Tag: MRI

Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study

Abstract:

Cognitive impairment represents a leading residual symptom of COVID-19 infection, which lasts for months after the virus clearance. Up-to-date scientific reports documented a wide spectrum of brain changes in COVID-19 survivors following the illness’s resolution, mainly related to neurological and neuropsychiatric consequences.

Preliminary insights suggest abnormal brain metabolism, microstructure, and functionality as neural under-layer of post-acute cognitive dysfunction. While previous works focused on brain correlates of impaired cognition as objectively assessed, herein we investigated long-term neural correlates of subjective cognitive decline in a sample of 58 COVID-19 survivors with a multimodal imaging approach.

Diffusion Tensor Imaging (DTI) analyses revealed widespread white matter disruption in the sub-group of cognitive complainers compared to the non-complainer one, as indexed by increased axial, radial, and mean diffusivity in several commissural, projection and associative fibres. Likewise, the Multivoxel Pattern Connectivity analysis (MVPA) revealed highly discriminant patterns of functional connectivity in resting-state among the two groups in the right frontal pole and in the middle temporal gyrus, suggestive of inefficient dynamic modulation of frontal brain activity and possible metacognitive dysfunction at rest.

Beyond COVID-19 actual pathophysiological brain processes, our findings point toward brain connectome disruption conceivably translating into clinical post-COVID cognitive symptomatology. Our results could pave the way for a potential brain signature of cognitive complaints experienced by COVID-19 survivors, possibly leading to identify early therapeutic targets and thus mitigating its detrimental long-term impact on quality of life in the post-COVID-19 stages.

Source: Paolini M, Palladini M, Mazza MG, Colombo F, Vai B, Rovere-Querini P, Falini A, Poletti S, Benedetti F. Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study. Eur Neuropsychopharmacol. 2022 Dec 12;68:1-10. doi: 10.1016/j.euroneuro.2022.12.002. Epub ahead of print. PMID: 36640728. https://www.sciencedirect.com/science/article/pii/S0924977X22009130 (Full study)

Pulmonary Dysfunction after Pediatric COVID-19

Abstract:

Background: Long COVID occurs in lower frequency in children and adolescents than in adults. Morphologic and free-breathing phase-resolved functional low-field MRI may identify persistent pulmonary manifestations after SARS-CoV-2 infection.

Purpose: To characterize both morphologic and functional changes of lung parenchyma on low-field MRI in children and adolescents with post COVID-19 compared with healthy controls.

Materials and Methods: Between August and December 2021, a cross-sectional, prospective clinical trial using low-field MRI was performed in children and adolescents from a single academic medical center. The primary outcome was the frequency of morphologic changes on MRI. Secondary outcomes included MRI-derived functional proton ventilation and perfusion parameters. Clinical symptoms, the duration from positive RT-PCR test and serological parameters were compared with imaging results. Nonparametric tests for pairwise and corrected tests for groupwise comparisons were applied to assess differences in healthy controls, recovered participants and with long COVID.

Results: A total of 54 participants post COVID-19 infection (mean age, 11 years ±3 [SD], 56 males) and 9 healthy controls (mean age, 10 years ±3 [SD], 70 males) were included: 29 (54%) in the COVID-19 group had recovered from infection and 25 (46%) were classified as having long COVID on the day of enrollment. Morphologic abnormality was identified in one recovered participant. Both ventilated and perfused lung parenchyma (V/Q match) was reduced from 81±6.1% in healthy controls to 62±19% (P =.006) in the recovered group and 60±20% (P=.003) in the long COVID group. V/Q match was lower in post COVID patients with infection less than 180 days (63±20%, P=.03), 180 to 360 days (63±18%, P=0.03) and 360 days ago (41±12%, P<.001) as compared with the never-infected healthy controls (81±6.1%).

Conclusion: Low-field MRI showed persistent pulmonary dysfunction in both children and adolescents recovered from COVID-19 and with long COVID.

ClinicalTrials.gov: NCT04990531

Source: Heiss R, Tan L, Schmidt S, Regensburger AP, Ewert F, Mammadova D, Buehler A, Vogel-Claussen J, Voskrebenzev A, Rauh M, Rompel O, Nagel AM, Lévy S, Bickelhaupt S, May MS, Uder M, Metzler M, Trollmann R, Woelfle J, Wagner AL, Knieling F. Pulmonary Dysfunction after Pediatric COVID-19. Radiology. 2022 Sep 20:221250. doi: 10.1148/radiol.221250. Epub ahead of print. PMID: 36125379.

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

Abstract:

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.

Source: MacIntosh BJ, Ji X, Chen JJ, Gilboa A, Roudaia E, Sekuler AB, Gao F, Chad JA, Jegatheesan A, Masellis M, Goubran M, Rabin J, Lam B, Cheng I, Fowler R, Heyn C, Black SE, Graham SJ. Brain structure and function in people recovering from COVID-19 after hospital discharge or self-isolation: a longitudinal observational study protocol. CMAJ Open. 2021 Nov 30;9(4):E1114-E1119. doi: 10.9778/cmajo.20210023. PMID: 34848552; PMCID: PMC8648350. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648350/ (Full text)

Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystem medical condition with heterogeneous symptom expression. Currently, there is no effective cure or treatment for the standard care of patients. A variety of ME/CFS symptoms can be linked to the vital life functions of the brainstem, the lower extension of the brain best known as the hub relaying information back and forth between the cerebral cortex and various parts of the body.

Objective/Methods: Over the past decade, Magnetic Resonance Imaging (MRI) studies have emerged to understand ME/CFS with interesting findings, but there has lacked a synthesized evaluation of what has been found thus far regarding the involvement of the brainstem. We conducted this study to review and evaluate the recent MRI findings via a literature search of the MEDLINE database, from which 11 studies met the eligibility criteria.

Findings: Data showed that MRI studies frequently reported structural changes in the white and gray matter. Abnormalities of the functional connectivity within the brainstem and with other brain regions have also been found. The studies have suggested possible mechanisms including astrocyte dysfunction, cerebral perfusion impairment, impaired nerve conduction, and neuroinflammation involving the brainstem, which may at least partially explain a substantial portion of the ME/CFS symptoms and their heterogeneous presentations in individual patients.

Conclusions: This review draws research attention to the role of the brainstem in ME/CFS, helping enlighten future work to uncover the pathologies and mechanisms of this complex medical condition, for improved management and patient care.

Source: Nelson T, Zhang LX, Guo H, Nacul L, Song X. Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings. Front Neurol. 2021 Dec 17;12:769511. doi: 10.3389/fneur.2021.769511. PMID: 34975729; PMCID: PMC8718708. https://www.frontiersin.org/articles/10.3389/fneur.2021.769511/full (Full text)

Limbic Perfusion Is Reduced in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness characterized by a diverse range of debilitating symptoms including autonomic, immunologic, and cognitive dysfunction. Although neurological and cognitive aberrations have been consistently reported, relatively little is known regarding the regional cerebral blood flow (rCBF) in ME/CFS.

In this study, we studied a cohort of 31 ME/CSF patients (average age: 42.8 ± 13.5 years) and 48 healthy controls (average age: 42.9 ± 12.0 years) using the pseudo-continuous arterial spin labeling (PCASL) technique on a whole-body clinical 3T MRI scanner. Besides routine clinical MRI, the protocol included a session of over 8 min-long rCBF measurement. The differences in the rCBF between the ME/CSF patients and healthy controls were statistically assessed with voxel-wise and AAL ROI-based two-sample t-tests. Linear regression analysis was also performed on the rCBF data by using the symptom severity score as the main regressor.

In comparison with the healthy controls, the patient group showed significant hypoperfusion (uncorrected voxel wise p ≤ 0.001, FWE p ≤ 0.01) in several brain regions of the limbic system, including the anterior cingulate cortex, putamen, pallidum, and anterior ventral insular area. For the ME/CFS patients, the overall symptom severity score at rest was significantly associated with a reduced rCBF in the anterior cingulate cortex. The results of this study show that brain blood flow abnormalities in the limbic system may contribute to ME/CFS pathogenesis.

Source: Li X, Julin P, Li TQ. Limbic Perfusion Is Reduced in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Tomography. 2021 Nov 1;7(4):675-687. doi: 10.3390/tomography7040056. PMID: 34842817.  https://www.mdpi.com/2379-139X/7/4/56 (Full text)

Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study

Abstract:

PURPOSE: To examine progressive brain changes associated with chronic fatigue syndrome (CFS).

MATERIALS AND METHODS: We investigated progressive brain changes with longitudinal MRI in 15 CFS and 10 normal controls (NCs) scanned twice 6 years apart on the same 1.5 Tesla (T) scanner. MR images yielded gray matter (GM) volumes, white matter (WM) volumes, and T1- and T2-weighted signal intensities (T1w and T2w). Each participant was characterized with Bell disability scores, and somatic and neurological symptom scores. We tested for differences in longitudinal changes between CFS and NC groups, inter group differences between pooled CFS and pooled NC populations, and correlations between MRI and symptom scores using voxel based morphometry. The analysis methodologies were first optimized using simulated atrophy.

RESULTS: We found a significant decrease in WM volumes in the left inferior fronto-occipital fasciculus (IFOF) in CFS while in NCs it was unchanged (family wise error adjusted cluster level P value, PFWE < 0.05). This longitudinal finding was consolidated by the group comparisons which detected significantly decreased regional WM volumes in adjacent regions (PFWE< 0.05) and decreased GM and blood volumes in contralateral regions (PFWE < 0.05). Moreover, the regional GM and WM volumes and T2w in those areas showed significant correlations with CFS symptom scores (PFWE < 0.05).

CONCLUSION: The results suggested that CFS is associated with IFOF WM deficits which continue to deteriorate at an abnormal rate. J. Magn. Reson. Imaging 2016;44:1301-1311.

© 2016 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

 

Source: Shan ZY, Kwiatek R, Burnet R, Del Fante P, Staines DR, Marshall-Gradisnik SM, Barnden LR. Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study. J Magn Reson Imaging. 2016 Nov;44(5):1301-1311. doi: 10.1002/jmri.25283. Epub 2016 Apr 28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111735/ (Full article)

 

Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue

Abstract:

Reduced basal ganglia function has been associated with fatigue in neurologic disorders, as well as in patients exposed to chronic immune stimulation. Patients with chronic fatigue syndrome (CFS) have been shown to exhibit symptoms suggestive of decreased basal ganglia function including psychomotor slowing, which in turn was correlated with fatigue. In addition, CFS patients have been found to exhibit increased markers of immune activation.

In order to directly test the hypothesis of decreased basal ganglia function in CFS, we used functional magnetic resonance imaging to examine neural activation in the basal ganglia to a reward-processing (monetary gambling) task in a community sample of 59 male and female subjects, including 18 patients diagnosed with CFS according to 1994 CDC criteria and 41 non-fatigued healthy controls. For each subject, the average effect of winning vs. losing during the gambling task in regions of interest (ROI) corresponding to the caudate nucleus, putamen, and globus pallidus was extracted for group comparisons and correlational analyses.

Compared to non-fatigued controls, patients with CFS exhibited significantly decreased activation in the right caudate (p = 0.01) and right globus pallidus (p = 0.02). Decreased activation in the right globus pallidus was significantly correlated with increased mental fatigue (r2 = 0.49, p = 0.001), general fatigue (r2 = 0.34, p = 0.01) and reduced activity (r2 = 0.29, p = 0.02) as measured by the Multidimensional Fatigue Inventory. No such relationships were found in control subjects.

These data suggest that symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks.

 

Source: Miller AH, Jones JF, Drake DF, Tian H, Unger ER, Pagnoni G. Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue. PLoS One. 2014 May 23;9(5):e98156. doi: 10.1371/journal.pone.0098156. ECollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032274/ (Full article)

 

Longitudinal MRI shows no cerebral abnormality in chronic fatigue syndrome

Abstract:

MRI has previously provided conflicting results when used to search for brain abnormalities in sufferers of chronic fatigue syndrome (CFS). Eighteen CFS patients and nine healthy volunteers each underwent MRI on two occasions, one year apart. The resulting images were examined for abnormalities in brain atrophy, deep white matter hyperintensities (WMH) and cerebral blood and cerebrospinal fluid (CSF) flow.

Mean proportionate CSF volume was not significantly different between subject groups. All participants showed a slight increase in CSF between scans, but no significant difference was found between those with CFS and those without. Between-group comparisons of ventricular volume revealed no significant differences at study commencement and no significant change over the year. No significant inter-group differences were found for any of the cerebral blood and CSF flow parameters. Low levels of WMH were found in all participants. Objective scoring of WMH using Scheltens’ scale revealed no change in summary components (prosencephalic deep white matter hyperintensities, basal ganglia hyperintensities and infratentorial hyperintensities) or in individual component variables between the baseline and 1 year follow-up scans. No abnormal patterns in rate and extent of brain atrophy, ventricle volume, white matter lesions, cerebral blood flow or aqueductal CSF flow were detected in the CFS population.

These results throw open the debate into whether MRI scanning can reveal diagnostic signs of CFS and clinically questions the diagnoses of CFS made on the basis of previous research conclusions.

 

Source: Perrin R, Embleton K, Pentreath VW, Jackson A. Longitudinal MRI shows no cerebral abnormality in chronic fatigue syndrome. Br J Radiol. 2010 May;83(989):419-23. doi: 10.1259/bjr/85621779. Epub 2010 Mar 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473570/ (Full article)

 

Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome

Abstract:

Chronic Fatigue Syndrome (CFS) is an unexplained illness that is characterized by severe fatigue. Some have suggested that CFS is a “functional somatic syndrome” in which symptoms of fatigue are inappropriately attributed to a serious illness. However, brain magnetic resonance imaging (MRI) data suggest that there may be an organic abnormality associated with CFS.

To understand further the significance of brain MRI abnormalities, we examined the relationship between MRI identified brain abnormalities and self-reported physical functional status in 48 subjects with CFS who underwent brain MR imaging and completed the Medical Outcomes Study SF-36. Brain MR images were examined for the presence of abnormalities based on 5 general categories previously shown to be sensitive to differentiating CFS patients from healthy controls.

There were significant negative relationships between the presence of brain abnormalities and both the physical functioning (PF) (rho=-.31, p=.03), and physical component summary PCS (rho=-.32, p=.03) subscales of the SF-36. CFS patients with MRI identified brain abnormalities scored significantly lower on both PF (t(1,46) =2.3, p=.026) and the PCS (t(1,41) =2.4, p=.02) than CFS subjects without an identified brain abnormality. When adjusted for age differences only the PF analysis remained significant. However, the effect sizes for both analyses were large indicating meaningful differences in perceived functional status between the groups.

These results demonstrate that the presence of brain abnormalities in CFS are significantly related to subjective reports of physical function and that CFS subjects with MRI brain abnormalities report being more physically impaired than those patients without brain abnormalities.

 

Source: Cook DB, Lange G, DeLuca J, Natelson BH. Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome. Int J Neurosci. 2001 Mar;107(1-2):1-6. http://www.ncbi.nlm.nih.gov/pubmed/11328679

 

Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome

Abstract:

Presence of MRI brain abnormalities in patients with Chronic Fatigue Syndrome (CFS) was determined and the profile of MRI abnormalities was compared between 39 CFS patients, 18 with (CFS-Psych) and 21 without (CFS-No Psych) a DSM-III-R Axis I psychiatric diagnosis since illness onset, and 19 healthy, sedentary controls (HC).

Two neuroradiologists, blind to group membership, separately read the MR films using a detailed protocol for rating and categorizing abnormal signal changes. When findings were incongruent, the two neuroradiologists met to try to reach consensus, otherwise a third neuroradiologist evaluated the MR images and served as a tie-breaker.

The CFS-No Psych group showed a significantly larger number of brain abnormalities on T2 weighted images than the CFS-Psych and HC groups. Cerebral changes in the CFS-No Psych group consisted mostly of small, punctate, subcortical white matter hyperintensities, found predominantly in the frontal lobes. No significant difference was found when both CFS groups were combined and compared to the HC group.

The use of stratification techniques is an important strategy in understanding the pathophysiology of CFS. This frontal lobe pathology could explain the more severe cognitive impairment previously reported in this subset of CFS patients.

Comment in: Brain MRI abnormalities exist in chronic fatigue syndrome. [J Neurol Sci. 1999]

 

Source: Lange G, DeLuca J, Maldjian JA, Lee H, Tiersky LA, Natelson BH. Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome. J Neurol Sci. 1999 Dec 1;171(1):3-7. http://www.ncbi.nlm.nih.gov/pubmed/10567042