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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

Glutamate detection in pons and thalamus using proton magnetic resonance spectroscopy (1H-MRS) after an intervention is of interest for studying various brain disorders. However, 1H-MRS in these brain regions is challenging and time-consuming, especially in longitudinal study designs. 1H-MRS of more cortical structures at the ultrahigh magnetic field strength of 7T yields an improved spectral output, including separation of the glutamate signal from the glutamine signal, in a shorter and more feasible scan time, as compared to conventional clinical field strengths. For this purpose, we compared the feasibility of 1H-MRS at 3T and 7T in pons and thalamus by applying a longitudinal study design of repeated measures on same day and three separate days at both field strength in five healthy participants. Total 1H-MRS acquisition time was reduced by a factor 3.75 for pons and by a factor 3 for thalamus at 7T as compared to 3T. We found higher spectral signal-to-noise ratio (SNR) (p <0.001), lower linewidth (p = 0.001) and lower Cramér–Rao lower bounds (CRLB) (p <0.001) for the combined glutamate and glutamine signal (Glx) in thalamus at 7T as compared to 3T. In pons, CRLB of Glx and SNR were lower at 7T (p = 0.002 and p = 0.006), with no differences in linewidth compared to 3T. Mean within-subject variability of Glx concentration estimates was lower at 7T compared to 3T for both pons and thalamus. At 7T, it was possible to assess glutamate and γ-aminobutyric acid (GABA) simultaneously in pons and thalamus. In conclusion, 1H-MRS at 7T resulted in improved spectral quality while allowing shorter scan times than at 3T as well as estimation of the pure glutamate signal in pons and thalamus. This opens up the opportunity for multimodal study designs and multiregional subcortical 1H-MRS research. Glutamate and GABA measurement at 7T in pons and thalamus is adva

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).

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 7.0T 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 3.0T and 7.0T. 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 3.0T and 7.0T 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= 0.379). We found a decrease in standard deviation from our original angiography analysissoftware (QMra) to a newer (LAVA) software package (p < 0.001). Furthermore, we found that the dilation aftersildenafil 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 findingsfrom earlier. The implemented software update improved variance in circumference measurements in the intraduralmiddle meningeal artery, which should be exploited in future studies.

Introduction: Subject movements lead to severe artifacts in magnetic resonance (MR) brain imaging. In this study we evaluate the diagnostic image quality in T1-weighted, T2-weighted, and time-of-flight angiographic MR sequences when using a flexible, navigator-based prospective motion correction system (iMOCO). Methods: Five healthy volunteers were scanned during different movement scenarios with and without (+/-) iMOCO activated. An experienced neuroradiologist graded images for image quality criteria (grey-white-matter discrimination, basal ganglia, and small structure and vessel delineation), and general image quality on a four-grade scale. Results: In scans with deliberate motion, there was a significant improvement in the image quality with iMOCO compared to the scans without iMOCO in both general image impression (T1 pp<0.01, T2 p<0.01, TOF p = 0.03) and in anatomical grading (T1 p<0.01, T2 p<0.01, TOF p= 0.01). Subjective image quality was considered non-diagnostic in 91% of the scans with motion -iMOCO, but only in 4% of the scans with motion +iMOCO. iMOCO performed bestin the T1-weighted sequence and least well in the angiography sequence. iMOCO was not shown to have any negative effect on diagnostic image quality, as no significant difference in diagnostic quality was seen between scans -iMOCO and +iMOCO with no deliberate movement. Conclusion: The evaluation showed that iMOCO enables substantial improvements in image quality in scans affected by subject movement, recovering important diagnostic information in an otherwise unusable scan.