was more hindered or restricted. • For the first time an estimate of the restricted compartment radius was provided. • The radius may reflect vacuole size, which is a key discriminator of sCJD subtypes., Graphical abstract more...

Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved is not well defined in IPD. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques, including arterial spin labelling (ASL) quantification of cerebral perfusion, can reveal altered neurovascular status (NVS) in IPD. Fourteen participants with IPD (mean ± SD age 65.1 ± 5.9 years) and 14 age and cardiovascular risk factor matched control participants (mean ± SD age 64.6 ± 4.2 years) underwent a 3T MRI scan protocol. ASL images were collected before, during and after a 6 minute hypercapnic challenge. FLAIR images were used to determine white matter lesion score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from the ASL data both at rest and during hypercapnia. Cerebrovascular reactivity (CVR) images were calculated, depicting the change in CBF and AAT relative to the change in end-tidal CO2. A significant (p = 0.005) increase in whole brain averaged baseline AAT was observed in IPD participants (mean ± SD age 1532 ± 138 ms) compared to controls (mean ± SD age 1335 ± 165 ms). Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA) scores. These findings provide further evidence of alterations in NVS in IPD., Highlights • Investigation of neurovascular status (NVS) in IPD using arterial spin labelling • Diffuse prolonged arterial arrival time in IPD compared to controls • Reduced regional CBF in the IPD group correlated with cognitive impairment. • Clinical evidence of altered NVS in IPD warrants further research. more...

Highlights • Computational neuroimaging captures focal brainstem pathology in motor neuron diseases in contrast to both healthy- and disease controls. • ALS patients exhibit progressive medulla oblongata, pontine and mesencephalic volume loss over time. • Brainstem atrophy in ALS and PLS is dominated by medulla oblongata volume reductions. • Vertex analyses of ALS patients reveal flattening of the medullary pyramids bilaterally. • Morphometric analyses in ALS detect density reductions in the mesencephalic crura consistent with corticospinal tract degeneration., Background Brainstem pathology is a hallmark feature of ALS, yet most imaging studies focus on cortical grey matter alterations and internal capsule white matter pathology. Brainstem imaging in ALS provides a unique opportunity to appraise descending motor tract degeneration and bulbar lower motor neuron involvement. Methods A prospective longitudinal imaging study has been undertaken with 100 patients with ALS, 33 patients with PLS, 30 patients with FTD and 100 healthy controls. Volumetric, vertex and morphometric analyses were conducted correcting for demographic factors to characterise disease-specific patterns of brainstem pathology. Using a Bayesian segmentation algorithm, the brainstem was segmented into the medulla, pons and mesencephalon to measure regional volume reductions, shape analyses were performed to ascertain the atrophy profile of each study group and region-of-interest morphometry was used to evaluate focal density alterations. Results ALS and PLS patients exhibit considerable brainstem atrophy compared to both disease- and healthy controls. Volume reductions in ALS and PLS are dominated by medulla oblongata pathology, but pontine atrophy can also be detected. In ALS, vertex analyses confirm the flattening of the medullary pyramids bilaterally in comparison to healthy controls and widespread pontine shape deformations in contrast to PLS. The ALS cohort exhibit bilateral density reductions in the mesencephalic crura in contrast to healthy controls, central pontine atrophy compared to disease controls, peri-aqueduct mesencephalic and posterior pontine changes in comparison to PLS patients. Conclus ions: Computational brainstem imaging captures the degeneration of both white and grey matter components in ALS. Our longitudinal data indicate progressive brainstem atrophy over time, underlining the biomarker potential of quantitative brainstem measures in ALS. At a time when a multitude of clinical trials are underway worldwide, there is an unprecedented need for accurate biomarkers to monitor disease progression and detect response to therapy. Brainstem imaging is a promising addition to candidate biomarkers of ALS and PLS. more...

Objective To evaluate, in vivo, the impact of ongoing chronic migraine (CM) attacks on the endogenous μ-opioid neurotransmission. Background CM is associated with cognitive-emotional dysfunction. CM is commonly associated with frequent acute medication use, including opioids. Methods We scanned 15 migraine patients during the spontaneous headache attack (ictal phase): 7 individuals with CM and 8 with episodic migraine (EM), as well as 7 healthy controls (HC), using positron emission tomography (PET) with the selective μ-opioid receptor (μOR) radiotracer [11C]carfentanil. Migraineurs were scanned in two paradigms, one with thermal pain threshold challenge applied to the site of the headache, and one without thermal challenge. Multivariable analysis was performed between the μ-opioid receptor availability and the clinical data. Results μOR availability, measured with [11C]carfentanil nondisplaceable binding potential (BPND), in the left thalamus (P-value = 0.005) and left caudate (P-value = 0.003) were decreased in CM patients with thermal pain threshold during the ictal phase relative to HC. Lower μOR BPND in the right parahippocampal region (P-value = 0.001) and right amygdala (P-value = 0.002) were seen in CM relative to EM patients. Lower μOR BPND values indicate either a decrease in μOR concentration or an increase in endogenous μ-opioid release in CM patients. In the right amygdala, 71% of the overall variance in μOR BPND levels was explained by the type of migraine (CM vs. EM: partial-R2 = 0.47, P-value, Graphical abstract Unlabelled Image, Highlights • Increased endogenous μ-opioid neurotransmission in limbic system of chronic migraineurs • Right amygdala opioid dysfunction is 71% explained by attack frequency, severity and sensitivity. • Amygdala dysfunction links cognitive-emotional brain mechanisms to migraine suffering. more...

Long-term episodic memory deficits in Alzheimer's disease (AD) are well characterised but, until recently, short-term memory (STM) function has attracted far less attention. We employed a recently-developed, delayed reproduction task which requires participants to reproduce precisely the remembered location of items they had seen only seconds previously. This paradigm provides not only a continuous measure of localization error in memory, but also an index of relational binding by determining the frequency with which an object is misplaced to the location of one of the other items held in memory. Such binding errors in STM have previously been found on this task to be sensitive to medial temporal lobe (MTL) damage in focal lesion cases. Twenty individuals with pathological mutations in presenilin 1 or amyloid precursor protein genes for familial Alzheimer's disease (FAD) were tested together with 62 healthy controls. Participants were assessed using the delayed reproduction memory task, a standard neuropsychological battery and structural MRI.Overall, FAD mutation carriers were worse than controls for object identity as well as in gross localization memory performance. Moreover, they showed greater misbinding of object identity and location than healthy controls. Thus they would often mislocalize a correctly-identified item to the location of one of the other items held in memory. Significantly, asymptomatic gene carriers – who performed similarly to healthy controls on standard neuropsychological tests – had a specific impairment in object-location binding, despite intact memory for object identity and location. Consistent with the hypothesis that the hippocampus is critically involved in relational binding regardless of memory duration, decreased hippocampal volume across FAD participants was significantly associated with deficits in object-location binding but not with recall precision for object identity or localization. Object-location binding may therefore provide a sensitive cognitive biomarker for MTL dysfunction in a range of diseases including AD. more...