Scott Semple

Left Ventricular Hypertrophy with Strain and Aortic Stenosis

Background— ECG left ventricular hypertrophy with strain is associated with an adverse prognosis in aortic stenosis. We investigated the mechanisms and outcomes associated with ECG strain. Methods and Results— One hundred and two patients (age, 70 years [range, 63–75 years]; male, 66%; aortic valve area, 0.9 cm2 [range, 0.7–1.2 cm2]) underwent ECG, echocardiography, and cardiovascular magnetic resonance. They made up the mechanism cohort. Myocardial fibrosis was determined with late gadolinium enhancement (replacement fibrosis) and T1 mapping (diffuse fibrosis). The relationship between ECG strain and cardiovascular magnetic resonance was then assessed in an external validation cohort (n=64). The outcome cohort was made up of 140 patients from the Scottish Aortic Stenosis and Lipid Lowering Trial Impact on Regression (SALTIRE) study and was followed up for 10.6 years (1254 patient-years). Compared with those without left ventricular hypertrophy (n=51) and left ventricular hypertrophy without ECG strain (n=30), patients with ECG strain (n=21) had more severe aortic stenosis, increased left ventricular mass index, more myocardial injury (high-sensitivity plasma cardiac troponin I concentration, 4.3 ng/L [interquartile range, 2.5–7.3 ng/L] versus 7.3 ng/L [interquartile range, 3.2–20.8 ng/L] versus 18.6 ng/L [interquartile range, 9.0–45.2 ng/L], respectively; P<0.001) and increased diffuse fibrosis (extracellular volume fraction, 27.4±2.2% versus 27.2±2.9% versus 30.9±1.9%, respectively; P<0.001). All patients with ECG strain had midwall late gadolinium enhancement (positive and negative predictive values of 100% and 86%, respectively). Indeed, late gadolinium enhancement was independently associated with ECG strain (odds ratio, 1.73; 95% confidence interval, 1.08–2.77; P=0.02), a finding confirmed in the validation cohort. In the outcome cohort, ECG strain was an independent predictor of aortic valve replacement or cardiovascular death (hazard ratio, 2.67; 95% confidence interval, 1.35–5.27; P<0.01). Conclusion— ECG strain is a specific marker of midwall myocardial fibrosis and predicts adverse clinical outcomes in aortic stenosis.

MRI using ultrasmall superparamagnetic particles of iron oxide in patients under surveillance for abdominal aortic aneurysms to predict rupture or surgical repair: MRI for abdominal aortic aneurysms to predict rupture or surgery-the MA(3)RS study.

Introduction Population screening for abdominal aortic aneurysms (AAA) halves the associated mortality and has led to the establishment of national screening programmes. Prediction of aneurysm growth and rupture is challenging and currently relies on serial diameter measurements with ultrasound. Recently, a novel MRI-based technique using ultrasmall superparamagnetic particles of iron oxide (USPIO) has demonstrated considerable promise as a method of identifying aneurysm inflammation and expansion. Methods and analysis The MA3RS study is a prospective observational multicentre cohort study of 350 patients with AAA in three centres across Scotland. All participants will undergo MRI with USPIO and aneurysm expansion will be measured over 2u2005years with CT in addition to standard clinical ultrasound surveillance. The relationship between mural USPIO uptake and subsequent clinical outcomes, including expansion, rupture and repair, will be evaluated and used to determine whether the technique augments standard risk prediction markers. To ensure adequate sensitivity to answer the primary question, we need to observe 130 events (composite of rupture or repair) with an estimated event rate of 41% over 2u2005years of follow-up. The MA3RS study is currently recruiting and expects to report in 2017. Discussion This is the first study to evaluate the use of USPIO-enhanced MRI to provide additional information to aid risk prediction models in patients with AAA. If successful, this study will lay the foundation for a large randomised controlled trial targeted at applying this technique to determine clinical management. Trial registration number Current Controlled Trials: ISRCTN76413758.

Ultra-small superparamagnetic particles of iron oxide in magnetic resonance imaging of cardiovascular disease

Ultra-small superparamagnetic particles of iron oxide (USPIO) are iron-oxide based contrast agents that enhance and complement in vivo magnetic resonance imaging (MRI) by shortening T1, T2, and T2* relaxation times. USPIO can be employed to provide immediate blood pool contrast, or to act as subsequent markers of cellular inflammation through uptake by inflammatory cells. They can also be targeted to specific cell-surface markers using antibody or ligand labeling. This review will discuss the application of USPIO contrast in MRI studies of cardiovascular disease.

Brain Development in Fetuses of Mothers with Diabetes: A Case-Control MR Imaging Study

BACKGROUND AND PURPOSE: Offspring exposed to maternal diabetes are at increased risk of neurocognitive impairment, but its origins are unknown. With MR imaging, we investigated the feasibility of comprehensive assessment of brain metabolism (1H-MRS), microstructure (DWI), and macrostructure (structural MRI) in third-trimester fetuses in women with diabetes and determined normal ranges for the MR imaging parameters measured. MATERIALS AND METHODS: Women with singleton pregnancies with diabetes (n = 26) and healthy controls (n = 26) were recruited prospectively for MR imaging studies between 34 and 38 weeks gestation. RESULTS: Data suitable for postprocessing were obtained from 79%, 71%, and 46% of women for 1H-MRS, DWI, and structural MRI, respectively. There was no difference in the NAA/Cho and NAA/Cr ratios (mean [SD]) in the fetal brain in women with diabetes compared with controls (1.74 [0.79] versus 1.79 [0.64], P = .81; and 0.78 [0.28] versus 0.94 [0.36], P = .12, respectively), but the Cho/Cr ratio was marginally lower (0.46 [0.11] versus 0.53 [0.10], P = .04). There was no difference in mean [SD] anterior white, posterior white, and deep gray matter ADC between patients and controls (1.16 [0.12] versus 1.16 [0.08], P = .96; 1.54 [0.16] versus 1.59 [0.20], P = .56; and 1.49 [0.23] versus 1.52 [0.23], P = .89, respectively) or volume of the cerebrum (243.0 mL [22.7 mL] versus 253.8 mL [31.6 mL], P = .38). CONCLUSIONS: Acquiring multimodal MR imaging of the fetal brain at 3T from pregnant women with diabetes is feasible. Further study of fetal brain metabolism in maternal diabetes is warranted.

IN VIVO ASSESSMENT OF CELLULAR INFLAMMATION FOLLOWING ACUTE MYOCARDIAL INFARCTION

Background Inflammation following myocardial infarction has detrimental effects on reperfusion, myocardial remodelling and left ventricular function. MRI using ultrasmall superparamagnetic particles of iron oxide (USPIO) can be used to detect cellular inflammation in tissues. Methods 15 patients were recruited up to 5u2005days after ST-segment elevation myocardial infarction. Nine patients underwent cardiac MRI (3 Tesla) at baseline, and at 24 and 48u2005h following infusion of USPIO (4u2005mg/kg; Ferumoxytol, AMAG). Six control patients underwent the same scanning protocol without infusion of USPIO. T2*-weighted multi-gradient-echo sequences were acquired and R2* maps (inverse of T2*) were generated to assess USPIO accumulation. Baseline scans were registered to subsequent 24 and 48u2005h scans and the infarct zone was defined on Gadolinium-enhanced T2-weighted images. An “object map” was created that defined corresponding regions of interest (ROI) on all scans for each subject. The ROIs included infarct zone, peri-infarct zone, remote myocardium, liver, blood pool and skeletal muscle. The R2* values for each ROI was calculated. Results In the control group, the R2* value in the infarct zone remained constant: baseline, 0.047 s−1 (95% CI 0.034 to 0.059); 24u2005h, 0.043 s−1 (95% CI 0.035 to 0.052) and 48u2005h, 0.040 s−1 (95% CI 0.024 to 0.056). In the infarct zone, the R2* value increased from a baseline of 0.041 s−1 (95% CI 0.029 to 0.053) to 0.164 s−1 (95% CI 0.125 to 0.204) at 24u2005h and 0.128 s−1 (95% CI 0.097 to 0.158) at 48u2005h following USPIO administration (p<0.01; non-parametric repeated measure one-way ANOVA, Dunns post test comparison). Conclusion USPIO are taken up into the infarcted myocardium following acute myocardial infarction and can be quantified by MRI. This approach appears to image infarct-related cellular inflammation and represents an important novel method of assessing recovery following acute myocardial infarction.Abstract 084 Figure 1 In this subject, late gadolinium enhancement had revealed an infarct of the anterior left ventricular wall. Panels A and B are R2 acquisition images of the same subject taken on day 1 (A, pre-USPIO), and day 2 (B post-USPIO) in a patient given ferumoxytol. The white arrow indicates the area of infarction corresponding to the late gadolinium enhancement. In this area there is sequential higher uptake of USPIO as indicated by the red/green colour in this area. This is consistent with neutrophil and macrophage influx. Ferumoxytol is also taken up by the liver reticulo-endothelial system (grey arrow). These findings are confirmed by the quantitative analysis of the R2* signal (Panel C).Abstract 084 Figure 2 Comparison of R2* signal in different tissues. Highest uptake of USPIO is seen in the infarct zone, liver and blood pool. There is a small increase in R2* signal in the remote myocardium. There is no increase in R2* signal in the control group for any tissue.