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To determine if myocardial perfusion cardiac magnetic resonance (MR) imaging can show changes in myocardial blood flow (MBF) during the cold pressor test (CPT) and can allow identification of the differing endothelial function of smokers and nonsmokers when compared during adenosine stress.The study was approved by the institutional ethics review board and all participants gave informed written consent. Twenty-nine healthy volunteers (19 nonsmokers, 10 smokers; mean age ± standard deviation, 22 years ± 4) underwent 1.5-T MR imaging and analysis. Myocardial perfusion was assessed during rest, peak CPT, and adenosine hyperemia with a saturation-recovery gradient-echo pulse sequence (spatial resolution, 2.4 × 2.4 × 10 mm). Global, endocardial, and epicardial MBF were calculated by using Fermi-constrained deconvolution. Paired and independent t test statistical analyses were used to compare the responses between tests and groups. Regression analysis was performed to identify predictors of MBF change.MBF at rest was similar between the nonsmoking and smoking groups (0.97 mL/g/min ± 0.4 vs 0.96 mL/g/min ± 0.3, respectively; P = .96). Nonsmokers responded to CPT with a 47% increase in MBF (1.43 mL/g/min ± 0.5) and smokers responded with a 27% increase (1.22 mL/g/min ± 0.4; P.001). An endocardial-to-epicardial gradient existed at rest (nonsmokers, 1.10 [P = .002]; smokers, 1.30 [P = .01]) and CPT (nonsmokers, 1.19 [P.001] smokers, 1.28 [P = .04]) but reversed during adenosine stress (nonsmokers, 0.89 [P = .03]; smokers, 0.92 [P = .42]).Myocardial perfusion cardiac MR imaging during CPT can allow assessment of changes in MBF globally and in the separate myocardial layers in healthy smokers and nonsmokers. This allows the combined assessment of endothelium-dependent (CPT) and endothelium-independent (adenosine stress test) MBF reserve in a single study.

Purpose: To assess the reproducibility of semiquantitative and quantitative analysis of first-pass myocardial perfusion cardiovascular magnetic resonance (CMR) in healthy volunteers. Materials and Methods: Eleven volunteers underwent myocardial perfusion CMR during adenosine stress and rest on 2 separate days. Perfusion data were acquired in a single mid-ventricular section in two cardiac phases to permit cardiac phase reproducibility comparisons. Semiquantitative analysis was performed to derive normalized upslopes of myocardial signal intensity profiles (myocardial perfusion index, MPI). The quantitative analysis estimated absolute myocardial blood flow (MBF) using Fermi-constrained deconvolution. The perfusion reserve index was calculated by dividing stress by rest data. Two observers performed all the measurements independently. One observer repeated all first scan measurements 4 weeks later. Results: The reproducibility of perfusion CMR was highest for semiquantitative analysis with an intraobserver coefficient of variability (CoV) of 3%–7% and interobserver CoV of 4%–10%. Semiquantitative interstudy comparison was less reproducible (CoV of 13%–27%). Quantitative intraobserver CoV of 10%–18%, interobserver CoV of 8%–15% and interstudy CoV of 20%–41%. Reproducibility of systolic and diastolic phases and the endocardial and epicardial myocardial layer showed similar reproducibility on both semiquantitative and quantitative analysis. Conclusion: The reproducibility of CMR myocardial perfusion estimates is good, but varies between intraobserver, interobserver, and interstudy comparisons. In this study semiquantitative analysis was more reproducible than quantitative analysis. J. Magn. Reson. Imaging 2013;37:865–874. © 2013 Wiley Periodicals, Inc.

This study aims to quantify subendocardial and subepicardial myocardial blood flow (MBF) from dynamic contrast-enhanced MRI and to compare semi-quantitative and quantitative analysis methods. 17 healthy volunteers (9 males, mean age 34 ± 8) were scanned during adenosine stress and at rest. A “semi-quantitative” myocardial perfusion index (MPI) was calculated based on maximal upslopes of signal intensity-time profiles for a mid-ventricular myocardial slice. In addition, absolute MBF (ml/g/min) was estimated using Fermi-constrained deconvolution. On semi-quantitative analysis, the ratio of subendocardial to subepicardial MPI was 0.98 ± 0.1 at stress and 1.16 ± 0.09 at rest, P < 0.0001. The MPRI (i.e. the ratio of stress over rest MPI) for the subendocardium was 1.54 ± 0.3 versus 1.81 ± 0.35 for the subepicardium, P = 0.03. For quantitative analysis, the ratio of subendocardial to subepicardial MBF was 0.91 ± 0.11 at stress versus 1.17 ± 0.16 at rest, P < 0.0001. The subendocardial MBF reserve was also lower than in the subepicardium (2.6 ± 0.75 vs. 3.32 ± 0.93, P = 0.027). In conclusion, semi-quantitative and quantitative analysis of dynamic contrast-enhanced MRI shows higher subendocardial blood flow at rest and reduced subendocardial perfusion reserve compared to the subepicardium.

Quantitative analysis of cardiac dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) perfusion datasets is dependent on the drawing (manually or automatically) of myocardial contours. The required accuracy of these contours for myocardial blood flow (MBF) estimation is not well understood. This study investigates the relationship between myocardial contour errors and MBF errors. Myocardial contours were manually drawn on DCE-MRI perfusion datasets of healthy volunteers imaged in systole. Systematic and random contour errors were simulated using spline curves and the resulting errors in MBF were calculated. The degree of contour error was also evaluated by two recognized segmentation metrics. We derived contour error tolerances in terms of the maximum deviation (MD) a contour could deviate radially from the 'true' contour expressed as a fraction of each volunteer's mean myocardial width (MW). Significant MBF errors were avoided by setting tolerances of MD ≤ 0.4 MW, when considering the whole myocardium, MD ≤ 0.3 MW, when considering six radial segments, and MD ≤ 0.2 MW for further subdivision into endo- and epicardial regions, with the exception of the anteroseptal region, which required greater accuracy. None of the considered segmentation metrics correlated with MBF error; thus, both segmentation metrics and MBF errors should be used to evaluate contouring algorithms.

Myocardial blood flow varies during the cardiac cycle in response to pulsatile changes in epicardial circulation and cyclical variation in myocardial tension. First-pass assessment of myocardial perfusion by dynamic contrast-enhanced MRI is one of the most challenging applications of MRI because of the spatial and temporal constraints imposed by the cardiac physiology and the nature of dynamic contrast-enhanced MRI signal collection. Here, we describe a dynamic contrast-enhanced MRI method for simultaneous assessment of systolic and diastolic myocardial blood flow. The feasibility of this method was demonstrated in a study of 17 healthy volunteers at rest and under adenosine-induced vasodilatory stress. We found that myocardial blood flow was independent of the cardiac phase at rest. However, under adenosine-induced hyperemia, myocardial blood flow and myocardial perfusion reserve were significantly higher in diastole than in systole. Furthermore, the transmural distribution of myocardial blood flow and myocardial perfusion reserve was cardiac phase dependent, with a reversal of the typical subendocardial to subepicardial myocardial blood flow gradient in systole, but not diastole, under stress. The observed difference between systolic and diastolic myocardial blood flow must be taken into account when assessing myocardial blood flow using dynamic contrast-enhanced MRI. Furthermore, targeted assessment of systolic or diastolic perfusion using dynamic contrast-enhanced MRI may provide novel insights into the pathophysiology of ischemic and microvascular heart disease.

Background Type 2 Diabetes Mellitus (T2DM) and prediabetes are associated with an increased cardiovascular risk and heart failure independent of the presence of obstructive coronary artery disease, caused in part by myocardial microvascular dysfunction. Recent studies have reported contractile dysfunction and increased rotation with the onset of diabetic cardiomyopathy in uncomplicated T2DM patients. Independently, higher resting myocardial blood flow (MBF) has been reported in T2DM. The objective of this study was to determine whether there is a correlation between LV Epicardial Rotation (LV ER) and resting MBF in T2DM patients with angiographically normal coronaries, measured by tissue tagging and perfusion cardiovascular Magnetic Resonance (CMR). Methods Sixty five patients with no coronary stenosis >30% on invasive angiography were recruited and categorized into T2DM, prediabetes and normal controls groups according to American Diabetes Association guidelines. All patients underwent rest and adenosine stress myocardial perfusion CMR at a single mid-LV location, cine imaging covering the entire heart and myocardial tissue tagging in three LV short axis locations (apical, mid LV and basal). LV volumes and mass were calculated from cine images. LV rotation in three myocardial layers (endocardial, midmyocardial and epicardial) was calculated from CSPAMM tissue images using Tag Track (Gyrotools, Zurich). For this study, only rest MBF was calculated using Fermi-constrained deconvolution for the entire myocardium. Results Patient characteristics and results are shown in Table 1. Patients with T2DM had significantly higher resting MBF than the two other groups. Corresponding mid LV ER was higher in T2DM patients compared to patients with prediabetes and normal controls (Figure 1) (not statistically significant). Univariate analysis showed a significant positive correlation between MBF and LV ER in the entire study population (Pearson coefficient (r) of 0.25, p = 0.05). In the individual groups, the linear determination coefficient (R2) showed that LV ER in T2DM patients had stronger positive correlation (R2 = 0.31) with resting MBF than in patients with prediabetes (R2 = 0.16) and controls (R2 = 0.29), Figure 1. Conclusions T2DM patients when compared to age-matched patients with prediabetes and normal controls have higher peak LV ER. Resting MBF correlates with LV ER. These results suggest that LV ER analysis in uncomplicated T2DM patients may be useful for non-invasive screening of early subtle contractile dysfunction associated with microvascular dysfunction in diabetes patients.

To compare myocardial blood flow (MBF) at systole and diastole and determine the diagnostic accuracy of both phases in patients suspected of having coronary artery disease (CAD).The study was approved by the regional ethics committee, and all patients gave written informed consent. After coronary angiography, 40 patients (27 men; mean age, 64 years ± 8) underwent stress-rest perfusion magnetic resonance (MR) imaging at 1.5 T, with images aquired simultaneously at end systole and middiastole. Patients were classified as having CAD (stenosis .70%) or no significant CAD. In patients with CAD, myocardial segments were classified as stenosis-dependent (downstream of significant stenosis) or remote. MBF and myocardial perfusion reserve (MPR) were calculated for each segment, and mean values in each phase were compared with paired t tests. The diagnostic accuracy of each phase was determined with receiver operating characteristic (ROC) analysis.Twenty-one of the 40 patients (53%) had CAD. Resting MBF was similar in both phases for patients with and patients without CAD (P.05). Stress MBF was greater in diastole than systole in normal, remote, and stenosis-dependent segments (3.75 mL/g/min ± 1.50 vs 3.15 mL/g/min ± 1.10, respectively, for normal segments; 2.75 mL/g/min ± 1.20 vs 2.38 mL/g/min ± 0.99, respectively, for remote segments; 2.49 mL/g/min ± 1.07 vs 2.23 mL/g/min ± 0.90, respectively, for stenosis-dependent segments; P.01). MPR was greater in diastole than systole in all segment groups (P.05). The diagnostic accuracies at diastole and systole were similar (area under the ROC curve = 0.79 and 0.82, respectively; P = .30).Myocardial perfusion MR estimates of stress MBF and MPR were greater in diastole than systole in patients with and patients without CAD. However, both phases had similar diagnostic accuracy. These observations may be relevant to other dynamic perfusion methods, including computed tomography and echocardiography.

This study has shown that in patients with suspected and confirmed CAD, estimates of MBF by perfusion-CMR are significantly higher in diastole than systole during maximal hyperemic stress.

We have calculated the inter-study reproducibility of myocardial strain and twist measured by CSPAMM and calculated the number of subjects required to detect a significant change in these parameters.

k-t Sensitivity-encoded (k-t SENSE) acceleration has been used to improve spatial resolution, temporal resolution, and slice coverage in first-pass cardiac magnetic resonance myocardial perfusion imaging. This study compares the effect of investing the speed-up afforded by k-t SENSE acceleration in spatial or temporal resolution. Ten healthy volunteers underwent adenosine stress myocardial perfusion imaging using four saturation-recovery gradient echo perfusion sequences: a reference sequence accelerated by sensitivity encoding (SENSE), and three k-t SENSE–accelerated sequences with higher spatial resolution (“k-t High”), shorter acquisition window (“k-t Fast”), or a shared increase in both parameters (“k-t Hybrid”) relative to the reference. Dark-rim artifacts and image quality were analyzed. Semiquantitative myocardial perfusion reserve index (MPRI) and Fermi-derived quantitative MPR were also calculated. The k-t Hybrid sequence produced highest image quality scores at rest (P = 0.015). Rim artifact thickness and extent were lowest using k-t High and k-t Hybrid sequences (P < 0.001). There were no significant differences in MPRI and MPR values derived by each sequence. Maximizing spatial resolution by k-t SENSE acceleration produces the greatest reduction in dark rim artifact. There is good agreement between k-t SENSE and standard acquisition methods for semiquantitative and fully quantitative myocardial perfusion analysis. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.

Introduction Dynamic contrast enhanced myocardial perfusion MRI (DCE-MRI) has the potential to be superior to other currently available imaging techniques for the assessment of myocardial ischaemia. Quantitative analysis of cardiac perfusion is currently not routinely carried out because of the time consuming process of manually segmenting the myocardium from large DCE-MRI datasets. A range of automated segmentation algorithms have been proposed which quote results in terms of distance error or estimated myocardial blood flow (MBF). However, the relationship between these two evaluation measures is not clear, making objective comparisons of algorithm performance difficult.

Introduction First pass cardiac magnetic resonance (CMR) myocardial perfusion imaging (MPI) requires the acquisition of large amounts of image data in a short time. Acceleration techniques like k-t SENSE exploit spatiotemporal correlations to speed up data acquisition. In myocardial perfusion CMR k-t SENSE has been used to improve spatial resolution, temporal resolution or slice coverage with improvements of endocardial dark rim artefacts reported. To date, there has been no direct comparison between these strategies.

Animal experiments using labelled microspheres have shown that at rest, blood flow to the subendocardial layer is higher than to the subepicardium. With increasing levels of stress this transmural gradient of myocardial blood flow is reduced, so that the endocardium has a lower perfusion reserve than the epicardium [1]. The causes for this observation include higher compressive forces and higher resting metabolic activity in the endocardium. If microvascular function is impaired, endocardial perfusion reserve is reduced further [2]. Myocardial perfusion-CMR is usually performed with coverage of several myocardial sections to allow detection of ischemic perfusion defects. Consequently, compromises regarding image quality and motion artefact are made. For the study of global physiological phenomena and diffuse myocardial disease, optimised acquisition of a single section may be more useful.

Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk of heart failure independently of underlying coronary artery disease (CAD) [1]. Myocardial blood flow (MBF) and MBF reserve can be abnormal in patients with T2DM due to myocardial microvascular dysfunction, contributing to the development of heart failure [2]. The myocardial layers may be affected differently by this disease process.

Methods 12 healthy volunteers (6 males, mean age 33±7 years) underwent CMR studies on a 1.5T system (Intera CV, Philips Healthcare, The Netherlands). Tagged CMR images were acquired at the apex, mid-ventricle and base with a CSPAMM pulse sequence (field of view: 300mm, matrix 128 x 128, slice thickness 10mm, tag separation 8mm, 18 phases, typical TR/TE 30ms/6ms, flip angle 25 degrees). In 6 volunteers repeat data sets were acquired after a mean interval of 8±3 days. Data were analysed by two independent observers using Tagtrack software (Gyrotools, CH). Circumferential Langranian strain, radial Langranian strain and rotation were calculated for the three short axis slices. Endocardial and epicardial borders were drawn, and a midline calculated automatically. Left ventricular twist was calculated by subtracting the basal rotation from the apical rotation. The mean difference between paired measurements, the standard deviation (SD) of the differences and the coefficient of variability (Co-V) were calculated.

Methods Thirty-nine patients with 3VD at X-ray coronary angiography and 39 matched patients with no significant coronary disease were identified from the CE-MARC study population [1]. Patients were matched by age, gender, hypertension and diabetes. CMR adenosine stress perfusion imaging was undertaken using a saturation-recovery gradient echo pulse sequence producing three image slices per R-R interval. Visual and Fermi deconvolutionderived CMR myocardial perfusion reserve (MPR) analyses were performed. Gated SPECT imaging was performed and interpreted by an experienced observer blinded to other test results.

Methods 10 volunteers (7 male, mean age 38 years) were studied on a 1.5 T Philips Intera system during adenosine induced hyperaemia (140 mcg/kg/min for 3 minutes, 0.05 mmol/ kg Gd-DTPA) and at rest. A pulse sequence optimised for acquisition of a single midventricular slice at systole was used (saturation recovery segmented gradient echo, 2 × SENSE TR/TE/flip 2.7 ms/1.0/15°, typical FOV 380 × 380 mm, matrix 160 × 160, slice thickness 10 mm, preparation pulse delay 150 ms, shot duration 130 ms). Endo and epicardial contours were drawn and the slice segmented into 6 equidistant sectors. These were further subdivided into epicardial, mid-myocardial and endocardial thirds. Based on LV and blood pool time intensity curves, an inhouse mathematical Fermi Function deconvolution algorithm was implemented to estimate absolute myocardial blood flow [2].

Summary Dynamic contrast-enhanced (DCE) MRI was performed in 16 healthy subjects to measure myocardial microvascular characteristics. In addition, repeatability was assessed in 11 of those subjects who underwent a second examination. The results showed that Gd-DTPA transport in the myocardium is not perfusion limited at rest or under adenosine stress. Background DCE MRI has been used to estimate myocardial perfusion (blood flow, Fb) but there has been little work published on using this technique to measure related microvascular characteristics, such as microvessel permeability-surface area product (PS) and interstitial volume (extra-vascular extra-cellular volume, ve). The reason may be that transport of Gd-DTPA in resting myocardium is thought to be perfusion limited (with near complete first pass extraction). This study aimed to assess the potential of measuring microvascular characteristics in healthy individuals at rest and under adenosine stress and to assess the repeatability of the measurements.

Methods 11 volunteers (6 males, mean age 33 ± 7 years) underwent CMR perfusion on 2 separate days (mean interstudy delay = 84 ± 111 days, median delay = 7 days) on a 1.5 T Philips Intera system during adenosine-induced hyperaemia (140 mcg/kg/min, 0.05 mmol/kg Gd-DTPA) and rest. A pulse sequence optimised for acquisition of a single midventricular slice at systole was used (saturation recovery segmented gradient echo, 2 × SENSE TR/TE/flip 2.7 ms/1.0/ 15°, typical FOV 380 × 380 mm, matrix 160 × 160, slice thickness 10 mm, preparation pulse delay 150 ms, shot duration 130 ms). Endoand epicardial contours were drawn. "Semi"-quantitative analysis calculated maximal upslopes of myocardial signal intensity of the entire slice, normalised to the LV blood-pool (Myocardial perfusion index, MPI) using MASS 6.0 (Medis, Leiden, The Netherlands). The myocardial perfusion reserve index (MPRI) was calculated as the ratio of hyperaemic over rest MPI.