First-pass Perfusion Cardiovascular Magnetic Resonance Research Articles

Prognostic value of first pass perfusion transit time beyond the pulmonary circulation

Abstract Background Pulmonary transit time (PTT), defined as the time required for a bolus of contrast agent to pass from the right cavities to the left cavities, is an emerging parameter reflective of cardiopulmonary hemodynamics that can be measured in first-pass perfusion cardiovascular magnetic resonance (CMR). Transit times along the left heart (LHTT) and perfusion times of peripheral organs have not been explored so far. Purpose To assess the prognostic value of LHTT and peripheral organs perfusion time in a cohort of patients with left ventricular (LV) disfunction. Methods 50 consecutive patients with LV disfunction (ejection fraction ≤45%) and 56 normal controls who underwent a CMR at our institution were selected. Transit time was calculated as the peak-to-peak time interval between two different areas of the cardiovascular system. PTT was assessed between right ventricle (RV) and left ventricle. LHTT was assessed between left atrium and ascending aorta. Myocardial perfusion time (MyoPT) was measured between left ventricle and the peak of myocardial perfusion. Peripheral organ perfusion (kidney, KPT; spleen, SPT and liver, LPT) between abdominal aorta and the peak organ perfusion. The primary end point was a composite of cardiovascular death, hospitalization, ventricular arrhythmias and the need of any cardiac invasive intervention within the first year. Results Compared with controls, LV disfunction patients presented higher PTT (7.4 [5.9-8.4] vs 11.9 [9.5-13.9] s, p<0.001), LHTT (1.9 [1.05-2.3] vs 3.3 [1.9-4.8] s, p<0.01), MyoPT (9.9 [7.8-11.5] vs 13.1 [9.7-18.6] s, p<0.01), KPT (9.4[7.8-11.2] vs 11.5[8.3-15.5] s, p = 0.012). SPT showed a non-significant trend (9.4[8.1-11.9] vs 11.5[7.9-13.4]s , p = 0.058) . There were no differences in LPT (28.9[24.4-35] vs 33.3[23.3-41.1] s, p = 0.267). Among the patients with LV disfunction, 16 subjects reached the composite end-point; compared to those who did not, these patients had significant higher values of PTT (10.1 [8.7-13.7] vs 13.4[10-15.7] s, p = 0.04), LHTT (2.3[1.8-4] vs 4.3 [3.3-5.8] s, p = 0.008) and MyoPT (10.5[8.8-17.5] vs 13.3[11.9-20.5] s, p = 0.049). SPT showed a non-significant trend (10.3[6.9-12.6] vs 12.6[10.9-17.1] s, p = 0.078), KPT and LPT showed no significant differences. Patients with worse prognosis also presented lower LV ejection fraction (LV: 34.7± 9.5 vs 25.5±9 %, p<0.001) but no significant differences in RV ejection fraction: 52.9±14 vs 49.3±13.8 %, p = 0.473). Due to the small number of events we did not performed a multivariate analysis. KPT showed a weak but significant positive correlation with the creatinine measured at the time of the CMR study (r = 0.262, p = 0.024) and also at follow-up (r = 0.247, p = 0.042). Conclusions Transit time is a surrogate marker of the heamodynamic status that can be assessed beyond the pulmonary circulation. LHTT and organ perfusion times are markedly altered in patients with LV disfunction and are associated with poor prognosis.

An acute increase in Left Atrial volume and left ventricular filling pressure during Adenosine administered myocardial hyperaemia: CMR First-Pass Perfusion Study

ObjectiveTo investigate whether left atrial (LA) volume and left ventricular filling pressure (LVFP) assessed by cardiovascular magnetic resonance (CMR) change during adenosine delivered myocardial hyperaemia as part of a first-pass stress perfusion study.Methods and resultsWe enrolled 33 patients who had stress CMR. These patients had a baseline four-chamber cine and stress four-chamber cine, which was done at peak myocardial hyperaemic state after administering adenosine. The left and right atria were segmented in the end ventricular diastolic and systolic phases. Short-axis cine stack was segmented for ventricular functional assessment. At peak hyperaemic state, left atrial end ventricular systolic volume just before mitral valve opening increased significantly from baseline in all (91 ± 35ml vs. 81 ± 33ml, P = 0.0002), in males only (99 ± 35ml vs. 88 ± 33ml, P = 0.002) and females only (70 ± 26ml vs. 62 ± 22ml, P = 0.02). The right atrial end ventricular systolic volume increased less significantly from baseline (68 ± 21ml vs. 63 ± 20ml, P = 0.0448). CMR-derived LVFP (equivalent to pulmonary capillary wedge pressure) increased significantly at the peak hyperaemic state in all (15.1 ± 2.9mmHg vs. 14.4 ± 2.8mmHg, P = 0.0002), females only (12.9 ± 2.1mmHg vs. 12.3 ± 1.9mmHg, P = 0.029) and males only (15.9 ± 2.8mmHg vs. 15.2 ± 2.7mmHg, P = 0.002) cohorts.ConclusionLeft atrial volume assessment by CMR can measure acute and dynamic changes in preloading conditions on the left ventricle. During adenosine administered first-pass perfusion CMR, left atrial volume and LVFP rise significantly.

Malperfusion in dilated cardiomyopathy: One more link in the pathologic chain?

Dilated cardiomyopathy (DCM) is considered the primary non-ischemic heart disease, but there are controversial data regarding the microcirculatory disturbance in these patients. While the major epicardial vessels are always intact in these patients, the malperfusion of the myocardium of the left ventricle (LV) may be present, and the role of this malperfusion in the progression of the disease is not clear. The non-invasive echocardiographic assessment of the coronary blood flow reveals that it may be increased at rest and decreased during pharmacological stress, leading to a decreased coronary flow reserve.1 Beyond echocardiographic studies, microvascular dysfunction in DCM has been previously investigated with various imaging modalities. Bietenbeck M. et al. performed the quantitative myocardial first-pass perfusion cardiovascular magnetic resonance (CMR) imaging and coronary sinus flow measurements at rest and during maximal vasodilatation which is a well-validated approach for the quantification of global myocardial blood flow in CMR. The blood flow parameters were reduced at rest and during stress in both groups of patients with DCM and hypertrophic cardiomyopathy.2 Interestingly, in another study, it was shown that myocardial blood flow assessed by the CMR in DCM could be elevated at rest with a substantial decrease during the stress-test with adenosine. This corresponds well with the previous echocardiographic findings and also can reflect the possible stress-induced stunning instead of chronic hypoperfusion in DCM.3 Another promising in microcirculation evaluation, though not a fully available modality, is PET. In a study by Yamaguchi et al., the authors observed the regional 18-fluorodesoxiglucose uptake in all patients with ischemic cardiomyopathy in the fasting state, while patients with DCM showed variable patterns of uptake. Nevertheless, when going to glucose loading state, the DCM patients demonstrated mostly non-reversing patterns of uptake, which allows PET to distinguish DCM from ischemic cardiomyopathy.4 (99 m)Tc-methoxy-isobutyl-isonitrile and (123)I-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid dual single photon emission computed tomography also provides valuable data on perfusion-metabolism mismatches, which carry the prognostic role in DCM.5 Myocardial contrast echocardiography (MCE) being a more simple, bedside method has been previously found to be helpful in differentiating the DCM and ischemic heart disease in patients with acute onset of heart failure.6 However, another group of authors has the confronting results: the contrast replenishment rate was similar in patients with coronary artery disease and without it.7 In this issue of the Journal of Clinical Ultrasound Sha Tang et al, for the first time the MCE was combined with speckle tracking strain analysis in a layer-specific manner in patients with DCM and compared with the same parameters in healthy volunteers.8 While the poor global and regional LV systolic function assessed by speckle tracking strain in DCM patients in comparison to healthy subjects is awaited, the authors performed the comprehensive analysis of the interaction between segmental parameters by dividing the myocardium into standard segments plus three layers in each segment. Therefore, the data on gradients in strain and perfusion parameters becomes the mainstay of this study. The idea of layer-specific strain analysis is not new, but still can be regarded as a pure experimental method with no clinical implication. For example, in the work by Nagata Y et al. the authors offer Endo/Epi strain ratio for gradient assessment.9 Therefore, the authors demonstrated an interesting correlation between MCE perfusion and longitudinal function at rest in DCM patients with the diffuse pattern of impairment in all segments and layers. Considering the aforementioned CMR-based and PET-based studies, which showed a substantial decrease in coronary flow reserve between rest and stress, the MCE with pharmacological stress could be the rational development of basic ideas, presented in this study. Moreover, the dynamic nature of MCE can give the opportunity for dynamic malperfusion assessment in patients with DCM during stress. In addition, new insights into the pathophysiology of DCM may provide the basis for new clinical trials of various agents, intended to restore the damaged microcirculatory link in the chain of global LV deterioration. The authors have nothing to disclosure. Open Access funding enabled and organized by Projekt DEAL. Not applicable.

First-pass perfusion cardiovascular magnetic resonance parameters as surrogate markers for left ventricular diastolic dysfunction: a validation against cardiac catheterization

The non-invasive assessment of left ventricular (LV) diastolic dysfunction remains a challenge. The role of first-pass perfusion cardiac magnetic resonance (CMR) parameters in quantitative hemodynamic analyses has been reported. We therefore aimed to validate the diagnostic ability and accuracy of such parameters against cardiac catheterization for LV diastolic dysfunction in patients with left heart disease (LHD). We retrospectively enrolled 77 LHD patients who underwent CMR imaging and cardiac catheterization. LV diastolic dysfunction was defined as pulmonary capillary wedge pressure (PCWP) or LV end-diastolic pressure (LVEDP) > 12 mmHg on catheterization. On first-pass perfusion CMR imaging, pulmonary transit time (PTT) was measured as the time for blood to pass from the left ventricle to the right ventricle (RV) through the pulmonary vasculature. Pulmonary transit beat (PTB) was the number of cardiac cycles within the interval, and pulmonary blood volume indexed to body surface area (PBVi) was the product of PTB and RV stroke volume index (RVSVi). Of the 77 LHD patients, 53 (68.83%) were found to have LV diastolic dysfunction, and showed significantly higher PTTc, PTB, and PBVi (p < 0.05) compared with those without. In multivariate analyses, only PTTc and PTB were identified as independent predictors of LV diastolic dysfunction (p < 0.05). With an optimal cutoff of 11.9 s, PTTc yielded the best diagnostic performance for LV diastolic dysfunction (area under the curve = 0.83, p < 0.001). PTTc may represent a non-invasive quantitative surrogate marker for the detection and assessment of diastolic dysfunction in LHD patients. • PTTc yielded the best diagnostic accuracy for diastolic dysfunction, with an optimal cutoff of 11.9 s, and a specificity of 100%. • PTTc and PTB were found to be independent predictors of LV diastolic dysfunction across different multivariate models with high reproducibility. • PTTc is a promising non-invasive surrogate marker for the detection and assessment of diastolic dysfunction in LHD patients.

Automated Segmental Analysis of Fully Quantitative Myocardial Blood Flow Maps by First-Pass Perfusion Cardiovascular Magnetic Resonance.

First pass gadolinium-enhanced cardiovascular magnetic resonance (CMR) perfusion imaging allows fully quantitative pixel-wise myocardial blood flow (MBF) assessment, with proven diagnostic value for coronary artery disease. Segmental analysis requires manual segmentation of the myocardium. This work presents a fully automatic method of segmenting the left ventricular myocardium from MBF pixel maps, validated on a retrospective dataset of 247 clinical CMR perfusion studies, each including rest and stress images of three slice locations, performed on a 1.5T scanner. Pixel-wise MBF maps were segmented using an automated pipeline including region growing, edge detection, principal component analysis, and active contours to segment the myocardium, detect key landmarks, and divide the myocardium into sectors appropriate for analysis. Automated segmentation results were compared against a manually defined reference standard using three quantitative metrics: Dice coefficient, Cohen Kappa and myocardial border distance. Sector-wise average MBF and myocardial perfusion reserve (MPR) were compared using Pearson’s correlation coefficient and Bland-Altman Plots. The proposed method segmented stress and rest MBF maps of 243 studies automatically. Automated and manual myocardial segmentation had an average (± standard deviation) Dice coefficient of 0.86 ± 0.06, Cohen Kappa of 0.86 ± 0.06, and Euclidian distances of 1.47 ± 0.73 mm and 1.02 ± 0.51 mm for the epicardial and endocardial border, respectively. Automated and manual sector-wise MBF and MPR values correlated with Pearson’s coefficient of 0.97 and 0.92, respectively, while Bland-Altman analysis showed bias of 0.01 and 0.07 ml/g/min. The validated method has been integrated with our fully automated MBF pixel mapping pipeline to aid quantitative assessment of myocardial perfusion CMR.

Quantitative myocardial first-pass cardiovascular magnetic resonance perfusion imaging using hyperpolarized [1-13C] pyruvate

BackgroundThe feasibility of absolute myocardial blood flow quantification and suitability of hyperpolarized [1-13C] pyruvate as contrast agent for first-pass cardiovascular magnetic resonance (CMR) perfusion measurements are investigated with simulations and demonstrated in vivo in a swine model.MethodsA versatile simulation framework for hyperpolarized CMR subject to physical, physiological and technical constraints was developed and applied to investigate experimental conditions for accurate perfusion CMR with hyperpolarized [1-13C] pyruvate. Absolute and semi-quantitative perfusion indices were analyzed with respect to experimental parameter variations and different signal-to-noise ratio (SNR) levels. Absolute myocardial blood flow quantification was implemented with an iterative deconvolution approach based on Fermi functions. To demonstrate in vivo feasibility, velocity-selective excitation with an echo-planar imaging readout was used to acquire dynamic myocardial stress perfusion images in four healthy swine. Arterial input functions were extracted from an additional image slice with conventional excitation that was acquired within the same heartbeat.ResultsSimulations suggest that obtainable SNR and B0 inhomogeneity in vivo are sufficient for the determination of absolute and semi-quantitative perfusion with ≤25% error. It is shown that for expected metabolic conversion rates, metabolic conversion of pyruvate can be neglected over the short duration of acquisition in first-pass perfusion CMR. In vivo measurements suggest that absolute myocardial blood flow quantification using hyperpolarized [1-13C] pyruvate is feasible with an intra-myocardial variability comparable to semi-quantitative perfusion indices.ConclusionThe feasibility of quantitative hyperpolarized first-pass perfusion CMR using [1-13C] pyruvate has been investigated in simulations and demonstrated in swine. Using an approved and metabolically active compound is envisioned to increase the value of hyperpolarized perfusion CMR in patients.

Effects of hyperaemia on left ventricular longitudinal strain in patients with suspected coronary artery disease : Afirst-pass stress perfusion cardiovascular magnetic resonance imaging study.

AimsMyocardial perfusion imaging during hyperaemic stress is commonly used to detect coronary artery disease. The aim of this study was to investigate the relationship between left ventricular global longitudinal strain (GLS), strain rate (GLSR), myocardial early (E’) and late diastolic velocities (A’) with adenosine stress first-pass perfusion cardiovascular magnetic resonance (CMR) imaging.Methods and results44 patients met the inclusion criteria and underwent CMR imaging. The CMR imaging protocol included: rest/stress horizontal long-axis (HLA) cine, rest/stress first-pass adenosine perfusion and late gadolinium enhancement imaging. Rest and stress HLA cine CMR images were analysed using feature-tracking software for the assessment of myocardial deformation. The presence of perfusion defects was scored on a binomial scale. In patients with hyperaemia-induced perfusion defects, rest global longitudinal strain GLS (−16.9 ± 3.7 vs. −19.6 ± 3.4; p-value = 0.02), E’ (−86 ± 22 vs. −109 ± 38; p-value = 0.02), GLSR (69 ± 31 vs. 93 ± 38; p-value = 0.01) and stress GLS (−16.5 ± 4 vs. −21 ± 3.1; p < 0.001) were significantly reduced when compared with patients with no perfusion defects. Stress GLS was the strongest independent predictor of perfusion defects (odds ratio 1.43 95% confidence interval 1.14–1.78, p-value <0.001). A threshold of −19.8% for stress GLS demonstrated 78% sensitivity and 73% specificity for the presence of hyperaemia-induced perfusion defects.ConclusionsAt peak myocardial hyperaemic stress, GLS is reduced in the presence of a perfusion defect in patients with suspected coronary artery disease. This reduction is most likely caused by reduced endocardial blood flow at maximal hyperaemia because of transmural redistribution of blood flow in the presence of significant coronary stenosis.Electronic supplementary materialThe online version of this article (10.1007/s12471-017-1071-3) contains supplementary material, which is available to authorized users.

Analysis of spatiotemporal fidelity in quantitative 3D first-pass perfusion cardiovascular magnetic resonance

BackgroundWhole-heart first-pass perfusion cardiovascular magnetic resonance (CMR) relies on highly accelerated image acquisition. The influence of undersampling on myocardial blood flow (MBF) quantification has not been systematically investigated yet. In the present work, the effect of spatiotemporal scan acceleration on image reconstruction accuracy and MBF error was studied using a numerical phantom and validated in-vivo.MethodsUp to 10-fold scan acceleration using k-t PCA and k-t SPARSE-SENSE was simulated using the MRXCAT CMR numerical phantom framework. Image reconstruction results were compared to ground truth data in the k-f domain by means of modulation transfer function (MTF) analysis. In the x-t domain, errors pertaining to specific features of signal intensity-time curves and MBF values derived using Fermi model deconvolution were analysed. In-vivo first-pass CMR data were acquired in ten healthy volunteers using a dual-sequence approach assessing the arterial input function (AIF) and myocardial enhancement. 10x accelerated 3D k-t PCA and k-t SPARSE-SENSE were compared and related to non-accelerated 2D reference images.ResultsMTF analysis revealed good recovery of data upon k-t PCA reconstruction at 10x undersampling with some attenuation of higher temporal frequencies. For 10x k-t SPARSE-SENSE the MTF was found to decrease to zero at high spatial frequencies for all temporal frequencies indicating a loss in spatial resolution. Signal intensity-time curve errors were most prominent in AIFs from 10x k-t PCA, thereby emphasizing the need for separate AIF acquisition using a dual-sequence approach. These findings were confirmed by MBF estimation based on AIFs from fully sampled and undersampled simulations. Average in-vivo MBF estimates were in good agreement between both accelerated and the fully sampled methods. Intra-volunteer MBF variation for fully sampled 2D scans was lower compared to 10x k-t PCA and k-t SPARSE-SENSE data.ConclusionQuantification of highly undersampled 3D first-pass perfusion CMR yields accurate MBF estimates provided the AIF is obtained using fully sampled or moderately undersampled scans as part of a dual-sequence approach. However, relative to fully sampled 2D perfusion imaging, intra-volunteer variation is increased using 3D approaches prompting for further developments.

Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance

BackgroundPerfusion cardiovascular magnetic resonance (CMR) performed with inadequate adenosine stress leads to false-negative results and suboptimal clinical management. The recently proposed marker of adequate stress, the “splenic switch-off” sign, detects splenic blood flow attenuation during stress perfusion (spleen appears dark), but can only be assessed after gadolinium first-pass, when it is too late to optimize the stress response. Reduction in splenic blood volume during adenosine stress is expected to shorten native splenic T1, which may predict splenic switch-off without the need for gadolinium.MethodsTwo-hundred and twelve subjects underwent adenosine stress CMR: 1.5 T (n = 104; 75 patients, 29 healthy controls); 3 T (n = 108; 86 patients, 22 healthy controls). Native T1spleen was assessed using heart-rate-independent ShMOLLI prototype sequence at rest and during adenosine stress (140 μg/kg/min, 4 min, IV) in 3 short-axis slices (basal, mid-ventricular, apical). This was compared with changes in peak splenic perfusion signal intensity (ΔSIspleen) and the “splenic switch-off” sign on conventional stress/rest gadolinium perfusion imaging. T1spleen values were obtained blinded to perfusion ΔSIspleen, both were derived using regions of interest carefully placed to avoid artefacts and partial-volume effects.ResultsNormal resting splenic T1 values were 1102 ± 66 ms (1.5 T) and 1352 ± 114 ms (3 T), slightly higher than in patients (1083 ± 59 ms, p = 0.04; 1295 ± 105 ms, p = 0.01, respectively). T1spleen decreased significantly during adenosine stress (mean ΔT1spleen ~ −40 ms), independent of field strength, age, gender, and cardiovascular diseases. While ΔT1spleen correlated strongly with ΔSIspleen (rho = 0.70, p < 0.0001); neither indices showed significant correlations with conventional hemodynamic markers (rate pressure product) during stress. By ROC analysis, a ΔT1spleen threshold of ≥ −30 ms during stress predicted the “splenic switch-off” sign (AUC 0.90, p < 0.0001) with sensitivity (90%), specificity (88%), accuracy (90%), PPV (98%), NPV (42%).ConclusionsAdenosine stress and rest splenic T1-mapping is a novel method for assessing stress responses, independent of conventional hemodynamic parameters. It enables prediction of the visual “splenic switch-off” sign without the need for gadolinium, and correlates well to changes in splenic signal intensity during stress/rest perfusion imaging. ΔT1spleen holds promise to facilitate optimization of stress responses before gadolinium first-pass perfusion CMR.

Cardiovascular magnetic resonance detects the progression of impaired myocardial perfusion reserve and increased left-ventricular mass in mice fed a high-fat diet.

BackgroundImpaired myocardial perfusion reserve (MPR) is prevalent in obesity and diabetes, even in the absence of obstructive coronary artery disease (CAD), and is prognostic of adverse events. We sought to establish the time course of reduced MPR and to investigate associated vascular and tissue properties in mice fed a high-fat diet (HFD), as they are an emerging model of human obesity, diabetes, and reduced MPR without obstructive CAD.MethodsC57Bl/6 mice fed a HFD or a low-fat diet (control) were imaged at 6, 12, 18 and 24 weeks post-diet. The cardiovascular magnetic resonance (CMR) protocol included multi-slice cine imaging to assess ejection fraction (EF), left-ventricular (LV) mass, LV wall thickness (LVWT), and LV volumes, and first-pass perfusion CMR to quantify MPR. Coronary vascular reactivity, aortic atherosclerosis, myocardial capillary density and tissue fibrosis were also assessed.ResultsBody weight was increased in HFD mice at 6–24 weeks post-diet (p < 0.05 vs. control). MPR in HFD mice was reduced and LV mass and LVWT were increased in HFD mice at 18 and 24 weeks post-diet (p < 0.05 vs. control). Coronary arteriolar vascular reactivity to adenosine and acetylcholine were reduced in HFD mice (p < 0.05 vs. control). There were no significant differences in cardiac volumes, EF, or capillary density measurements between the two groups. Histology showed interstitial fibrosis in HFD and no aortic atherosclerosis in either group.ConclusionsC57Bl/6 mice fed a HFD for 18–24 weeks have progressively increased LV mass and impaired MPR with fibrosis, normal capillary density and no aortic plaque. These results establish C57Bl/6 mice fed a HFD for 18–24 weeks as a model of impaired MPR without obstructive CAD due to obesity and diabetes.

Variability in quantitative cardiac magnetic resonance perfusion analysis.

By taking advantage of its high spatial resolution, noninvasive and nontoxic nature first-pass perfusion cardiovascular magnetic resonance (CMR) has rendered an indispensable tool for the noninvasive detection of reversible myocardial ischemia. A potential advantage of perfusion CMR is its ability to quantitatively assess perfusion reserve within a myocardial segment, as expressed semi- quantitatively by myocardial perfusion reserve index (MPRI) and fully- quantitatively by absolute myocardial blood flow (MBF). In contrast to the high accuracy and reliability of CMR in evaluating cardiac function and volumes, perfusion CMR is adversely affected by multiple potential reasons during data acquisition as well as post-processing. Various image acquisition techniques, various contrast agents and doses as well as variable blood flow at rest as well as variable reactions to stress all influence the acquired data. Mechanisms underlying the variability in perfusion CMR post processing, as well as their clinical significance, are yet to be fully elucidated. The development of a universal, reproducible, accurate and easily applicable tool in CMR perfusion analysis remains a challenge and will substantially enforce the role of perfusion CMR in improving clinical care.

Myocardial perfusion reserve index during adenosine stress magnetic resonance for the detection of coronary artery disease - ready for prime time?

In the work recently published in Cardiovascular Diagnosis and Therapy, Goykhman et al. (1) evaluated the inter- and intra-observer variability of myocardial perfusion reserve indexes (MPRI) during first-pass perfusion cardiovascular magnetic resonance (CMR). Studies were conducted on 20 adenosine stress studies of 10 female patients with stable angina and 10 healthy volunteers. Data analysis was performed using a commercially available software tool. The authors found that variations are present in measurement of MPRI observed in post processing of perfusion data. This may affect the diagnosis of inducible perfusion abnormalities and therefore the diagnostic classification and risk stratification of patients with suspected or known ischemic heart disease.

Long-Term Impact of Undetected Kawasaki Syndrome on Coronary Morphology and Physiology

A 68-year-old white man presented for work-up of recurring atypical resting chest pain in the setting of known coronary artery disease. ECG and chest x-ray on admission can be viewed in Figures 1 and 2. Two years previously, invasive angiography was performed because of unstable angina revealing dilative coronary sclerosis of all coronaries with a proximal right coronary artery stenosis, which was treated with percutaneous intervention by another cardiologist at that time (Figure 3 and online-only Data Supplement Movies I–III). Figure 1. Twelve-lead ECG on admission demonstrating left-axis deviation, ectopic beats, and nonsignificant ST-segment abnormalities. Figure 2. Chest x-ray on admission revealing a normal-size heart, aspects of pulmonary emphysema, and small amounts of fluid in the right costophrenic angle. Figure 3. First invasive coronary angiography of the left (LCA) ( A ) and the right (RCA) ( B ) coronary arteries performed by another cardiologist 2 years previously. Note the proximal RCA stenosis (white arrows) in the setting of diffuse dilative coronary sclerosis ( C ), which was treated by percutaneous intervention. To evaluate possible progress of coronary artery disease, adenosine stress first-pass perfusion cardiovascular magnetic resonance (CMR) using a 1.5T Magnetom Aera (Siemens Healthcare, Erlangen, Germany) was performed. However, no myocardial ischemia could be detected by CMR in …

The DD genotype of the angiotensin converting enzyme gene independently associates with CMR-derived abnormal microvascular perfusion in patients with a first anterior ST-segment elevation myocardial infarction treated with thrombolytic agents

Introduction The role of the angiotensin converting enzyme (ACE) gene on the result of thrombolysis at the microvascular level has not been addressed so far. We analyzed the implications of the insertion/deletion (I/D) polymorphism of the ACE gene on the presence of abnormal cardiovascular magnetic resonance (CMR)-derived microvascular perfusion after ST-segment elevation myocardial infarction (STEMI). Materials and Methods We studied 105 patients with a first anterior STEMI treated with thrombolytic agents and an open left anterior descending artery. Microvascular perfusion was assessed using first-pass perfusion CMR at 7 ±1 days. CMR studies were repeated 184 ± 11 days after STEMI. The ACE gene insertion/deletion (I/D) polymorphism was determined using polymerase chain reaction amplification. Results Overall genotype frequencies were II-ID 58% and DD 42%. Abnormal perfusion (≥ 1 segment) was detected in 56% of patients. The DD genotype associated to a higher risk of abnormal microvascular perfusion (68% vs. 47%, p = 0.03) and to a larger extent of perfusion deficit (median [percentile 25 - percentile 75]: 4 [0-6] vs. 0 [0-4] segments, p = 0.003). Once adjusted for baseline characteristics, the DD genotype independently increased the risk of abnormal microvascular perfusion (odds ratio [95% confidence intervals]: 2.5 [1.02-5.9], p = 0.04). Moreover, DD patients displayed a larger infarct size (35 ± 17 vs. 27 ± 15 g, p = 0.01) and a lower ejection fraction at 6 months (48 ± 14 vs. 54 ± 14%, p = 0.03). Conclusions The DD genotype associates to a higher risk of abnormal microvascular perfusion after STEMI.

139 Determination of myocardial OEF with a CMR method in a stenotic dog study

Methods Thirteen dogs were divided into four groups (Table 1). Stenosis was created by using an occluder in the proximal left anterior descending coronary artery (LAD) in an open-chest model. Single-slice T2-weighted images were gathered by use of a 2-D segmented turbo spin-echo (TSE) sequence with double inversion recovery pulses. T2 maps can be generated with these T2-weighted images with different TE’s acquired in a single breathhold. This T2-imaging was performed several times during rest and during either Dipyridamole or Dobutamineinduced hyperemia. Using a two-compartment model validated in normal dogs [1], the OEF during hyperemia can be determined assuming resting OEF of 0.6, which is based on OEF values measured in normal dogs using an arterial and coronary sinus blood sampling approach at rest [3]. It is assumed that this value changes little with moderate stenosis [4], but for severe stenoses, this may be a potential source of error. The model also requires input of MBV values both at rest and during pharmaceutical hyperemia. These values were determined with a validated first-pass perfusion cardiovascular magnetic resonance (CMR) method [4]. OEF values were determined in the stenotic LAD region and a remote normal left-circumflex (LCX) subtended region. Results There is no significant change in OEF values calculated using assumed MBV and MBV measured with the quantitative CMR first-pass method. Nevertheless, the former slightly overestimated the later (0.3% in LAD-perfused and 5.8% in LCX-perfused regions) (Figure 1). This difference may explain why the former method slightly overestimated the “true” OEF values measured in normal dogs using the arterial-venous blood sampling approach [1]. The changes in OEF with measured MBV are shown in Figure 2. With the injection of Dipyridamole, while normal LAD region demonstrates reduced OEF of 0.31 (48% reduction), OEF in the LAD region changes to 0.54 (11% decrease) and 0.6 (0% change) in dogs with 70% and 90% stenosis, respectively. During the Dobutamine-induced hyperemia, dogs with stenosis had slight changes in OEF in the LAD region, but an increase to 0.69 (14% increase) and decrease to 0.46 (23%) in the LCX region with 50% and 70–90% stenosis, respectively (P = NS). This is consistent with our previous observation [2].

Myocardial perfusion in hypertensive patients with normal coronary angiograms

Pressure-induced left ventricular hypertrophy is one of the mechanisms responsible for an impaired coronary vasodilating capacity leading to myocardial ischemia and angina. The aim of the study was to investigate myocardial perfusion using cardiovascular magnetic resonance in patients with arterial hypertension and a history of chest pain and normal coronary angiography, and to estimate the influence of left ventricular hypertrophy on the parameters of myocardial perfusion. The study included 102 patients (mean age 55.4 +/- 7.7 years) with well controlled hypertension and 12 healthy volunteers. In 96 patients, myocardial first-pass perfusion cardiovascular magnetic resonance both at rest and during an infusion of adenosine 140 microg/kg/min was performed. Semiquantitative perfusion analysis was performed by using the upslope of myocardial signal enhancement to derive the myocardial perfusion index and the myocardial perfusion reserve index. The study group was divided according to the presence of left ventricular hypertrophy in the cardiovascular magnetic resonance examination: group with left ventricular hypertrophy (n = 40) and without left ventricular hypertrophy (n = 56). Independent of the presence of left ventricular hypertrophy, there were significant differences in baseline myocardial perfusion index between hypertensive patients and controls (0.13 +/- 0.07 vs. 0.04 +/- 0.01; P < 0.001), and in stress myocardial perfusion index (hypertensive patients 0.21 +/- 0.10 vs. controls 0.09 +/- 0.03; P < 0.001). In hypertensive patients, the myocardial perfusion reserve index was reduced in the mid and apical portions of the left ventricle (1.71 +/- 1.1 vs. 2.52 +/- 0.83; P < 0.02). There was no significant correlation of myocardial perfusion reserve index with left ventricular mass or hypertrophy. In patients with mild or moderate hypertension and a history of chest pain with normal coronary angiography, there is regional myocardial perfusion reserve impairment that is independent of the presence of left ventricular hypertrophy and may be a reason for angina.

Myocardial first-pass perfusion cardiovascular magnetic resonance: history, theory, and current state of the art.

In less than two decades, first-pass perfusion cardiovascular magnetic resonance (CMR) has undergone a wide range of changes with the development and availability of improved hardware, software, and contrast agents, in concert with a better understanding of the mechanisms of contrast enhancement. The following review provides a perspective of the historical development of first-pass CMR, the developments in pulse sequence design and contrast agents, the relevant animal models used in early preclinical studies, the mechanism of artifacts, the differences between 1.5T and 3T scanning, and the relevant clinical applications and protocols. This comprehensive overview includes a summary of the past clinical performance of first-pass perfusion CMR and current clinical applications using state-of-the-art methodologies.

Quantification of Myocardial Blood Volume During Dipyridamole and Doubtamine Stress: A Perfusion CMR Study

Myocardial blood volume (MBV) may provide complementary information about myocardial oxygen needs and viability. The aim of this study is to examine a Cardiovascular Magnetic Resonance (CMR) perfusion method to quantify the changes in MBV, in comparison with the radiolabeled 99mTc-Red-Blood-Cell (RBC) method. Normal mongrel dogs (n=12) were used in this study. Eight dogs were injected intravenously with dipyridamole, and 4 dogs were given dobutamine during the MR scans. CMR first-pass perfusion imaging was performed at rest and during the pharmacological stress. An intravascular contrast agent, Gadomer (Schering AG, Berlin, Germany), was injected (0.015 mmol/kg) as a bolus during the scans. A perfusion quantification method was applied to obtain MBV maps. Radiolabeled-RBCs were injected at the end of the study to measure reference MBV at rest (n=4), during dipyridamole vasodilation (n=4), and during dobutamine stress (n=4). Myocardial blood flow (MBF) increased approximately 3-fold with both dipyridamole and dobutamine injections. Transmural MBV values measured by CMR were closely correlated with those measured by 99mTc method (CMR:MBV=6.2+/-1.3, 7.2+/-0.8, and 8.3+/-0.5 mL/100 g, at rest, with dipyridamole, and with dobutamine, respectively. 99mTc-RBC: MBV=6.1+/-0.5, 7.0+/-0.9, and 8.6+/-0.7 mL/100 g). Dobutamine stress significantly increased MBV by CMR (33%) and 99mTc methods (35%). During dipyridamole induced vasodilation, MBV increased non-significantly by 14% with the 99mTc method and 1% with CMR method, which agreed well with other reports. First-pass perfusion CMR with the injection of intravascular contrast agents is a promising non-invasive approach for the assessment of MBV both at rest and pharmacologically induced stress.

Cardiovascular Magnetic Resonance Perfusion Imaging at 3-Tesla for the Detection of Coronary Artery Disease: A Comparison With 1.5-Tesla

This study was designed to establish the diagnostic accuracy of cardiovascular magnetic resonance (CMR) perfusion imaging at 3-Tesla (T) in suspected coronary artery disease (CAD). Myocardial perfusion imaging is considered one of the most compelling applications for CMR at 3-T. The 3-T systems provide increased signal-to-noise ratio and contrast enhancement (compared with 1.5-T), which can potentially improve spatial resolution and image quality. Sixty-one patients (age 64 +/- 8 years) referred for elective diagnostic coronary angiography (CA) for investigation of exertional chest pain were studied (before angiogram) with first-pass perfusion CMR at both 1.5- and 3-T and at stress (140 microg/kg/min intravenous adenosine, Adenoscan, Sanofi-Synthelabo, Guildford, United Kingdom) and rest. Four short-axis images were acquired during every heartbeat using a saturation recovery fast-gradient echo sequence and 0.04 mmol/kg Gd-DTPA bolus injection. Quantitative CA served as the reference standard. Perfusion deficits were interpreted visually by 2 blinded observers. We defined CAD angiographically as the presence of > or =1 stenosis of > or =50% diameter in any of the main epicardial coronary arteries or their branches with a diameter of > or =2 mm. The prevalence of CAD was 66%. All perfusion images were found to be visually interpretable for diagnosis. We found that 3-T CMR perfusion imaging provided a higher diagnostic accuracy (90% vs. 82%), sensitivity (98% vs. 90%), specificity (76% vs. 67%), positive predictive value (89% vs. 84%), and negative predictive value (94% vs. 78%) for detection of significant coronary stenoses compared with 1.5-T. The diagnostic performance of 3-T perfusion imaging was significantly greater than that of 1.5-T in identifying both single-vessel disease (area under receiver-operator characteristic [ROC] curve: 0.89 +/- 0.05 vs. 0.70 +/- 0.08; p < 0.05) and multivessel disease (area under ROC curve: 0.95 +/- 0.03 vs. 0.82 +/- 0.06; p < 0.05). There was no difference between field strengths for the overall detection of coronary disease (area under ROC curve: 0.87 +/- 0.05 vs. 0.78 +/- 0.06; p = 0.23). Our study showed that 3-T CMR perfusion imaging is superior to 1.5-T for prediction of significant single- and multi-vessel coronary disease, and 3-T may become the preferred CMR field strength for myocardial perfusion assessment in clinical practice.

Contrast–dose relation in first‐pass myocardial MR perfusion imaging

To determine the regime of linear contrast enhancement in human first-pass perfusion cardiovascular magnetic resonance (CMR) imaging to improve accuracy in myocardial perfusion quantification. A total of 10 healthy subjects were studied on a clinical 1.5T MR scanner. Seven doses of Gd-DTPA ranging from 0.00125 to 0.1 mmol/kg of body weight (b.w.) were administered as equal volumes by rapid bolus injection (6 mL/second). Resting periods of 15 minutes were introduced after delivery of Gd doses >0.01 mmol/kg b.w. For each subject, two series of rest perfusion scans were performed using two different multislice saturation-recovery perfusion sequences. Maximum contrast enhancement and maximum upslope were obtained in the blood pool of the left ventricular (LV) cavity and in the myocardium. The range of linear contrast-dose relation was determined by linear regression analysis. MR signal intensity increased linearly for contrast agent concentrations up to 0.01 mmol/kg b.w. in the LV blood pool and up to 0.05 mmol/kg b.w. in the myocardium. For Gd concentrations exceeding these thresholds the signal intensity response was not linear with respect to the contrast agent dose. Quantitative evaluation of cardiac MR perfusion data needs to account for signal saturation in both the LV blood pool and the myocardium.