Dataset Information

High-Resolution Dynamic 31P-MR Spectroscopic Imaging for Mapping Mitochondrial Function.

ABSTRACT: OBJECTIVE:To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using 31P-MR spectroscopic imaging (MRSI). METHODS:We developed a novel method for high-resolution dynamic 31P-MRSI. The method synergistically integrates physics-based models of spectral structures, biochemical modeling of molecular dynamics, and subspace learning to capture spatiospectral variations. Fast data acquisition was achieved using rapid spiral trajectories and sparse sampling of (k, t, T)-space; image reconstruction was accomplished using a low-rank tensor-based framework. RESULTS:The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4[Formula: see text]2 mm3 and 1.28 s, respectively. This allowed for in vivo mapping of the time-constant of phosphocreatine resynthesis, a well established index of mitochondrial oxidative capacity. Multiple rounds of in vivo experiments were performed to demonstrate reproducibility, and in vitro experiments were used to validate the accuracy of the estimated metabolite maps. CONCLUSIONS:A new model-based method is proposed to achieve high-resolution dynamic 31P-MRSI. The proposed method's ability to delineate metabolic heterogeneity was demonstrated in rat hindlimb. SIGNIFICANCE:Abnormal mitochondrial metabolism is a key cellular dysfunction in many prevalent diseases such as diabetes and heart disease; however, current understanding of mitochondrial function is mostly gained from studies on isolated mitochondria under nonphysiological conditions. The proposed method has the potential to open new avenues of research by allowing in vivo and longitudinal studies of mitochondrial dysfunction in disease development and progression.

SUBMITTER: Clifford B

PROVIDER: S-EPMC7384926 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High-Resolution Dynamic <sup>31</sup>P-MR Spectroscopic Imaging for Mapping Mitochondrial Function.

Clifford Bryan B Gu Yuning Y Liu Yuchi Y Kim Kihwan K Huang Sherry S Li Yudu Y Lam Fan F Liang Zhi-Pei ZP Yu Xin X

IEEE transactions on bio-medical engineering 20200128 10

<h4>Objective</h4>To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using <sup>31</sup>P-MR spectroscopic imaging (MRSI).<h4>Methods</h4>We developed a novel method for high-resolution dynamic <sup>31</sup>P-MRSI. The method synergistically integrates physics-based models of spectral structures, biochemical modeling of molecular dynamics, and subspace learning to capture spatiospectral variations. Fast data acquisition was achieved using rapid spi ...[more]

PMID: 32011244

Similar Datasets

Project description:Nonalcoholic fatty liver disease (NAFLD) is a growing health problem, and a major challenge in NAFLD management is identifying which patients are at risk of progression to more serious disease. Simple measurements of liver fat content are not strong predictors of clinical outcome, but biomarkers related to fatty acid composition (ie, saturated vs. unsaturated fat) may be more effective. MR spectroscopic imaging (MRSI) methods allow spatially resolved, whole-liver measurements of chemical composition but are traditionally limited by slow acquisition times. In this work we present an accelerated MRSI acquisition based on spin echo single point imaging (SE-SPI), which, using appropriate sampling and compressed sensing reconstruction, allows free-breathing acquisition in a mouse model of fatty liver disease. After validating the technique's performance in oil/water phantoms, we imaged mice that had received a normal diet or a methionine and choline deficient (MCD) diet, some of which also received supplemental injections of iron to mimic hepatic iron overload. SE-SPI was more resistant to the line-broadening effects of iron than single-voxel spectroscopy measurements, and was consistently able to measure the amplitudes of low-intensity spectral peaks that are important to characterizing fatty acid composition. In particular, in the mice receiving the MCD diet, SE-SPI showed a significant decrease in a metric associated with unsaturated fat, which is consistent with the literature. This or other related metrics may therefore offer more a specific biomarker of liver health than fat content alone. This preclinical study is an important precursor to clinical testing of the proposed method. MR-based quantification of fatty acid composition may allow for improved characterization of non-alcoholic fatty liver disease. A spectroscopic imaging method with appropriate sampling strategy allows whole-liver mapping of fat composition metrics in a free-breathing mouse model. Changes in metrics like the surrogate unsaturation index (UIs) are visible in mice receiving a diet which induces fat accumulation in the liver, as compared to a normal diet; such metrics may prove useful in future clinical studies of liver disease.

Project description:Background Isocitrate dehydrogenase (IDH) mutations are highly frequent in glioma, producing high levels of the oncometabolite D-2-hydroxyglutarate (D-2HG). Hence, D-2HG represents a valuable imaging marker for IDH-mutated human glioma. Purpose To develop and evaluate a super-resolution three-dimensional (3D) MR spectroscopic imaging strategy to map D-2HG and tumor metabolism in IDH-mutated human glioma. Materials and Methods Between March and September 2018, participants with IDH1-mutated gliomas and healthy participants were prospectively scanned with a 3-T whole-brain 3D MR spectroscopic imaging protocol optimized for D-2HG. The acquired D-2HG maps with a voxel size of 5.2 × 5.2 × 12 mm were upsampled to a voxel size of 1.7 × 1.7 × 3 mm using a super-resolution method that combined weighted total variation, feature-based nonlocal means, and high-spatial-resolution anatomic imaging priors. Validation with simulated healthy and patient data and phantom measurements was also performed. The Mann-Whitney U test was used to check that the proposed super-resolution technique yields the highest peak signal-to-noise ratio and structural similarity index. Results Three participants with IDH1-mutated gliomas (mean age, 50 years ± 21 [standard deviation]; two men) and three healthy participants (mean age, 32 years ± 3; two men) were scanned. Twenty healthy participants (mean age, 33 years ± 5; 16 men) underwent a simulation of upsampled MR spectroscopic imaging. Super-resolution upsampling improved peak signal-to-noise ratio and structural similarity index by 62% (P < .05) and 7.3% (P < .05), respectively, for simulated data when compared with spline interpolation. Correspondingly, the proposed method significantly improved tissue contrast and structural information for the acquired 3D MR spectroscopic imaging data. Conclusion High-spatial-resolution whole-brain D-2-hydroxyglutarate imaging is possible in isocitrate dehydrogenase 1-mutated human glioma by using a super-resolution framework to upsample three-dimensional MR spectroscopic images acquired at lower resolution. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Huang and Lin in this issue.

Project description:Phosphorus magnetic resonance spectroscopic imaging (31P MRSI) is of particular interest for investigations of patients with brain tumors as it enables to non-invasively assess altered energy and phospholipid metabolism in vivo. However, the limited sensitivity of 31P MRSI hampers its broader application at clinical field strengths. This study aimed to identify the additional value of 31P MRSI in patients with glioma at ultra-high B 0 = 7T, where the increase in signal-to-noise ratio may foster its applicability for clinical research. High-quality, 3D 31P MRSI datasets with an effective voxel size of 5.7 ml were acquired from the brains of seven patients with newly diagnosed glioma. An optimized quantification model was implemented to reliably extract an extended metabolic profile, including low-concentrated metabolites such as extracellular inorganic phosphate, nicotinamide adenine dinucleotide [NAD(H)], and uridine diphosphoglucose (UDPG), which may act as novel tumor markers; a background signal was extracted as well, which affected measures of phosphomonoesters beneficially. Application of this model to the MRSI datasets yielded high-resolution maps of 12 different 31P metabolites, showing clear metabolic differences between white matter (WM) and gray matter, and between healthy and tumor tissues. Moreover, differences between tumor compartments in patients with high-grade glioma (HGG), i.e., gadolinium contrast-enhancing/necrotic regions (C+N) and peritumoral edema, could also be suggested from these maps. In the group of patients with HGG, the most significant changes in metabolite intensities were observed in C+N compared to WM, i.e., for phosphocholine +340%, UDPG +54%, glycerophosphoethanolamine -45%, and adenosine-5'-triphosphate -29%. Furthermore, a prominent signal from mobile phospholipids appeared in C+N. In the group of patients with low-grade glioma, only the NAD(H) intensity changed significantly by -28% in the tumor compared to WM. Besides the potential of 31P MRSI at 7T to provide novel insights into the biochemistry of gliomas in vivo, the attainable spatial resolutions improve the interpretability of 31P metabolite intensities obtained from malignant tissues, particularly when only subtle differences compared to healthy tissues are expected. In conclusion, this pilot study demonstrates that 31P MRSI at 7T has potential value for the clinical research of glioma.

Dataset Information

High-Resolution Dynamic 31P-MR Spectroscopic Imaging for Mapping Mitochondrial Function.

Publications

High-Resolution Dynamic <sup>31</sup>P-MR Spectroscopic Imaging for Mapping Mitochondrial Function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets