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Fleischman A.,Harvard University | Makimura H.,Harvard University | Stanley T.L.,Harvard University | McCarthy M.A.,Harvard University | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Elderly subjects have reduced mitochondrial function. However, it remains unclear whether the decline in mitochondrial function begins earlier in the life span. Objective: The objective of the study was to determine skeletal muscle mitochondrial oxidative phosphorylation by 31phosphorous- magnetic resonance spectroscopy (MRS) across a variety of age groups. Design: This was a cross-sectional study of 121 healthy normal-weight and overweight individuals from age 8 to 55 yr. Setting: The study was conducted at a single university medical center in Boston, MA. Participants: Participants included 68 children and 53 adults from the Boston community. Interventions and Main Outcome Measures: Phosphocreatine (PCr) recovery was evaluated by 31phosphorous-MRS after submaximal exercise. Subjects were also evaluated with anthropometric measurements, metabolic profiles, and measures of physical activity. Results: PCr recovery determined by 31phosphorous- MRS is positively associated with age in univariate analysis in a cohort of individuals aged 8-55 yr (r = +0.55, P < 0.0001). Stratification of subjects into four age groups (prepubertal and early pubertal children, pubertal and postpubertal children < 18 yr, young adults aged 18-39 yr, and middle aged adults aged 40-55 yr) demonstrates prolongation of PCr recovery with increasing age across the four groups (P < 0.0001 by ANOVA). The relationship between PCr recovery and age remains strong when controlling for gender; race; ethnicity; body mass index; measures of physical activity and inactivity; and anthropometric, nutritional, and metabolic parameters (P < 0.004). Conclusions: Skeletal muscle PCr recovery measured by 31phosphorous- MRS is prolonged with age, even in children and young adults. Copyright © 2010 by The Endocrine Society. Source


McCormack S.E.,Harvard University | McCarthy M.A.,Harvard University | Farilla L.,Harvard University | Hrovat M.I.,Harvard University | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Periods of rapid growth require an increase in energy use and substrate formation. Mitochondrial function contributes to each of these and therefore may play a role in longitudinal growth. Methods: Twenty-nine children and adolescents of ages 8-15 yr were enrolled in a comprehensive longitudinal assessment of glucose homeostasis and mitochondrial function. Fasting laboratory studies and an estimate of mitochondrial function (as assessed by the time to recovery of phosphocreatine (PCr) concentration after submaximal quadriceps extension/flexion exercise using 31P magnetic resonance spectroscopy) were obtained at baseline and annually for 2 yr. Results: Data were complete for 23 subjects. Subjects were 11.3 ± 1.9 (SD) yr old at the beginning of the study; 61% were male. Average annualized growth velocity at 1 yr for boys was 7.1 ± 1.5 cm/yr and for girls 6.5 ± 1.7 cm/yr. More rapid recovery of PCr concentration, suggestive of greater skeletal muscle oxidative phosphorylation capacity at baseline, was associated with faster growth velocity in the subsequent year (r 2 = 0.29; P = 0.008). In multivariate modeling, baseline mitochondrial function remained significantly and independently associated with growth (R 2 for model = 0.51; P = 0.05 for effect of phosphocreatine recovery time constant), controlling for age, gender, Tanner stage, body mass index Z-score, and height Z-score. Conclusions: We report a novel association between time to recovery of PCr concentration after submaximal exercise and faster annual linear growth in healthy children. Future studies are needed to determine the physiological mechanisms and clinical consequences of this observation. Copyright © 2011 by The Endocrine Society. Source


Patz S.,Harvard University | Muradyan I.,Harvard University | Hrovat M.I.,Mirtech, Inc. | Dabaghyan M.,Harvard University | And 3 more authors.
New Journal of Physics | Year: 2011

We used hyperpolarized 129Xe NMR to measure pulmonary alveolar surface area per unit gas volume SA/Vgas, alveolar septal thickness h and capillary transit time τ, three critical determinants of the lung's primary role as a gas exchange organ. An analytical solution for a simplified diffusion model is described, together with a modification of the xenon transfer contrast imaging technique utilizing 90° radio-frequency pulses applied to the dissolved phase, rather than traditional 180° pulses. With this approach, three-dimensional (3D) maps of SA/Vgas were obtained. We measured global SA/Vgas, h and τ in four normal subjects, two subjects with mild interstitial lung disease (ILD) and two subjects with mild chronic obstructive pulmonary disease (COPD). In normals, SA/Vgas decreased with increasing lung volume from ∼320 to 80 cm-1; bothh ∼13μm and τ ∼ 1.5 s were relatively constant. For the two ILD subjects, h was, respectively, 36 and 97% larger than normal, quantifying an increased gas/blood tissue barrier; SA/Vgas and τ were normal. The two COPD subjects. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft. Source


Muradyan I.,Brigham and Womens Hospital | Muradyan I.,University of New Hampshire | Butler J.P.,Brigham and Womens Hospital | Butler J.P.,Harvard University | And 12 more authors.
Journal of Magnetic Resonance Imaging | Year: 2013

Purpose: To implement and characterize a single-breath xenon transfer contrast (SB-XTC) method to assess the fractional diffusive gas transport F in the lung: to study the dependence of F and its uniformity as a function of lung volume; to estimate local alveolar surface area per unit gas volume S A/VGas from multiple diffusion time measurements of F; to evaluate the reproducibility of the measurements and the necessity of B 1 correction in cases of centric and sequential encoding. Materials and Methods: In SB-XTC three or four gradient echo images separated by inversion/saturation pulses were collected during a breath-hold in eight healthy volunteers, allowing the mapping of F (thus SA/VGas) and correction for other contributions such as T1 relaxation, RF depletion and B1 inhomogeneity from inherently registered data. Results: Regional values of F and its distribution were obtained; both the mean value and heterogeneity of F increased with the decrease of lung volume. Higher values of F in the bases of the lungs in supine position were observed at lower volumes in all volunteers. Local SA/VGas (with a mean ± standard deviation of SA/VGas = 89±30 cm-1) was estimated in vivo near functional residual capacity. Calibration of SB-XTC on phantoms highlighted the necessity for B1 corrections when k-space is traversed sequentially; with centric ordering B 1 distribution correction is dispensable. Conclusion: The SB-XTC technique is implemented and validated for in vivo measurements of local S A/VGas. © 2012 Wiley Periodicals, Inc. Source


Wu Y.,Childrens Hospital | Wu Y.,Massachusetts General Hospital | Wu Y.,Harvard University | Hrovat M.I.,Mirtech, Inc. | And 11 more authors.
Journal of Magnetic Resonance Imaging | Year: 2010

Purpose: To demonstrate water- and fat-suppressed proton projection MRI (WASPI) in a clinical scanner to visualize the solid bone matrix in animal and human subjects. Materials and Methods: Pig bone specimens and polymer pellets were used to optimize the WASPI method in terms of soft-tissue suppression, image resolution, signal-tonoise ratio, and scan time on a 3T MRI scanner. The ankles of healthy 2-3-month-old live Yorkshire pigs were scanned with the optimized method. The method was also applied to the wrists of six healthy adult human volunteers to demonstrate the feasibility of the WASPI method in human subjects. A transmit/receive coil built with proton-free materials was utilized to produce a strong B1 field. A fast transmit/receive switch was developed to reduce the long receiver dead time that would otherwise obscure the signals. Results: Clear 3D WASPI images of pig ankles and human wrists, showing only the solid bone matrix and other tissues with high solid content (eg, tendons), with a spatial resolution of 2.0 mm in all three dimensions were obtained in as briefly as 12 minutes. Conclusion: WASPI of the solid matrix of bone in humans and animals in vivo is feasible. © 2010 Wiley-Liss, Inc. Source

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