Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals.

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.

MRI Assessment of Cerebral Blood Flow in Nonhospitalized Adults Who Self-Isolated Due to COVID-19.

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.

Brain structure and function in people recovering from COVID-19 after hospital discharge or self-isolation: a longitudinal observational study protocol.

BACKGROUND: The detailed extent of neuroinvasion or deleterious brain changes resulting from COVID-19 and their time courses remain to be determined in relation to "long-haul" COVID-19 symptoms. Our objective is to determine whether there are alterations in functional brain imaging measures among people with COVID-19 after hospital discharge or self-isolation. METHODS: This paper describes a protocol for NeuroCOVID-19, a longitudinal observational study of adults aged 20-75 years at Sunnybrook Health Sciences Centre in Toronto, Ontario, that began in April 2020. We aim to recruit 240 adults, 60 per group: people who contracted COVID-19 and were admitted to hospital (group 1), people who contracted COVID-19 and self-isolated (group 2), people who experienced influenza-like symptoms at acute presentation but tested negative for COVID-19 and self-isolated (group 3, control) and healthy people (group 4, control). Participants are excluded based on premorbid neurologic or severe psychiatric illness, unstable cardiovascular disease, and magnetic resonance imaging (MRI) contraindications. Initial and 3-month follow-up assessments include multiparametric brain MRI and electroencephalography. Sensation and cognition are assessed alongside neuropsychiatric assessments and symptom self-reports. We will test the data from the initial and follow-up assessments for group differences based on 3 outcome measures: MRI cerebral blood flow, MRI resting state fractional amplitude of low-frequency fluctuation and electroencephalography spectral power. INTERPRETATION: If neurophysiologic alterations are detected in the COVID-19 groups in our NeuroCOVID-19 study, this information could inform future research regarding interventions for long-haul COVID-19. The study results will be disseminated to scientists, clinicians and COVID-19 survivors, as well as the public and private sectors to provide context on how brain measures relate to lingering symptoms.

A DSP based multi-frequency 3D electrical impedance tomography system.

This paper describes the design of a multi-frequency Electrical impedance tomography (EIT) system, which provides a flexible mechanism for addressing up to 48 electrodes for imaging conductivity and permittivity distributions. A waveform generator based on a digital signal processor is used to produce sinusoidal waveforms with the ability to select frequencies in the range of 0.1-125 kHz. A software based phase-sensitive demodulation technique is used to extract amplitudes and phases from the raw measurements. Signal averaging and automatic gain control are also implemented in voltage and phase measurements. System performance was validated using a Cardiff-Cole Phantom and a saline filled cylindrical tank. The signal-to-noise ratio (SNR) using saline tank was greater than 60 dB and the maximum reciprocity error less than 4% for most frequencies. The common-mode rejection ratio (CMRR) was nearly 60 dB at 50 kHz. Image reconstruction performance was assessed using data acquired through a range of frequencies. This EIT system offers image reconstruction of both conductivity and permittivity distributions in three dimensions. The imaging results are presented in time difference and frequency difference imaging.

A novel approach for EIT regularization via spatial and spectral principal component analysis.

Electrical impedance tomography, EIT, is an imaging modality in which the internal conductivity distribution of an object is reconstructed based on voltage measurements on the boundary. This reconstruction problem is a nonlinear and ill-posed inverse problem, which requires regularization to ensure a stable solution. Most popular regularization approaches enforce smoothness in the inverse solution. In this paper, we propose a novel approach to build a subspace for regularization using a spectral and spatial multi-frequency analysis approach. The approach is based on the construction of a subspace for the expected conductivity distributions using principal component analysis. It is shown via simulations that the reconstructed images obtained with the proposed method are better than with the standard regularization approach. Using this approach, the percentage of misclassified finite elements was reduced up to twelve fold from the initial percentages after five iterations. The advantage of this technique is that prior information is extracted from the characteristic response of an object at different frequencies and spatially across the finite elements.

Dogleg trust-region application in electrical impedance tomography.

This paper presents a trust-region implementation for image reconstruction of conductivity changes in electrical impedance tomography. A dogleg trust-region algorithm is applied in different cases to detect abnormalities. The dogleg algorithm approximates a Levenberg-Marquardt step within the trust region of the model function with a quadratic model. The comparison of Levenberg-Marquardt and dogleg algorithms is presented using the reconstructed images. This comparison of two techniques suggests the implementation of the dogleg method could result in the reduction of the execution time to less than 50% of that of the Levenberg-Marquardt algorithm without any quantifiable loss of quality of reconstructed images.