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We present a novel high-field optical quantum magnetometer based on saturated absorption spectroscopy on the extreme angular-momentum states of the cesium D2 line. With key features including continuous readout, high sampling rate, and sensitivity and accuracy in the ppm range, it represents a competitive alternative to conventional techniques for measuring magnetic fields of several teslas. The prototype has four small separate field probes, and all support electronics and optics are fitted into a single 19-inch rack to make it compact, mobile, and robust. The field probes are fiber coupled and made from nonmetallic components, allowing them to be easily and safely positioned inside a 7 T MRI scanner. We demonstrate the capabilities of this magnetometer by measuring two different MRI sequences, and we show how it can be used to reveal imperfections in the gradient coil system, to highlight the potential applications in medical MRI. We propose the term EXAAQ (EXtreme Angular-momentum Absorption-spectroscopy Quantum) magnetometry, for this novel method.

Creatine transporter deficiency (CTD), caused by pathogenic variants in SLC6A8, is the second most common cause of X-linked intellectual disability. Symptoms include intellectual disability, epilepsy, and behavioral disorders and are caused by reduced cerebral creatine levels. Targeted treatment with oral supplementation is available, however the treatment efficacy is still being investigated. There are clinical and theoretical indications that heterozygous females with CTD respond better to supplementation treatment than hemizygous males. Unfortunately, heterozygous females with CTD often have more subtle and uncharacteristic clinical and biochemical phenotypes, rendering diagnosis more difficult. We report a new female case who presented with learning disabilities and seizures. After determining the diagnosis with molecular genetic testing confirmed by proton magnetic resonance spectroscopy (1H-MRS), the patient was treated with supplementation treatment including creatine, arginine, and glycine. After 28 months of treatment, the patient showed prominent clinical improvement and increased creatine levels in the brain. Furthermore, we provide a review of the 32 female cases reported in the current literature including a description of phenotypes, genotypes, diagnostic approaches, and effects of supplementation treatment. Based on this, we find that supplementation treatment should be tested in heterozygous female patients with CTD, and a prospective treatment underlines the importance of diagnosing these patients. The diagnosis should be suspected in a broad clinical spectrum of female patients and can only be made by molecular genetic testing. 1H-MRS of cerebral creatine levels is essential for establishing the diagnosis in females, and especially valuable when assessing variants of unknown significance.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population.METHODS: Cross-sectional study including patients with type 2 diabetes with CKD stages 3-5 (N = 50) or without CKD (N = 50). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 with or without proteinuria. Three methods were used to detect significant liver fibrosis defined as either ≥8 kilopascal measured by transient elastography (FibroScan®), fibrosis-4 (FIB-4) score ≥2.67, or NAFLD fibrosis score (NFS) >0.675.RESULTS: Significant liver fibrosis was found in 38% and 28% of the patients with and without CKD, respectively, using at least one of the three methods. Both FIB-4 score and NFS were significantly higher in patients with CKD (p < 0.0009 and p < 0.0001, respectively), although insignificant after adjustments for age, sex, body mass index, and duration of diabetes. In patients without CKD, a significant association between steatosis and fibrosis was observed (p = 0.0007).CONCLUSION: Our data do not support any strong independent association between liver fibrosis and established CKD as assessed by FibroScan, FIB-4 score, and NFS, respectively.

Background: Nonalcoholic fatty liver disease (NAFLD) is suggested as a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally in parallel to the increasing incidences of obesity and type 2 diabetes. Diabetes remains the leading cause of CKD, but the co-existence of NAFLD, CKD, and type 2 diabetes is not well elucidated. Here, we evaluated the prevalence of NAFLD in patients with type 2 diabetes with and without CKD. Methods: This was a cross-sectional study including 50 patients with type 2 diabetes and CKD stages 3-5 (no dialysis), and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy and magnetic resonance imaging proton density fat fraction. NAFLD was defined as liver fat fraction >= 5.6% according to guidelines. Results: Mean age was 72 +/- 4.9 years in patients with CKD and 65.9 +/- 7.8 years in patients without CKD (p < 0.0001). Three out of four participants were men. BMI was 28.6 +/- 3.5 kg/m(2) and 27 +/- 4.0 kg/m(2) in patients with and without CKD, respectively (p = 0.0087). NAFLD was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (p = 0.6845). Median (IQR) liver fat fraction was 4.7% (3.0-8.5) and 4.1% (2.9-7.7) in patients with and without CKD, respectively (difference in geometric means 5.3%, 95% CI -23; 45, p = 0.7463). Conclusion: These findings do not support any association between NAFLD and CKD (stages 3-5) in patients with type 2 diabetes.

Type 2 diabetes causes substantial long-term damage in several organs including the brain. Cognitive decline is receiving increased attention as diabetes has been established as an independent risk factor along with the identification of several other pathophysiological mechanisms. Early detection of detrimental changes in cerebral blood flow regulation may represent a useful clinical marker for development of cognitive decline for at-risk persons. Technically, reliable evaluation of neurovascular coupling is possible with several caveats but needs further development before it is clinically convenient. Different modalities including ultrasound, positron emission tomography and magnetic resonance are used preclinically to shed light on the many influences on vascular supply to the brain. In this narrative review, we focus on the complex link between type 2 diabetes, cognition, and neurovascular coupling and discuss how the disease-related pathology changes neurovascular coupling in the brain from the organ to the cellular level. Different modalities and their respective pitfalls are covered, and future directions suggested.

Type 2 diabetes causes substantial long-term damage in several organs including the brain. Cognitive decline is receiving increased attention as diabetes has been established as an independent risk factor along with the identification of several other pathophysiological mechanisms. Early detection of detrimental changes in cerebral blood flow regulation may represent a useful clinical marker for development of cognitive decline for at-risk persons. Technically, reliable evaluation of neurovascular coupling is possible with several caveats but needs further development before it is clinically convenient. Different modalities including ultrasound, positron emission tomography and magnetic resonance are used preclinically to shed light on the many influences on vascular supply to the brain. In this narrative review, we focus on the complex link between type 2 diabetes, cognition, and neurovascular coupling and discuss how the disease-related pathology changes neurovascular coupling in the brain from the organ to the cellular level. Different modalities and their respective pitfalls are covered, and future directions suggested.

Proton MR spectroscopy (1H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field, we performed 1H-MRS in 60 healthy human volunteers to asses age-related differences in metabolite levels and their relation to cognitive ageing. Sex was balanced, and participants were assigned to a younger, middle, and older group according to their age, ranging from 18 to 79 years. They underwent 7T 1H-MRS of the ACC, DLPFC, hippocampus, and thalamus and performed a visuospatial working memory task outside the scanner. A multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all regions. Higher levels in the middle than the younger group were observed for myo-inositol (mIns) in DLPFC and hippocampus and total choline (tCho) in ACC. Higher levels in the older than the younger group were observed for mIns in hippocampus and thalamus, total creatine (tCr) and tCho in ACC and hippocampus; lower levels of glutamate (Glu) were observed in DLPFC. Higher levels in the older than the middle group were observed for mIns in hippocampus, tCr in ACC and hippocampus, tCho in hippocampus, and total N-acetyl aspartate (tNAA) in hippocampus. Working memory performance correlated negatively with tCr and tCho levels in ACC and mIns levels in hippocampus and thalamus, but not with tNAA or glutamate levels. As NAA and Glu are commonly regarded to reflect neuronal health and function and concentrations of mIns, tCr, and tCho are higher in glia than neurons, the findings of this study suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. SIGNIFICANCE STATEMENT Neurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy (1H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. 1H-MRS at ultr

Proton MR spectroscopy (1H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field, we performed 1H-MRS in 60 healthy human volunteers to asses age-related differences in metabolite levels and their relation to cognitive ageing. Sex was balanced, and participants were assigned to a younger, middle, and older group according to their age, ranging from 18 to 79 years. They underwent 7T 1H-MRS of the ACC, DLPFC, hippocampus, and thalamus and performed a visuospatial working memory task outside the scanner. A multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all regions. Higher levels in the middle than the younger group were observed for myo-inositol (mIns) in DLPFC and hippocampus and total choline (tCho) in ACC. Higher levels in the older than the younger group were observed for mIns in hippocampus and thalamus, total creatine (tCr) and tCho in ACC and hippocampus; lower levels of glutamate (Glu) were observed in DLPFC. Higher levels in the older than the middle group were observed for mIns in hippocampus, tCr in ACC and hippocampus, tCho in hippocampus, and total N-acetyl aspartate (tNAA) in hippocampus. Working memory performance correlated negatively with tCr and tCho levels in ACC and mIns levels in hippocampus and thalamus, but not with tNAA or glutamate levels. As NAA and Glu are commonly regarded to reflect neuronal health and function and concentrations of mIns, tCr, and tCho are higher in glia than neurons, the findings of this study suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites.SIGNIFICANCE STATEMENT Neurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy (1H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. 1H-MRS at ul

Background: Sildenafil and calcitonin gene-related peptide are vasoactive substances that induce migraine attacks in patients. The intradural arteries are thought to be involved, but these have never been examined in vivo. Sildenafil is the only migraine-inducing compound for which cephalic, extracranial artery dilation is not reported. Here, we investigate the effects of sildenafil and calcitonin gene-related peptide on the extracranial and intradural parts of the middle meningeal artery. Methods: In a double-blind, randomized, three-way crossover, placebo-controlled head-to-head comparison study, MR-angiography was recorded in healthy volunteers at baseline and twice after study drug (sildenafil/ calcitonin gene-related peptide/saline) administration. Circumferences of extracranial and intradural middle meningeal artery segments were measured using semi-automated analysis software. The area under the curve for circumference change was compared using paired t-tests between study days. Results: Twelve healthy volunteers completed the study. The area under the curve Baseline-120min was significantly larger on both the sildenafil and the calcitonin gene-related peptide day in the intradural middle meningeal artery (calcitonin gene-related peptide, p = 0.013; sildenafil, p = 0.027) and the extracranial middle meningeal artery (calcitonin gene-related peptide, p = 0.0003; sildenafil, p = 0.021), compared to placebo. Peak intradural middle meningeal artery dilation was 9.9% (95% CI [2.9–16.9]) after sildenafil (T 30min ) and 12.5% (95% CI [8.1–16.8]) after calcitonin gene-related peptide (T 30min ). Peak dilation of the extracranial middle meningeal artery after calcitonin gene-related peptide (T 30min ) was 15.7% (95% CI [11.2–20.1]) and 18.9% (95% CI [12.8–24.9]) after sildenafil (T 120min ). Conclusion: An important novel finding is that both sildenafil and calcitonin gene-related peptide dilate intradural art

Background: Sildenafil and calcitonin gene-related peptide both dilate the intradural segments of the middle meningeal artery measured with 3.0 tesla (T) MR angiography. Here we hypothesized that an increase in field strength to 7.0 T and concomitant enhanced voxel resolution would lower variance in measurements of dilation in the intradural middle meningeal artery. Methods: Five subjects completed two sessions at respectively 3.0 T and 7.0 T. Each session comprised MR angiography scans once before and twice after administration of sildenafil, calcitonin gene-related peptide or placebo in a three-way, crossover, double-blind, placebo-controlled design. Results: Standard deviations of arterial circumference revealed no difference between 3.0 T and 7.0 T measurements (p = 0.379). We found a decrease in standard deviation from our original angiography analysis software (QMra) to a newer (LAVA) software package (p < 0.001). Furthermore, we found that the dilation after sildenafil and calcitonin gene-related peptide were comparable between 3.0 T and 7.0 T. Conclusions: Our findings suggest no gain from the increase in voxel resolution but cemented dilatory findings from earlier. The implemented software update improved variance in circumference measurements in the intradural middle meningeal artery, which should be exploited in future studies. Trial registration: The study is part of a parent study, which is registered at ClinicalTrials.gov (NCT03143465).