Peter J. Kenny

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.

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.

Theory for Noninvasive Measurement of Oxygen Extraction Fraction by Intravenous Bolus Injection or Bolus Inhalation of 15-Oxygen

Oxygen extraction fraction (OEF) in human subjects has been measured by the continuous inhalation (Jones et al. 1976) or bolus inhalation method (Mintun et al. 1983). However, arterial sampling is necessary to measure the arterial tracer concentration. We have developed a theory and a mathematical procedure by which OEF can be measured noninvasively in humans by positron emission tomography (PET). Our model has not only a possibility of being noninvasive, but also many advantages over the previously established methods. Three tracers are administered by intravenous bolus injection or bolus inhalation: (1) O-15 labeled O2 as an OEF tracer, (2) a diffusible tracer, as a reference tracer for the OEF study, and also as a cerebral blood flow (CBF) tracer, (3) carbon monoxide, as a cerebral blood volume (CBV) tracer.