The impact of water exchange on estimates of myocardial extracellular volume calculated using contrast enhanced T1 measurements: A preliminary analysis in patients with severe aortic stenosis.

PURPOSE: Guidelines recommend measuring myocardial extracellular volume (ECV) using T1 -mapping before and 10-30 min after contrast agent administration. Data are then analyzed using a linear model (LM), which assumes fast water exchange (WX) between the ECV and cardiomyocytes. We investigated whether limited WX influences ECV measurements in patients with severe aortic stenosis (AS). METHODS: Twenty-five patients with severe AS and 5 healthy controls were recruited. T1 measurements were made on a 3 T Siemens system using a multiparametric saturation-recovery single-shot acquisition (a) before contrast; (b) 4 min post 0.05 mmol/kg gadobutrol; and (c) 4 min, (d) 10 min, and (e) 30 min after an additional gadobutrol dose (0.1 mmol/kg). Three LM-based ECV estimates, made using paired T1 measurements (a and b), (a and d), and (a and e), were compared to ECV estimates made using all 5 T1 measurements and a two-site exchange model (2SXM) accounting for WX. RESULTS: Median (range) ECV estimated using the 2SXM model was 25% (21%-39%) for patients and 26% (22%-29%) for controls. ECV estimated in patients using the LM at 10 min following a cumulative contrast dose of 0.15 mmol/kg was 21% (17%-32%) and increased significantly to 22% (19%-35%) at 30 min (p = 0.0001). ECV estimated using the LM was highest following low dose gadobutrol, 25% (19%-38%). CONCLUSION: Current guidelines on contrast agent dose for ECV measurements may lead to underestimated ECV in patients with severe AS because of limited WX. Use of a lower contrast agent dose may mitigate this effect.

First pilot study of extracellular volume MRI measurement in peripheral muscle of systemic sclerosis patients suggests diffuse fibrosis.

OBJECTIVES: Peripheral muscle involvement in SSc may comprise myositis or a non-inflammatory myopathy. There is little understanding of the nature of SSc myopathy. This pilot study aimed to evaluate the presence of diffuse fibrosis in the peripheral muscle of patients with SSc by determining extracellular volume (ECV) MRI measurement. METHODS: SSc patients, with either suspected myopathy or no muscle involvement, and healthy controls (HCs) had native T1 and ECV MRI quantification of the thigh and creatine-kinase (CK) measured. Suspected myopathy was defined as current / history of minimally raised CK (>320; <600 IU/l) ± presence of clinical signs/symptoms (including proximal lower-limb muscle weakness and/or myalgia) ± a Manual Muscle Testing (MMT) 8 score of <5 in the thighs. RESULTS: Twelve SSc patients and 10 HCs were recruited. Of the 12 patients, 9 had limited cutaneous SSc, 4 had interstitial lung disease, and 7 had suspected myopathy. The higher skeletal muscle ECV was recorded for SSc patients compared with HCs [mean (s.d.) 23 (11)%, vs 11 (4)%, P = 0.04]. Peripheral muscle ECV was associated with CK (rho = 0.554, P = 0.061) and was higher in SSc patients with myopathy than in those with no myopathy [mean (s.d.) 28 (10) vs 15 (5), P = 0.023]. It was determined that an ECV of 22% best identified myopathy (with a sensitivity of 71% and a specificity of 80%). CONCLUSION: This hypothesis-generating study showed higher ECV in SSc patients compared with HCs, as well as association of ECV with suspected myopathy, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. Further studies are needed to understand the nature of SSc myopathy.

Clinical associations with stage B heart failure in adults with type 2 diabetes.

BACKGROUND: There is a high prevalence of asymptomatic (American Heart Association Stage B) heart failure (SBHF) in people with type 2 diabetes (T2D). We aimed to identify associations between clinical characteristics and markers of SBHF in adults with T2D, which may allow therapeutic interventions prior to symptom onset. METHODS: Adults with T2D from a multi-ethnic population with no prevalent cardiovascular disease [n = 247, age 52 ± 12 years, glycated haemoglobin A1c (HbA1c) 7.4 ± 1.1% (57 ± 12 mmol/mol), duration of diabetes 61 (32, 120) months] underwent echocardiography and adenosine stress perfusion cardiovascular magnetic resonance imaging. Multivariable linear regression analyses were performed to identify independent associations between clinical characteristics and markers of SBHF. RESULTS: In a series of multivariable linear regression models containing age, sex, ethnicity, smoking history, number of glucose-lowering agents, systolic blood pressure (BP) duration of diabetes, body mass index (BMI), HbA1c, serum creatinine, and low-density lipoprotein (LDL)-cholesterol, independent associations with: left ventricular mass:volume were age (ß = 0.024), number of glucose-lowering agents (ß = 0.022) and systolic BP (ß = 0.027); global longitudinal strain were never smoking (ß = -1.196), systolic BP (ß = 0.328), and BMI (ß = -0.348); myocardial perfusion reserve were age (ß = -0.364) and male sex (ß = 0.458); and aortic distensibility were age (ß = -0.629) and systolic BP (ß = -0.348). HbA1c was not independently associated with any marker of SBHF. CONCLUSIONS: In asymptomatic adults with T2D, age, systolic BP, BMI, and smoking history, but not glycaemic control, are the major determinants of SBHF. Given BP and BMI are modifiable, these may be important targets to reduce the development of symptomatic heart failure.

Cardiovascular Determinants of Aerobic Exercise Capacity in Adults With Type 2 Diabetes.

OBJECTIVE: To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO2) in adults with type 2 diabetes (T2D), a group at high risk of developing heart failure. RESEARCH DESIGN AND METHODS: Cross-sectional study. We prospectively enrolled a multiethnic cohort of asymptomatic adults with T2D and no history, signs, or symptoms of cardiovascular disease. Age-, sex-, and ethnicity-matched control subjects were recruited for comparison. Participants underwent bioanthropometric profiling, cardiopulmonary exercise testing, and cardiovascular magnetic resonance with adenosine stress perfusion imaging. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO2. RESULTS: A total of 247 adults with T2D (aged 51.8 ± 11.9 years, 55% males, 37% black or south Asian ethnicity, HbA1c 7.4 ± 1.1% [57 ± 12 mmol/mol], and duration of diabetes 61 [32-120] months) and 78 control subjects were included. Subjects with T2D had increased concentric left ventricular remodeling, reduced myocardial perfusion reserve (MPR), and markedly lower aerobic exercise capacity (peak VO2 18.0 ± 6.6 vs. 27.8 ± 9.0 mL/kg/min; P < 0.001) compared with control subjects. In a multivariable linear regression model containing age, sex, ethnicity, smoking status, and systolic blood pressure, only MPR (ß = 0.822; P = 0.006) and left ventricular diastolic filling pressure (E/e') (ß = -0.388; P = 0.001) were independently associated with peak VO2 in subjects with T2D. CONCLUSIONS: In a multiethnic cohort of asymptomatic people with T2D, MPR and diastolic function are key determinants of aerobic exercise capacity, independent of age, sex, ethnicity, smoking status, or blood pressure.

Feasibility of MRI based extracellular volume fraction and partition coefficient measurements in thigh muscle.

OBJECTIVE: This study aimed to assess the feasibility of extracellular volume-fraction (ECV) measurement, and time to achieve contrast equilibrium (CE), in healthy muscles, and to determine whether in-flow and partial-volume errors in the femoral artery affect measurements, and if there are differences in the partition coefficient (λ) between muscles. METHODS: T1 was measured in the biceps femoris, vastus intermedius, femoral artery and aorta of 10 healthy participants. This was repeated alternately between the thigh and aorta for ≥25 min following a bolus of gadoterate meglumine. λ was calculated for each muscle/blood measurement. Time to CE was assessed semi-quantitatively. RESULTS: 8/10 participants achieved CE. Time to CE = 19±2 min (mean ± 95% confidence interval). Measured λ: biceps femoris/aorta = 0.210±0.034, vastus intermedius/aorta = 0.165±0.015, biceps femoris/femoral artery = 0.265±0.054, vastus intermedius/femoral artery = 0.211±0.026. There were significant differences in λ between the muscles when using the same vessel (p < 0.05), and between λ calculated in the same muscle when using different vessels (p < 0.05). CONCLUSION: ECV measurements in the thigh are clinically feasible. The use of the femoral artery for the blood measurement is associated with small but significant differences in λ. ECV measurements are sensitive to differences between muscles within the healthy thigh. ADVANCES IN KNOWLEDGE: This paper determines the time to contrast equilibrium in the healthy thigh and describes a method for measuring accurately ECV in skeletal muscle. This can aid in the diagnosis and understanding of inflammatory auto-immune diseases.

Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial.

OBJECTIVE: To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training. RESEARCH DESIGN AND METHODS: This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (∼810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison. RESULTS: Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s-1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, LV mass/volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (ß = 0.132, P = 0.002) but did not improve with the MRP (ß = 0.016, P = 0.731). CONCLUSIONS: In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function.

Quantitative Myocardial Perfusion Imaging Versus Visual Analysis in Diagnosing Myocardial Ischemia: A CE-MARC Substudy.

OBJECTIVES: This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography. BACKGROUND: Visual analysis of perfusion cardiovascular magnetic resonance studies for assessing myocardial perfusion has been shown to have high diagnostic accuracy for coronary artery disease. However, only a few small studies have assessed the diagnostic accuracy of quantitative myocardial perfusion. METHODS: This retrospective study included 128 patients randomly selected from the CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) study population such that the distribution of risk factors and disease status was proportionate to the full population. Visual analysis results of cardiovascular magnetic resonance perfusion images, by consensus of 2 expert readers, were taken from the original study reports. Quantitative myocardial blood flow estimates were obtained using Fermi-constrained deconvolution. The reference standard for myocardial ischemia was a quantitative coronary x-ray angiogram stenosis severity of ≥70% diameter in any coronary artery of >2 mm diameter, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver-operating characteristic curve analysis. RESULTS: The area under the curve for visual analysis was 0.88 (95% confidence interval: 0.81 to 0.95) with a sensitivity of 81.0% (95% confidence interval: 69.1% to 92.8%) and specificity of 86.0% (95% confidence interval: 78.7% to 93.4%). For quantitative stress myocardial blood flow the area under the curve was 0.89 (95% confidence interval: 0.83 to 0.96) with a sensitivity of 87.5% (95% confidence interval: 77.3% to 97.7%) and specificity of 84.5% (95% confidence interval: 76.8% to 92.3%). There was no statistically significant difference between the diagnostic performance of quantitative and visual analyses (p = 0.72). Incorporating rest myocardial blood flow values to generate a myocardial perfusion reserve did not significantly increase the quantitative analysis area under the curve (p = 0.79). CONCLUSIONS: Quantitative perfusion has a high diagnostic accuracy for detecting coronary artery disease but is not superior to visual analysis. The incorporation of rest perfusion imaging does not improve diagnostic accuracy in quantitative perfusion analysis.

Patient-specific coronary blood supply territories for quantitative perfusion analysis.

Myocardial perfusion imaging, coupled with quantitative perfusion analysis, provides an important diagnostic tool for the identification of ischaemic heart disease caused by coronary stenoses. The accurate mapping between coronary anatomy and under-perfused areas of the myocardium is important for diagnosis and treatment. However, in the absence of the actual coronary anatomy during the reporting of perfusion images, areas of ischaemia are allocated to a coronary territory based on a population-derived 17-segment (American Heart Association) AHA model of coronary blood supply. This work presents a solution for the fusion of 2D Magnetic Resonance (MR) myocardial perfusion images and 3D MR angiography data with the aim to improve the detection of ischaemic heart disease. The key contribution of this work is a novel method for the mediated spatiotemporal registration of perfusion and angiography data and a novel method for the calculation of patient-specific coronary supply territories. The registration method uses 4D cardiac MR cine series spanning the complete cardiac cycle in order to overcome the under-constrained nature of non-rigid slice-to-volume perfusion-to-angiography registration. This is achieved by separating out the deformable registration problem and solving it through phase-to-phase registration of the cine series. The use of patient-specific blood supply territories in quantitative perfusion analysis (instead of the population-based model of coronary blood supply) has the potential of increasing the accuracy of perfusion analysis. Quantitative perfusion analysis diagnostic accuracy evaluation with patient-specific territories against the AHA model demonstrates the value of the mediated spatiotemporal registration in the context of ischaemic heart disease diagnosis.

A comparison of cardiovascular magnetic resonance and single photon emission computed tomography (SPECT) perfusion imaging in left main stem or equivalent coronary artery disease: a CE-MARC substudy.

BACKGROUND: Assessment of left main stem (LMS) stenosis has prognostic and therapeutic implications. Data on assessment of LMS disease by cardiovascular magnetic resonance (CMR) and single photon emission computed tomography (SPECT) are limited. CE-MARC is the largest prospective comparison of CMR and SPECT against quantitative invasive coronary angiography (QCA) for detection of coronary artery disease (CAD), and provided the framework for this evaluation. The aims of this study were to compare diagnostic accuracy of visual and quantitative perfusion CMR to SPECT in patients with LMS stable CAD. METHODS: Fifty-four patients from the CE-MARC study were included: 27 (4%) with significant LMS or LMS-equivalent disease on QCA, and 27 age/sex-matched patients with no flow-limiting CAD. All patients underwent multi-parametric CMR, SPECT and QCA. Performance of visual and quantitative perfusion CMR by Fermi-constrained deconvolution to detect LMS disease was compared with SPECT. RESULTS: Of 27 patients in the LMS group, 22 (81%) had abnormal CMR and 16 (59%) had abnormal SPECT. All patients with abnormal CMR had abnormal perfusion by visual analysis. CMR demonstrated significantly higher area under the curve (AUC) for detection of disease (0.95; 0.85-0.99) over SPECT (0.63; 0.49-0.76) (p = 0.0001). Global mean stress myocardial blood flow (MBF) by CMR in LMS patients was significantly lower than controls (1.77 ± 0.72 ml/g/min vs. 3.28 ± 1.20 ml/g/min, p < 0.001). MBF of <2.08 ml/g/min had sensitivity of 78% and specificity of 85% for diagnosis of LMS disease, with an AUC (0.87; 0.75-0.94) not significantly different to visual CMR analysis (p = 0.18), and more accurate than SPECT (p = 0.003). CONCLUSION: Visual stress perfusion CMR had higher diagnostic accuracy than SPECT to detect LMS disease. Quantitative perfusion CMR had similar performance to visual CMR perfusion analysis.

Investigation into diagnostic accuracy of common strategies for automated perfusion motion correction.

Respiratory motion is a significant obstacle to the use of quantitative perfusion in clinical practice. Increasingly complex motion correction algorithms are being developed to correct for respiratory motion. However, the impact of these improvements on the final diagnosis of ischemic heart disease has not been evaluated. The aim of this study was to compare the performance of four automated correction methods in terms of their impact on diagnostic accuracy. Three strategies for motion correction were used: (1) independent translation correction for all slices, (2) translation correction for the basal slice with transform propagation to the remaining two slices assuming identical motion in the remaining slices, and (3) rigid correction (translation and rotation) for the basal slice. There were no significant differences in diagnostic accuracy between the manual and automatic motion-corrected datasets ([Formula: see text]). The area under the curve values for manual motion correction and automatic motion correction were 0.93 and 0.92, respectively. All of the automated motion correction methods achieved a comparable diagnostic accuracy to manual correction. This suggests that the simplest automated motion correction method (method 2 with translation transform for basal location and transform propagation to the remaining slices) is a sufficiently complex motion correction method for use in quantitative myocardial perfusion.

Sensitivity of quantitative myocardial dynamic contrast-enhanced MRI to saturation pulse efficiency, noise and t1 measurement error: Comparison of nonlinearity correction methods.

PURPOSE: To compare methods designed to minimize or correct signal nonlinearity in quantitative myocardial dynamic contrast-enhanced (DCE) MRI. METHODS: DCE-MRI studies were simulated and data acquired in eight volunteers. Signal nonlinearity was corrected using either a dual-bolus approach or model-based correction using proton-density weighted imaging (conventional or dual-sequence acquisition) or T1 data (native or bookend). Scanning of healthy and infarcted myocardium at 3 T was simulated, including noise, saturation imperfection and T1 measurement error. Data were analyzed using model-based deconvolution with a one-compartment (mono-exponential) model. RESULTS: Substantial variation between methods was demonstrated in volunteers. In simulations the dual-bolus method proved stable for realistic levels of saturation efficiency but demonstrated bias due to residual nonlinearity. Model-based methods performed ideally in the absence of confounding error sources and were generally robust to noise or saturation imperfection, except for native T1 based correction which was highly sensitive to the latter. All methods demonstrated large variation in accuracy above an over-saturation level where baseline signal was nulled. For the dual-sequence approach this caused substantial bias at the saturation efficiencies observed in volunteers. CONCLUSION: The choice of nonlinearity correction method in myocardial DCE-MRI impacts on accuracy and precision of estimated parameters, particularly in the presence of nonideal saturation.

Comparison of the Diagnostic Performance of Four Quantitative Myocardial Perfusion Estimation Methods Used in Cardiac MR Imaging: CE-MARC Substudy.

PURPOSE: To compare the diagnostic performance of four tracer kinetic analysis methods to quantify myocardial perfusion from magnetic resonance (MR) imaging cardiac perfusion data sets in terms of their ability to lead to the diagnosis of myocardial ischemia. MATERIALS AND METHODS: The study was approved by the regional ethics committee, and all patients gave written consent. A representative sample of 50 patients with suspected ischemic heart disease was retrospectively selected from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease trial data set. Quantitative myocardial blood flow (MBF) was estimated from rest and adenosine stress MR imaging perfusion data sets by using four established methods. A matching diagnosis of both an inducible defect as assessed with single photon emission computed tomography and a luminal stenosis of 70% or more as assessed with quantitative x-ray angiography was used as the reference standard for the presence of myocardial ischemia. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis for each method, with stress MBF and myocardial perfusion reserve (MPR) serving as continuous measures. RESULTS: Area under the ROC curve with stress MBF and MPR as the outcome measures, respectively, was 0.86 and 0.92 for the Fermi model, 0.85 and 0.87 for the uptake model, 0.85 and 0.80 for the one-compartment model, and 0.87 and 0.87 for model-independent deconvolution. There was no significant difference between any of the models or between MBF and MPR, except that the Fermi model outperformed the one-compartment model if MPR was used as the outcome measure (P = .02). CONCLUSION: Diagnostic performance of quantitative myocardial perfusion estimates is not affected by the tracer kinetic analysis method used.

Susceptibility-weighted cardiovascular magnetic resonance in comparison to T2 and T2 star imaging for detection of intramyocardial hemorrhage following acute myocardial infarction at 3 Tesla.

BACKGROUND: Intramyocardial hemorrhage (IMH) identified by cardiovascular magnetic resonance (CMR) is an established prognostic marker following acute myocardial infarction (AMI). Detection of IMH by T2-weighted or T2 star CMR can be limited by long breath hold times and sensitivity to artefacts, especially at 3T. We compared the image quality and diagnostic ability of susceptibility-weighted magnetic resonance imaging (SW MRI) with T2-weighted and T2 star CMR to detect IMH at 3T. METHODS: Forty-nine patients (42 males; mean age 58 years, range 35-76) underwent 3T cardiovascular magnetic resonance (CMR) 2 days following re-perfused AMI. T2-weighted, T2 star and SW MRI images were obtained. Signal and contrast measurements were compared between the three methods and diagnostic accuracy of SW MRI was assessed against T2w images by 2 independent, blinded observers. Image quality was rated on a 4-point scale from 1 (unusable) to 4 (excellent). RESULTS: Of 49 patients, IMH was detected in 20 (41%) by SW MRI, 21 (43%) by T2-weighted and 17 (34%) by T2 star imaging (p = ns). Compared to T2-weighted imaging, SW MRI had sensitivity of 93% and specificity of 86%. SW MRI had similar inter-observer reliability to T2-weighted imaging (κ = 0.90 and κ = 0.88 respectively); both had higher reliability than T2 star (κ = 0.53). Breath hold times were shorter for SW MRI (4 seconds vs. 16 seconds) with improved image quality rating (3.8 ± 0.4, 3.3 ± 1.0, 2.8 ± 1.1 respectively; p < 0.01). CONCLUSIONS: SW MRI is an accurate and reproducible way to detect IMH at 3T. The technique offers considerably shorter breath hold times than T2-weighted and T2 star imaging, and higher image quality scores.

The microvascular effects of insulin resistance and diabetes on cardiac structure, function, and perfusion: a cardiovascular magnetic resonance study.

AIMS: Type 2 diabetes mellitus is an independent risk factor for the development of heart failure. To better understand the mechanism by which this occurs, we investigated cardiac structure, function, and perfusion in patients with and without diabetes. METHODS AND RESULTS: Sixty-five patients with no stenosis >30% on invasive coronary angiography were categorized into diabetes (19) and non-diabetes (46) which was further categorized into prediabetes (30) and controls (16) according to the American Diabetes Association guidelines. Each patient underwent comprehensive cardiovascular magnetic resonance assessment. Left-ventricular (LV) mass, relative wall mass (RWM), Lagrangian circumferential strain, LV torsion, and myocardial perfusion reserve (MPR) were calculated. LV mass was higher in diabetics than non-diabetics (112.8 ± 39.7 vs. 91.5 ± 21.3 g, P = 0.01) and in diabetics than prediabetics (112.8 ± 39.7 vs. 90.3 ± 18.7 g, P = 0.02). LV torsion angle was higher in diabetics than non-diabetics (9.65 ± 1.90 vs. 8.59 ± 1.91°, P = 0.047), and MPR was lower in diabetics than non-diabetics (2.10 ± 0.76 vs. 2.84 ± 1.25 mL/g/min, P = 0.01). There was significant correlation between MPR and early diastolic strain rate (r = -0.310, P = 0.01) and LV torsion (r = -0.306, P = 0.01). In multivariable linear regression analysis, non-diabetics waist-hip ratio, but not body mass index, had a significant association with RWM (Beta = 0.34, P = 0.02). CONCLUSION: Patients with diabetes have increased LV mass, LV torsion, and decreased MPR. There is a significant association between decreased MPR and increased LV torsion suggesting a possible mechanistic link between microvascular disease and cardiac dysfunction in diabetes.

Cardiac MR imaging to measure myocardial blood flow response to the cold pressor test in healthy smokers and nonsmokers.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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]). CONCLUSION: 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.

Myocardial blood flow at rest and stress measured with dynamic contrast-enhanced MRI: comparison of a distributed parameter model with a Fermi function model.

PURPOSE: To assess the feasibility of simultaneously measuring blood flow (Fb ), Gd-DTPA extraction fraction (E), and distribution volume (vd ) in healthy myocardium at rest and under adenosine stress using dynamic contrast-enhanced MRI. METHODS: Sixteen volunteers were examined at 1.5 T and 11 returned for a repeat study. The data were analyzed using a distributed parameter (DP) 2-region model to arrive at estimates of Fb , E, blood volume, and interstitial volume. For comparison, estimates of Fb were also obtained using a Fermi function model. RESULTS: DP model fits were successful in 49 of the 54 data sets. Estimates obtained using DP and Fermi models did not differ for either rest Fb or myocardial perfusion reserve though DP estimates of stress Fb were lower than Fermi estimates. The repeatability of the DP parameters Fb , E, and vd was better than or equal to the repeatability of Fermi-Fb . E at rest and under stress was estimated to be 66% and 57%, respectively. CONCLUSION: The results suggest that characteristics of the microvasculature of healthy myocardium can be reliably determined using dynamic contrast-enhanced MRI at rest and under stress and that delivery of Gd-DTPA to the myocardium is not flow-limited.

Cardiovascular magnetic resonance physics for clinicians: Part II.

This is the second of two reviews that is intended to cover the essential aspects of cardiovascular magnetic resonance (CMR) physics in a way that is understandable and relevant to clinicians using CMR in their daily practice. Starting with the basic pulse sequences and contrast mechanisms described in part I, it briefly discusses further approaches to accelerate image acquisition. It then continues by showing in detail how the contrast behaviour of black blood fast spin echo and bright blood cine gradient echo techniques can be modified by adding rf preparation pulses to derive a number of more specialised pulse sequences. The simplest examples described include T2-weighted oedema imaging, fat suppression and myocardial tagging cine pulse sequences. Two further important derivatives of the gradient echo pulse sequence, obtained by adding preparation pulses, are used in combination with the administration of a gadolinium-based contrast agent for myocardial perfusion imaging and the assessment of myocardial tissue viability using a late gadolinium enhancement (LGE) technique. These two imaging techniques are discussed in more detail, outlining the basic principles of each pulse sequence, the practical steps required to achieve the best results in a clinical setting and, in the case of perfusion, explaining some of the factors that influence current approaches to perfusion image analysis. The key principles of contrast-enhanced magnetic resonance angiography (CE-MRA) are also explained in detail, especially focusing on timing of the acquisition following contrast agent bolus administration, and current approaches to achieving time resolved MRA. Alternative MRA techniques that do not require the use of an endogenous contrast agent are summarised, and the specialised pulse sequence used to image the coronary arteries, using respiratory navigator gating, is described in detail. The article concludes by explaining the principle behind phase contrast imaging techniques which create images that represent the phase of the MR signal rather than the magnitude. It is shown how this principle can be used to generate velocity maps by designing gradient waveforms that give rise to a relative phase change that is proportional to velocity. Choice of velocity encoding range and key pitfalls in the use of this technique are discussed.

Systolic versus diastolic acquisition in myocardial perfusion MR imaging.

PURPOSE: 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). MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Estimates of systolic and diastolic myocardial blood flow by dynamic contrast-enhanced MRI.

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.