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Biomedical subjects

G M Pohost

Publications and source records attributed to G M Pohost.

At least 109 records · Page 6Linked to original sources

Fatty-acyl iminopolycarboxylates: lipophilic bifunctional contrast agents for NMR imaging.

New fatty-acyl contrast agents, N3-2'-myristoyloxyethyl-N6-2'-hydroxyethyl-1, 8-dioxotriethylenetetraamine-N,N,N',N'-tetraacetic acid (MHE-DTTA) and N3,N6-bis(2'-myristoyloxyethyl)-1,8-dioxo- triethylenetetraamine-N,N,N',N'-tetraacetic acid (BME-DTTA) were prepared by sequential alkylation, acylation, and catalytic hydrogenation from bis(hydroxyethyl)-ethylenediamine with satisfactory yields (overall 36-46%). The 1:1 gadolinium complexes of the ligands MHE-DTTA and BME-DTTA were incorporated into liposomes and their relaxivities in vitro were determined. The relaxivities of both agents were similar and were greater than those of Gd3+ aquoion, Gd(EDTA), and Gd(DTPA) at both 0.23 T and 0.47 T. The relaxivities of these two agents increased from the lower to the higher magnetic field, indicating a positive field dependence. This is advantageous because of the widespread use of high-field (B0 greater than 0.5 T) NMR imaging instruments. Stability constants (log K) of Gd(MHE-DTTA) and Gd(BME-DTTA) were found to be 15.27 +/- 2.21 and 16.78 +/- 0.36, respectively. LD50 of both compounds was greater than 0.2 mmol/kg. These stabilities and lower limits of LD50 indicate the possible in vivo application of these agents.

Animals↗

Diagnosis and quantitation of myocardial infarction.

In order to provide timely and proper therapy for patients with myocardial infarction, accurate diagnosis is essential. To assess the impact of therapy and to aid in long-term prognostication, it is also desirable to quantitate accurately the extent of infarct size. For diagnostic purposes, the conventional methods of clinical evaluation, 12-lead electrocardiography, and analysis of serum enzymes are accurate. However, more sophisticated approaches, such as radionuclide, echocardiographic, and magnetic resonance imaging, can be useful adjuncts for diagnosis. In contrast, the sizing of infarcts is often best performed using imaging methods. This paper reviews the application of various techniques to accomplish the goals of accurate diagnosis and quantitation of myocardial infarction.

Clinical Enzyme Tests↗

Nuclear magnetic resonance imaging for assessment and follow-up of patients with valve disease.

Nuclear magnetic resonance (NMR) imaging now offers a powerful means of assessing a variety of clinically important parameters in patients with valvular heart disease. NMR approaches will probably be most useful in patients with chronic valvular regurgitation, in which there continues to be uncertainty regarding the optimum timing for surgical intervention. In these patients it is possible to simultaneously assess both the valvular regurgitation and the resulting changes in myocardial structure and function. In patients with aortic stenosis, NMR can be applied to the assessment of left ventricular mass, both before and after valvuloplasty or valve replacement. In mitral stenosis, NMR may be applied to the assessment of right ventricular volumes and function. NMR may be used for the detection of prosthetic valve regurgitation when Doppler studies are equivocal. Finally, NMR imaging may be applied in patients with congenital or aortic root disease to evaluate valvular function in addition to diagnostic assessment of such patients. The future development of isotropic three-dimensional acquisition approaches, ultrafast imaging strategies, automated surface detection techniques, and more rapid function and flow analysis could considerably enhance the use of the current NMR approaches. The application of spectroscopic techniques could provide a means of monitoring myocardial metabolic abnormalities in ventricles exposed to chronic overload. Meanwhile, in patients with valvular regurgitation and stenosis, it would seem timely to initiate long-term serial NMR studies to further define natural history and the effects of various medical regimens and to ultimately help determine optimum medical and interventional regimens.

Aortic Valve Insufficiency↗

Accuracy of digital Holter monitoring of extent and duration of ischemic episodes compared to analog recording.

Analog amplitude-modulated Holter devices are in widespread use for arrhythmia detection, but their reliability remains questioned for ST-segment analysis. In contrast, recently developed digital Holter devices immediately digitize and analyze the electrocardiogram (ECG) on-line and may therefore be more reliable for ST-segment analysis. To test this hypothesis, the results of digital, on-line, 2-channel ST-segment analysis were directly compared to those of analog amplitude-modulated recordings in identical leads (CM5 and CM3), using a stripchart recorder meeting the American Heart Association specifications as the standard. Thirty-five patients (25 with coronary artery disease and 10 control subjects) underwent graded treadmill exercise testing. The reference ECG mean value for ST-segment depression in CM5 was -1.4 +/- 1.2 mm and in CM3 -0.5 +/- 1.2 mm. For digital analysis, the mean values and correlation coefficients for CM5 were -1.5 +/- 1.1 mm (r = 0.97) and for CM3 -0.8 +/- 1.3 mm (r = 0.93). For analog recording, the results for CM5 were -2.1 +/- 1.7 mm (r = 0.88) and for CM3 -1.3 +/- 1.9 mm (r = 0.85). The mean duration of ST-segment depression with the reference ECG was 7.1 +/- 4.1 minutes. Digital Holter showed a significantly better agreement (7.4 +/- 4.4 min, r = 0.97) than analog Holter (9.6 +/- 5.6 min, r = 0.84). Because analog amplitude-modulated Holter recordings overestimated the degree and duration of ischemic episode, digital, on-line and full disclosure devices should be preferred to assess myocardial ischemia.

Algorithms↗

Detection of intramyocardial hemorrhage using high-field proton (1H) nuclear magnetic resonance imaging.

Proton (1H) nuclear magnetic resonance (NMR) imaging has been used to define zones of myocardial infarction (MI), which appear as areas of relatively increased signal intensity (SI). However, zones of decreased SI have been observed within the areas of infarction and have been postulated to result from intramyocardial hemorrhage. To explore this phenomenon further, ex vivo spin-echo 1H NMR imaging at 1.5 Tesla was performed in 17 dogs after 24 hr (n = 9) and after 72 hr (n = 8) of coronary artery occlusion. In all dogs, a zone of increased SI (118 +/- 9% compared with normal myocardium) was observed in the distribution of the occluded coronary artery. In 12 of the 17 dogs, zones of decreased SI (92 +/- 8% compared with normal) were seen within or around the central zone of increased SI. Gross inspection and histological assessment of sliced myocardium usually disclosed hemorrhage in the regions of decreased SI. In three of the five dogs with no apparent zones of decreased SI on NMR, the infarct was small, and only minor hemorrhage was observed by gross inspection, whereas in the remaining two dogs no hemorrhage was seen. Myocardial flow in the hemorrhagic regions was significantly higher than in the necrotic core (59 +/- 29% vs. 31 +/- 24% compared with control, P less than 0.05). Image-derived calculation of T2 relaxation times in the different infarcted regions revealed a significant shortening of T2 in the infarcted hemorrhagic zones with decreased SI compared with the infarct zones with increased SI (49 +/- 8 msec vs. 66 +/- 8 msec, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PC-based system for retrospective cardiac and respiratory gating of NMR data.

A method and a means for retrospectively clustering NMR k-space measurement profiles with respect to both cardiac and respiratory phases were developed to explore strategies for (1) reducing cardiovascular and respiratory flow/motion image artifacts and (2) improving T1 and T2 characterization of the heart. The image data are collected at a uniform rate so that echo (TE) and repetition (TR) times are independent of the varying cardiac cycle R-R interval and/or respiratory motions. Cardiac (C) time, respiratory (R) time or diaphragm position, and NMR data acquisition (A) cycle time are collected by microcomputer in parallel with free running (untriggered) image collection on a standard magnetic resonance imager. After the raw data equivalent of multiple images are collected, the C-A-R phase timing data are uploaded from the microcomputer to the scanner's minicomputer for use in a normalized C-R phase plane clustering of the image raw data. Each profile's position in the C-R phase plane is determined and then clustered into a new set of data, one image being equivalent for each desired C-R phase combination. These raw data are then zero-filled and (optionally) filtered to compensate for the nonuniform k-space sampling and, finally, reconstructed. Cardiac "cines" made from these retrospectively gated images are comparable to similarly phased triggered images. When high time resolution is required, retrospective gating can be expected to show improvements over triggering, especially toward the critical latter part of the cardiac cycle, where coronary artery filling occurs. The system described can readily be assembled from generally available components.

Electrocardiography↗

Relations of the myocardial imaging agents 99mTc-MIBI and 201T1 to myocardial blood flow in a canine model of myocardial ischemic insult.

Myocardial imaging with thallium 201 has proven to be an important clinical procedure to assess the severity of the myocardial ischemic insult. Uptake of 201Tl is related to perfusion to and extraction by intact myocardium. Recently, a newer group of agents based on 99mTc alkyl isonitriles has been developed and appears promising for myocardial imaging. Although the distribution of this new agent has been shown to be related to myocardial perfusion, its dependence on myocardial integrity has not been established. This study compared the distribution of 99mTc-2-methoxy-isobutyl-isonitrile (99mTc-MIBI) with that of 201Tl in a clinically relevant canine model of ischemic insult. Fifteen adult dogs underwent 2 hours of occlusion by left anterior descending coronary artery ligation followed by reperfusion. In one group of dogs, 201Tl and 99mTc-MIBI were administered 5 minutes before 35 minutes of reflow (group 1, n = 5). In the other animals, the agents were given 5 minutes after onset of reflow, and dogs were killed after 10 (group 2, n = 5) and 35 minutes of reperfusion (group 3, n = 5). 99mTc-MIBI activity was significantly correlated with 201Tl activity (r = 0.91, 0.77, and 0.92, for groups 1, 2, and 3, respectively). Both 201Tl and 99mTc-MIBI activities were correlated similarly with blood flow in all models. In groups 1 and 2, 201Tl and 99mTc-MIBI activities correlated directly with microsphere-determined blood flow, whereas in group 3, they correlated inversely. The present study shows that in these models of myocardial ischemic insult, 99mTc-MIBI distribution is closely related to that of 201Tl.

Animals↗

Left ventricular volume measurement using cardiac axis nuclear magnetic resonance imaging. Validation by calibrated ventricular angiography.

Proton nuclear magnetic resonance (NMR) imaging has the potential to serially assess left ventricular (LV) volumes with optimal accuracy because it is a high-resolution, three-dimensional, noninvasive modality. Previous NMR studies to assess LV volumes have been suboptimal, as they have used either planes aligned with the axes of the body, which are compromised by partial volume effects, or spin-echo techniques that have been time-consuming to acquire and analyze. Accordingly, for LV volume measurement, we developed a gradient-echo (cine) NMR strategy that uses two orthogonal planes intersecting along the intrinsic long axis of the heart (two-chamber and four-chamber). This approach was validated against calibrated contrast biplane LV cineangiography (CATH) and also compared with a previously reported short-axis spin-echo NMR method. Twenty-one patients underwent CATH and NMR (long-axis, n = 21; short-axis, n = 14) within a 3-day interval. Although both long- and short-axis NMR LV volumes and ejection fractions correlated well with CATH (r greater than 0.90, p less than 0.001 in all), end-diastolic volumes by both long-axis (161 +/- 85 ml) and short-axis (151 +/- 81 ml) NMR were systematically less than those by CATH (182 +/- 85 ml) (p less than 0.05). Consequently, ejection fractions by long-axis (48 +/- 17%) and short-axis (49 +/- 17%) NMR consistently underestimated those by CATH (54 +/- 16%, p less than 0.05). End-systolic volumes by long-axis (94 +/- 71 ml) and short-axis (87 +/- 72 ml) NMR were not significantly different from those by CATH (92 +/- 69 ml). Both NMR techniques had low intraobserver and interobserver variation (less than 11%); however, short-axis spin-echo NMR involved longer acquisition/reconstruction (35 versus 18 minutes) and analysis (25 versus 10 minutes) times. We conclude that both short-axis spin-echo and long-axis gradient-echo NMR approaches reliably estimate LV volumes. Currently, the long-axis strategy appears more practical for clinical use because the scan and analysis times are relatively short.

Adult↗

Demonstration of increased myocardial lipid with postischemic dysfunction ("myocardial stunning") by proton nuclear magnetic resonance spectroscopy.

Histopathologic studies have demonstrated accumulation of lipid droplets in myocardium subjected to greater than or equal to 6 h of ischemic insult. Proton nuclear magnetic resonance (NMR) spectroscopy can provide a noninvasive means to evaluate changes in tissue lipid and, potentially, to characterize the ischemic insult. To determine whether lipids accumulate with a brief ischemic insult, myocardial lipid content was evaluated by 1H NMR spectroscopy of ex-vivo samples from seven dogs in a model of postischemic dysfunction created by 15 min of left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Regional myocardial function was assessed by measuring segment length shortening with use of a pair of ultrasonic crystals placed in the ischemic zone and in the control zone. During the occlusion, all dogs had significant ischemia of the occlusion zone as measured by radiolabeled microspheres (0.08 +/- 0.08 versus 0.88 +/- 0.09 ml/g per min for the control zone), and all dogs developed systolic stretching of the ischemic zone segment. Myocardial lipid content was significantly elevated in the samples from the coronary occlusion zone (p less than 0.02). The increase in lipid signal may result from the ischemia-induced decrease in beta oxidation and resultant accumulation of fatty acyl esters (for example, fatty acids, triglycerides and acylcarnitines). In conclusion, this study shows that myocardium subjected to a brief (approximately 15 min) coronary occlusion followed by 3 h of reperfusion demonstrates a significant increase in NMR-detectable lipid content.

Animals↗

Assessment of myocardial infarct size by means of T2-weighted 1H nuclear magnetic resonance imaging.

Proton (1H) nuclear magnetic resonance (NMR) imaging is thought to depict zones of recent myocardial infarction in contrast to noninfarcted myocardium. This is related to T2 increases in infarct zones that have been verified previously by relaxometry measurements in excised myocardial samples. Accordingly the present study was undertaken to evaluate a 1H NMR imaging method to optimize T2 contrast and measure infarct size in a high-field imaging system (1.5 T). To accomplish this, NMR images were acquired every other R wave with echo times of 30 and 100 msec. The first echo image was used for myocardial border definition and the second echo image, which highlighted the myocardial infarction, for infarct border definition. This T2-weighted approach yielded a significant correlation between infarct size by NMR and pathologic methods. However, NMR imaging tended to overestimate infarct size, and the NMR image depicted abnormal signal well beyond the extent of the pathology-determined infarct. There was a significant relationship between NMR-imaged infarct size and myocardial mass with microsphere-determined reduction in blood flow of 25% or more. These data suggest that T2-weighted NMR imaging depicts not only infarct but also some reversibly injured myocardium.

Animals↗

The value of cine nuclear magnetic resonance imaging for assessing regional ventricular function.

Previous nuclear magnetic resonance (NMR) imaging studies to assess left ventricular function have used multiple axial planes, which are compromised by partial volume effects and are time consuming to acquire and analyze. Accordingly, an imaging approach using cine NMR and planes aligned with the true cardiac axes of the left ventricle was developed in views comparable with left ventricular cineangiography. Cine NMR imaging was used to assess regional wall motion and was validated by comparison with biplane left ventricular cineangiography. Fifty-nine patients underwent cineangiographic and NMR studies within 72 h. A poor quality NMR study precluded analysis in 4. leaving a study group of 55 patients (mean age 58 +/- 12: 17 women). Cine NMR movie loops were acquired in two long-axis planes: 1) right anterior oblique plane, parallel to the septum, and 2) four chamber orthogonal plane, perpendicular to the septum (this view is comparable to the angiographic left anterior oblique view). To assess regional wall motion, the left ventricle in both cine NMR and cineangiographic images was divided into five segments and graded on a five point grading scale from 3 for normal through 0 for akinesia and -1 for dyskinesia. Regional wall thickening was used qualitatively to aid in the analysis of wall motion. For the 275 segments compared in the right anterior oblique view, agreement was within one grade in 263 (95.6%) of 275 segments, whereas absolute agreement was observed in 171 (62%) of 275 segments. In the left anterior oblique view, of 200 segments evaluated, agreement within one grade was achieved in 184 segments (92%) and agreement was complete in 132 (66%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Summary of a consensus concerning death and ischemic events after coronary artery bypass grafting.

The early and long-term results of myocardial revascularization are reviewed for four unidentified community hospitals, for Katholieke Universiteit (Leuven, Belgium), and for the University of Alabama at Birmingham at two different times. After operation, approximately 77% of patients are free from all ischemic events at 5 years and nearly 50% are free at 10 years. Over 90% of patients survive 5 years, and approximately 80% survive 10 years. Some of the incremental risk factors for early death after operation include older age; degree of left ventricular dysfunction; hemodynamic instability at the time of operation; recent myocardial infarction; number of diseased coronary vessels; associated mitral incompetence, ventricular aneurysm, or ventricular tachycardia; longer aortic cross-clamp time; and non-use of the internal mammary artery for revascularization. The number of diseased coronary arteries and the aggressiveness of the atherosclerotic process, degree of left ventricular dysfunction, older age, and non-use of the internal mammary artery are risk factors for reduced long-term survival.

Actuarial Analysis↗

Overview of cardiovascular nuclear magnetic resonance imaging.

Application of NMR technology to the evaluation of the cardiovascular system is still in its infancy. NMR can frequently yield information equivalent to echocardiography or angiography but cost, long imaging times, and lack of portability have discouraged widespread use. To date, NMR has not replaced standard imaging modalities in the evaluation of most cardiovascular disease states, although it appears to have a unique role in the delineation of great vessel pathology, the evaluation of congenital heart disease, and the delineation of cardiac and paracardiac masses. Appearance of tissue and flowing blood and contrast between structures are highly dependent on magnetic field strength and the imaging pulse sequence used. Published comparisons between NMR and other imaging modalities have to be interpreted and extrapolated with caution, and sensitivity and specificity of NMR imaging in different disease entities should be further validated. With technological improvements, shortening of examination times and data processing times and true three-dimensional imaging may be possible in the near future. Ultimately, however, the clinical importance of NMR will depend on the development of unique applications such as examination of regional cardiac metabolism, noninvasive coronary and peripheral angiography, myocardial perfusion imaging, and improved tissue characterization.

Aortic Diseases↗