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Acute ischemic stroke patients benefit from reperfusion in a short time-window after debut. Later treatment may be indicated if viable brain tissue is demonstrated and this outweighs the inherent risks of late reperfusion. Magnetic resonance imaging (MRI) with hyperpolarized [1-13C]pyruvate is an emerging technology that directly images metabolism. Here, we investigated its potential to detect viable tissue in ischemic stroke. Stroke was induced in pigs by intracerebral injection of endothelin 1. During ischemia, the rate constant of pyruvate-to-lactate conversion, kPL, was 52% larger in penumbra and 85% larger in the infarct compared to the contralateral hemisphere (P = 0.0001). Within the penumbra, the kPL was 50% higher in the regions that later infarcted compared to non-progressing regions (P = 0.026). After reperfusion, measures of pyruvate-to-lactate conversion were slightly decreased in the infarct compared to contralateral. In addition to metabolic imaging, we used hyperpolarized pyruvate for perfusion-weighted imaging. This was consistent with conventional imaging for assessment of infarct size and blood flow. Lastly, we confirmed the translatability of simultaneous assessment of metabolism and perfusion with hyperpolarized MRI in healthy volunteers. In conclusion, hyperpolarized [1-13C]pyruvate may aid penumbral characterization and increase access to reperfusion therapy for late presenting patients.

INTRODUCTION: Carotid revascularisation improves haemodynamic compromise in cerebral circulation as an additional benefit to the primary goal of reducing future thromboembolic risk. We determined the effect of carotid artery stenting on cerebral perfusion and oxygenation using a perfusion-weighted MRI algorithm that is based on assessment of capillary transit-time heterogeneity together with other perfusion and metabolism-related metrics. PATIENTS AND METHODS: A consecutive series of 33 patients were evaluated by dynamic susceptibility contrast perfusion-weighted MRI prior to and within 24 h of the endovascular procedure. The level of relative change induced by stenting, and relationship of these changes with respect to baseline stenosis degree were analysed. RESULTS: Stenting led to significant increase in cerebral blood flow (p  2s decreased from 24 ml to 12 ml (p = 0.009), with CTH > 2s from 29 ml to 19 ml (p = 0.041), and with RTH

The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annually. The most common complication of diabetes is peripheral neuropathy, which has a prevalence as high as 50% and is characterized by damage to neurons, Schwann cells and blood vessels within the nerve. The pathogenic mechanisms of diabetic neuropathy remain poorly understood, impeding the development of targeted therapies to treat nerve degeneration and its most disruptive consequences of sensory loss and neuropathic pain. Involvement of Schwann cells has long been proposed, and new research techniques are beginning to unravel a complex interplay between these cells, axons and microvessels that is compromised during the development of diabetic neuropathy. In this Review, we discuss the evolving concept of Schwannopathy as an integral factor in the pathogenesis of diabetic neuropathy, and how disruption of the interactions between Schwann cells, axons and microvessels contribute to the disease.

Hypoparathyroidism (HypoPT) is a disease with no/or inadequate production/secretion of parathyroid hormone (PTH) from the parathyroid glands. Low levels of PTH result in hypocalcemia, which is often treated with calcium supplementation and active vitamin-D analogs. However, increasing evidence suggests that HypoPT has a profound impact on several organ systems. Quality of life (QOL) is reduced in patients with HypoPT, partly due to symptoms related to the central nervous system—including subjective feelings of confusion, a reduced ability to focus and think clearly (ie, "brain fog"). However, the extent to which these complex symptoms relate to quantifiable changes in patients' cognitive performance as determined by neuropsychological tests remains unclear. The brains of HypoPT patients may reveal tissue calcifications, but the extent to which long-term brain exposure to low PTH levels and/or changing calcium levels affects brain structure is unknown. In a cross-sectional study, we investigated PTH levels, QOL, cognitive impairment, and brain structure in well-treated post-surgical and non-surgical hypoparathyroid patients compared with healthy controls. QOL was quantified by the SF36v2, WHO-5 wellbeing Index, and two disease-specific questionnaires—the HPQ28 and Hypoparathyroidism Symptom Diary. Cognitive functions were tested using comprehensive neuropsychological. Brain structure was quantified by morphological analyses of magnetic resonance imaging images. We found reduced QOL and cognitive functioning in terms of processing speed, executive functions, visual memory, and auditory memory in HypoPT. Furthermore, HypoPT revealed a reduced volume of the hippocampus—and the size of the thalamus in postsurgical patients was associated with the disease duration. Importantly, patients reporting severe brain fog had a smaller hippocampus than those with less brainfog. HypoPT is associated with quantifiable cognitive deficits and changes in brain structure that align with patient symptoms. Our exploratory study warrants further studies of the neurobiological impact of PTH and of the impact of PTH replacements therapy on patients' cognitive functioning. Lay Summary: Hypoparathyroidism (HypoPT) is a disease with insufficient or no production of parathyroid hormone (PTH) from the parathyroid glands resulting in low plasma levels of PTH and calcium. One of the reported symptoms and complications of HypoPT is low quality of life (QOL) and mild impaired cognitive function, often described as "brain fog." We have compared patients with HypoPT and healthy controls in regard to QOL, cognitive function, and brain structure. We have used QOL questionnaires, neuropsychological tests, and magnetic resonance imaging (MRI). We found a reduced QOL and cognitive function in patients with HypoPT. Furthermore, MRI showed a difference in brain structure, with a reduced volume of the hippocampus area, especially in those reporting severe symptoms of "brain fog." Disease duration was found to be associated with the size of the thalamus. Our study suggests that there might be an association between HypoPT patients' symptoms of cognitive deficits and changes in brain structure. [ABSTRACT FROM AUTHOR]

Recent studies have shown significant changes to brain microstructure during sleep and anesthesia. In vivo optical microscopy and magnetic resonance imaging (MRI) studies have attributed these changes to anesthesia and sleep‐related modulation of the brain's extracellular space (ECS). Isoflurane anesthesia is widely used in preclinical diffusion MRI (dMRI) and it is therefore important to investigate if the brain's microstructure is affected by anesthesia to an extent detectable with dMRI. Here, we employ diffusion kurtosis imaging (DKI) to assess brain microstructure in the awake and anesthetized mouse brain (n = 22). We find both mean diffusivity (MD) and mean kurtosis (MK) to be significantly decreased in the anesthetized mouse brain compared with the awake state (p < 0.001 for both). This effect is observed in both gray matter and white matter. To further investigate the time course of these changes we introduce a method for time‐resolved fast DKI. With this, we show the time course of the microstructural alterations in mice (n = 5) as they transition between states in an awake‐anesthesia‐awake paradigm. We find that the decrease in MD and MK occurs rapidly after delivery of gas isoflurane anesthesia and that values normalize only slowly when the animals return to the awake state. Finally, time‐resolved fast DKI is employed in an experimental mouse model of brain edema (n = 4), where cell swelling causes the ECS volume to decrease. Our results show that isoflurane affects DKI parameters and metrics of brain microstructure and point to isoflurane causing a reduction in the ECS volume. The demonstrated DKI methods are suitable for in‐bore perturbation studies, for example, for investigating microstructural modulations related to sleep/wake‐dependent functions of the glymphatic system. Importantly, our study shows an effect of isoflurane anesthesia on rodent brain microstructure that has broad relevance to preclinical dMRI. [ABSTRACT FROM AUTHOR]

The pathophysiological development of Alzheimer's disease (AD) begins in the brain years before the onset of clinical symptoms. The accumulation of beta‐amyloid (Aβ) is thought to be the first cortical pathology to occur. Carrying one apolipoprotein E (APOE) ε4 allele increases the risk of developing AD at least 2–3 times and is associated with earlier Aβ accumulation. Although it is difficult to identify Aβ‐related cognitive impairment in early AD with standard cognitive tests, more sensitive memory tests may be able to do this. We sought to examine associations between Aβ and performance on three tests within three subdomains of memory, verbal, visual, and associative memory, to elucidate which of these tests were sensitive to Aβ‐related cognitive impairment in at‐risk subjects. 55 APOE ε4 carriers underwent MRI, 11C‐Pittsburgh Compound B (PiB) PET, and cognitive testing. A composite cortical PiB SUVR cut‐off score of 1.5 was used to categorise subjects as either APOE ε4 Aβ+ or APOE ε4 Aβ−. Correlations were carried out using cortical surface analysis. In the whole APOE ε4 group, we found significant correlations between Aβ load and performance on verbal, visual, and associative memory tests in widespread cortical areas, the strongest association being with performance on associative memory tests. In the APOE ε4 Aβ+ group, we found significant correlations between Aβ load and performance of verbal and associative, but not visual, memory in localised cortical areas. Performance on verbal and associative memory tests provides sensitive markers of early Aβ‐related cognitive impairment in at‐risk subjects. [ABSTRACT FROM AUTHOR]