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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 citas

Cómo se estudió

Diseño
Estudio de casos y controles (clasificado por nuestro filtro de IA)
Estudiado en
Personas
Resultado principal
Marcadores de salud y funcionamiento

Quién lo pagó

Financiación
Financiación independiente
Universidad u hospital
University of Pennsylvania
Organización sin fines de lucro
Pediatric Endocrine Society
Gobierno
National Institutes of Health
Gobierno
National Institute of Diabetes and Digestive and Kidney Diseases
Gobierno
National Institute of Biomedical Imaging and Bioengineering
Gobierno
National Center for Advancing Translational Sciences
Gobierno
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Gobierno
NICHD NIH HHS
Gobierno
NCATS NIH HHS
Gobierno
NIBIB NIH HHS
Gobierno
NIDDK NIH HHS
Subvenciones
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)

Según 11 financiadores declarados.

Publicación

Publicado
2016-11-02 · JCI Insight · vol. 1 · número 18 · pág. e88207
Editorial
American Society for Clinical Investigation
Citado
49 citas · más que el 91% de estudios similares · 3.1× el promedio de su campo
Impacto
Entre el 10 % más citado de su campo
Referencias
54 trabajos
Acceso
Acceso abierto (revista)
Áreas de investigación
Advanced MRI Techniques and Applications · Lanthanide and Transition Metal Complexes · Electron Spin Resonance Studies
Palabras clave
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 autores

  • Catherine DeBrosse🇺🇸University of Pennsylvania
  • Ravi Prakash Reddy Nanga🇺🇸University of Pennsylvania
  • Neil E. Wilson🇺🇸University of Pennsylvania
  • Kevin D’Aquilla🇺🇸University of Pennsylvania
  • Mark A. Elliott🇺🇸University of Pennsylvania
  • Hari Hariharan🇺🇸University of Pennsylvania
  • Felicia Yan🇺🇸Children's Hospital of Philadelphia
  • Kristin Wade🇺🇸Children's Hospital of Philadelphia
  • Sara Nguyen🇺🇸Children's Hospital of Philadelphia
  • Diana Worsley🇺🇸Children's Hospital of Philadelphia
  • Chevonne Parris-Skeete🇺🇸Children's Hospital of Philadelphia
  • Elizabeth M. McCormick🇺🇸Children's Hospital of Philadelphia
  • Rui Xiao🇺🇸University of Pennsylvania
  • Zuela Zolkipli Cunningham🇺🇸Children's Hospital of Philadelphia
  • Lauren Michelle Fishbein🇺🇸University of Colorado Denver
  • Katherine L. Nathanson🇺🇸University of Pennsylvania
  • David R. Lynch🇺🇸Children's Hospital of Philadelphia
  • Virginia A. Stallings🇺🇸Children's Hospital of Philadelphia; University of Pennsylvania
  • Marc Yudkoff🇺🇸Children's Hospital of Philadelphia; University of Pennsylvania
  • Marni J. Falk🇺🇸Children's Hospital of Philadelphia; University of Pennsylvania
  • Ravinder D Reddy🇺🇸University of Pennsylvania
  • Shana Erin McCormack🇺🇸 · autor de correspondenciaChildren's Hospital of Philadelphia; University of Pennsylvania

Resumen

El texto original del estudio, en el idioma en que se publicó.

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.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.

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