Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection.

BACKGROUND: A neurocognitive phenotype of post-COVID-19 infection has recently been described that is characterized by a lack of awareness of memory impairment (i.e., anosognosia), altered functional connectivity in the brain's default mode and limbic networks, and an elevated monocyte count. However, the relationship between these cognitive and brain functional connectivity alterations in the chronic phase with the level of cytokines during the acute phase has yet to be identified. AIM: Determine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6-9 months after infection. METHODS: We analyzed the predictive value of the concentration of acute cytokines (IL-1RA, IL-1ß, IL-6, IL-8, IFNγ, G-CSF, GM-CSF) (cytokine panel by multiplex immunoassay) in the plasma of 39 patients (mean age 59 yrs, 38-78) in relation to their anosognosia scores for memory deficits via stepwise linear regression. Then, associations between the different cytokines and brain functional connectivity patterns were analyzed by MRI and multivariate partial least squares correlations for the whole group. RESULTS: Stepwise regression modeling allowed us to show that acute TNFα levels predicted (R2 = 0.145; ß = -0.38; p = .017) and were associated (r = -0.587; p < .001) with scores of anosognosia for memory deficits observed 6-9 months post-infection. Finally, high TNFα levels were associated with hippocampal, temporal pole, accumbens nucleus, amygdala, and cerebellum connectivity. CONCLUSION: Increased plasma TNFα levels in the acute phase of COVID-19 predict the presence of long-term anosognosia scores and changes in limbic system functional connectivity.

Frequency of Abnormally Low Neuropsychological Scores in Post-COVID-19 Syndrome: the Geneva COVID-COG Cohort.

OBJECTIVE: Several studies have reported poor long-term neuropsychological performances in patients following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but none has yet considered the effect of administering multiple intercorrelated neuropsychological tests and assessed the frequency of cognitive deficits in a normative population. Our aim was therefore to assess the presence of cumulative neuropsychological deficits in an actual post-coronavirus disease of 2019 (COVID-19) comparison group versus one simulated using Monte-Carlo methods. METHOD: Validated neuropsychological Monte-Carlo simulation methods were applied to scores from a battery of neuropsychological tests (memory, executive, attentional, perceptual, logical reasoning, language, and ideomotor praxis) administered to 121 patients who had had mild, moderate, or severe COVID-19 (mean age: 56.70 years; 32% women), 222 ± 43 days post-infection. The cumulative percentages of the three severity subgroups were compared with the results of a false discovery rate-corrected probability analysis based on normative data. RESULTS: The cumulative percentages of deficits in memory and executive functions among the severe and moderate patients were significantly higher than those estimated for the normative population. Moderate patients also had significantly more deficits in perception and logical reasoning. In contrast, the mild group did not have significantly more cumulative deficits. CONCLUSIONS: Moderate and severe forms of COVID-19 cause greater long-term neuropsychological deficits than those that would be found in a normative population, reinforcing the hypothesis of long-term effects of SARS-CoV-2 on cognitive function, independent of the severity of the initial infection.

Resting-State Brain Activity for Early Prediction Outcome in Postanoxic Patients in a Coma with Indeterminate Clinical Prognosis.

BACKGROUND AND PURPOSE: Early outcome prediction of postanoxic patients in a coma after cardiac arrest proves challenging. Current prognostication relies on multimodal testing, using clinical examination, electrophysiologic testing, biomarkers, and structural MR imaging. While this multimodal prognostication is accurate for predicting poor outcome (ie, death), it is not sensitive enough to identify good outcome (ie, consciousness recovery), thus leaving many patients with indeterminate prognosis. We specifically assessed whether resting-state fMRI provides prognostic information, notably in postanoxic patients in a coma with indeterminate prognosis early after cardiac arrest, specifically for good outcome. MATERIALS AND METHODS: We used resting-state fMRI in a prospective study to compare whole-brain functional connectivity between patients with good and poor outcomes, implementing support vector machine learning. Then, we automatically predicted coma outcome using resting-state fMRI and also compared the prediction based on resting-state fMRI with the outcome prediction based on DWI. RESULTS: Of 17 eligible patients who completed the study procedure (among 351 patients screened), 9 regained consciousness and 8 remained comatose. We found higher functional connectivity in patients recovering consciousness, with greater changes occurring within and between the occipitoparietal and temporofrontal regions. Coma outcome prognostication based on resting-state fMRI machine learning was very accurate, notably for identifying patients with good outcome (accuracy, 94.4%; area under the receiver operating curve, 0.94). Outcome predictors using resting-state fMRI performed significantly better (P < .05) than DWI (accuracy, 60.0%; area under the receiver operating curve, 0.63). CONCLUSIONS: Indeterminate prognosis might lead to major clinical uncertainty and significant variations in life-sustaining treatments. Resting-state fMRI might bridge the gap left in early prognostication of postanoxic patients in a coma by identifying those with both good and poor outcomes.

Large Neck and Strong Ostium Inflow as the Potential Causes for Delayed Occlusion of Unruptured Sidewall Intracranial Aneurysms Treated by Flow Diverter.

BACKGROUND AND PURPOSE: Flow diverter-induced hemodynamic change plays an important role in the mechanism of intracranial aneurysm occlusion. Our aim was to explore the relationship between aneurysm features and flow-diverter treatment of unruptured sidewall intracranial aneurysms. MATERIALS AND METHODS: MR imaging, 4D phase-contrast, was prospectively performed before flow diverter implantation in each patient with unruptured intracranial aneurysm. Two postprocedure follow-ups were scheduled at 6 and 12 months. Responses were grouped according to whether the aneurysms were occluded or remnant. Preprocedural aneurysm geometries and ostium hemodynamics in 38 patients were compared between the 2 groups at 6 and 12 months. Receiver operating characteristic curve analyses were performed for significant geometric and hemodynamic continuous parameters. RESULTS: After the 6-month assessment, 21 of 41 intracranial aneurysms were occluded, and 9 additional aneurysms were occluded at 12 months. Geometrically, the ostium maximum diameter was significantly larger in the remnant group at 6 and 12 months (both P < .001). Hemodynamically, the proximal inflow zone was more frequently observed in the remnant group at 6 months. Several preprocedural ostium hemodynamic parameters were significantly higher in the remnant group. As a prediction for occlusion, the areas under the curve of the ostium maximum diameter (for 6 and 12 months), systolic inflow rate ratio (for 6 months), and systolic inflow area (for 12 months) reached 0.843, 0.883, 0.855, and 0.860, respectively. CONCLUSIONS: Intracranial aneurysms with a large ostium and strong ostium inflow may need a longer time for occlusion. Preprocedural 4D flow MR imaging can well illustrate ostium hemodynamics and characterize aneurysm treatment responses.

How Flow Reduction Influences the Intracranial Aneurysm Occlusion: A Prospective 4D Phase-Contrast MRI Study.

BACKGROUND AND PURPOSE: Flow-diverter stents are widely used for the treatment of wide-neck intracranial aneurysms. Various parameters may influence intracranial aneurysm thrombosis, including the flow reduction induced by flow-diverter stent implantation, which is assumed to play a leading role. However, its actual impact remains unclear due to the lack of detailed intra-aneurysmal flow measurements. This study aimed to clarify this relationship by quantitatively measuring the intra-aneurysmal flow using 4D phase-contrast MR imaging. MATERIALS AND METHODS: We acquired prospective pre- and post-stent implantation 4D phase-contrast MR imaging data of a consecutive series of 23 patients treated with flow-diverter stents. Velocity field data were combined with the intraprocedural 3D angiogram vessel geometries for precise intracranial aneurysm extraction and partial volume correction. Intra-aneurysmal hemodynamic modifications were compared with occlusion outcomes at 6 and 12 months. RESULTS: The averaged velocities at systole were lower after flow-diverter stent implantation for all patients and ranged from 21.7 ± 7.1 cm/s before to 7.2 ± 2.9 cm/s after stent placement. The velocity reduction was more important for the group of patients with aneurysm thrombosis at 6 months (68.8%) and decreased gradually from 66.2% to 55% for 12-month thrombosis and no thrombosis, respectively (P = .08). CONCLUSIONS: We propose an innovative approach to measure intracranial flow changes after flow-diverter stent implantation. We identified a trend between flow reduction and thrombosis outcome that brings a new insight into current understanding of the flow-diversion treatment response.

Feasibility of a Synthetic MR Imaging Sequence for Spine Imaging.

BACKGROUND AND PURPOSE: Synthetic MR imaging is a method that can produce multiple contrasts from a single sequence, as well as quantitative maps. Our aim was to determine the feasibility of a synthetic MR image for spine imaging. MATERIALS AND METHODS: Thirty-eight patients with clinical indications of infectious, degenerative, and neoplastic disease underwent an MR imaging of the spine (11 cervical, 8 dorsal, and 19 lumbosacral MR imaging studies). The SyntAc sequence, with an acquisition time of 5 minutes 40 seconds, was added to the usual imaging protocol consisting of conventional sagittal T1 TSE, T2 TSE, and STIR TSE. RESULTS: Synthetic T1-weighted, T2-weighted, and STIR images were of adequate quality, and the acquisition time was 53% less than with conventional MR imaging. The image quality was rated as "good" for both synthetic and conventional images. Interreader agreement concerning lesion conspicuity was good with a Cohen κ of 0.737. Artifacts consisting of white pixels/spike noise across contrast views, as well as flow artifacts, were more common in the synthetic sequences, particularly in synthetic STIR. There were no statistically significant differences between readers concerning the scores assigned for image quality or lesion conspicuity. CONCLUSIONS: Our study shows that synthetic MR imaging is feasible in spine imaging and produces, in general, good image quality and diagnostic confidence. Furthermore, the non-negligible time savings and the ability to obtain quantitative measurements as well as to generate several contrasts with a single acquisition should promise a bright future for synthetic MR imaging in clinical routine.

Normal Values of Magnetic Relaxation Parameters of Spine Components with the Synthetic MRI Sequence.

BACKGROUND AND PURPOSE: SyMRI is a technique developed to perform quantitative MR imaging. Our aim was to analyze its potential use for measuring relaxation times of normal components of the spine and to compare them with values found in the literature using relaxometry and other techniques. MATERIALS AND METHODS: Thirty-two spine MR imaging studies (10 cervical, 5 dorsal, 17 lumbosacral) were included. A modified multiple-dynamic multiple-echo sequence was added and processed to obtain quantitative T1 (millisecond), T2 (millisecond), and proton density (percentage units [pu]) maps for each patient. An ROI was placed on representative areas for CSF, spinal cord, intervertebral discs, and vertebral bodies, to measure their relaxation. RESULTS: Relaxation time means are reported for CSF (T1 = 4273.4 ms; T2 = 1577.6 ms; proton density = 107.5 pu), spinal cord (T1 = 780.2 ms; T2 = 101.6 ms; proton density = 58.7 pu), normal disc (T1 = 1164.9 ms; T2 = 101.9 ms; proton density = 78.9 pu), intermediately hydrated disc (T1 = 723 ms; T2 = 66.8 ms; proton density = 60.8 pu), desiccated disc (T1 = 554.4 ms; T2 = 55.6 ms; proton density = 47.6 ms), and vertebral body (T1 = 515.3 ms; T2 = 100.8 ms; proton density = 91.1 pu). Comparisons among the mean T1, T2, and proton density values showed significant differences between different spinal levels (cervical, dorsal, lumbar, and sacral) for CSF (proton density), spinal cord (T2 and proton density), normal disc (T1, T2, and proton density), and vertebral bodies (T1 and proton density). Significant differences were found among mean T1, T2, and proton density values of normal, intermediately hydrated, and desiccated discs. CONCLUSIONS: Measurements can be easily obtained on SyMRI and correlated with previously published values obtained using conventional relaxometry techniques.

Vessel calibre and flow splitting relationships at the internal carotid artery terminal bifurcation.

OBJECTIVE: Vessel lumen calibres and flow rates are thought to be related by mathematical power laws, reflecting the optimization of cardiac versus metabolic work. While these laws have been confirmed indirectly via measurement of branch calibres, there is little data confirming power law relationships of flow distribution to branch calibres at individual bifurcations. APPROACH: Flow rates and diameters of parent and daughter vessels of the internal carotid artery terminal bifurcation were determined, via robust and automated methods, from 4D phase-contrast magnetic resonance imaging and 3D rotational angiography of 31 patients. MAIN RESULTS: Junction exponents were 2.06 ± 0.44 for relating parent to daughter branch diameters (geometrical exponent), and 2.45 ± 0.75 for relating daughter branch diameters to their flow division (flow split exponent). These exponents were not significantly different, but showed large inter- and intra-individual variations, and with confidence intervals excluding the theoretical optimum of 3. Power law fits of flow split versus diameter ratio and pooled flow rates versus diameters showed exponents of 2.17 and 1.96, respectively. A significant negative correlation was found between age and the geometrical exponent (r = -0.55, p = 0.003) but not the flow split exponent. We also found a dependence of our results on how lumen diameter is measured, possibly explaining some of the variability in the literature. SIGNIFICANCE: Our study confirms that, on average, division of flow to the middle and anterior cerebral arteries is related to these vessels' relative calibres via a power law, but it is closer to a square law than a cube law as commonly assumed.

Dynamic Contrast-Enhanced MR Perfusion of Intradural Spinal Lesions.

Fifteen patients with intradural spinal lesions were examined with an optimized dynamic contrast-enhanced MR perfusion sequence at 1.5T and 3T. SNR and mean contrast-to-noise ratio were better on 3T compared with 1.5T (P ≤ .05). The goodness of fit of the Tofts and Tofts extended pharmacokinetic models was similar between 1.5T and 3T. Thus, dynamic contrast-enhanced MR perfusion of intradural spinal canal lesions is technically feasible at 1.5T and 3T, with better image quality at 3T.

Clinicoradiologic Correlations of Cerebral Microbleeds in Advanced Age.

BACKGROUND AND PURPOSE: The presence of cerebral microbleeds has been associated with dementia and cognitive decline, although studies report conflicting results. Our aim was to determine the potential role of the presence and location of cerebral microbleeds in early stages of cognitive decline. MATERIALS AND METHODS: Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively intact community-dwelling controls and 72 subjects with mild cognitive impairment were analyzed with respect to the presence and distribution of cerebral microbleeds. A neuropsychological follow-up of controls was performed at 18 months post inclusion and identified cases with subtle cognitive deficits were referred to as controls with a deteriorating condition. Group differences in radiologic parameters were studied by using nonparametric tests, 1-way analysis of variance, and Spearman correlation coefficients. RESULTS: Cerebral microbleed prevalence was similar in subjects with mild cognitive impairment and controls with stable and cognitively deteriorating conditions (25%-31.9%). In all diagnostic groups, lobar cerebral microbleeds were more common. They occurred in 20.1% of all cases compared with 6.5% of cases with deep cerebral microbleeds. None of the investigated variables (age, sex, microbleed number, location and depth, baseline Mini-Mental State Examination score, and the Fazekas score) were significantly associated with cognitive deterioration with the exception of education of >12 years showing a slight but significant protective effect (OR, 0.44; 95% CI, 0.22-0.92; P = .028). The Mini-Mental State Examination and the Buschke total score were correlated with neither the total number nor lobar-versus-deep location of cerebral microbleeds. CONCLUSIONS: Cerebral microbleed presence, location, and severity are not related to the early stages of cognitive decline in advanced age.

Virtual-versus-Real Implantation of Flow Diverters: Clinical Potential and Influence of Vascular Geometry.

BACKGROUND AND PURPOSE: Intracranial stents have become extremely important in the endovascular management of complex intracranial aneurysms. Sizing and landing zone predictions are still very challenging steps in the procedure. Virtual stent deployment may help therapeutic planning, device choice, and hemodynamic simulations. We aimed to assess the predictability of our recently developed virtual deployment model by comparing in vivo and virtual stents implanted in a consecutive series of patients presenting with intracranial aneurysms. MATERIALS AND METHODS: Virtual stents were implanted in patient-specific geometries of intracranial aneurysms treated with the Pipeline Embolization Device. The length and cross-section of virtual and real stents measured with conebeam CT were compared. The influence of vessel geometry modifications occurring during the intervention was analyzed. RESULTS: The virtual deployment based on pre- and poststent implantation 3D rotational angiography overestimated (underestimated) the device length by 13% ± 11% (-9% ± 5%). These differences were highly correlated (R2 = 0.67) with the virtual-versus-real stent radius differences of -6% ± 7% (5% ± 4%) for predictions based on pre- and poststent implantation 3D rotational angiography. These mismatches were due principally to implantation concerns and vessel-shape modifications. CONCLUSIONS: The recently proposed geometric model was shown to predict accurately the deployment of Pipeline Embolization Devices when the stent radius was well-assessed. However, unpredictable delivery manipulations and variations of vessel geometry occurring during the intervention might impact the stent implantation.

Evaluation of electrode position in deep brain stimulation by image fusion (MRI and CT).

INTRODUCTION: Imaging has an essential role in the evaluation of correct positioning of electrodes implanted for deep brain stimulation (DBS). Although MRI offers superior anatomic visualization of target sites, there are safety concerns in patients with implanted material; imaging guidelines are inconsistent and vary. The fusion of postoperative CT with preoperative MRI images can be an alternative for the assessment of electrode positioning. The purpose of this study was to assess the accuracy of measurements realized on fused images (acquired without a stereotactic frame) using a manufacturer-provided software. METHODS: Data from 23 Parkinson's disease patients who underwent bilateral electrode placement for subthalamic nucleus (STN) DBS were acquired. Preoperative high-resolution T2-weighted sequences at 3 T, and postoperative CT series were fused using a commercially available software. Electrode tip position was measured on the obtained images in three directions (in relation to the midline, the AC-PC line and an AC-PC line orthogonal, respectively) and assessed in relation to measures realized on postoperative 3D T1 images acquired at 1.5 T. RESULTS: Mean differences between measures carried out on fused images and on postoperative MRI lay between 0.17 and 0.97 mm. CONCLUSION: Fusion of CT and MRI images provides a safe and fast technique for postoperative assessment of electrode position in DBS.

Arterial Spin-Labeling Parameters Influence Signal Variability and Estimated Regional Relative Cerebral Blood Flow in Normal Aging and Mild Cognitive Impairment: FAIR versus PICORE Techniques.

BACKGROUND AND PURPOSE: Arterial spin-labeling is a noninvasive method to map cerebral blood flow, which might be useful for early diagnosis of neurodegenerative diseases. We directly compared 2 arterial spin-labeling techniques in healthy elderly controls and individuals with mild cognitive impairment. MATERIALS AND METHODS: This prospective study was approved by the local ethics committee and included 198 consecutive healthy controls (mean age, 73.65 ± 4.02 years) and 43 subjects with mild cognitive impairment (mean age, 73.38 ± 5.85 years). Two pulsed arterial spin-labeling sequences were performed at 3T: proximal inversion with a control for off-resonance effects (PICORE) and flow-sensitive alternating inversion recovery technique (FAIR). Relative cerebral blood flow maps were calculated by using commercial software and standard parameters. Data analysis included spatial normalization of gray matter-corrected relative CBF maps, whole-brain average, and voxelwise comparison of both arterial spin-labeling sequences. RESULTS: Overall, FAIR yielded higher relative CBF values compared with PICORE (controls, 32.7 ± 7.1 versus 30.0 ± 13.1 mL/min/100 g, P = .05; mild cognitive impairment, 29.8 ± 5.4 versus 26.2 ± 8.6 mL/min/100 g, P < .05; all, 32.2 ± 6.8 versus 29.3 ± 12.3 mL/min/100 g, P < .05). FAIR had lower variability (controls, 36.2% versus 68.8%, P < .00001; mild cognitive impairment, 18.9% versus 22.9%, P < .0001; all, 34.4% versus 64.9% P < .00001). The detailed voxelwise analysis revealed a higher signal for FAIR, notably in both convexities, while PICORE had higher signal predominantly in deep cerebral regions. CONCLUSIONS: Overall, FAIR had higher estimated relative CBF and lower interindividual variability than PICORE. In more detail, there were regional differences between both arterial spin-labeling sequences. In summary, these results highlight the need to calibrate arterial spin-labeling sequences.