Effects of exercise and lifestyle modification on fitness, insulin resistance, skeletal muscle oxidative phosphorylation and intramyocellular lipid content in obese children and adolescents.

BACKGROUND: Obesity is associated with poor fitness and adverse metabolic consequences in children. OBJECTIVE: To investigate how exercise and lifestyle modification may improve fitness and insulin sensitivity in this population. DESIGN AND SUBJECTS: Randomized controlled trial, 21 obese (body mass index ≥ 95% percentile) subjects, ages 10 to 17 years. METHODS: Subjects were given standardized healthful lifestyle advice for 8 weeks. In addition, they were randomized to an in-home supervised exercise intervention (n = 10) or control group (n = 11). MEASUREMENTS: Fasting laboratory studies (insulin, glucose, lipid profile) and assessments of fitness, body composition, skeletal muscle oxidative phosphorylation and intramyocellular lipid content (IMCL), were performed at baseline and study completion. RESULTS: Subjects were 13.0 ± 1.9 (standard deviation) years old, 72% female and 44% non-white. Exercise improved fitness (P = 0.03) and power (P = 0.01), and increased IMCL (P = 0.02). HOMA-IR decreased among all subjects in response to lifestyle modification advice (P = 0.01), regardless of exercise training assignment. In univariate analysis in all subjects, change in cardiovascular fitness was associated with change in HOMA-IR. In exploratory analyses, increased IMCL was associated with greater resting energy expenditure (r = 0.78, P = 0.005) and a decrease in fasting respiratory quotient (r = -0.70, P = 0.02) (n = 11). CONCLUSIONS: Change in fitness was found to be related to change in insulin resistance in response to lifestyle modification and exercise in obese children. IMCL increased with exercise in these obese children, which may reflect greater muscle lipid oxidative capacity.

A System for Open-Access He Human Lung Imaging at Very Low Field.

We describe a prototype system built to allow open-access very-low-field MRI of human lungs using laser-polarized (3)He gas. The system employs an open four-coil electromagnet with an operational B(0) field of 4 mT, and planar gradient coils that generate gradient fields up to 0.18 G/cm in the x and y direction and 0.41 G/cm in the z direction. This system was used to obtain (1)H and (3)He phantom images and supine and upright (3)He images of human lungs. We include discussion on challenges unique to imaging at 50 -200 kHz, including noise filtering and compensation for narrow-bandwidth coils.

3He lung imaging in an open access, very-low-field human magnetic resonance imaging system.

The human lung and its functions are extremely sensitive to gravity; however, the conventional high-field magnets used for most laser-polarized (3)He MRI of the human lung restrict subjects to lying horizontally. Imaging of human lungs using inhaled laser-polarized (3)He gas is demonstrated in an open-access very-low-magnetic-field (<5 mT) MRI instrument. This prototype device employs a simple, low-cost electromagnet, with an open geometry that allows variation of the orientation of the imaging subject in a two-dimensional plane. As a demonstration, two-dimensional lung images were acquired with 4-mm in-plane resolution from a subject in two orientations: lying supine and sitting in a vertical position with one arm raised. Experience with this prototype device will guide optimization of a second-generation very-low-field imager to enable studies of human pulmonary physiology as a function of subject orientation.

Measuring surface-area-to-volume ratios in soft porous materials using laser-polarized xenon interphase exchange nuclear magnetic resonance.

We demonstrate a minimally invasive nuclear magnetic resonance (NMR) technique that enables determination of the surface-area-to-volume ratio (S/V) of soft porous materials from measurements of the diffusive exchange of laser-polarized 129Xe between gas in the pore space and 129Xe dissolved in the solid phase. We apply this NMR technique to porous polymer samples and find approximate agreement with destructive stereological measurements of S/V obtained with optical confocal microscopy. Potential applications of laser-polarized xenon interphase exchange NMR include measurements of in vivo lung function in humans and characterization of gas chromatography columns.

Analytic reconstruction of magnetic resonance imaging signal obtained from a periodic encoding field.

We have proposed a two-dimensional PERiodic-Linear (PERL) magnetic encoding field geometry B(x,y) = g(y)y cos(q(x)x) and a magnetic resonance imaging pulse sequence which incorporates two fields to image a two-dimensional spin density: a standard linear gradient in the x dimension, and the PERL field. Because of its periodicity, the PERL field produces a signal where the phase of the two dimensions is functionally different. The x dimension is encoded linearly, but the y dimension appears as the argument of a sinusoidal phase term. Thus, the time-domain signal and image spin density are not related by a two-dimensional Fourier transform. They are related by a one-dimensional Fourier transform in the x dimension and a new Bessel function integral transform (the PERL transform) in the y dimension. The inverse of the PERL transform provides a reconstruction algorithm for the y dimension of the spin density from the signal space. To date, the inverse transform has been computed numerically by a Bessel function expansion over its basis functions. This numerical solution used a finite sum to approximate an infinite summation and thus introduced a truncation error. This work analytically determines the basis functions for the PERL transform and incorporates them into the reconstruction algorithm. The improved algorithm is demonstrated by (1) direct comparison between the numerically and analytically computed basis functions, and (2) reconstruction of a known spin density. The new solution for the basis functions also lends proof of the system function for the PERL transform under specific conditions.

Skeletal muscle chemoreflex and pHi in exercise ventilatory control.

To determine whether skeletal muscle hydrogen ion mediates ventilatory drive in humans during exercise, 12 healthy subjects performed three bouts of isotonic submaximal quadriceps exercise on each of 2 days in a 1.5-T magnet for 31P-magnetic resonance spectroscopy (31P-MRS). Bilateral lower extremity positive pressure cuffs were inflated to 45 Torr during exercise (BLPPex) or recovery (BLPPrec) in a randomized order to accentuate a muscle chemoreflex. Simultaneous measurements were made of breath-by-breath expired gases and minute ventilation, arterialized venous blood, and by 31P-MRS of the vastus medialis, acquired from the average of 12 radio-frequency pulses at a repetition time of 2.5 s. With BLPPex, end-exercise minute ventilation was higher (53.3 +/- 3.8 vs. 37.3 +/- 2.2 l/min; P < 0.0001), arterialized PCO2 lower (33 +/- 1 vs. 36 +/- 1 Torr; P = 0.0009), and quadriceps intracellular pH (pHi) more acid (6.44 +/- 0.07 vs. 6.62 +/- 0.07; P = 0.004), compared with BLPPrec. Blood lactate was modestly increased with BLPPex but without a change in arterialized pH. For each subject, pHi was linearly related to minute ventilation during exercise but not to arterialized pH. These data suggest that skeletal muscle hydrogen ion contributes to the exercise ventilatory response.

Abnormal skeletal muscle oxidative capacity after lung transplantation by 31P-MRS.

Although lung transplantation improves exercise capacity by removal of a ventilatory limitation, recipients' postoperative maximum oxygen uptake (VO2max) remains markedly abnormal. To determine if abnormal skeletal muscle oxidative capacity contributes to this impaired aerobic capacity, nine lung transplant recipients and eight healthy volunteers performed incremental quadriceps exercise to exhaustion with simultaneous measurements of pulmonary gas exchange, minute ventilation, blood lactate, and quadriceps muscle pH and phosphorylation potential by 31P-magnetic resonance spectroscopy (31P-MRS). Five to 38 mo after lung transplantation, peak VO2 was decreased compared with that of normal control subjects (6.7 +/- 0.4 versus 12.3 +/- 1.0 ml/min/kg, p < 0.001), even after accounting for differences in age and lean body weight. Neither ventilation, arterial O2 saturation nor mild anemia could account for the decrease in aerobic capacity. Quadriceps muscle intracellular pH (pH(i)) was more acidic at rest (7.07 +/- 0.01 versus 7.12 +/- 0.01 units, p < 0.05) and fell during exercise from baseline values at a lower metabolic rate (282 +/- 21 versus 577 +/- 52 ml/min, p < 0.001). Regressions for pH(i) versus VO2, phosphocreatine/inorganic phosphate ratio (PCr/Pi) versus VO2, and blood lactate versus pH(i) were not different. Among transplant recipients, the metabolic rate at which pH(i) fell correlated closely with VO2max (r = 0.87, p < 0.01). The persistent decrease in VO2max after lung transplantation may be related to abnormalities of skeletal muscle oxidative capacity.

Dietary effects on exercising muscle metabolism and performance by 31P-MRS.

To determine how diet modulates short-term exercise capacity, skeletal muscle pH and bioenergetic state were examined by 31P-magnetic resonance spectroscopy in nine healthy volunteers. Subjects performed incremental quadriceps exercise to exhaustion after 5 days of high-carbohydrate (HCHO) or high-fat (HFAT) diet randomly assigned in crossover fashion and separated by a 2.5-day period of ad libitum mixed diet. Simultaneous measurements were made of pulmonary gas exchange, minute ventilation, and quadriceps muscle pH and phosphorylation potential. At rest and peak exercise, respiratory exchange ratio and minute ventilation were higher after HCHO than after HFAT (P < 0.05), reflecting greater CHO utilization. Peak O2 consumption (VO2) was not increased after HCHO (P > 0.05), but exercise duration was (339 +/- 34 s for HCHO vs. 308 +/- 25 s for HFAT; P < 0.05). HCHO was associated with a blunted early fall of phosphocreatine (PCr)/Pi vs. VO2 (-4.1 +/- 0.7 x 10(-2) min/ml for HCHO vs. -5.6 +/- 1.2 x 10(-2) min/ml for HFAT; P < 0.05). On both study days, the slope of PCr/Pi vs. VO2, before and after the PCr threshold, was correlated with exercise time. The results suggest that a diet rich in CHO improves exercise efficiency through beneficial effects on intracellular phosphorylation potential.

Effects related to temperature changes during MR imaging.

Magnetic resonance (MR) imaging has been proposed as a method of monitoring the interstitial laser heating of tissue for the clinical treatment of tumors (laser hyperthermia). The treatment causes considerable temperature changes over the time that image data are acquired, and therefore an analysis of the time-dependent effects of heating is required. The problem is expressed mathematically, and computer-simulated images are compared with those obtained from experimental heating and imaging of gel phantoms. Results show that at the rates of heating typical for laser hyperthermia and even with the relatively slow standard imaging techniques used, generation of artifact is not a major concern. It is also shown that a spatial spin signal magnitude distribution, evolving in time, is effectively sampled at the time to when the low-numbered phase-encoding steps are collected at to. It is noted, however, that substantial temperature changes during image data acquisition make accurate temperature determination difficult and place limits on MR imaging for quantitative spatial temperature mapping.

Simultaneous multinuclear magnetic resonance imaging and spectroscopy.

A technique has been developed to perform simultaneous multinuclear magnetic resonance imaging and spatially localized spectroscopy. It is inherently superior in terms of time efficiency over current approaches which use sequential or interleaved methods. The pulse sequence uses a parallel excitation and acquisition scheme to acquire multislice proton images concurrently with phosphorus-31 spectroscopic images. Because the phosphorus signal is necessarily collected in the presence of a gradient, an essential element of the technique is an algorithm to extract pure chemical-shift information.