The time window of MRI of murine atherosclerotic plaques after administration of CB2 receptor targeted micelles: inter-scan variability and relation between plaque signal intensity increase and gadolinium content of inversion recovery prepared versus non-prepared fast spin echo.

Single fast spin echo scans covering limited time frames are mostly used for contrast-enhanced MRI of atherosclerotic plaque biomarkers. Knowledge on inter-scan variability of the normalized enhancement ratio of plaque (NER(plaque)) and relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo is limited. Study aims were: evaluation of (1) timing of MRI after intravenous injection of cannabinoid-2 receptor (CB2-R) (expressed by human and mouse plaque macrophages) targeted micelles; (2) inter-scan variability of inversion-recovery fast spin echo and fast spin echo; (3) relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo and fast spin echo. Inversion-recovery fast spin echo/fast spin echo imaging was performed before and every 15 min up to 48 h after injection of CB2-R targeted or control micelles using several groups of mice measured in an interleaved fashion. NER(plaque) (determined on inversion-recovery fast spin echo images) remained high (∼2) until 48 h after injection of CB2-R targeted micelles, whereas NER(plaque) decreased after 36 h in the control group. The inter-scan variability and relation between NER(plaque) and gadolinium (assessed with inductively coupled plasma- mass spectrometry) were compared between inversion-recovery fast spin echo and fast spin echo. Inter-scan variability was higher for inversion-recovery fast spin echo than for fast spin echo. Although gadolinium and NER(plaque) correlated well for both techniques, the NER of plaque was higher for inversion-recovery fast spin echo than for fast spin echo. In mice injected with CB2-R targeted micelles, NER(plaque) can be best evaluated at 36-48 h post-injection. Because NER(plaque) was higher for inversion-recovery fast spin echo than for fast spin echo, but with high inter-scan variability, repeated inversion-recovery fast spin echo imaging and averaging of the obtained NER(plaque) values is recommended.

Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects.

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 half-time (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 mumol min(-1) kg(-1), p < 0.05 [all mean +/- SEM]). PCr half-time 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.