Albert J. Gilson

Measurement of Cerebral Blood Flow in the Rat with Intravenous Injection of [11C]Butanol by External Coincidence Counting: A Repeatable and Noninvasive Method in the Brain

No method has been reported for measuring CBF, repeatedly and noninvasively, in the rat brain. A new method is described, which is noninvasive to the brain, skull, or cervical large vessels. Two pairs of coincidence detectors were positioned, one over the rat brain and the other at the loop of a catheter inserted into the femoral artery. The coincidence head curve and arterial curve were recorded after intravenous injection of 1-[11C]butanol in 15 rats. CBF was calculated by one-compartment curve fitting (CBFo) from 1-min data and with the recirculation corrected height/area method from 3-min data (CBFh · 3min) and 5-min data (CBFh · 5min). CBFo agreed well with CBFh · 5min, although a slight overestimation was observed in CBFh · 3min. The normal CBFo in the normocapnic group (n = 6, paco2 36.7 ± 2.3 mm Hg) was 1.76 ± 0.49 ml/g min (mean ± SD). A good correlation was observed between CBFo (y) and Paco2 (x), and the regression line was y = 0.0629x – 0.715 (r = 0.88, p < 0.0001). We concluded that this method gives the stable blood flow values noninvasively and with a minimum loss of blood (<0.28 ml per measurement). Applications of this method include activation studies, studies on the effect of drugs and treatments, and water and oxygen extraction fraction studies using different tracers in the same rat.

Radioisotopic labelling by surface catalysis—I. Preparation and quality control of 131I-4-iodoantipyrine☆

Abstract A new method of radioiodination, apparently involving halogen exchange by surface catalysis, has been developed for the synthesis of 131I-4-iodoantipyrine (131I-4-IAP) in high specific activity. On a silica gel surface, for instance, radioiodide reacts with antipyrine (AP) in hydrochloric acid at pH 1.0 to form 131I-4-IAP in a radiochemical yield of 82.2 ± 1.8%. Subsequent separation of the 131I-4-IAP from the AP by thin layer chromatography (TLC) has afforded greater than 99.5% radiochemically pure 131I-4-IAP. Quality control procedures utilizing TLC and high performance liquid chromatography have been developed.

A Noninvasive Technique for the Study of Cardiac Hemodynamics Utilizing C15O2 Inhalation1

A new technique for the study of cardiac hemodynamics is described which utilizes single-breath inhalation of C15O2 (T 1/2 = 124 sec.) and the recording of activity vs. time curves with scintillation counters placed externally over the left ventricle and right lung. The results from 10 normal volunteers and 28 patients with acquired or congenital heart disease have been compared to the findings at cardiac catheterization. The technique is safe, rapid, and nontraumatic, and yielded no false positives or negatives in this series.

Chemical recovery of thallium-203 following production and separation of lead-201

Because of the cost and limited availability of isotopically enriched thallium (>92%203Tl), its use in the203Tl(p, 3n)201Pb nuclear reaction necessitates chemical recovery. An adaptive method has been developed and evaluated. After the separation of201Pb, the203Tl(I) is oxidized to203Tl(III) by Cl2, Br2 or [Fe(CN)6]−2, precipitated as Tl(OH)3 with NaOH and subsequently converted to Tl2O3 by heating. Due to potential loss during recovery, the solubilities of Tl(OH)3 and Tl2O3 in aqueous solution as a function of pH have been studied using the internal tracer202Tl (T=12.2d), produced during cyclotron irradiation. Effective solubility product constants have been determined to be 5.4·10−48 and 2.5·10−47 for Tl(OH)3 and Tl2O3, respectively.

Alchemy with Short-Lived Radionuclides

A variety of short-lived radionuclides are produced and subsequently incorporated into radiopharmaceutical compounds in the radionuclide production program currently being conducted at the Cyclotron Facility of Mount Sinai Medical Center. The recovery of high specific activity oxygen-15 labelled water prepared by means of an inexpensive system operating in conjunction with an on-line radiogas target routinely utilized for oxygen-15 labelled carbon dioxide studies is currently receiving particular attention.

Simplified Techniques for Radioangiographic Analysis

A variety of equipment is available and in use today that allows the formation of curves of activity as a function of time from selected cardiac chambers and lung fields in conjunction with the radionuclide cardiac-flow study. These radionuclide indicator-dilution (RID) curves can be analyzed to yield information about the hemodynamic status of cardiopulmonary circulation. In this study, RID curves were obtained from a scintillation camera, interfaced to a small on-line computer, and studies were performed pre- and postoperatively on patients undergoing heart surgery. The results from the preoperative studies have been compared with cardiac catheterization data which were available in every case.

A Quantitative Model for the Measurement of Cerebral Vascular Extraction Fraction In vivo following Intravenous Injection: Simulation Studies

A mathematical method has been developed by which the cerebral vascular extraction fraction of flow- and diffusion-limited tracers injected intravenously can be measured quantitatively. Successive injections of three tracers are required: a test tracer such as 15O-labeled water; a completely diffusible tracer as a reference tracer and also as a flow tracer; and a tracer for cerebral blood volume (CBV). The arterial tracer concentration curves and total integrated head counts of the test and reference tracers, as well as CBF and CBV values, are required to calculate the extraction fraction. No calibration is required between the head counts and arterial curves. No decay correction of the head and arterial activity is required, because isotopic decay is explicitly included in the equation. The effect of nonextracted test tracer can be corrected. Simulation studies have shown that the calculated extraction fraction values are not sensitive to measurement error in CBF, CBV, partition coefficient, change in measurement time, or time shift effect between the arterial and head data. If there is mixing of two different tissues in the brain, the calculated extraction fraction values are close to the weighted mean values of extraction fraction by relative weight of the tissues. It is concluded that it is possible to apply this method to human studies with a positron emission tomograph scanner and to animal studies with external coincidence detectors.

Detection of Left-to-Right Shunts by Inhalation of Oxygen-15-Labeled Carbon Dioxide

The general properties of 15O-labeled carbon dioxide have been reviewed1,2 and published.3 The most striking property of this gas is that, when inhaled, it causes the sudden labeling of pulmonary venous blood water and, subsequently, a mathematically predictable clearance from the lungs into the left heart. This property, as we will see, can be most useful in the detection and quantitation of left-to-right intracardiac shunts. We will outline the general methods of shunt detection and quantitation here, and with this as background, a method utilizing the special properties of C15O2 inhalation will be developed and demonstrated.

The Use of C15O2 in the Evaluation of Cardiac Abnormalities

Carbon dioxide labeled with oxygen- 15 (t 1/2 = 124 sec) is a uniquely useful tracer for cardiopulmonary studies because it can be introduced selectively into the left heart by the simple noninvasive process of inhalation and breath-holding. Externally placed scintillation counters coupled with a high-speed multichannel recorder can be used to measure the rate of clearance of the tracer from the lungs and the rate of filling and emptying of the left heart. The presence of left-to-right intracardiac shunts or mitral or aortic valvular lesions can be inferred from the count rate vs. time curves. Scintigraphic images of the left ventricle in systole and diastole may be made using standard commercially available scintillation camera systems.

Left Heart Imaging Following C15O2 Inhalation

Cyclotron produced C15O2, administered by inhalation, has been used to obtain gated images of the left heart in systole and diastole. The inhaled gas rapidly crosses the alveolar membrane and labels the water fraction of the lung capillary blood which then proceeds directly into the left heart. This method of administration has the advantage of being totally non-invasive; because there is no venopuncture involved, sterility and non-pyrogenicity of the radiopharmaceutical do not have to be established. A standard commercially available scintillation camera (with high energy collimator) interfaced to a minicomputer was used for this study. Improved visualization of the left ventricle is obtained because of absence of activity in the right heart and low internal absorption of the 511 keV annihilation radiation.