Christie McComb

Microvascular Resistance Predicts Myocardial Salvage and Infarct Characteristics in ST-Elevation Myocardial Infarction

Background The pathophysiology of myocardial injury and repair in patients with ST‐elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function. Methods and Results The index of microvascular resistance (IMR) was measured by means of a pressure‐ and temperature‐sensitive coronary guidewire in 108 patients with ST‐elevation myocardial infarction (83% male) at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early (2 days; n=108) and late (3 months; n=96) after myocardial infarction. T2‐weighted‐ and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95% confidence interval 0.82 to 0.92) per 20% increase in IMR; P<0.001. In patients with anterior myocardial infarction, IMR was a multivariable predictor of early and late myocardial salvage, with multiplicative effects of 0.82 (95% confidence interval 0.75 to 0.90; P<0.001) and 0.92 (95% confidence interval 0.88 to 0.96; P<0.001), respectively. IMR also predicted the presence and extent of microvascular obstruction and myocardial hemorrhage. Conclusion Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST‐elevation myocardial infarction. (J Am Heart Assoc. 2012;1:e002246 doi: 10.1161/JAHA.112.002246)

Deficits in Trabecular Bone Microarchitecture in Young Women With Type 1 Diabetes Mellitus

The pathophysiological mechanism of increased fractures in young adults with type 1 diabetes mellitus (T1DM) is unclear. We conducted a case‐control study of trabecular bone microarchitecture and vertebral marrow adiposity in young women with T1DM. Thirty women with T1DM with a median age (range) age of 22.0 years (16.9, 36.1) attending one outpatient clinic with a median age at diagnosis of 9.7 years (0.46, 14.8) were compared with 28 age‐matched healthy women who acted as controls. Measurements included MRI‐based assessment of proximal tibial bone volume/total volume (appBV/TV), trabecular separation (appTb.Sp), vertebral bone marrow adiposity (BMA), and abdominal adipose tissue and biochemical markers of GH/IGF‐1 axis (IGF‐1, IGFBP3, ALS) and bone turnover. Median appBV/TV in cases and controls was 0.3 (0.22, 0.37) and 0.33 (0.26, 0.4), respectively (p = 0.018) and median appTb.Sp in T1DM was 2.59 (2.24, 3.38) and 2.32 (2.03, 2.97), respectively (p = 0.012). The median appBV/TV was 0.28 (0.22, 0.33) in those cases with retinopathy (n = 15) compared with 0.33 (0.25, 0.37) in those without retinopathy (p = 0.02). Although median visceral adipose tissue in cases was higher than in controls at 5733 mm3 (2030, 11,144) and 3460 mm3 (1808, 6832), respectively (p = 0.012), there was no difference in median BMA, which was 31.1% (9.9, 59.9) and 26.3% (8.5, 49.8) in cases and controls, respectively (p = 0.2). Serum IGF‐1 and ALS were also lower in cases, and the latter showed an inverse association to appTbSp (r = –0.30, p = 0.04). Detailed MRI studies in young women with childhood‐onset T1DM have shown clear deficits in trabecular microarchitecture of the tibia. Underlying pathophysiological mechanisms may include a microvasculopathy.

Inter-study reproducibility of arterial spin labelling magnetic resonance imaging for measurement of renal perfusion in healthy volunteers at 3 Tesla

BackgroundMeasurement of renal perfusion is a crucial part of measuring kidney function. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast. We studied the reproducibility of ASL MRI in normal volunteers.MethodsASL MRI was performed in healthy volunteers on 2 occasions using a 3.0 Tesla MRI scanner with flow-sensitive alternating inversion recovery (FAIR) perfusion preparation with a steady state free precession (True-FISP) pulse sequence. Kidney volume was measured from the scanned images. Routine serum and urine biochemistry were measured prior to MRI scanning.Results12 volunteers were recruited yielding 24 kidneys, with a mean participant age of 44.1 ± 14.6 years, blood pressure of 136/82 mmHg and chronic kidney disease epidemiology formula estimated glomerular filtration rate (CKD EPI eGFR) of 98.3 ± 15.1 ml/min/1.73 m2. Mean kidney volumes measured using the ellipsoid formula and voxel count method were 123.5 ± 25.5 cm3, and 156.7 ± 28.9 cm3 respectively. Mean kidney perfusion was 229 ± 41 ml/min/100 g and mean cortical perfusion was 327 ± 63 ml/min/100 g, with no significant differences between ASL MRIs. Mean absolute kidney perfusion calculated from kidney volume measured during the scan was 373 ± 71 ml/min. Bland Altman plots were constructed of the cortical and whole kidney perfusion measurements made at ASL MRIs 1 and 2. These showed good agreement between measurements, with a random distribution of means plotted against differences observed. The intra class correlation for cortical perfusion was 0.85, whilst the within subject coefficient of variance was 9.2%. The intra class correlation for whole kidney perfusion was 0.86, whilst the within subject coefficient of variance was 7.1%.ConclusionsASL MRI at 3.0 Tesla provides a repeatable method of measuring renal perfusion in healthy subjects without the need for administration of exogenous compounds. We have established normal values for renal perfusion using ASL MRI in a cohort of healthy volunteers.

Defining myocardial tissue abnormalities in end-stage renal failure with cardiac magnetic resonance imaging using native T1 mapping

Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking–derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.

A Novel Method for Estimating Myocardial Strain: Assessment of Deformation Tracking Against Reference Magnetic Resonance Methods in Healthy Volunteers

We developed a novel method for tracking myocardial deformation using cardiac magnetic resonance (CMR) cine imaging. We hypothesised that circumferential strain using deformation-tracking has comparable diagnostic performance to a validated method (Displacement Encoding with Stimulated Echoes- DENSE) and potentially diagnostically superior to an established cine-strain method (feature-tracking). 81 healthy adults (44.6 ± 17.7 years old, 47% male), without any history of cardiovascular disease, underwent CMR at 1.5 T including cine, DENSE, and late gadolinium enhancement in subjects >45 years. Acquisitions were divided into 6 segments, and global and segmental peak circumferential strain were derived and analysed by age and sex. Peak circumferential strain differed between the 3 groups (DENSE: −19.4 ± 4.8%; deformation-tracking: −16.8 ± 2.4%; feature-tracking: −28.7 ± 4.8%) (ANOVA with Tukey post-hoc, F-value 279.93, p < 0.01). DENSE and deformation-tracking had better reproducibility than feature-tracking. Intra-class correlation co-efficient was >0.90. Larger magnitudes of strain were detected in women using deformation-tracking and DENSE, but not feature-tracking. Compared with a reference method (DENSE), deformation-tracking using cine imaging has similar diagnostic performance for circumferential strain assessment in healthy individuals. Deformation-tracking could potentially obviate the need for bespoke strain sequences, reducing scanning time and is more reproducible than feature-tracking.

Non-Contrast Renal Magnetic Resonance Imaging to Assess Perfusion and Corticomedullary Differentiation in Health and Chronic Kidney Disease

Aims: Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD. Methods: We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look-locker inversion and flow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion. Results: T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 ± 37 vs. 279 ± 69 ml/min/100 g; p < 0.001) and whole kidney (146 ± 24 vs. 221 ± 38 ml/min/100 g; p < 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p < 0.001) and whole kidney (r = -0.50, p < 0.001). There was correlation between eGFR and both cortical (r = 0.73, p < 0.01) and whole kidney (r = 0.69, p < 0.01) perfusion. Conclusions: Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD.

Myocardial strain in healthy adults across a broad age range as revealed by cardiac magnetic resonance imaging at 1.5 and 3.0T: Associations of myocardial strain with myocardial region, age, and sex

To assess myocardial strain using cine displacement encoding with stimulated echoes (DENSE) using 1.5T and 3.0T MRI in healthy adults.

MRI-based abnormalities in young adults at risk of adverse bone health due to childhood-onset metabolic & endocrine conditions

Traditional methods of bone densitometry may not provide a comprehensive assessment of bone health. We aimed to assess bone micro‐architecture and bone marrow adiposity (BMA) by MRI in adults with osteogenesis imperfecta (OI) and endocrinopathy including GH deficiency and/or hypogonadism.

Myocardial strain estimated from standard cine MRI closely represents strain estimated from dedicated strain-encoded MRI

A method of non-rigid image registration was developed and evaluated for the purpose of quantifying myocardial displacement and strain from cine MRI using DENSE MRI as the reference standard. The objective of this paper was to study the potential use of cine MRI with image registration, as a means of measuring strain. The local displacement of the left ventricle was modelled by free-form deformations using b-splines. Cardiac MRI images were obtained from four healthy volunteers at 1.5T and analysed by the implementation of image registration algorithms in cine data and with DENSE view in DENSE data. The results indicated there was less than 3% difference between the strain values obtained from cine and DENSE scans averaging across the regions of the left ventricle in healthy subjects (n=4). There lies great potential in the implementation of cine MRI as a means of strain estimation. As such the measurement of strain from standard cine MRI poses an appealing and potentially clinically useful new option for assessing patients with myocardial dysfunction.

Diagnostic accuracy of 3.0-T magnetic resonance T1 and T2 mapping and T2-weighted dark-blood imaging for the infarct-related coronary artery in Non-ST-segment elevation myocardial infarction

Background Patients with recent non–ST‐segment elevation myocardial infarction commonly have heterogeneous characteristics that may be challenging to assess clinically. Methods and Results We prospectively studied the diagnostic accuracy of 2 novel (T1, T2 mapping) and 1 established (T2‐weighted short tau inversion recovery [T2W‐STIR]) magnetic resonance imaging methods for imaging the ischemic area at risk and myocardial salvage in 73 patients with non–ST‐segment elevation myocardial infarction (mean age 57±10 years, 78% male) at 3.0‐T magnetic resonance imaging within 6.5±3.5 days of invasive management. The infarct‐related territory was identified independently using a combination of angiographic, ECG, and clinical findings. The presence and extent of infarction was assessed with late gadolinium enhancement imaging (gadobutrol, 0.1 mmol/kg). The extent of acutely injured myocardium was independently assessed with native T1, T2, and T2W‐STIR methods. The mean infarct size was 5.9±8.0% of left ventricular mass. The infarct zone T1 and T2 times were 1323±68 and 57±5 ms, respectively. The diagnostic accuracies of T1 and T2 mapping for identification of the infarct‐related artery were similar (P=0.125), and both were superior to T2W‐STIR (P<0.001). The extent of myocardial injury (percentage of left ventricular volume) estimated with T1 (15.8±10.6%) and T2 maps (16.0±11.8%) was similar (P=0.838) and moderately well correlated (r=0.82, P<0.001). Mean extent of acute injury estimated with T2W‐STIR (7.8±11.6%) was lower than that estimated with T1 (P<0.001) or T2 maps (P<0.001). Conclusions In patients with non–ST‐segment elevation myocardial infarction, T1 and T2 magnetic resonance imaging mapping have higher diagnostic performance than T2W‐STIR for identifying the infarct‐related artery. Compared with conventional STIR, T1 and T2 maps have superior value to inform diagnosis and revascularization planning in non–ST‐segment elevation myocardial infarction. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02073422.