Colin D. McKnight

The lumbosacral enlargement (LSE) of the spinal cord is understudied in people with multiple sclerosis (pwMS), and there is not a consensus on the impact of age, sex, height, or weight on MRI-derived morphometrics in this region. The LSE is relevant to study in pwMS as it is involved in the control of motor and sensory functions of the lower limbs and autonomic functions which are commonly affected in MS. This study aimed to characterize biological variability of morphometric measures of the LSE cord and gray matter in healthy controls (HCs), compare these measures between HCs and people with relapsing-remitting MS (pwRRMS), and assess correlations between morphometrics and lower-extremity disability and bladder symptoms in pwRRMS. An optimized T2*-weighted, axial multi-echo gradient echo anatomical MRI scan was acquired at 3T, images were automatically segmented, and whole-cord and gray matter cross-sectional areas for the lumbosacral spinal levels of 60 HCs and 42 pwRRMS were computed. We observed no significant main effects of age, height, weight, or sex on LSE whole-cord or gray matter cross-sectional areas (CSA) in HCs, but there were spinal level interactions with age and weight. We detected whole-cord and gray matter atrophy in the LSE of pwRRMS compared to HCs, and the effects of disease status on these measures were partially mitigated when controlling for MS lesion to cord CSA ratio within the LSE. There were no significant associations between LSE cross-sectional area measures and sensorimotor function, bladder symptoms, or clinical disability scores. However, vibration sensation in the great toe and Expanded Disability Status Scale (EDSS) scores were significantly associated with lesion to cord CSA ratio. Overall, this study found that there is little variability linked to age, sex, height, or weight in cross-sectional area measures for the healthy lumbosacral spinal cord, and lesions and atrophy were both detected in these spinal levels for a pwRRMS cohort. Although there were no associations between atrophy and symptoms, potentially due to the relatively low level of clinical disability in this cohort, these findings support the inclusion of the LSE in future imaging studies that aim to probe the full extent of spinal cord pathology in MS.

Neurofluids, including cerebrospinal fluid (CSF) and interstitial fluid, circulate through regulated central nervous system pathways to clear cerebral waste and support brain health, with elevated CSF flow hyperdynamicity and regurgitation through the cerebral aqueduct associating with aging and neurodegeneration. Sleep exerts state-dependent effects on neurofluid circulation, yet similar modulation during unique waking states, such as meditation, remains underexplored. Notably, mindfulness meditation shares several regulatory features with sleep, with core meditation practices representing distinct arousal states. We investigated whether the focused attention (FA) style of mindfulness meditation modulates neurofluid dynamics directionally opposite to aging and consistent with sleep. Using phase-contrast MRI, we assessed absolute CSF flow and velocity through the aqueduct, and using blood oxygenation level–dependent (BOLD) MRI, we assessed CSF fluctuations near the cervicomedullary junction together with total supratentorial gray matter fluctuations. Assessments were repeated in meditation-naïve adults during mind wandering (MW) without (n = 13; repeatability controls) and with (n = 14; breath controls) respiration rate modulation and in adept meditators (n = 23) during MW and FA meditation. No aqueduct CSF flow changes were observed in control groups. In meditators, aqueduct absolute CSF flow motion decreased from MW to FA meditation (4.60 ± 2.27 mL/min to 4.17 ± 2.10 mL/min, P = 0.005) owing to reduced regurgitant cranially directed CSF flow velocity. On BOLD, this paralleled increased low-frequency (0.0614 to 0.0887 Hz) CSF fluctuations ( P = 0.0138), which were inversely correlated with gray matter fluctuations during FA meditation. Findings suggest that mindfulness meditation may represent a nonpharmacological, waking state capable of modulating neurofluid dynamics in a directionally similar manner to sleep and opposite to aging and neurodegeneration.

Background: There is limited knowledge on the post-glymphatic structures such as the parasagittal dural (PSD) space and the arachnoid granulations (AGs) in multiple sclerosis (MS). Objectives: To evaluate differences in volume and macromolecular content of PSD and AG between people with newly diagnosed MS (pwMS), clinically isolated syndrome (pwCIS), or radiologically isolated syndrome (pwRIS) and healthy controls (HCs) and their associations with clinical and radiological disease measures. Methods: A total of 69 pwMS, pwCIS, pwRIS, and HCs underwent a 3.0 Tesla magnetic resonance imaging (MRI) including selective inversion recovery quantitative magnetization transfer imaging to compute the macromolecular-to-free water pool-size-ratio (PSR) and the free water relaxation rate (R _1f ), T ₂ -weighted (T ₂ -w) volumetric isotropic turbo-spin-echo to segment the PSD and AG, T ₂ -w fluid-attenuated inversion recovery images to compute T ₂ -lesions burden, and a T ₁ -w sequence to quantify chronic black holes (cBHs) burden and brain parenchymal fraction. Results: After adjusting for age and sex, larger frontal ( p = 0.006) and parietal ( p = 0.047) PSD volumes along with larger parietal AG volumes ( p = 0.033) were measured in patients compared to HCs. Parietal PSD volume correlated with cBH PSR ( r = −0.430, p = 0.032). Conclusion: Upon diagnosis, enlarged structures in the post-glymphatic system may be observed, indicating a need for further investigation of their role.

Intravenous arachnoid granulations (AGs) are protrusions of the arachnoid membrane into the venous lumen and function as contributors to the cerebrospinal fluid (CSF) flow circuit. Patients with Parkinson disease (PD) often present with accumulation of alpha synuclein. Previous works have provided evidence for neurofluid circulation dysfunction in neurodegenerative diseases associated with changes in CSF egress, which may have implications regarding AG morphology. The present study aims to investigate group differences in AG volumetrics between healthy and PD participants, as well as relationships between AG characteristics and clinical assessments. Generalized linear models revealed significant increases in AG volumetrics and number in PD compared to healthy controls. Partial Spearman-rank correlation analyses demonstrated significant relationships between AG metrics and motor and cognitive assessments. Finally, AG volumetrics were positively correlated with objective actigraphy measures of sleep dysfunction, but not self-report sleep symptoms.

Background: Imaging investigation of cerebrospinal fluid (CSF) in multiple sclerosis (MS) is understudied. Development of noninvasive methods to detect pathological CSF changes would have a profound effect on MS diagnosis and would offer insight into MS pathophysiology and mechanisms of neurological impairment. Objective: We propose magnetization transfer (MT) MRI as a tool to detect macromolecular changes in spinal CSF. Methods: MT and quantitative MT (qMT) data were acquired in the cervical region in 27 people with relapsing-remitting multiple sclerosis (pwRRMS) and 38 age and sex-matched healthy controls (HCs). MT ratio (MTR), the B₁, B₀, and R₁ corrected qMT-derived pool size ratio (PSR) were quantified in the spinal cord and CSF of each group. Results: Both CSF MTR and CSF qMT-derived PSR were significantly increased in pwRRMS compared to HC ( p = 0.027 and p = 0.020, respectively). CSF PSR of pwRRMS was correlated to Expanded Disability Status Scale Scores ( p = 0.045, R = 0.352). Conclusion: Our findings demonstrate increased CSF macromolecular content in pwRRMS and link CSF macromolecular content with clinical impairment. This highlights the potential role of CSF in processing products of demyelination.

One of the pathological hallmarks of Alzheimer’s and related diseases is the increased accumulation of protein amyloid-β in the brain parenchyma. As such, recent studies have focused on characterizing protein and related clearance pathways involving perivascular flow of neurofluids, but human studies of these pathways are limited owing to limited methods for evaluating neurofluid circulation non-invasively in vivo. Here, we utilize non-invasive MRI methods to explore surrogate measures of CSF production, bulk flow, and egress in the context of independent PET measures of amyloid-β accumulation in older adults. Participants (N = 23) were scanned at 3.0T with 3D T₂-weighted turbo spin echo, 2D perfusion-weighted pseudo-continuous arterial spin labeling, and phase contrast angiography to quantify parasagittal dural space volume, choroid plexus perfusion, and net CSF flow through the aqueduct of Sylvius respectively. All participants also underwent dynamic PET imaging with amyloid-β tracer ¹¹C-Pittsburgh Compound B to quantify global cerebral amyloid-β accumulation. Spearman’s correlation analyses revealed a significant relationship between global amyloid-β accumulation and parasagittal dural space volume (rho = 0.529, p = 0.010), specifically in the frontal (rho = 0.527, p = 0.010), and parietal (rho = 0.616, p = 0.002) subsegments. No relationships were observed between amyloid-β and choroid plexus perfusion nor net CSF flow. Findings suggest that parasagittal dural space hypertrophy, and its possible role in CSF-mediated clearance, may be closely related to global amyloid-β accumulation. These findings are discussed in the context of our growing understanding of the physiological mechanisms of amyloid-β aggregation and clearance via neurofluids.

Supplementary Figure from Selective Cell Size MRI Differentiates Brain Tumors from Radiation Necrosis

Supplementary Figure from Selective Cell Size MRI Differentiates Brain Tumors from Radiation Necrosis

Supplementary Figure from Selective Cell Size MRI Differentiates Brain Tumors from Radiation Necrosis