Christian M. Wacker

MR-IMPACT: comparison of perfusion-cardiac magnetic resonance with single-photon emission computed tomography for the detection of coronary artery disease in a multicentre, multivendor, randomized trial.

AIMS To determine in a multicentre, multivendor trial the diagnostic performance for perfusion-cardiac magnetic resonance (perfusion-CMR) in comparison with coronary X-ray angiography (CXA) and single-photon emission computed tomography (SPECT). METHODS AND RESULTS Of 241 eligible patients from 18 centres, 234 were randomly dosed with 0.01, 0.025, 0.05, 0.075, or 0.1 mmol/kg Gd-DTPA-BMA (Omniscantrade mark, GE-Healthcare) per stress (0.42 mg/kg adenosine) and rest perfusion study. Coronary artery disease (CAD) was defined as diameter stenosis > or =50% on quantitative CXA. Five CMR and eight SPECT studies (of 225 complete studies) were excluded from analyses due to inadequate quality (three blinded readers scored per modality). The comparison of CMR vs. SPECT was based on receiver operating characteristic (ROC) analysis. Perfusion-CMR at the optimal CM dose (0.1 mmol/kg) had similar performance as SPECT, if only the SPECT studies of the 42 patients with this dose were considered [area under ROC curve (AUC): 0.86 +/- 0.06 vs. 0.75 +/- 0.09 for SPECT, P = 0.12]; however, diagnostic performance of perfusion-CMR was better vs. the entire SPECT population (AUC: 0.67 +/- 0.05, n = 212, P = 0.013). CONCLUSIONS In this multicentre, multivendor trial, ROC analyses suggest perfusion-CMR as a valuable alternative to SPECT for CAD detection showing equal performance in the head-to-head comparison. Comparing perfusion-CMR with the entire SPECT population suggests CMR superiority over SPECT, which warrants further evaluation in larger trials.

MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial

AIMS Perfusion-cardiac magnetic resonance (CMR) has emerged as a potential alternative to single-photon emission computed tomography (SPECT) to assess myocardial ischaemia non-invasively. The goal was to compare the diagnostic performance of perfusion-CMR and SPECT for the detection of coronary artery disease (CAD) using conventional X-ray coronary angiography (CXA) as the reference standard. METHODS AND RESULTS In this multivendor trial, 533 patients, eligible for CXA or SPECT, were enrolled in 33 centres (USA and Europe) with 515 patients receiving MR contrast medium. Single-photon emission computed tomography and CXA were performed within 4 weeks before or after CMR in all patients. The prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were 5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD. Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary endpoint, the safety profile of the CMR examination was evaluated. For CMR and SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower confidence level for the difference of +0.02, indicating superiority of CMR over SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively (lower confidence level for the difference: -0.17), indicating inferiority of CMR vs. SPECT. No severe adverse events occurred in the 515 patients. CONCLUSION In this large multicentre, multivendor study, the sensitivity of perfusion-CMR to detect CAD was superior to SPECT, while its specificity was inferior to SPECT. Cardiac magnetic resonance is a safe alternative to SPECT to detect perfusion deficits in CAD.

Changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole : Assessment using T*2 and T1 measurements

The aim of this pilot‐study was to evaluate changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole (DIP) by means of MRI. Twenty healthy volunteers were examined using a multi‐echo gradient‐echo sequence. The differential myocardial signal response due to the blood oxygen level dependent (BOLD) effect was studied under variable conditions of myocardial oxygen supply caused by the vasodilator DIP. Unlike contrast agents (CA) methods, which require at least two injections of CA and DIP, the presented methods require only a single infusion of DIP. To assess changes in myocardial perfusion, a saturation recovery TurboFLASH (SRTFL) sequence with centric reordering for T1 measurements was used with global and slice‐selective spin‐preparation (five volunteers). The signal response was measured at baseline conditions and when myocardial blood flow was increased during pharmacological stress with DIP. Administration of DIP induced a 17 ± 9% increase in T*2. Enhanced perfusion resulted in a 15 ± 5% decrease of T1 after slice‐selective spin preparation and a calculated increase in absolute perfusion of about 5.1 ml/(g × min), which reflects coronary reserve.

Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial).

OBJECTIVES The Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release. BACKGROUND No data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel. METHODS After bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h. RESULTS A total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05). CONCLUSIONS Troponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.

Superior diagnostic performance of perfusion-cardiovascular magnetic resonance versus SPECT to detect coronary artery disease: The secondary endpoints of the multicenter multivendor MR-IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary Artery Disease Trial)

BackgroundPerfusion-cardiovascular magnetic resonance (CMR) is generally accepted as an alternative to SPECT to assess myocardial ischemia non-invasively. However its performance vs gated-SPECT and in sub-populations is not fully established. The goal was to compare in a multicenter setting the diagnostic performance of perfusion-CMR and gated-SPECT for the detection of CAD in various populations using conventional x-ray coronary angiography (CXA) as the standard of reference.MethodsIn 33 centers (in US and Europe) 533 patients, eligible for CXA or SPECT, were enrolled in this multivendor trial. SPECT and CXA were performed within 4 weeks before or after CMR in all patients. Prevalence of CAD in the sample was 49% and 515 patients received MR contrast medium. Drop-out rates for CMR and SPECT were 5.6% and 3.7%, respectively (ns). The study was powered for the primary endpoint of non-inferiority of CMR vs SPECT for both, sensitivity and specificity for the detection of CAD (using a single-threshold reading), the results for the primary endpoint were reported elsewhere. In this article secondary endpoints are presented, i.e. the diagnostic performance of CMR versus SPECT in subpopulations such as multi-vessel disease (MVD), in men, in women, and in patients without prior myocardial infarction (MI). For diagnostic performance assessment the area under the receiver-operator-characteristics-curve (AUC) was calculated. Readers were blinded versus clinical data, CXA, and imaging results.ResultsThe diagnostic performance (= area under ROC = AUC) of CMR was superior to SPECT (p = 0.0004, n = 425) and to gated-SPECT (p = 0.018, n = 253). CMR performed better than SPECT in MVD (p = 0.003 vs all SPECT, p = 0.04 vs gated-SPECT), in men (p = 0.004, n = 313) and in women (p = 0.03, n = 112) as well as in the non-infarct patients (p = 0.005, n = 186 in 1–3 vessel disease and p = 0.015, n = 140 in MVD).ConclusionIn this large multicenter, multivendor study the diagnostic performance of perfusion-CMR to detect CAD was superior to perfusion SPECT in the entire population and in sub-groups. Perfusion-CMR can be recommended as an alternative for SPECT imaging.Trial registrationClinicalTrials.gov, Identifier: NCT00977093

The relationship between the BOLD-induced T(2) and T(2)(*): a theoretical approach for the vasculature of myocardium.

Recently the blood oxygenation level–dependent (BOLD)‐related T2* of myocardium was derived as an analytical function of intracapillary blood volume, blood oxygenation, and nuclear spin diffusion. The basis of this approach was to approximate the diffusion‐induced field fluctuations a nuclear spin is subjected to by strong collision dynamics, i.e., the field fluctuations are uncorrelated. The same analysis is now performed for spin echo experiments that gives myocardial T2 as a function of the parameters above and the echotime. An analytical relationship between T2 and T2* relaxation is derived. The dependence of T2 on diffusion, echo time, and blood oxygenation is congruent with simulation and experimental data. Magn Reson Med 42:1004–1010, 1999.

Theory of the BOLD effect in the capillary region: An analytical approach for the determination of T*2 in the capillary network of myocardium

This article presents an analytical approach for the quantification of the blood oxygen level dependent (BOLD) effect in the capillary region. The capillary geometry of myocardium is considered. The relaxation rate R  *2 is determined as a function of the capillary radius Rc, the intracapillary volume fraction RBV, and the diffusion coefficient D. When the intracapillary volume fraction is small, the approximation R  *2 = RBV · τ−1 · (√1 + (τδω)2 − 1) is valid, with the correlation time τ = (R  c2 /4D) · (|ln RBV|/(1 − RBV)). The predictions of this model agree well with numerical simulations and experimental data of others and with data recently measured by our group. Magn Reson Med 41:51‐62, 1999.

Quantitative assessment of myocardial perfusion with a spin-labeling technique: Preliminary results in patients with coronary artery disease

To determine perfusion and coronary reserve in human myocardium without contrast agent using a spin labeling technique.

ECG-gated 23Na-MRI of the human heart using a 3D-radial projection technique with ultra-short echo times

Pathological changes in tissue often manifest themselves in an altered sodium gradient between intra- and extracellular space due to a malfunctioning Na+–K+ pump, resulting in an increase in total sodium concentration in ischaemic regions. Therefore, 23Na-MRI has the potential to non-invasively differentiate viable from non-viable tissue by detecting concentration changes of intra- and extracellular sodium. As the in vivo sodium signal shows a bi-exponential T2 decay, with a short component of less than 1 ms, the accurate quantification of the total sodium content requires imaging techniques with ultra-short echo times (TE) below 0.5 ms. A 3D-radial projection technique has been developed which allows the acquisition of ECG-triggered sodium images of the human heart with a TE of 0.4 ms. With this pulse sequence 23Na-MRI volunteer measurements of the head or the heart were performed in less than 18 min on a 1.5-T clinical scanner with an isotropic resolution of 10 mm3. The signal to noise ratio of the radial projection technique is twofold higher than that of a Cartesian gradient echo pulse sequence (TE = 3.2 ms). Radial 23Na-MRI provides a tool for clinical studies, aiming at the differentiation of viable and non-viable tissue.

BOLD-MRI in ten patients with coronary artery disease: evidence for imaging of capillary recruitment in myocardium supplied by the stenotic artery

Changes of myocardial oxygenation can be studied by measurements of the apparent transverse relaxation timeT2*, which is correlated with the oxygenation state of hemoglobin. In this study, ten patients with coronary artery disease (CAD) underwent blood oxygenation level dependent (BOLD)T2* measurements using a segmented gradient echo pulse sequence with ten echoes.T2* measurements were performed in a single short-axis slice of the heart at rest and under pharmacological stress with dipyridamole (DIP), which increases myocardial blood flow. For comparison, all patients underwent X-ray angiography and stress-echocardiography within 4 days after the MR exam. In one patient, MR examination was repeated 10 weeks after percutaneous transluminal coronary angioplasty (PTA). In the differentialT2* maps, expected ischemic areas of myocardium were identified in six patients. In these regions,T2* values (30±8 ms) were significantly reduced when compared to the remaining myocardium (48±9 ms,P<0.01). In four patients, the myocardial region of interest could not be assessed owing to severe susceptibility artifacts in the ischemic region. The success of the PTA treatment could be visualized from a more homogeneous DIP induced increase inT2* within the ischemic myocardium (from 26±1 to 29±1 ms before PTA versus 26±1 to 31±4 ms after PTA,P<0.001.