Park, Young Woo

AbstractBackgroundApproximately 10% of patients with acute SARS‐CoV‐2 infection present with persistent symptoms recognized as the long‐COVID. Neurological and cognitive symptoms are prevalent in long‐COVID, requiring a deeper understanding of the biological basis of this condition for potential therapeutic interventions. Cerebrovascular complications are observed during acute infection, underscoring the importance of understanding cerebrovascular outcomes. Our objective was to investigate white matter hyperintensities (WMH) as a potential indicator of microvascular disease associated with long‐COVID in the brainMethodParticipants with long‐COVID (n=71; hospitalized, n=9, non‐hospitalized, n=62 during the acute infection) and controls (n=50) who did not have a reported infection were recruited from the community at five US sites that participated in the COVID‐Brain‐Advanced‐Imaging‐Network (COVID‐BRAIN) project. To be included, participants with long‐COVID had to experience neurological or cognitive sequelae within 6 months after a confirmed infection and continued to show at least one neurological symptom. Clinical evaluation and MRI were performed an average of 20±10 months after the acute infection. WMH volumes were measured from the 3D T2‐weighted FLAIR MRIs using a semi‐automated approach for the WMH segmentation. A linear regression model predicting log transformed WMH volume was used to investigate the association of age, groups (hospitalized long‐COVID, non‐hospitalized long‐COVID, controls), and the interaction of these two predictors along with an adjustment for total intracranial volume. Additionally, predicted regression lines have been plotted on the untransformed WMH scale.ResultWe observed a greater age‐dependent increase in WMH volumes in the hospitalized patients with long‐COVID compared to the control group (group*age interaction, p=0.005). We did not observe this difference in slopes in the non‐hospitalized patients with long‐COVID compared to the controls. Figure shows the slopes of WMH volume as a percentage of the total intracranial volume by age in the three groups.ConclusionOur preliminary observation in this ongoing long‐Covid study suggests that hospitalization during acute COVID is associated with the age‐dependent increase in microvascular injury in the white matter. Older adults with acute infection that require hospitalization are more susceptible to cerebrovascular adverse outcomes than controls or those who do not require hospitalization. Impact of such microvascular changes on cognitive outcomes and persistence of post‐COVID symptoms is yet to be studied.

AbstractBackgroundApproximately 10% of patients with acute SARS‐CoV‐2 infection present with persistent symptoms recognized as the long‐COVID. Neurological and cognitive symptoms are prevalent in long‐COVID, requiring a deeper understanding of the biological basis of this condition for potential therapeutic interventions. Cerebrovascular complications are observed during acute infection, underscoring the importance of understanding cerebrovascular outcomes. Our objective was to investigate white matter hyperintensities (WMH) as a potential indicator of microvascular disease associated with long‐COVID in the brainMethodParticipants with long‐COVID (n = 71; hospitalized,n = 9,non‐hospitalized,n = 62 during the acute infection) and controls(n = 50) who did not have a reported infection were recruited from the community at five US sites that participated in the COVID‐Brain‐Advanced‐Imaging‐Network (COVID‐BRAIN) project. To be included, participants with long‐COVID had to experience neurological or cognitive sequelae within 6 months after a confirmed infection and continued to show at least one neurological symptom. Clinical evaluation and MRI were performed an average of 20±10 months after the acute infection. WMH volumes were measured from the 3D T2‐weighted FLAIR MRIs using a semi‐automated approach for the WMH segmentation. A linear regression model predicting log transformed WMH volume was used to investigate the association of age, groups (hospitalized long‐COVID, non‐hospitalized long‐COVID, controls), and the interaction of these two predictors along with an adjustment for total intracranial volume. Additionally, predicted regression lines have been plotted on the untransformed WMH scale.ResultWe observed a greater age‐dependent increase in WMH volumes in the hospitalized patients with long‐COVID compared to the control group (group*age interaction, p = 0.005). We did not observe this difference in slopes in the non‐hospitalized patients with long‐COVID compared to the controls. Figure shows the slopes of WMH volume as a percentage of the total intracranial volume by age in the three groups.ConclusionOur preliminary observation in this ongoing long‐Covid study suggests that hospitalization during acute COVID is associated with the age‐dependent increase in microvascular injury in the white matter. Older adults with acute infection that require hospitalization are more susceptible to cerebrovascular adverse outcomes than controls or those who do not require hospitalization. Impact of such microvascular changes on cognitive outcomes and persistence of post‐COVID symptoms is yet to be studied.

AbstractBackgroundProton MR Spectroscopy (1H MRS) provides non‐invasive measurements of alterations in brain biochemistry associated with neuronal and glial abnormalities in neurodegeneration. 1H MRS with along with automated voxel placement (AVP) improves the precision of 1H MRS metabolite measurements. Our objective was to investigate the association of 1H MRS metabolites obtained by the advanced sLASER single voxel 1H MRS protocol with early tau deposition as measured by AV‐1451 PET and Aβ deposition as measured by 11C‐Pittsburgh compound B (PiB) PET in cognitively unimpaired older adults.MethodCognitively unimpaired adults with median (range) age of 77 (66, 94) from the population‐based Mayo Clinic Study of Aging (MCSA) participated in the single‐voxel 1H MRS study (n=40). All participants had an MRI, 11C‐PiB and AV‐1451 PET examinations. The posterior cingulate cortex (PCC) and the left hippocampus (LHC) were chosen for the 1H MRS voxel locations because of their vulnerability to early AD pathology. Right hippocampus was not studied due to time constraints of the MR examination. 1H MRS was performed at 3T (Siemens) using an optimized sLASER protocol with AVP. Standardized uptake value ratios (SUVR) were calculated for global cortical and regional (PCC, LHC) PiB and AV‐1451. Associations between log transformed SUVRs and the concentration of MRS‐measured metabolites (µmol/g) were assessed using age‐adjusted Pearson correlations.ResultThe median (range) global PiB SUVR was 1.42 (1.20‐2.81) and AV‐1451 SUVR was 1.20 (0.94, 1.46). In the PCC, higher AV‐1451 SUVR was associated with lower N‐acetylaspartate (NAA) (r=‐0.375; p=0.019) and glutamate (r=‐0.354; p=0.027) concentrations. Higher global PIB SUVR was associated with higher myo‐inositol in the LHC (r=0.361; p=0.039).ConclusionLower levels of NAA, a marker of neuronal health, and the neurotransmitter glutamate are associated with local tau pathology in the PCC, suggesting early neuronal dysfunction in relation to tau accumulation. The association of hippocampal myo‐inositol, a putative glial marker, with the global cortical Aβ pathology suggests that myo‐inositol elevation may be an indicator of neuroinflammatory response to Aβ related pathology.

PurposeAdvanced MRS protocols improve data quality and reproducibility relative to vendor‐provided protocols; however, they are challenging to incorporate into the clinical workflow and require local MRS expertise for successful implementation. Here, we developed an automated advanced MRS acquisition protocol at 3T to facilitate acquisition of high‐quality spectroscopic data without local MRS expertise.MethodsFirst, a B0 shimming protocol was selected for automation by comparing 3 widely used B0 algorithms (2 vendor protocols and FAST(EST)MAP). Next, voxel‐based B0 and B1 calibrations were incorporated into the consensus‐recommended semi‐LASER sequence and combined with an automated VOI prescription tool, a recently developed method for automated voxel prescription. The efficiency of collecting single‐voxel data from a clinical cohort (N = 40) with the automated protocol (calibration time and fraction of usable datasets) was compared with the nonautomated semi‐LASER protocol (N = 35) whereby all prescan calibrations were executed manually in the academic hospital setting with rotating MR technologists in the neuroradiology unit.ResultsA multi‐iteration FAST(EST)MAP protocol resulted in narrower water linewidths than vendor’s B0 shim protocols for data acquired from 6 brain locations (p < 1e‐5) and was selected for automation. The automated B0 and B1 calibrations resulted in a time saving of ~4.5 minutes per voxel relative to the same advanced protocol executed manually. All spectra acquired with the automated protocol were usable, whereas only 86% of those collected with the manual protocol were usable and spectral quality was more variable.ConclusionThe plug‐and‐play advanced MRS protocol allows automated acquisition of high‐quality MRS data with high success rate and consistency on a clinical 3T platform.

PurposeTo develop a fast and automated volume‐of‐interest (VOI) prescription pipeline (AutoVOI) for single‐voxel MRS that removes the need for manual VOI placement, allows flexible VOI planning in any brain region, and enables high inter‐ and intra‐subject consistency of VOI prescription.MethodsAutoVOI was designed to transfer pre‐defined VOIs from an atlas to the 3D anatomical data of the subject during the scan. The AutoVOI pipeline was optimized for consistency in VOI placement (precision), enhanced coverage of the targeted tissue (accuracy), and fast computation speed. The tool was evaluated against manual VOI placement using existing T1‐weighted data sets and corresponding VOI prescriptions. Finally, it was implemented on 2 scanner platforms to acquire MRS data from clinically relevant VOIs that span the cerebrum, cerebellum, and the brainstem.ResultsThe AutoVOI pipeline includes skull stripping, non‐linear registration of the atlas to the subject's brain, and computation of the VOI coordinates and angulations using a minimum oriented bounding box algorithm. When compared against manual prescription, AutoVOI showed higher intra‐ and inter‐subject spatial consistency, as quantified by generalized Dice coefficients (GDC), lower intra‐ and inter‐subject variability in tissue composition (gray matter, white matter, and cerebrospinal fluid) and higher or equal accuracy, as quantified by GDC of prescribed VOI with targeted tissues. High quality spectra were obtained on Siemens and Philips 3T systems from 6 automatically prescribed VOIs by the tool.ConclusionRobust automatic VOI prescription is feasible and can help facilitate clinical adoption of MRS by avoiding operator dependence of manual selection.