Stuart Clare

We present the reliability of ultra-high field T ₂ * MRI at 7T, as part of the UK7T Network’s “Travelling Heads” study. T ₂ *-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R ₂ * maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R ₂ * mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5 - 3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R ₂ * mapping at 7T, in readiness for future multi-site clinical studies. Methods: Ten healthy volunteers were scanned with harmonised single- and multi-echo T ₂ *-weighted gradient echo pulse sequences. Participants were scanned five times at each “home” site and once at each of four other sites. The five sites had 1x Philips, 2x Siemens Magnetom, and 2x Siemens Terra scanners. QSM and R ₂ * maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm ( https://github.com/fil-physics/Publication-Code ). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. Results and Discussion: Mean susceptibility (χ) and R ₂ * values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001 – 0.005 ppm (χ) and 0.0005 – 0.001 ms ^-1 (R ₂ *). For χ this is 2.1-4.8 fold better than 3T reports, and 1.1-3.4 fold better for R ₂ *. The median ICC from within- and cross-site R ₂ * data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B ₀ inhomogeneity such as the inferior frontal cortex. Across sites, R ₂ * values were more consistent than QSM in subcortical structures due to differences in B ₀ -shimming. On a between-subject level, our measured χ and R ₂ * cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. Conclusion: The harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R ₂ * at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acids, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional ¹H MRS-detectable differences between IDH1 and IDH2 mutations, and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 37 ± 11, 13 males) were recruited for magnetic resonance spectroscopy (MRS) using semi-localization by adiabatic selective refocusing pulse sequence at an ultra-high-field (7T). For 20 patients, the tumor mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n = 15) and IDH2 (n = 5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.48 ± 1.01vs.0.72 ± 0.38, P_c < 0.001) and myo-Inositol/tCho (2.70 ± 0.90 vs. 1.46 ± 0.51, P_c = 0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show the improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine.

Purpose: In typical MRI protocols, time is spent acquiring a field map to calculate the shim settings for best image quality. We propose a fast template‐based field map prediction method that yields near‐optimal shims without measuring the field.Methods: The template‐based prediction method uses prior knowledge of the B₀ distribution in the human brain, based on a large database of field maps acquired from different subjects, together with subject‐specific structural information from a quick localizer scan. The shimming performance of using the template‐based prediction is evaluated in comparison to a range of potential fast shimming methods.Results: Static B₀ shimming based on predicted field maps performed almost as well as shimming based on individually measured field maps. In experimental evaluations at 7 T, the proposed approach yielded a residual field standard deviation in the brain of on average 59 Hz, compared with 50 Hz using measured field maps and 176 Hz using no subject‐specific shim.Conclusions: This work demonstrates that shimming based on predicted field maps is feasible. The field map prediction accuracy could potentially be further improved by generating the template from a subset of subjects, based on parameters such as head rotation and body mass index. Magn Reson Med 80:171–180, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Mutations in the isocitrate dehydrogenase genes (IDH1/2) occur often in diffuse gliomas, where they are associated with abnormal accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). Monitoring 2-HG levels could provide prognostic information in this disease, but detection strategies that are noninvasive and sufficiently quantitative have yet to be developed. In this study, we address this need by presenting a proton magnetic resonance spectroscopy (¹H-MRS) acquisition scheme that uses an ultrahigh magnetic field (≥7T) capable of noninvasively detecting 2-HG with quantitative measurements sufficient to differentiate mutant cytosolic IDH1 and mitochondrial IDH2 in human brain tumors. Untargeted metabolomics analysis of in vivo ¹H-MRS spectra discriminated between IDH-mutant tumors and healthy tissue, and separated IDH1 from IDH2 mutations. High-quality spectra enabled the quantification of neurochemical profiles consisting of at least eight metabolites, including 2-HG, glutamate, lactate, and glutathione in both tumor and healthy tissue voxels. Notably, IDH2 mutation produced more 2-HG than IDH1 mutation, consistent with previous findings in cell culture. By offering enhanced sensitivity and specificity, this scheme can quantitatively detect 2-HG and associated metabolites that may accumulate during tumor progression, with implications to better monitor patient responses to therapy. Cancer Res; 76(1); 43–49. ©2015 AACR.

The Whitehall II (WHII) study of British civil servants provides a unique source of longitudinal data to investigate key factors hypothesized to affect brain health and cognitive ageing. This paper introduces the multi-modal magnetic resonance imaging (MRI) protocol and cognitive assessment designed to investigate brain health in a random sample of 800 members of the WHII study. A total of 6035 civil servants participated in the WHII Phase 11 clinical examination in 2012–2013. A random sample of these participants was included in a sub-study comprising an MRI brain scan, a detailed clinical and cognitive assessment, and collection of blood and buccal mucosal samples for the characterisation of immune function and associated measures. Data collection for this sub-study started in 2012 and will be completed by 2016. The participants, for whom social and health records have been collected since 1985, were between 60–85 years of age at the time the MRI study started. Here, we describe the pre-specified clinical and cognitive assessment protocols, the state-of-the-art MRI sequences and latest pipelines for analyses of this sub-study. The integration of cutting-edge MRI techniques, clinical and cognitive tests in combination with retrospective data on social, behavioural and biological variables during the preceding 25 years from a well-established longitudinal epidemiological study (WHII cohort) will provide a unique opportunity to examine brain structure and function in relation to age-related diseases and the modifiable and non-modifiable factors affecting resilience against and vulnerability to adverse brain changes.