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Biomedical subjects

E A Hoffman

Publications and source records attributed to E A Hoffman.

At least 19 recordsLinked to original sources

Evaluation of congenital heart disease with MR imaging: current and coming attractions.

Nearly 10 years of experience in the use of MR imaging for the diagnosis of congenital heart disease has accumulated. Although MR imaging is superior to other techniques in showing certain structures and abnormalities such as small central pulmonary arteries in tetralogy of Fallot, aortic coarctations, and venous connections in heterotaxia syndromes, it remains an ancillary tool to echocardiography and cardiac catheterization. In this review, we examine present limitations and advantages of conventional MR in the evaluation of congenital anomalies of the heart and great vessels and explore future developments that might bring MR imaging into the diagnostic mainstream. Key improvements now in development are ultrafast MR systems for acquisition of multiple real-time MR images (in 30 msec or less) and on-line three-dimensional computer reconstruction of the heart and great vessels. Improved display and understanding of complex anatomy, as well as more extensive functional analysis of hearts before and after surgery, should be the benefits of such developments.

Adolescent

Evaluation of the upper airway in patients with obstructive sleep apnea.

Multiple methods have been used to study the structure and physiological behavior of the upper airway (UA) in patients with obstructive sleep apnea (OSA). Valuable information may be obtained from the physiologic measurement of pressure and resistance along the UA, as well as from imaging techniques that include: direct or fiberoptic visualization, cephalometric roentgenograms, fluoroscopy, acoustic reflection, computerized tomography, and magnetic resonance imaging. This review summarizes the information that each of these methods has contributed to our understanding of the UA. The results obtained with these different methodologies have generally been complementary with structural narrowing being identified in the majority of patients with OSA. This narrowing is usually focal and located in the velopharyngeal or retropalatal segment of the UA. This is also the predominant site of initial UA collapse. Although obesity with enlargement of soft tissue structures is considered the predominant mechanism leading to UA narrowing, abnormal craniofacial development on a genetic or developmental basis plays an important contributory role.

Airway Obstruction

Circumferential myocardial shortening in the normal human left ventricle. Assessment by magnetic resonance imaging using spatial modulation of magnetization.

BACKGROUND: Conventional cardiac imaging methods do not depict true segmental myocardial shortening, since they cannot determine segment length between fixed points in the myocardium. METHODS AND RESULTS: We used electrocardiographically gated magnetic resonance imaging with spatial modulation of magnetization to noninvasively "tag" the myocardium with dark stripes at uniform 7-mm intervals center to center at end diastole. We then determined end-systolic stripe separation and thereby calculated circumferential shortening. When end systole was not reached in the first image series, a second temporally overlapped series starting in late systole was used to determine late-systolic shortening. Septal, anterior, lateral, and inferior segments were assessed at endocardium, midwall, and epicardium on five midventricular short-axis sections each in 10 normal volunteers. A transmural gradient in circumferential shortening was observed, with the percentage of endocardial segment shortening consistently greater than epicardial segment shortening (epicardial, 22 +/- 5%; midwall, 30 +/- 6%; and endocardial, 44 +/- 6%; p less than 0.0001 by analysis of variance). Circumferential shortening varied from apex to base with slices closer to the base of the left ventricle showing less shortening at the midwall (28 +/- 9%) and endocardium (39 +/- 6%) than more apical slices at the midwall (34 +/- 13%) and endocardium (49 +/- 9%) (p less than 0.05 and p less than 0.01, respectively, by analysis of variance). CONCLUSIONS: Transmural and longitudinal heterogeneity of circumferential shortening is present in the normal human left ventricle. Magnetic resonance imaging with spatial modulation of magnetization is a powerful new tool for assessment of circumferential shortening and provides information unobtainable with conventional imaging methods.

Adult

Enhanced antibody response in the presence of partial adenosine deaminase inhibition.

The enzyme adenosine deaminase (ADA) catalyzes the conversion of adenosine and 2'-deoxyadenosine to inosine and 2'-deoxyinosine, respectively. In the absence of ADA activity, 2'-deoxyadenosine is phosphorylated to deoxyadenosine triphosphate. This study concerned the effects of the ADA inhibitor 2'-deoxycoformycin on the murine in vitro immune response to sheep red blood cells (Mishell-Dutton cultures). In the presence of 10(-7) M 2'-deoxycoformycin or 1 mM 2'-deoxyadenosine, there was a significant increase in the plaque-forming cell response when calculated as plaques per 10(6) viable cells recovered. Cultures containing 10(-7) M 2'-deoxycoformycin retained approximately 10% of residual ADA activity of control cultures. Partial ADA deficiency was not preferentially toxic for cells capable of suppressing plaque cell generation. However, there was a decrease of recovered viable cells in all ADA-deficient cultures. There was no change in the percentage of recovered cells which were L3T4+ or Lyt 2+. A significant decrease was observed in a population of cells expressing surface immunoglobulins. The number of plaque-forming cells/10(3) recovered B cells increased significantly. We conclude that partial ADA deficiency results in selective toxicity to a population of non-antigen-specific B cells. Further studies with antigen-specific cells are necessary to determine the possible mechanism(s) by which cellular activation may prevent susceptibility to the toxic effects of ADA deficiency.

Adenosine Deaminase Inhibitors

Geometry and kinematics of dog ribs.

Five anesthetized supine beagle dogs were scanned using a fast, multislice computed tomographic X-ray technique to determine the orientation of the ribs at total lung capacity (TLC) and functional residual capacity (FRC). A plane was fit to each rib using a coordinate system in which the z-axis was aligned approximately cephalocaudally and the x-z-plane coincided with the sagittal midplane. The orientation of each plane was described by "pump-handle" and "bucket-handle" angles. The ribs rotated downward and inward during a passive deflation of the lungs from TLC to FRC. Rib displacement was not uniform: bucket-handle motion was predominant in the upper ribs, and pump- and bucket-handle motions were equal in the lower ribs. The change in the pump-handle angles between TLC and FRC was approximately 6 degrees for ribs 3-8, and the change in the bucket-handle angles decreased with rib number from 16 degrees for rib 3 to 6 degrees for rib 8. Rib shape was described by fitting an ellipse to the data for each rib; the ribs became larger and more circular with increasing rib number.

Animals

Three-dimensional canine renovascular structure and circulation visualized in situ with the dynamic spatial reconstructor.

The dynamic spatial reconstructor--a unique, high speed, volume-scanning, X-ray computed tomographic imaging system--was utilized to examine canine renovascular anatomy and renal circulation in situ. In each of the four kidneys examined in this study initial scans were done during bolus injections of angiographic contrast material into the renal artery. A subsequent scan was then performed following an injection of methyl-methacrylate-based casting compound that had been contrast enhanced with ethiodol. After the scans, each kidney was removed, and its parenchyma was digested in potassium hydroxide to expose the vascular cast. Comparison of casts with their reconstructed images and with images obtained during injection of contrast material showed that interlobar arteries and occasionally arcuate arteries could be clearly detected. Although discrete vessels less than 1 mm in diameter could not be resolved, dynamic changes in parenchymal distribution of density during passage of contrast material allowed interpretation of flow through the multiple capillary beds of the kidney. Such analysis indicated that maximal density was in the outer-middle zone of the cortex throughout the duration of the scan. Analysis of artery-to-vein transit time showed arrival of contrast material in the renal vein as soon as 3 sec, and continuation for longer than 8 sec, after the renal artery bolus. In conclusion, renal circulation in the dog can be discretely visualized with the dynamic spatial reconstructor up to the level of the arcuate arteries; however, capillary flow as a whole can be followed through the cortex, and the results suggest the presence of both rapid and slow components of peritubular circulation.

Animals

Heart-lung interaction: effect on regional lung air content and total heart volume.

To study the interactions between and within the heart and lungs, end-diastolic (ED) and end-systolic (ES) volumes and intrathoracic location of the heart, and the regional air content, volume and geometry of the lungs, were measured from three-dimensional image data generated with the Dynamic Spatial Reconstructor (DSR). The DSR was used to scan the full thoracic extent of anesthetized dogs and sloths at selected transpulmonary pressures. The results show that the dependent to nondependent gradient of regional lung opacity (or conversely regional air content) in the supine animal was not present in the prone animals. While the rib cage and diaphragm of the dog deformed markedly, the shape of the sloth's rib cage and diaphragm remained essentially constant with change in body orientation. As a consequence of these findings, we deduce that the observed change in gradient of regional lung air content in both dog and sloth are in response to changes in the intrathoracic position of the heart which alter ventral lung geometry and not a response to changes in rib cage or diaphragm geometry. In a second series of studies we reconstructed the 3-D extent of the heart at ED and ES in supine anesthetized dogs and demonstrated that the total heart volume (THV) (i.e. contained by the pericardial sac) during sinus rhythm differs by less than 5% between ED and ES. The DSR image data show that this is achieved by the epicardial apex remaining essentially fixed and that the plane containing the atrio-ventricular valves moves like a plunger towards the apex in systole. When atrial fibrillation is present, the THV no longer remains constant and decreases during systole, presumably because of increased stiffness of the atrial myocardium. We conclude from the experimental results that the heart plays an important role in determining regional differences in alveolar expansion, and that by maintaining a constant THV, the heart minimizes energy expenditure which would be caused by moving the lung.

Animals

Measurement of three-dimensional anatomy and function of pulmonary arteries with high-speed x-ray computed tomography.

Pulmonary arterial geometry was quantitatively evaluated in five dogs. One was a control dog, two were subjected to monocrotaline administration, and two had a subclavian-to-pulmonary artery shunt. Measurements of pulmonary arterial anatomy were made with the dynamic spatial reconstructor (DSR), a high-temporal-resolution, volumetric, roentgenographic, computed tomographic scanner. In the control dog, pulmonary arterial cross-sectional areas and segment lengths were measured both from images generated from DSR scans obtained during injection of contrast medium and from a methylmethacrylate cast of the same vascular tree. The correlations between the DSR and cast-based measurements of cross-sectional area and segment lengths were 0.98 and 0.97, respectively. Over periods of eight and 11 months' observation, the pulmonary arterial pressure in the two dogs with surgically created left-to-right shunts increased from 29/15 to 42/17 mm Hg and 19/12 to 25/16 mm Hg, respectively. The cross-sectional areas increased progressively in the proximal portion of the main lobar arteries, remained unchanged in the midportion, and decreased in the distal portion of these arteries. Similar changes occurred in one of the two dogs treated with monocrotaline injections, while in the other the taper of the distal vessels did not change significantly. Pulmonary vascular resistance, computed from cardiac output and pulmonary artery pressure, increased proportionately to the decrease of the cross-sectional areas of distal vessel in both the monocrotaline administration dogs; the resistance decreased proportionately to the increase of the pulmonary arterial cross-sectional areas in both of the surgical dogs.

Animals

Quantification of thoracic volumes by three-dimensional imaging.

End-expiratory thoracic cavity volume (Vthx) was measured in eight volunteers lying supine by three-dimensional X-ray computed tomography using the Dynamic Spatial Reconstructor. Untrapped end-expiratory pulmonary gas volume at functional residual capacity (FRC) was determined by nitrogen clearance. Both measurements were done before and after induction of anesthesia-paralysis. After induction of anesthesia-paralysis, Vthx and FRC were consistently and significantly (P less than 0.01) reduced by 0.28 +/- 0.22 (SD) and 0.59 +/- 0.24 liter, respectively. The reduction of FRC was larger than the reduction of Vthx (delta Vthx) in six of the eight subjects, a finding suggesting that intrathoracic fluid (blood) plus trapped gas volume (Vtt) increased. Changes in Vthx were partitioned into volume changes from the thoracic rib cage (delta Vrc) and from shape and/or position changes of the diaphragm (delta Vdi). delta Vrc contributed significantly (0.17 +/- 0.15 liter, P less than 0.02) to delta Vthx, whereas delta Vdi contributed only in four of the eight subjects. We conclude that delta Vrc, delta Vdi, and delta Vtt contribute to the reduction of FRC after induction of anesthesia-paralysis in humans; the relative contribution of them varies among subjects.

Adult

Geometry and respiratory displacement of human ribs.

The three-dimensional coordinates of points in the ribs of two supine relaxed males, holding their breath at functional residual capacity (FRC) and with their glottis closed at total lung capacity (TLC), were obtained from volumetric X-ray computed tomographical images. The orientation of planes that best fit the data for each rib at each lung volume and the circular arcs that fit the points in the planes of the ribs were determined, and average values of these geometrical parameters for ribs 3-7 are reported. The planes of the ribs at TLC can be described as displaced from the planes at FRC by a rotation about an axis that passes near the spine. The pump handle and bucket handle components of rotation are 11 and 13 degrees, respectively, for rib 3 and both decrease with increasing rib number to 7 and 10 degrees at rib 7. The angles between the axes of rotation and the midplane are approximately 35 degrees for all 5 ribs. The radii of the circular arcs fit to the data at TLC are slightly larger than those at FRC, and this suggests that there is a small component of rotation normal to the plane of the rib.

Adult

Accuracy of pulmonary vascular dimensions estimated with the dynamic spatial reconstructor.

Measurements of pulmonary artery conduit dimensions were obtained in two children after first-stage right ventricular outflow tract reconstruction for congenital pulmonary atresia. These conduits provide an opportunity for evaluation of measurement accuracy of intrathoracic vascular structures that is not possible with the same objectivity in the native vascular tree. Patients were scanned in the dynamic spatial reconstructor (DSR), a high-speed CT scanner, during injection (0.7-1.2 ml/kg) of contrast agent into the pulmonary artery conduit. As the DSR is a volume imaging system, all angles of view are always available from one angiogram, and it can provide images of oblique planes through the structure of interest. In the patient with the 12-mm diameter conduit (113 mm2 area), the cross-sectional area of DSR measurement was 115 +/- 5 mm2 (mean value +/- SD), the roll film value was 84 +/- 6 mm2, and the cineangiogram value was 97 +/- 3 mm2. In the patient with the 8-mm diameter conduit (50 mm2 area), the cross-sectional area of DSR measurement was 47 +/- 5 mm2, the roll film value was 36 +/- 3 mm2, and the cine film value was 35 +/- 4 mm2. The DSR scan (8 s) involved 0.63-0.95 R/s exposure at the sternum, whereas the biplane cineangiogram (3-5 s) involved 0.8 R/s. Based on these data, we conclude that a single DSR scan provides accurate measurements of pulmonary anatomy and vessel dimensions.

Child

Three-dimensional cardiac anatomy and function in heart disease in adults: initial results with the dynamic spatial reconstructor.

The dynamic spatial reconstructor, or DSR, is a unique high-speed volume-imaging x-ray scanner based on computed tomographic principles. In this report, we present data obtained from the first feasibility DSR studies of adult patients with heart disease. Information from three patients--one with hypertrophic obstructive cardiomyopathy, one with calcific aortic valvular disease, and one with a left ventricular aneurysm--is described in detail. The mean DSR scanning time for each patient was 20 seconds, and the mean total irradiation to the sternum was 15.3 R. Transverse cross sections were reconstructed and then retrospectively reformatted to provide operator-selected oblique sections in space (for example, long-axis and short-axis sections of the left ventricle), to follow these sections through time (such as from end-diastole through end-systole), and to create three-dimensional displays (for instance, of the left ventricular chamber). Unique quantitative measurements of structure and function were made by using these images. For generation of most imaging data, only one injection of contrast material into the right side of the heart is necessary. Clinically useful three-dimensional dynamic imaging data can be acquired from adult patients with heart disease by using the DSR. Compared with conventional angiocardiography, DSR studies can provide information with less x-ray exposure and fewer angiographic injections.

Adult

Anatomy and function of the heart and intrathoracic vessels in congenital heart disease: evaluation with the Dynamic Spatial Reconstructor.

The Dynamic Spatial Reconstructor is a unique high speed volume imaging X-ray scanner based on computed tomographic principles. It has several potential advantages over conventional angiographic methods, including reduced invasion, reduced rate of false negative results and increased accuracy of measurements of structure and function. To evaluate the utility of the Dynamic Spatial Reconstructor in the investigation of congenital heart disease, scanning was performed in several pediatric patients with pulmonary valve atresia. Early results show that three-dimensional images of the cardiac chambers and intrathoracic vessels can be acquired and displayed with the system. All the information necessary for quantitative analysis of the pulmonary arteries can be obtained with a single scan involving injection of 0.6 to 2.0 cc/kg of contrast agent and radiation exposure of 0.54 to 0.95 rad/s over 5 to 8 seconds.

Angiography

Shape and dimensions of cardiac chambers: importance of CT section thickness and orientation.

Three-dimensional (3D) computed tomography (CT) scan data were used to quantitate the geometry of all heart chambers. The Dynamic Spatial Reconstructor (DSR) was used to scan dogs with in situ casts of the cardiac chambers. Chamber volumes estimated from DSR images were accurate within 5% of water displacement volume measurements of the actual casts for chambers greater than 11 ml and within 10% of water displacement volumes for chambers less than 11 ml. Anatomic features of the actual cast correlated closely with anatomy visible in computer-generated surface images of the 3D DSR image data. The important effect of reconstructed section thickness and orientation on the fidelity of 3D cardiac geometry is demonstrated.

Animals

Invariant total heart volume in the intact thorax.

Fast multisliced computerized tomography (Dynamic Spatial Reconstructor or DSR) was used to study the change in total heart volume (content of the pericardial sac) between end diastole (ED) and end systole (ES) with lungs held at 0 and 15 cmH2O airway inflation pressure (Paw). Nine dogs were anesthetized and scanned in the DSR. At 0 cmH2O airway pressure, mean total heart volume changed, on the average, only 2.7 +/- 0.6% (SE) of its ED volume comparing ED with ES. With lungs inflated to 15 cmH2O Paw, total heart volume decreased 12 +/- 0.5%. However, at this new heart volume, the change in total heart volume between ED and ES was only 1.7 +/- 0.5%. The data indicate that the epicardial apex of the heart remains relatively stationary while the atrioventricular groove moves toward the apex during systole and away from the apex during diastole. Thus the atria and ventricles empty and fill reciprocally even when the pericardial contents do not fully distend the pericardial sac. The invariant total heart volume observed in these species would minimize the work of the heart by maximizing the percentage of work expended to move blood and minimizing the work expended to move tissue (i.e., lung).

Animals

Cardiogenic motion of right lung parenchyma in anesthetized intact dogs.

Cardiogenic motion of the right lung parenchyma (CGLM) was measured in six morphine-pentobarbital-anesthetized dogs (11-16 kg) under conditions of varying paced and spontaneous sinus heart rates. Motion of 1-mm-diameter percutaneously implanted radiopaque lung parenchymal markers were measured using a computer-based biplane video-roentgenographic assembly. Correlation of the amplitudes and phases of marker motions to the R wave of the electrocardiogram (ECG) were determined utilizing a modified fast Fourier transform algorithm. Of initial importance was the observation that CGLM was significantly greater than the variability of repeated measurements. The total amplitudes of motion of the markers (where AT = square root A2X + A2Y + A2Z and AX, AY, AZ are the amplitudes of marker motion along the orthogonal X, Y, and Z body axes) in the right apical, cardiac, and diaphragmatic lobes were 0.025 +/- 0.005 (SE), 0.046 +/- 0.005, and 0.023 +/- 0.025 cm, respectively, (P less than 0.01, cardiac lobe vs. others). The total amplitude of motion observed in the cardiac lobe was equivalent to earlier observations of total amplitude (0.045 +/- 0.004 cm) of marker motion in response to high frequency airway oscillation at a pump stroke volume of 22-26 ml. An analysis of the higher harmonics of marker oscillation suggested that the second harmonic of CGLM is also larger than the variability of our measurements.

Anesthesia, Intravenous

Effect of body orientation on regional lung expansion: a computed tomographic approach.

The Dynamic Spatial Reconstructor (DSR) was used to study in vivo lung geometry and function. By replacing the lungs of three dogs with potato flakes and ping-pong balls of known air content and scanning these realistic phantoms in the DSR we have estimated accuracy of lung density to be within 7% and have demonstrated a high (+/- 3%) internal consistency (relative density within dogs). Change in total lung air content (y) as calculated from DSR volume imaging of anesthetized dogs matched the known inflation steps (x) to within 7% [range was 1-7% with a mean of 3 +/- 0.5% (SE)]. A gradient of decreasing percent lung air content was measured in the ventral-dorsal direction at functional residual capacity (FRC) in the supine body posture (y = 3.29% air content/cm lung height + 46.48% air content; r = 0.90). Regional lung air content change with lung inflation was greatest in the dependent lung regions. In contrast, regional lung air content at FRC was approximately uniform along the ventral-dorsal direction with the dog in the prone posture and was 66 +/- 0.6% (SE). Ventral-dorsal gradients in lung air content measured within an isogravimetric plane of the dogs in the left or right lateral body posture suggest that regional differences in lung air content cannot be explained solely on the basis of a direct gravitational effect on the lung. Evidence is presented to suggest a possible major role of the intrathoracic position of the mediastinal contents in determining these lung air content distributions.

Animals