Biomedical subjects
Publications and source records attributed to M M Ter-Pogossian.
Renal blood flow measurements have been carried out by means of positron emission tomography (PET) to facilitate the detection of radiation-induced injuries. The advantages of the method employed in animal experiments are described.
The development of positron emission tomography (PET) took place through the combination of the following recognitions: (1) a handful of short-lived, positron-emitting radionuclides, carbon-11, nitrogen-13, and oxygen-15, exhibit chemical properties that render them particularly suitable for the tracing of important physiological pathways, and (2) the radiation emitted as a result of the annihilation of positrons in matter exhibited physical properties that made it well-suited for nuclear medicine imaging, particularly for tomographic reconstruction. The scientific building blocks that were necessary for the structure of PET were contributed over a period of several decades by many investigators in physics, mathematics, chemistry, and fundamental biology.
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Emission tomography can be used to monitor, in vivo and regionally, the utilization of metabolic substrates labeled with positron-emitting radioisotopes produced by a cyclotron. The concept was validated by measuring brain glucose utilization with carbon--11-labeled glucose in rhesus monkeys.
Imaging of the brain by positron emission tomography can be optimized for sensitivity by dedicating the design of the tomograph to this application. We have designed a multislice positron emission tomograph (PETT V) for imaging the human brain and the whole body of small experimental animals. The detector system of PETT V consists of a circular array of 48 NaI(Tl) scintillation detectors, each fitted with two photomultiplier tubes, with one dimensional positioning capability. Suitable sampling is achieved by rotation of the circular array of detectors and by a wobbling motion of the detector circle. The proposed system is capable of providing seven slices simultaneously, with a spatial resolution in the plane of the slice from 7 to 15 mm and with slice thicknesses of 7 and 14 mm. The minimum scanning time is 1 sec. The estimated overall sensitivity of PETT V is 350,000 counts/sec/mCi in a 20 cm diameter phantom for a resolution of approximately 1.5 x 1.5 cm. The system is under construction.
We designed, built, and tested a positron emission tomograph (PETT IV) capable of providing seven slices of the human body simultaneously. PETT IV utilizes a moving hexagonal array of 48 scintillation detectors placed around the subject. Each detector consists of a cylindrical activated sodium iodide crystal optically coupled to two photomultiplier tubes. The multislice capability is achieved by comparing the light outputs of the two photomultiplier tubes in each detector. The images are displayed either as transverse or as longitudinal tomographic sections. This system provides high sensitivity and resolution, and permits rapid and accurate three-dimensional imaging of the head and body.
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Computer tomography (CT) is a radiological imaging method which yields transverse tomographic images reflecting with high accuracy the spatial distribution of x-ray attenuation in the part examined. The contrast resolution achieved by CT permits the visualization of soft tissue structure heretofore invisible with conventional radiographic procedure. The CT image is reconstructed by a computer applied algorithm, from a series of x-ray attenuation measurements obtained at different angles around the subject, by means of radiation detectors; The signal to noise ratio for these measurements is optimized by reducing the contribution of scattered radiation and of system noise. The CT principle of image reconstruction is also applicable in nuclear medicine imaging, with the goal of achieving contrast improvement and quantitative assessment of radionuclide distribution over conventional "projection" techniques. In this application, however, the attenuation of the radiation in the tissue interposed between the radionuclide and the detector must be taken into account to yield quantitatively accurate images. Furthermore, the variation of the field of view of the collimator as a function of distance contributes another unwanted variable to the reconstruction process. A mathematically rigorous tomographic reconstruction which would account for these variables is unavailable for gamma ray-emitting radionuclides, although approximate solutions of that problem have led to the satisfactory images of the head. Images of larger inhomogeneous organs are less quantitative. The detection of coincidence annihilation counting of positron-emitting radionuclides allows the accurate correction for the attenuation of that radiation in tissues and permits depth independent collimation which renders these radionuclide particularly suitable for their imaging by CT. A number of CT devices designed for the imaging of positron emitting radionuclides are yielding nuclear medicine images of quality and potential clinical usefulness unequaled by more conventional projection techniques.
To assess myocardial infarction quantitatively in 15 mm thick transverse sections of the canine heart in vivo we utilized a new technique, positron emission transaxial tomography (PETT) and cyclotron-produced 11C-palmitate (11C-P) injected intravenously. Results were compared to regional myocardial creatine phosphokinase (CPK) depletion, diminished 14C-palmitate accumulation in tissue extracts, and infarction estimated morphometrically 48 hours after coronary occlusion. CPK activity and 14C-P content declined in parallel in transmural biopsies (N=44) from normal and ischemic zones (r=.92) in six dogs; and infarct in 10 mm thick cross sections of the entire left ventricle estimated morphometrically (N=26) in six other animals correlated with CPK depletion in contiguous 2.5 mm thick slices (r=.92). When the percentage of infarction in 15 mm thick cross sections was assessed tomographically in six other dogs 48 hours after coronary occlusion with 11C-P injected intravenously, results correlated with infarction in corresponding cross sections from the same hearts estimated morphometrically (r=.97, N=9) and by analysis of CPK depletion (r=.93, N=9). Thus, PETT permits estimation of infarction in cross sections of the left ventricle in vivo after intravenous injection of 11C-palmitate.
Ischemic myocardial injury has been detected recently in isolated perfused hearts and intact experimental animals with positron-emitting 11C-palmitate and reconstructive tomography providing cross-sectional images of the heart free from superimposed activity in overlying structures. To evaluate the applicability of positron emission transaxial tomography in detecting infarction in man, 10 normal human subjects and 12 patients who sustained documented acute myocardial infarction three to 12 months previously were studied. Tomograms were obtained after intravenous injection of 5 to 10 mCi of 11C-labeled palmitate, a physiological substrate of myocardium. Tomograms from all normal subjects exhibited homogeneous distribution of 11C-palmitate throughout each 1.5 cm thick cross section of the ventricle. Tomograms from all patients with remote anterior or inferior and posterior myocardial infarction exhibited diminished accumulation of 11C-palmitate delineating regions corresponding to the electrocardiographic locus of infarction. The distribution of 11C-palmitate detectable by positron emission transaxial tomography in a series of cross sections from apex to base in the same normal subject or patient with remote myocardial infarction was analogous to that observed in normal dogs and animals with experimentally induced myocardial infarction.
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Radiopharmaceuticals incorporated directly into the metabolic pathways in myocardium provide a useful means for evaluating such processes. Palmitic acid, a major physiologic substrate of myocardium, has a well-understood role in myocardial metabolism. Accordingly, 11C-palmitic acid was the substrate chosen for use in conjunction with positron emission transaxial tomography to obtain images of canine myocardium. This procedure provides high-contrast images of tranverse sections of the myocardium, with good target-to-nontarget ratios (in the image), over a period of 5 to 85 minutes. Clearance half-times for blood and myocardial tissue were found to be 4.8 and 330 min, respectively. In normal myocardium, images obtained with 11C-palmitic acid were those obtained with 13NH3 and 11CO-hemoglobin. In vivo images of hearts with myocardial infarcts showed a clear delineration of infarcts and normal tissue.
The polyamines putrescine, spermine, and spermidine were methylated by the addition of carbon-11-labeled formaledehyde followed by sodium borohydride. High labeling yields wrbon-11-labeled formaldehyde followed by sodium borohydride. High labeling yields were obtained and the final products were purified by simply boiling the solution. This decomposed the excess sodium borohydride and removed the volatile impurities. The final radiochemical purity of all the methylated compounds was above 85%. All three methyltated compounds accumulated in the prostates of male rats and the distribution of N-methyl-1,4-diaminobutane (the putrescine analog) was very similar to that previously obtained with tritiated putrescine. The uptake of the putrescine analog in both the prostate and in mouse tumor was slightly higher than that obtained with the other two analogs studied. Utilizing a positron transaxial tomographic scanner and the putrescine analog, we have been able to image the prostate gland of a dog.
A series of experiments was undertaken to evaluate the response of a positron emission transverse tomograph (PETT) to measured radionuclide concentrations similar to those encountered in human studies. The correlation between the response of the imaging system (mean PETT number/min), and the concentration of the radioactivity producing the output data, was linear with a computed sensitivity of 2720 PETT number/min, per micronCi/ml, per picture element, for a radionuclide (100% beta+) contained in either of two phantoms and imaged with a reduction of 1.5 cm. It was concluded that the output data are essentially independent of the imaged object's physical dimensions for the range of 18-28-cm diam and faithfully reflect the regional radioactivity concentration within the object, provided valid attenuation correction is achieved and the sampled area is not compromised by the imaging system's limitations of spatial resolution.
To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.
The extraction of 11C-labeled methanol, ethanol, and isopropanol, as well as 15O-labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by external detection of the time course of these tracers subsequent to their internal carotid artery injection. The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min-1. At a cerebral blood flow of 50 ml/100 g min-1 only about 93% of an injected bolus of labeled water freely exchanges with brain, compared with methanol (93%), ethanol (97%), and isopropanol (99%). The brain capillary permeability-surface area (PS) products computed from these data were 0.023 cm3/s g-1 (water), 0.024 cm3/s g-1 (methanol), 0.030 cm3/s g-1 (ethanol), and 0.062 cm3/s g-1 (isopropanol). This sequence of PS products is consistent with the individual lipid solubilities of the alcohols studied and underscores the unique brain permeability characteristics of lipid-insoluble water.
This study was designed to provide direct experimental evidence in support of the method employing radioactive 15O-tagged hemoglobin for the in vivo and regional measurement of the cerebral oxygen utilization rate (CMRO2). This was accomplished by simultaneously measuring in vivo the mean CMRO2 in monkeys and human beings by the 15O method and a direct appeal to the Fick principle using measured arteriovenous oxygen differences of brain. The correlation between the 2 methods was excellent, with a correlation coefficient of 0.90 (P less than 0.001) in monkeys and 0.88 (P less than 0.001) in human beings.