Warda Syeda, Yasmin Blunck, Amanda Ng, Jon Cleary, Leigh Johnston

Bi-exponential models of T2*-weighted sodium data are prone to producing noisy parameter maps and low contrast between brain tissue types.  Further, inherently low SNR has, to this point, necessitated a constant fast fraction weight. Here, a continuum model of sodium T2*-decay is introduced and applied to in vivo human multi-echo 7T data, producing high quality, high contrast parameter maps, and informative voxelwise estimates of the relative weighting between fast and slow decay components.

Xucheng Zhu, Jeremy Gordon, Robert Bok, Peder Larson

We designed and optimized a dynamic double spin echo (DSE) acquisition scheme for hyperpolarized(HP) ¹³C metabolites dynamic diffusion weighted imaging(DWI). Compared to traditional DSE sequence, our sequence could provide higher SNR for longer dynamic imaging duration. Our studies on TRAMP mice indicate a dynamic change of HP lactate ADC over time, which might have potential to improve the assessment of aggressive cancers.

Jeffrey Brender, Shun Kishimoto, Hellmut Merkle, Galen Reed, Ralph Hurd, Albert Chen, Jan Ardenkjaer-Larsen, Jeeva Munasinghe, Keita Saito, Tomohiro Seki, Nobu Oshima, Kazu Yamamoto, James Mitchell, Murali Krishna

We show here a new method of imaging glucose metabolism in vivo by ¹³C MRS without DNP that relies on a simple but efficient postprocessing procedure using the higher dimensional analogue of SVD, tensor decomposition.  Using this procedure, without sacrificing accuracy, we achieve an order of magnitude increase in SNR in both DNP and non-hyperpolarized single voxel experiments. In CSI imaging experiments, we see an approximately 30 fold increase in SNR, enough that the glucose to lactate conversions can be imaged with a time resolution of 12 seconds and an overall spatial resolution that compares favorably to 18F-FDG PET.

Henk De Feyter, Kevin Behar, Peter Brown, Scott McIntyre, Terence Nixon, Douglas Rothman, Robin de Graaf

Deuterium Metabolic Imaging (DMI) is a novel approach providing high 3D spatial resolution metabolic data from both animal models and human subjects. DMI relies on ²H MRSI in combination with administration of ²H-labeled substrates. We show how DMI combined with administration of [6,6’-²H₂]-glucose can image glucose uptake and metabolism at high spatial resolution in human brain at 4T. We provide longitudinal and transverse relaxation times of ²H-labeled brain metabolites at 4T and 11.7T to support further development and optimization of DMI applications. 

Ming Lu, Xiao-Hong Zhu, Yi Zhang, Wei Chen

Recently, we developed a novel Deuterium MRS (DMRS) approach for simultaneously measuring cerebral glucose consumption rate and TCA cycle flux in rat brains at 16.4 T. Instead of using a clamp protocol in ¹³C MRS studies, our DMRS approach utilizes a brief i.v. infusion of glucose isotope. In this work, we aimed to establish a completely noninvasive delivery of the tracer into brain. By using oral uptake, DMRS detection sensitivity was evaluated and metabolic rates were quantified. Our results demonstrated the feasibility of using oral uptake for DMRS applications, which makes it highly suitable and promising for translation to patients.

Ludger Starke, Sonia Waiczies, Thoralf Niendorf, Andreas Pohlmann

Low sensitivity remains a major challenge on the way to utilizing the full potential of ¹⁹F-MRI, despite its unique detection specificity for imaging inflammation. Compressed sensing allows the reconstruction of high quality images from severely undersampled data by relying on prior statistical knowledge. We show that investing the gained acquisition speed into increased averaging improves the detection of ¹⁹F-nanoparticles in an EAE mouse model. Thus compressed sensing helps to improve the sensitivity of ¹⁹F-MRI. This paves the way to enhanced spatial and temporal resolution for future in vivo studies.

Nicholas Brennan, Kenneth Fishbein, David Reiter, Richard Spencer, Luigi Ferrucci

Systemic inflammation has been shown to play a role in both the aging process and disease progression. However, the effect of inflammation on mitochondrial function has not been fully elucidated. We hypothesized that increased systemic inflammation, assessed through measurement of conventional markers of inflammation, would be accompanied by a decrease in mitochondrial function, as assessed by ³¹P MRS of leg muscle.  Our results suggest that increased systemic inflammation may adversely affect mitochondrial function.

Charlie Wang, Yuchi Liu, Yuning Gu, Sherry Huang, Mark Griswold, Nicole Seiberlich, Xin Yu

Magnetic Resonance Fingerprinting (MRF) allows the quantification of multiple tissue parameters with high efficiency. Previously, we developed an MRF based ³¹P spectroscopic method for fast and robust measurement of ATP synthesis via creatine kinase (CK).  In the current study, we explored the potential of combining the CK-MRF method with fast imaging for metabolic mapping of the CK reaction rate in small laboratory animals.  CK-MRF imaging was performed in the hindlimb of four rats.  CK rates of different muscle compartments were compared.

Bryan Clifford, Yuning Gu, Yudu Li, Yuchi Liu, Fan Lam, Zhi-Pei Liang, Xin Yu

Dynamic 31P-MRS/MRSI is often used to assess mitochondrial oxidative capacity in skeletal muscle by monitoring the depletion and recovery of the phosphocreatine concentration during ischemia-reperfusion experiments. In animal models, standard methods are unable to provide the spatiotemporal resolution needed to discern spatial heterogeneity of the recovery process ($$$<$$$10 s/frame, $$$\approx$$$1 mm³ per voxel). To address this problem, we have improved a recently proposed low-rank tensor based method for accelerated high-resolution dynamic 31P-MRSI to provide in vivo results with 1.5x1.5x2 mm³ nominal spatial resolution, 36 ppm spectral bandwidth, 0.14 ppm spectral resolution, and 5.1 s temporal resolution.

Pavithra Viswanath, Russell Pieper, Joanna Phillips, Sabrina Ronen

Virtually every cancer studied so far shows elevated choline and ethanolamine phospholipid metabolism, which has emerged as a metabolic hallmark of cancer. Here, we show that, unusually, low-grade gliomas carrying a mutation in isocitrate dehydrogenase 1 (IDHmut) down-regulate phosphatidylcholine and phosphatidylethanolamine biosynthesis and steady-state levels. Mechanistically, this down-regulation is mediated via autophagic degradation of the endoplasmic reticulum, the site of phospholipid biosynthesis. Importantly, the autophagy inhibitor chloroquine restores phospholipid levels and abrogates IDHmut tumor growth, identifying a potential therapeutic opportunity. Thus, our study demonstrates that IDHmut gliomas uniquely down-regulate phospholipid biosynthesis and that this phenomenon can be exploited for therapy.