Oliver M. Weber

Magnetic Resonance Imaging Analysis of Right Ventricular Pressure-Volume Loops In Vivo Validation and Clinical Application in Patients With Pulmonary Hypertension

Background—The aims of this study were to validate MRI-derived right ventricular (RV) pressure-volume loops for assessment of RV myocardial contractility and then to apply this technique in patients with chronic RV pressure overload for assessment of myocardial contractility, ventricular pump function, and VA coupling. Methods and Results—Flow-directed catheters were guided under MR fluoroscopy (1.5 T) into the RV for invasive pressure measurements. Simultaneously, ventricular volumes and myocardial mass were assessed from cine MRI. From sampled data, RV pressure-volume loops were constructed, and maximal ventricular elastance indexed to myocardial mass (Emax_i) was derived by use of a single-beat estimation method. This MRI method was first validated in vivo (6 swine), with conductance techniques used as reference. Bland-Altman test showed good agreement between methods (Emax_i=5.1±0.5 versus 5.8±0.7 mm Hg · mL−1 · 100 g−1, respectively; P=0.08). Subsequently, the MRI method was applied in 12 subjects: 6 control subjects and 6 patients with chronic RV pressure overload from pulmonary hypertension. In these patients, indexes of RV pump function (cardiac index), Emax_i, and VA coupling (Emax/Ea) were assessed. In patients with pulmonary hypertension, RV pump function was decreased (cardiac index, 2.2±0.5 versus 2.9±0.4 L · min−1 · m−2; P<0.01), myocardial contractility was enhanced (Emax_I, 9.2±1.1 versus 5.0±0.9 mm Hg · mL−1 · 100 g−1; P<0.01), and VA coupling was inefficient (Emax/Ea, 1.1±0.3 versus 1.9±0.4; P<0.01) compared with control subjects. Conclusions—RV myocardial contractility can be determined from MRI-derived pressure-volume loops. Chronic RV pressure overload was associated with reduced RV pump function despite enhanced RV myocardial contractility. The proposed MRI approach is a promising tool to assess RV contractility in the clinical setting.

Whole-heart steady-state free precession coronary artery magnetic resonance angiography.

Current implementations of coronary artery magnetic resonance angiography (MRA) suffer from limited coverage of the coronary arterial system. Whole‐heart coronary MRA was implemented based on a free‐breathing steady‐state free‐precession (SSFP) technique with magnetization preparation. The technique was compared to a similar implementation of conventional, thin‐slab coronary MRA in 12 normal volunteers. Three thin‐slab volumes were prescribed: 1) a transverse slab, covering the left main (LM) artery and proximal segments of the left anterior ascending (LAD) and left circumflex (LCX) coronary arteries; 2) a double‐oblique slab covering the right coronary artery (RCA); and 3) a double‐oblique slab covering the proximal and distal segments of the LCX. The whole‐heart data set was reformatted in identical orientations. Visible vessel length, vessel sharpness, and vessel diameter were determined and compared separately for each vessel. Whole‐heart coronary MRA visualized LM/LAD (11.7 ± 3.4 cm) and LCX (6.9 ± 3.6 cm) over a significantly longer distance than the transverse volume (LM/LAD, 6.1 ± 1.1 cm, P < 0.001; LCX, 4.2 ± 1.2 cm, P < 0.05). Improvements in visible vessel length for RCA and LCX in the whole‐heart approach vs. their respective targeted volumes were not significant. It is concluded that the whole‐heart coronary MRA technique improves visible vessel length and facilitates high‐quality coronary MRA of the complete coronary artery tree in a single measurement. Magn Reson Med 50:1223–1228, 2003.

Placement of deep brain stimulator electrodes using real-time high-field interventional magnetic resonance imaging

A methodology is presented for placing deep brain stimulator electrodes under direct MR image guidance. The technique utilized a small, skull‐mounted trajectory guide that is optimized for accurate alignment under MR fluoroscopy. Iterative confirmation scans are used to monitor device alignment and brain penetration. The methodology was initially tested in a human skull phantom and proved capable of achieving submillimeter accuracy over a set of 16 separate targets that were accessed. The maximum error that was obtained in this preliminary test was 2 mm, motivating use of the technique in a clinical study. Subsequently, a total of eight deep brain stimulation electrodes were placed in five patients. Satisfactory placement was achieved on the first pass in seven of eight electrodes, while two passes were required with one electrode. Mean error from the intended target on the first pass was 1.0 ± 0.8 mm (range = 0.1–1.9 mm). All procedures were considered technical successes and there were no intraoperative complications; however, one patient did develop a postoperative infection. Magn Reson Med, 2005.

Detection of glutathione in the human brain in vivo by means of double quantum coherence filtering

The feasibility of selective in vivo detection of glutathione (l‐γ‐glutamyl‐l‐cysteinyl‐glycine, GSH) in the human brain by means of 1H magnetic resonance spectroscopy (MRS) at 1.5 T is demonstrated. A double quantum coherence (DQC) filtering sequence was used in combination with PRESS volume selection. The strongly coupled cysteinyl CH2 compound of GSH was found to be the most suitable target for spectral editing. Analytical calculations employing a product operator description of the cysteinyl ABX three‐spin system were made in order to optimize the inherent yield of the sequence. A pulse phase calibration procedure, which precedes the spectrum acquisition, secures maximal signal yield independently of the spatial localization of the volume of interest and thus comparability between individual examinations. In vitro tests show that the DQC filtering method provides good discrimination between the GSH signal at 2.9 ppm and the interfering resonances of creatine, γ‐aminobutyric acid (GABA) and aspartate. In measurements in the frontal lobe of 12 healthy volunteers a mean ratio of GSH signal to tissue water signal of 5.7 ± 2.3 × 10−5 was found, corresponding to a mean GSH tissue concentration of 2–5 mmol/L. The proposed technique allows for the detection of a biologically highly relevant metabolite at moderate field strength. Magn Reson Med 42:283–289, 1999.

MR imaging assessment of cardiac function

Magnetic resonance (MR) imaging is an accurate and reproducible technique for assessment of ventricular function. Although echocardiography is the mainstay for evaluation of cardiac function, dobutamine stress MR imaging has been shown to be as safe as echocardiography for patients with coronary artery disease and more accurate in patients with suboptimal echocardiographic image quality. This article reviews MR imaging techniques, methods of pharmacologic stress, and clinical applications for assessment of cardiac function, primarily left ventricular function. J. Magn. Reson. Imaging 2004;19:789–799.

Magnetic Resonance–Guided Cardiac Catheterization in a Swine Model of Atrial Septal Defect

Background—Radiation exposure during cardiac catheterization, limited image planes, and poor soft tissue definition are disadvantages of x-ray fluoroscopy that could be overcome with the use of MRI. This study evaluates the feasibility of real-time MRI (MR fluoroscopy) to guide left and right heart catheterization. Methods and Results—Anesthetized pigs (n=7) with defects of the atrial septum were catheterized using venous and arterial access. A prototype active tracking catheter was used to obtain blood pressures and samples from cardiac chambers and great vessels using antegrade, transseptal, and retrograde approaches. MR fluoroscopy was used for catheter steering. Velocity-encoded cine MRI was used to measure pulmonary and aortic blood flow to calculate vascular resistances. Image planes used during catheter manipulation used rapid sequencing to planes directed by the operator to include the tip of the catheter and the chamber to be entered. All areas of interest were effectively entered, and samples were obtained. In the presence of an acute atrial septal defect, a Qp/Qs ratio of 1.3±0.2 was measured, and no significant differences in pressure between inferior vena cava, right atrium, and left atrium were found. Pulmonary and aortic flow were 4.9±0.6 and 3.7±0.4 L/min, and pulmonary and systemic vascular resistance were 312±134 and 2006±336 dyne · s · cm−5. Conclusions—Left and right heart catheterization using MR guidance is feasible. The combination of hemodynamic catheterization data with anatomic and functional MRI may significantly improve the evaluation of patients with congenital heart disease while avoiding radiation exposure.

MR Evaluation of Cardiovascular Physiology in Congenital Heart Disease: Flow and Function

Cardiovascular magnetic resonance (CMR) has become the method of choice in the evaluation of a number of questions in congenital heart disease. In addition to morphology, modern CMR techniques allow the visualization of function and flow in a temporally resolved manner. Among the pathologies where these methods play a major role are shunts, septal defects, aortic coarctation, anomalies of the pulmonary arteries, and valvular regurgitation. This paper explains the basics of functional and flow encoded CMR and discusses their application in the assessment of several types of congenital heart disease.

Effects of vigabatrin intake on brain GABA activity as monitored by spectrally edited magnetic resonance spectroscopy and positron emission tomography

A deficit in gamma-aminobutyric acid (GABA) levels in the brain or the cerebrospinal fluid (CSF) is found in many epilepsy patients. Frequency and severity of seizures may be reduced by treatment with GABA increasing medicaments as e.g. vigabatrin, an irreversible inhibitor of GABA-transaminase. For a better understanding of the associated effects, healthy volunteers were examined with magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) before and after intake of different doses of vigabatrin. For the MRS examinations, a dedicated localized spectral editing method was developed to determine GABA levels. The 11C-flumazenil (FMZ)-PET protocol allowed determination of GABA-A receptor binding. The results show a clear and dose-dependent increase in the brain GABA levels after the medication period as compared to the baseline values. The GABA-A receptor binding, on the other hand, did not change significantly.

Scarred myocardium imposes additional burden on remote viable myocardium despite a reduction in the extent of area with late contrast MR enhancement.

Magnetic resonance imaging (MRI) can simultaneously detect and quantify myocardial dysfunction and shrinkage in contrast-enhanced areas postinfarction. This ability permits the investigation of our hypothesis that transformation of infracted myocardium to scarred tissue imposes additional burdens on peri-infarcted and remote myocardium. Pigs (n=8) were subjected to reperfused infarction. Gd-DOTA-enhanced inversion recovery gradient echo sequence (IR-GRE) imaging was performed 3 days and 8 weeks postinfarction. Global and regional left ventricular (LV) function was evaluated by cine MRI. Triphenyltetrazolium chloride (TTC) stain was used to delineate infarction while hematoxylin and eosin (H & E) and Masson’s trichrome stains were used to characterize remodeled myocardium. Late contrast-enhanced MRIs showed a decrease in the extent of enhanced areas from 17±2% at 3 days to13±1% LV mass at 8 weeks. TTC infarction size was 12±1% LV mass. Cine MRIs showed expansion in dysfunctional area due to unfavorable remodeling, ischemia, or strain. Ejection fraction was reduced in association with increased end-diastolic and end-systolic volumes. Scarred myocardium contained collagen fibers and remodeled thick-walled vessels embedded in collagen. Sequential MRI showed greater LV dysfunction despite the shrinkage in extent of enhanced areas 2 months postinfarction. The integration of late enhancement and cine MRI incorporates anatomical and functional evaluation of remodeled hearts.

MRI in guiding and assessing intramyocardial therapy.

Cardiovascular intervention, using MRI guidance, is challenging for clinical applications. Real-time imaging sequences with high spatial resolution are needed for monitoring intramyocardial delivery of drug, gene, or stem cell therapies. New generation MR scanners make local intramyocardial and vascular wall therapies feasible. Contrast-enhanced MRI is used for assessing myocardial ischemia, infarction, and scar tissue. Active (microcoils) and passive (T1 and T2* mechanisms) tracking methods have been used for visualization of endovascular catheters. Safety issues related to potential heating of endovascular devices is still a major obstacle for MRI-guided interventions. Fabrication of MRI-compatible interventional devices is limited. Noninvasive imaging strategies will be critical in defining spatial and temporal characteristics of angiogenesis and myocardial repair as well as in assessing the efficacy of new therapies in ischemic heart disease. MRI contrast media improve the capability of MRI by delineating the target and vascular tree. Labeling stem cells enables MRI to trace distribution, differentiation, and survival in myocardium and vascular wall. In the long term, MRI in guiding and assessing intramyocardial therapy may circumvent the limitations of peripherally administered cell therapy, X-ray angiography, and nuclear imaging. MRI represents a highly attractive discipline whose systematic development will foster the implementation of new cardiac and vascular therapies.