Microstructural alterations in hypoxia-related BRAIN centers after COVID-19 by using DTI: A preliminary study.

PURPOSE: To investigate whether the diffusion tensor imaging (DTI) parameters alterations in the in hypoxia-related neuroanatomical localizations in patients after COVID-19. Additionally, the relationship between DTI findings and the clinical severity of the disease is evaluated. METHODS: The patients with COVID-19 were classified into group 1 (total patients, n = 74), group 2 (outpatient, n = 46), and group 3 (inpatient, n = 28) and control (n = 52). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated from the bulbus, pons, thalamus, caudate nucleus, globus pallidum, putamen, and hippocampus. DTI parameters were compared between groups. Oxygen saturation, D dimer and lactate dehydrogenase (LDH) values associated with hypoxia were analyzed in inpatient group. Laboratory findings were correlated with ADC and FA values. RESULTS: Increased ADC values in the thalamus, bulbus and pons were found in group 1 compared to control. Increased FA values in the thalamus, bulbus, globus pallidum and putamen were detected in group 1 compared to control. The FA and ADC values obtained from putamen were higher in group 3 compared to group 2. There was a negative correlation between basal ganglia and hippocampus FA values and plasma LDH values. The ADC values obtained from caudate nucleus were positively correlated with plasma D Dimer values. CONCLUSION: ADC and FA changes may reveal hypoxia-related microstructural damage after COVID-19 infection. We speculated that the brainstem and basal ganglia can affected during the subacute period.

Cognitive, Motor, & Negative Valence Systems in Neurologic Pasc: A Preliminary Study

Background: Nervous system post-acute sequelae of COVID-19 (NS-PASC) include cognitive and mental health symptoms. To further define these, we applied a Research Domain Criteria (RDoC) approach to examine motor, positive valence (PV) and negative valence (NV) systems, and social processing data in The COVID Mind Study of NS-PASC. Method(s): NS-PASC participants (>3 months after COVID-19) referred from a NeuroCOVID Clinic and non-COVID controls from New Haven, CT and Baltimore, MD completed an RDoC test battery for cognition (language, declarative and working memory, cognitive control, perception), motor, PV, NV, and social processes. To date, 3T MRI with diffusion tensor imaging was performed in 11 NS-PASC to assess white matter integrity (global white matter fractional anisotropy [FA]) as a contributor to alterations identified on the RDoC tests. Analysis of Covariance examined group differences after adjusting for sex, race, ethnicity, age, and years of education. Result(s): 25 NS-PASC participants (age 43.4+/-11.3 yrs, 76% female, 402 days after COVID-19 symptom onset) and 29 controls (age 46.2.6+/-13.1 yrs, 66% female) completed the battery. Controls were more racially diverse and less educated than NS-PASC (43% vs. 12% Black, p=0.005;14.5 vs. 16.1 yrs of education, p< 0.05). Means and statistics for RDoC between NS-PASC and controls are shown in Table. NS-PASC performed worse in language, verbal working and declarative memory, and perception and reported greater cognitive control difficulties (e.g., behavioral inhibition, set shifting) without issues on performance-based metrics (Stroop, Trail Making Test-Part B), and had slower motor function. NS-PASC reported more NV issues including greater symptoms of depression, rumination in response to depressive mood, apathy, childhood trauma, anxiety, and perceived stress. There were no differences in PV and social processing. In a subset of NS-PASC participants who underwent MRI, there was a dynamic range of FA values with a mean of 0.509 (IQR 0.481 - 0.536). Conclusion(s): Our findings extend previous PASC studies characterizing cognitive and mental health alterations, indicating that additional RDoC assessments warrant focus, including alterations in motor and the negative valence system. In future analyses, we will examine white matter integrity as a pathophysiologic contributor to these RDoC systems.

Post-Covid Cognitive Impairment Mri Brain Scan Abnormalities: A Potential Biomarker

Background: Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. We hypothesized that PASC CI patients would have brain inflammation and BBB disruption using advanced MR imaging. Method(s): In this prospective longitudinal study, 14 patients with PASC CI (mild and non-hospitalised) were enrolled (mean age of 45;10 F and 4 M) and 10 sex and age matched healthy controls. 13 had a follow up MR at 9-12 months (mean 10 months). All participants underwent DCE perfusion (an index of BBB integrity with Ktrans as the measurement), Diffusion Tensor Imaging (DTI) and single voxel MR spectroscopy (MRS) of the frontal cortex/white matter and the brainstem in addition to brain anatomical MRI. Between group analyses were used to determine which MRI outcomes were significantly different from controls in patients with PASC CI. Result(s): The PASCI CI group showed significantly increased (ie BBB impairment) Ktrans, and increased region (Frontal white matter and Brain Stem)-specific areas in the brain (p=< 0.005), reduction in NAA (ie neuronal injury) and mild reduction of Glx (ie excitotoxicity) in the frontal white matter and brain stem (p=0.004), and reduction in white matter integrity (increased diffusivity -greater radial and mean diffusivity). Increased Ktrans was correlated with increased both radial and mean diffusivity (r=0.9) in all tested brain regions. Ktrans significantly improved in the follow up MR (p= 002596 Z=-2.794872) with no difference between subjects and controls indicating BBB normalisation (p= 0.442418, z= -0.144841). White matter integrity also improved especially in the fractional anisotropy values in the executive networks (p=< 0.00045). MRS showed significant improvement in the NAA in the frontal white matter but Glx remain high as compared to the controls (p=0.0006). Conclusion(s): PASC CI was characterised by reversible diffuse BBB impairment, neuronal/axonal and excitotoxic injury. BBB impairment was associated with white matter disruption. These are suggestive biomarkers for the presence, severity and prognosis of PASC CI. Such biomarkers could underpin appropriate trial design and timing of intervention.

Feasibility of diffusion-tensor and correlated diffusion imaging for studying white-matter microstructural abnormalities: Application in COVID-19.

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at the study initiation and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a viable single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

Abnormal brain diffusivity in participants with persistent neuropsychiatric symptoms after COVID-19.

Objectives: We aimed to compare brain white matter integrity in participants with post-COVID-19 conditions (PCC) and healthy controls. Methods: We compared cognitive performance (NIH Toolbox®), psychiatric symptoms and diffusion tensor imaging (DTI) metrics between 23 PCC participants and 24 controls. Fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities were measured in 9 white matter tracts and 6 subcortical regions using MRICloud. Results: Compared to controls, PCC had similar cognitive performance, but greater psychiatric symptoms and perceived stress, as well as higher FA and lower diffusivities in multiple white matter tracts (ANCOVA-p-values≤0.001-0.048). Amongst women, PCC had higher left amygdala-MD than controls (sex-by-PCC p=0.006). Regardless of COVID-19 history, higher sagittal strata-FA predicted greater fatigue (r=0.48-0.52, p<0.001) in all participants, and higher left amygdala-MD predicted greater fatigue (r=0.61, p<0.001) and anxiety (r=0.69, p<0.001) in women, and higher perceived stress (r=0.45, p=0.002) for all participants. Conclusions: Microstructural abnormalities are evident in PCC participants averaged six months after COVID-19. The restricted diffusivity (with reduced MD) and higher FA suggest enhanced myelination or increased magnetic susceptibility from iron deposition, as seen in stress conditions. The higher amygdala-MD in female PCC suggests persistent neuroinflammation, which might contribute to their fatigue, anxiety, and perceived stress.

Using DTI tractography to guide tDCS interventions in a complex acquired brain Injury neurorehabilitation protocol - a case report

51-year-old man (C.P.) had a diffuse-axonal-injury after falling from a 5-meter height, followed by a 22-minute anoxia due to a cardiac arrest. In the ICU, he tested positive to COVID-19, and needed intubation. After coronavirus infection, C.P. presented Guillain-Barre syndrome. 2months after discharge, he was admitted to rehabilitation. DTI tractography for evaluation of the structural integrity of white matter tracts revealed: i) Lesions in the basal ganglia;ii) Sequelary lesions in the right frontal, cortical, subcortical, temporal, parieto-occipital and cerebellar hemispheres;iii) Asymmetry of the corticospinal tracts - less fibers on the left;iv) Poor definition of the fibers of the right arcuate fasciculus;v)Asymmetrical thinning of the cortico-ponto-cerebellar tracts, worse on the left, and more discreetly in the spinocerebellar tracts. Based on this, C.P. underwent 4 different 30-session tDCS protocols consisting of twice-daily 20min 2mA sessions (10min interval), 5days/week (120sessions total), combined with physiotherapy, cognitive, swallowing and speech therapy. Montages: Pr1 (anode: Cz - 5x10cm;cathode: 10th Thoracic Vertebra - 5x7cm);Pr2 (1 - anode:C3;cathode:Fp2 / 2 - anode: Cerebellum;cathode:Fp2);Pr3 (anode:F3;cathode:Fp2) and Pr4 (anode:Cp5;cathode:Fp2). Except for Pr1, electrode size for all protocols were 5x7cm. We used the Coma Recovery Scale (CRS-R) and Rancho Los Amigos Scale (RLAS) for clinical assessments at the baseline and after every 10 sessions until the end of the intervention. At the baseline, C.P. presented a minimal responsive state of consciousness (CRS-R: 3;RLAS: Level 1) and tolerated well the tDCS interventions. CRS-R scores gradually improved in various domains during the treatment. At the end, RLAS score was level 5 and CRS-R, 19. Our preliminary results suggest DTI tractography may be a potential biomarker to guide more personalized tDCS interventions for complex cases of patients with acquired brain injuries. A second DTI tractography will be made in the future for comparison purposes. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: Acquired Brain Injury, Traumatic Brain Injury, COVID-19, Guillain Barre SyndromeCopyright © 2023

Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study.

Cognitive impairment represents a leading residual symptom of COVID-19 infection, which lasts for months after the virus clearance. Up-to-date scientific reports documented a wide spectrum of brain changes in COVID-19 survivors following the illness's resolution, mainly related to neurological and neuropsychiatric consequences. Preliminary insights suggest abnormal brain metabolism, microstructure, and functionality as neural under-layer of post-acute cognitive dysfunction. While previous works focused on brain correlates of impaired cognition as objectively assessed, herein we investigated long-term neural correlates of subjective cognitive decline in a sample of 58 COVID-19 survivors with a multimodal imaging approach. Diffusion Tensor Imaging (DTI) analyses revealed widespread white matter disruption in the sub-group of cognitive complainers compared to the non-complainer one, as indexed by increased axial, radial, and mean diffusivity in several commissural, projection and associative fibres. Likewise, the Multivoxel Pattern Connectivity analysis (MVPA) revealed highly discriminant patterns of functional connectivity in resting-state among the two groups in the right frontal pole and in the middle temporal gyrus, suggestive of inefficient dynamic modulation of frontal brain activity and possible metacognitive dysfunction at rest. Beyond COVID-19 actual pathophysiological brain processes, our findings point toward brain connectome disruption conceivably translating into clinical post-COVID cognitive symptomatology. Our results could pave the way for a potential brain signature of cognitive complaints experienced by COVID-19 survivors, possibly leading to identify early therapeutic targets and thus mitigating its detrimental long-term impact on quality of life in the post-COVID-19 stages.

Structural brain changes in patients with persistent headache after COVID-19 resolution.

Headache is among the most frequently reported symptoms after resolution of COVID-19. We assessed structural brain changes using T1- and diffusion-weighted MRI processed data from 167 subjects: 40 patients who recovered from COVID-19 but suffered from persistent headache without prior history of headache (COV), 41 healthy controls, 43 patients with episodic migraine and 43 patients with chronic migraine. To evaluate gray matter and white matter changes, morphometry parameters and diffusion tensor imaging-based measures were employed, respectively. COV patients showed significant lower cortical gray matter volume and cortical thickness than healthy subjects (p < 0.05, false discovery rate corrected) in the inferior frontal and the fusiform cortex. Lower fractional anisotropy and higher radial diffusivity (p < 0.05, family-wise error corrected) were observed in COV patients compared to controls, mainly in the corpus callosum and left hemisphere. COV patients showed higher cortical volume and thickness than migraine patients in the cingulate and frontal gyri, paracentral lobule and superior temporal sulcus, lower volume in subcortical regions and lower curvature in the precuneus and cuneus. Lower diffusion metric values in COV patients compared to migraine were identified prominently in the right hemisphere. COV patients present diverse changes in the white matter and gray matter structure. White matter changes seem to be associated with impairment of fiber bundles. Besides, the gray matter changes and other white matter modifications such as axonal integrity loss seemed subtle and less pronounced than those detected in migraine, showing that persistent headache after COVID-19 resolution could be an intermediate state between normality and migraine.

Brain FDG PET imaging of patients with persistent post- COVID-19 fatigue

Aim/Introduction: A recent report prepared by the Centers for Disease Control and Prevention indicates that 71% of patients experience persistent fatigue even after recovery from the acute phase of COVID-19 infection. We investigated if post-COVID-19 fatigue is associated with alterations in brain metabolism and microstructure to better understand the underlying neurobiological mechanism. Material(s) and Method(s): Brain F-18 FDG PET and diffusion tensor magnetic resonance imaging (DTIMR) were performed in 12 patients experiencing persistent post- COVID-19 fatigue that lasted more than six weeks post-discharge from hospitalization or discontinued home isolation after acute SARS-CoV-2 infection (fatigue group, Male:Female = 6:6, mean > SD age 35.7 > 13.8 years, Chalder fatigue scale score 8.3 > 2.2, time since COVID-19 diagnosis 7.9 > 5.5 months) and 9 recovered patients without such fatigue (non-fatigue group, M:F = 3:6, age 25.6 > 9.2, fatigue score 1.6 > 1.5, time since COVID-19 diagnosis 8.0 > 6.0 months). A commercially available normative brain FDG PET database (MIMneuro, v7.0.5, MIM Software, Inc.) was used to derive z scores for regional cerebral glucose metabolism. Fractional anisotropy (FA) values were extracted from DTI-MR datasets. Twotailed t-tests were performed for group comparison and P < 0.05 was considered statistically significant. Result(s): The fatigue group demonstrated significantly higher regional cerebral glucose metabolism in the left inferior and middle cerebellar peduncle (P = 0.001 and 0.043, respectively), left middle temporal gyrus (P = 0.002), left parahippocampal gyrus (P = 0.029), primary visual cortex (P = 0.031), supplementary motor area (P = 0.036), supramarginal gyrus (P = 0.044), and lower metabolism in the left precentral gyrus (P = 0.001) when compared to the non-fatigue group. The fatigue group also demonstrated significantly higher FA values in the left and right middle frontal gyrus (P = 0.014 and 0.038, respectively), left precentral gyrus (P = 0.024), right superior frontal gyrus (P =0.032), right postcentral gyrus (P = 0.047), left superior parietal gyrus (P = 0.048), and corpus callosum (P = 0.016) when compared to the nonfatigue group. Conclusion(s): Patients experiencing persistent fatigue after recovering from acute SARS-CoV-2 infection demonstrated significant changes in regional cerebral glucose metabolism and microstructure, when compared to those individuals without on-going fatigue symptoms. The altered cerebral metabolic and microstructural profile may help to better understand the neurobiological mechanism for management of patients suffering from lingering post-COVID-19 fatigue.

Brain FDG PET imaging of patients with persistent post- COVID-19 fatigue

Aim/Introduction: A recent report prepared by the Centers for Disease Control and Prevention indicates that 71% of patients experience persistent fatigue even after recovery from the acute phase of COVID-19 infection. We investigated if post-COVID-19 fatigue is associated with alterations in brain metabolism and microstructure to better understand the underlying neurobiological mechanism. Material(s) and Method(s): Brain F-18 FDG PET and diffusion tensor magnetic resonance imaging (DTIMR) were performed in 12 patients experiencing persistent post- COVID-19 fatigue that lasted more than six weeks post-discharge from hospitalization or discontinued home isolation after acute SARS-CoV-2 infection (fatigue group, Male:Female = 6:6, mean > SD age 35.7 > 13.8 years, Chalder fatigue scale score 8.3 > 2.2, time since COVID-19 diagnosis 7.9 > 5.5 months) and 9 recovered patients without such fatigue (non-fatigue group, M:F = 3:6, age 25.6 > 9.2, fatigue score 1.6 > 1.5, time since COVID-19 diagnosis 8.0 > 6.0 months). A commercially available normative brain FDG PET database (MIMneuro, v7.0.5, MIM Software, Inc.) was used to derive z scores for regional cerebral glucose metabolism. Fractional anisotropy (FA) values were extracted from DTI-MR datasets. Twotailed t-tests were performed for group comparison and P < 0.05 was considered statistically significant. Result(s): The fatigue group demonstrated significantly higher regional cerebral glucose metabolism in the left inferior and middle cerebellar peduncle (P = 0.001 and 0.043, respectively), left middle temporal gyrus (P = 0.002), left parahippocampal gyrus (P = 0.029), primary visual cortex (P = 0.031), supplementary motor area (P = 0.036), supramarginal gyrus (P = 0.044), and lower metabolism in the left precentral gyrus (P = 0.001) when compared to the non-fatigue group. The fatigue group also demonstrated significantly higher FA values in the left and right middle frontal gyrus (P = 0.014 and 0.038, respectively), left precentral gyrus (P = 0.024), right superior frontal gyrus (P =0.032), right postcentral gyrus (P = 0.047), left superior parietal gyrus (P = 0.048), and corpus callosum (P = 0.016) when compared to the nonfatigue group. Conclusion(s): Patients experiencing persistent fatigue after recovering from acute SARS-CoV-2 infection demonstrated significant changes in regional cerebral glucose metabolism and microstructure, when compared to those individuals without on-going fatigue symptoms. The altered cerebral metabolic and microstructural profile may help to better understand the neurobiological mechanism for management of patients suffering from lingering post-COVID-19 fatigue.

Multi-Modal Neuroimaging Neural Network-Based Feature Detection for Diagnosis of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative brain disease, and it is challenging to mine features that distinguish AD and healthy control (HC) from multiple datasets. Brain network modeling technology in AD using single-modal images often lacks supplementary information regarding multi-source resolution and has poor spatiotemporal sensitivity. In this study, we proposed a novel multi-modal LassoNet framework with a neural network for AD-related feature detection and classification. Specifically, data including two modalities of resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were adopted for predicting pathological brain areas related to AD. The results of 10 repeated experiments and validation experiments in three groups prove that our proposed framework outperforms well in classification performance, generalization, and reproducibility. Also, we found discriminative brain regions, such as Hippocampus, Frontal_Inf_Orb_L, Parietal_Sup_L, Putamen_L, Fusiform_R, etc. These discoveries provide a novel method for AD research, and the experimental study demonstrates that the framework will further improve our understanding of the mechanisms underlying the development of AD.

Diffusion tensor tractography of the fornix in cerebral amyloid angiopathy, mild cognitive impairment and Alzheimer's disease.

PURPOSE: Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and clinical entity that occurs independently and with co-existent Alzheimer's disease (AD) and small vessel disease. We compared diffusion tensor imaging (DTI) metrics of the fornix, the primary efferent tract of the hippocampus between CAA, AD and Mild Cognitive Impairment (MCI) and healthy controls. METHODS: Sixty-eight healthy controls, 32 CAA, 21 AD, and 26 MCI patients were recruited at two centers. Diffusion tensor images were acquired at 3 T with high spatial resolution and fluid-attenuated inversion recovery (FLAIR) to suppress cerebrospinal fluid (CSF) and minimize partial volume effects on the fornix. The fornix was delineated with deterministic tractography to yield mean diffusivity (MD), axial diffusivity (AXD), radial diffusivity (RD), fractional anisotropy (FA) and tract volume. Volumetric measurements of the hippocampus, thalamus, and lateral ventricles were obtained using T1-weighted MRI. RESULTS: Diffusivity (MD, AXD, and RD) of the fornix was highest in AD followed by CAA compared to controls; the MCI group was not significantly different from controls. FA was similar between groups. Fornix tract volume was âˆ¼ 30% lower for all three patient groups compared to controls, but not significantly different between the patient groups. Thalamic and hippocampal volumes were preserved in CAA, but lower in AD and MCI compared to controls. Lateral ventricular volumes were increased in CAA, AD and MCI. Global cognition, memory, and executive function all correlated negatively with fornix diffusivity across the combined clinical group. CONCLUSION: There were significant diffusion changes of the fornix in CAA, AD and MCI compared to controls, despite relatively intact thalamic and hippocampal volumes in CAA, suggesting the mechanisms for fornix diffusion abnormalities may differ in CAA compared to AD and MCI.

Magnetic Resonance Neurography Reveals Smoking-Associated Decrease in Sciatic Nerve Structural Integrity in Type 2 Diabetes.

OBJECTIVE: It is controversially discussed in how far smoking contributes to diabetic polyneuropathy (DPN) in type 2 diabetes (T2D). Diffusion-weighted magnetic resonance neurography (MRN) at 3 Tesla has been shown to provide objective values for structural nerve integrity in patients with T2D. The aim of this study was to investigate the contribution of cigarette smoking on structural nerve integrity in T2D. METHODS: This cross-sectional prospective cohort study investigated the structural integrity of the sciatic nerve in 10 smokers, 40 never-smokers, and 20 ex-smokers with T2D and 10 healthy control subjects, using diffusion tensor imaging MRN at 3 Tesla and semi-automated nerve fiber tracking. Results were correlated with clinical, electrophysiological, and serological data. RESULTS: The sciatic nerve's fractional anisotropy (FA), a parameter for structural nerve integrity, was significantly lower in smokers with T2D when compared to controls (p = 0.002) and never-smokers (p = 0.015), and lower in ex-smokers when compared to controls (p = 0.015). In addition, sciatic nerve radial diffusivity, a marker of myelin damage, was increased in smokers versus controls and never-smokers (p = 0.048, p = 0.049, respectively). Furthermore, FA in T2D patients was negatively correlated with clinical and electrophysiological markers of DPN. FA also showed negative correlations with the pulse wave velocity, a marker of arterial stiffness and associated microangiopathy, in controls (r = -0.70; p = 0.037), never-smokers (r = -0.45; p = 0.004), ex-smokers (r = -0.55; p = 0.009), and a similar trend in smokers (r = -0.63; p = 0.076). Negative correlations were found between FA and skin auto-fluorescence, a marker of tissue advanced glycation end product accumulation and therefore long-term glycemic stress in T2D, in never-smokers (r = -0.39; p = 0.020) and smokers (r = -0.84; p = 0.004), but not in ex-smokers (r = -0.07; p = 0.765). CONCLUSION: The findings indicate that smoking contributes to sciatic nerve damage in T2D, potentially worsening DPN due to glycemic stress and less microangiopathy-associated myelin damage in active smokers, while angiopathic effects predominate in ex-smokers. To stop smoking may therefore pose a promising preventive measure to slow the progression of DPN in T2D.

Brain correlates of depression, post-traumatic distress, and inflammatory biomarkers in COVID-19 survivors: A multimodal magnetic resonance imaging study.

Psychiatric sequelae substantially contribute to the post-acute burden of disease associated with COVID-19, persisting months after clearance of the virus. Brain imaging shows white matter (WM) hypodensities/hyperintensities, and the involvement of grey matter (GM) in prefrontal, anterior cingulate (ACC) and insular cortex after COVID, but little is known about brain correlates of persistent psychopathology. With a multimodal approach, we studied whole brain voxel-based morphometry, diffusion-tensor imaging, and resting-state connectivity, to correlate MRI measures with depression and post-traumatic distress (PTSD) in 42 COVID-19 survivors without brain lesions, at 90.59 â€‹± â€‹54.66 days after COVID. Systemic immune-inflammation index (SII) measured in the emergency department, which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, predicted worse self-rated depression and PTSD, widespread lower diffusivity along the main axis of WM tracts, and abnormal functional connectivity (FC) among resting state networks. Self-rated depression and PTSD inversely correlated with GM volumes in ACC and insula, axial diffusivity, and associated with FC. We observed overlapping associations between severity of inflammation during acute COVID-19, brain structure and function, and severity of depression and post-traumatic distress in survivors, thus warranting interest for further study of brain correlates of the post-acute COVID-19 syndrome. Beyond COVID-19, these findings support the hypothesis that regional GM, WM microstructure, and FC could mediate the relationship between a medical illness and its psychopathological sequelae, and are in agreement with current perspectives on the brain structural and functional underpinnings of depressive psychopathology.

Cerebral Micro-Structural Changes in COVID-19 Patients - An MRI-based 3-month Follow-up Study.

BACKGROUND: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2. METHODS: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information. FINDINGS: In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss (p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss (p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level (p value <0.05). INTERPRETATION: Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2. FUNDING: Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.