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Biomedical subjects

S Schaefer

Publications and source records attributed to S Schaefer.

At least 109 records · Page 6Linked to original sources

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)

Animals↗

Response of myocardial metabolites to graded regional ischemia: 31P NMR spectroscopy of porcine myocardium in vivo.

The changes in myocardial high energy phosphates and pH during regional ischemia, and their potential role in mediating functional abnormalities, is unclear. To determine the degree of regional blood flow reduction required to induce changes in high energy phosphates and pH, and to correlate these metabolic changes with alterations in blood flow, 31P nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional blood flow and phosphate compounds were made during various steady-state degrees of regional ischemia in which subendocardial blood flow was reduced by as much as 80%. ATP did not fall over the total range of graded ischemia, while phosphocreatine (PCr), inorganic phosphate (Pi), and pH all changed progressively after blood flow was reduced below 50% of normal. The ratio of PCr/Pi (a measure of the energy reserve of the myocardium) was strongly correlated to subendocardial blood flow (r = 0.94) and declined by 25% when blood flow was reduced by only 21% below normal. These findings indicate that PCr/Pi is a sensitive marker of ischemia and support the hypothesis that the in vivo energy status of the myocardium is closely coupled to myocardial blood flow.

Adenosine Triphosphate↗

Magnetic resonance spectroscopy of the heart.

MRS has clearly established itself as an important investigative tool for the study of cardiac metabolism and energetics. In animal models, it can provide insight into basic metabolic processes in both health and disease. Its nondestructive nature and capacity for serial measurements in the same system have given scientists the ability to monitor changes in biologic systems over time, while its ability to measure different nuclei, and hence different metabolic processes, gives it immense flexibility. In relative contrast to animal studies, human cardiac MRS is in its infancy. To date, cardiac 31P spectroscopy has been successfully implemented in only a few centers. These studies have primarily examined normal subjects to establish the feasibility of such examinations with a variety of techniques. The few reports of metabolic abnormalities detected by 31P NMR have been limited by problems of accurate spatial localization and large sample volumes. The ultimate utility of human spectroscopy, with phosphorus or any other nucleus, will depend on the success of efforts to increase the sensitivity and spatial selectivity of the NMR experiment. These efforts include utilizing systems of higher field strength and homogeneity, as well as improving pulse sequences and radio frequency coil designs. In addition, demonstration of some degree of sensitivity and specificity of metabolic abnormalities in disease states will be necessary before clinical use is indicated. If these requirements are met, human cardiac spectroscopy may provide useful information about cardiac metabolic processes and, combined with proton NMR imaging, may enable complete noninvasive evaluation with one technology. The rapid advances over the past few years attest to the feasibility of this goal.

Animals↗

Magnetic resonance spectroscopy. Evaluation of ischemic heart disease.

Magnetic resonance spectroscopy (MRS) is a valuable tool for the study of myocardial ischemia. Phosphorus (31P) MRS can detect changes in high-energy phosphates resulting from ischemia and has been used to determine the sensitivity of metabolic changes to ischemia as well as to investigate the metabolic factors important for myocardial dysfunction. The mechanisms mediating postischemic dysfunction have been investigated using 31P MRS, as have interventions to limit metabolic and functional damage from ischemia. These investigations have laid the groundwork for human cardiac studies. While abnormalities following myocardial infarction have been shown in man, further work must be performed to reliably acquire localized spectra under conditions of ischemia.

Adenosine Triphosphate↗

Effect of increasing heart rate on left ventricular performance in patients with normal cardiac function.

The influence of an increase in heart rate on left ventricular (LV) contractile performance was assessed in patients with normal LV function. In 19 patients (3 men, 16 women) ages 55 +/- 9 years (mean +/- standard deviation) with normal global and segmental LV function and normal coronary arteries, LV dP/dt max was measured at baseline heart rate and during atrial pacing at baseline +5, baseline +25 and baseline +45 beats/min. In 10 of the patients, intravascular volume was not altered during pacing and, as a result, echocardiographically measured LV end-diastolic dimension decreased (5.4 +/- 0.4 at baseline vs 4.9 +/- 0.5 cm at baseline +45 beats/min, p less than 0.05). In these patients, LV dP/dt max increased modestly (1,571 +/- 237 at baseline vs 1,760 +/- 199 mm Hg/s at baseline +45 beats/min, p less than 0.05). In the other 9 patients, intravascular volume was expanded rapidly (by saline infusion) during pacing and, as a result, LV end-diastolic dimension was held constant (5.2 +/- 0.6 at baseline vs 5.1 +/- 0.6 cm at baseline +45 beats/min, difference not significant). In these patients, LV dP/dt max increased substantially with pacing (1,505 +/- 228 at baseline vs 2,050 +/- 258 mm Hg/s at baseline +45 beats/min, p less than 0.05). Thus, an increase in heart rate induces a modest increase in LV dP/dt max in patients in whom LV preload (as reflected by end-diastolic dimension) is allowed to decrease; in contrast, it causes a marked increase in LV dP/dt max in those in whom LV preload is maintained constant.

Adult↗

Clinical and hemodynamic characteristics of patients with inducible pulsus alternans.

Pulsus alternans can be found in some patients with abnormal left ventricular function and also can develop after spontaneous premature beats. The purposes of this study were to: (1) determine the inducibility of pulsus alternans in a series of patients referred for routine cardiac catheterization and (2) define the clinical and hemodynamic characteristics of those who develop pulsus alternans. In 104 patients referred for right and left heart catheterization, atrial premature beats and rapid atrial pacing were used to try to provoke pulsus alternans. The 29 patients who developed pulsus alternans in response to these maneuvers were older (63 +/- 6 vs 59 +/- 10 years, p less than 0.01) and had a greater incidence of valvular heart disease (45% vs 23%, p less than 0.01) and congestive heart failure (38% vs 17%, p less than 0.05). Aortic stenosis was the most prevalent valve lesion found. Those who developed pulsus alternans in response to pacing were further characterized by higher left ventricular systolic (143 +/- 42 vs 121 +/- 23 mm Hg, p less than 0.02) and end-diastolic pressures (17 +/- 9 vs 13 +/- 6 mm Hg, p less than 0.05), higher pulmonary artery systolic pressure (35 +/- 14 vs 29 +/- 11 mm Hg, p less than 0.04), and lower left ventricular ejection fractions (0.42 +/- 0.13 vs 0.53 +/- 0.14, p less than 0.001). Eight patients (28%) with inducible pulsus alternans had a normal left ventricular ejection fraction (greater than 0.50) and left ventricular end-diastolic pressure (less than 13 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Gadolinium-DTPA-enhanced nuclear magnetic resonance imaging of reperfused myocardium: identification of the myocardial bed at risk.

Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced nuclear magnetic resonance (NMR) imaging can be useful in the identification of reperfused myocardium. However, the effects of dose and the time of administration and the relation of the extent of the region of enhancement to the myocardial bed at risk have not been evaluated. In this study, dogs were given Gd-DTPA (0.1 mM/kg body weight [n = 21] or 0.34 mM/kg [n = 7]) or saline solution (n = 5) after various periods of occlusion and reperfusion. Twenty-five dogs were killed after 1 or 2 h of reperfusion and the excised hearts were imaged. Images were analyzed for presence, intensity and extent of a region of increased signal. All images in dogs given Gd-DTPA had easily identifiable regions of increased signal in the distribution of the reperfused myocardial bed. Analysis of the extent of these regions in spin-echo images of excised hearts when Gd-DTPA was administered after 5 min of reperfusion demonstrated a correlation coefficient of 0.72 with the bed at risk as determined postmortem with a dye perfusion technique. These images consistently overestimated the infarct size. Signal intensity of the reperfused myocardium increased to a maximum of 1.67 times control (p less than 0.05) in spin-lattice relaxation time (T1)-weighted sequences as the dose of Gd-DTPA increased. This was due to a higher concentration of Gd-DTPA in the reperfused myocardium with resultant shortening of the T1 relaxation time. When Gd-DTPA was given after 90 min of reperfusion, NMR images did not identify the bed at risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nuclear magnetic resonance imaging-guided phosphorus-31 spectroscopy of the human heart.

Phosphorus-31 nuclear magnetic resonance spectroscopy can determine the status of high energy phosphates in vivo. However, its application to human cardiac studies requires precise spatial localization without significant contamination from other tissues. Using image-selected in-vivo spectroscopy (ISIS), a technique that allows three-dimensional localization of the volume of interest, 12 subjects were studied to determine the feasibility and reproducibility of phosphorus-31 spectroscopy of the human heart. Nuclear magnetic resonance imaging was performed using a commercial 1.5 tesla system to define the volume of interest. Phosphorus-31 spectra were obtained from the septum and anteroapical region of the left ventricle in 10 studies. Relative peak heights and areas were determined for high energy phosphates. The mean phosphocreatine to adenosine triphosphate ratio was 1.33 +/- 0.19 by height analysis and 1.23 +/- 0.27 by area analysis. Duplicate measurements in four subjects showed a reproducibility of less than or equal to 10% in three of the subjects. All spectra showed significant signal contribution from the 2,3 diphosphoglycerate in chamber red cells without evidence of skeletal muscle contamination. These results demonstrate the feasibility of image-guided phosphorus-31 spectroscopy for human cardiac studies and indicate the potential of this technique to study metabolic disturbances in human myocardial disease.

Adenosine Triphosphate↗

A combined frontotemporal and lateral infratemporal fossa approach to the skull base.

A variety of neoplasms involve both the infratemporal fossa and the base of the middle cranial fossa, in medial proximity to the cavernous sinus and orbital apex. To provide simultaneous access to both the intracranial and extracranial aspects of these tumors, a temporal or frontotemporal craniotomy may be combined with a lateral exposure of the infratemporal fossa. The approach, which is readily achieved by a neurosurgeon and an otolaryngologist acting as a team, involves a unilateral frontotemporal incision extended inferiorly onto the neck, a lateral facial flap reflected anteriorly, and transection of the zygoma followed by its reflection inferolaterally with the temporalis muscle. This exposure provides excellent visualization of both the intradural and extradural aspects of the anterior portion of the cavernous sinus, allowing for an aggressive resection of neoplasms involving this region. Experience with this procedure is reported here in the management of nine patients: three with nasopharyngeal angiofibromas, three with low-grade malignancies of the upper aerodigestive tract, and three with sphenoid ridge meningiomas.

Adenocarcinoma↗

In vivo induction and reversal of nitroglycerin tolerance in human coronary arteries.

The mechanism by which tolerance to the clinical effects of organic nitrates develops has not been elucidated. This study was done to determine whether an intravenous infusion of nitroglycerin induces tolerance in the coronary vascular bed and whether such tolerance is reversed by the sulfhydryl-group donor N-acetylcysteine. We studied 19 subjects--17 with coronary artery disease and 2 without it--who had a mean age (+/- SD) of 54 +/- 9 years. Coronary sinus blood flow, which approximates blood flow to the left ventricle, was measured before and during intracoronary injections of nitroglycerin (10, 25, 50, and 100 micrograms). The patients then received a 24-hour intravenous infusion of saline (n = 7) or of nitroglycerin, 45 +/- 13 micrograms per minute (n = 12), after which the responses of coronary sinus flow to the same doses of intracoronary nitroglycerin used earlier were measured. In the seven patients given saline, the four doses of intracoronary nitroglycerin caused similar percentage increases in coronary sinus flow before and after the saline infusion. In the 12 patients given intravenous nitroglycerin, the four intracoronary doses caused percentage increases in coronary flow before the infusion of 30 +/- 9, 35 +/- 14, 41 +/- 12, and 52 +/- 15, respectively. After the infusion, the same doses of nitroglycerin caused smaller (P less than 0.05) percentage increases (16 +/- 6, 21 +/- 11, 23 +/- 12, and 27 +/- 11, respectively), indicating the development of partial tolerance. Subsequently, 7 of the 12 patients received N-acetylcysteine, after which intracoronary nitroglycerin caused percentage increases in coronary sinus flow similar to the values measured before the intravenous nitroglycerin was given (34 +/- 13, 32 +/- 8, 38 +/- 11, and 44 +/- 16, respectively). We conclude that the coronary vasodilator effect of nitroglycerin is attenuated by an intravenous infusion of nitroglycerin (that is, partial tolerance develops) and that tolerance to the agent can be reversed by administration of the sulfhydryl-group donor N-acetylcysteine. The mechanism by which N-acetylcysteine reverses tolerance will require further investigation.

Acetylcysteine↗

Analysis of spin-echo rephasing with pulsatile flow in 2D FT magnetic resonance imaging.

The effects of pulsatile flow on spin phases in spin-echo magnetic resonance imaging are considered. General expressions for the spin phases of the first four echoes are derived in terms of the Fourier coefficients of flow. These expressions are valid for any time-dependent acceleration and, hence, are not restricted to constant acceleration. The derived expressions are then theoretically evaluated for aortic flow and examined at different points in the cardiac cycle. Our results show that rephasing may occur at certain points in the cardiac cycle for either even or odd echoes depending upon the particular Fourier coefficients of the velocity function and the spin-echo delay time. However, even-echo rephasing is not always necessarily valid. Furthermore, the possibility of determining the flow velocities in the body with an appropriate series of imaging studies is also discussed.

Aorta↗

Even-echo rephasing and constant velocity flow.

It has been shown previously that for constant magnetic field gradients, constant velocity flow leads to even-echo rephasing for all echo delay times. We show that for flow which is not pluglike, even-echo rephasing also occurs for the pulsed readout gradients used in magnetic resonance imaging if and only if the gradients begin at the time the 90 degrees pulse is applied. We also show for these gradients that even-echo rephasing for all echo delay times in the case of nonpluglike flow implies a constant flow velocity at the point considered. Furthermore, it suffices to assume the vanishing of the spin-echo phase for any even echo, since the vanishing of any even echo for all echo delay times implies that all other even echoes also vanish identically. The odd echoes are then all equal to each other and proportional to the flow velocity. If acceleration is present, it may then be seen that for nonpluglike flow, even-echo rephasing may only be present for some but not all echo delay times. However, for the typical slice selection gradients used in magnetic resonance imaging or for usual readout gradients starting after the 90 degrees pulse is applied, it is shown that for constant velocity flow the even-echo phases do not vanish identically. Hence, rephasing cannot always occur for nonpluglike flow in either of these situations. Furthermore, the spin-echo phases are proportional to the flow velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Episodic reactive dysphonia: a case study.

This case study exemplifies successful diagnosis through stroboscopic fiberoptic examination, illustrates the critical importance of a careful case history, and demonstrates potential hazards of supposedly benign environmental substances for hypersensitive individuals.

Adult↗

Nuclear magnetic resonance imaging in Marfan's syndrome.

Detection and evaluation of aortic root and other cardiovascular abnormalities in patients with Marfan's 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.

Adolescent↗