Michel M. Ter-Pogossian

The Effects of Changes in PaCO2 Cerebral Blood Volume, Blood Flow, and Vascular Mean Transit Time

The relationships between cerebral blood volume (CBV), cerebral blood flow (CBF), and the cerebral vascular mean transit time (t®v) during acute changes in the PaCO2 over a range of 15 to 76 torr were investigated in vivo in rhesus monkeys by serially determining the mean transit time of a vascular tracer, 15O-labeled carboxyhemoglobin, and the mean transit time of a diffusible tracer, 15O-labeled water. Over this range of PaCO2, a significant linear relationship of CBV = 0.041 PaCO2 + 2.0 was found. For each one torr change in PaCO2, there is a change in CBV of 0.041 ml/100 gm of perfused tissue. At a normocarbic value of PaCO2 (∼37 torr), an average value of 3.5 ml/100 gm was found. A nonlinear relationship of CBV and CBF was found. This relationship is expressed in the equation, CBV = 0.80 CBF0.38. A significant linear relationship was found between CBF and PaCO2. This was described by the equation, CBF = 1.8 PaCO2 − 16.75. For each one torr change in the PaCO2, there is a 1.8 ml/100 gm per minute change in the CBF. At a normocarbic value of PaCO2(∼37 torr), an average value of CBF of 50 ml/100 gm per minute was found. The relationship of CBV and t®v was nonlinear and was expressed in the equation, t®C15O = 41 CBF−0.62.

Evidence of the Limitations of Water as a Freely Diffusible Tracer in Brain of the Rhesus Monkey

The extraction of 15O-labeled water by the brain during a single capillary transit was studied in vivo in 20 adult rhesus monkeys by external detection of the time course of the tracer subsequent to the internal carotid injection of 0.2 ml of whole blood labeled with H215O. The data showed that labeled water does not freely equilibrate with the exchangeable water in the brain when the mean cerebral blood flow exceeds 30 ml/100 g min−1. At the normal cerebral blood flow in the rhesus monkey (∼50 ml/100 g min−1), only 90% of the H215O is extracted during a single capillary transit. In addition, cerebral blood flow was determined with H215O and 133Xe in these monkeys using residue detection and employing the central volume principle. The data supported the hypothesis that a diffusible tracer, H215O, need not be in complete equilibrium between the phases of a system for the application of the central volume principle to be valid. Finally, the brain capillary permeability-surface area product was computed from these data; it was approximately 0.023 cm3/sec g−1.

A Matheematical Model for Positron-Emission Tomography Systems Having Time-of-Flight Measurements

Improvements in high speed electronics and scintillation-crystal technology now permit usable differential time-of-flight measurements to be made in tomography systems that employ coincidence detection of the annihilation photons created with positron emitting radionuclides. A mathematical model for these new measurements is developed in this paper. Reconstruction algorithms and their signal-to-noise ratio performance are given.

Temporal dependence of beneficial effects of coronary thrombolysis characterized by positron tomography

To delineate beneficial effects of intracoronary thrombolysis on myocardial metabolism in vivo and their dependence on the interval after coronary occlusion prior to reperfusion, we studied 23 closed-chest dogs. Coronary occlusion was produced with a thrombogenic copper coil to performance of cardiac positron emission tomography with 11C-palmitate. Jeopardized zones were calculated by summation by myocardial regions exhibiting less than 50 percent of the peak left ventricular wall radioactivity, and residual metabolic activity within jeopardized zones quantified based on the average counts compared with average counts in normal myocardium. After tomography, streptokinase was infused into the coronary artery (4,000 units per minute), resulting in angiographically demonstrable restoration of patency. Repeat tomography performed 90 minutes after the initial study with a second injection of 11C-palmitate demonstrated reduction of jeopardized zones by 51 +/- 6.3 percent (SE) and by 21 +/- 1.8 (p less than 0.01 based on paired comparisons) when refusion was initiated 1 to 2 (in four dogs) or 2 to 4 (in six dogs) hours after occlusion. Metabolic activity in initially jeopardized regions increased by 111 +/- 24.3 percent and 61.8 +/- 12.6 (p less than 0.01 for each). When streptokinase was infused later after occlusion, significant salutary metabolic effects did not occur. These results indicate that positron tomography may be useful in the clinical delineation of the efficacy of thrombolytic therapy in restoring myocardial metabolism and underscore the marked dependence of such efficacy on the duration of the interval of ischemia prior to the onset of reperfusion.

PETT VI: a positron emission tomograph utilizing cesium fluoride scintillation detectors.

We designed and built a positron emission transverse tomograph (PETT VI), designed specifically for fast dynamic studies in the human brain, and for cardiac studies in experimental animals. The scintillation detectors incorporated into this device are fitted with cesium fluoride crystals. Cesium fluoride was selected for this purpose because its short fluoresence decay allows the use of a short coincidence resolving time with a concomitant reduction of unwanted random coincidences. PETT VI utilizes four rings of 72 detectors simultaneously yielding seven tomographic sections. The system can be operated in either a low or high resolution mode with intrinsic geometrical resolutions in the plane of section of 7.1 to 11.7 mm full width at half maximum (FWHM), for a slice thickness with a resolution at the center of 13.9 mm FWHM. The maximum sensitivity of the system for seven slices in the low resolution mode is 322,000 cps/μCi/cc in a 20 cm diameter phantom. The contribution of random coincidences before subtraction in PETT VI was found to be approximately 14% of the counts in the phantom image with a source of approximately 3.5 mCi of a positron emitting radionuclide dispersed in a 20 cm diameter tissue equivalent phantom with a concentration of 1 μCi/cc. The short coincidence resolving time of the system permits rapid data acquisition for attenuation corrections and clinical dynamic studies with data acquisition times of less than a minute.

Detection of remote myocardial infarction in patients with positron emission transaxial tomography and intravenous 11C-palmitate.

Ischemic myocardial injury has been detected recently in isolated perfused hearts and intact experimental animals with positron-emitting “C-paImitate 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 “C-labeled palmitate, a physiological substrate of myocardium. Tomograms from all normal subjects ex- hibited homogeneous distribution of “IC-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 “IC-palmitate delineating regions corresponding to the electrocardiographic locus of infarction. The distribution of “IC-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.

Regional assessment of myocardial metabolic integrity in vivo by positron-emission tomography with 11C-labeled palmitate.

SUMMARYTo determine whether positron emission tomography (PET) after the combined administration of 11C-palmitate intravenously to image myocardium and 11CO by inhalation to image the cardiac blood pool with 11CO-hemoglobin provides quantitative delineation of the locus and extent of myocardial infarction, 28 patients with suspected myocardial infarction were studied. Twenty-one patients had electrocardiographically documented transmural infarction and in seven, the diagnosis of infarction was ultimately excluded based on enzymatic and electrocardiographic criteria. To assess reproducibility, four patients were studied on two occasions 1 month apart. Inferior and apical infarcts were readily localized with sagittal and coronal as opposed to transaxial reconstructions. Complete electrocardiographic and tomographic concordance was observed for the locus of all transmural infarcts. Reproducibility of tomographic estimates was within 10%. Tomographic estimation of the extent of infarction with 11C-palmitate in a subset of patients in whom right ventricular contributions to overall enzyme release could be exluded was facilitated by delineation of the endocardial border with the 11CO-hemoglobin cardiac blood pool image in the same plane. The correlation between enzymatic (serial plasma MB-CK method) and tomographic estimates of infarct size was close (r = 0.92). Thus, as has been shown in experimental animals, PET with 11C-palmitate permits quantification and localization of myocardial infarcts in patients.

The measure in vivo of regional cerebral oxygen utilization by means of oxyhemoglobin labeled with radioactive oxygen-15

Regional cerebral oxygen utilization rate is measured in vivo by the following method:A small volume of blood with radioactive oxygen-15-tagged hemoglobin is rapidly injected into the internal carotid artery of the patient under study. The first injection is followed by the injection carried out under identical circumstances but with blood labeled with water-(15)O. After each injection, the distribution of the radioactive label in the brain is measured and recorded, as a function of time, by six collimated scintillation probes placed over the subjects head. The recording, subsequent to the first injection, reflects (a) the arrival of the labeled oxygen into the tissues, (b) its partial conversion into water of metabolism, and (c) the washout of labeled water from the brain. The ratio of the amount of labeled water formed to the amount of oxygen perfusing the tissues, which can be derived from the recording, is a measure of fractional oxygen utilization. The second injection provides a measure of blood flow by the interpretation of the washout of labeled water from brain tissues. The product, fractional oxygen utilization x blood flow x arterial oxygen content, gives a measure of oxygen utilization rate. Some aspects of the validity of this method are tested by the injection of a nondiffusible indicator, carboxyhemoglobin-(15)O. Regional cerebral oxygen utilization rates for a series of patients with cerebral pathology are reported.

Quantification of infarction in cross sections of canine myocardium in vivo with positron emission transaxial tomography and 11C-palmitate.

SUMMARYTo 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 144C-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). ThIls, PETT permits estimation of infarction in cross sections of the left ventricle In vivo after intravenous injection of 11C-palmitate.

The Determination of Regional Cerebral Blood Flow by Means of Water Labeled with Radioactive Oxygen 15

THE NUMBER of methods devised for the in vivo evaluation of regional cerebral flow (rCBF) attest to the elusiveness of this parameter. One of the methods for this purpose is the injection, into the internal carotid artery of a subject, of a diffusible indicator labeled with a gammaemitting radioisotope, followed by the external measurement of the rate of washout of the indicator from various regions of the brain. This approach (1, 2), a modification of the Kety–Schmidt method (3–5), has most frequently utilized saline solutions of radioactive inert gases such as krypton 85 (1, 2) and xenon 133 (6). At this time, 133Xe appears to be the most widely used diffusible indicator despite inherent limitations which include: (a) a different solubility in lipids and in water; (b) a brain–blood partition coefficient difficult to evaluate accurately; and (c) the low–energy electromagnetic radiation of 133Xe. The first two factors render absolute flow determinations by this indicator uncertain and the third one favors...