Development of a P magnetic resonance spectroscopy technique to quantify NADH and NAD at 3 T.

NADH and NAD act as electron donors and acceptors and NAD was shown to stimulate mitochondrial biogenesis and metabolic health. We here develop a non-invasive Phosphorous Magnetic Resonance Spectroscopy (P-MRS) method to quantify these metabolites in human skeletal muscle on a clinical 3 T MRI scanner. This new MR-sequence enables NADH and NAD+ quantification by suppressing α-ATP signal, normally overlapping with NADH and NAD.

A Flow-based Truncated Denoising Diffusion Model for super-resolution Magnetic Resonance Spectroscopic Imaging.

Magnetic Resonance Spectroscopic Imaging (MRSI) is a non-invasive imaging technique for studying metabolism and has become a crucial tool for understanding neurological diseases, cancers and diabetes. High spatial resolution MRSI is needed to characterize lesions, but in practice MRSI is acquired at low resolution due to time and sensitivity restrictions caused by the low metabolite concentrations. Therefore, there is an imperative need for a post-processing approach to generate high-resolution MRSI from low-resolution data that can be acquired fast and with high sensitivity.

High-quality lipid suppression and B0 shimming for human brain H MRSI.

Magnetic Resonance Spectroscopic Imaging (MRSI) is a powerful technique that can map the metabolic profile in the brain non-invasively. Extracranial lipid contamination and insufficient B homogeneity however hampers robustness, and as a result has hindered widespread use of MRSI in clinical and research settings. Over the last six years we have developed highly effective extracranial lipid suppression methods with a second order gradient insert (ECLIPSE) utilizing inner volume selection (IVS) and outer volume suppression (OVS) methods.

Indirect H-[C] MRS of the human brain at 7 T using a C-birdcage coil and eight transmit-receive H-dipole antennas with a 32-channel H-receive array.

The neuronal tricarboxylic acid and glutamate/glutamine (Glu/Gln) cycles play important roles in brain function. These processes can be measured in vivo using dynamic H-[C] MRS during administration of C-labeled glucose. Proton-observed carbon-edited (POCE) MRS enhances the signal-to-noise ratio (SNR) compared with direct C-MRS.

Parallel detection of multi-contrast MRI and Deuterium Metabolic Imaging (DMI) for time-efficient characterization of neurological diseases.

Deuterium Metabolic Imaging (DMI) is a novel method that can complement traditional anatomical magnetic resonance imaging (MRI) of the brain. DMI relies on the MR detection of metabolites that become labeled with deuterium (H) after administration of a deuterated substrate and can provide images with highly specific metabolic information. However, clinical adoption of DMI is complicated by its relatively long scan time.

Preserved Edge Convolutional Neural Network for Sensitivity Enhancement of Deuterium Metabolic Imaging (DMI).

Purpose: Common to most MRSI techniques, the spatial resolution and the minimal scan duration of Deuterium Metabolic Imaging (DMI) are limited by the achievable SNR. This work presents a deep learning method for sensitivity enhancement of DMI.

Methods: A convolutional neural network (CNN) was designed to estimate the 2H-labeled metabolite concentrations from low SNR and distorted DMI FIDs.

Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI).

Introduction: There is a lack of robust metabolic imaging techniques that can be routinely applied to characterize lesions in patients with brain tumors. Here we explore in an animal model of glioblastoma the feasibility to detect uptake and metabolism of deuterated choline and describe the tumor-to-brain image contrast.

Methods: RG2 cells were incubated with choline and the level of intracellular choline and its metabolites measured in cell extracts using high resolution H NMR.

Design and realization of a multi-coil array for B field control in a compact 1.5T head-only MRI scanner.

Purpose: To design and implement a multi-coil (MC) array for B field generation for image encoding and simultaneous advanced shimming in a novel 1.5T head-only MRI scanner.

Methods: A 31-channel MC array was designed following the unique constraints of this scanner design: The vertically oriented magnet is very short, stopping shortly above the shoulders of a sitting subject, and includes a window for the subject to see through.

Measurement of neuro-energetics and neurotransmission in the rat olfactory bulb using H and H-[C] NMR spectroscopy.

The olfactory bulb (OB) plays a fundamental role in the sense of smell and has been implicated in several pathologies, including Alzheimer's disease. Despite its importance, high metabolic activity and unique laminar architecture, the OB is not frequently studied using MRS methods, likely due to the small size and challenging location. Here we present a detailed metabolic characterization of OB metabolism, in terms of both static metabolite concentrations using H MRS and metabolic fluxes associated with neuro-energetics and neurotransmission by tracing the dynamic C flow from intravenously administered [1,6-C]-glucose, [2-C]-glucose and [2-C]-acetate to downstream metabolites, including [4-C]-glutamate, [4-C]-glutamine and [2-C]-GABA.

imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status - A pilot study combining PET and deuterium metabolic imaging.

Recanalization therapy after acute ischemic stroke enables restoration of cerebral perfusion. However, a significant subset of patients has poor outcome, which may be caused by disruption of cerebral energy metabolism. To assess changes in glucose metabolism subacutely and chronically after recanalization, we applied two complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and deuterium (H) metabolic imaging (DMI), after 60-minute transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice.

Short symmetric and highly selective asymmetric first and second order gradient modulated offset independent adiabaticity (GOIA) pulses for applications in clinical MRS and MRSI.

Gradient modulated RF pulses, especially gradient offset independent adiabaticity (GOIA) pulses, are increasingly gaining attention for high field clinical magnetic resonance spectroscopy and spectroscopic imaging (MRS/MRSI) due to the lower peak B amplitude and associated power demands achievable relative to its non-modulated adiabatic full passage counterparts. In this work we describe the development of two GOIA RF pulses: 1) A power efficient, 3.0 ms wideband uniform rate with smooth truncation (WURST) modulated RF pulse with 15 kHz bandwidth compatible with a clinically feasible peak B amplitude of 0.

Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans.

Background: Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC).

Interleaved fluid-attenuated inversion recovery (FLAIR) MRI and deuterium metabolic imaging (DMI) on human brain in vivo.

Purpose: To integrate deuterium metabolic imaging (DMI) with clinical MRI through an interleaved MRI and DMI acquisition workflow. Interleaved MRI-DMI was enabled with hardware and pulse sequence modifications, and the performance was demonstrated using fluid-attenuated inversion recovery (FLAIR) MRI as an example.

Methods: Interleaved FLAIR-DMI was developed by interleaving the H excitation and acquisition time windows into the intrinsic delay periods presented in the FLAIR method.

Human brain functional MRS reveals interplay of metabolites implicated in neurotransmission and neuroenergetics.

While functional MRI (fMRI) localizes brain activation and deactivation, functional MRS (fMRS) provides insights into the underlying metabolic conditions. There is much interest in measuring task-induced and resting levels of metabolites implicated in neuroenergetics (e.g.

High-Resolution Magnetic Resonance Spectroscopic Imaging using a Multi-Encoder Attention U-Net with Structural and Adversarial Loss.

Common to most medical imaging techniques, the spatial resolution of Magnetic Resonance Spectroscopic Imaging (MRSI) is ultimately limited by the achievable SNR. This work presents a deep learning method for 1H-MRSI spatial resolution enhancement, based on the observation that multi-parametric MRI images provide relevant spatial priors for MRSI enhancement. A Multi-encoder Attention U-Net (MAU-Net) architecture was constructed to process a MRSI metabolic map and three different MRI modalities through separate encoding paths.

Deuterium metabolic imaging in the human brain at 9.4 Tesla with high spatial and temporal resolution.

Purpose: To present first highly spatially resolved deuterium metabolic imaging (DMI) measurements of the human brain acquired with a dedicated coil design and a fast chemical shift imaging (CSI) sequence at an ultrahigh field strength of B = 9.4 T. H metabolic measurements with a temporal resolution of 10 min enabled the investigation of the glucose metabolism in healthy human subjects.

Simultaneous Recording of the Uptake and Conversion of Glucose and Choline in Tumors by Deuterium Metabolic Imaging.

Increased glucose and choline uptake are hallmarks of cancer. We investigated whether the uptake and conversion of [H]choline alone and together with that of [6,6'-H]glucose can be assessed in tumors via deuterium metabolic imaging (DMI) after administering these compounds. Therefore, tumors with human renal carcinoma cells were grown subcutaneously in mice.

Deuterium metabolic imaging - Back to the future.

Deuterium metabolic spectroscopy (DMS) and imaging (DMI) have recently been described as simple and robust MR-based methods to map metabolism with high temporal and/or spatial resolution. The metabolic fate of a wide range of suitable deuterated substrates, including glucose and acetate, can be monitored with deuterium MR methods in which the favorable MR characteristics of deuterium prevent many of the complications that hamper other techniques. The short T relaxation times lead to good MR sensitivity, while the low natural abundance prevents the need for water or lipid suppression.

NMR visibility of deuterium-labeled liver glycogen in vivo.

Purpose: Deuterium metabolic imaging (DMI) combined with [6,6'- H ]-glucose has the potential to detect glycogen synthesis in the liver. However, the similar chemical shifts of [6,6'- H ]-glucose and [6,6'- H ]-glycogen in the H NMR spectrum make unambiguous detection and separation difficult in vivo, in contrast to comparable approaches using C MRS. Here the NMR visibility of H-labeled glycogen is investigated to better understand its potential contribution to the observed signal in liver following administration of [6,6'- H ]-glucose.

Deuterium Metabolic Imaging of the Healthy and Diseased Brain.

Altered brain metabolism contributes to pathophysiology in cerebrovascular and neurodegenerative diseases such as stroke and Alzheimer's disease. Current clinical tools to study brain metabolism rely on positron emission tomography (PET) requiring specific hardware and radiotracers, or magnetic resonance spectroscopy (MRS) involving technical complexity. In this review we highlight deuterium metabolic imaging (DMI) as a novel translational technique for assessment of brain metabolism, with examples from brain tumor and stroke studies.

Metabolic underpinnings of activated and deactivated cortical areas in human brain.

Neuroimaging with functional MRI (fMRI) identifies activated and deactivated brain regions in task-based paradigms. These patterns of (de)activation are altered in diseases, motivating research to understand their underlying biochemical/biophysical mechanisms. Essentially, it remains unknown how aerobic metabolism of glucose to lactate (aerobic glycolysis) and excitatory-inhibitory balance of glutamatergic and GABAergic neuronal activities vary in these areas.

Water and lipid suppression techniques for advanced H MRS and MRSI of the human brain: Experts' consensus recommendations.

The neurochemical information provided by proton magnetic resonance spectroscopy (MRS) or MR spectroscopic imaging (MRSI) can be severely compromised if strong signals originating from brain water and extracranial lipids are not properly suppressed. The authors of this paper present an overview of advanced water/lipid-suppression techniques and describe their advantages and disadvantages. Moreover, they provide recommendations for choosing the most appropriate techniques for proper use.

Characterization of Kinetic Isotope Effects and Label Loss in Deuterium-Based Isotopic Labeling Studies.

Deuterium metabolic imaging (DMI) is a novel, 3D, magnetic resonance (MR)-based method to map metabolism of deuterated substrates . The replacement of protons with deuterons could potentially lead to kinetic isotope effects (KIEs) in which metabolic rates of deuterated substrates are reduced due to the presence of a heavier isotope. Knowledge of the extent of KIE and H label loss due to exchange reactions is required for DMI-based measurements of absolute metabolic rates.

Contribution of macromolecules to brain H MR spectra: Experts' consensus recommendations.

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases.