Jose Katz

Estimation of right ventricular mass in normal subjects and in patients with primary pulmonary hypertension by nuclear magnetic resonance imaging

OBJECTIVES This study was designed to test the accuracy of nuclear magnetic resonance (NMR) imaging as a noninvasive technique for estimating right ventricular mass in normal subjects and in patients with primary pulmonary hypertension. BACKGROUND An accurate means of noninvasively estimating right ventricular mass may allow better characterization of the degree of right-sided pressure or volume overload caused by underlying cardiac or pulmonary diseases. METHODS End-diastolic short-axis electrocardiogram (ECG)-gated spin echo NMR images of the heart were obtained in vivo in 13 patients with primary pulmonary hypertension and 10 normal adult volunteers. Both right and left ventricular mass were computed by summing the myocardial slice volumes over all slices spanning the myocardium and multiplying by myocardial density. This technique of myocardial mass determination was verified by imaging 10 calf hearts and comparing the NMR-determined right and left myocardial mass with the actual mass determined by weighing the right and left ventricles. RESULTS In the calf heart study, an excellent correlation was obtained between the directly measured ventricular mass and the NMR-calculated mass, for both the right and the left ventricle. Patients with primary pulmonary hypertension had an elevated right ventricular mass index compared with that of normal subjects (62.69 +/- 8.72 g/m2 vs. 23.32 +/- 1.36 g/m2, p < 0.0005). There was no significant difference in left ventricular mass index between the two groups. Both mean intraobserver and inter-observer variability in myocardial mass determination were low. Linear regression analysis between right ventricular mass index and mean pulmonary artery pressure was significant (r = 0.75, p < 0.003). CONCLUSIONS Electrocardiogram-gated spin echo NMR imaging of the heart may be used for quantitating right ventricular mass in normal subjects and in patients with primary pulmonary hypertension, in whom it may also provide an alternative noninvasive technique for estimating mean pulmonary artery pressure.

Direct quantitation of right and left ventricular volumes with nuclear magnetic resonance imaging in patients with primary pulmonary hypertension

To test the utility of electrocardiographically gated spin echo nuclear magnetic resonance (NMR) imaging in quantitating right and left ventricular volumes and function in patients with primary pulmonary hypertension, right and left ventricular end-diastolic and end-systolic volumes, stroke volumes and ejection fractions were determined in 11 patients with primary pulmonary hypertension and in 10 subjects with normal echocardiographic findings. Ventricular chamber volumes were computed by summing the ventricular chamber volumes of each NMR slice at end-diastole and end-systole. This technique was verified by comparison of results obtained by this method and with the water displacement volumes of eight water-filled latex balloons and ventricular casts of eight excised bovine hearts. In the patients with primary pulmonary hypertension, right ventricular volume indexes were 121 +/- 45 ml/m2 at end-diastole and 70.1 +/- 41.6 ml/m2 at end-systole; both values were significantly greater than values in the normal subjects (67.9 +/- 13.4 and 27.9 +/- 7.5 ml/m2, respectively). Left ventricular end-diastolic volume index was significantly less in the patients (44.9 +/- 9.7 ml/m2) than in the normal subjects (68.9 +/- 13.1 ml/m2). There was no significant difference in left ventricular end-systolic volume between the two groups (24.4 +/- 8.6 and 27.1 +/- 7.8 ml/m2, respectively). Right and left ventricular ejection fractions in the patients with primary pulmonary hypertension (0.43 +/- 0.21 and 0.46 +/- 0.15, respectively) were significantly less than values in normal subjects (0.59 +/- 0.09 and 0.6 +/- 0.11, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Three-dimensional Echocardiographic Volume Computation by Polyhedral Surface Reconstruction: In Vitro Validation and Comparison to Magnetic Resonance Imaging

Two-dimensional echocardiographic methods of left ventricular volume computation are limited by geometric assumptions and image plane positioning error in the nonvisualized dimension. We evaluated a three-dimensional (3D echocardiographic method that addresses these limitations. Our method uses a volume computation algorithm based on polyhedral surface reconstruction (PSR) and nonparallel, unequally spaced, nonintersecting short-axis planes. Seventeen balloon phantoms were subjected to volume computation by the 3D echocardiography-PSR method and by magnetic resonance imaging (MRI) and compared to true volumes determined by water displacement. The results for 3D echocardiography-PSR were: accuracy = 2.27%, interobserver variability = 4.33%, r = 0.999, SEE = 2.45 ml, and p less than 0.001. Results for MRI were 8.01%, 13.78%, r = 0.995, SEE = 7.01 ml, and p less than 0.001. There was no statistically significant difference between the methods. We conclude that precise image plane positioning and use of the 3D echocardiographic-PSR volume computation method achieves high accuracy and reproducibility in vitro. The excellent in vitro correlation between 3D echocardiography-PSR and MRI indicates that MRI may also serve as an in vivo standard of comparison.

Estimation of Pulmonary Artery Pressure in Patients with Primary Pulmonary Hypertension by Quantitative Analysis of Magnetic Resonance Images

The use of magnetic resonance (MR) images for estimating mean pulmonary artery pressure (PAP) was tested by comparing main pulmonary artery (MPA) and middescending thoracic aorta (AO) caliber in 12 patients with primary pulmonary hypertension (PPH) with measurements made in eight other patients who were observed for diseases other than heart disease (controls). The ratio MPA/AO and the ratios of vessel caliber normalized to body surface area (MPAI and AOI, respectively) were computed. The PAP was obtained in all PPH patients and compared with caliber measurements. The PPH MPA (3.6 ± 0.8 cm) was significantly larger than the control MPA (2.9 ± 0.3 cm, p = 0.02); the PPH MPAI (2.8 ± 0.7 cm/M2) was significantly greater than the control MPA (1.7 ± 0.2 cm/M2, p < 0.0001). Control AO (2.2 ± 0.3 cm) was significantly greater than PPH AO (1.6 ± 0.4 cm, p <0.0001); there was no significant difference between control AOI (1.3 ± 0.2 cm/M2) and PPH AOI (1.2 ± 0.2 cm/M2, p = 0.25). The PPH MPA/AO (2.3 ± 0.6) was significantly greater than the control MPA/AO (1.3 ± 0.1, p < 0.0001); overlap between MPA in the two groups was eliminated by indexing values to AO caliber (MPA/AO). Among PPH patients there was strong correlation between PAP and MPA/AO (PAP = 24 x MPA/AO + 3.7, r = 0.7, p < 0.01). Increased MPA/AO denotes the presence of pulmonary hypertension and may be used to estimate PAP.

Estimation of myocardial water content using transverse relaxation time from dual spin-echo magnetic resonance imaging

Dual spin-echo magnetic resonance imaging may be used for calculation of transverse myocardial relaxation time from the signal intensity of the echoes considered. In this study, the ability of myocardial transverse relaxation time (T2) to quantitate myocardial edema of the right ventricle (RV) and left ventricle (LV) was tested. Dual spin-echo magnetic resonance images of the entire hearts were obtained and T2 of the RV and LV myocardium calculated from the signal intensities within multiple regions of interest distributed over the myocardium. Six hearts were intermittently perfused through an aortic cannula with three perfusates of decreasing osmolality. Biopsies were obtained for water content (WC) analysis both before and after imaging the hearts at baseline and post-perfusion. A seventh (control) heart was not perfused; instead dual spin-echo imaging was performed at the same time intervals as in the perfused hearts. Prior to any intervention, there was no significant difference between baseline RV (79.49 +/- 2.10%) and LV (77.99 +/- 2.44%, p = .2) myocardial water content; RV myocardial T2 (59.9 +/- 5.8 msec) was slightly but not significantly longer than that of the LV (54.6 +/- 5.7 msec, p = .1). After induction of edema, strong correlation was found between right ventricular myocardial water content measurements and right ventricular T2 (RV WC = 68.5 + 0.19 x RV T2; N = 27, R = 0.92, p < .0001, SEE = 1.56%). Similarly, strong correlation was found between left ventricular myocardial water content and T2 (LV WC = 62.1 + 0.29 x LV T2; N = 27, R = 0.92, p < .0001, SEE = 1.80%).(ABSTRACT TRUNCATED AT 250 WORDS)

Nuclear magnetic resonance imaging in Marfan's syndrome

Detection and evaluation of aortic root and other cardiovascular abnormalities in patients with Marfans syndrome are important in determining appropriate therapy and preventing premature mortality. To evaluate the role of nuclear magnetic resonance imaging (NMR) in this syndrome, 10 patients were evaluated using a 0.35 tesla commercial nuclear magnetic resonance imaging system. Findings from these studies were compared with data from other noninvasive tests as well as surgical follow-up. Results from these examinations indicate that NMR-derived measurements of aortic root diameter agree closely with echocardiographic measurements. In addition, NMR provides more complete anatomic detail than does echocardiography and can be utilized to assess and follow up virtually all patients with this syndrome.

Metabolic inhibition in the perfused rat heart: evidence for glycolytic requirement for normal sodium homeostasis.

Subcellular compartmentalization of energy stores to support different myocardial processes has been exemplified by the glycolytic control of the ATP-sensitive K+ channel. Recent data suggest that the control of intracellular sodium (Nai) may also rely on glycolytically derived ATP; however, the degree of this dependence is unclear. To examine this question, isolated, perfused rat hearts were exposed to hypoxia, to selectively inhibit oxidative metabolism, or iodoacetate (IAA, 100 μmol/l), to selectively inhibit glycolysis. Nai and myocardial high-energy phosphate levels were monitored using triple-quantum-filtered (TQF)23Na and31P magnetic resonance spectroscopy, respectively. The effects of ion exchange mechanisms (Na+/Ca2+, Na+/H+) on Nai were examined by pharmacological manipulation of these channels. Nai, as monitored by shift reagent-aided TQF 23Na spectral amplitudes, increased by ∼220% relative to baseline after 45 min of perfusion with IAA, with or without rapid pacing. During hypoxia, Nai increased by ∼200% during rapid pacing but did not increase in unpaced hearts or when the Na+/H+exchange blocker ethylisopropylamiloride (EIPA, 10 μmol/l) was used. Neither EIPA nor a low-Ca2+perfusate (50 μmol/l) could prevent the rise in Nai during perfusion with IAA. Myocardial function and high-energy phosphate stores were preserved during inhibition of glycolysis with IAA and continued oxidative metabolism. These results suggest that glycolysis is required for normal Na+ homeostasis in the perfused rat heart, possibly because of preferential fueling of Na-K-adenosinetriphosphatase by glycolytically derived ATP.Subcellular compartmentalization of energy stores to support different myocardial processes has been exemplified by the glycolytic control of the ATP-sensitive K+ channel. Recent data suggest that the control of intracellular sodium (Nai) may also rely on glycolytically derived ATP; however, the degree of this dependence is unclear. To examine this question, isolated, perfused rat hearts were exposed to hypoxia, to selectively inhibit oxidative metabolism, or iodoacetate (IAA, 100 mumol/l), to selectively inhibit glycolysis. Nai and myocardial high-energy phosphate levels were monitored using triple-quantum-filtered (TQF) 23Na and 31P magnetic resonance spectroscopy, respectively. The effects of ion exchange mechanisms (Na+/Ca2+, Na+/H+) on Nai were examined by pharmacological manipulation of these channels. Nai, as monitored by shift reagent-aided TQF 23Na spectral amplitudes, increased by approximately 220% relative to baseline after 45 min of perfusion with IAA, with or without rapid pacing. During hypoxia, Nai increased by approximately 200% during rapid pacing but did not increase in unpaced hearts or when the Na+/H+ exchange blocker ethylisopropylamiloride (EIPA, 10 mumol/l) was used. Neither EIPA nor a low-Ca2+ perfusate (50 mumol/l) could prevent the rise in Nai during perfusion with IAA. Myocardial function and high-energy phosphate stores were preserved during inhibition of glycolysis with IAA and continued oxidative metabolism. These results suggest that glycolysis is required for normal Na+ homeostasis in the perfused rat heart, possibly because of preferential fueling of Na-K-adenosinetriphosphatase by glycolytically derived ATP.

Magnetic resonance imaging for quantitation of right ventricular volume in patients with pulmonary hypertension.

Evaluation of right ventricular function in patients with right-sided heart failure is difficult because of the complex anatomy of the right ventricle; the distinct geometry of the dilating, failing right ventricle; its variance from the typical oblate spheroid shape used to model the left ventricle; associated cardiac lesions in patients with right ventricular failure (including tricuspid and pulmonary regurgitation); and the inherent risk of conventional contrast ventriculography. With magnetic resonance techniques, tomographic images of the heart may be obtained at multiple points in the cardiac cycle without the use of intravascular contrast agents. From the end-diastolic and end-systolic images, chamber volume may then be determined directly without any modeling assumptions as to the geometry of the ventricular chamber.

Fractal analysis of pulmonary arteries: the fractal dimension is lower in pulmonary hypertension

We analyzed the spatial structure of contact radiographs of barium-filled pulmonary arteries of rats raised in room air and in two environments that induce pulmonary arterial hypertension (PAH)—hypoxia and hyperoxia. We found that the spatial structure of the pulmonary arteries was fractal in both the control and the hypertensive lungs. The fractal dimension of the pulmonary arteries of the control lungs was 1.62 ± 0.01 (mean ± SEM), which is greater than that of both the hypoxic lungs 1.50 ± 0.03 (p < 0.01) and the hyperoxic lungs 1.44 ± 0.01 (p < 0.01). There was no significant difference between the hypoxic and hyperoxic lungs. The fractal dimension may be a useful clinical index to quantify pathologic changes in the pulmonary arterial tree.

In vivo nuclear magnetic resonance imaging of myocardial perfusion using the paramagnetic contrast agent manganese gluconate

Previous nuclear magnetic resonance (NMR) imaging studies have indicated that coronary occlusion does not produce sufficient changes in standard tissue relaxation times to allow the detection of acute ischemia. To identify acute myocardial perfusion abnormalities, the use of the paramagnetic agent manganese gluconate combined with calcium gluconate (MnGlu/CaGlu) was investigated in canine models of acute coronary artery occlusion. In vitro studies showed that MnGlu/CaGlu was a more efficient relaxing agent than gadolinium-DTPA (relaxivity of 7.8 versus 5.1 s-1 mM-1) and demonstrated affinity for normal myocardium. The distribution of MnGlu/CaGlu as measured by manganese-54 tracer studies was proportional to myocardial blood flow in both normal and ischemic tissue. Hearts excised from dogs after coronary artery occlusion and administration of 0.035 mM/kg MnGlu/CaGlu were imaged ex vivo using a relatively spin-lattice relaxation time (T1)-weighted gradient reversal technique (repetition time [TR] 50 ms and echo time [TE] 9 ms). These images showed increased signal intensity in the normally perfused myocardium with a mean signal intensity ratio of hypoperfused to normal myocardium of 0.55 +/- 0.12 (mean +/- SD). In vivo images obtained in nine dogs after coronary artery occlusion and administration of the same dose of MnGlu/CaGlu demonstrated the region of hypoperfused myocardium in six dogs with a signal intensity ratio of hypoperfused to normal myocardium of 0.64 +/- 0.23 (p less than 0.05 versus control). When a higher dose of 0.1 mM/kg MnGlu/CaGlu was utilized and in vivo imaging was performed using a relatively spin-spin relaxation time (T2)-weighted (TR gated, TE 60 ms) spin-echo sequence in six dogs, the signal intensity of normal myocardium was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)