Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders
DeBrosse C, Nanga RPR, Wilson N, D'Aquilla K, Elliott M, Hariharan H, Yan F, Wade K, Nguyen S, Worsley D, Parris-Skeete C, McCormick E, Xiao R, Cunningham ZZ, Fishbein L, Nathanson KL, Lynch DR, Stallings VA, Yudkoff M, Falk MJ, Reddy R, McCormack SE
JCI insight · 39 citations
How it was studied
- Design
- Case-control study (classified by our AI screen)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- University or hospital
- University of Pennsylvania
- Nonprofit
- Pediatric Endocrine Society
- Government
- National Institutes of Health
- Government
- National Institute of Diabetes and Digestive and Kidney Diseases
- Government
- National Institute of Biomedical Imaging and Bioengineering
- Government
- National Center for Advancing Translational Sciences
- Government
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Government
- NICHD NIH HHS
- Government
- NCATS NIH HHS
- Government
- NIBIB NIH HHS
- Government
- NIDDK NIH HHS
- Grants
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK-019525); Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54-HD086984); University of Pennsylvania (UL1-TR-000003); National Institute of Biomedical Imaging and Bioengineering (T32 EB020087); National Institute of Biomedical Imaging and Bioengineering (P41 EB015893); National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK102659); National Institute of Diabetes and Digestive and Kidney Diseases (K12 DK094723); National Center for Advancing Translational Sciences (UL1-TR-001878); National Institutes of Health (NIH R03); National Center for Advancing Translational Sciences (UL1‐TR000003); National Institutes of Health (R03-DK082446); National Institutes of Health (UL1-TR-000003); National Institutes of Health (P41 EB015893); National Institutes of Health (EB015893); National Institutes of Health (K23 DK102659); National Institutes of Health (DK 19525); National Institutes of Health (K12DK094723)
Based on 11 listed funder(s).
Publication
- Published
- 2016-11-02 · JCI Insight · vol. 1 · issue 18 · p. e88207
- Publisher
- American Society for Clinical Investigation
- Cited
- 49 citations · more than 91% of similar papers · 3.1× the field average
- Impact
- Top 10% most cited in its field
- References
- 54 works
- Access
- Open access (journal)
- Research areas
- Advanced MRI Techniques and Applications · Lanthanide and Transition Metal Complexes · Electron Spin Resonance Studies
- Keywords
- Creatine, Oxidative phosphorylation, Skeletal muscle, Creatine kinase, Phosphocreatine, Creatine Monohydrate, Internal medicine, Magnetic resonance imaging, Gastrocnemius muscle, Mitochondrion, Endocrinology, Mitochondrial disease, In vivo, Biology, Mitochondrial DNA, Chemistry, Medicine, Biochemistry, Pathology, Energy metabolism, Genetics
- MeSH
- muscle, skeletal, mitochondria, muscle, humans, mitochondrial diseases, creatine, phosphocreatine, magnetic resonance imaging, exercise test, oxidative phosphorylation, phosphorylation, adult, middle aged, female, male
22 authors
From US
- Catherine DeBrosseUniversity of Pennsylvania
- Ravi Prakash Reddy NangaUniversity of Pennsylvania
- Neil E. WilsonUniversity of Pennsylvania
- Kevin D’AquillaUniversity of Pennsylvania
- Mark A. ElliottUniversity of Pennsylvania
- Hari HariharanUniversity of Pennsylvania
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 (τCr) of free Cr. In this study, we found that individuals with genetic mitochondrial diseases had significantly (P = 0.026) prolonged postexercise τCr in the medial gastrocnemius muscle, suggestive of less OXPHOS capacity. Additionally, we observed that lower resting CrCEST was associated with prolonged τPCr, 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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
Community trust
Loading…
How much do you trust this study's findings?
Comments
Sign in to rate, comment on or flag this study.Sign inSomething wrong here?
Flag this study if its information, labels or funding look wrong. An editor reviews every flag.
Sign in to rate, comment on or flag this study.Sign inEducational information about published research. Not medical advice, and not a recommendation to start or stop anything.