Arterial Spin Labeling-Based MR Angiography for Cerebrovascular Diseases: Principles and Clinical Applications.

Arterial spin labeling (ASL) is a noninvasive imaging technique that labels the proton spins in arterial blood and uses them as endogenous tracers. Brain perfusion imaging with ASL is becoming increasingly common in clinical practice, and clinical applications of ASL for intracranial magnetic resonance angiography (MRA) have also been demonstrated. Unlike computed tomography (CT) angiography and cerebral angiography, ASL-based MRA does not require contrast agents. ASL-based MRA overcomes most of the disadvantages of time-of-flight (TOF) MRA. Several schemes have been developed for ASL-based MRA; the most common method has been pulsed ASL, but more recently pseudo-continuous ASL, which provides a higher signal-to-noise ratio (SNR), has been used more frequently. New methods that have been developed include direct intracranial labeling methods such as velocity-selective ASL and acceleration-selective ASL. MRA using an extremely short echo time (eg, silent MRA) or ultrashort echo-time (TE) MRA can suppress metal susceptibility artifacts and is ideal for patients with a metallic device implanted in a cerebral vessel. Vessel-selective 4D ASL MRA can provide digital subtraction angiography (DSA)-like images. This review highlights the principles, clinical applications, and characteristics of various ASL-based MRA techniques. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

An International Standardized Magnetic Resonance Imaging Protocol for Diagnosis and Follow-up of Patients with Multiple Sclerosis: Advocacy, Dissemination, and Implementation Strategies.

Standardized magnetic resonance imaging (MRI) protocols are important for the diagnosis and monitoring of patients with multiple sclerosis (MS). The Consortium of Multiple Sclerosis Centers (CMSC) convened an international panel of MRI experts to review and update the current guidelines. The objective was to update the standardized MRI protocol and clinical guidelines for diagnosis and follow-up of MS and develop strategies for advocacy, dissemination, and implementation. Conference attendees included neurologists, radiologists, technologists, and imaging scientists with expertise in MS. Representatives from the CMSC, Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, US Department of Veteran Affairs, National Multiple Sclerosis Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis companies were present. Before the meeting, CMSC members were surveyed about standardized MRI protocols, gadolinium use, need for diffusion-weighted imaging, and the central vein sign. The panel worked to make the CMSC and MAGNIMS MRI protocols similar so that the updated guidelines could ultimately be accepted by international consensus. Advocacy efforts will promote the importance of standardized MS MRI protocols. Dissemination will include publications, meeting abstracts, educational programming, webinars, "meet the expert" teleconferences, and examination cards. Implementation will require comprehensive and coordinated efforts to make the protocol easy to access and use. The ultimate vision, and goal, is for the guidelines to be universally useful, usable, and used as the standard of care for patients with MS.

Organothiol Monolayer Formation Directly on Muscovite Mica.

Organothiol monolayers on metal substrates (Au, Ag, Cu) and their use in a wide variety of applications have been extensively studied. Here, the growth of layers of organothiols directly onto muscovite mica is demonstrated using a simple procedure. Atomic force microscopy, surface X-ray diffraction, and vibrational sum-frequency generation IR spectroscopy studies revealed that organothiols with various functional endgroups could be self-assembled into (water) stable and adaptable ultra-flat organothiol monolayers over homogenous areas as large as 1 cm2 . The strength of the mica-organothiol interactions could be tuned by exchanging the potassium surface ions for copper ions. Several of these organothiol monolayers were subsequently used as a template for calcite growth.

Patients with type 1 diabetes exhibit altered cerebral metabolism during hypoglycemia.

Patients with type 1 diabetes mellitus (T1DM) experience, on average, 2 to 3 hypoglycemic episodes per week. This study investigated the effect of hypoglycemia on cerebral glucose metabolism in patients with uncomplicated T1DM. For this purpose, hyperinsulinemic euglycemic and hypoglycemic glucose clamps were performed on separate days, using [1-13C]glucose infusion to increase plasma 13C enrichment. In vivo brain 13C magnetic resonance spectroscopy was used to measure the time course of 13C label incorporation into different metabolites and to calculate the tricarboxylic acid cycle flux (VTCA) by a one-compartment metabolic model. We found that cerebral glucose metabolism, as reflected by the VTCA, was not significantly different comparing euglycemic and hypoglycemic conditions in patients with T1DM. However, the VTCA was inversely related to the HbA1C and was, under hypoglycemic conditions, approximately 45% higher than that in a previously investigated group of healthy subjects. These data suggest that the brains of patients with T1DM are better able to endure moderate hypoglycemia than those of subjects without diabetes.

Steady-state brain glucose concentrations during hypoglycemia in healthy humans and patients with type 1 diabetes.

The objective of this study was to investigate the relationship between plasma and brain glucose levels during euglycemia and hypoglycemia in healthy subjects and patients with type 1 diabetes mellitus (T1DM). Hyperinsulinemic euglycemic (5 mmol/L) and hypoglycemic (3 mmol/L) [1-(13)C]glucose clamps were performed in eight healthy subjects and nine patients with uncomplicated T1DM (HbA(1c) 7.7 ± 1.4%). Brain glucose levels were measured by (13)C magnetic resonance spectroscopy. Linear regression analysis was used to fit the relationship between plasma and brain glucose levels and calculate reversible Michaelis-Menten (MM) kinetic parameters. Brain glucose values during euglycemia (1.1 ± 0.4 µmol/g vs. 1.1 ± 0.3 µmol/g; P = 0.95) and hypoglycemia (0.5 ± 0.2 µmol/g vs. 0.6 ± 0.3 µmol/g; P = 0.52) were comparable between healthy subjects and T1DM patients. MM kinetic parameters of combined data were calculated to be maximum transport rate/cerebral metabolic rate of glucose (T(max)/CMR(glc)) = 2.25 ± 0.32 and substrate concentration at half maximal transport (K(t)) = 1.53 ± 0.88 mmol/L, which is in line with previously published data obtained under hyperglycemic conditions. In conclusion, the linear MM relationship between plasma and brain glucose can be extended to low plasma glucose levels. We found no evidence that the plasma to brain glucose relationship or the kinetics describing glucose transport over the blood-brain barrier differ between healthy subjects and patients with uncomplicated, reasonably well-controlled T1DM.

Effect of acute hypoglycemia on human cerebral glucose metabolism measured by ¹³C magnetic resonance spectroscopy.

OBJECTIVE: To investigate the effect of acute insulin-induced hypoglycemia on cerebral glucose metabolism in healthy humans, measured by (13)C magnetic resonance spectroscopy (MRS). RESEARCH DESIGN AND METHODS: Hyperinsulinemic glucose clamps were performed at plasma glucose levels of 5 mmol/L (euglycemia) or 3 mmol/L (hypoglycemia) in random order in eight healthy subjects (four women) on two occasions, separated by at least 3 weeks. Enriched [1-(13)C]glucose 20% w/w was used for the clamps to maintain stable plasma glucose labeling. The levels of the (13)C-labeled glucose metabolites glutamate C4 and C3 were measured over time in the occipital cortex during the clamp by continuous (13)C MRS in a 3T magnetic resonance scanner. Time courses of glutamate C4 and C3 labeling were fitted using a one-compartment model to calculate metabolic rates in the brain. RESULTS: Plasma glucose (13)C isotopic enrichment was stable at 35.1 ± 1.8% during euglycemia and at 30.2 ± 5.5% during hypoglycemia. Hypoglycemia stimulated release of counterregulatory hormones (all P < 0.05) and tended to increase plasma lactate levels (P = 0.07). After correction for the ambient (13)C enrichment values, label incorporation into glucose metabolites was virtually identical under both glycemic conditions. Calculated tricarboxylic acid cycle rates (V(TCA)) were 0.48 ± 0.03 µmol/g/min during euglycemia and 0.43 ± 0.08 µmol/g/min during hypoglycemia (P = 0.42). CONCLUSIONS: These results indicate that acute moderate hypoglycemia does not affect fluxes through the main pathways of glucose metabolism in the brain of healthy nondiabetic subjects.

Optimized [1-(13)C]glucose infusion protocol for 13C magnetic resonance spectroscopy at 3T of human brain glucose metabolism under euglycemic and hypoglycemic conditions.

The effect of insulin-induced hypoglycemia on cerebral glucose metabolism is largely unknown. (13)C MRS is a unique tool to study cerebral glucose metabolism, but the concurrent requirement for [1-(13)C]glucose administration limits its use under hypoglycemic conditions. To facilitate (13)C MRS data analysis we designed separate [1-(13)C]glucose infusion protocols for hyperinsulinemic euglycemic and hypoglycemic clamps in such a way that plasma isotopic enrichment of glucose was stable and comparable under both glycemic conditions. (13)C MR spectra were acquired with optimized (13)C MRS measurement techniques to obtain high quality (13)C MR spectra with these protocols.