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

Shan, Zack; Kwiatek, Richard; Burnet, Richard; Fante, Peter Del; Staines, Donald; Marshall‐Gradisnik, Sonya; Barnden, Leighton

doi:10.1002/jmri.25283

Cited by 59 publications

(68 citation statements)

References 40 publications

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“…Regional IFOF WM volumes were significantly decreased here in patients with CFS compared with NCs. This finding supports our previous observation of progressive WM atrophy in the left IFOF in CFS, although 15 of the 40 CFS patients and 10 of the 14 NCs in this study were also used in that longitudinal study. WM atrophy in the left IFOF also correlated with PSQI.…”

Section: Discussionsupporting

confidence: 92%

“…The three‐dimensional anatomic images were segmented into GM, WM, and cerebrospinal fluid images using SPM12 (Wellcome Trust Centre for Neuroimaging, London, UK), in which a unified probabilistic framework that combined image segmentation, tissue classification, and bias correction within the same generative model was implemented . The empirical parameter for Markov random field removal of isolated voxel assignments was set to 4, in accordance with our previous validation results . Global GM and WM volumes were computed in SPM12 by summing all voxel values in the GM and WM images.…”

Section: Methodsmentioning

confidence: 99%

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Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome

et al. 2017

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Funding information The Judith Jane Mason FoundationUnrefreshing sleep is a hallmark of chronic fatigue syndrome/myalgic encephalomyelitis (CFS).This study examined brain structure variations associated with sleep quality in patients with CFS. 38 patients with CFS (34.8 ± 10.1 years old) and 14 normal controls (NCs) (34.7 ± 8.4 years old) were recruited. All subjects completed the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index (PSQI), and Chalder Fatigue Scale (CFQ) questionnaires. Brain MRI measures included global and regional grey and white matter volumes, magnetization transfer T 1 weighted (MT-T1w) intensities, and T 1 weighted (T1w) and T 2 weighted spin echo signal intensities. We performed voxel based group comparisons of these regional brain MRI measures and regressions of these measures with the PSQI and CFQ scales adjusted for age, anxiety and depression, and the appropriate global measure. In CFS patients, negative correlations were observed in the medial prefrontal cortex (mPFC) between PSQI and MT-T1w intensities (family-wise error corrected cluster, P FWE < 0.05) and between PSQI and T1w intensities (P FWE < 0.05). In the same mPFC location, both MT and T1w intensities were lower in CFS patients compared with NCs (uncorrected voxel P < 0.001). This study is the first to report that brain structural differences are associated with unrefreshing sleep in CFS. This result refutes the suggestion that unrefreshing sleep is a misperception in CFS patients and further investigation of this symptom is warranted. Sleep plays an important role in human health and well-being, with its recuperative, restorative, and learning consolidation properties. 4,5Unrefreshing sleep is a hallmark of ME/CFS that causes patients to wake up feeling tired even after extended periods of sleep, to experience excessive daytime sleepiness, and to have difficulty falling asleep and staying asleep. Therefore, unrefreshing sleep results at least in worsening fatigue symptoms and adds to the 'illness burden' in CFS patients. 6 Roughly 91% of CFS patients report unrefreshing sleep regardless of adequate sleep duration. 7 The effect of unrefreshing sleep is of importance in CFS aetiology because sleep disturbance can cause fatigue, myalgia, and poor attention. 8 A recent path analysis study, exploring the interrelationship of different symptoms in CFS, found that poor sleep quality directly impacted on

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome

et al. 2017

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“…The use of magnetic resonance imaging (MRI) has increased because it allows for noninvasive evaluation of patients without ionizing radiation and provides superior soft tissue contrast in comparison with computed tomography (CT). With these attributes, MRI has great potential for use in longitudinal studies . A longitudinal study is when data is acquired for the same subjects over a period of time and may have different designs based on the type of study, such as prospective or retrospective .…”

Section: Introductionmentioning

confidence: 99%

“…With these attributes, MRI has great potential for use in longitudinal studies. [1][2][3][4][5] A longitudinal study is when data is acquired for the same subjects over a period of time and may have different designs based on the type of study, such as prospective or retrospective. 6 An example of a prospective longitudinal study is the recent DCE-MRI study evaluating mandible changes in patients that were scanned before chemoradiotherapy treatment started, 3-4 weeks after initiation of treatment, and 6-8 weeks after treatment concluded.…”

Section: Introductionmentioning

confidence: 99%

Accuracy of deformable image registration on magnetic resonance images in digital and physical phantoms

et al. 2017

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Purpose Accurate deformable image registration is necessary for longitudinal studies. The error associated with commercial systems has been evaluated using computed tomography (CT). Several in-house algorithms have been evaluated for use with magnetic resonance imaging (MRI), but there is still relatively little information about MRI deformable image registration. This work presents an evaluation of two deformable image registration systems, one commercial (Velocity) and one in-house (demons-based algorithm), with MRI using two different metrics to quantify the registration error. Methods The registration error was analyzed first with synthetic MR images. These images were generated from inter-patient and intra-patient variation models trained on 28 patients. Four synthetic posttreatment images were generated for each of four synthetic pretreatment images, resulting in 16 image registrations for both the T1- and T2-weighted images. The synthetic post-treatment images were registered to their corresponding synthetic pre-treatment image. The registration error was calculated between the known deformation vector field and the generated deformation vector field from the image registration system. The registration error was also analyzed using a porcine phantom with ten implanted 0.35-mm diameter gold markers. The markers were visible on CT but not MRI. CT, T1-weighted MR, and T2-weighted MR images were taken in four different positions. The markers were contoured on the CT images and rigidly registered to their corresponding MR images. The MR images were deformably registered and the distance between the projected marker location and true marker location was measured as the registration error. Results The synthetic images were evaluated only on Velocity. Root mean square errors (RMSEs) of 0.76 mm in the left-right (LR) direction, 0.76 mm in the anteroposterior (AP) direction, and 0.69 mm in the superior-inferior (SI) direction were observed for the T1-weighted MR images. RMSEs of 1.1 mm in the LR direction, 0.75 mm in the AP direction, and 0.81 mm in the SI direction were observed for the T2-weighted MR images. The porcine phantom MR images, when evaluated with Velocity, had RMSEs of 1.8, 1.5, and 2.7 mm in the LR, AP, and SI directions for the T1-weighted images and 1.3, 1.2, and 1.6 mm in the LR, AP, and SI directions for the T2-weighted images. When the porcine phantom images were evaluated with the in-house demons-based algorithm, RMSEs were 1.2, 1.5, 2.1 mm in the LR, AP, and SI directions for the T1-weighted images and 0.81, 1.1, and 1.1 mm in the LR, AP, and SI directions for the T2-weighted images. Conclusions The MRI registration error was low for both Velocity and the in-house demons-based algorithm according to both image evaluation methods, with all RMSEs below 3 mm. This implies that both image registration systems can be used for longitudinal studies using MRI.

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“…2 In addition to fatigue, other symptoms associated with the central nervous system often appear, such as impaired short-term memory or concentration, headaches, and unrefreshing sleep. Correspondingly, structural [3][4][5][6] and functional [7][8][9][10] neuroimaging studies have investigated possible brain changes associated with ME/CFS. However, cerebral imaging studies comparing ME/CFS subjects with controls have been indeterminate.…”

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confidence: 99%

Brain abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome: Evaluation by diffusional kurtosis imaging and neurite orientation dispersion and density imaging

Kimura

Sato

Ota

et al. 2018

Magnetic Resonance Imaging

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Background Diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) metrics provide more specific information regarding pathological changes than diffusion tensor imaging (DTI). Purpose To detect microstructural abnormalities in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS) patients by using DKI and NODDI metrics. Study Type Prospective. Population Twenty ME/CFS patients and 23 healthy controls were recruited. Field Strength/Sequence Three‐b value DWI (b‐values = 0, 1000, and 2000 sec/mm2) and 3D T1‐weighted images were at 3.0T. Assessment Mean kurtosis (MK), neurite density index (NDI), orientation dispersion index (ODI), fractional anisotropy (FA), and mean diffusivity (MD) were calculated. Statistical Testing The two‐sample t‐test analysis in SPM12 software was used to compare the differences between ME/CFS and control groups. Results In the ME/CFS patients, we observed significant FA decreases in the genu of the corpus callosum and the anterior limb of the right internal capsule (P < 0.05), but no significant difference in MD (P = 0.164); there were also significant MK decreases in the right frontal area, anterior cingulate gyrus, superior longitudinal fasciculus (SLF), and left parietal area (P < 0.05). Significant NDI decreases were observed in the right posterior cingulate gyrus, SLF, and left frontal area of the ME/CFS patients (P < 0.05). Significant ODI decreases were seen in the bilateral occipital areas, right superior temporal gyrus, the anterior limb of internal capsule, and the posterior cingulate gyrus (P < 0.05), and significant ODI increases were revealed in the bilateral occipital and right temporal areas (P < 0.05). Data Conclusion Right SLF abnormalities may be a diagnostic marker for ME/CFS. Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:818–824.

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

Cited by 59 publications

References 40 publications

Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome

Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome

Accuracy of deformable image registration on magnetic resonance images in digital and physical phantoms

Brain abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome: Evaluation by diffusional kurtosis imaging and neurite orientation dispersion and density imaging

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