M. Eline Kooi

In vivo detection of hemorrhage in human atherosclerotic plaques with magnetic resonance imaging

To investigate the performance of high‐resolution T1‐weighted (T1w) turbo field echo (TFE) magnetic resonance imaging (MRI) for the identification of the high‐risk component intraplaque hemorrhage, which is described in the literature as a troublesome component to detect.

Improved ejection fraction after exercise training in obesity is accompanied by reduced cardiac lipid content

CONTEXT Skeletal muscle and cardiac lipid accumulation are associated with diminished insulin sensitivity and cardiac function, respectively. In skeletal muscle, physical activity paradoxically increases fat accumulation, despite improvement in insulin sensitivity. Whether cardiac muscle responds similarly remains unknown. OBJECTIVE The objective of the study was to investigate cardiac lipid content and cardiac function after a 12-wk training program. DESIGN This was an intervention study with pre/postmeasurements. SETTING The study was conducted at Maastricht University Medical Center. PARTICIPANTS Participants included 14 healthy, male overweight/obese subjects (age 58.4 +/- 0.9 yr, body mass index 29.9 +/- 0.01 kg/m(2)). INTERVENTION Intervention included a supervised 12-wk training program with three sessions per week (endurance and strength training). MAIN OUTCOME MEASURES Maximal whole-body oxygen uptake, fasting plasma parameters, systolic function (by CINE-magnetic resonance imaging), and cardiac lipid content (by proton magnetic resonance spectroscopy) were measured. RESULTS Maximal whole-body oxygen uptake increased (from 2559 +/- 131 to 2702 +/- 124 ml/min after training, P = 0.05). Plasma concentrations of glucose decreased (from 6.3 +/- 0.2 to 5.7 +/- 0.2 mmol/liter, P < 0.001); plasma triacylglycerols and (free) fatty acids did not change. Also, body weight (from 94.2 +/- 3.6 to 92.9 +/- 3.6 kg, P = 0.10) and fat percentage (from 33.6 +/- 1.7 to 32.5 +/- 2.0%, P = 0.14) was unchanged. Left ventricular ejection fraction improved (from 52.2 +/- 1.3 to 54.2 +/- 1.2%, P = 0.02), and cardiac lipid content in the septum was decreased after training (0.99 +/- 0.15 to 0.54 +/- 0.04%, P = 0.02). CONCLUSIONS Twelve weeks of endurance/strength training significantly reduced cardiac lipid content in overweight subjects and was paralleled by improved ejection fraction. This is in line with a lipotoxic action of (excess) cardiac lipids on cardiac function, although a causal relationship cannot be derived from this study. Further research is needed to clarify the clinical relevance of cardiac lipid content in the etiology of cardiovascular complications.

Functional MRI reveals declined prefrontal cortex activation in patients with epilepsy on topiramate therapy

Functional magnetic resonance imaging of covert word generation was used to examine brain activation abnormalities associated with topiramate-induced cognitive language impairment in patients with epilepsy. Compared with a control epilepsy group, in the topiramate-treated group, there was significantly less activation in the language-mediating regions of the prefrontal cortex; the topiramate group also had significantly lower neuropsychological language scores. These findings suggest that topiramate has a critical effect on the cerebral neural systems that mediate expressive language.

Multimodality Imaging of Carotid Artery Plaques 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography, Computed Tomography, and Magnetic Resonance Imaging

Background and Purpose— This study’s objective was to compare 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET), CT, and MRI of carotid plaque assessment. Materials and Methods— Fifty patients with symptomatic carotid atherosclerosis underwent 18F-FDG PET/CT and MRI. Correlations and agreement between imaging findings were assessed by Spearman and Pearson rank correlation tests, t tests, and Bland-Altman plots. Results— Spearman &rgr; between plaque 18F-FDG standard uptake values and CT/MRI findings varied from −0.088 to 0.385. Maximum standard uptake value was significantly larger in plaques with intraplaque hemorrhage (1.56 vs 1.47; P=0.032). Standard uptake values did not significantly differ between plaques with an intact and thick fibrous cap and plaques with a thin or ruptured fibrous cap on MRI. (1.21 vs 1.23; P=0.323; and 1.45 vs 1.54; P=0.727). Pearson &rgr; between CT and MRI measurements varied from 0.554 to 0.794 (P<0.001). For lipid-rich necrotic core volume, the CT–MRI correlation was stronger in mildly (≤10%) than in severely (>10%) calcified plaques (Pearson &rgr; 0.730 vs 0.475). Mean difference in measurement ±95% limits of agreement between CT and MRI for minimum lumen area, volumes of vessel wall, lipid-rich necrotic core, calcifications, and fibrous tissue were 0.4±18.1 mm2 (P=0.744), −41.9 ±761.7 mm3 (P=0.450), 78.4±305.0 mm3 (P<0.001), 180.5±625.7 mm3 (P=0.001), and −296.0±415.8 mm3 (P<0.001), respectively. Conclusions— Overall, correlations between 18F-FDG PET and CT/MRI findings are weak. Correlations between CT and MRI measurements are moderate to strong, but there is considerable variation in absolute differences.

Symptomatic Patients With Mild and Moderate Carotid Stenosis: Plaque Features at MRI and Association With Cardiovascular Risk Factors and Statin Use

Background and Purpose— The objectives of this study were to assess plaque characteristics in symptomatic patients with mild and moderate carotid stenosis and to explore associations with cardiovascular risk factors and statin use. Methods— One hundred patients with transient ischemic attack or stroke with ipsilateral mild and moderate carotid stenosis underwent MR plaque imaging. Results— Patients with moderate stenosis had plaques with a higher prevalence of intraplaque hemorrhage (48.7% versus 19.7%, P=0.002) and a thin and/or ruptured fibrous cap (61.5% versus 36.1%, P=0.013), and larger lipid-rich necrotic core percentage (12.3% versus 6.8%, P=0.042) and smaller fibrous tissue percentage (82.7% versus 88.4%, P=0.024). Increasing age was positively associated with intraplaque hemorrhage (OR [per year]=1.08; 95% CI, 1.02 to 1.14; P=0.011). Statin use was negatively associated with intraplaque hemorrhage (OR=0.30; 95% CI, 0.10 to 0.93; P=0.038), a thin and/or ruptured fibrous cap (OR=0.34; 95% CI, 0.13 to 0.89; P=0.028), and with lipid-rich necrotic core percentage (B=−7.91; 95% CI, −13.60 to −2.22; P=0.007). Statin use was positively associated with fibrous tissue percentage (B=7.77; 95% CI, 2.40 to 13.14; P=0.005). Conclusions— We found that symptomatic patients with moderate stenosis have a higher prevalence of complicated plaques than patients with mild stenosis. Exploratory analysis showed that increasing age was positively associated with intraplaque hemorrhage, whereas statin use was negatively associated with complicated plaque features.

Comparison of lipid-rich necrotic core size in symptomatic and asymptomatic carotid atherosclerotic plaque: Initial results.

To investigate the potential difference in the size of the lipid‐rich necrotic core (LRNC) in carotid plaques of symptomatic patients versus asymptomatic patients. Pathological studies established that a large LRNC is an important feature of vulnerable atherosclerotic plaque. Previously, we have demonstrated a high correlation between semiquantitative analysis of the LRNC size in T1‐weighted (w) turbo field echo (TFE) MR images and histology.

MRI of carotid atherosclerosis to identify TIA and stroke patients who are at risk of a recurrence

To evaluate the potential of carotid plaque MRI to predict transient ischemic attack (TIA) and stroke recurrence in previously symptomatic patients.

Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction

BackgroundIncreased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training in healthy overweight subjects. The beneficial effect of exercise training on cardiovascular risk is well established and the decrease in cardiac lipid content with exercise training in healthy overweight subjects was accompanied by improved ejection fraction. It is yet unclear whether diabetic patients respond similarly to physical activity training and whether a lowered lipid content in the heart is necessary for improvements in cardiac function. Here, we investigated whether exercise training is able to lower cardiac lipid content and improve cardiac function in type 2 diabetic patients.MethodsEleven overweight-to-obese male patients with type 2 diabetes mellitus (age: 58.4 ± 0.9 years, BMI: 29.9 ± 0.01 kg/m2) followed a 12-week training program (combination endurance/strength training, three sessions/week). Before and after training, maximal whole body oxygen uptake (VO2max) and insulin sensitivity (by hyperinsulinemic, euglycemic clamp) was determined. Systolic function was determined under resting conditions by CINE-MRI and cardiac lipid content in the septum of the heart by Proton Magnetic Resonance Spectroscopy.ResultsVO2max increased (from 27.1 ± 1.5 to 30.1 ± 1.6 ml/min/kg, p = 0.001) and insulin sensitivity improved upon training (insulin stimulated glucose disposal (delta Rd of glucose) improved from 5.8 ± 1.9 to 10.3 ± 2.0 μmol/kg/min, p = 0.02. Left-ventricular ejection fraction improved after training (from 50.5 ± 2.0 to 55.6 ± 1.5%, p = 0.01) as well as cardiac index and cardiac output. Unexpectedly, cardiac lipid content in the septum remained unchanged (from 0.80 ± 0.22% to 0.95 ± 0.21%, p = 0.15).ConclusionsTwelve weeks of progressive endurance/strength training was effective in improving VO2max, insulin sensitivity and cardiac function in patients with type 2 diabetes mellitus. However, cardiac lipid content remained unchanged. These data suggest that a decrease in cardiac lipid content in type 2 diabetic patients is not a prerequisite for improvements in cardiac function.Trial registrationISRCTN: ISRCTN43780395

Comparison of single‐sequence T1w TFE MRI with multisequence MRI for the quantification of lipid‐rich necrotic core in atherosclerotic plaque

To prospectively determine the accuracy of semiquantitative analysis of the amount of lipid‐rich necrotic core (LRNC) in atherosclerotic plaque using multi‐ as well as single‐sequence T1‐weighted (w) turbo field echo (TFE) MRI. Histology served as a reference standard.

Long–echo time MR spectroscopy for skeletal muscle acetylcarnitine detection

Animal models suggest that acetylcarnitine production is essential for maintaining metabolic flexibility and insulin sensitivity. Because current methods to detect acetylcarnitine involve biopsy of the tissue of interest, noninvasive alternatives to measure acetylcarnitine concentrations could facilitate our understanding of its physiological relevance in humans. Here, we investigated the use of long-echo time (TE) proton magnetic resonance spectroscopy (1H-MRS) to measure skeletal muscle acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE 1H-MRS to measure acetylcarnitine in endurance-trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE 1H-MRS protocol was implemented for successful detection of skeletal muscle acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS (31P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle acetylcarnitine concentration showed a reciprocal distribution, with mean acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring acetylcarnitine concentrations with 1H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of acetylcarnitine, possibly underlying decreased insulin sensitivity.