Dataset Information

Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders.

ABSTRACT: Systemic mitochondrial energy deficiency is implicated in the pathophysiology of many age-related human diseases. Currently available tools to estimate mitochondrial oxidative phosphorylation (OXPHOS) capacity in skeletal muscle in vivo lack high anatomic resolution. Muscle groups vary with respect to their contractile and metabolic properties. Therefore, muscle group-specific estimates of OXPHOS would be advantageous. To address this need, a noninvasive creatine chemical exchange saturation transfer (CrCEST) MRI technique has recently been developed, which provides a measure of free creatine. After exercise, skeletal muscle can be imaged with CrCEST in order to make muscle group-specific measurements of OXPHOS capacity, reflected in the recovery rate (?Cr) of free Cr. In this study, we found that individuals with genetic mitochondrial diseases had significantly (P = 0.026) prolonged postexercise ?Cr in the medial gastrocnemius muscle, suggestive of less OXPHOS capacity. Additionally, we observed that lower resting CrCEST was associated with prolonged ?PCr, with a Pearson's correlation coefficient of -0.42 (P = 0.046), consistent with previous hypotheses predicting that resting creatine levels may correlate with 31P magnetic resonance spectroscopy-based estimates of OXPHOS capacity. We conclude that CrCEST can noninvasively detect changes in muscle creatine content and OXPHOS capacity, with high anatomic resolution, in individuals with mitochondrial disorders.

SUBMITTER: DeBrosse C

PROVIDER: S-EPMC5085612 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders.

DeBrosse Catherine C Nanga Ravi Prakash Reddy RPR Wilson Neil N D'Aquilla Kevin K Elliott Mark M Hariharan Hari H Yan Felicia F Wade Kristin K Nguyen Sara S Worsley Diana D Parris-Skeete Chevonne C McCormick Elizabeth E Xiao Rui R Cunningham Zuela Zolkipli ZZ Fishbein Lauren L Nathanson Katherine L KL Lynch David R DR Stallings Virginia A VA Yudkoff Marc M Falk Marni J MJ Reddy Ravinder R McCormack Shana E SE

JCI insight 20161103 18

Systemic mitochondrial energy deficiency is implicated in the pathophysiology of many age-related human diseases. Currently available tools to estimate mitochondrial oxidative phosphorylation (OXPHOS) capacity in skeletal muscle in vivo lack high anatomic resolution. Muscle groups vary with respect to their contractile and metabolic properties. Therefore, muscle group-specific estimates of OXPHOS would be advantageous. To address this need, a noninvasive creatine chemical exchange saturation tra ...[more]

PMID: 27812541

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Project description:Chemical exchange saturation transfer (CEST) has emerged as a novel MRI contrast mechanism that is well suited for molecular imaging studies. This new mechanism can be used to detect small amounts of contrast agent through the saturation of rapidly exchanging protons on these agents, allowing a wide range of applications. CEST technology has a number of indispensable features, such as the possibility of simultaneous detection of multiple 'colors' of agents and of changes in their environment (e.g. pH, metabolites, etc.) through MR contrast. Currently, a large number of new imaging schemes and techniques are being developed to improve the temporal resolution and specificity and to correct for the influence of B0 and B1 inhomogeneities. In this review, the techniques developed over the last decade are summarized with the different imaging strategies and post-processing methods discussed from a practical point of view, including the description of their relative merits for the detection of CEST agents. The goal of the present work is to provide the reader with a fundamental understanding of the techniques developed, and to provide guidance to help refine future applications of this technology. This review is organized into three main sections ('Basics of CEST contrast', 'Implementation' and 'Post-processing'), and also includes a brief Introduction and Summary. The 'Basics of CEST contrast' section contains a description of the relevant background theory for saturation transfer and frequency-labeled transfer, and a brief discussion of methods to determine exchange rates. The 'Implementation' section contains a description of the practical considerations in conducting CEST MRI studies, including the choice of magnetic field, pulse sequence, saturation pulse, imaging scheme, and strategies to separate magnetization transfer and CEST. The 'Post-processing' section contains a description of the typical image processing employed for B0 /B1 correction, Z-spectral interpolation, frequency-selective detection and improvement of CEST contrast maps.

Dataset Information

Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders.

Publications

Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders.

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