Comparison of Global Cerebral Blood Flow Measured by Phase-Contrast Mapping MRI with O-15-H2O Positron Emission Tomography

PURPOSE: To compare mean global cerebral blood flow (CBF) measured by phase‐contrast mapping magnetic resonance imaging (PCM MRI) and by (15)O‐H(2)O positron emission tomography (PET) in healthy subjects. PCM MRI is increasingly being used to measure mean global CBF, but has not been validated in vivo against an accepted reference technique. MATERIALS AND METHODS: Same‐day measurements of CBF by (15)O‐H(2)O PET and subsequently by PCM MRI were performed on 22 healthy young male volunteers. Global CBF by PET was determined by applying a one‐tissue compartment model with measurement of the arterial input function. Flow was measured in the internal carotid and vertebral arteries by a noncardiac triggered PCM MRI sequence at 3T. The measured flow was normalized to total brain weight determined from a volume‐segmented 3D T (1)‐weighted anatomical MR‐scan. RESULTS: Mean CBF was 34.9 ± 3.4 mL/100 g/min measured by (15)O‐H(2)O PET and 57.0 ± 6.8 mL/100 g/min measured by PCM MRI. The measurements were highly correlated (P = 0.0008, R(2) = 0.44), although values obtained by PCM MRI were higher compared to (15)O‐H(2)O PET (absolute and relative differences were 22.0 ± 5.2 mL/100 g/min and 63.4 ± 14.8%, respectively). CONCLUSION: This study confirms the use of PCM MRI for quantification of global CBF, but also that PCM MRI systematically yields higher values relative to (15)O‐H(2)O PET, probably related to methodological bias. Level of Evidence: 3 J. Magn. Reson. Imaging 2017;45:692–699

Asymmetric dimethylarginine in somatically healthy schizophrenia patients treated with atypical antipsychotics:a case-control study

BACKGROUND: Schizophrenia is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, and the L-arginine:ADMA ratio are markers of endothelial dysfunction that predict mortality and adverse outcome in a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L-arginine: ADMA ratio are positively correlated to measures of oxidative stress. METHODS: We included 40 schizophrenia patients treated with AAP, but without somatic disease or drug abuse, and 40 healthy controls. Plasma concentrations of ADMA and L-arginine were determined by high-performance liquid chromatography. Data were related to markers of systemic oxidative stress on DNA, RNA and lipids, as well as measures of medication load, duration of disease and current symptomatology. RESULTS: Plasma ADMA and the L-arginine:ADMA ratio did not differ between schizophrenia patients and controls. Furthermore, ADMA and the L-arginine:ADMA ratio showed no correlations with oxidative stress markers, medication load, or Positive and Negative Syndrome Scale scores. CONCLUSIONS: Schizophrenia and treatment with AAP was not associated with increased levels of plasma ADMA or the L-arginine:ADMA ratio. Furthermore, plasma levels of ADMA were not associated with levels of systemic oxidative stress in vivo

Central nervous system frontiers for the use of erythropoietin

Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical models of CNS disorders. Epoetin alfa has also been shown to prevent the loss of autoregulation of cerebral blood flow in a model of subarachnoid hemorrhage. The mechanisms of EPO-induced neuroprotection include prevention of glutamate-induced toxicity, inhibition of apoptosis, anti-inflammatory effects, antioxidant effects, and stimulation of angiogenesis. Collectively, these findings suggest that epoetin alfa may have potential therapeutic utility in patients with ischemic CNS injury. ERYTHROPOIETIN: EFFECTS BEYOND ERYTHROPOIESIS Erythropoietin (EPO) is a naturally occurring glyco-protein hormone with a primary biologic function of regulating erythropoiesis in response to decreased ox