Frederick J. Bonte

Use of Biplane Cinefluorography for Measurement of Ventricular Volume

A biplane cinefluorographic technic for measuring ventricular volume is described and its accuracy and limitations are assessed. Although rather complicated and time-consuming at present, the method permits construction of volume curves and estimation of stroke volume of the left ventricle for several successive contractions in the intact animal or man. This method may prove most useful for physiologic research and ultimately for diagnostic purposes.

A New Method for Radionuclide Imaging of Acute Myocardial Infarction in Humans

A new method of visualizing acute myocardial infarction in humans following intravenous injection of 15 mCi-5 mg of 99mTc stannous pyrophosphate in 23 patients is reported. Fifteen patients had histories suggestive of acute myocardial infarction and subsequently developed electrocardiogram and enzyme changes that confirmed the clinical diagnosis. Eleven of the 15 patients were scanned 3-5 days postinfarction, and all had positive scintigrams. The four remaining patients were scanned 7-10 days after their myocardial infarction; two had positive scintigrams. In those 8 patients with chest pain but without ECG and enzyme changes suggestive of myocardial infarction, scintigrams were negative. Positive scintigrams in the patients with myocardial infarction are thought to be due to incorporation of pyrophosphate into the crystalline structure of the hydroxyapatite found within the mitochondria of irreversibly damaged myocardial cells. The location of the acute myocardial infarction by scintigram correlated well with ECG localization in the 13 patients with positive scintigrams. This imaging method shows promise in 1) identifying the presence of acute myocardial infarction in patients with chest pain, 2) determining the location of acute myocardial infarction with a high degree of accuracy, 3) detecting the extension of the infarction, and 4) the possibility of determining the size of acute myocardial infarctions.

A new method for radionuclide imaging of myocardial infarcts.

Lesions such as ischemia, which result in myocardial cell death, are accompanied by cellular influx of calcium ions which localize within the mitochondria in the crystalline structure hydroxy-apatite. Using 99mTc-stannous pyrophosphate, an agent which labels hydoxyapatite for bone scanning, the authors have produced scintillation camera images of experimental myocardial infarcts in dogs. Tracer localization disappears with time, suggesting application of this method to fresh infarcts.

Sites and mechanisms of localization of technetium 99m phosphorus radiopharmaceuticals in acute myocardial infarcts and other tissues

This study was performed to elucidate the localization at the cellular level of technetium-99m phosphorus ((99m)Tc-P) radiopharmaceuticals in acute myocardial infarcts and the mechanisms responsible for (99m)Tc-P uptake in acute myocardial infarcts and other tissues. In 20 dogs with proximal left anterior descending coronary arterial ligation for 1-3 days, elevated calcium levels were measured at all sites of increased (99m)Tc-P uptake (acute myocardial infarcts, necrotic thoracotomy muscle, lactating breast, and normal bone); however, a consistent linear relationship between (99m)Tc-P and calcium levels was not observed. A strong correlation (r = 0.95 and 0.99, n = 2 dogs) was demonstrated between levels of (3)H-diphosphonate and (99m)Tc-P in infarcted myocardium. Autoradiographic studies with (3)H-diphosphonate revealed extensive labeling in the infarct periphery which contained necrotic muscle cells with features of severe calcium overloading, including widespread hypercontraction as well as more selective formation of mitochondrial calcific deposits. Autoradiography also demonstrated labeling of a small population of damaged border zone muscle cells which exhibited prominent accumulation of lipid droplets and focal, early mitochondrial calcification. Cell fractionation studies revealed major localization of both (99m)Tc-P and calcium in the soluble supernate and membrane-debris fractions of infarcted myocardium and less than 2% of total (99m)Tc-P and calcium in the mitochondrial fractions; however, electron microscopic examination showed that mitochondria with calcific deposits were not preserved in the mitochondrial fractions. In vitro studies evaluating the role of serum protein binding on tissue uptake of (99m)Tc-P agents demonstrated that, in spite of significant complexing with serum proteins, serum (99m)Tc-P activity retained the ability to adsorp to calcium hydroxyapatite and amorphous calcium phosphate. In vivo studies showed that concentration of human serum albumin (labeled with iodine-131) in infarcted myocardium reached a maximum of only 3.8 times normal after a circulation time of 96 h, whereas (99m)Tc-P uptake was at least 10 times normal after a circulation time as short as 1 h. It is concluded that: (a) (99m)Tc-P uptake in acutely infarcted myocardium, and possibly other types of soft tissue damage, is limited to necrotic and severely injured cells; (b) concentration of (99m)Tc-P results from selective adsorption of (99m)Tc-P with various forms of tissue calcium stores, including amorphous calcium phosphate, crystalline hydroxyapatite, and calcium complexed with myofibrils and other macromolecules, possibly supplemented by calcium-independent complexing with organic macromolecules; and (c) lack of a linear relationship between (99m)Tc-P and tissue calcium levels mainly results from local differences in composition and physicochemical properties of tissue calcium stores and from local variations in levels of blood flow for delivery of (99m)Tc-P agents.

Hypofrontality and cognitive impairment in schizophrenia: Dynamic single-photon tomography and neuropsychological assessment of schizophrenic brain function

Regional cerebral blood flow (rCBF) was assessed in 40 chronic male schizophrenic patients (20 medicated, 20 unmedicated) and 31 matched normal controls with Dynamic Single-photon Emission Computed Tomography (D-SPECT). Blind analyses of normalized color-coded tomograms revealed significant bifrontal and bitemporal rCBF deficits in the patient group. Frontal flow deficits were most prominent in paranoid patients (n = 21) and right temporal deficits were most prominent in nonparanoid patients (n = 19). These relative regional declines were observed within the context of significantly elevated hemispheric blood flow in schizophrenics compared with controls. Reduced left frontal rCBF was associated with neuropsychological impairment on the Wisconsin Card Sorting Test and Luria-Nebraska Battery. Increased hemispheric CBF was correlated with the presence of positive schizophrenic symptoms. Medication status was unrelated to rCBF. These findings demonstrate that hypofrontality has important implications for cognitive function in some schizophrenic individuals.

Normal Distribution of Regional Cerebral Blood Flow Measured by Dynamic Single-Photon Emission Tomography:

Regional CBF (rCBF) was measured quantitatively using the inert-gas washout technique with xenon-133 and single-photon emission computed tomography. Tomographic data were reconstructed by filtered back projection, and flow was calculated according to the double-integral method. Ninety-seven subjects ranging in age from 20 to 59 years received a single examination; eight of these received a second examination within 1 h of the first; seven others received a second examination separated from the first by 1–10 days. Transverse-section images were obtained at 2, 6, and 10 cm above and parallel to the canthomeatal line (CML). Cortical gray matter flows were obtained from 12 brain regions in the slice 6 cm above the CML, and cerebellar and inferior cerebral gray matter flows were obtained from 4 regions in the slice 2 cm above the CML. Mean gray matter flow was 72 ± 12 ml/min/100 g, with highest flows in the parietal lobes and visual cortex. No significant differences in rCBF occurred when a second study followed the first by 30 min to 10 days. Right-sided rCBF was slightly higher than left in all regions except frontal and parietal lobes where there was no difference. Flow was higher in women than in men and declined mildly with age for both sexes (slope = −0.33 ml/min/100 g/year; p < 0.05).

Acute subendocardial myocardial infarction in patients. Its detection by Technetium 99-m stannous pyrophosphate myocardial scintigrams.

Eighty-eight patients admitted to a coronary care unit with chest pain of varying etiology but without ECG evidence of an acute transmural myocardial infarction had myocardial scintigrams using technetium-99m stannour pyrophosphate (99m-Tc-PYP). Seventeen of these patients had ECG and enzymatic evidence suggestive of acute subendocardial myocardial infarction. In each of these the scintigrams were postivie demonstrating increased 99m-Tc-PYP uptake either in a faintly but diffusely positive pattern or in a well-localized strongly positive one. The remaining 71 patients did not evolve ECG or enzymatic evidence of acute myocardial infarction. In each of these patients the myocardial scintigram was negative. Thus 99m-Tc-PYP myocardial scintigrams are capable of identifying the presence of acute subendocardial myocardial infarction in patients. The absolute frequency with shich subendocardial myocardial infarction can be recognized utilizing this technique will have to be established in a larger number of patients in the future.

Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs.

In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate (99mTc-PYP) and thallium-201 (201T1), tissue levels of 99mTc-PYP and 201T1 uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 201T1 upatke in the same regions. Marked 99mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of 99mTc-PYP and 201T1 explained the filling defects on 201T1 myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the 99mTc-PYP myocardial scintigram, and showed marked uptake of 99mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion. Thus, the data indicate that the status of regional myocardial perfusion is a key determinant for the occurrence of distinctive patterns of myocardial necrosis and for the scintigraphic detection of acute myocardial infarcts with 99mTc-PYP and 201T1.

Influence of temperature on the radiation response of mammalian cells in tissue culture.

Mammalian cells in tissue culture were irradiated at 5 un. Concent 85% C, 37 un. Concent 85% C, or 40 un. Concent 85% C. Cells irradiated at 5 un. Concent 85% C demonstrate radioresistance compared to cells irradiated at 40 un. Concent 85% C by a factor of 1.59. It is suggested that low temperature results in protection rather than enhances recovery. The nature of this protection is not known but it is thought to be associated closely with slowed rate processes and recombination of molecules in the metionic state before deieterious reactions can take place. (auth)

SPECT study of regional cerebral blood flow in Alzheimer disease

A common cause of dementia in late midlife and old age is Alzheimer disease (AD), which affects more than one in 20 individuals over the age of 65. Past studies of regional cerebral blood flow (rCBF) in patients with AD have suggested blood flow abnormalities, but findings have differed. We have studied 37 patients diagnosed as having AD with inhalation and washout of 133Xe and single-photon emission computed tomography (SPECT), obtaining evidence of abnormal rCBF patterns in 19. Flow reductions were most common in the temporoparietal regions and were occasionally found in the frontal areas. Investigators using positron-emission tomography (PET) have identified similar findings with respect to rCBF and regional oxygen, glucose, and protein metabolism. The SPECT determination of rCBF, which gives information similar to that provided by PET, may assume importance in the diagnosis of AD and in the differential diagnosis of the dementias.