Spinal cord evaluation in multiple sclerosis: clinical and radiological associations, present and future.

Spinal cord disease is important in most people with multiple sclerosis, but assessment remains less emphasized in patient care, basic and clinical research and therapeutic trials. The North American Imaging in Multiple Sclerosis Spinal Cord Interest Group was formed to determine and present the contemporary landscape of multiple sclerosis spinal cord evaluation, further existing and advanced spinal cord imaging techniques, and foster collaborative work. Important themes arose: (i) multiple sclerosis spinal cord lesions (differential diagnosis, association with clinical course); (ii) spinal cord radiological-pathological associations; (iii) 'critical' spinal cord lesions; (iv) multiple sclerosis topographical model; (v) spinal cord atrophy; and (vi) automated and special imaging techniques.

The use of 7T MRI in multiple sclerosis: review and consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.

The use of ultra-high-field 7-Tesla (7T) MRI in multiple sclerosis (MS) research has grown significantly over the past two decades. With recent regulatory approvals of 7T scanners for clinical use in 2017 and 2020, the use of this technology for routine care is poised to continue to increase in the coming years. In this context, the North American Imaging in MS Cooperative (NAIMS) convened a workshop in February 2023 to review the previous and current use of 7T technology for MS research and potential future research and clinical applications.

Serum glial fibrillary acidic protein as a marker of brain MRI metrics in multiple sclerosis: A scoping review.

Background And Purpose: Magnetic resonance imaging (MRI) is heavily relied upon for the diagnosis and monitoring of multiple sclerosis (MS), a chronic, demyelinating disease of the central nervous system. Serum biomarkers may serve as an accessible tool for increasing sensitivity, improving accessibility, corroborating symptoms, and providing additional data to guide clinical management. This scoping review investigates the current understanding of how the serum biomarker glial fibrillary acidic protein (sGFAP) relates to brain MRI metrics.

The myelin water imaging transcriptome: myelin water fraction regionally varies with oligodendrocyte-specific gene expression.

Identifying sensitive and specific measures that can quantify myelin are instrumental in characterizing microstructural changes in neurological conditions. Neuroimaging transcriptomics is emerging as a valuable technique in this regard, offering insights into the molecular basis of promising candidates for myelin quantification, such as myelin water fraction (MWF). We aimed to demonstrate the utility of neuroimaging transcriptomics by validating MWF as a myelin measure.

Stress integration by an ascending adrenergic-melanocortin circuit.

Stress is thought to be an important contributing factor for eating disorders; however, neural substrates underlying the complex relationship between stress and appetite are not fully understood. Using in vivo recordings from awake behaving mice, we show that various acute stressors activate catecholaminergic nucleus tractus solitarius (NTS) projections in the paraventricular hypothalamus (PVH). Remarkably, the resulting adrenergic tone inhibits MC4R-expressing neurons (PVH), which are known for their role in feeding suppression.

Advanced Magnetic Resonance Imaging Biomarkers of the Injured Spinal Cord: A Comparative Study of Imaging and Histology in Human Traumatic Spinal Cord Injury.

A significant problem in the diagnosis and management of traumatic spinal cord injury (tSCI) is the heterogeneity of secondary injury and the prediction of neurological outcome. Imaging biomarkers specific to myelin loss and inflammation after tSCI would enable detailed assessment of the pathophysiological processes underpinning secondary damage to the cord. Such biomarkers could be used to biologically stratify injury severity and better inform prognosis for neurological recovery.

Imaging chronic active lesions in multiple sclerosis: a consensus statement.

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis and have implications for non-relapsing biological progression. In recent years, the discovery of innovative MRI and PET-derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with multiple sclerosis, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted and T2-weighted scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL.

POMC Neuron BBSome Regulation of Body Weight is Independent of its Ciliary Function.

The BBSome, a complex of several Bardet-Biedl syndrome (BBS) proteins including BBS1, has emerged as a critical regulator of energy homeostasis. Although the BBSome is best known for its involvement in cilia trafficking, through a process that involve BBS3, it also regulates the localization of cell membrane receptors underlying metabolic regulation. Here, we show that inducible gene deletion selectively in proopiomelanocortin (POMC) neurons cause a gradual increase in body weight, which was associated with higher fat mass.

Opioidergic signaling contributes to food-mediated suppression of AgRP neurons.

Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR).

AgRP neurons encode circadian feeding time.

Food intake follows a predictable daily pattern and synchronizes metabolic rhythms. Neurons expressing agouti-related protein (AgRP) read out physiological energetic state and elicit feeding, but the regulation of these neurons across daily timescales is poorly understood. Using a combination of neuron dynamics measurements and timed optogenetic activation in mice, we show that daily AgRP-neuron activity was not fully consistent with existing models of homeostatic regulation.

The CALIPR framework for highly accelerated myelin water imaging with improved precision and sensitivity.

Quantitative magnetic resonance imaging (MRI) techniques are powerful tools for the study of human tissue, but, in practice, their utility has been limited by lengthy acquisition times. Here, we introduce the Constrained, Adaptive, Low-dimensional, Intrinsically Precise Reconstruction (CALIPR) framework in the context of myelin water imaging (MWI); a quantitative MRI technique generally regarded as the most rigorous approach for noninvasive, in vivo measurement of myelin content. The CALIPR framework exploits data redundancy to recover high-quality images from a small fraction of an imaging dataset, which allowed MWI to be acquired with a previously unattainable sequence (fully sampled acquisition 2 hours:57 min:20 s) in 7 min:26 s (4.

Adrenergic modulation of melanocortin pathway by hunger signals.

Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access.

Hunger potentiated.

Dieting often fails in the long run becuase of an ever-growing urge to eat. In this issue of Cell Metabolism, Grzelka et al. unveil a brain circuit that is potentiated during caloric restriction and incites rebound increases in food consumption and body weight.

Nonaqueous magnetization following adiabatic and selective pulses in brain: T1 and cross-relaxation dynamics.

Inversion pulses are commonly employed in MRI for -weighted contrast and relaxation measurements. In the brain, it is often assumed that adiabatic pulses saturate the nonaqueous magnetization. We investigated this assumption using solid-state NMR to monitor the nonaqueous signal directly following adiabatic inversion and compared this with signals following hard and soft inversion pulses.

Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits.

Objective: Serotonin (5HT) is a well-known anorexigenic molecule, and 5HT neurons of dorsal raphe nucleus (DRN) have been implicated in suppression of feeding; however, the downstream circuitry is poorly understood. Here we explored major projections of DRN neurons for their capacity to modulate feeding.

Methods: We used optogenetics to selectively activate DRN axonal projections in hypothalamic and extrahypothalamic areas and monitored food intake.

Myelin biomarkers in the healthy adult brain: Correlation, reproducibility, and the effect of fiber orientation.

Purpose: We investigated the correlation, reproducibility, and effect of white matter fiber orientation for three myelin-sensitive MRI techniques: magnetization transfer ratio (MTR), inhomogeneous magnetization transfer ratio (ihMTR), and gradient and spin echo-derived myelin water fraction (MWF).

Methods: We measured the three metrics in 17 white and three deep grey matter regions in 17 healthy adults at 3 T.

Results: We found a strong correlation between ihMTR and MTR (r = 0.

Myelin heterogeneity for assessing normal appearing white matter myelin damage in multiple sclerosis.

Background And Purpose: Conventional MRI measures of multiple sclerosis (MS) disease severity, such as lesion volume and brain atrophy, do not provide information about microstructural tissue changes, which may be driving physical and cognitive progression. Myelin damage in normal-appearing white matter (NAWM) is likely an important contributor to MS disability. Myelin water fraction (MWF) provides quantitative measurements of myelin.

A pilot study comparing myelin measurements from myelin water imaging and C-PIB PET in multiple sclerosis.

MRI-based myelin water fraction (MWF) and PET-based Pittsburgh compound B (PiB) imaging both have potential to measure myelin in multiple sclerosis (MS). We characterised the differences in MWF and PiB binding in MS lesions relative to normal-appearing white matter and assessed the correlation between MWF and PiB binding in 11 MS participants and 3 healthy controls within 14 white matter regions of interest. Both PiB binding and MWF were reduced in MS lesions relative to NAWM, and a modest within subject correlation between MWF and PiB binding was found.

Critical Role for Macrophages in the Developmental Programming of Pancreatic β-Cell Area in Offspring of Hypertensive Pregnancies.

Preeclampsia is a pregnancy-specific complication with long-term negative outcomes for offspring, including increased susceptibility to type 2 diabetes (T2D) in adulthood. In a rat reduced uteroplacental perfusion pressure (RUPP) model of chronic placental ischemia, maternal hypertension in conjunction with intrauterine growth restriction mimicked aspects of preeclampsia and resulted in female embryonic day 19 (e19) offspring with reduced β-cell area and increased β-cell apoptosis compared with offspring of sham pregnancies. Decreased pancreatic β-cell area persisted to postnatal day 13 (PD13) in females and could influence whether T2D developed in adulthood.

Myelin Content and Gait Impairment in Older Adults with Cerebral Small Vessel Disease and Mild Cognitive Impairment.

We investigated whether myelin is associated with gait parameters in older adults with cerebral small vessel disease (cSVD). Cross-sectional data from sixty-four participants with cSVD and mild cognitive impairment were analyzed. Myelin was assessed via MRI multi-echo gradient and spin echo T relaxation sequence, indexed as myelin water fraction (MWF).

Myelin water imaging in relapsing multiple sclerosis treated with ocrelizumab and interferon beta-1a.

Background: Myelin water imaging is a magnetic resonance imaging (MRI) technique that quantifies myelin damage and repair in multiple sclerosis (MS) via the myelin water fraction (MWF).

Objective: In this substudy of a phase 3 therapeutic trial, OPERA II, MWF was assessed in relapsing MS participants assigned to interferon beta-1a (IFNb-1a) or ocrelizumab (OCR) during a two-year double-blind period (DBP) followed by a two-year open label extension (OLE) with ocrelizumab treatment.

Methods: MWF in normal appearing white matter (NAWM), including both whole brain NAWM and 5 white matter structures, and chronic lesions, was assessed in 29 OCR and 26 IFNb-1a treated participants at weeks 0, 24, 48 and 96 (DBP), and weeks 144 and 192 (OLE), and in white matter for 23 healthy control participants at weeks 0, 48 and 96.

Myelin and Physical Activity in Older Adults With Cerebral Small Vessel Disease and Mild Cognitive Impairment.

Background: Myelin loss is a feature of cerebral small vessel disease (cSVD). Although physical activity levels may exert protective effects over cSVD pathology, its specific relationship with myelin content in people living with the cSVD is unknown. Thus, we investigated whether physical activity levels are associated with myelin in community-dwelling older adults with cSVD and mild cognitive impairment.