MR-Safe Cartesian Platform for Active Cardiac Shimming: Preliminary Validation.

OBJECTIVE: Implanted Cardioverter Defibrillators (ICDs) induce a large (100 parts per million) inhomogeneous magnetic field in the magnetic resonance imaging (MRI) scanner which cannot be corrected by the scanner's built-in shim coils, leading to significant image artifacts that can make portions of the heart unreadable. To compensate for the field inhomogeneity, an active shim coil capable of countering the field deviation in user-defined regions was designed that must be optimally placed at patient-specific locations. We aim to develop and evaluate an MR-safe robotic solution for automated shim coil positioning. METHODS: We designed and fabricated an MR-safe Cartesian platform that holds the shim coil inside the scanner. The platform consists of three lead screw stages actuated by pneumatic motors, achieving decoupled translations of 140 mm in each direction. The platform is made of plastics and fiberglass with the control electronics placed outside the scanner room, ensuring MR safety. Mechanical modeling was derived to provide design specifications. RESULTS: Experiments show that the platform achieves less than 2 mm average motion error and 0.5 mm repeatability in all directions, and reduces the adjustment time from 5 min to a few seconds. Phantom and animal trials were conducted, showing that the proposed system is able to position a heavy shim coil ( kg) for improved ICD artifact suppression. CONCLUSION: This robotic platform provides an effective method for reliable shim coil positioning inside the scanner. SIGNIFICANCE: This work contributes to improving cardiac MRI quality that could facilitate accurate diagnosis and treatment planning for patients with implanted ICDs.

Balanced-force shim system for correcting magnetic-field inhomogeneities in the heart due to implanted cardioverter defibrillators.

Background: In the US, 1.4 million people have implanted ICDs for reducing the risk of sudden death due to ventricular arrhythmias. Cardiac MRI (cMR) is of particular interest in the ICD patient population as cMR is the optimal imaging modality for distinguishing cardiac conditions that predispose to sudden death, and it is the best method to plan and guide therapy. However, all ICDs contain a ferromagnetic transformer which imposes a large inhomogeneous magnetic field in sections of the heart, creating large image voids that can mask important pathology. A shim system was devised to resolve these ICD issues. A shim coil system (CSS) that corrects ICD artifacts over a user-selected Region-of-Interest (ROI), was constructed and validated. Methods: A shim coil was constructed that can project a large magnetic field for distances of ~15 cm. The shim-coil can be positioned safely anywhere within the scanner bore. The CSS includes a cantilevered beam to hold the shim coil. Remotely controlled MR-conditional motors allow 2 mm-accuracy three-dimensional shim-coil position. The shim coil is located above the subjects and the imaging surface-coils. Interaction of the shim coil with the scanner's gradients was eliminated with an amplifier that is in a constant current mode. Coupling with the scanners' radio-frequency (rf) coils, was reduced with shielding, low-pass filters, and cable shield traps. Software, which utilizes magnetic field (B0) mapping of the ICD inhomogeneity, computes the optimal location for the shim coil and its corrective current. ECG gated single- and multiple-cardiac-phase 2D GRE and SSFP sequences, as well as 3D ECG-gated respiratory-navigated IR-GRE (LGE) sequences were tested in phantoms and N = 3 swine with overlaid ICDs. Results: With all cMR sequences, the system reduced artifacts from >100 ppm to <25 ppm inhomogeneity, which permitted imaging of the entire left ventricle in swine with ICD-related voids. Continuously acquired Gradient recalled echo or Steady State Free Precession images were used to interactively adjust the shim current and coil location. Conclusion: The shim system reduced large field inhomogeneities due to implanted ICDs and corrected most ICD-related image distortions. Externally-controlled motorized translation of the shim coil simplified its utilization, supporting an efficient cardiac MRI workflow.

A portable single-sided magnet system for remote NMR measurements of pulmonary function.

In this work, we report initial results from a light-weight, low field magnetic resonance device designed to make relative pulmonary density measurements at the bedside. The development of this device necessarily involves special considerations for the magnet, RF and data acquisition schemes as well as a careful analysis of what is needed to provide useful information in the ICU. A homogeneous field region is created remotely from the surface of the magnet such that when the magnet is placed against the chest, an NMR signal is measured from a small volume in the lung. In order to achieve portability, one must trade off field strength and therefore spatial resolution. We report initial measurements from a ping-pong ball size region in the lung as a function of lung volume. As expected, we measured decreased signal at larger lung volumes since lung density decreases with increasing lung volume. Using a CPMG sequence with ΔTE=3.5 ms and a 20 echo train, a signal to noise ratio ~1100 was obtained from an 8.8mT planar magnet after signal averaging for 43 s. This is the first demonstration of NMR measurements made on a human lung with a light-weight planar NMR device. We argue that very low spatial resolution measurements of different lobar lung regions will provide useful diagnostic information for clinicians treating Acute Respiratory Distress Syndrome as clinicians want to avoid ventilator pressures that cause either lung over distension (too much pressure) or lung collapse (too little pressure).

Single-breath xenon polarization transfer contrast (SB-XTC): implementation and initial results in healthy humans.

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)/V(Gas) 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 S(A)/V(Gas)) and correction for other contributions such as T(1) relaxation, RF depletion and B(1) 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 S(A)/V(Gas) (with a mean ± standard deviation of S(A)/V(Gas) = 89 ± 30 cm(-1)) was estimated in vivo near functional residual capacity. Calibration of SB-XTC on phantoms highlighted the necessity for B(1) 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)/V(Gas).

Skeletal muscle mitochondrial function is associated with longitudinal growth velocity in children and adolescents.

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 (31)P 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.

Bone mineral imaged in vivo by 31P solid state MRI of human wrists.

PURPOSE: To implement solid state (31)P MRI ((31)P SMRI) in a clinical scanner to visualize bone mineral. MATERIALS AND METHODS: Wrists of seven healthy volunteers were scanned. A quadrature wrist (31)P transmit/receive coil provided strong B(1) and good signal-to-noise ratio (SNR). A (1)H-(31)P frequency converter was constructed to enable detection of the (31)P signal by means of the (1)H channel. Data points lost in the receiver dead time were recovered by a second acquisition with longer dwell time and lower gradient strength. RESULTS: Three-dimensional (31)P images, showing only bone mineral of the wrist, were obtained with a clinical 3 Tesla (T) scanner. In the best overall case an image with isotropic resolution of ∼5.1 mm and SNR of 30 was obtained in 37 min. (31)P NMR properties (resonance line width 2 kHz and T(1) 17-19 s) of in vivo human bone mineral were measured. CONCLUSION: In vivo (31)P SMRI visualization of human wrist bone mineral with a clinical MR scanner is feasible with suitable modifications to circumvent the scanners' limitations in reception of short-T(2) signals. Frequency conversion methodology is useful for implementing (31)P SMRI measurements on scanners which do not have multinuclear capability or for which the multinuclear receiver dead time is excessive.

Increased skeletal muscle phosphocreatine recovery after sub-maximal exercise is associated with increased carotid intima-media thickness.

BACKGROUND: The association between skeletal muscle mitochondrial function and CVD risk in healthy subjects is unknown. METHODS: Forty subjects were evaluated for CVD risk with lipid profile, oral glucose tolerance test and measurement of carotid intima-media thickness (cIMT). Skeletal muscle mitochondrial function was determined by phosphocreatine recovery after sub-maximal exercise with (31)Phosphorous-MRS and represented as τPCr. RESULTS: τPCr was positively associated with age (r=+0.41; P=0.009) and cIMT (r=+0.50; P=0.001) on univariate analyses. In multivariate regression analysis controlling for age, the association between τPCr and cIMT remained significant (ß=0.003; P=0.03). This association remained significant after controlling for traditional risk factors for CVD including age, gender, tobacco use, BMI, blood pressure, cholesterol and fasting glucose in a combined model (ß=0.003; P=0.04; R(2)=0.53; P=0.008 for overall model). CONCLUSIONS: These data suggest a novel association between skeletal muscle τPCr and increased cIMT, independent of age or traditional CVD risk factors.

The association of growth hormone parameters with skeletal muscle phosphocreatine recovery in adult men.

CONTEXT: Previous studies have suggested a relationship between GH and mitochondrial function. However, little is known about the relationship of specific GH indices and in vivo measures of mitochondrial function in humans. OBJECTIVE: The objective of this study was to determine the association between GH, IGF-I, and phosphocreatine (PCr) recovery, a measure of mitochondrial function, in otherwise healthy adults. DESIGN: Thirty-seven healthy men and women were studied at a single university medical center. Subjects underwent GH stimulation testing with GH releasing hormone-arginine and measurement of IGF-I. Mitochondrial function was determined by PCr recovery after submaximal exercise by (31)Phosphorous magnetic resonance spectroscopy. Subjects underwent assessment of lean and fat mass with use of dual energy X-ray absorptiometry. RESULTS: There were no differences in PCr recovery between men and women (men 20.7±1.5 vs. women 24.8±1.4 mM/min; P > 0.05). IGF-I (r = 0.33; P = 0.04) was associated with PCr recovery in all subjects. Among men, IGF-I (r = 0.69; P = 0.003), peak stimulated GH (r = 0.52; P = 0.04), and GH area under the curve (AUC) (r = 0.53; P = 0.04) were significantly associated with PCr recovery. However, neither IGF-I, peak stimulated GH, nor GH AUC (all P > 0.05) were associated with PCr recovery in women. After adjusting for age, race, and physical activity, IGF-I remained significantly associated with PCr recovery (ß = 0.10; P = 0.02) among men. CONCLUSIONS: IGF-I, peak stimulated GH, and GH AUC are associated with skeletal muscle PCr recovery in men.

Skeletal muscle phosphocreatine recovery after submaximal exercise in children and young and middle-aged adults.

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 (31)phosphorous-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 (31)phosphorous-MRS after submaximal exercise. Subjects were also evaluated with anthropometric measurements, metabolic profiles, and measures of physical activity. RESULTS: PCr recovery determined by (31)phosphorous-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 (31)phosphorous-MRS is prolonged with age, even in children and young adults.

Bone matrix imaged in vivo by water- and fat-suppressed proton projection MRI (WASPI) of animal and human subjects.

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-to-noise 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 B(1) 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.

Quantitative (31)P NMR spectroscopy and (1)H MRI measurements of bone mineral and matrix density differentiate metabolic bone diseases in rat models.

In this study, bone mineral density (BMD) of normal (CON), ovariectomized (OVX), and partially nephrectomized (NFR) rats was measured by (31)P NMR spectroscopy; bone matrix density was measured by (1)H water- and fat-suppressed projection imaging (WASPI); and the extent of bone mineralization (EBM) was obtained by the ratio of BMD/bone matrix density. The capability of these MR methods to distinguish the bone composition of the CON, OVX, and NFR groups was evaluated against chemical analysis (gravimetry). For cortical bone specimens, BMD of the CON and OVX groups was not significantly different; BMD of the NFR group was 22.1% (by (31)P NMR) and 17.5% (by gravimetry) lower than CON. For trabecular bone specimens, BMD of the OVX group was 40.5% (by (31)P NMR) and 24.6% (by gravimetry) lower than CON; BMD of the NFR group was 26.8% (by (31)P NMR) and 21.5% (by gravimetry) lower than CON. No significant change of cortical bone matrix density between CON and OVX was observed by WASPI or gravimetry; NFR cortical bone matrix density was 10.3% (by WASPI) and 13.9% (by gravimetry) lower than CON. OVX trabecular bone matrix density was 38.0% (by WASPI) and 30.8% (by gravimetry) lower than CON, while no significant change in NFR trabecular bone matrix density was observed by either method. The EBMs of OVX cortical and trabecular specimens were slightly higher than CON but not significantly different from CON. Importantly, EBMs of NFR cortical and trabecular specimens were 12.4% and 26.3% lower than CON by (31)P NMR/WASPI, respectively, and 4.0% and 11.9% lower by gravimetry. Histopathology showed evidence of osteoporosis in the OVX group and severe secondary hyperparathyroidism (renal osteodystrophy) in the NFR group. These results demonstrate that the combined (31)P NMR/WASPI method is capable of discerning the difference in EBM between animals with osteoporosis and those with impaired bone mineralization.

Mitochondrial function and insulin resistance in overweight and normal-weight children.

BACKGROUND: Obesity has become an epidemic in children, associated with an increase in insulin resistance and metabolic dysfunction. Mitochondrial function is known to be an important determinant of glucose metabolism in adults. However, little is known about the relationship between mitochondrial function and obesity, insulin resistance, energy expenditure, and pubertal development in children. METHODS: Seventy-four participants, 37 overweight (> or = 85th percentile body mass index for age and sex) and 37 normal-weight (< 85th percentile) without personal or family history of diabetes mellitus were enrolled. Subjects were evaluated with an oral glucose tolerance test, metabolic markers, resting energy expenditure, Tanner staging, and (31)P magnetic resonance spectroscopy of skeletal muscle for mitochondrial function. RESULTS: Overweight and normal-weight children showed no difference in muscle ATP synthesis [phosphocreatine (PCr) recovery after exercise] (32.4 +/- 2.3 vs. 34.1 +/- 2.1, P = 0.58). However, insulin-resistant children had significantly prolonged PCr recovery when compared with insulin-sensitive children, by homeostasis model assessment for insulin resistance quartile (ANOVA, P = 0.04). Similarly, insulin-resistant overweight children had PCr recovery that was prolonged compared with insulin-sensitive overweight children (P = 0.01). PCr recovery was negatively correlated with resting energy expenditure in multivariate modeling (P = 0.03). Mitochondrial function worsened during mid-puberty in association with insulin resistance. CONCLUSION: Reduced skeletal muscle mitochondrial oxidative phosphorylation, assessed by PCr recovery, is associated with insulin resistance and an altered metabolic phenotype in children. Normal mitochondrial function may be associated with a healthier metabolic phenotype in overweight children. Further studies are needed to investigate the long-term physiological consequences and potential treatment strategies targeting children with reduced mitochondrial function.

Quantitative bone matrix density measurement by water- and fat-suppressed proton projection MRI (WASPI) with polymer calibration phantoms.

The density of the organic matrix of bone substance is a critical parameter necessary to clinically evaluate and distinguish structural and metabolic pathological conditions such as osteomalacia in adults and rickets in growing children. Water- and fat-suppressed proton projection MRI (WASPI) was developed as a noninvasive means to obtain this information. In this study, a density calibration phantom was developed to convert WASPI intensity to true bone matrix density. The phantom contained a specifically designed poly(ethylene oxide)/poly(methyl methacrylate) (PEO/PMMA) blend, whose MRI properties (T(1), T(2), and resonance linewidth) were similar to those of solid bone matrix (collagen, tightly bound water, and other immobile molecules), minimizing the need to correct for differences in T(1) and/or T(2) relaxation between the phantom and the subject. Cortical and trabecular porcine bone specimens were imaged using WASPI with the calibration phantom in the field of view (FOV) as a stable intensity reference. Gravimetric and amino acid analyses were carried out on the same specimens after WASPI, and the chemical results were found to be highly correlated (r(2) = 0.98 and 0.95, respectively) to the WASPI intensity. By this procedure the WASPI intensity can be used to obtain the true bone matrix mass density in g cm(-3).

Human pulmonary imaging and spectroscopy with hyperpolarized 129Xe at 0.2T.

RATIONALE AND OBJECTIVES: Using a novel (129)Xe polarizer with high throughput (1-2 L/hour) and high polarization (approximately 55%), our objective was to demonstrate and characterize human pulmonary applications at 0.2T. Specifically, we investigated the ability of (129)Xe to measure the alveolar surface area per unit volume of gas, S(A)/V(gas). MATERIALS AND METHODS: Variable spin echo time (TE) gradient and radiofrequency (RF) echoes were used to obtain estimates of the lung's contribution to both T(2)* and T(2). Standard multislice ventilation images were obtained and signal-to-noise ratio (SNR) determined. Whole-lung, time-dependent measurements of (129)Xe diffusion from gas to septal tissue were obtained with a chemical shift saturation recovery (CSSR) method. Four healthy subjects were studied, and the Butler et al CSSR formalism (J Phys Condensed Matter 2002; 14:L297-L304) was used to calculate S(A)/V(gas). A single-breath version of the xenon transfer contrast (SB-XTC) method was implemented and used to image (129)Xe diffusion between alveolar gas and septal tissue. A direct comparison of CSSR and SB-XTC was performed. RESULTS: T(2)*=135+/-29 ms amd T(2)=326.2+/-9.5 ms. Maximum SNR=36 for ventilation images from inhalation of 1L 86% (129)Xe and voxel volume =0.225 mL. CSSR analysis showed S(A)/V(gas) decreased with increasing lung volume in a manner very similar to that observed from histology measurements; however, the absolute value of S(A)/V(gas) was approximately 40% smaller than histology values. SB-XTC images in different postures demonstrate gravitationally dependent values. Initial comparison of CSSR with XTC showed fairly good agreement with expected ratios. CONCLUSIONS: Hyperpolarized (129)Xe human imaging and spectroscopy are very promising methods to provide functional information about the lung.

Hyperpolarized (129)Xe MRI: a viable functional lung imaging modality?

The majority of researchers investigating hyperpolarized gas MRI as a candidate functional lung imaging modality have used (3)He as their imaging agent of choice rather than (129)Xe. This preference has been predominantly due to, (3)He providing stronger signals due to higher levels of polarization and higher gyromagnetic ratio, as well as its being easily available to more researchers due to availability of polarizers (USA) or ease of gas transport (Europe). Most researchers agree, however, that hyperpolarized (129)Xe will ultimately emerge as the imaging agent of choice due to its unlimited supply in nature and its falling cost. Our recent polarizer technology delivers vast improvements in hyperpolarized (129)Xe output. Using this polarizer, we have demonstrated the unique property of xenon to measure alveolar surface area noninvasively. In this article, we describe our human protocols and their safety, and our results for the measurement of the partial pressure of pulmonary oxygen (pO(2)) by observation of (129)Xe signal decay. We note that the measurement of pO(2) by observation of (129)Xe signal decay is more complex than that for (3)He because of an additional signal loss mechanism due to interphase diffusion of (129)Xe from alveolar gas spaces to septal tissue. This results in measurements of an equivalent pO(2) that accounts for both traditional T(1) decay from pO(2) and that from interphase diffusion. We also provide an update on new technological advancements that form the foundation for an improved compact design polarizer as well as improvements that provide another order-of-magnitude scale-up in xenon polarizer output.

Water- and fat-suppressed proton projection MRI (WASPI) of rat femur bone.

Investigators often study rats by microCT to investigate the pathogenesis and treatment of skeletal disorders in humans. However, microCT measurements provide information only on bone mineral content and not the solid matrix. CT scans are often carried out on cancellous bone, which contains a significant volume of marrow cells, stroma, water, and fat, and thus the apparent bone mineral density (BMD) does not reflect the mineral density within the matrix, where the mineral crystals are localized. Water- and fat-suppressed solid-state proton projection imaging (WASPI) was utilized in this study to image the solid matrix content (collagen, tightly bound water, and other immobile molecules) of rat femur specimens, and meet the challenges of small sample size and demanding submillimeter resolution. A method is introduced to recover the central region of k-space, which is always lost in the receiver dead time when free induction decays (FIDs) are acquired. With this approach, points near the k-space origin are sampled under a small number of radial projections at reduced gradient strength. The typical scan time for the current WASPI experiments was 2 hr. Proton solid-matrix images of rat femurs with 0.4-mm resolution and 12-mm field of view (FOV) were obtained. This method provides a noninvasive means of studying bone matrix in small animals.

Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults.

Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30-40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (-0.8 +/- 0.5 vs. +0.7 +/- 0.3 mg.kg(-1).min(-1), P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/nuclear DNA (-52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9). (31)P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures (r2 = 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity.

An open magnet utilizing ferro-refraction current magnification.

Ferro-refraction is the field magnification that is obtained when a current segment is near a high magnetic permeable boundary. It is shown that ferro-refraction may be used in the design of magnets for NMR or MRI to increase the efficiency of these magnets. The field may be modeled analytically with the Biot--Savart law and the inclusion of mirror image currents. Ferro-refraction is particularly useful in the design of monohedral magnets, magnets producing a remote homogeneous region which have the magnetic sources arranged to one side. These magnets have also been called planar magnets. Two designs for a monohedral magnet which produce good agreement between experimental and analytic results are presented.