Purpose: We introduce FSL‐MRS, an end‐to‐end, modular, open‐source MRS analysis toolbox. It provides spectroscopic data conversion, preprocessing, spectral simulation, fitting, quantitation, and visualization.Methods: The FSL‐MRS package is modular. Its programs operate on data in a standard format (Neuroimaging Informatics Technology Initiative [NIfTI]) capable of storing single‐voxel and multivoxel spectroscopy, including spatial orientation information. The FSL‐MRS toolbox includes tools for preprocessing of raw spectroscopy data, including coil combination, frequency and phase alignment, and filtering. A density matrix simulation program is supplied for generation of basis spectra from simple text‐based descriptions of pulse sequences. Fitting is based on linear combination of basis spectra and implements Markov chain Monte Carlo optimization for the estimation of the full posterior distribution of metabolite concentrations. Validation of the fitting is carried out on independently created simulated data, phantom data, and three in vivo human data sets (257 single‐voxel spectroscopy and 8 MRSI data sets) at 3 T and 7 T. Interactive HTML reports are automatically generated by processing and fitting stages of the toolbox. The FSL‐MRS package can be used on the command line or interactively in the Python language.Results: Validation of the fitting shows low error in simulation (median error of 11.9%) and in phantom (3.4%). Average correlation between a third‐party toolbox (LCModel) and FSL‐MRS was high (0.53‐0.81) in all three in vivo data sets.Conclusion: The FSL‐MRS toolbox is designed to be flexible and extensible to new forms of spectroscopic acquisitions. Custom fitting models can be specified within the framework for dynamic or multivoxel spectroscopy. It is available as part of the FMRIB Software Library.

Background: The failing heart is traditionally described as metabolically inflexible and oxygen starved, causing energetic deficit and contractile dysfunction. Current metabolic modulator therapies aim to increase glucose oxidation to increase oxygen efficiency of adenosine triphosphate production, with mixed results. Methods: To investigate metabolic flexibility and oxygen delivery in the failing heart, 20 patients with nonischemic heart failure with reduced ejection fraction (left ventricular ejection fraction 34.9±9.1) underwent separate infusions of insulin+glucose infusion (I+G) or Intralipid infusion. We used cardiovascular magnetic resonance to assess cardiac function and measured energetics using phosphorus-31 magnetic resonance spectroscopy. To investigate the effects of these infusions on cardiac substrate use, function, and myocardial oxygen uptake (MV o ₂ ), invasive arteriovenous sampling and pressure–volume loops were performed (n=9). Results: At rest, we found that the heart had considerable metabolic flexibility. During I+G, cardiac glucose uptake and oxidation were predominant (70±14% total energy substrate for adenosine triphosphate production versus 17±16% for Intralipid; P =0.002); however, no change in cardiac function was seen relative to basal conditions. In contrast, during Intralipid infusion, cardiac long-chain fatty acid (LCFA) delivery, uptake, LCFA acylcarnitine production, and fatty acid oxidation were all increased (LCFA 73±17% of total substrate versus 19±26% total during I+G; P =0.009). Myocardial energetics were better with Intralipid compared with I+G (phosphocreatine/adenosine triphosphate 1.86±0.25 versus 2.01±0.33; P =0.02), and systolic and diastolic function were improved (LVEF 34.9±9.1 baseline, 33.7±8.2 I+G, 39.9±9.3 Intralipid; P <0.001). During increased cardiac workload, LCFA uptake and oxidation were again increased during both infusions. There was no evidence of systolic dysfunction or lactate efflux at 65% maximal heart rate, suggesting that a metabolic switch to fat did not cause clinically meaningful ischemic metabolism. Conclusions: Our findings show that even in nonischemic heart failure with reduced ejection fraction with severely impaired systolic function, significant cardiac metabolic flexibility is retained, including the ability to alter substrate use to match both arterial supply and changes in workload. Increasing LCFA uptake and oxidation is associated with improved myocardial energetics and contractility. Together, these findings challenge aspects of the rationale underlying existing metabolic therapies for heart failure and suggest that strategies promoting fatty acid oxidation may form the basis for future therapies.

Background: Obesity is strongly associated with exercise intolerance and the development of heart failure. Whereas myocardial energetics and diastolic function are impaired in obesity, systolic function is usually preserved. This suggests that the rate of ATP delivery is maintained, but this has never been explored in human obesity. We hypothesized that ATP transfer rate through creatine kinase (CK) ( k _f ^CKrest ) would be increased, compensating for depleted energy stores (phosphocreatine/ATP), but potentially limiting greater ATP delivery during increased workload. We hypothesized that these changes would normalize with weight loss. Methods: We recruited 80 volunteers (35 controls [body mass index 24±3 kg/m ² ], 45 obese [body mass index 35±5 kg/m ² ]) without coexisting cardiovascular disease. Participants underwent body composition analysis, magnetic resonance imaging of abdominal, liver, and myocardial fat content, left ventricular function, and ³¹ P magnetic resonance spectroscopy to assess phosphocreatine/ATP and CK kinetics, at rest and during dobutamine stress. Obese volunteers were assigned to a dietary weight loss intervention, before reexamination. Results: At rest, although myocardial phosphocreatine/ATP was 14% lower in obesity (1.9±0.3 versus 2.2±0.2, P <0.001), k _f ^Ckrest was 33% higher (0.23±0.07 s ^–1 versus 0.16±0.08 s ^–1 , P =0.002), yielding no difference in overall resting ATP delivery (obese 2.5±0.9 µmol·g ^–1 ·s ^–1 versus control 2.2±1.1 µmol·g ^–1 ·s ^–1 , P =0.232). In controls, increasing cardiac workload led to an increase in both k _f ^CK (+86%, P <0.001) and ATP delivery (+80%, P <0.001). However, in obesity, similar stress led to no significant increase in either k _f ^CK ( P =0.117) or ATP delivery ( P =0.608). This was accompanied by reduced systolic augmentation (absolute increase in left ventricular ejection fraction, obese +16±7% versus control +21±4%, P =0.031). Successful weight loss (–11±5% body weight) was associated with improvement of these energetic changes such that there was no significant difference in comparison with controls. Conclusions: In the obese resting heart, the myocardial CK reaction rate is increased, maintaining ATP delivery despite reduced phosphocreatine/ATP. During increased workload, although the nonobese heart increases ATP delivery through CK, the obese heart does not; this is associated with reduced systolic augmentation and exercise tolerance. Weight loss reverses these energetic changes. This highlights myocardial energy delivery through CK as a potential therapeutic target to improve symptoms in obesity-related heart disease, and a fascinating modifiable pathway involved in the progression to heart failure, as well.

Purpose: Multiple data formats in the MRS community currently hinder data sharing and integration. NIfTI‐MRS is proposed as a standard spectroscopy data format, implemented as an extension to the Neuroimaging informatics technology initiative (NIfTI) format. This standardized format can facilitate data sharing and algorithm development as well as ease integration of MRS analysis alongside other imaging modalities.Methods: A file format using the NIfTI header extension framework incorporates essential spectroscopic metadata and additional encoding dimensions. A detailed description of the specification is provided. An open‐source command‐line conversion program is implemented to convert single‐voxel and spectroscopic imaging data to NIfTI‐MRS. Visualization of data in NIfTI‐MRS is provided by development of a dedicated plugin for FSLeyes, the FMRIB Software Library (FSL) image viewer.Results: Online documentation and 10 example datasets in the proposed format are provided. Code examples of NIfTI‐MRS readers are implemented in common programming languages. Conversion software, spec2nii, currently converts 14 formats where data is stored in image‐space to NIfTI‐MRS, including Digital Imaging and Communications in Medicine (DICOM) and vendor proprietary formats.Conclusion: NIfTI‐MRS aims to solve issues arising from multiple data formats being used in the MRS community. Through a single conversion point, processing and analysis of MRS data are simplified, thereby lowering the barrier to use of MRS. Furthermore, it can serve as the basis for open data sharing, collaboration, and interoperability of analysis programs. Greater standardization and harmonization become possible. By aligning with the dominant format in neuroimaging, NIfTI‐MRS enables the use of mature tools present in the imaging community, demonstrated in this work by using a dedicated imaging tool, FSLeyes, for visualization.

Increasing numbers of 7 T (7 T) magnetic resonance imaging (MRI) scanners are in research and clinical use. 7 T MRI can increase the scanning speed, spatial resolution and contrast-to-noise-ratio of many neuroimaging protocols, but technical challenges in implementation have been addressed in a variety of ways across sites. In order to facilitate multi-centre studies and ensure consistency of findings across sites, it is desirable that 7 T MRI sites implement common high-quality neuroimaging protocols that can accommodate different scanner models and software versions. With the installation of several new 7 T MRI scanners in the United Kingdom, the UK7T Network was established with an aim to create a set of harmonized structural and functional neuroimaging sequences and protocols. The Network currently includes five sites, which use three different scanner platforms, provided by two different vendors. Here we describe the harmonization of functional and anatomical imaging protocols across the three different scanner models, detailing the necessary changes to pulse sequences and reconstruction methods. The harmonized sequences are fully described, along with implementation details. Example datasets acquired from the same subject on all Network scanners are made available. Based on these data, an evaluation of the harmonization is provided. In addition, the implementation and validation of a common system calibration process is described.

We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network's “Travelling Heads” study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* 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 R2* mapping at 7T, in readiness for future multi-site clinical studies. Ten healthy volunteers were scanned with harmonised single- and multi-echo T2*-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 1× Philips, 2× Siemens Magnetom, and 2× Siemens Terra scanners. QSM and R2* 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. Mean susceptibility (χ) and R2* 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 (R2*). For χ this is 2.1–4.8 fold better than 3T reports, and 1.1–3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured χ and R2* 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. The harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* 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.