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.

Diffusion-weighted imaging measurements of central smell regions in COVID-19 patients: insular gyrus, corpus amygdala, and thalamus.

OBJECTIVE: The aim of this study was to investigate central smell centers with cranial magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in COVID-19. PATIENTS AND METHODS: This retrospective study evaluated cranial MRI images of 54 adults. The experimental group (Group 1), consisting of 27 patients with positive COVID-19 real-time polymerase chain reaction (RT-PCR) assays, was compared to the control group (Group 2), comprising 27  healthy controls without COVID-19. The apparent diffusion coefficient (ADC) values were measured in the corpus amygdala, thalamus, and insular gyrus in both groups. RESULTS: Thalamus ADC values of the COVID-19 group were significantly lower compared to the control group bilaterally. However, no differences were found in the insular gyrus and corpus amygdala ADC values between the two groups. Positive correlations were observed between the insular gyrus and corpus amygdala ADC values and the thalamus ADC values. Insular gyrus ADC values (right) were higher in females. Left insular gyrus and corpus amygdala ADC values were higher in COVID-19 patients with smell loss. Right insular gyrus and left corpus amygdala ADC values were lower in COVID-19 patients with lymphopenia. CONCLUSIONS: Diffusion restriction in olfactory areas can be considered an obvious indicator that the COVID-19 virus affects and damages the immune system at the neuronal level. Given the urgency and lethality of the current pandemic, acute onset odor loss should be considered a high suspicion-adhesive index for patients with SARS-CoV-2 infection. Therefore, the sense of smell should be considered and evaluated simultaneously with other neurological symptoms. DWI should be widely used as an early imaging method for central nervous system (CNS) infections, especially in relation to COVID-19.

DTI of the Olfactory Bulb in COVID-19-Related Anosmia: A Pilot Study.

This study aimed to assess the utility of DTI in the detection of olfactory bulb dysfunction in COVID-19-related anosmia. It was performed in 62 patients with COVID-19-related anosmia and 23 controls. The mean diffusivity and fractional anisotropy were calculated by 2 readers. The difference between the fractional anisotropy and mean diffusivity values of anosmic and control olfactory bulbs was statistically significant (P = .001). The threshold of fractional anisotropy and mean diffusivity to differentiate a diseased from normal olfactory bulb were 0.22 and 1.5, with sensitivities of 84.4% and 96.8%, respectively, and a specificity of 100%.

Brain diffusion alterations in patients with COVID-19 pathology and neurological manifestations.

BACKGROUND AND OBJECTIVE: COVID-19 neurological manifestations have been progressively recognized. Among available MRI techniques, diffusion weighted imaging (DWI) shows promise to study microstructure, inflammation, and edema. Previous DWI studies reported alterations in brain diffusivity in COVID-19 patients, as assessed by morphologic evaluation of brain DWI scans only. The aim of this study was to assess and quantify brain diffusion alterations in COVID-19 patients with neurological manifestations. METHODS: 215 COVID-19 patients with neurological manifestations (olfactory and/or other neurological disorders) and 36 normal controls were compared and studied with DWI and T1-weighted MRI scans. MRI scans were processed by a semi-automatic processing procedure specifically developed for the purpose of this study, and the Apparent Diffusion Coefficient (ADC) was quantified in different brain tissues and individual white matter (WM) and gray matter (GM) regions. Differences in ADC values were assessed between COVID-19 patients and normal controls, as well as in the COVID-19 patient population grouped by hospitalization and neurological symptoms. RESULTS: Among COVID-19 patients (median [IQR] = 52 [42 - 60] years of age, 58 % females), 91 were hospitalized and 26 needed intensive care. 84 patients had hyposmia/ageusia only, while 131 ones showed other neurological disorders. COVID-19 patients showed significantly increased ADC values in the WM and in several GM regions (p < 0.001). ADC values were significantly correlated with MRI time from disease onset (p < 0.05). Hospitalized patients showed significantly higher ADC alteration than non-hospitalized patients in all brain tissues; similarly, COVID-19 patients with neurological disorders showed significantly higher ADC values than those with olfactory loss only. ADC alteration was highest in patients with cognitive or memory disorder and in those with encephalitis or meningitis. ADC values were neither associated with the duration of hospitalization nor with the need for intensive care. CONCLUSION: Current findings suggest DWI potential as a non-invasive marker of neuroinflammation in COVID-19, and the transient nature of the same. Future longitudinal studies are needed to confirm our findings.

Cerebral microvascular injuries in severe COVID-19 infection: progression of white matter hyperintensities post-infection.

A range of neuroradiological findings has been reported in patients with COVID-19, some mimicking cerebral small vessel disease (CSVD). We present a case of a man in his 50s with severe COVID-19, who was Glasgow Coma Scale 3 and tetraparetic after sedation was ceased in the intensive care unit. Return of consciousness and motor activity was slow. An MRI 1 month after debut of symptoms demonstrated white matter hyperintensities on T2-weighted Fluid Attenuated Inversion Recovery (T2-FLAIR) and many small areas with impaired diffusion in primarily supratentorial and infratentorial white matter on Diffusion-Weighted Imaging (DWI). In the following months, the patient made a remarkable clinical recovery. Despite clinical improvement, an MRI after 7 months showed that white matter hyperintensities had progressed and become confluent. Both MRIs demonstrated findings resembling CSVD, which could relate to a COVID-19-specific process affecting cerebral microvasculature.

Diffusional Characteristics of Brain Matter after Stroke.

We analyzed characteristics of diffusion and its kurtosis obtained using diffusion-kurtosis MRI in the hemisphere contralateral to the one affected by acute cerebrovascular accident. Diffusion characteristics in the white and gray matter were compared using analysis of covariance (ANCOVA) in healthy subjects and stroke patients with consideration for the age and sex factors. Significant differences between the groups were revealed for apparent diffusion coefficient and mean kurtosis in the white matter. Age dependence was studied using regression analysis and, according to the results of ANCOVA, this factor was found to be significant for apparent diffusion coefficient and diffusion kurtosis in the white matter. Metrics are proposed that can be used to determine the risk of stroke.

Ependymal restricted diffusion and injury to the olfactory system on a ventriculoencephalitis associated with COVID-19.

We describe the case of a 42-year-old female with COVID-19 and acute psychomotor agitation and without comorbidities. Brain MRI showed injury to the olfactory system associated with diffusion weighted imaging restriction in the ependymal surface of the lateral ventriculus suggesting ventriculoencephalitis.

COVID-19 Associated Wake-Up Stroke Treated With DWI/FLAIR Mismatch Guided Intravenous Alteplase: A Case Report.

INTRODUCTION: Wake-up strokes are challenging to manage due to unknown time of onset. Recently, the wake-up trial demonstrated that recombinant tissue plasminogen activator (rtPA) could be administered based on the magnetic resonance imaging (MRI)- diffusion weighted imaging/fluid attenuated inversion recovery mismatch. Many still doubt the safety results due to the higher rate of hemorrhagic conversion reported. Although it was statistically insignificant, the study was terminated early. Furthermore, Corona virus disease-19 is associated with coagulopathy and a higher risk of hemorrhagic conversion. CASE REPORT: A 46-year-old fully functioning male presented with a wake-up right hemiparesis, right facial droop, and expressive aphasia. His National Institute of Health Stroke Scale was 4 upon arrival. Last known well state was >4.5 hours. He tested positive for SARS-CoV-2 viral infection. He had left distal-M2 occlusion. He was deemed not a candidate for rtPA. Hyperacute-MRI protocol showed diffusion weighted imaging/fluid attenuated inversion recovery mismatch. The patient received rtPA at 6.5 hours from the last knwn well state. Follow-up MRI-susceptibility weighted imaging revealed fragmented clot. The stroke burden was less than that shown on the initial computed tomography-perfusion scans implying saved penumbra. There was no hemorrhagic conversion despite low fibrinogen levels. CONCLUSION: The hyperacute-MRI protocol for wake-up COVID-19 associated strokes might be a safe option.

C-reactive protein and white matter microstructural changes in COVID-19 patients with encephalopathy.

Encephalopathy is a neurological complication of COVID-19. The objective of this exploratory study is to investigate the link between systemic inflammation and brain microstructural changes (measured by diffusion-weighted imaging) in patients with COVID-19 encephalopathy. 20 patients with COVID-19 encephalopathy (age: 67.3 [Formula: see text] 10.0 years; 90% men) hospitalized in the Geneva University Hospitals for a SARS-CoV-2 infection between March and May 2020 were included in this retrospective cohort study. COVID-19 encephalopathy was diagnosed following a comprehensive neurobiological evaluation, excluding common causes of delirium, such as hypoxemic or metabolic encephalopathy. We investigated the correlation between systemic inflammation (measured by systemic C-reactive protein (CRP)) and brain microstructural changes in radiologically normal white matter (measured by apparent diffusion coefficient (ADC)) in nine spatially widespread regions of the white matter previously associated with delirium. Systemic inflammation (CRP = 60.8 ± 50.0 mg/L) was positively correlated with ADC values in the anterior corona radiata (p = 0.0089), genu of the corpus callosum (p = 0.0064) and external capsule (p = 0.0086) after adjusting for patients' age. No statistically significant association between CRP and ADC was found in the other six white matter regions. Our findings indicate high risk of white matter abnormalities in COVID-19 encephalopathy patients with high peripheral inflammatory markers, suggesting aggressive imaging monitoring may be warranted in these patients. Future studies should clarify a possible specificity of the spatial patterns of CRP-white matter microstructure association in COVID-19 encephalopathy patients and disentangle the role of individual cytokines on brain inflammatory mechanisms.

[A case of cerebral embolism with Coronavirus disease 2019].

A 63-year-old man, who had persistent fever for a month, was admitted to the hospital with sudden left arm palsy with a National Institutes of Health Stroke Scale score of 3. Consequently, brain MRI showed hyperintensity of the bilateral occipital, right parietal, and right frontal lobes on diffusion-weighted imaging. Moreover, FLAIR presented hyperintensity of the left occipital lobe. Magnetic resonance angiography detected the deficit of the blood-flow signal of the horizontal segment of the middle cerebral artery. He was diagnosed with acute ischemic stroke. In addition, chest CT showed ground-glass opacities, and test to detect SARS-CoV-2 was positive. Cerebral embolism was suspected. However, the source was unknown. His ischemic stroke was possibly associated with coagulation abnormality caused by coronavirus disease 2019.

Focal Cerebral Arteriopathy in a Young Adult Following SARS-CoV2 Reinfection.

Ten days after SARS-Cov2 reinfection with mild gastrointestinal symptoms and headache that occurred 2 months after an initial infection, a previously healthy 37-year-old woman developed fluctuating facial and upper limb paresthesia and weakness. Diffusion-weighted magnetic resonance imaging revealed ischemic lesions in the right parietal region of different stages within the same vascular territory. A cerebral angiography demonstrated an isolated focal arteriopathy with no other arterial involvement. Focal cerebral arteriopathy is exceedingly rare among adults and most commonly triggered by varicella-zoster virus reactivation. We present a case of focal cerebral arteriopathy in a patient with a recent reinfection with SARS-CoV-2.

Cytotoxic lesions of the corpus callosum in children: Etiology, clinical and radiological features, and prognosis.

OBJECTIVES: Cytotoxic lesions of the corpus callosum (CLOCCs) are secondary lesions associated with entities like infection manifested by restricted diffusion on diffusion-weighted cranial magnetic resonance imaging. Our objectives are to evaluate the clinic-radiological spectrum of pediatric patients with cytotoxic lesions of the corpus callosum (CC). METHODS: Children (0-18 years) admitted between February 2017 and May 2020 with splenial lesions showing diffusion restriction on MRI, either isolated or within involvement of other parts of the brain, were included retrospectively. The primary lesions of the CC (e.g. acute disseminated encephalomyelitis, acute ischemic infarction, and glioblastoma multiforme) were excluded. CLOCCs were divided into infection-associated, metabolic disorder-associated, and trauma-associated lesions, as well as CLOCCs involving other entities. Data were collected from the medical databases. RESULTS: Forty-one patients were determined to have CLOCCs. Twenty-five (61%) were infection-associated, nine (22%) were trauma-associated, and three (7%) were metabolic disorder-associated cases, including 2 inherited disorders of metabolism. There were four (10%) patients with other entities, three with epilepsy, and one had an apparent life-threatening event. Six patients had a known etiology among the infection-associated group; one had multisystem inflammatory syndrome caused by COVID-19 and one had been infected by COVID-19 without any complications. All the infection-associated patients with isolated splenial lesions recovered totally, although six patients required intensive care hospitalization. Four trauma-associated patients had sequela lesions. CONCLUSIONS: CLOCCs are associated with a spectrum of diseases, including the new coronavirus, COVID-19 infection. Infection-associated CLOCCs has the best prognosis, although severe cases may occur. Sequelae are possible based on the etiology.

Early postmortem brain MRI findings in COVID-19 non-survivors.

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuroinvasiveness 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 CT scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility. RESULTS: Among the 62 patients who died of COVID-19 from March 31, 2020, to April 24, 2020, at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical microbleeds and macrobleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES; 1 decedent), and nonspecific deep white matter changes (1 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.

Spinal cord infarction in a 41-year-old male patient with COVID-19.

The severe acute respiratory syndrome coronavirus disease 2019 (COVID-19) pandemic, became rapidly recognised by variable phonotypic expressions that involve most major body organs. Neurological complications of severe acute respiratory syndrome coronavirus disease are increasingly encountered in patients with COVID-19 infection, more frequently in patients with severe infection, and develop as a consequence of the neurotropic potential of this virus, secondary cytokine storm and acquired syndrome of COVID-19 coagulopathy. Spinal cord involvement after COVID-19 more commonly includes infectious transverse myelitis, para and post infection myelopathy and, rarely, spinal cord ischaemia related to increased coagulopathy with thromboembolic consequences. We herein report a COVID-19-positive patient with increased coagulopathy and vertebral artery thrombosis leading to posterior circulation and subsequent spinal cord infarction.

Posterior circulation stroke presenting as a new continuous cough: not always COVID-19.

A 19-year-old man was admitted with a 2-week history of continuous cough along with a day history of acute onset unsteadiness and hiccups. Given the current pandemic, he was initially suspected to have COVID-19, however he tested negative on two occasions. Subsequent brain magnetic resonance imaging (MRI)confirmed a small left acute and subacute lateral medullary infarction with chest X-ray suggesting aspiration pneumonia with right lower lobe collapse. This is a distinctive case of posterior circulation stroke presenting with a new continuous cough in this era of COVID-19 pandemic. We anticipate based on MRI findings that his persistent cough was likely due to silent aspiration from dysphagia because of the subacute medullary infarction. It is therefore imperative that healthcare workers evaluate people who present with new continuous cough thoroughly to exclude any other sinister pathology. We should also be familiar with the possible presentations of posterior circulation stroke in this pandemic era.

Clinical, Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy.

BACKGROUND AND PURPOSE: Patients infected with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) can develop a spectrum of neurological disorders, including a leukoencephalopathy of variable severity. Our aim was to characterize imaging, lab, and clinical correlates of severe coronavirus disease 2019 (COVID-19) leukoencephalopathy, which may provide insight into the SARS-CoV-2 pathophysiology. MATERIALS AND METHODS: Twenty-seven consecutive patients positive for SARS-CoV-2 who had brain MR imaging following intensive care unit admission were included. Seven (7/27, 26%) developed an unusual pattern of "leukoencephalopathy with reduced diffusivity" on diffusion-weighted MR imaging. The remaining patients did not exhibit this pattern. Clinical and laboratory indices, as well as neuroimaging findings, were compared between groups. RESULTS: The reduced-diffusivity group had a significantly higher body mass index (36 versus 28 kg/m2, P < .01). Patients with reduced diffusivity trended toward more frequent acute renal failure (7/7, 100% versus 9/20, 45%; P = .06) and lower estimated glomerular filtration rate values (49 versus 85 mL/min; P = .06) at the time of MRI. Patients with reduced diffusivity also showed lesser mean values of the lowest hemoglobin levels (8.1 versus 10.2 g/dL, P < .05) and higher serum sodium levels (147 versus 139 mmol/L, P = .04) within 24 hours before MR imaging. The reduced-diffusivity group showed a striking and highly reproducible distribution of confluent, predominantly symmetric, supratentorial, and middle cerebellar peduncular white matter lesions (P < .001). CONCLUSIONS: Our findings highlight notable correlations between severe COVID-19 leukoencephalopathy with reduced diffusivity and obesity, acute renal failure, mild hypernatremia, anemia, and an unusual brain MR imaging white matter lesion distribution pattern. Together, these observations may shed light on possible SARS-CoV-2 pathophysiologic mechanisms associated with leukoencephalopathy, including borderzone ischemic changes, electrolyte transport disturbances, and silent hypoxia in the setting of the known cytokine storm syndrome that accompanies severe COVID-19.

[Predictive value of combination of MRI tumor regression grade and apparent diffusion coefficient for pathological complete remission after neoadjuvant treatment of locally advanced rectal cancer].

Objective: Pelvic high-resolution magnetic resonance imaging (MRI) has now become a standard method for evaluating the efficacy of neoadjuvant treatment for locally advanced rectal cancer (LARC). However, this traditional morphological qualitative assessment method based on T2-weighted imaging (T2WI) is not effective in predicting pathological complete remission (pCR). The purpose of this study is to investigate whether combining the magnetic resonance tumor regression grade (mrTRG) with apparent diffusion coefficient (ADC) can improve diagnostic value for pCR after preoperative neoadjuvant chemoradiotherapy (nCRT) of LARC. Methods: This was a diagnostic study. Clinicopathological data of 134 LARC patients who received nCRT and radical surgery in the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2019 were retrospectively analyzed. All the patients underwent MRI which included T2WI and DWI sequences before and 8 weeks after nCRT. Two radiologists independently drew ROIs on T2WI and DWI to estimate mrTRG stage and calculate the mean ADC value. Receiver operating characteristics (ROC) method was applied to evaluate the predict value of mrTRG combined with mean ADC value for pCR. Results: Of 134 LARC patients, 85 were male and 49 were female with median age of 58 (28-82) years. After nCRT, MRI suggested 21 patients (15.7%) had clinical complete remission (cCR), e.g. mrTRG stage 1-2. Postoperative pathology revealed 31 (23.1%) patients had pCR. The evaluations of mrTRG and ADC value by the two readers were highly consistent, and the intra-group correlation coefficients were 0.83 (95% CI: 0.703-0.881) and 0.96 (95% CI: 0.989-0.996), respectively. There was a negative correlation between mrTRG and pCR (r(s)=-0.505, P<0.01), and a positive correlation between mean ADC value and pCR (r(s)=0.693, P<0.01). The ROC curve showed that mrTRG alone had a medium predictive value for pCR, with an area under the curve (AUC) of 0.832 (95% CI: 0.743-0.921); the mean ADC value had a higher predictive value for pCR, with AUC of 0.906 (95% CI: 0.869-0.962). The predictive value of the combined model of mrTRG and ADC value for pCR was significantly better than that of mrTRG alone (P=0.015), and the AUC was 0.908 (95% CI: 0.849-0.968). Conclusion: Both mrTRG and mean ADC value can be non-invasive methods to predict the efficacy of nCRT for LARC. Combining the mean ADC value with mrTRG can result in better pCR prediction.