Objectives:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuro-invasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). This study investigates the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework.Methods:In this prospective, monocentric, case series study, consecutive patients who fulfilled the following inclusion criteria benefited from an early postmortem structural brain MRI: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest computerized tomographic (CT) scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility.Results:Among the 62 patients who died from COVID-19 from 31/03/2020 to 24/04/2020 at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent). Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality was observed.Conclusions:Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. Brainstem MRI findings do not support a brain-related contribution to respiratory distress in COVID-19.

Partial volume effect is an important source of bias in PET images that can be lowered by accounting for the point spread function (PSF) of the scanner. We measured such a PSF in various points of a clinical PET scanner and modelled it as a product of matrices acting in image space, taking the asymmetrical, shift-varying and non-Gaussian character of the PSF into account (AMP modelling), and we integrated this accurate image space modelling into a conventional list-mode OSEM algorithm (EM-AMP reconstruction). We showed on the one hand that when a sufficiently high number of iterations are considered, the AMP modelling lead to better recovery coefficients at reduced background noise compared to reconstruction where no or only partial resolution modelling is performed, and on the other hand that for a small number of iterations, a Gaussian modelling gave the best recovery coefficients. Moreover, we have demonstrated that a deconvolution based on the AMP system response model leads to the same recovery coefficients as the corresponding EM-AMP reconstruction, but at the expense of an increased background noise.

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ImportanceThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuro-invasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). Brain magnetic resonance imaging (MRI) data in COVID-19 patients are scarce due to difficulties to obtain such examination in infected unstable patients during the COVID-19 outbreak.ObjectiveTo investigate the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework.DesignProspective, case series study with postmortem brain MRI obtained early (<24h) after death.SettingMonocentric study.ParticipantsFrom 31/03/2020 to 24/04/2020, consecutive decedents who fulfilled the following inclusion criteria were included: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest computerized tomographic (CT) scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility.Main Outcome(s) andMeasure(s)Signs of acute brain injury and MRI signal abnormalities along the olfactory tract and brainstem were searched independently by 3 neuroradiologists, then reviewed with neurologists and clinicians.ResultsAmong the 62 patients who died from COVID-19 during the inclusion period, 19 decedents fulfilled inclusion criteria. Subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent) were observed. Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality.Conclusions and RelevancePostmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19 that might be triggered by the virus-induced endothelial disturbances. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. The absence of brainstem MRI abnormalities does not support a brain-related contribution to respiratory distress in COVID-19.Key PointsQuestionIs there common brain MRI abnormalities patterns in non-survivors of coronavirus disease 2019 ?FindingsIn a case series of 19 non-survivors of severe COVID-19 disease, early postmortem brain MRI demonstrated patterns evocative of intracranial vasculopathy in 4 decedents: subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent). Asymmetric olfactory bulbs were found in 4 other decedents but without downstream olfactory tract abnormalities.MeaningPostmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19 that might be triggered by virus-induced endothelial disturbances.

Human brain activity is intrinsically organized into resting-state networks (RSNs) that transiently activate or deactivate at the sub-second timescale. Few neuroimaging studies have addressed how Alzheimer's disease (AD) affects these fast temporal brain dynamics, and how they relate to the cognitive, structural and metabolic abnormalities characterizing AD. We aimed at closing this gap by investigating both brain structure and function using magnetoencephalography (MEG) and hybrid positron emission tomography-magnetic resonance (PET/MR) in 10 healthy elders, 10 patients with subjective cognitive decline (SCD), 10 patients with amnestic mild cognitive impairment (aMCI) and 10 patients with typical Alzheimer’s disease with dementia (AD). The fast activation/deactivation state dynamics of RSNs were assessed using hidden Markov modeling (HMM) of power envelope fluctuations at rest measured with MEG. Correlations were sought between temporal properties of HMM states and participants' cognitive test scores, whole hippocampal grey matter volume and regional brain glucose metabolism. The posterior default-mode network (DMN) was less often activated and for shorter durations in AD patients than matched healthy elders. No significant difference was found in patients with SCD or aMCI. The time spent by participants in the activated posterior DMN state did not correlate significantly with cognitive scores, nor with the whole hippocampal volume. However, it correlated positively with the regional glucose consumption in the right dorsolateral prefrontal cortex (DLPFC). AD patients present alterations of posterior DMN power activation dynamics at rest that identify an additional electrophysiological correlate of AD-related synaptic and neural dysfunction. The right DLPFC may play a causal role in the activation of the posterior DMN, possibly linked to the occurrence of mind wandering episodes. As such, these data might suggest a neural correlate of the decrease in mind wandering episodes reported in pathological aging.

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SUMMARYPurpose: Metabolic changes have been described in the nonepileptic temporal lobe of patients with unilateral mesiotemporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS). To better understand the functional correlate of this metabolic finding, we have sought to characterize brain regions in patients with MTLE that show correlation between unilateral episodic memory performances, as assessed by intracarotid amobarbital test (IAT), and interictal regional cerebral metabolism measured by [18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: Resting FDG-PET was performed interictally in 26 patients with unilateral MTLE caused by HS (16 female, mean age: 36 years; 16 left HS). Using statistical parametric mapping (SPM8), we performed a group comparison analysis comparing brain metabolism in the patients and in 54 adult controls (27 female, mean age: 32 years), with FDG-PET data of right HS patients being flipped. IAT scores of nonepileptic hemisphere functions (amobarbital injection ipsilateral to HS) were used as covariates of interest in a correlation analysis with regional brain metabolism. Key Findings: The group comparison analysis revealed significant hypometabolic areas in a widespread temporofrontal network ipsilateral to HS. In addition, a significant increase in metabolism was found in mesial and lateral temporal regions contralateral to HS. Significant positive correlations were found between IAT scores of nonepileptic hemisphere functions and mesial temporal metabolism in this hemisphere. Significance: This study demonstrates the existence of significant increase in relative regional cerebral glucose metabolism in mesial and lateral temporal regions contralateral to the epileptic focus in patients with unilateral MTLE associated with HS. The positive correlation in these brain regions between IAT scores and metabolism supports the role of disease-induced plasticity mechanisms contralateral to HS in the preservation of episodic memory processes.

Background: Two major concerns with respect to task-based motor functional magnetic resonance imaging (fMRI) are inadequate participants' performance as well as intra-and inter-subject variability in execution of the motor action. New method: This study validates the use of an MRI-compatible stimulator based on a pneumatic artificial muscle (PAM) for block-design fMRI mapping of the primary sensorimotor (SM1) cortex in a series of fifteen right-handed healthy subjects. The PAM stimulator elicits computer-controlled timely and reproducible passive movements of fingers/toes. Participants performed comparable active and passive PAM-induced flexion-extensions of the index fingers. Results: Passive movement of the right index finger and passive alternating right and left index finger movement resulted in a significant increase in blood-oxygen-level-dependent (BOLD) signal in contralateral SM1 cortex in 14/15 and 15/15 subjects respectively. Similar networks were recruited by active and passive index finger movements. However, at the group level, active movement induced significantly higher increases in BOLD signal than passive movement in contralateral SM1 cortex (p < 0.05 Family Wise Error [FWE] corrected), supplementary motor area (p < 0.001 uncorrected), ipsilateral cerebellum (p < 0.001 uncorrected), and bilateral putamina (p < 0.001 uncorrected). Comparison with existing method(s): As compared to the several MRI-compatible robotic devices for computercontrolled passive movement of the fingers that were introduced in the past decades, the proposed PAM-based stimulator is smaller, handier, and easier to use in the MRI setting. Conclusions: PAM-based stimulators can be reliably used for passive sensorimotor fMRI mapping in healthy subjects. Using this approach, bilateral SM1 cortices can be mapped accurately during a single 6-min blockdesign fMRI protocol.