Assessment of a diffusion phantom for quality assurance in brain microstructure diffusion MRI studies.

Diffusion-weighted imaging (DWI) is a key contrast mechanism in MRI which allows for the assessment of microstructural properties of brain tissues by measuring the displacement of water molecules. Several diffusion models, including the tensor (DTI), kurtosis (DKI), and neurite orientation dispersion and density imaging (NODDI), are commonly used in both research and clinical practice. However, there is currently no standardized method for validating the stability and repeatability of these models over time.

Computational modelling of myocardial metabolism in patients with advanced heart failure.

Aims: Perturbations of myocardial metabolism and energy depletion are well-established hallmarks of heart failure (HF), yet methods for their systematic assessment remain limited in humans. This study aimed to determine the ability of computational modelling of patient-specific myocardial metabolism to assess individual bioenergetic phenotypes and their clinical implications in HF.

Methods And Results: Based on proteomics-derived enzyme quantities in 136 cardiac biopsies, personalized computational models of myocardial metabolism were generated in two independent cohorts of advanced HF patients together with sex- and body mass index-matched non-failing controls.

Immunomodulation by AZD1656 reverses cardiac dysfunction, metabolic remodelling and reduces infarct size in type 2 diabetic cardiomyopathy.

Type 2 Diabetes (T2D) can lead to diabetic cardiomyopathy (dbCM), which is characterised by chronic, systemic inflammation, disrupted metabolism and impaired cardiac function. However, whether cardiac inflammation is present in dbCM and causally linked to metabolic remodelling remains unknown. AZD1656 (AZD), an activator of glucokinase, was postulated to provide glycaemic control in T2D by acting on in the pancreas and liver.

Hyperpolarized C-MRS can Quantify Lactate Production and Oxidative PDH Flux in Murine Skeletal Muscle During Exercise.

Existing techniques for the non-invasive in vivo study of dynamic changes in skeletal muscle metabolism are subject to several limitations, for example, poor signal-to-noise ratios which result in long scan times and low temporal resolution. Hyperpolarized [1-C]pyruvate magnetic resonance spectroscopy (HP-MRS) allows the real-time visualization of in vivo metabolic processes and has been used extensively to study cardiac metabolism, but has not resolved oxidative phosphorylation in contracting skeletal muscle. Combining HP-MRS with an in vivo muscle hindlimb electrical stimulation protocol that modelled voluntary exercise to exhaustion allows the simultaneous real-time assessment of both metabolism and function.

Accurate and precise in vivo liver 3D T mapping at 3T.

Purpose: To develop an accurate and precise liver 3D mapping method using only scanner-agnostic sequences.

Methods: While the spoiled gradient-recalled echo sequence is widely available on clinical scanners, variable flip angle mapping methods based on this sequence provide biased estimates, with the largest systematic error arising from inhomogeneities. To correct for this, the flip angle was mapped using a 2D gradient-echo double-angle method approach.

H and P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID.

Background Emerging evidence suggests mitochondrial dysfunction may play a role in the fatigue experienced by individuals with post-COVID-19 condition (PCC), commonly called long COVID, which can be assessed using MR spectroscopy. Purpose To compare mitochondrial function between participants with fatigue-predominant PCC and healthy control participants using MR spectroscopy, and to investigate the relationship between MR spectroscopic parameters and fatigue using the 11-item Chalder fatigue questionnaire. Materials and Methods This prospective, observational, single-center study (June 2021 to January 2024) included participants with PCC who reported moderate to severe fatigue, with normal blood test and echocardiographic results, alongside control participants without fatigue symptoms.

Evaluation of an integrated variable flip angle protocol to estimate coil B for hyperpolarized MRI.

Purpose: The purpose of this work is to validate a simple and versatile integrated variable flip angle (VFA) method for mapping B in hyperpolarized MRI, which can be used to correct signal variations due to coil inhomogeneity.

Theory And Methods: Simulations were run to assess performance of the VFA B mapping method compared to the currently used constant flip angle (CFA) approach. Simulation results were used to inform the design of VFA sequences, validated in four volunteers for hyperpolarized xenon-129 imaging of the lungs and another four volunteers for hyperpolarized carbon-13 imaging of the human brain.

The age-dependent development of abnormal cardiac metabolism in the peroxisome proliferator-activated receptor α-knockout mouse.

Background And Aims: Peroxisome proliferator-activated receptor α (PPARα) is crucial for regulating cardiac β-oxidation in the heart, liver, and kidney. Ageing can induce cardiac metabolic alterations, but the role of PPARα has not been extensively characterised. The aim of this research was to investigate the role of PPARα in the aged heart.

Enabling SENSE accelerated 2D CSI for hyperpolarized carbon-13 imaging.

As hyperpolarized (HP) carbon-13 (C) metabolic imaging is clinically translated, there is a need for easy-to-implement, fast, and robust imaging techniques. However, achieving high temporal resolution without decreasing spatial and/or spectral resolution, whilst maintaining the usability of the imaging sequence is challenging. Therefore, this study looked to accelerate HP C MRI by combining a well-established and robust sequence called two-dimensional Chemical Shift Imaging (2D CSI) with prospective under sampling and SENSitivity Encoding (SENSE) reconstruction.

Hyperpolarized C and P MRS detects differences in cardiac energetics, metabolism, and function in obesity, and responses following treatment.

Obesity is associated with important changes in cardiac energetics and function, and an increased risk of adverse cardiovascular outcomes. Multi-nuclear MRS and MRI techniques have the potential to provide a comprehensive non-invasive assessment of cardiac metabolic perturbation in obesity. A rat model of obesity was created by high-fat diet feeding.

AICAR confers prophylactic cardioprotection in doxorubicin-induced heart failure in rats.

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects, leading to heart failure (HF). Impaired mitochondrial function is thought to be key factor driving progression into HF. We have previously shown in a rat model of DOX-HF that heart failure with reduced ejection fraction correlates with mitochondrial loss and dysfunction.

Compartment-based reconstruction of acquisition-weighted P cardiac MRSI reduces sensitivity to cardiac motion and scan planning.

P magnetic resonance spectroscopic imaging (P MRSI) is a powerful technique for investigating the metabolic effects of treatments for heart failure , allowing a better understanding of their mechanism of action in patient cohorts. Unfortunately, cardiac P MRSI is fundamentally limited by low SNR, which leads to compromises in acquisition, such as no cardiac or respiratory gating or low spatial resolution, in order to achieve reasonable scan times. Spectroscopy with linear algebra modeling (SLAM) reconstruction may be able to address these challenges and therefore improve repeatability by incorporating a segmented localizer into the reconstruction.

The effect of and correction for through-slice dephasing on 2D gradient-echo double angle mapping.

Purpose: To show that variations through slice and slice profile effects are two major confounders affecting 2D dual angle maps using gradient-echo signals and thus need to be corrected to obtain accurate maps.

Methods: The 2D gradient-echo transverse complex signal was Bloch-simulated and integrated across the slice dimension including nonlinear variations in inhomogeneities through slice. A nonlinear least squares fit was used to find the factor corresponding to the best match between the two gradient-echo signals experimental ratio and the Bloch-simulated ratio.

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology.

Hyperpolarized carbon 13 MRI (C MRI) is a novel imaging approach that can noninvasively probe tissue metabolism in both normal and pathologic tissues. The process of hyperpolarization increases the signal acquired by several orders of magnitude, allowing injected C-labeled molecules and their downstream metabolites to be imaged in vivo, thus providing real-time information on kinetics. To date, the most important reaction studied with hyperpolarized C MRI is exchange of the hyperpolarized C signal from injected [1-C]pyruvate with the resident tissue lactate pool.

Directly Bound Deuterons Increase X-Nuclei Hyperpolarization using Dynamic Nuclear Polarization.

Deuterated C sites in sugars (D-glucose and 2-deoxy-D-glucose) showed 6.3-to-17.5-fold higher solid-state dynamic nuclear polarization (DNP) levels than their respective protonated sites at 3.

Optimal flip angles for in vivo liver 3D T mapping and B mapping at 3T.

Purpose: The spoiled gradient recalled echo (SPGR) sequence with variable flip angles (FAs) enables whole liver mapping at high spatial resolutions but is strongly affected by inhomogeneities. The aim of this work was to study how the precision of acquired maps is affected by the and ranges observed in the liver at 3T, as well as how noise propagates from the acquired signals into the resulting map.

Theory: The variance was estimated through the Fisher information matrix with a total noise variance including, for the first time, the map noise as well as contributions from the SPGR noise.

Compartment-based reconstruction of 3D acquisition-weighted P cardiac magnetic resonance spectroscopic imaging at 7 T: A reproducibility study.

Even at 7 T, cardiac P magnetic resonance spectroscopic imaging (MRSI) is fundamentally limited by low signal-to-noise ratio (SNR), leading to long scan times and poor temporal and spatial resolutions. Compartment-based reconstruction algorithms such as magnetic resonance spectroscopy with linear algebraic modeling (SLAM) and spectral localization by imaging (SLIM) may improve SNR or reduce scan time without changes to acquisition. Here, we compare the repeatability and SNR performance of these compartment-based methods, applied to three different acquisition schemes at 7 T.

Developing a metabolic clearance rate framework as a translational analysis approach for hyperpolarized C magnetic resonance imaging.

Hyperpolarized carbon-13 magnetic resonance imaging is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a formalism for quantifying the metabolic information in hyperpolarized imaging. This study investigated a novel perfusion formalism and metabolic clearance rate (MCR) model in pre-clinical stroke and in the healthy human brain.

Maternal Cardiac Changes in Women With Obesity and Gestational Diabetes Mellitus.

Objective: We investigated if women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function, or tissue characteristics.

Research Design And Methods: Thirty-eight healthy, pregnant women and 30 women with GDM were recruited. Participants underwent phosphorus MRS and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine [PCr] to ATP ratio), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS), and mitral in-flow E-wave to A-wave ratio.

Increased cardiac Pi/PCr in the diabetic heart observed using phosphorus magnetic resonance spectroscopy at 7T.

Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously demonstrated decreased energy reserves in the form of phosphocreatine to adenosine-tri-phosphate ratio (PCr/ATP) in the hearts of patients with type 2 diabetes (T2DM). Recent 31P-MRS techniques using 7T systems, e.g.

Lactate saturation limits bicarbonate detection in hyperpolarized C-pyruvate MRI of the brain.

Purpose: To investigate the potential effects of [1- C]lactate RF saturation pulses on [ C]bicarbonate detection in hyperpolarized [1- C]pyruvate MRI of the brain.

Methods: Thirteen healthy rats underwent MRI with hyperpolarized [1- C]pyruvate of either the brain (n = 8) or the kidneys, heart, and liver (n = 5). Dynamic, metabolite-selective imaging was used in a cross-over experiment in which [1- C]lactate was excited with either 0° or 90° flip angles.

Assessing the effect of anesthetic gas mixtures on hyperpolarized C pyruvate metabolism in the rat brain.

Purpose: To determine the effect of altering anesthetic oxygen protocols on measurements of cerebral perfusion and metabolism in the rodent brain.

Methods: Seven rats were anesthetized and underwent serial MRI scans with hyperpolarized [1- C]pyruvate and perfusion weighted imaging. The anesthetic carrier gas protocol used varied from 100:0% to 90:10% to 60:40% O :N O.

Evaluation of Acute Supplementation With the Ketone Ester ()-3-Hydroxybutyl-(R)-3-Hydroxybutyrate (deltaG) in Healthy Volunteers by Cardiac and Skeletal Muscle P Magnetic Resonance Spectroscopy.

In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23-70 years for cardiac P-MRS, and 16 aged 60-75 years for skeletal muscle P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG, was administered after the baseline scan.