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. The CNN was trained with synthetic data that represent a range of SNR levels typically encountered in vivo. The estimation precision was further improved by fine-tuning the CNN with MRI-based edge-preserving regularization for each DMI dataset. The proposed processing method, PReserved Edge ConvolutIonal neural network for Sensitivity Enhanced DMI (PRECISE-DMI), was applied to simulation studies and in vivo experiments to evaluate the anticipated improvements in SNR and investigate the potential for inaccuracies. Results: PRECISE-DMI visually improved the metabolic maps of low SNR datasets, and quantitatively provided higher precision than the standard Fourier reconstruction. Processing of DMI data acquired in rat brain tumor models resulted in more precise determination of 2H-labeled lactate and glutamate + glutamine levels, at increased spatial resolution (from >8 to 2 $\mu$L) or shortened scan time (from 32 to 4 min) compared to standard acquisitions. However, rigorous SD-bias analyses showed that overuse of the edge-preserving regularization can compromise the accuracy of the results. Conclusion: PRECISE-DMI allows a flexible trade-off between enhancing the sensitivity of DMI and minimizing the inaccuracies. With typical settings, the DMI sensitivity can be improved by 3-fold while retaining the capability to detect local signal variations

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. DMI is an MRS-based method that enables detection of deuterated substrates, such as glucose, and their metabolic products, such as lactate, glutamate and glutamine. It provides additional detail of downstream metabolites compared to analogous approaches like fluorodeoxyglucose (FDG)-PET, and can be implemented and executed on clinical and preclinical MR systems. We foresee that DMI, with future improvements in spatial and temporal resolutions, holds promise to become a valuable MR imaging (MRI) method for non-invasive mapping of glucose uptake and its downstream metabolites in healthy and diseased brain

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

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Selective proton-observed, carbon-edited (selPOCE) MRS method for measurement of glutamate and glutamine 13C-labeling in the human frontal cortex

Purpose: 13C magnetic resonance spectroscopy (MRS) in combination with infusion of 13C-labeled substrates has led to unique insights into human brain metabolism and neurotransmitter cycling. However, the low sensitivity of direct 13C MRS and high radiofrequency power requirements has limited 13C MRS studies to predominantly data acquisition in large volumes of the occipital cortex. The purpose of this study is to develop an MRS technique for localized detection of 13C-labeling of glutamate and glutamine in the human frontal lobe. Methods: We used an indirect (1H-[13C]), proton-observed, carbon-edited MRS sequence (selPOCE) for detection of 13C-labeled metabolites in relatively small volumes located in the frontal lobe at 4 T. The SelPOCE method allows for selective and separate detection of glutamate and glutamine resonances, which significantly overlap at magnetic field strengths used for clinical MRI. Results: Phantom data illustrate how selPOCE can be tuned to selectively detect 13C labeling in different metabolites. Three-dimensional specific absorption rate simulations of radiofrequency power deposition show that the selPOCE method operates comfortably within the global and local Food and Drug Administration specific absorption rate guidelines. In vivo selPOCE data are presented, which were acquired from a 45-mL volume in the frontal lobe of healthy subjects. The in vivo data show the time-dependent 13C-labeling of glutamate and glutamine during intravenous infusion of [1-13C]-glucose. Metrics describing spectral fitting quality of the glutamate and glutamine resonances are reported. Conclusions: The SelPOCE sequence allows the detection of 13C-labeling in glutamate and glutamine from a relatively small volume in the human frontal lobe at low radiofrequency power requirements. Magn Reson Med 80:11–20, 2018

Myofibrillar distribution of succinate dehydrogenase activity and lipid stores differs in skeletal muscle tissue of paraplegic subjects

Lack of physical activity has been related to an increased risk of developing insulin resistance. This study aimed to assess the impact of chronic muscle deconditioning on whole body insulin sensitivity, muscle oxidative capacity, and intramyocellular lipid ( IMCL ) content in subjects with paraplegia. Nine subjects with paraplegia and nine able-bodied, lean controls were recruited. An oral glucose tolerance test was performed to assess whole body insulin sensitivity. IMCL content was determined both in vivo and in vitro using 1H-magnetic resonance spectroscopy and fluorescence microscopy, respectively. Muscle biopsy samples were stained for succinate dehydrogenase ( SDH ) activity to measure muscle fiber oxidative capacity. Subcellular distributions of IMCL and SDH activity were determined by defining subsarcolemmal and intermyofibrillar areas on histological samples. SDH activity was 57 ± 14% lower in muscle fibers derived from subjects with paraplegia when compared with controls ( P < 0.05 ), but IMCL content and whole body insulin sensitivity did not differ between groups. In muscle fibers taken from controls, both SDH activity and IMCL content were higher in the subsarcolemmal region than in the intermyofibrillar area. This typical subcellular SDH and IMCL distribution pattern was lost in muscle fibers collected from subjects with paraplegia and had changed toward a more uniform distribution. In conclusion, the lower metabolic demand in deconditioned muscle of subjects with paraplegia results in a significant decline in muscle fiber oxidative capacity and is accompanied by changes in the subcellular distribution patterns of SDH activity and IMCL. However, loss of muscle activity due to paraplegia is not associated with substantial lipid accumulation in skeletal muscle tissue

On the magnetic field dependence of deuterium metabolic imaging

Deuterium metabolic imaging (DMI) is a novel MR-based method to spatially map metabolism of deuterated substrates such as [6,6’-2H2]-glucose in vivo. Compared with traditional 13C-MR-based metabolic studies, the MR sensitivity of DMI is high due to the larger 2H magnetic moment and favorable T1 and T2 relaxation times. Here, the magnetic field dependence of DMI sensitivity and transmit efficiency is studied on phantoms and rat brain postmortem at 4, 9.4 and 11.7 T. The sensitivity and spectral resolution on human brain in vivo are investigated at 4 and 7 T before and after an oral dose of [6,6’-2H2]-glucose. For small animal surface coils (Ø 30 mm), the experimentally measured sensitivity and transmit efficiency scale with the magnetic field to a power of +1.75 and −0.30, respectively. These are in excellent agreement with theoretical predictions made from the principle of reciprocity for a coil noise-dominant regime. For larger human surface coils (Ø 80 mm), the sensitivity scales as a +1.65 power. The spectral resolution increases linearly due to near-constant linewidths. With optimal multireceiver arrays the acquisition of DMI at a nominal 1 mL spatial resolution is feasible at 7 T

On the magnetic field dependence of deuterium metabolic imaging

Deuterium metabolic imaging (DMI) is a novel MR-based method to spatially map metabolism of deuterated substrates such as [6,6'-2H2]-glucose in vivo. Compared with traditional 13C-MR-based metabolic studies, the MR sensitivity of DMI is high due to the larger 2H magnetic moment and favorable T1 and T2 relaxation times. Here, the magnetic field dependence of DMI sensitivity and transmit efficiency is studied on phantoms and rat brain postmortem at 4, 9.4 and 11.7 T. The sensitivity and spectral resolution on human brain in vivo are investigated at 4 and 7 T before and after an oral dose of [6,6'-2H2]-glucose. For small animal surface coils (Ø 30 mm), the experimentally measured sensitivity and transmit efficiency scale with the magnetic field to a power of +1.75 and −0.30, respectively. These are in excellent agreement with theoretical predictions made from the principle of reciprocity for a coil noise-dominant regime. For larger human surface coils (Ø 80 mm), the sensitivity scales as a +1.65 power. The spectral resolution increases linearly due to near-constant linewidths. With optimal multireceiver arrays the acquisition of DMI at a nominal 1 mL spatial resolution is feasible at 7 T