Microvascular blood volume-to-flow relationships in porcine heart wall: whole body CT evaluation in vivo.

The goal of this study was to evaluate the functional behavior of recruitable (mostly capillary) and nonrecruitable (mostly arterioles and venules) components of the intramyocardial microvasculature in the in situ heart of intact experimental animals. For this purpose fast X-ray computerized tomography (CT) scans were performed in a group of anesthetized pigs. Each scan was performed during an aortic root angiogram and was repeated after sequential injections of a suspension of nonradioactive microspheres into a selected coronary artery. Regional myocardial perfusion (F, ml.g-1.min-1) and intramyocardial blood volume (rho, ml/g) were estimated from the dynamic CT image sequences. For the intramyocardial microcirculation, rho = AF + B square root of F [where A = 0.016 min and B = 0.076 (ml.min/g)1/2] was shown to describe the rho-to-F relationship over the entire range of flows observed. With increasing embolization with 15-microns diameter microspheres, the coefficients A and B changed in a way consistent with A describing the transit time through the functionally recruitable component and B/ square root of F describing the transit time through the functionally nonrecruitable component of the microcirculation.

Myocardial microcirculation as evaluated with CT.

This study explores use of whole-body CT imaging to separately quantitate the physiological behavior of the nonrecruitable (e.g., arterioles) and recruitable (mostly capillary) components of the intramyocardial microcirculation. In two groups of dogs, one with microembolization and one with epicardial artery stenosis, we demonstrate that intramyocardial blood volume (rho) and blood flow (F) follow the relationship rho = AF + BF1/2 where A represents the transit time of the recruitable and BF-1/2 is the transit time of the nonrecruitable components. These transit times are shown to change in different, but characteristic, patterns.

Dynamic intramyocardial blood volume: evaluation with a radiological opaque marker method.

In this study the change of intramyocardial blood volume within one cardiac cycle was deduced from the time sequence of the volume delineated by radiopaque markers attached to the left ventricular wall. These data were compared with the change in the volume of the same region of myocardium estimated from the change in angiographic opacification of the heart wall. Five dogs were anesthetized, and four pairs of 2-mm-diameter lead beads were attached to the epicardial and endocardial regions. Two scans using the dynamic spatial reconstructor (a high-speed computed tomographic scanner) were performed during aortograms, one under control conditions and the other during adenosine infusion. The results have shown that the increases of myocardial volume defined by the beads (delta Vbead, % of volume at control) were comparable to the increase of intramyocardial blood volumes estimated by the increase in wall opacity (delta Vblood, % of muscle); delta Vblood = 0.93 delta Vbead + 1.54%; r = 0.987.

Myocardial volume perfused by coronary artery branches. A three-dimensional X-ray computed tomographic evaluation in pigs.

RATIONALE AND OBJECTIVES: The authors tested the hypothesis that the cumulative length of arterial branches is related to the volume of tissue they perfuse. This experiment investigates the potential value of this approach for assessing the volume of myocardium at risk in cases of coronary occlusion. METHODS: The volume of myocardium perfused by coronary arterial branches and the cumulative length of the main feeder branches perfusing that volume were measured in vivo in pig hearts from multislice computed tomographic (CT) images of the heart, recorded during an aortic root injection of nonionic contrast agent. RESULTS: The relationship between the volume (V, in milliliters) of perfused myocardium and the length (L, in millimeters) of the left anterior descending artery was V = 42.4 x 10(-0.011L) (r = -0.892); for the right coronary artery, V = 37.0 x 10(-0.008L) (r = -0.888); and for the left circumflex coronary artery, V = 27.7 x 10(-0.011L) (r = -0.883). CONCLUSIONS: These results suggest that the maximum volume of myocardium at risk of infarction due to blockage along a coronary artery could possibly be estimated from the three-dimensional geometry of the epicardial coronary arterial tree.

Reconstructing the cross sections of coronary arteries from biplane angiograms.

An algorithm that reconstructs the cross sections of the lumens of coronary arteries from two mutually orthogonal X-ray projections is described. The algorithm accommodates the possibility of elliptical, crescent, or star shapes. It represents each biplane projection of a transverse slice of the arterial lumen as a binary-valued image. The single-coordinate moments of these two projection images are equal to those of the slice. Since the cross-coordinate moments of the slice are not available from the projections, an algorithm to estimate these moments based on assumptions of smoothness and connectivity is developed. Once all the missing moments are estimated, the image of the slice can be estimated by inverting these moments, using the uniqueness theorem governing the relation between an image and its moments. Preliminary tests of the algorithm on synthetic data, on hardware phantoms and on a segment of a barium-enhanced in vitro coronary artery are reported.

Myocardial volume perfused by coronary artery branches--a three-dimensional x-ray CT evaluation in human cadaver hearts.

The volume of myocardium perfused by coronary arterial branches and cumulative length of the main feeder branches perfusing that volume were measured from multislice computed tomography images of human cadaver hearts with barium sulfate gel injected into the coronary arteries. Previously we have shown in in vivo pig hearts that the relationship between the volume (V), in mL, of perfused myocardium and the length (L), is well conveyed by V = M x 10(-aL) where M is total mass of myocardium perfused by a major epicardial artery and a is constant congruent to 0.01 mm-1. In the nine human hearts studied, this relationship was V = 115 x 10(-0.006L), r = -0.894 for the LAD; V = 48 x 10(-0.009L), r = -0.7663 for the LCX and V = 103 x 10(-0.004L), r = -0.673 for the RCA. These results suggest that the angiographically delineated volume of myocardium at risk of infarction, due to acute blockage along a coronary artery, could possibly be estimated from the 3D branching geometry of the epicardial coronary arterial tree.

Detection of mild coronary stenoses using the Dynamic Spatial Reconstructor.

The accuracy of the Dynamic Spatial Reconstructor (DSR) in the detection of moderate coronary artery stenoses was examined in 20 closed-chest dogs. Twenty-eight hollow plastic cylinders were embolized into the left coronary arteries and produced 25% to 56% reductions in arterial lumina diameter. For each dog, one three-dimensional (3-D) image of the heart was reconstructed from each DSR scan recorded during injection of contrast into the aortic root. Analysis involved blinded visual analysis by four independent observers of multiview projection images computed from the single 3-D image. Postmortem coronary angiograms of the isolated heart were considered definitive for location of the stenoses. Overall sensitivity of detection by DSR was 89% and specificity 81%. Sensitivity of detecting stenoses greater than or equal to 50% was 98%. Receiver operating characteristics (ROC) analysis showed that detection of stenoses in the left coronary arteries is of equal sensitivity and specificity.

Measurement of ultrasonic nonlinear parameter in excised fat tissues.

This paper reports sound speed co, adiabatic acoustic nonlinear parameter B/A, and isothermal nonlinear parameter (B/A)' of 33 samples of excised human and animal fats and some simple mixtures, e.g., skim milk and powdered milk. Tissues were obtained from different parts of the body and the measurements were made in the temperature range of 20 degrees C to 37 degrees C. All the fats were highly nonlinear. Although there was a considerable overlap in the values of acoustic nonlinearity of different body fats, in general their values followed the order: mesenteric fat greater than subcutaneous fat greater than omentum fat greater than breast fat. Temperature coefficients of co and B/A, and the difference between adiabatic and isothermal nonlinearity, correlated highly with water/fat content of tissues. A reciprocal relationship between B/A and co, similar to that proposed for liquids, was observed for soft tissues but not for solutions of powdered milk in skim milk. No significant correlation was observed between acoustic measurements and the age of human subjects from which fat tissues were obtained.

Measurement and use of acoustic nonlinearity and sound speed to estimate composition of excised livers.

The acoustic nonlinearity parameter B/A and sound speed c have been determined for excised normal and abnormal human livers at 20-37 degrees C. These values are compared with analytic measurements of fat and water content of tissues. The results show that normal liver containing 71.0% water and 2.9% fat by weight has a B/A value of 6.75 and sound speed of 1592 m/s at 37 degrees C. Both these parameters increase at an average rate of 0.026 degrees C and 1.5 m/s/degrees C, respectively, as the temperature is raised from 20 to 37 degrees C. Fatty liver (24% fat by weight) exhibits highest B/A (9.12) and lowest c (1522 m/s) of all the livers studied. In contrast to normal livers sound speed in such a liver was found to decrease with temperature. Based on the acoustic and composition measurements, quantitative correlations of B/A and c with fat-water composition have been developed. Inversion of these relationships provide a simple method to determine composition of a tissue sample from B/A and c measurements.

Regional myocardial volume perfused by the coronary artery branch: estimation in vivo.

Seven closed-chest dogs were anesthetized with intramuscular Innovar and a N2O/O2 gas mixture. Maximal coronary vasodilation was induced by intra-aortic injection of nitroglycerin (200 micrograms/kg) and continuous infusion of adenosine (1 mg/kg/min) into the main pulmonary artery. Superselective coronary arteriograms were obtained at varying distances along the left circumflex and left anterior descending coronary arteries during scans using the dynamic spatial reconstructor rapid tomographic x-ray scanner. At end-diastole the images of the coronary arteries and opacified myocardium were analyzed for cross-sectional area (CSA) of the coronary artery lumen and regional myocardial volume (Vdsr) perfused by that coronary artery. Postmortem regional myocardial volume (Vpath) was related to the volume perfused by the same artery measured in vivo by the dynamic spatial reconstructor as follows: Vdsr = 4.56 + 0.93 Vpath (r = .98, p less than .001). In addition, the cross-sectional area of the coronary artery supplying a volume of myocardium was related to that volume as follows: Vdsr = - 1.95 + 6.34 CSAmax (r = .88, p less than .001). This suggests that a maximally dilated coronary artery luminal cross-sectional area is linearly related to the volume of muscle it perfuses. We speculate that this relationship may be useful in expressing the physiologic significance of coronary arterial narrowing.

Hemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor.

Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti-Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels.

A method for quantitative display of three-dimensional regional myocardial function.

The DSR (dynamic spatial reconstructor), a multiple X-ray source scanner that generates stop action three-dimensional (3-D) images of a cylindrical volume, was used for quantitative imaging of left ventricular 3-D wall geometry and function in experimentally induced canine left ventricular myocardial infarction. Impaired regional myocardial function was induced by myocardial ischemia or infarction in four mongrel dogs by closed-chest occlusion of the proximal left anterior descending (LAD) coronary artery. At intervals of 6-14 weeks post occlusion, the dogs were scanned with the DSR during biatrial contrast injection. The 3-D shape, extent, and function of hypokinetic myocardium was measured from the DSR images utilizing measurement of the rate of local systolic wall thickening to detect regions of normal, ischemic, or scarred myocardium. The results were compared to scar size and anatomic distribution measured at postmortem examination. The anatomic extent and relationship of hypocontractile to normally contracting muscle was visualized by computer generated, pseudo 3-D shaded surface displays of the left ventricular chamber and by topographic projections of regional wall thickening rates onto a map of the left ventricular endocardial surface. The location of myocardial infarction and the surrounding zone of impaired function is clearly defined by this 3-D CT scanning procedure. The display method presented here provides both localization and quantification of the volume of ischemic and infarcted myocardium.

Measurement of the acoustic nonlinearity parameter B/A in human tissues by a thermodynamic method.

A thermodynamic method for measuring the acoustic nonlinearity parameter B/A in tissues is presented. It is based on the measurement of change in phase velocity as a function of time as the hydrostatic pressure of the sample is quickly reduced from a known value. This technique circumvents the effect of the attenuation in the medium and does not require a prior knowledge of the thermodynamic parameters of the tissues. The method is used to estimate nonlinearity parameters for normal and malignant tissues in the temperature range 20 degrees to 37 degrees C. The values and the temperature dependence of these parameters are found to vary with the nature of the tissues.

Morphologic quantitation of pseudointima and effects of antiplatelet drugs on vascular prostheses in goats.

The natural process of endothelialization, pseudointimal formation, and connective tissue incorporation of the expanded PTFE grafts in the goat was documented through histologic examination of specimens harvested at 2, 4, 6, and 8 weeks. The goats demonstrated a progressive increase in pseudointimal pannus ingrowth from the anastomoses at a rate of 11.3 mm over a 12 week period. Histologic changes according to time of vascular graft incorporation in the goat model were found to be comparable to those of the dog, pig, and calf models reported in the literature. Platelet-inhibiting drugs, aspirin, dipyridamole, nifedipine, and ibuprofen were administered to goats after replacement of their infrarenal aorta with 5 cm of 8 mm diameter expanded PTFE grafts. The effects of the drugs on graft endothelialization and anastomotic pseudointimal formation was compared with those in the untreated control group after 12 weeks. Aspirin and dipyridamole had no detrimental effect on the healing process compared with the untreated control group. Studies with nifedipine and ibuprofen did not demonstrate a decrease in pseudointimal hyperplasia. Antiplatelet treatment resulted in no significant change in the rate of endothelialization of expanded PTFE grafts.

Ultrasound transmission computed tomography of the breast.

A preliminary clinical study of ultrasound transmission computed tomography of the breast (UTCTB) was undertaken to evaluate its capacity in the detection of breast abnormalities and to establish criteria for distinguishing benign from malignant lesions. Only patients with palpable and/or mammographically evident lesions were selected for study; complete analysis was accomplished in 78 cases. Visual and computer interpretations of reconstructed UTCTB scans were based on changes in speed of sound wave transmission and attenuation between the suspicious area and the surrounding tissue. In the computer-aided classification, discriminant functions were derived to predict the presence or absence of carcinoma. Visual analysis was subject to a low sensitivity. The presence of high speed transmission within a lesion usually indicated malignancy, although the converse was not true. Computer-aided preliminary screening of UTCTB scans by a trained technician may have the potential of contributing to interpretation accuracy; however, this finding must be highly qualified, given the methodologic constraints of the study.

Cytotoxicity of mononuclear cells for autologous colonic epithelial cells in colonic diseases.

Macrophage-depleted isolates of mononuclear cells from the colonic mucosas of 25 patients with chronic ulcerative colitis or Crohn's colitis were cytotoxic for autologous colonic epithelial cells, as were mononuclear cells from their peripheral blood. This was markedly reduced by trypsinizing the mononuclear cells and was restored by a 1-h exposure of the trypsinized cells to 25% vol/vol heat-inactivated autologous plasma. Trypsinization of the target cells had no effect on cytotoxicity. Mononuclear cells that adhered to plates coated with heat-aggregated immunoglobulin G contained the effectors. It was suggested that this phenomenon was a form of antibody-dependent cell-mediated cytotoxicity in which the effector cells rather than the targets were "armed" by antibody. Cytotoxicity for autologous colonic epithelial cells was also shown by colonic mononuclear cells but not by mononuclear cells from the peripheral blood in a group of 40 patients with colorectal tumors, and by 1 of 4 patients with diverticulitis. This cytotoxicity was markedly reduced by trypsinizing the colonic mononuclear cells but was not restored by exposing the trypsinized cells to autologous plasma. Colonic mononuclear cells that adhered to plates coated with heat-aggregated immunoglobulin G contained the effectors. It seems likely that this cytotoxicity was spontaneous cell-mediated cytotoxicity.

Mass of left ventricular myocardium estimated with dynamic spatial reconstructor.

Using the Dynamic Spatial Reconstructor (DSR), a unique multiple X-ray source, high-repetition-rate CAT scanner, we estimated left ventricular (LV) myocardial volume and chamber volume of eight dogs ranging from 2.5 to 32.5 kg. Dogs were given subcutaneous morphine (3 mg/kg) and anesthetized with intravenous pentobarbital sodium (22 mg/kg). A bolus of 1 ml/kg body wt contrast medium was injected into the superior vena cava and 60/s scans repeated over 7 s were performed. Each 0.0167-s scan generated image data for 120 1.8-mm-thick transverse slices, in the dextro and levo phases of the angiograms. Retrospective reformatting of the scan data was used to generate images of thin slices perpendicular to the aortoapical axis of the LV. The LV muscle and chamber volumes were estimated from their outlines in each imaged slice using a manually operated trackball interfaced to a computer. Values of the LV muscle ranged from 18.0 to 146.8 cm3 by DSR and showed a good correlation with the postmortem values (r = 0.99, y = 0.94x + 4.1). Ratios of volume of the myocardium to chamber volume ranged from 1.19 to 3.10.

Toxic shock syndrome. A fatal case with autopsy findings.

Although the clinical and laboratory features of the toxic shock syndrome have recently been further defined, the pathologic lesions attending this disorder are as yet primarily unstudied. We present the autopsy findings in a fatal case of toxic shock syndrome, which occurred in a 17-year-old girl. These observations are used as a focus for the discussion of possible pathophysiologic mechanisms operative in this disease and are contrasted with autopsy findings in several other pathologic entities that are often confused with toxic shock syndrome.