Fully automatic segmentation of brain lacunas resulting from resective surgery using a 3D deep learning model.

The rapid and constant development of deep learning (DL) strategies is pushing forward the quality of object segmentation in images from diverse fields of interest. In particular, these algorithms can be very helpful in delineating brain abnormalities (lesions, tumors, lacunas, etc), enabling the extraction of information such as volume and location, that can inform doctors or feed predictive models. In this study, we describe ResectVol DL, a fully automatic tool developed to segment resective lacunas in brain images of patients with epilepsy. ResectVol DL relies on the nnU-Net framework that leverages the 3D U-Net deep learning architecture. T1-weighted MRI datasets from 120 patients (57 women; 31.5 ± 15.9 years old at surgery) were used to train (n=78) and test (n=48) our tool. Manual segmentations were carried out by five different raters and were considered as ground truth for performance assessment. We compared ResectVol DL with two other fully automatic methods: ResectVol 1.1.2 and DeepResection, using the Dice similarity coefficient (DSC), Pearson's correlation coefficient, and relative difference to manual segmentation. ResectVol DL presented the highest median DSC (0.92 vs. 0.78 and 0.90), the highest correlation coefficient (0.99 vs. 0.63 and 0.94) and the lowest median relative difference (9 vs. 44 and 12 %). Overall, we demonstrate that ResectVol DL accurately segments brain lacunas, which has the potential to assist in the development of predictive models for postoperative cognitive and seizure outcomes.

Graph analysis of cortical reorganization after virtual reality-based rehabilitation following stroke: a pilot randomized study.

Introduction: Stroke is the leading cause of functional disability worldwide. With the increase of the global population, motor rehabilitation of stroke survivors is of ever-increasing importance. In the last decade, virtual reality (VR) technologies for rehabilitation have been extensively studied, to be used instead of or together with conventional treatments such as physiotherapy or occupational therapy. The aim of this work was to evaluate the GestureCollection VR-based rehabilitation tool in terms of the brain changes and clinical outcomes of the patients. Methods: Two groups of chronic patients underwent a rehabilitation treatment with (experimental) or without (control) complementation with GestureCollection. Functional magnetic resonance imaging exams and clinical assessments were performed before and after the treatment. A functional connectivity graph-based analysis was used to assess differences between the connections and in the network parameters strength and clustering coefficient. Results: Patients in both groups showed improvement in clinical scales, but there were more increases in functional connectivity in the experimental group than in the control group. Discussion: The experimental group presented changes in the connections between the frontoparietal and the somatomotor networks, associative cerebellum and basal ganglia, which are regions associated with reward-based motor learning. On the other hand, the control group also had results in the somatomotor network, in its ipsilateral connections with the thalamus and with the motor cerebellum, which are regions more related to a purely mechanical activity. Thus, the use of the GestureCollection system was successfully shown to promote neuroplasticity in several motor-related areas.

Isometric tongue endurance and incomplete laryngeal vestibule closure in Parkinson's disease.

BACKGROUND: Dysphagia is a common symptom of Parkinson's disease (PD). A delay in laryngeal vestibule closure (LVC) and a reduction in tongue pressure, may affect swallowing safety and increase the risk of pulmonary aspiration. OBJECTIVE: To verify the relationship between tongue pressure and airway protection in PD patients: (1) comparing tongue pressure measures and physiological events in the pharyngeal phase of swallowing between PD and controls and (2) analysing the association between tongue pressure and LVC in the PD group. METHODS: Twenty-three patients with idiopathic PD (64.9 years) and 24 healthy controls (64.1 years) participated in this study. All participants underwent the following procedures to verify tongue pressure measurements using the Iowa Oral Performance Instrument: maximum anterior and posterior pressure, isotonic and isometric tongue endurance and anterior and posterior tongue pressure during saliva swallowing. To verify swallowing safety, videofluoroscopic swallowing studies focusing on the pharyngeal phase were performed based on the MBSImP protocol. RESULTS: Compared to healthy controls, PD exhibited a statistically significant decline in tongue pressure tasks: posterior maximum pressure, isotonic endurance, anterior and posterior isometric endurance and tongue pressure during posterior swallowing. Patients with PD had worse pharyngeal scores, including LVC scores, than controls. PD and incomplete LVC had lower anterior isometric endurance scores when compared to those with complete LVC. CONCLUSION: PD with incomplete LVC scored lower in the anterior isometric endurance task. We observed a potential clinical use of this task for the assessment and management of dysphagia in patients with PD.

Whole-brain DTI parameters associated with tau protein and hippocampal volume in Alzheimer's disease.

The causes of the neurodegenerative processes in Alzheimer's disease (AD) are not completely known. Recent studies have shown that white matter (WM) damage could be more severe and widespread than whole-brain cortical atrophy and that such damage may appear even before the damage to the gray matter (GM). In AD, Amyloid-beta (Aß42 ) and tau proteins could directly affect WM, spreading across brain networks. Since hippocampal atrophy is common in the early phase of disease, it is reasonable to expect that hippocampal volume (HV) might be also related to WM integrity. Our study aimed to evaluate the integrity of the whole-brain WM, through diffusion tensor imaging (DTI) parameters, in mild AD and amnestic mild cognitive impairment (aMCI) due to AD (with Aß42 alteration in cerebrospinal fluid [CSF]) in relation to controls; and possible correlations between those measures and the CSF levels of Aß42 , phosphorylated tau protein (p-Tau) and total tau (t-Tau). We found a widespread WM alteration in the groups, and we also observed correlations between p-Tau and t-Tau with tracts directly linked to mesial temporal lobe (MTL) structures (fornix and hippocampal cingulum). However, linear regressions showed that the HV better explained the variation found in the DTI measures (with weak to moderate effect sizes, explaining from 9% to 31%) than did CSF proteins. In conclusion, we found widespread alterations in WM integrity, particularly in regions commonly affected by the disease in our group of early-stage disease and patients with Alzheimer's disease. Nonetheless, in the statistical models, the HV better predicted the integrity of the MTL tracts than the biomarkers in CSF.

Subacute functional connectivity correlates with cognitive recovery six months after stroke.

BACKGROUND AND PURPOSE: Cognitive impairment is a common consequence of stroke, and the rewiring of the surviving brain circuits might contribute to cognitive recovery. Studies investigating how the functional connectivity of networks change across time and whether their remapping relates to cognitive recovery in stroke patients are scarce. We aimed to investigate whether resting-state functional connectivity was associated with cognitive performance in stroke patients and if any alterations in these networks were correlated with cognitive recovery. METHODS: Using an fMRI ROI-ROI approach, we compared the ipsilesional, contralesional and interhemispheric functional connectivity of three resting-state networks involved in cognition - the Default Mode (DMN), Salience (SN) and Central Executive Networks (CEN), in subacute ischemic stroke patients (time 1, n = 37, stroke onset: 24.32 ± 7.44 days, NIHSS: 2.66 ± 3.45) with cognitively healthy controls (n = 20). Patients were reassessed six months after the stroke event (time 2, n = 20, stroke onset: 182.05 ± 8.17 days) to verify the subsequent reorganization of functional connections and whether such reorganization was associated with cognitive recovery. RESULTS: At time 1, patients had weaker interhemispheric connectivity in the DMN than controls; better cognitive performance at time 1 was associated with stronger interhemispheric and ipsilesional DMN connectivity, and weaker contralesional SN connectivity. At time 2, there were no changes in functional connectivity in stroke patients, compared to time 1. Better cognitive recovery measured at time 2 (time 2 - time 1) was associated with stronger functional connectivity in the DMN, and weaker interhemispheric subacute connectivity in the SN, both from time 1. CONCLUSIONS: Stroke disrupts the functional connectivity of the DMN, not only at the lesioned hemisphere but also between hemispheres. Six months after the stroke event, we could not detect the remapping of networks. Cognitive recovery was associated with the connectivity of both the DMN and SN of time 1. Our findings may be helpful for facilitating further understanding of the potential mechanisms underlying post-stroke cognitive performance.

Structural signature in SCA1: clinical correlates, determinants and natural history.

Spinocerebellar ataxia type 1 is an autosomal dominant disorder caused by a CAG repeat expansion in ATXN1, characterized by progressive cerebellar and extracerebellar symptoms. MRI-based studies in SCA1 focused in the cerebellum and connections, but there are few data about supratentorial/spinal damage and its clinical relevance. We have thus designed this multimodal MRI study to uncover the structural signature of SCA1. To accomplish that, a group of 33 patients and 33 age-and gender-matched healthy controls underwent MRI on a 3T scanner. All patients underwent a comprehensive neurological and neuropsychological evaluation. We correlated the structural findings with the clinical features of the disease. In addition, we evaluated the disease progression looking at differences in SCA1 subgroups defined by disease duration. Ataxia and pyramidal signs were the main symptoms. Neuropsychological evaluation disclosed cognitive impairment in 53% with predominant frontotemporal dysfunction. Gray matter analysis unfolded cortical thinning of primary and associative motor areas with more restricted impairment of deep structures. Deep gray matter atrophy was associated with motor handicap and poor cognition skills. White matter integrity loss was diffuse in the brainstem but restricted in supratentorial structures. Cerebellar cortical thinning was found in multiple areas and correlated not only with motor disability but also with verbal fluency. Spinal cord atrophy correlated with motor handicap. Comparison of MRI findings in disease duration-defined subgroups identified a peculiar pattern of progressive degeneration.

Cognitive Reserve Relates to Functional Network Efficiency in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition. fMRI studies of the human connectome have recently reported that AD patients present diminished functional efficiency in resting-state networks, leading to a loss in information flow and cognitive processing. No study has investigated, however, whether CR modifies the effects of the pathology in functional network efficiency in AD patients. We analyzed the relationship between CR, pathophysiology and network efficiency, and whether CR modifies the relationship between them. Fourteen mild AD, 28 amnestic mild cognitive impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and graph metrics to measure network efficiency. We found no relationship between CR and CSF biomarkers; CR was related to higher network efficiency in all groups; and abnormal levels of CSF protein biomarkers were related to more efficient networks in the AD group. Education modified the effects of tau-related pathology in the aMCI and mild AD groups. Although higher CR might not protect individuals from developing AD pathophysiology, AD patients with higher CR are better able to cope with the effects of pathology-presenting more efficient networks despite pathology burden. The present study highlights that interventions focusing on cognitive stimulation might be useful to slow age-related cognitive decline or dementia and lengthen healthy aging.

Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels.

BACKGROUND: In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF). METHODS: We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease. RESULTS: Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas. LIMITATIONS: The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used. CONCLUSION: We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.

Spinal cord diffusion tensor imaging in patients with sensory neuronopathy.

INTRODUCTION: We investigated whether MR diffusion tensor imaging (DTI) analysis of the cervical spinal cord could aid the (differential) diagnosis of sensory neuronopathies, an underdiagnosed group of diseases of the peripheral nervous system. METHODS: We obtained spinal cord DTI and T2WI at 3 T from 28 patients, 14 diabetic subjects with sensory-motor distal polyneuropathy, and 20 healthy controls. We quantified DTI-based parameters and looked at the hyperintense T2W signal at the spinal cord posterior columns. Fractional anisotropy and mean diffusivity values at C2-C3 and C3-C4 levels were compared between groups. We also compared average fractional anisotropy (mean of values at C2-C3 and C3-C4 levels). A receiver operating characteristic (ROC) curve was used to determine diagnostic accuracy of average fractional anisotropy, and we compared its sensitivity against the hyperintense signal in segregating patients from the other subjects. RESULTS: Mean age and disease duration were 52 ± 10 and 11.4 ± 9.3 years in the patient group. Eighteen subjects had idiopathic disease and 6 dysimmune etiology. Fractional anisotropy at C3-C4 level and average fractional anisotropy were significantly different between patients and healthy controls (p < 0.001 and <0.001) and between patients and diabetic subjects (p = 0.019 and 0.027). Average fractional anisotropy presented an area under the curve of 0.838. Moreover, it had higher sensitivity than visual detection of the hyperintense signal (0.86 vs. 0.54), particularly for patients with short disease duration. CONCLUSION: DTI-based analysis enables in vivo detection of posterior column damage in sensory neuronopathy patients and is a useful diagnostic test for this condition. It also helps the differential diagnosis between sensory neuronopathy and distal polyneuropathies.

Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large-scale RSNs is differently affected in patients with right- and left-MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting-state functional-MRIs of 99 subjects (52 controls, 26 right- and 21 left-MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF(2) C-toolbox, which provided ROI-wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right-MTLE. Both groups showed abnormal correlation between the dorsal-DMN and the posterior salience, as well as between the dorsal-DMN and the executive-control network. Patients with left-MTLE also showed reduced correlation between the dorsal-DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left-MTLE expressed a low cluster coefficient, whereas the altered connections on right-MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right- and left-MTLE patients with HS have widespread abnormal interactions of large-scale brain networks; however, all parameters evaluated indicate that left-MTLE has a more intricate bihemispheric dysfunction compared to right-MTLE. Hum Brain Mapp 37:3137-3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Neuroimaging in Sensory Neuronopathy.

Sensory neuronopathies (SN) are a group of disorders characterized by primary damage to the dorsal root ganglia neurons. Clinical features include multifocal areas of hypoaesthesia, pain, dysautonomia, and sensory ataxia, which is the major source of disability. Diagnosis relies upon clinical assessment and nerve conductions studies, but sometimes it is difficult to distinguish SN from similar conditions, such as axonal polyneuropathies and some myelopathies. In this scenario, underdiagnosis is certainly an important issue for SN patients and additional diagnostic tools are needed. MRI is able to evaluate the dorsal columns of the spinal cord and has proven useful in the workup of SN patients. Although T2 weighted hyperintensity restricted to the posterior fasciculi without contrast enhancement is the typical finding, additional abnormalities have been recently reported. The aim of this review is to gather available information on neuroimaging findings of SN, discuss their clinical correlates and the potential impact of novel MRI-based techniques.