Tag: MRI

Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study

Abstract:

Background: Diverse neurological symptoms are experienced by long COVID and COVID-19 recovered individuals. However, the long-term effects of SARS-CoV-2 in the brain of both groups are underexplored. This study aimed to investigate changes in tissue microstructural and brain neurochemical levels in long COVID and recovered COVID-19 patients compared to healthy controls.

Methods: We recruited 47 participants (long COVID = 19, COVID-recovered healthy controls = 12, and healthy controls without COVID-19 infection = 16) who underwent 3T MRI scans. We acquired T1 and T2 weighted images to assess myelin signal, diffusion weighted images to assess tissue microstructure, and magnetic resonance spectroscopy data to estimate brain neurochemical levels.

Findings: Our multimodal MRI study showed altered T1w/T2w signal between long COVID vs COVID-recovered-healthy controls, long COVID vs healthy controls, and COVID-recovered-healthy controls vs healthy controls. Furthermore, T1w/T2w signal intensity was significantly correlated with physical and cognitive function. Diffusion weighted imaging also showed altered tissue microstructure in these three group comparisons. However, brain neurochemicals were only significantly different between long COVID vs COVID-recovered-healthy controls.

Interpretation: This is one of the first studies to report different myelin signal and brain neurochemical changes between long COVID, COVID-recovered-healthy controls, and healthy controls without SARS-CoV-2 infection. These brain changes provide compelling evidence for the long-term effects of SARS-CoV-2 on brain function.

Source: Thapaliya K, Marshall-Gradisnik S, Inderyas M, Barnden L. Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study. Brain Behav Immun Health. 2025 Nov 25;50:101142. doi: 10.1016/j.bbih.2025.101142. PMID: 41404601; PMCID: PMC12704066. https://pmc.ncbi.nlm.nih.gov/articles/PMC12704066/ (Full text)

Brain MRI findings in patients with post COVID-19 condition: frequency and longitudinal changes in a nationwide cohort study

Abstract:

Background: Prolonged neurological symptoms following COVID-19 are common, yet few longitudinal studies describe brain MRI findings in this patient group. The use of contrast enhanced sequences is particularly lacking. We address this knowledge gap by reporting the frequency and longitudinal changes in brain MRI findings among patients with post COVID-19 condition exhibiting neurological symptoms.

Methods: This prospective multicenter study included 140 adult patients referred for persistent neurological symptoms following COVID-19. Brain MRI was performed at both 6 and 12 months after infection onset, reporting white matter hyperintensities, cerebral microbleeds, and additional pathological findings including contrast enhancement. White matter hyperintensities were compared with a healthy control group.

Results: The prevalence of white matter hyperintensities was comparable to healthy controls, and microbleeds were found at rates comparable to population studies, with longitudinal changes being infrequent. Lesions consistent with inflammation or demyelination were present in 4% (5/120) of patients at 6 months. Cranial nerve enhancement was found in 7% (7/94) of patients, persisting up to 12 months, predominantly affecting the oculomotor nerve. However, enhancement occurred without clinically detected ocular muscle paresis.

Conclusion: Our findings indicate that brain MRI primarily serves to exclude differential diagnoses in post COVID-19 condition, with limited clinical benefit of repeated imaging in the absence of new symptoms. However, signs of long-term inflammatory processes can be observed, and detection is improved by contrast enhanced sequences.

Source: Furevik LL, Lapina O, Lindland ES, Høgestøl EA, Geier OM, Devik K, Farmen AH, Flemmen HØ, Harbo HF, Morsund ÅH, Novotny V, Ofte HK, Pedersen KO, Popperud TH, Ratajczak-Tretel B, Samsonsen C, Selnes P, Torkildsen Ø, Undseth RM, Aamodt AH, Beyer MK, Boldingh MI. Brain MRI findings in patients with post COVID-19 condition: frequency and longitudinal changes in a nationwide cohort study. Front Neurol. 2025 Nov 13;16:1662263. doi: 10.3389/fneur.2025.1662263. PMID: 41323230; PMCID: PMC12658414. https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1662263/full (Full text)

Review of Neuroimaging Methods in ME/CFS

Abstract:

The brain is the most complex organ in the human body, and is involved in memory, speech, and movement, as well as regulating the functions of many other organs within the body. Various imaging techniques have detected subtle brain changes in vivo in ME/CFS. This chapter explores different neuroimaging studies used to investigate structural, functional, neurochemical, and tissue microstructural alterations in ME/CFS. These include magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT).

Source: Thapaliya K, Inderyas M, Barnden L. Review of Neuroimaging Methods in ME/CFS. Methods Mol Biol. 2025;2920:257-277. doi: 10.1007/978-1-0716-4498-0_15. PMID: 40372688.  https://link.springer.com/protocol/10.1007/978-1-0716-4498-0_15

Cluster analysis to identify long COVID phenotypes using 129Xe magnetic resonance imaging: a multicentre evaluation

Abstract:

Background: Long COVID impacts ∼10% of people diagnosed with coronavirus disease 2019 (COVID-19), yet the pathophysiology driving ongoing symptoms is poorly understood. We hypothesised that 129Xe magnetic resonance imaging (MRI) could identify unique pulmonary phenotypic subgroups of long COVID. Therefore, we evaluated ventilation and gas exchange measurements with cluster analysis to generate imaging-based phenotypes.

Methods: COVID-negative controls and participants who previously tested positive for COVID-19 underwent 129Xe MRI ∼14 months post-acute infection across three centres. Long COVID was defined as persistent dyspnoea, chest tightness, cough, fatigue, nausea and/or loss of taste/smell at MRI; participants reporting no symptoms were considered fully recovered. 129Xe MRI ventilation defect percent (VDP) and membrane-to-gas (Mem/Gas), red blood cell-to-membrane (RBC/Mem) and red blood cell-to-gas (RBC/Gas) ratios were used in k-means clustering for long COVID, and measurements were compared using ANOVA with post-hoc Bonferroni correction.

Results: We evaluated 135 participants across three centres: 28 COVID-negative (mean±sd age 40±16 years), 34 fully recovered (42±14 years) and 73 long COVID (49±13 years). RBC/Mem (p=0.03) and forced expiratory volume in 1 s (FEV1) (p=0.04) were different between long COVID and COVID-negative; FEV1 and all other pulmonary function tests (PFTs) were within normal ranges. Four unique long COVID clusters were identified compared with recovered and COVID-negative. Cluster 1 was the youngest with normal MRI and mild gas trapping; Cluster 2 was the oldest, characterised by reduced RBC/Mem but normal PFTs; Cluster 3 had mildly increased Mem/Gas with normal PFTs; and Cluster 4 had markedly increased Mem/Gas with concomitant reduction in RBC/Mem and restrictive PFT pattern.

Conclusions: We identified four 129Xe MRI long COVID phenotypes with distinct characteristics. 129Xe MRI can dissect pathophysiological heterogeneity of long COVID to enable personalised patient care.

Source: Eddy RL, Mummy D, Zhang S, Dai H, Bechtel A, Schmidt A, Frizzell B, Gerayeli FV, Leipsic JA, Leung JM, Driehuys B, Que LG, Castro M, Sin DD, Niedbalski PJ. Cluster analysis to identify long COVID phenotypes using 129Xe magnetic resonance imaging: a multicentre evaluation. Eur Respir J. 2024 Mar 28;63(3):2302301. doi: 10.1183/13993003.02301-2023. PMID: 38331459; PMCID: PMC10973687. https://pmc.ncbi.nlm.nih.gov/articles/PMC10973687/ (Full text)

A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation

Abstract:

Background/Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological disorder characterized by post-exertional malaise. Despite its clinical relevance, the disease mechanisms of ME/CFS are not fully understood. The previous studies targeting brain function or metabolites have been inconclusive in understanding ME/CFS complexity. We combined single-voxel magnetic resonance spectroscopy (SV-MRS) and functional magnetic resonance imaging (fMRI). Our objectives were to examine the feasibility of the multimodal MRI protocol, identify possible differences between ME/CFS and healthy controls (HCs), and relate MRI findings with clinical symptoms.

Methods: We enrolled 18 female ME/CFS participants (mean age: 39.7 ± 12.0 years) and five HCs (mean age: 45.6 ± 14.5 years). SV-MRS spectra were acquired from three voxels of interest: the anterior cingulate gyrus (ACC), brainstem (BS), and left dorsolateral prefrontal cortex (L-DLPFC). Whole-brain fMRI used n-back task testing working memory and executive function. The feasibility was assessed as protocol completion rate and time. Group differences in brain metabolites and fMRI activation between ME/CFS and HCs were compared and correlated with behavioral and symptom severity measurements.

Results: The completion rate was 100% regardless of participant group without causing immediate fatigue. ME/CFS appeared to show a higher N-Acetylaspartate in L-DLPFC compared to HCs (OR = 8.49, p = 0.040), correlating with poorer fatigue, pain, and sleep quality scores (p‘s = 0.001-0.015). An increase in brain activation involving the frontal lobe and the brainstem was observed in ME/CFS compared to HCs (Z > 3.4, p‘s < 0.010).

Conclusions: The study demonstrates the feasibility of combining MRS and fMRI to capture neurochemical and neurophysiological features of ME/CFS in female participants. Further research with larger cohorts of more representative sampling and follow-ups is needed to validate these apparent differences between ME/CFS and HCs.

Source: Kaur R, Greeley B, Ciok A, Mehta K, Tsai M, Robertson H, Debelic K, Zhang LX, Nelson T, Boulter T, Siu W, Nacul L, Song X. A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation. Medicina (Kaunas). 2024 Aug 22;60(8):1370. doi: 10.3390/medicina60081370. PMID: 39202651. https://www.mdpi.com/1648-9144/60/8/1370 (Full text)

Brain microstructural changes and fatigue after COVID-19

Abstract:

Background: Fatigue and cognitive complaints are the most frequent persistent symptoms in patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess fatigue and neuropsychological performance and investigate changes in the thickness and volume of gray matter (GM) and microstructural abnormalities in the white matter (WM) in a group of patients with mild-to-moderate coronavirus disease 2019 (COVID-19).

Methods: We studied 56 COVID-19 patients and 37 matched controls using magnetic resonance imaging (MRI). Cognition was assessed using Montreal Cognitive Assessment and Cambridge Neuropsychological Test Automated Battery, and fatigue was assessed using Chalder Fatigue Scale (CFQ-11). T1-weighted MRI was used to assess GM thickness and volume. Fiber-specific apparent fiber density (FD), free water index, and diffusion tensor imaging data were extracted using diffusion-weighted MRI (d-MRI). d-MRI data were correlated with clinical and cognitive measures using partial correlations and general linear modeling.

Results: COVID-19 patients had mild-to-moderate acute illness (95% non-hospitalized). The average period between real-time quantitative reverse transcription polymerase chain reaction-based diagnosis and clinical/MRI assessments was 93.3 (±26.4) days. The COVID-19 group had higher total CFQ-11 scores than the control group (p < 0.001). There were no differences in neuropsychological performance between groups. The COVID-19 group had lower FD in the association, projection, and commissural tracts, but no change in GM. The corona radiata, corticospinal tract, corpus callosum, arcuate fasciculus, cingulate, fornix, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus were involved. CFQ-11 scores, performance in reaction time, and visual memory tests correlated with microstructural changes in patients with COVID-19.

Conclusions: Quantitative d-MRI detected changes in the WM microstructure of patients recovering from COVID-19. This study suggests a possible brain substrate underlying the symptoms caused by SARS-CoV-2 during medium- to long-term recovery.

Source: Bispo DDC, Brandão PRP, Pereira DA, Maluf FB, Dias BA, Paranhos HR, von Glehn F, de Oliveira ACP, Regattieri NAT, Silva LS, Yasuda CL, Soares AASM, Descoteaux M. Brain microstructural changes and fatigue after COVID-19. Front Neurol. 2022 Nov 10;13:1029302. doi: 10.3389/fneur.2022.1029302. PMID: 36438956; PMCID: PMC9685991. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685991/ (Full text)

Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects

Abstract:

Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association between them.

To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy controls chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with Long COVID assessed by ACE III screening test (Overall Cognitive level – OCLz= -0.39± 0.12) was significantly below the infection recovered-controls (OCLz= +0.32± 0.16, p< 0.01).

We observed that 48% of patients with Long COVID had episodic memory deficit, with 27% also impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus.

In addition, lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in widespread areas of the patients’ cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency.

This study shows that patients with neurological Long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.

Source: Serrano Del Pueblo VM, Serrano-Heras G, Romero Sánchez CM, Piqueras Landete P, Rojas-Bartolome L, Feria I, Morris RGM, Strange B, Mansilla F, Zhang L, Castro-Robles B, Arias-Salazar L, López-López S, Payá M, Segura T, Muñoz-López M. Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects. Brain. 2024 Apr 2:awae101. doi: 10.1093/brain/awae101. Epub ahead of print. PMID: 38562097. https://pubmed.ncbi.nlm.nih.gov/38562097/

Imbalanced Brain Neurochemicals in long COVID and ME/CFS: A Preliminary Study using MRI

Abstract:

Purpose: Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients experience multiple complex symptoms, potentially linked to imbalances in brain neurochemicals. This study aims to measure brain neurochemical levels in long COVID and ME/CFS patients as well as healthy controls to investigate associations with severity measures.

Methods: Magnetic resonance spectroscopy (MRS) data was acquired with a 3T Prisma MRI scanner. We measured absolute levels of brain neurochemicals in the posterior cingulate cortex in long COVID (n=17), ME/CFS (n=17), and healthy controls (n=10) using Osprey software. The statistical analyses were performed using SPSS version 29. Age and sex were included as nuisance covariates.

Results: Glutamate levels were significantly higher in long COVID (p=0.02) and ME/CFS (p=0.017) than in healthy controls. No significant difference was found between the two patient cohorts. Additionally, N-acetyl-aspartate levels were significantly higher in long COVID patients (p=0.012). Importantly, brain neurochemical levels were associated with self-reported severity measures in long COVID and ME/CFS.

Conclusion: Our study identified significantly elevated Glutamate and N-acetyl-aspartate levels in long COVID and ME/CFS patients compared with healthy controls. No significant differences in brain neurochemicals were observed between the two patient cohorts, suggesting a potential overlap in their underlying pathology. These findings suggest that imbalanced neurochemicals contribute to the complex symptoms experienced by long COVID and ME/CFS patients.

Source: Thapaliya K, Marshall-Gradisnik S, Eaton-Fitch N, Eftekhari Z, Inderyas M, Barnden L. Imbalanced Brain Neurochemicals in long COVID and ME/CFS: A Preliminary Study using MRI. Am J Med. 2024 Apr 6:S0002-9343(24)00216-X. doi: 10.1016/j.amjmed.2024.04.007. Epub ahead of print. PMID: 38588934. https://www.sciencedirect.com/science/article/pii/S000293432400216X (Full text)

Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a neurological disorder characterized by extreme fatigue that lasts for a long time and doesn’t alleviate with rest. The number of the cases has been increasing during the era of COVID-19 pandemic.

Acupuncture may have some effect on chronic fatigue syndrome, but its mechanism remains unclear. This article was to summarize the specific manifestations of abnormal central mechanism in patients with chronic fatigue syndrome through laboratory tests and neuroimaging.

It was found from the laboratory evaluation that there were changes in the structure of the frontal cortex, thalamus and other brain tissues; factors, including IFN-α and IL-10 in cerebrospinal fluid were found abnormal; results of oxidative and nitrosative stress and changes in neurobiochemical substances, e.g. hypothalamus hormone levels and neurotransmitter concentrations, were observed.

With magnetic resonance imaging and positron emission tomography, it was shown that the partial brain of persons with chronic fatigue syndrome had morphological changes with diminished grey matter and white; changes in cerebral blood flow velocity caused by decreased perfusion and functional activity with abnormal connectivity in brain were detected.

In addition, there was significant decrease in glucose metabolism accompanied with neuroinflammatory response; metabolic disorders of serotonergic, cholinergic, glutamatergic and γ-aminobutyric acid energy neurotransmitters were also discovered.

The regulatory effect of acupuncture on the above central neurological abnormalities in chronic fatigue syndrome model animals was elaborated, and the direction for further research was analyzed in order to provide ideas for further research on the central mechanism of acupuncture treatment for chronic fatigue syndrome.

Source: Li BB, Feng CW, Qu YY, Sun ZR, Chen T, Wang YL, Wang QY, Lu J, Shao YY, Yang TS. Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome. World J Acupunct Moxibustion.  doi: 10.1016/j.wjam.2023.03.002 [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061266/ (Full text)