Trial Report Advanced Imaging Analysis Reveals Altered Volume Segmentation, Structural Characteristics, and Fractional Anisotropy in ME/CFS and PCS, 2023, Ziaja et

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Advanced Imaging Analysis Reveals Altered Volume Segmentation, Structural Characteristics, and Fractional Anisotropy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Patients

Abstract
The onset of Long COVID (LC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) may be related to a virus-or immune mediated disruption. Such inflammatory processes have an impact on the brain's interconnectivity. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) represents a complex condition whose onset is potentially linked to viral infections or immune-mediated disturbances, instigating inflammatory processes with repercussions on brain interconnectivity.

This case study explores the intricate relationship between viral infections and vector markers within diverse brain networks, employing Fractional Anisotropy (FA) imaging as a primary investigative tool. A comprehensive analysis of 120 brain volumes is conducted, tracking changes over time and capturing unique characteristics. Automated fibre quantification facilitates the comparison of FA along 4 specific tracts.

METHODS • We analyzed four main fiber tracts out of a total of 42 in the Diffusion MRI White-Matter Tract Atlas, and we examined 16 volume segmentations of various brain regions. • The tract atlas, acquired from the Center for Biomedical Imaging at Massachusetts General Hospital and Harvard Medical School, underwent manual annotation. • TRACULA, FREESURFER, CONN functional connectivity toolbox version 21a, HOROS, and FSLeye software were utilized for the reconstruction of the tracts based on the atlas. • Diffusion Tensor Imaging (DTI), a modified form of magnetic resonance imaging, was employed to assess the movement of water molecules in the brain, enabling the visualization of nerve fibres in white matter. • In the data processing phase, DCM files were imported into Horos and converted for subsequent analysis using TRACULA and FreeSurfer. • Fractional Anisotropy (FA) was utilized to measure the diffusion of water molecules in the tissue. Parameters such as anisotropy (FA Avg), representing myelin sheath inflammation and conductivity, were subjected to analysis. • Various brain regions, including the amygdala, hypothalamus, lateral ventricles, cerebellum white matter volume, cerebellum cortex, hippocampus, thalamus, and fornix, underwent examination.

RESULTS • The average age of participants was 35 years (with a standard deviation of ±15 years), and all participants were right-handed. • Measurements were conducted on 10 participants with Long Covid in both 2021 and 2023, focusing on changes in the FA Avg conductivity and volume of specific brain regions. • Individuals diagnosed with ME/CFS and Long Covid exhibited significant increases in the right posterior hypothalamic segmentation, along with a decrease and deformation anomaly in the structural integrity of the interior anterior region. • Enlargement of the tubular right of the tegmentum of the caudal part of the hypothalamus (mammillothalamic tract) was associated with the speed of skeletal muscle tremors. • The reduction in amygdala volume played a central role in the emotional evaluation of mechanoreceptive information, leading to a decrease in sensorimotor interaction and neuromuscular interaction with the central body of the corpus callosum, accompanied by a reduction in FA Avg (Fig. 3). • Significant volume increases were observed in the White Matter Segmentation Fiber Tracts of the Fornix on both the left and right sides from 2021 to 2023 in the Long Covid group. • The thickening of these fibre bundles contributed to a reduction in FA Avg conductivity of the Fornix vectors from front to back, impacting the volume of the Amygdala and Hippocampus and disrupting the balance in Fornix function. • The Fornix, a crucial component of the limbic system, plays a role in the storage of short-term and long-term memory, learning, and modulation of neurotransmitters (dopamine, serotonin, and acetylcholine). • These findings provide insights into the persistent symptoms of Long Covid and ME/CFS, emphasising the need for further patient data for validation.

RESULTS • The observed volume increases in both sides of the Fornix, coupled with right-sided hypothalamic inflammation and a reduction in the right Amygdala, indicate potential microstructural alterations in white matter. This suggests a progressive decline in the conductivity of Fractional Anisotropy (FA) over time in the Anterior Commissure, Fornix, and the central body of the Corpus Callosum in individuals with ME/CFS and LC. These findings not only hold promise as biomarkers for identifying both conditions but also offer potential insights for therapeutic interventions. Furthermore, the demonstrated utility of fractional anisotropy as a diagnostic biomarker suggests its applicability in distinguishing and diagnosing ME/CFS and LC. Fig. 4. Illustrates the Hypothalamus, subdivided into nuclei for neuroendocrine, behavioural, and autonomic homeostasis (Shapiro et al., 2022). The anterior regulates thermoregulation and sleep, while the posterior promotes arousal. Left dominance in circadian rhythm, thyroid activity, thermoregulation, and immune responses; right dominance in cardiovascular responses to stress (Xavier et al., 2009). Yellow shading highlights volume changes in the interior anterior right side, associated with bedridden status in Long Covid patients

https://www.researchgate.net/publication/375921957_Advanced_Imaging_Analysis_Reveals_Altered_Volume_Segmentation_Structural_Characteristics_and_Fractional_Anisotropy_in_Myalgic_EncephalomyelitisChronic_Fatigue_Syndrome_and_Long_COVID_Patients