1H-MRS detected lipolysis in diabetic rat hearts requires neutral lipase.

PURPOSE: Triacylglycerol (TAG) lipolysis increases in diabetic hearts. However, it is not known which pathway for lipolysis catalyzes this process. Thus, using 1H-magnetic resonance spectroscopy (MRS), we determined whether TAG lipolysis in diabetic rat hearts requires acid lipase or neutral lipase activity. METHODS: Rats were given IP injections of 110 mg streptozotocin (STZ)/kg. Forty-eight to 72 h after this treatment, all rats exhibited ketotic diabetes. The hearts of these ketotic rats were isolated, perfused isovolumically, and analyzed using 1H-MRS. RESULTS: The content of methylene protons (CH2)n--and otherfatty acid protons, measured using 1H-MRS, increased in hearts isolatedfrom STZ-treated compared to untreated rats. This increase in heart--(CH2)n--was directly related to the chemical content of heart TAGs. If isolated diabetic hearts were perfused with either glucose or glucose plus the acid lipase inhibitor methylamine, then heart content of TAG, measured as (CH2)n, decreased at rates of approximately 130 nmol TAG/gdw/min throughout a 55-min perfusion. If diabetic hearts were pretreated with the neutral lipase inhibitor diethyl-p-nitro-phenylphosphate (DNPP) and perfused with glucose, then heart TAG content, measured as (CH2)n, did not change during perfusion. CONCLUSIONS: 1H-MRS can detect the TAG and the net lipolysis of TAG in diabetic rat hearts. Net TAG lipolysis in diabetic rat hearts requires neutral lipase.

Cardiac MR spectroscopy in the new millennium.

Spectroscopy is close to becoming an integral part of the clinical MR examination to achieve a complete morphological, functional, and metabolic evaluation of the human heart. 31P-NMR spectroscopy is used to noninvasively assess human myocardial energy metabolism. Abnormalities in the phosphocreatine (PCr) to ATP ratio are observed in ischemic heart disease, heart failure, transplanted hearts, and hypertrophic cardiomyopathy. NMR spectroscopy 31P spectra obtained at rest, during exercise or pharmacological stress allow the observation of the earliest metabolic responses of myocardial ischemia. 1 spectroscopy can evaluate the concentration of intracellular creatine and myocardial lipids as a means of evaluating myocardial viability. The increase in total 23Na in ischemic tissue provides information about the extent and location of viable tissue. Higher magnetic fields, gradient strength, and technological advances in pulse sequence and localization will result in better spatial and temporal resolution improving the clinical utility of the technique.

Validation of rapid velocity encoded cine imaging of a dynamically complex flow field using turbo block regional interpolation scheme for k space.

Block regional interpolation scheme for k space (BRISK) is a sparse sampling approach to allow rapid magnetic resonance imaging of dynamic events. Rapid velocity encoded cine (VEC) imaging with Turbo BRISK is potentially an important clinical diagnostic technique for cardiovascular diseases. Previously we applied BRISK and Turbo BRISK to imaging pulsatile flow in a straight tube. To evaluate the capabilities of Turbo BRISK imaging in more complex dynamic flow fields such as might exist in the human vasculature, an in vitro curved tube model, similar in geometry to the aortic arch, was fabricated and imaged under pulsatile flow conditions. Velocity maps were obtained using conventional VEC and Turbo BRISK (turbo factors 1 through 5). Comparison of the flow fields obtained with each higher order turbo factor showed excellent agreement with conventional VEC with minimal loss of information. Similarly, flow maps showed good agreement with the profiles from a laser Doppler velocimetry model. Turbo-5 BRISK, for example, allowed a 94% savings in imaging time, reducing the conventional imaging time from over 8 min to a near breath-hold imaging period of 31 s. Turbo BRISK shows excellent promise toward the development of a clinical tool to evaluate complex dynamic intravascular flow fields.

Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms.

BACKGROUND: After hospitalization for chest pain, women are more likely than men to have normal coronary-artery angiograms. In such women, myocardial ischemia in the absence of clinically significant coronary-artery obstruction has long been suspected. Most methods for the detection of the metabolic effects of myocardial ischemia are highly invasive. Phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy is a noninvasive technique that can directly measure high-energy phosphates in the myocardium and identify metabolic evidence of ischemia. METHODS: We enrolled 35 women who were hospitalized for chest pain but who had no angiographically significant coronary-artery obstructions and 12 age- and weight-matched control women with no evidence of heart disease. Myocardial high-energy phosphates were measured with 31P-NMR spectroscopy at 1.5 tesla before, during, and after isometric handgrip exercise at a level that was 30 percent of the maximal voluntary grip strength. We measured the change in the ratio of phosphocreatine to ATP during exercise. RESULTS: Seven (20 percent) of the 35 women with chest pain and no angiographically significant stenosis had decreases in the phosphocreatine:ATP ratio during exercise that were more than 2 SD below the mean value in the control subjects without chest pain. There were no significant differences between the two groups with respect to hemodynamic variables at rest and during exercise, risk factors for ischemic heart disease, findings on magnetic resonance imaging and radionuclide perfusion studies of the heart, or changes in brachial flow during the infusion of acetylcholine. CONCLUSIONS: Our results provide direct evidence of an abnormal metabolic response to handgrip exercise in at least some women with chest pain consistent with the occurrence of myocardial ischemia but no angiographically significant coronary stenoses. The most likely cause is microvascular coronary artery disease.

The 31P-NMR stress test: an approach for detecting myocardial ischemia.

31P-NMR spectroscopy has the potential to assess myocardial damage directly and noninvasively by ascertaining the relative abundances of phosphorus-containing compounds relevant to metabolism under stress conditions. Decrease in the PCr/ATP ratio during exercise is an indicator of the level of stress to which the myocardium is subject. This ratio will remain constant under mild to moderate exercise conditions in a healthy subject, but may show a precipitous decrease even under mild exercise when regions of the myocardium are ischemic. The studies examined here indicate that cardiac patients with some forms of ischemia showed a PCr/ATP ratio decrease even under light exercise, while no decrease was observed in patients whose heart disease was known to be nonischemic. Hypertension and nonstenotic chest pain in women can, in some cases, produce a decrease in PCr/ATP ratio. Only the hypertensive patients showed a significant difference in the prestress PCr/ATP ratio when compared with controls. These studies suggest that 31P-NMR spectroscopy before and during mild exercise in the bore of the magnet can be a useful indicator of the presence or absence of an ischemic component to myocardial disorder.

Hemodynamic evaluation with TURBO BRISK--a rapid phase contrast angiography technique.

Hemodynamic imaging by phase contrast angiography was significantly accelerated by selective interpolation and segmentation in k-space using TURBO BRISK. The method was tested in vitro on three independent flowfields, representative of human blood rheology: a straight tube simulating the descending aorta, a curved tube simulating the aortic arch and a two-chamber orifice flow model simulating valvular regurgitation. The results were compared to data obtained by Laser Doppler Velocimetry (LDV) and showed good agreement. For the straight tube, the flow velocity obtained by five TURBO BRISK methods with increasing segmentation factors and corresponding time savings showed good agreement with LDV. For the curved tube, the velocity showed good general agreement with some differences in the decelerating part of the cycle, and in the low-velocity secondary flow structures. The orifice flow evaluation, the most time consuming case, was performed by the control volume method. It showed good agreement with actual flows through the orifice. Data acquisitions for TURBO-4 BRISK could be performed in 20s for each velocity component. The method shows promise for breath-hold acquisitions in clinical applications, including calculation of blood flow volumes through diseased arteries, measurement of blood backflow volumes through dysfunctional heart valves to time valve replacement operations, and evaluation of arterial wall shear stress, an important factor in the genesis of atherosclerosis.

31P-magnetic resonance spectroscopy studies of cardiac transplant patients at rest.

Studies in animal models and patients have suggested that 31P-magnetic resonance spectroscopy (MRS) may be useful in diagnosing transplant rejection, but such studies often are confounded by the late inclusion of patients after transplantation. The present study examined the utility of 31P-MRS in the diagnosis of acute allograft rejection during the first posttransplant month. Thirteen recent heart transplant recipients underwent 57 resting 31P-MRS studies within 24 hr of a biopsy. Subjects lay supine with a 10-cm surface coil placed over the heart. A 1-dimensionsal chemical shift imaging protocol was used to collect spectral information. Spectra from the heart were weighted for distance from the coil and summed before analysis. ANOVA and Duncan's multiple range test were used to analyze the data comparing phosphocreatine (PCr)/ATP ratios with biopsy scores. Transplant patients had significantly lower myocardial PCr/ATP ratios when compared with a normal control group (1.27 +/- 0.27 versus 1.61 +/- 0.22, p < 0.001). However, when the patient group was classified by biopsy score, the expected order of score, 0 > 1 > 2 > 3, was not obtained. Rather, the order was 2 > 0 > 1 > 3. Although the difference between scores 2 and 3 was significant (1.46 versus 1.14, alpha = 0.05 level), the lower three groups were statistically indistinguishable. In addition, the PCr/ ATP ratios were not predictive of future biopsies. Although significantly lower than normal control subjects, resting myocardial PCr/ATP ratios of transplant subjects are not useful in assessing thelevel of rejection. It is suggested that the measurement may be more predictive in mildly exercised myocardium.

ACE inhibitors in HF restore canine pulmonary endothelial function and ANG II vasoconstriction.

Chronic mitral regurgitation (MR) in dogs results in pulmonary congestion and increased cardiac angiotensin-converting enzyme (ACE) activity and angiotensin (ANG) II levels. ACE could contribute to altered pulmonary vasomotion in heart failure, and ACE inhibitor (ACEI) therapy may normalize pulmonary vasomotion. We evaluated pulmonary artery (PA) responses to ANG II and bradykinin (BK) in control dogs, in dogs with 4 mo of MR, in MR dogs treated with the ACEI ramipril (MR + R), and in control dogs treated with ramipril (C + R). Mean PA systolic pressure increased in MR dogs (21 +/- 4 mmHg) but was normal in MR + R dogs (13 +/- 1 mmHg). Constriction of PA rings to ANG II was depressed in MR dogs. ACEI treatment (MR + R) restored ANG II responsiveness, but peak ANG II response (3.6 +/- 0.2 g) in MR + R dogs remained lower than in C + R dogs (4.7 +/- 0.2 g). Endothelium-dependent relaxation to BK was decreased (-87 +/- 4% C, -65 +/- 4% MR; P < 0.05). Ramipril (MR + R) restored relaxation to BK. This demonstrates that pulmonary congestion results in impaired pulmonary vasomotion to ANG II and BK, which ACEIs could normalize, supporting the use of ACEIs in clinical management of chronic congestive heart failure.

Dobutamine stress echocardiography in women with chest pain. Pilot phase data from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE).

OBJECTIVES: The aim of this project was to assess the utility of dobutamine stress echocardiography (DSE) for evaluation of women with suspected ischemic heart disease. BACKGROUND: Most investigations addressing efficacy of diagnosis and treatment of coronary artery disease (CAD) have been performed in predominantly male populations. As part of the Women's Ischemia Syndrome Evaluation (WISE) study, DSE was assessed in women participating at the University of Florida clinical site. METHODS: Women with chest pain or other symptoms suggestive of myocardial ischemia and clinically indicated coronary angiography were eligible for the WISE study. Enrolled subjects underwent DSE using a modified protocol. Coronary stenosis was assessed by core laboratory quantitative coronary angiography (QCA). RESULTS: The 92 women studied ranged in age from 34 to 82 years (mean 57.5). All women had > or = 1 major risk for CAD, and most (89, 97%) had > or = 2 risk factors. In 78 women (85%), left ventricular wall motion was normal at baseline and during peak infusion. The remaining 14 women had wall motion abnormalities during DSE. By QCA, 25 women (27%) had > or = 50% coronary stenosis, including 10 with single-vessel obstruction. Dobutamine stress echocardiography was abnormal in 10 of these 25 women, yielding overall sensitivity of 40%, and 60% for multivessel stenosis. Exclusion of women with inadequate heart rate response yielded overall sensitivity of 50%, and 81.8% for multivessel stenosis. Dobutamine stress echocardiography was normal in 54 of the 67 women with < 50% coronary narrowing, specificity 80.6%. CONCLUSIONS: Dobutamine stress echocardiography reliably detects multivessel stenosis in women with suspected CAD. However, DSE is usually negative in women with single-vessel stenosis, and in the larger subset without coronary stenosis. Ongoing protocols of the WISE study are expected to improve diagnostic accuracy in women with single-vessel disease, as well as provide important data in the substantial number of women with chest pain but without epicardial coronary artery stenosis.

Rapid velocity-encoded cine imaging with turbo-BRISK.

Velocity-encoded cine (VEC) imaging is potentially an important clinical diagnostic technique for cardiovascular diseases. Advances in gradient technology combined with segmentation approaches have made possible breathhold VEC imaging, allowing data to be obtained free of respiratory artifacts. However, when using conventional segmentation approaches, spatial and temporal resolutions are typically compromised to accommodate short breathhold times. Here we apply a sparse sampling technique, turbo-BRISK (i.e., segmented block regional interpolation scheme for k-space) to VEC imaging, allowing increased spatial and temporal resolution to be obtained in a short breathhold period. BRISK is a sparse sampling technique with interpolation used to generate unsampled data. BRISK was implemented to reduce the scan time by 70% compared with a conventional scan. Further, turbo-BRISK scans, using segmentation factors up to 5, reduce the scan time by up to 94%. Phantom and in vivo results are presented that demonstrate the accuracy of turbo-BRISK VEC imaging. In vitro validation is performed using conventional magnetic resonance VEC. Pulsatile centerline flow velocity measurements obtained with turbo-BRISK acquisitions were correlated with conventional magnetic resonance imaging measurements and achieved r values of 0.99 +/- 0.004 (mean +/- SD) with stroke volumes agreeing to within 4%. A potential limitation of BRISK is reduced accuracy for rapidly varying velocity profiles. We present low- and high-resolution data sets to illustrate the resolution dependence of this phenomenon and demonstrate that at conventional resolutions, turbo-BRISK can accurately represent rapid velocity changes. In vivo results indicate that centerline velocity waveforms in the descending aorta correlate well with conventional measurements with an average r value of 0.98 +/- 0.01.

Magnetic resonance angiography.

Since the emergence of magnetic resonance (MR) imaging, its clinical applications have seen a logarithmic growth. The advantage of MR imaging is that it offers a vast amount of important clinical information with minimal risk to the patient, and promises to reduce the need for angiographic studies with their attendant morbidity and mortality. We review the applications and recent advances of MR imaging to include coronary imaging of native, bypassed and stented vessels, carotid arteries, peripheral arteries, and the aorta. In addition, we discuss issues of patient preferences and the future directions of MR imaging. We predict that the clinical utility of MR angiography will grow with refinements that will improve speed, resolution, and even the use of spectroscopy to characterize plaque.