W. Patricia Bandettini

Extracellular volume fraction mapping in the myocardium, part 2: initial clinical experience

BackgroundDiffuse myocardial fibrosis, and to a lesser extent global myocardial edema, are important processes in heart disease which are difficult to assess or quantify with cardiovascular magnetic resonance (CMR) using conventional late gadolinium enhancement (LGE) or T1-mapping. Measurement of the myocardial extracellular volume fraction (ECV) circumvents factors that confound T1-weighted images or T1-maps. We hypothesized that quantitative assessment of myocardial ECV would be clinically useful for detecting both focal and diffuse myocardial abnormalities in a variety of common and uncommon heart diseases.MethodsA total of 156 subjects were imaged including 62 with normal findings, 33 patients with chronic myocardial infarction (MI), 33 with hypertrophic cardiomyopathy (HCM), 15 with non-ischemic dilated cardiomyopathy (DCM), 7 with acute myocarditis, 4 with cardiac amyloidosis, and 2 with systemic capillary leak syndrome (SCLS). Motion corrected ECV maps were generated automatically from T1-maps acquired pre- and post-contrast calibrated by blood hematocrit. Abnormally-elevated ECV was defined as >2SD from the mean ECV in individuals with normal findings. In HCM the size of regions of LGE was quantified as the region >2 SD from remote.ResultsMean ECV of 62 normal individuals was 25.4 ± 2.5% (m ± SD), normal range 20.4%-30.4%. Mean ECV within the core of chronic myocardial infarctions (without MVO) (N = 33) measured 68.5 ± 8.6% (p < 0.001 vs normal). In HCM, the extent of abnormally elevated ECV correlated to the extent of LGE (r = 0.72, p < 0.001) but had a systematically greater extent by ECV (mean difference 19 ± 7% of slice). Abnormally elevated ECV was identified in 4 of 16 patients with non-ischemic DCM (38.1 ± 1.9% (p < 0.001 vs normal) and LGE in the same slice appeared “normal” in 2 of these 4 patients. Mean ECV values in other disease entities ranged 32-60% for cardiac amyloidosis (N = 4), 40-41% for systemic capillary leak syndrome (N = 2), and 39-56% within abnormal regions affected by myocarditis (N = 7).ConclusionsECV mapping appears promising to complement LGE imaging in cases of more homogenously diffuse disease. The ability to display ECV maps in units that are physiologically intuitive and may be interpreted on an absolute scale offers the potential for detection of diffuse disease and measurement of the extent and severity of abnormal regions.

Magnetic resonance imaging delineates the ischemic area at risk and myocardial salvage in patients with acute myocardial infarction.

Background—The area at risk (AAR) is a key determinant of myocardial infarction (MI) size. We investigated whether magnetic resonance imaging (MRI) measurement of AAR would be correlated with an angiographic AAR risk score in patients with acute MI. Methods and Results—Bright-blood, T2-prepared, steady-state, free-precession MRI was used to depict the AAR in 50 consecutive acute MI patients, whereas infarct size was measured on gadolinium late-contrast-enhancement images. AAR was also estimated by the APPROACH and DUKE angiographic jeopardy scores and ST-segment elevation score. Myocardial salvage was calculated as AAR minus infarct size. Results are mean±SD unless specified otherwise. Patients were 61±12 years of age, 76% had an ST-segment elevation MI, and 20% had a prior MI. All underwent MRI 4±2 days after initial presentation. The relation between MRI and the APPROACH angiographic estimates of AAR was similar (overall size relative to left ventricular mass was 32±12% vs 30±12%, respectively, P=0.33), correlated well (r=0.78, P<0.0001), and had a 2.5% bias on Bland-Altman analysis. The DUKE jeopardy score underestimated AAR relative to infarct size and was correlated less well with MRI (r=0.39, P=0.0055). ST-segment elevation score underestimated infarct size in 19 subjects (50%) and was not correlated with MRI (r=0.27, P=0.06). Myocardial salvage varied according to Thrombolysis in Myocardial Infarction flow grade at the end of angiography/percutaneous coronary intervention (P=0.04), and Thrombolysis in Myocardial Infarction flow grade was a univariable predictor of myocardial salvage (P=0.011). In multivariable analyses, infarct size was predicted by T2-prepared, steady-state, free-precession MRI (P<0.0001). Conclusions—T2-prepared, steady-state, free-precession MRI delineates the AAR and enables estimation of myocardial salvage when coupled with a measurement of infarct size.

MultiContrast Delayed Enhancement (MCODE) improves detection of subendocardial myocardial infarction by late gadolinium enhancement cardiovascular magnetic resonance: a clinical validation study.

BackgroundMyocardial infarction (MI) documented by late gadolinium enhancement (LGE) has clinical and prognostic importance, but its detection is sometimes compromised by poor contrast between blood and MI. MultiContrast Delayed Enhancement (MCODE) is a technique that helps discriminate subendocardial MI from blood pool by simultaneously providing a T2-weighted image with a PSIR (phase sensitive inversion recovery) LGE image. In this clinical validation study, our goal was to prospectively compare standard LGE imaging to MCODE in the detection of MI.MethodsImaging was performed on a 1.5 T scanner on patients referred for CMR including a LGE study. Prospective comparisons between MCODE and standard PSIR LGE imaging were done by targeted, repeat imaging of slice locations. Clinical data were used to determine MI status. Images at each of multiple time points were read on separate days and categorized as to whether or not MI was present and whether an infarction was transmural or subendocardial. The extent of infarction was scored on a sector-by-sector basis.ResultsSeventy-three patients were imaged with the specified protocol. The majority were referred for vasodilator perfusion exams and viability assessment (37 ischemia assessment, 12 acute MI, 10 chronic MI, 12 other diagnoses). Forty-six patients had a final diagnosis of MI (30 subendocardial and 16 transmural). MCODE had similar specificity compared to LGE at all time points but demonstrated better sensitivity compared to LGE performed early and immediately before and after the MCODE (p = 0.008 and 0.02 respectively). Conventional LGE only missed cases of subendocardial MI. Both LGE and MCODE identified all transmural MI. Based on clinical determination of MI, MCODE had three false positive MI’s; LGE had two false positive MI’s including two of the three MCODE false positives. On a per sector basis, MCODE identified more infarcted sectors compared to LGE performed immediately prior to MCODE (p < 0.001).ConclusionWhile both PSIR LGE and MCODE were good in identifying MI, MCODE demonstrated more subendocardial MI’s than LGE and identified a larger number of infarcted sectors. The simultaneous acquisition of T1 and T2-weighted images improved differentiation of blood pool from enhanced subendocardial MI.

Cardiac Involvement with Lymphoma: A Review of the Literature

Current literature suggests that the incidence of cardiac involvement by lymphoma as identified by autopsy varies widely, ranging from 8.7% to 20%. Historically, many cases might have been clinically undetected; however, improved imaging techniques increasingly identify cardiac involvement incidentally. In addition, newer agents resulting in improved cancer therapy outcomes might alter the prevalence and location of metastatic deposits to include more unusual disease sites, including intracardiac locations. We present 2 cases and a review of the literature.

Characterization of myocardial T1-mapping bias caused by intramyocardial fat in inversion recovery and saturation recovery techniques

BackgroundQuantitative measurement of T1 in the myocardium may be used to detect both focal and diffuse disease processes such as interstitial fibrosis or edema. A partial volume problem exists when a voxel in the myocardium also contains fat. Partial volume with fat occurs at tissue boundaries or within the myocardium in the case of lipomatous metaplasia of replacement fibrosis, which is commonly seen in chronic myocardial infarction. The presence of fat leads to a bias in T1 measurement. The mechanism for this artifact for widely used T1 mapping protocols using balanced steady state free precession readout and the dependence on off-resonance frequency are described in this paper.MethodsSimulations were performed to illustrate the behavior of mono-exponential fitting to bi-exponential mixtures of myocardium and fat with varying fat fractions. Both inversion recovery and saturation recovery imaging protocols using balanced steady state free precession are considered. In-vivo imaging with T1-mapping, water/fat separated imaging, and late enhancement imaging was performed on subjects with chronic myocardial infarction.ResultsIn n = 17 subjects with chronic myocardial infarction, lipomatous metaplasia is evident in 8 patients (47%). Fat fractions as low as 5% caused approximately 6% T1 elevation for the out-of-phase condition, and approximately 5% reduction of T1 for the in-phase condition. T1 bias in excess of 1000 ms was observed in lipomatous metaplasia with fat fraction of 38% in close agreement with simulation of the specific imaging protocols.ConclusionsMeasurement of the myocardial T1 by widely used balanced steady state free precession mapping methods is subject to bias when there is a mixture of water and fat in the myocardium. Intramyocardial fat is frequently present in myocardial scar tissue due lipomatous metaplasia, a process affecting myocardial infarction and some non-ischemic cardiomyopathies. In cases of lipomatous metaplasia, the T1 biases will be additive or subtractive depending on whether the center frequency corresponds to the myocardium and fat being in-phase or out-of-phase, respectively. It is important to understand this mechanism, which may otherwise lead to erroneous interpretation.

Spectrum of Aortic Valve Abnormalities Associated With Aortic Dilation Across Age Groups in Turner Syndrome

Background—Congenital aortic valve fusion is associated with aortic dilation, aneurysm, and rupture in girls and women with Turner syndrome. Our objective was to characterize aortic valve structure in subjects with Turner syndrome and to determine the prevalence of aortic dilation and valve dysfunction associated with different types of aortic valves. Methods and Results—The aortic valve and thoracic aorta were characterized by cardiovascular MRI in 208 subjects with Turner syndrome in an institutional review board–approved natural history study. Echocardiography was used to measure peak velocities across the aortic valve and the degree of aortic regurgitation. Four distinct valve morphologies were identified: tricuspid aortic valve, 64% (n=133); partially fused aortic valve, 12% (n=25); bicuspid aortic valve, 23% (n=47); and unicuspid aortic valve, 1% (n=3). Age and body surface area were similar in the 4 valve morphology groups. There was a significant trend, independent of age, toward larger body surface area–indexed ascending aortic diameters with increasing valve fusion. Ascending aortic diameters were (mean±SD) 16.9±3.3, 18.3±3.3, and 19.8±3.9 mm/m2 (P<0.0001) for tricuspid aortic valve, partially fused aortic valve, and bicuspid aortic valve+unicuspid aortic valve, respectively. Partially fused aortic valve, bicuspid aortic valve, and unicuspid aortic valve were significantly associated with mild aortic regurgitation and elevated peak velocities across the aortic valve. Conclusions—Aortic valve abnormalities in Turner syndrome occur with a spectrum of severity and are associated with aortic root dilation across age groups. Partial fusion of the aortic valve, traditionally regarded as an acquired valve problem, had an equal age distribution and was associated with an increased ascending aortic diameters.

Safety and tolerability of regadenoson CMR.

Aims Knowledge of adverse events associated with regadenoson perfusion cardiac magnetic resonance (CMR) and patient tolerability has implications for patient safety and staff training. We sought to assess the safety and tolerability of regadenoson stress CMR. Materials and methods A group of 728 consecutive patients (median age 58, 44% female) and 25 normal volunteers (median age 21, 24% female) were recruited from August 2009 to March 2012 using a prospective, cross-sectional study design. Subjects were stressed using fixed-dose regadenoson and imaged using a 1.5T MRI scanner. Symptoms and adverse events including death, myocardial infarction (MI), ventricular tachycardia (VT)/ventricular fibrillation (VF), hospitalization, arrhythmias, and haemodynamic stability were assessed. Results There were no occurrences of death, MI, VT/VF, high-grade atrioventricular block, or stress-induced atrial fibrillation. Notable adverse events included one case of bronchospasm and one case of heart failure exacerbation resulting in hospitalization. The most common symptoms in patients were dyspnoea (30%, n = 217), chest discomfort (27%, n = 200), and headache (15%, n = 111). There was minimal change between baseline and peak systolic and diastolic blood pressure in both patients and volunteers (P > 0.05). A blunted heart rate response to regadenoson was noted in patients with body mass index (BMI) ≥30 kg/m2 (P < 0.001), and diabetes (P = 0.001). Conclusions Regadenoson CMR is well tolerated and can be performed safely with few adverse events.

Mechanisms for overestimating acute myocardial infarct size with gadolinium-enhanced cardiovascular magnetic resonance imaging in humans: a quantitative and kinetic study †

Aims It remains controversial whether cardiovascular magnetic resonance imaging with gadolinium only enhances acutely infarcted or also salvaged myocardium. We hypothesized that enhancement of salvaged myocardium may be due to altered extracellular volume (ECV) and contrast kinetics compared with normal and infarcted myocardium. If so, these mechanisms could contribute to overestimation of acute myocardial infarction (AMI) size. Methods and results Imaging was performed at 1.5T ≤ 7 days after AMI with serial T1 mapping and volumetric early (5 min post-contrast) and late (20 min post-contrast) gadolinium enhancement imaging. Infarcts were classified as transmural (>75% transmural extent) or non-transmural. Patients with non-transmural infarctions (n = 15) had shorter duration of symptoms before reperfusion (P = 0.02), lower peak troponin (P = 0.008), and less microvascular obstruction (P < 0.001) than patients with transmural infarcts (n = 22). The size of enhancement at 5 min was greater than at 20 min (18.7 ± 12.7 vs. 12.1 ± 7.0%, P = 0.003) in non-transmural infarctions, but similar in transmural infarctions (23.0 ± 10.0 vs. 21.9 ± 9.9%, P = 0.21). ECV of salvaged myocardium was greater than normal (39.5 ± 5.8 vs. 24.1 ± 3.1%) but less than infarcted myocardium (50.5 ± 6.0%, both P < 0.001). In kinetic studies of non-transmural infarctions, salvaged and infarcted myocardium had similar T1 at 4 min but different T1 at 8–20 min post-contrast. Conclusion The extent of gadolinium enhancement in AMI is modulated by ECV and contrast kinetics. Image acquisition too early after contrast administration resulted in overestimation of infarct size in non-transmural infarctions due to enhancement of salvaged myocardium.

Free-breathing T2* mapping using respiratory motion corrected averaging

BackgroundPixel-wise T2* maps based on breath-held segmented image acquisition are prone to ghost artifacts in instances of poor breath-holding or cardiac arrhythmia. Single shot imaging is inherently immune to ghost type artifacts. We propose a free-breathing method based on respiratory motion corrected single shot imaging with averaging to improve the signal to noise ratio.MethodsImages were acquired using a multi-echo gradient recalled echo sequence and T2* maps were calculated at each pixel by exponential fitting. For 40 subjects (2 cohorts), two acquisition protocols were compared: (1) a breath-held, segmented acquisition, and (2) a free-breathing, single-shot multiple repetition respiratory motion corrected average. T2* measurements in the interventricular septum and liver were compared for the 2-methods in all studies with diagnostic image quality.ResultsIn cohort 1 (N = 28) with age 51.4 ± 17.6 (m ± SD) including 1 subject with severe myocardial iron overload, there were 8 non-diagnostic breath-held studies due to poor image quality resulting from ghost artifacts caused by respiratory motion or arrhythmias. In cohort 2 (N = 12) with age 30.9 ± 7.5 (m ± SD), including 7 subjects with severe myocardial iron overload and 4 subjects with mild iron overload, a single subject was unable to breath-hold. Free-breathing motion corrected T2* maps were of diagnostic quality in all 40 subjects. T2* measurements were in excellent agreement (In cohort #1, T2*FB = 0.95 x T2*BH + 0.41, r2 = 0.93, N = 39 measurements, and in cohort #2, T2*FB = 0.98 x T2*BH + 0.05, r2 > 0.99, N = 22 measurements).ConclusionsA free-breathing approach to T2* mapping is demonstrated to produce consistently good quality maps in the presence of respiratory motion and arrhythmias.

Multimodality Imaging of a Dissecting Intramyocardial Hematoma Extending into the Left Atrial Wall Following Myocardial Infarction

Five days after the onset of substernal chest pain, a 60-year-old man with a history of hypertension, smoking (60 pack-years), severe bullous emphysema, and epilepsy presented with acutely worsening chest pain. Pharmacological management for non–ST-segment elevation myocardial infarction was initiated based on 12-lead ECG findings of subtle anterolateral ST segment changes (V2–V5) and a troponin I level of 6.36 ng/mL (normal <0.04 ng/mL). Invasive angiography demonstrated a distal occlusion of a right posterolateral branch and a nonocclusive stenosis in the distal circumflex artery (Figure 1A and ⇓B). Cineangiography showed two small craters of contrast protruding outside the contrast-filled left ventricular contour within a dyskinetic basal inferior wall (Figure 1C and ⇓D and online-only Data Supplement Movie I). Because the occlusion was distal, percutaneous coronary intervention was not performed. Transthoracic echocardiography showed heterogeneous echogenicity within a 28-mm-thick, dyskinetic, inferior left ventricular wall (online-only Data Supplement Movie II) and a mass protruding into the left atrium (Figure 2). This unusual mass was suspicious for an intramyocardial hematoma based on the clinical setting and its location within myocardium subtended by the occluded artery. Left ventricular ejection fraction was estimated visually to be 45%. There were wall motion abnormalities in the basal and midanterolateral, inferolateral, and inferior walls extending into the apical inferior wall. In retrospect, the anterolateral ST changes likely represented a combination of inferior and inferolateral infarct and ischemia. All antiplatelet and …