Robert C. Bahn

Clinical Imaging with Transmissive Ultrasonic Computerized Tomography

Transmission ultrasound computer-assisted tomography has been developed for detection and diagnosis of cancer in the breast. Pulses of ultrasound (8 MHz ±3 MHz) are transmitted through the breast in a coronal plane from a plurality of directions. The received signal is processed for arrival time and for changes in amplitude. The measured values for arrival time and attenuation are used in a convolution-back projection reconstruction algorithm to obtain estimates of the two-dimensional distribution of acoustic speed and attenuation within the scanned planes of the breast. Over 1000 images in breasts of approximately 150 patients have been scanned of whom 30 had biopsy proven cancer. Some common characteristics of the reconstructed images which are associated with cancer are 1) increased speed relative to the embedding tissue associated with 2) decreased attenuation in central region of the lesion usually with 3) a ring of higher attenuation at the border of the lesion. Current estimates of sensitivity and specificity of this system for cancer are approaching those of X-ray mammography techniques.

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.

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.

Spontaneous Calcific Embolization Associated with Calcific Aortic Stenosis

The problem of spontaneous calcific embolization was investigated at necropsy in 165 patients with calcific aortic stenosis. Minor coronary arteries contained calcific emboli in 18 patients (11 per cent), and major coronary arteries contained calcific emboli in 10 (6 per cent). Examination of the brain, kidney, and eye also disclosed spontaneous calcific emboli. In three instances of major coronary artery embolization, there was evidence of old silent infarction but no associated clinical disorder. Calcific embolization is apparently not rare in cases of calcific aortic stenosis, but this phenomenon does not appear to lead very often to extensive infarction or to clinically obvious disorders.

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.

Role of tryptophan metabolites in the hypoglycemia associated with neoplasia

Three patients who had hypoglycemia associated with neoplasia were studied. In one, total tryptophan and protein‐free metabolites of tryptophan in blood and tryptophan metabolites in urine were increased during hypoglycemia. In another, total tryptophan and protein‐free tryptophan metabolites in serum were increased markedly and tryptophan metabolites in urine were increased mostly during hypoglycemia; during normoglycemia, however, concentration of both total tryptophan and protein‐free tryptophan metabolites in serum and of protein‐free tryptophan metabolites in urine was mostly normal. In the third, during normoglycemia, concentrations of total tryptophan and protein‐free tryptophan metabolites in serum and of protein‐free tryptophan metabolites in urine were normal or nearly so. Thus, patients with hypoglycemia associated with neoplasia seemingly have increased concentrations of tryptophan and tryptophan metabolites in serum and urine during hypoglycemic periods. Intraperitoneal administration of indole‐3‐propionic acid, indole‐3‐butyric acid, and indole‐3‐aretic acid caused profound hypoglycemia in normal and alloxandiabetic mice while L‐tryptophan and kynurenic acid had no effect.

A hypoglycemic factor in leukemic tumors.

Summary A fall in blood sugar was observed in AKR mice inoculated with leukemic tumor BW5147. Marked amelioration of diabetes resulted from inoculation of alloxanized AKR mice with lymphatic leukemic tumor. Growth of this tumor was studied in normal and diabetic mice. Rate of tumor growth and blood sugar values were correlated. Increase in mass of tumor alone did not seem to explain hypoglycemia in these mice. Consequently, 3 extracts of tumor were made and tested for presence of a hypoglycemic factor. Blood sugar values of diabetic mice were determined before and after injection of tumor extracts. A saline extract did not show a hypoglycemic effect, nor did an extract made by insulin-extraction procedure. An acetone extract, however, exhibited moderate hypoglycemic activity. Time-response curves demonstrated that acetone-extractable material derived from 1 g of fresh tumor produced a fall in blood sugar of 7% at 15 minutes, 30% at 30 minutes, 25% at 1 hour, and 7% at 2 hours.

Calcific Embolization Associated with Valvotomy for Calcific Aortic Stenosis

Calcific emboli were observed in 38 of 62 patients (61 per cent) who died at varying intervals following aortic valvotomy for calcific aortic stenosis. Major coronary embolization occurred in 10 patients (16 per cent) and was considered to be a major cause of death of four patients. Minor coronary embolization occurred in 33 patients (53 per cent) and was not directly implicated as a cause of death in any patient. Calcific emboli occurred to other organs in eight patients (13 per cent). The technics instituted for reducing the incidence of embolization—occlusion of coronary ostia, diligence in detection and removal of any debris, and final aspiration of the left ventricle—appeared to have had a favorable effect.

Emission-computed tomography and its application to imaging of acute myocardial infarction in intact dogs using Tc-99m pyrophosphate.

The techniques of emission-computed tomography have been used to obtain in vivo quantitative estimates of the three-dimensional distribution of gamma-emitting radionuclides in dog hearts. Conjugate views, obtained for 60 equiangular projections around 360 degrees by rotating the object in front of a gamma camera, were used to reconstruct multiple-level emission transaxial images for various test objects, and for dogs with surgically induced acute myocardial infarcts. Corrections for attenuation were performed in the backprojection step of the convolution algorithm used for reconstruction. Quantitative estimates of the spatial extent and concentration of activity were obtained to within 10--15% rms error. Correlations were obtained between the radionuclide and histopathologic estimates of the extent and location of infarction.

Breast Imaging by Ultrasonic Computer-Assisted Tomography

The purpose of our applying acoustic tomographic methods in the breast is directed toward the early detection of carcinoma of the breast. Our rationale is based on the principle that early detection of cancer is not only dependent upon the spatial resolution of the physical method of detection but also depends upon sensitivity for detecting changes in basic properties of tissue which can be logically related to the normal and abnormal histologic elements and spatial organization of the organ under investigation. For the breast, detection of such changes demands methods which are capable of delineating the basic elements of the normal breast such as fat, inter- and intralobar connective tissue, ducts and acinar tissue as well as the localization of common lesions of the breast such as fibrocystic disease, cysts, fibroadenomas, medullary carcinoma, and scirrhous carcinoma. Development of such capabilities of histologic and spatial tissue differentiation should allow one not only to find an established advanced lesion, but also to detect early changes in the morphology of the normal breast by detecting focal changes in the acoustic properties of normal tissue constituents which may imply the presence or the potential of development of a neoplasm.