Background-One of the features of high-risk atherosclerotic plaques is a preponderance of macrophages. Experimental studies with hyperlipidemic rabbits have shown that ultrasmall superparamagnetic particles of iron oxide (USPIOs) accumulate in plaques with a high macrophage content and that this induces magnetic resonance (MR) signal changes. The purpose of our study was to investigate whether USPIO-enhanced MRI can also be used for in vivo detection of macrophages in human plaques. Methods and Results-MRI was performed on 11 symptomatic patients scheduled for carotid endarterectomy before and 24 (nϭ11) and 72 (nϭ5) hours after administration of USPIOs (Sinerem) at a dose of 2.6 mg Fe/kg. Histological and electron microscopical analyses of the plaques showed USPIOs primarily in macrophages within the plaques in 10 of 11 patients. Histological analysis showed USPIOs in 27 of 36 (75%) of the ruptured and rupture-prone lesions and 1 of 14 (7%) of the stable lesions. Of the patients with USPIO uptake, signal changes in the post-USPIO MRI were observed by 2 observers in the vessel wall in 67 of 123 (54%) and 19 of 55 (35%) quadrants of the T2*-weighted MR images acquired after 24 and 72 hours, respectively. For those quadrants with changes, there was a significant signal decrease of 24% (95% CI, 33% to 15%) in regions of interest in the images acquired after 24 hours, whereas no significant signal change was found after 72 hours. Conclusions-Accumulation

OBJECTIVE-A lower in vivo mitochondrial function has been reported in both type 2 diabetic patients and first-degree relatives of type 2 diabetic patients. The nature of this reduction is unknown. Here, we tested the hypothesis that a lower intrinsic mitochondrial respiratory capacity may underlie lower in vivo mitochondrial function observed in diabetic patients.RESEARCH DESIGN AND METHODS-Ten overweight diabetic patients, 12 first-degree relatives, and 16 control subjects, all men, matched for age and BMI, participated in this study. Insulin sensitivity was measured with a hyperinsulinemic-euglycemic clamp. Ex vivo intrinsic mitochondrial respiratory capacity was determined in permeabilized skinned muscle fibers using high-resolution respirometry and normalized for mitochondrial content. In vivo mitochondrial function was determined by measuring phosphocreatine recovery half-time after exercise using 31 P-magnetic resonance spectroscopy.RESULTS-Insulin-stimulated glucose disposal was lower in diabetic patients compared with control subjects (11.2 Ϯ 2.8 vs. 28.9 Ϯ 3.7 mol ⅐ kg Ϫ1 fat-free mass ⅐ min Ϫ1 , respectively; P ϭ 0.003), with intermediate values for first-degree relatives (22.1 Ϯ 3.4 mol ⅐ kg Ϫ1 fat-free mass ⅐ min Ϫ1 ). In vivo mitochondrial function was 25% lower in diabetic patients (P ϭ 0.034) and 23% lower in first-degree relatives, but the latter did not reach statistical significance (P ϭ 0.08). Interestingly, ADP-stimulated basal respiration was 35% lower in diabetic patients (P ϭ 0.031), and fluoro-carbonyl cyanide phenylhydrazone-driven maximal mitochondrial respiratory capacity was 31% lower in diabetic patients (P ϭ 0.05) compared with control subjects with intermediate values for first-degree relatives.CONCLUSIONS-A reduced basal ADP-stimulated and maximal mitochondrial respiratory capacity underlies the reduction in in vivo mitochondrial function, independent of mitochondrial content. A reduced capacity at both the level of the electron transport chain and phosphorylation system underlies this impaired mitochondrial capacity.

Hydrogen 1 (1H) magnetic resonance (MR) spectroscopy enables noninvasive in vivo quantification of metabolite concentrations in the brain. Currently, metabolite concentrations are most often presented as ratios (eg, relative to creatine) rather than as absolute concentrations. Despite the success of this approach, it has recently been suggested that relative quantification may introduce substantial errors and can lead to misinterpretation of spectral data and to erroneous metabolite values. The present review discusses relevant methods to obtain absolute metabolite concentrations with a clinical MR system by using single-voxel spectroscopy or chemical shift imaging. Important methodological aspects in an absolute quantification strategy are addressed, including radiofrequency coil properties, calibration procedures, spectral fitting methods, cerebrospinal fluid content correction, macromolecule suppression, and spectral editing. Techniques to obtain absolute concentrations are now available and can be successfully applied in clinical practice. Although the present review is focused on 1H MR spectroscopy of the brain, a large part of the methodology described can be applied to other tissues as well.

Aims/hypothesis Mitochondrial dysfunction and increased intramyocellular lipid (IMCL) content have both been implicated in the development of insulin resistance and type 2 diabetes mellitus, but the relative contributions of these two factors in the aetiology of diabetes are unknown. As obesity is an independent determinant of IMCL content, we examined mitochondrial function and IMCL content in overweight type 2 diabetes patients and BMI-matched normoglycaemic controls. Methods In 12 overweight type 2 diabetes patients and nine controls with similar BMI (29.4±1 and 29.3±0.9 kg/m 2 respectively) in vivo mitochondrial function was determined by measuring phosphocreatine recovery halftime (PCr half-time) immediately after exercise, using phosphorus-31 magnetic resonance spectroscopy. IMCL content was determined by proton magnetic resonance spectroscopic imaging and insulin sensitivity was measured with a hyperinsulinaemic-euglycaemic clamp. Results The PCr half-time was 45% longer in diabetic patients compared with controls (27.3±3.5 vs 18.7±0.9 s, p<0.05), whereas IMCL content was similar (1.37±0.30 vs 1.25±0.22% of the water resonance), and insulin sensitivity was reduced in type 2 diabetes patients (26.0±2.2 vs 18.9± 2.3 μmol min −1 kg −1 , p<0.05 [all mean±SEM]). PCr halftime correlated positively with fasting plasma glucose (r 2 =0.42, p < 0.01) and HbA 1c (r 2 = 0.48, p <0.05) in diabetic patients. Conclusions/interpretation The finding that in vivo mitochondrial function is decreased in type 2 diabetes patients compared with controls whereas IMCL content is similar suggests that low mitochondrial function is more strongly associated with insulin resistance and type 2 diabetes than a high IMCL content per se. Whether low mitochondrial function is a cause or consequence of the disease remains to be investigated.

Identification of carotid artery atherosclerosis is conventionally based on measurements of luminal stenosis and surface irregularities using in vivo imaging techniques including sonography, CT and MR angiography, and digital subtraction angiography. However, histopathologic studies demonstrate considerable differences between plaques with identical degrees of stenosis and indicate that certain plaque features are associated with increased risk for ischemic events. The ability to look beyond the lumen using highly developed vessel wall imaging methods to identify plaque vulnerable to disruption has prompted an active debate as to whether a paradigm shift is needed to move away from relying on measurements of luminal stenosis for gauging the risk of ischemic injury. Further evaluation in randomized clinical trials will help to better define the exact role of plaque imaging in clinical decision-making. However, current carotid vessel wall imaging techniques can be informative. The goal of this article is to present the perspective of the ASNR Vessel Wall Imaging Study Group as it relates to the current status of arterial wall imaging in carotid artery disease.