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Introduction: Post-acute COVID syndrome (PACS) is a growing concern, given its impact on mental health and quality of life. However, its effects on cerebral white matter remain poorly understood, particularly in non-hospitalized cohorts. The goals of this cross-sectional, observational study were to examine (1) whether PACS was associated with distinct alterations in white matter microstructure, compared to symptom-matched non-COVID viral infection; and (2) whether microstructural alterations correlated with indices of post-COVID emotional health. Methods: Data were collected for 54 symptomatic individuals who tested positive for COVID-19 (mean age 41 ± 12 yrs., 36 female) and 14 controls who tested negative for COVID-19 (mean age 41 ± 14 yrs., 8 female), with both groups assessed an average of 4-5 months after COVID testing. Diffusion magnetic resonance imaging data were collected, and emotional health was assessed via the NIH emotion toolbox, with summary scores indexing social satisfaction, well-being and negative affect. Results: Despite similar symptoms, the COVID-19 group had reduced mean and axial diffusivity, along with increased mean kurtosis and neurite dispersion, in deep white matter. After adjusting for social satisfaction, higher levels of negative affect in the COVID-19 group were also correlated with increased mean kurtosis and reduced free water in white matter. Discussion: These results provide preliminary evidence that indices of white matter microstructure distinguish PACS from symptomatic non-COVID infection. Moreover, white matter effects seen in PACS correlate with the severity of emotional sequelae, providing novel insights into this highly prevalent disorder.
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The brain is closely attuned to visceral signals from the body's internal environment, as evidenced by the numerous associations between neural, hemodynamic, and peripheral physiological signals. We show that these brain-body co-fluctuations can be captured by a single spatiotemporal pattern. Across several independent samples, as well as single-echo and multi-echo fMRI data acquisition sequences, we identify widespread co-fluctuations in the low-frequency range (0.01 - 0.1 Hz) between resting-state global fMRI signals, neural activity, and a host of autonomic signals spanning cardiovascular, pulmonary, exocrine and smooth muscle systems. The same brain-body co-fluctuations observed at rest are elicited by arousal induced by cued deep breathing and intermittent sensory stimuli, as well as spontaneous phasic EEG events during sleep. Further, we show that the spatial structure of global fMRI signals is maintained under experimental suppression of end-tidal carbon dioxide (PETCO2) variations, suggesting that respiratory-driven fluctuations in arterial CO2 accompanying arousal cannot explain the origin of these signals in the brain. These findings establish the global fMRI signal as a significant component of the arousal response governed by the autonomic nervous system.
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Post-acute COVID syndrome (PACS) is a global health concern and is often associated with debilitating symptoms. Post-COVID fatigue is a particularly frequent and troubling issue, and its underlying mechanisms remain incompletely understood. One potential contributor is micropathological injury of subcortical and brainstem structures, as has been identified in other patient populations. Texture-based analysis (TA) may be used to measure such changes in anatomical MRI data. The present study develops a methodology of voxel-wise TA mapping in subcortical and brainstem regions, which is then applied to T1-weighted MRI data from a cohort of 48 individuals who had PACS (32 with and 16 without ongoing fatigue symptoms) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19. Both groups were assessed an average of 4-5 months post-infection. There were no significant differences between PACS and control groups, but significant differences were observed within the PACS groups, between those with and without fatigue symptoms. This included reduced texture energy and increased entropy, along with reduced texture correlation, cluster shade and profile in the putamen, pallidum, thalamus and brainstem. These findings provide new insights into the neurophysiological mechanisms that underlie PACS, with altered tissue texture as a potential biomarker of this debilitating condition.
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Tronco Encefálico , COVID-19 , Fadiga , Imageamento por Ressonância Magnética , Síndrome de COVID-19 Pós-Aguda , Humanos , COVID-19/complicações , COVID-19/diagnóstico por imagem , Masculino , Feminino , Fadiga/diagnóstico por imagem , Fadiga/etiologia , Fadiga/patologia , Pessoa de Meia-Idade , Adulto , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Tálamo/diagnóstico por imagem , Tálamo/patologia , Idoso , Putamen/diagnóstico por imagem , Putamen/patologia , SARS-CoV-2RESUMO
To understand the consistently observed spatial distribution of white-matter (WM) aging, developmentally driven theories of retrogenesis have gained traction, positing that the order WM development predicts declines. Regions that develop first are often expected to deteriorate the last, i.e. "last-in-first-out". Alternatively, regions which develop most rapidly may also decline most rapidly in aging, or the "gains-predict-loss" model. The validity of such theories remains uncertain, in part due to lack of clarity on the definition of developmental order. Our recent findings also suggest that WM degeneration may vary by physiological parameters such as perfusion. Furthermore, it is informative to link perfusion to fibre metabolic need, which varies with fibre size. Here we address the question of whether WM degeneration is determined by development trajectory or physiological state across both microstructural and perfusion measures using data drawn from the Human Connectome Project in Aging (HCP-A). Our results indicate that developmental order of tract myelination provides the strongest support for the retrogenesis hypothesis, with the last to complete myelination the first to decline. Moreover, higher mean axon diameter and lower macrovascular density are associated with lower degrees of WM degeneration across measures. Tract perfusion, in turn also tends to be higher and the arterial transit time longer for tracts that appear first. These findings suggest that WM degeneration in different tracts may be governed by their developmental trajectories and physiology, and ultimately influenced by each tract's metabolic demand.
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Macrovascular biases have been a long-standing challenge for fMRI, limiting its ability to detect spatially specific neural activity. Recent experimental studies, including our own (Huck et al., 2023; Zhong et al., 2023), found substantial resting-state macrovascular BOLD fMRI contributions from large veins and arteries, extending into the perivascular tissue at 3 T and 7 T. The objective of this study is to demonstrate the feasibility of predicting, using a biophysical model, the experimental resting-state BOLD fluctuation amplitude (RSFA) and associated functional connectivity (FC) values at 3 Tesla. We investigated the feasibility of both 2D and 3D infinite-cylinder models as well as macrovascular anatomical networks (mVANs) derived from angiograms. Our results demonstrate that: 1) with the availability of mVANs, it is feasible to model macrovascular BOLD FC using both the mVAN-based model and 3D infinite-cylinder models, though the former performed better; 2) biophysical modelling can accurately predict the BOLD pairwise correlation near to large veins (with R 2 ranging from 0.53 to 0.93 across different subjects), but not near to large arteries; 3) compared with FC, biophysical modelling provided less accurate predictions for RSFA; 4) modelling of perivascular BOLD connectivity was feasible at close distances from veins (with R 2 ranging from 0.08 to 0.57), but not arteries, with performance deteriorating with increasing distance. While our current study demonstrates the feasibility of simulating macrovascular BOLD in the resting state, our methodology may also apply to understanding task-based BOLD. Furthermore, these results suggest the possibility of correcting for macrovascular bias in resting-state fMRI and other types of fMRI using biophysical modelling based on vascular anatomy.
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Introduction: Physiological nuisance contributions by cardiac and respiratory signals have a significant impact on resting-state fMRI data quality. As these physiological signals are often not recorded, data-driven denoising methods are commonly used to estimate and remove physiological noise from fMRI data. To investigate the efficacy of these denoising methods, one of the first steps is to accurately capture the cardiac and respiratory signals, which requires acquiring fMRI data with high temporal resolution. Methods: In this study, we used such high-temporal resolution fMRI data to evaluate the effectiveness of several data-driven denoising methods, including global-signal regression (GSR), white matter and cerebrospinal fluid regression (WM-CSF), anatomical (aCompCor) and temporal CompCor (tCompCor), ICA-AROMA. Our analysis focused on the consequence of changes in low-frequency, cardiac and respiratory signal power, as well as age-related differences in terms of functional connectivity (fcMRI). Results: Our results confirm that the ICA-AROMA and GSR removed the most physiological noise but also more low-frequency signals. These methods are also associated with substantially lower age-related fcMRI differences. On the other hand, aCompCor and tCompCor appear to be better at removing high-frequency physiological signals but not low-frequency signal power. These methods are also associated with relatively higher age-related fcMRI differences, whether driven by neuronal signal or residual artifact. These results were reproduced in data downsampled to represent conventional fMRI sampling frequency. Lastly, methods differ in performance depending on the age group. Discussion: While this study cautions direct comparisons of fcMRI results based on different denoising methods in the study of aging, it also enhances the understanding of different denoising methods in broader fcMRI applications.
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In recent years, low-frequency oscillations (LFOs) (0.01-0.1 Hz) have been a subject of interest in resting-state functional magnetic resonance imaging research. They are believed to have many possible driving mechanisms, from both regional and global sources. Internal fluctuations in the partial pressure of CO2 (PCO2) has long been thought of as one of these major driving forces, but its exact contributions compared with other mechanisms have yet to be fully understood. This study examined the effects of end-tidal PCO2 (PetCO2) oscillations on LF cerebral hemodynamics and cerebrospinal fluid (CSF) dynamics under "clamped PetCO2" and "free-breathing" conditions. Under clamped PetCO2, a participant's PetCO2 levels were fixed to their baseline average, whereas PetCO2 was not controlled in free breathing. Under clamped PetCO2, the fractional amplitude of hemodynamic LFOs in the occipital and sensorimotor cortex and temporal lobes were found to be significantly reduced. Additionally, the fractional amplitude of CSF LFOs, measured at the fourth ventricle, was found to be reduced by almost one-half. However, the spatiotemporal distributions of blood and CSF delay times, as measured by cross-correlation in the LF domain, were not significantly altered between conditions. This study demonstrates that, while PCO2 oscillations significantly mediate LFOs, especially those observed in the CSF, other mechanisms are able to maintain LFOs, with high correlation, even in their absence.
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Dióxido de Carbono , Humanos , Dióxido de Carbono/metabolismo , Masculino , Adulto , Imageamento por Ressonância Magnética , Feminino , Circulação Cerebrovascular/fisiologia , Volume de Ventilação Pulmonar/fisiologia , Hemodinâmica , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismoRESUMO
It is becoming increasingly common for studies to fit single-shell diffusion MRI data to a two-compartment model, which comprises a hindered cellular compartment and a freely diffusing isotropic compartment. These studies consistently find that the fraction of the isotropic compartment (f) is sensitive to white matter (WM) conditions and pathologies, although the actual biological source of changes infhas not been validated. In this work we put aside the biological interpretation offand study the sensitivity implications of fitting single-shell data to a two-compartment model. We identify a nonlinear transformation between the one-compartment model (diffusion tensor imaging, DTI) and a two-compartment model in which the mean diffusivities of both compartments are effectively fixed. While the analytic relationship implies that fitting this two-compartment model does not offer any more information than DTI, it explains why metrics derived from a two-compartment model can exhibit enhanced sensitivity over DTI to certain types of WM processes, such as age-related WM differences. The sensitivity enhancement should not be viewed as a substitute for acquiring multi-shell data. Rather, the results of this study provide insight into the consequences of choosing a two-compartment model when only single-shell data is available.
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Imagem de Tensor de Difusão , Substância Branca , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Encéfalo/diagnóstico por imagemRESUMO
Introduction: In the context of functional magnetic resonance imaging (fMRI), carbon dioxide (CO2) is a well-known vasodilator that has been widely used to monitor and interrogate vascular physiology. Moreover, spontaneous fluctuations in end-tidal carbon dioxide (PETCO2) reflects changes in arterial CO2 and has been demonstrated as the largest physiological noise source for denoising the low-frequency range of the resting-state fMRI (rs-fMRI) signal. However, the majority of rs-fMRI studies do not involve CO2 recordings, and most often only heart rate and respiration are recorded. While the intrinsic link between these latter metrics and CO2 led to suggested possible analytical models, they have not been widely applied. Methods: In this proof-of-concept study, we propose a deep-learning (DL) approach to reconstruct CO2 and PETCO2 data from respiration waveforms in the resting state. Results: We demonstrate that the one-to-one mapping between respiration and CO2 recordings can be well predicted using fully convolutional networks (FCNs), achieving a Pearson correlation coefficient (r) of 0.946 ± 0.056 with the ground truth CO2. Moreover, dynamic PETCO2 can be successfully derived from the predicted CO2, achieving r of 0.512 ± 0.269 with the ground truth. Importantly, the FCN-based methods outperform previously proposed analytical methods. In addition, we provide guidelines for quality assurance of respiration recordings for the purposes of CO2 prediction. Discussion: Our results demonstrate that dynamic CO2 can be obtained from respiration-volume using neural networks, complementing the still few reports in DL of physiological fMRI signals, and paving the way for further research in DL based bio-signal processing.
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BACKGROUND: Clinical neuroimaging studies often investigate group differences between patients and controls, yet multivariate imaging features may enable individual-level classification. This study aims to classify youth with bipolar disorder (BD) versus healthy youth using grey matter cerebral blood flow (CBF) data analyzed with logistic regressions. METHODS: Using a 3 Tesla magnetic resonance imaging (MRI) system, we collected pseudo-continuous, arterial spin-labelling, resting-state functional MRI (rfMRI) and T 1-weighted images from youth with BD and healthy controls. We used 3 logistic regression models to classify youth with BD versus controls, controlling for age and sex, using mean grey matter CBF as a single explanatory variable, quantitative CBF features based on principal component analysis (PCA) or relative (intensity-normalized) CBF features based on PCA. We also carried out a comparison analysis using rfMRI data. RESULTS: The study included 46 patients with BD (mean age 17 yr, standard deviation [SD] 1 yr; 25 females) and 49 healthy controls (mean age 16 yr, SD 2 yr; 24 females). Global mean CBF and multivariate quantitative CBF offered similar classification performance that was above chance. The association between CBF images and the feature map was not significantly different between groups (p = 0.13); however, the multivariate classifier identified regions with lower CBF among patients with BD (ΔCBF = -2.94 mL/100 g/min; permutation test p = 0047). Classification performance decreased when considering rfMRI data. LIMITATIONS: We cannot comment on which CBF principal component is most relevant to the classification. Participants may have had various mood states, comorbidities, demographics and medication records. CONCLUSION: Brain CBF features can classify youth with BD versus healthy controls with above-chance accuracy using logistic regression. A global CBF feature may offer similar classification performance to distinct multivariate CBF features.
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Transtorno Bipolar , Feminino , Humanos , Adolescente , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Córtex Cerebral , Substância Cinzenta/diagnóstico por imagemRESUMO
Diffusion magnetic resonance imaging studies often investigate white matter (WM) microstructural degeneration in aging by probing WM regions that exhibit negative age associations of fractional anisotropy (FA). However, WM regions in which FA is unassociated with age are not necessarily "spared" in aging. Besides the confound of inter-participant heterogeneity, FA conflates all intravoxel fiber populations and does not allow the detection of individual fiber-specific age associations. In this study of 541 healthy adults aged 36-100 years, we use fixel-based analysis to investigate age associations among each "fixel" within a voxel, representing individual fiber populations. We find age associations of fixel-based measures that indicate age-related differences in individual fiber populations amid complex fiber architectures. Different crossing fiber populations exhibit different slopes of age associations. Our findings may provide evidence of selective degeneration of intravoxel WM fibers in aging, which does not necessarily manifest as a change in FA and therefore escapes notice if conventional voxel-based analyses are relied upon alone.
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Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Envelhecimento , Anisotropia , Encéfalo/diagnóstico por imagemRESUMO
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.
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COVID-19 , Substância Branca , COVID-19/diagnóstico por imagem , COVID-19/patologia , Imagem de Tensor de Difusão , Estudos de Viabilidade , Substância Branca/diagnóstico por imagem , Substância Branca/ultraestrutura , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/ultraestrutura , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection. Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded. Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions. Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.
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The influence of the apolipoprotein E ε4 allele (APOE4) on brain microstructure of cognitively normal older adults remains incompletely understood, in part due to heterogeneity within study populations. In this study, we examined white-matter microstructural integrity in cognitively normal older adults as a function of APOE4 carrier status using conventional diffusion-tensor imaging (DTI) and the novel orthogonal-tensor decomposition (DT-DOME), accounting for the effects of age and sex. Age associations with white-matter microstructure did not significantly depend on APOE4 status, but did differ between sexes, emphasizing the importance of accounting for sex differences in APOE research. Moreover, we found the DT-DOME to be more sensitive than conventional DTI metrics to such age-related and sex effects, especially in crossing WM fiber regions, and suggest their use in further investigation of white matter microstructure across the life span in health and disease.
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OBJECTIVE: The role of vascular risk factors in age-related brain degeneration has long been the subject of intense study, but the role of obesity remains understudied. Given known sex differences in fat storage and usage, this study investigates sex differences in the association between adiposity and white matter microstructural integrity, an important early marker of brain degeneration. METHODS: This study assesses the associations between adiposity (abdominal fat ratio and liver proton density fat fraction) and brain health (measures of intelligence and white matter microstructure using diffusion-tensor imaging [DTI]) in a group of UK Biobank participants. RESULTS: This study finds that intelligence and DTI metrics are indeed associated with adiposity differently in males and females. These sex differences are distinct from those in the associations of DTI metrics with age and blood pressure. CONCLUSIONS: Taken together, these findings suggest that there are inherent sex-driven differences in how brain health is associated with obesity.
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Substância Branca , Humanos , Masculino , Feminino , Substância Branca/diagnóstico por imagem , Adiposidade , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Obesidade/diagnóstico por imagem , InteligênciaRESUMO
Conventionally, cerebrovascular reactivity (CVR) is estimated as the amplitude of the hemodynamic response to vascular stimuli, most commonly carbon dioxide (CO2). While the CVR amplitude has established clinical utility, the temporal characteristics of CVR (dCVR) have been increasingly explored and may yield even more pathology-sensitive parameters. This work is motivated by the current need to evaluate the feasibility of dCVR modeling in various experimental conditions. In this work, we present a comparison of several recently published/utilized model-based deconvolution (response estimation) approaches for estimating the CO2 response function h(t), including maximum a posteriori likelihood (MAP), inverse logit (IL), canonical correlation analysis (CCA), and basis expansion (using Gamma and Laguerre basis sets). To aid the comparison, we devised a novel simulation framework that incorporates a wide range of SNRs, ranging from 10 to -7 dB, representative of both task and resting-state CO2 changes. In addition, we built ground-truth h(t) into our simulation framework, overcoming the conventional limitation that the true h(t) is unknown. Moreover, to best represent realistic noise found in fMRI scans, we extracted noise from in-vivo resting-state scans. Furthermore, we introduce a simple optimization of the CCA method (CCAopt) and compare its performance to these existing methods. Our findings suggest that model-based methods can accurately estimate dCVR even amidst high noise (i.e. resting-state), and in a manner that is largely independent of the underlying model assumptions for each method. We also provide a quantitative basis for making methodological choices, based on the desired dCVR parameters, the estimation accuracy and computation time. The BEL method provided the highest accuracy and robustness, followed by the CCAopt and IL methods. Of the three, the CCAopt method has the lowest computational requirements. These findings lay the foundation for wider adoption of dCVR estimation in CVR mapping.
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Dióxido de Carbono , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiologia , Hemodinâmica , Simulação por Computador , Circulação Cerebrovascular/fisiologiaRESUMO
BACKGROUND: Neurological symptoms associated with coronavirus disease 2019 (COVID-19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post-COVID-19 timeframe. PURPOSE: To determine whether adults who experienced flu-like symptoms due to COVID-19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu-like symptoms but tested negative for COVID-19. STUDY TYPE: Prospective observational. POPULATION: A total of 39 adults who previously self-isolated at home due to COVID-19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis). FIELD STRENGTH AND SEQUENCES: A 3.0 T; T1-weighted magnetization-prepared rapid gradient and echo-planar turbo gradient-spin echo arterial spin labeling sequences. ASSESSMENT: Arterial spin labeling was used to estimate CBF. A self-reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID-19 and control groups and between those with (n = 11) and without self-reported ongoing fatigue (n = 28) within the COVID-19 group. STATISTICAL TESTS: Between-group and within-group comparisons of CBF were performed in a voxel-wise manner, controlling for age and sex, at a family-wise error rate of 0.05. RESULTS: Relative to controls, the COVID-19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t-statistic = 5.21). Within the COVID-19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self-reported on-going fatigue. DATA CONCLUSION: These cross-sectional data revealed regional CBF decreases in the COVID-19 group, suggesting the relevance of brain physiology in the post-COVID-19 timeframe. This research may help elucidate the heterogeneous symptoms of the post-COVID-19 condition. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.
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COVID-19 , Adulto , Feminino , Humanos , Masculino , Circulação Cerebrovascular/fisiologia , COVID-19/diagnóstico por imagem , Teste para COVID-19 , Estudos Transversais , Fadiga/diagnóstico por imagem , Imageamento por Ressonância Magnética , Marcadores de Spin , Pessoa de Meia-IdadeRESUMO
Changes in levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) may underlie aging-related changes in brain function. GABA and co-edited macromolecules (GABA+) can be measured with MEGA-PRESS magnetic resonance spectroscopy (MRS). The current study investigated how changes in the aging brain impact the interpretation of GABA+ measures in bilateral auditory cortices of healthy young and older adults. Structural changes during aging appeared as decreasing proportion of grey matter in the MRS volume of interest and corresponding increase in cerebrospinal fluid. GABA+ referenced to H2 O without tissue correction declined in aging. This decline persisted after correcting for tissue differences in MR-visible H2 O and relaxation times but vanished after considering the different abundance of GABA+ in grey and white matter. However, GABA+ referenced to creatine and N-acetyl aspartate (NAA), which showed no dependence on tissue composition, decreased in aging. All GABA+ measures showed hemispheric asymmetry in young but not older adults. The study also considered aging-related effects on tissue segmentation and the impact of co-edited macromolecules. Tissue segmentation differed significantly between commonly used algorithms, but aging-related effects on tissue-corrected GABA+ were consistent across methods. Auditory cortex macromolecule concentration did not change with age, indicating that a decline in GABA caused the decrease in the compound GABA+ measure. Most likely, the macromolecule contribution to GABA+ leads to underestimating an aging-related decrease in GABA. Overall, considering multiple GABA+ measures using different reference signals strengthened the support for an aging-related decline in auditory cortex GABA levels.