No abstract

Hyperpolarized (129)Xe human imaging and spectroscopy are very promising methods to provide functional information about the lung.

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.

-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 (Ϫ0.8 Ϯ 0.5 vs. ϩ0.7 Ϯ 0.3 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 , P ϭ 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/ nuclear DNA (Ϫ52%, P ϭ 0.005), with no change in placebo-treated subjects (ϩ8%, P ϭ 0.9).31 P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures (r 2 ϭ 0.5, P ϭ 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. human immunodeficiency virus; insulin resistance; magnetic resonance spectroscopy RECENT DATA SUGGEST that mitochondrial dysfunction precedes the development of diabetes in insulin-resistant offspring of patients with type 2 diabetes mellitus (DM) (15). Resistance to insulin action at the skeletal muscle is the earliest abnormality in such patients. Evaluation of gene expression in muscle samples from individuals with type 2 DM and impaired glucose tolerance has identified alterations in several genes involved in mitochondrial oxidative phosphorylation (12,14). For example, both peroxisomal proliferator activator receptor-␥ coactivator (PGC1) and nuclear respiratory factor (NRF) are reduced in prediabetic and diabetic human muscle tissue. These data suggest that both individuals with diabetes and those in the prediabetic state without the clinical effect of hyperglycemia show diminished gene expression of elements essential for the mitochondrial respiratory chain oxidative phosphorylation.Animal and human models of DM suggest that mitochondrial dysfunction is significantly related to the development of insulin resistance. Analysis of the muscle tissue from the insulin-resistant obese ob/ob mice compared with thin ob/ϩ littermates revealed a reduction in the expression of a subunit of mitochondrial ATP synthase (20). In addition,...