title: Method for controlled mitochondrial perturbation during phosphorus MRS in children.
abstract: Insulin resistance is increasingly prevalent in children and may be related to muscle mitochondrial dysfunction, necessitating development of mitochondrial assessment techniques. Recent studies used phosphorus magnetic resonance spectroscopy (P-MRS), a noninvasive technique appealing for clinical research. P-MRS requires exercise at a precise percentage of maximum volitional contraction (MVC). MVC measurement in children, particularly in those with a disease, is problematic because of variability in perception of effort and motivation. We therefore developed a method to predict MVC using maximal calf muscle cross-sectional area (MCSA) to assure controlled and reproducible muscle metabolic perturbations.
  
  
  METHODS
  Data were collected from 66 sedentary 12- to 20-yr-old participants. Plantarflexion MVC was assessed using an MRI-compatible exercise treadle device. MCSA of the calf muscles were measured from magnetic resonance images. Data from the first 26 participants were used to model the relation between MVC and MCSA (predicted MVC = 24.763 + 0.0047 MCSA). This model was then applied to the subsequent 40 participants.
  
  
  RESULTS
  MVC versus model-predicted mean MVC was 43.9 ± 0.8 kg versus 44.2 ± 1.81 (P = 0.90). P-MRS results when predicted and MVC were similar showed expected changes during MVC-based exercise. In contrast, MVC was markedly lower than predicted in four participants and produced minimal metabolic perturbation. Upon repeat testing, these individuals could perform their predicted MVC with coaching, which produced expected metabolic perturbations.
  
  
  CONCLUSIONS
  Compared with using MVC testing alone, using magnetic resonance imaging to predict muscle strength allows for a more accurate and standardized P-MRS protocol during exercise in children. This method overcomes a major obstacle in assessing mitochondrial function in youths. These studies have importance as we seek to determine the role of mitochondrial function in youths with insulin resistance and diabetes and response to interventions.
authors.affiliation: 1Division of Endocrinology, Department of Pediatrics, Children's Hospital Colorado, Anschutz Medical Campus, Aurora, CO; 2Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO; 3Department of Clinical and Diagnostic Sciences, University of Alabama at Birmingham, Birmingham, AL; 4Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO; and 5Department of Internal Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Melanie
authors.initials: M
authors.lastname: Cree-Green
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Newcomer
authors.forename: Mark
authors.initials: M
authors.lastname: Brown
authors.forename: Amber
authors.initials: A
authors.lastname: Hull
authors.forename: Amy D
authors.initials: AD
authors.lastname: West
authors.forename: Debra
authors.initials: D
authors.lastname: Singel
authors.forename: Jane E B
authors.initials: JE
authors.lastname: Reusch
authors.forename: Kim
authors.initials: K
authors.lastname: McFann
authors.forename: Judith G
authors.initials: JG
authors.lastname: Regensteiner
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Nadeau
mesh_terms: D000293:Adolescent; D002648:Child; D003430:Cross-Sectional Studies; D015444:Exercise; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology; D053580:Muscle Strength / Q000502:physiology; D010758:Phosphorus; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D010758:Phosphorus