Biomedical subjects

E L Ritman

Publications and source records attributed to E L Ritman.

At least 37 records · Page 2Linked to original sources

PubMed2000

Restoration of bone mass in the severely osteopenic senescent rat.

Studies in humans and rats suggest that age impairs the ability to form bone. This impairment may be due to a depletion or deficit in osteoprogenitor stem cells. Such a deficit would be expected to reduce the ability of the skeleton to respond to therapy designed to restore lost bone. This study evaluated whether severely osteopenic senescent rats are capable of responding to a potent anabolic factor in bone, prostaglandin E2 (PGE). Growing female Sprague Dawley rats were ovariectomized at 3 months and aged until the start of treatment at 23 months. Rats were treated daily with PGE (3 mg/kg sc) or vehicle for 56 days. Tibiae were harvested for bone histomorphometry and femora were obtained for mRNA analysis of bone matrix proteins. The cancellous bone area was fivefold greater in PGE-treated rats than in vehicle-treated controls and not different from age-matched ovary-intact rats. PGE approximately doubled the bone-forming surface and the mineral apposition rate and increased the bone formation rate fourfold. The increased cancellous bone area in PGE-treated rats was primarily due to an increase in osteoblasts over osteoclasts. One hundred percent of the endocortical surface and 72 +/- 9% of the periosteal surface of cortical bone was undergoing mineralization in PGE-treated rats, whereas no mineratization was evident in vehicle-treated rats. An architectural analysis of cancellous bone indicates that trabecular number and thickness were increased and separation decreased in the treated rats. Imaging by microcomputed tomography further revealed that with PGE treatment, trabeculae in the medial plane of the proximal tibial metaphysis were more robust and continuous with the endocortical surface. PGE also significantly induced message levels for the prepro-alpha (I) subunit of type I collagen (collagen), osteonectin, and osteocalcin. In summary, bone mass can be restored to severely osteopenic senescent rats, suggesting that aging does not necessarily diminish the capacity of the skeleton to form bone.

Aging↗

PubMed2000

Extraction of the hepatic vasculature in rats using 3-D micro-CT images.

High-resolution micro-computed tomography (CT) scanners now exist for imaging small animals. In particular, such a scanner can generate very large three-dimensional (3-D) digital images of the rat's hepatic vasculature. These images provide data on the overall structure and function of such complex vascular trees. Unfortunately, human operators have extreme difficulty in extracting the extensive vasculature contained in the images. Also, no suitable tree representation exists that permits straight-forward structural analysis and information retrieval. This work proposes an automatic procedure for extracting and representing such a vascular tree. The procedure is both computation and memory efficient and runs on current PCs. As the results demonstrate, the procedure faithfully follows human-defined measurements and provides far more information than can be defined interactively.

Angiography↗

PubMed2000

Microcomputed tomography of kidneys following chronic bile duct ligation.

BACKGROUND: In hepatic cirrhosis, renal sodium and water retention can occur prior to decreases in renal blood flow (RBF). This may be explained in part by redistribution of the intrarenal microcirculation toward the juxtamedullary nephrons. To appreciate this three-dimensional spatial redistribution better, we examined the intrarenal microcirculatory changes using microcomputed tomography (micro-CT) in rats subjected to chronic bile duct ligation (CBDL). METHODS: Six kidneys from control rats and eight kidneys from rats that had undergone CBDL for 21 days were perfusion fixed in situ at physiological pressure, perfused with silicon-based Microfil containing lead chromate, embedded in plastic, and scanned by micro-CT. The microvasculature in the reconstructed three-dimensional renal images was studied using computerized image-analysis techniques. To determine the physiological condition of the rats, parallel experiments were conducted on six control and six CBDL rats to measure mean arterial pressure (MAP), RBF, glomerular filtration rate (GFR), urine flow (UF) rate, and sodium excretion by conventional methods. RESULTS: The percentage of vasculature in the renal cortex from CBDL rats was significantly decreased (10.8 +/- 0.4% vs. 16.8 +/- 2.7% control values). However, the vascular volume fractions of the medullary tissues were not significantly altered. There were no significant differences in the number of glomeruli between groups (36,430 +/- 1908 CBDLs, 36,609 +/- 3167 controls). The CBDL rats had a similar GFR than the controls but a reduced MAP, RBF, UF, and sodium excretion. CONCLUSIONS: The results indicate that after CBDL, there is a selective decrease in cortical vascular filling, which may contribute to the salt and water retention that accompanies cirrhosis.

Animals↗

PubMed2000

Imaging Angiogenesis with Three-Dimensional Microscopic Computed Tomography.

An increasing number of patients with advanced coronary artery disease remain symptomatic, despite maximal interventional or medical treatment. A high demand exists for alternative anti-anginal therapies and ways to improve survival. One of the most intriguing new approaches to increase blood flow to ischemic myocardium is therapeutic angiogenesis, the induction of new vessel growth. Current methods involve local angiogenic growth factor administration, transfection of genes expressing angiogenic proteins, or direct myocardial revascularization. These new therapeutics are undergoing intensive basic and clinical investigation.

Journal Article↗

PubMed1999

Contrast-enhanced 3D MR breathhold imaging of porcine coronary arteries using fluoroscopic localization and bolus triggering.

The purpose of this study was to develop cardiac-gated contrast-enhanced 3D MRA for imaging the coronary arteries of pigs. Each major coronary artery was imaged individually in a single 3D slab in one breathhold. To permit acquisition within a breathhold, a limited number of partitions (12-16) were collected in a single, oblique, thin 3D slab. Typical resolution of the acquisition was 0.8 (X) x 1.6 (Y) x 1.6 (Z) mm. MR fluoroscopic localization was used to establish the 3D double-oblique orientation. Real-time MR fluoroscopy was also used to instantaneously trigger the 3D scan after detection in the aortic root of the intravenously administered contrast bolus. Six pigs were used in the study. Each pig was scanned on two separate days. Images routinely show the majority of the length of the three principal coronary arteries. Magn Reson Med 42:1159-1165, 1999.

Animals↗

PubMed1999

Evaluation of microvascular anatomy by micro-CT.

Observations indicate that adventitial vasa vasorum may play a role in the development and/or the progression of coronary atherosclerosis. There is a lack of information regarding the spatial three-dimensional pattern of the vasa vasorum in the coronary artery. This is due to the technical difficulties in visualizing the course of this fine vascular network with histologic methods. Microscopic computed tomography (micro-CT) is a novel technique that allows three-dimensional views of the entire microvascular structure. The current review summarizes our current advances in using this technique in visualization of the coronary circulation.

Animals↗

PubMed1999

Percutaneous transmyocardial revascularization induces angiogenesis: a histologic and 3-dimensional micro computed tomography study.

The purpose of this study was to visualize the spatial patterns and connection of channels created after percutaneous transmyocardial revascularization (PTMR) in normal porcine hearts, and to estimate the relative contributions of transmyocardial and coronary perfusion. Six pigs underwent PTMR creating channels using radiofrequency ablative energy. Three-dimensional computed tomography imaging of channels 1 hr after PTMR showed the direct connection of PTMR channels to the myocardial capillary network and to epicardial coronary vessels. In the heart, examined 28 day after PTMR, there was a fine, extensive, network of microvessels originating from the site of the original PTMR channel, also connecting the left ventricular cavity to myocardial capillaries. Histopathologic examination of the 1-hr specimens showed numerous regions of myocardial hemorrhage and associated inflammatory cell infiltration. In the 28-day specimens, newly developed new vascular network suggested neovascularization within the core of these channel remnants. The immunoreactivity for basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were intense within myocardium and neovascular structure surrounding PTMR channel remnants. The vascular connections occur by direct communication with existing myocardial vasculature acutely, and angiogenesis in these channel remnant chronically.

Animals↗

PubMed1999

Cardiac production of angiotensin II and its pharmacologic inhibition: effects on the coronary circulation.

Angiotensin II (AII), produced systemically as well as locally in the heart, affects the coronary circulation, as do consequences of its pharmacologic inhibition. AII is a powerful vasoconstrictor directly acting on vascular smooth muscle cells, modulating sympathetic innervation and calcium ion influx, and releasing other vasoconstrictor factors. In addition to these immediate actions, AII has longer-term biologic actions that influence cardiac endothelial function, vascular smooth muscle cell phenotype expression, and fibroblast proliferation. Moreover, the production of AII is interrelated with the vasodilator substances bradykinin, nitric oxide, and prostaglandins E2 and I2 (prostacyclin). Circulating hormonal actions of AII include fluid retention, direct vasoconstriction, and sympathetic neuromodulation, all resulting in increased left ventricular preload and afterload. Because of these local and hormonal characteristics, AII can immediately affect the myocardial balance of metabolic demand and supply and long term can induce structural vascular and myocardial alterations. Pharmacologic inhibition of AII production likely conveys myocardial and vascular protection in situations of acute myocardial oxygen debt. In the long term, inhibition of AII may attenuate structural changes in the coronary microcirculation related to various cardiomyopathies or acute tissue injury, and direct antiatherogenic effects may also occur.

Angiotensin II↗

PubMed1998

Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia.

Coronary arteries contain a network of vasa vasorum in the adventitia. The three-dimensional anatomy of the vasa vasorum in early coronary atherosclerosis is unknown. This study was designed to visualize and quantitate the three-dimensional spatial pattern of vasa vasorum in normal and experimental hypercholesterolemic porcine coronary arteries, using a novel computed tomography technique. Animals were killed after being fed either a high cholesterol diet (n = 4) or a control diet (n = 4) for 12 wk. The proximal left anterior descending coronary artery was removed from the heart, scanned, and reconstructed, and quantitation of vasa vasorum density was performed. Two different types of vasa vasorum were defined: first-order vasa vasorum ran longitudinally parallel to the vessel and second-order originated from first-order vasa circumferentially around the vessel wall. Compared with controls in hypercholesterolemic coronary arteries, there was a significant increase in the area of the vessel wall (3.86+/-0.22 vs. 8.07+/-0.45 mm2, respectively, P < 0.01) and in the density of vasa vasorum (1. 84+/-0.05/mm2 vs. 4.73+/-0.24/mm2; respectively, P = 0.0001). This occurred especially by an increase of second-order vasa vasorum and disorientation of normal vasa vasorum spatial pattern. This study suggests that adventitial neovascularization of vasa vasorum occurs in experimental hypercholesterolemic coronary arteries and may be a part of the early atherosclerotic remodeling process.

Animals↗

PubMed1998

Anatomy of the human biliary system studied by quantitative computer-aided three-dimensional imaging techniques.

The branching geometry of the normal, cholangiographically identifiable human biliary tree was studied with an innovative computer-aided three-dimensional (3D) imaging technique. In addition, a serially sectioned conventional paraffin block from a normal donor liver was used to create and quantitatively study a microscopic 3D image. Finally, a geometric model was developed to estimate the enlargement of biliary surfaces imparted by microvilli. The images created by these techniques could be viewed in stationary modes or rotating around any preselected axis. Approximately 7 (+/-3) intrahepatic duct orders were cholangiographically identified. Computerized measurements of the images from three normal livers suggested that the mean total volume of duct orders 1 to 7 shown in the cholangiograms was 16.6 cm3. The volume of the entire macroscopic duct system was estimated to be between 14 and 24 cm3 (mean, 20.4 cm3), with an internal surface of 336 to 575 cm2 (mean, 398 cm2). A geometric model based on electron micrographs suggested that this surface is magnified approximately 5.5-fold by the presence of microvilli. Volume and surface area (SA) measurements of all ducts in the same orders increased nearly exponentially from the first toward the seventh branching order (i.e., from the hilus toward the periphery of the liver), and probably beyond. The microscopic computerized reconstruction of a septal bile duct with its tributaries also allowed volume measurements; the imaged duct system represented 2.7% of the portal tract volume. The data presented herein may help to better evaluate branching patterns of the biliary tree and, eventually, the quantitative aspects of site-restricted cholangiocyte function and their role in the development of biliary diseases.

Biliary Tract↗

PubMed1998

Comparative characterization of the infarcted and reperfused ventricular wall muscles by finite element analysis and a myocardial muscle-blood composite model.

Two methods of characterizing the myocardial fiber bundles' property in the left ventricular wall are reviewed: (1) a myocardial muscle-blood composite model which assumes the myocardial muscle bundles to be incompressible but allows the intramural blood volume fraction to be taken into account, and (2) a two-dimensional finite element method for inverse determination of the myocardial Young's modulus during diastole by matching the computed and tomographically imaged cross-sectional areas near the mid-ventricular, short axis of the left ventricle at the end of diastole. The first method requires the measurements of ventricular wall thickness and the intramural blood volume fraction while the second method requires the image cross-sectional shapes and the corresponding left ventricular chamber pressures. This paper gives greater details of these two methods than in the previously presented progress reports and also presents a scheme for comparative characterization of the myocardial properties for an initial coronary artery occlusion and subsequent reperfusion study of the recently infarcted, left-ventricular wall regions. Furthermore, an attempt is made to correlate the data computed by the two methods. This may eventually lead to a reduction in the number of the required measurements needed for the two methods.

Animals↗

PubMed1998

Adventitial vasa vasorum in balloon-injured coronary arteries: visualization and quantitation by a microscopic three-dimensional computed tomography technique.

OBJECTIVES: The objective of this study was to examine the quantitative response of the adventitial vasa vasorum to balloon-induced coronary injury. BACKGROUND: Recent attention has focused on the role of vasa vasorum in atherosclerotic and restenotic coronary artery disease. However, the three-dimensional anatomy of these complex vessels is largely unknown, especially after angioplasty injury. The purpose of this study was to visualize and quantitate three-dimensional spatial patterns of vasa vasorum in normal and balloon injured porcine coronary arteries. We also studied the spatial growth of vasa vasorum in regions of neointimal formation. A novel imaging technique, microscopic computed tomography, was used for these studies. METHODS: Four pigs were killed 28 d after coronary balloon injury, and four pigs with uninjured coronary arteries served as normal controls. The coronary arteries were injected with a low-viscosity, radiopaque liquid polymer compound. Normal and injured coronary segments were scanned using a microscopic computed tomography technique. Three-dimensional reconstructed maximum intensity projection and voxel gradient shading images were displayed at different angles and voxel threshold values, using image analysis software. For quantitation, seven to 10 cross-sectional images (40 normal and 32 balloon injured cross-sections) were captured from each specimen at a voxel size of 21 microm. RESULTS: Normal vasa vasorum originated from the coronary artery lumen, principally at large branch points. Two different types of vasa were found and classified as first-order or second-order according to location and direction. In balloon-injured coronary arteries, adventitial vasa vasorum density was increased (3.16+/-0.17/mm2 vs. 1.90+/-0.06/mm2, p = 0.0001; respectively), suggesting neovascularization by 28 d after vessel injury. Also, in these injured arteries, the vasa spatial distribution was disrupted compared with normal vessels, with proportionally more second-order vasa vasorum. The diameters of first-order and second-order vasa were smaller in normal compared with balloon-treated coronary arteries (p = 0.012 first-order; p < 0.001, second-order; respectively). The density of newly formed vasa vasorum was proportional to vessel stenosis (r = 0.81, p = 0.0001). Although the total number of vasa was increased after injury, the total vascular area comprised of vasa was significantly reduced in injured vessels compared with normals (3.83+/-0.20% to 5.42+/-0.56%, p = 0.0185). CONCLUSIONS: Adventitial neovascularization occurs after balloon injury. The number of new vessels is proportional to vessel stenosis. These findings may hold substantial implications for the therapy of vascular disease and restenosis.

Angioplasty, Balloon, Coronary↗

PubMed1998

The effect of nitrous oxide on chest wall function in humans and dogs.

UNLABELLED: The purpose of this study was to determine the effects of nitrous oxide (N2O) on the chest wall of anesthetized humans and dogs. Six human subjects and six mongrel dogs were studied during 1 minimum alveolar anesthetic concentration halothane anesthesia before and during the substitution of 70% N2O for 70% N2 in the inspired gas mixture. On a separate occasion, measurements also were made in pentobarbital-anesthetized dogs. Respiratory muscle activity was measured using electromyographic (EMG) electrodes. Chest wall configuration was determined by using fast three-dimensional computed tomography in dogs and by using respiratory impedance plethysmography in humans. N2O consistently decreased inspiratory ribcage displacement, a decrease attributable in dogs to decreased inspiratory activation of parasternal intercostal muscles; parasternal intercostal activity was not present in anesthetized humans. The decrease in ribcage motion decreased the tidal volume in humans, but not in dogs, because displacement of the diaphragm was better preserved in dogs, in association with changes in diaphragm EMG activation. N2O significantly increased phasic expiratory muscle activity in halothane-anesthetized humans and pentobarbital-anesthetized dogs. Thus, as has been demonstrated for other anesthetics, the actions of N2O are caused by alterations in the distribution and timing of neural drive to the respiratory muscles, rather than by a global depression of respiratory motoneuron drive. IMPLICATIONS: In this study, we examined the effects of nitrous oxide on breathing in halothane-anesthetized dogs and humans. Nitrous oxide affected breathing by changing the distribution and timing of neural drive to the respiratory muscles in a species-dependent manner, rather than by causing a global depression of their activity.

Animals↗

PubMed1998

Three-dimensional imaging of vasculature and parenchyma in intact rodent organs with X-ray micro-CT.

A microcomputed tomography (micro-CT) scanner, which generates three-dimensional (3-D) images consisting of up to a billion cubic voxels, each 5-25 micron on a side, and which has isotropic spatial resolution, is described. Its main components are a spectroscopic X-ray source that produces selectable primary emission peaks at approximately 9, 18, or 25 keV and a fluorescing thin crystal plate that is imaged (at selectable magnification) with a lens onto a 2.5 x 2.5-cm, 1,024 x 1,024-pixel, charge-coupled device (CCD) detector array. The specimen is positioned close to the crystal and is rotated in 721 equiangular steps around 360 degrees between each X-ray exposure and its CCD recording. Tomographic reconstruction algorithms, applied to these recorded images, are used to generate 3-D images of the specimen. The system is used to scan isolated, intact, fixed rodent organs (e.g., heart or kidney) with the image contrast of vessel lumens enhanced with contrast medium. 3-D image display and analysis are used to address physiological questions about the internal structure-to-function relationships of the organs.

Animals↗

PubMed1998

Three-dimensional microcomputed tomography of renal vasculature in rats.

Current microscopic methods to view renal microvasculature reveal only a very limited portion of the total renal volume. Identification of connectivity for postglomerular vessels in the cortex and the medulla during functional states related to changes in sodium excretion will help better to understand the coupling of renal vasculature to tubular function. The purpose of this study was to investigate the possibility of visualizing the continuity of pre- and postglomerular vasculature using three-dimensional micro-computed tomography (micro-CT). Kidneys from normal rats were perfusion fixed in situ at physiological pressure, filled with latex microfil containing lead chromate, and embedded in plastic. The micro-CT scans of the intact kidneys were carried out on a rotating stage illuminated either by a synchrotron x-ray source or a conventional x-ray spectroscopy tube. Images were reconstructed by a filtered backprojection algorithm and volume-rendering techniques were utilized to display the vasculature. The reconstructed images clearly showed the large distribution vessels and the venous drainage of the kidneys, while pre- and postglomerular vessels and their vascular connections throughout the kidney were displayed in great detail. Efferent arterioles showed the characteristics of their peritubular capillary beds in the cortical and medullary regions. The vascular volume of the cortex was 27%, the outer stripe of the outer medulla 18%, the inner stripe of the outer medulla 30%, and the inner medulla 18%. In conclusion, micro-CT is a promising method to evaluate renal vascular architecture relative to physiological and pathological alterations.

Algorithms↗

PubMed1998

Micro-CT imaging of structure-to-function relationship of bone microstructure and associated vascular involvement.

We are exploring methods of quantitating the 3D microstructure of bone in a way that will provide quantitative information about the functional status of the bone. The basic strategy is to image the spatial distribution of a selected, local, marker of function (e.g., material properties or new bone formation) and relate this to the simultaneously imaged 3D anatomic microstructure. Many of these approaches are extensions of well-established 2D imaging techniques (e.g., use of fluorophores and autoradiography) to 3D micro-CT. Local stresses throughout the microstructure can be estimated from the 3D geometry (and change in that geometry in response to stress applied to the outside of the bones) and correlated to the local function. In addition to study of bone, we are also exploring calcification of arterial walls, both within the bone and outside the bone, such as coronary arteries. Arterial calcification in ovariectomised rats has been observed.

Animals↗

PubMed1997

Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain.

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

Animals↗

PubMed1997

3D architecture of myocardial microcirculation in intact rat heart: a study with micro-CT.

The branching geometry of the coronary arterial tree may play a significant role in the observed spatial heterogeneity in myocardial perfusion. To provide more insight into this possibility we used a micro-CT scanner to image the intact rat heart and its opacified coronary arterial tree, for quantitative analysis of the coronary arterial architecture. Results show a consistent pattern of branching throughout the heart wall.

Animals↗