Eugene E. Cook

Xenon enhanced CT for analysis of cerebral integrity, perfusion, and blood flow

Enhancement of the brain substance for CT evaluation using inhaled Xenon is confirmed. This technique was applied to the study of the normal and the embolized adolescent baboon. Healthy cerebral tissue enhances symmetrically, while abnormal areas show significantly diminished enhancement. At maximal enhancement, an indication of gross comparative cerebral perfusion is obtained. By obtaining serial CT scans over a 10 minute time interval, the clearance rate of Xenon (cerebral blood flow) may be evaluated. Xenon-enhanced CT enables a visual and numerical analysis of both brain morphology and physiology.

Neurogenic Hypertension: Etiology and Surgical Treatment, Ii. Observations in an Experimental Nonhuman Primate Model

In a companion paper (Ann Surg 1985; 201(3):391-398), clinical data which suggest that neurogenic hypertension may be caused by arterial compression of the left medulla oblongata was presented. A chronic pathophysiologic animal model of neurogenic hypertension using a substitute for arterial pulsation, the neurovascular compression simulator (NCS), was developed. This paper presents data that demonstrate how development of hypertension in a nonhuman primate baboon (5 subject animals, 5 control animals) can be caused by the NCS, and the blood pressure can subsequently return to normal following cessation of NCS activity. These experiments show that pulsatile compression of the left ventrolateral medulla oblongata results in cardiovascular changes consistent with the sequence found in human neurogenic hypertension. Arteriosclerosis and arterial ectasia in the human contribute to arterial elongation and looping at the base of the brain. An arterial loop, by causing pulsatile compression of neural structures, elicits an increase in blood pressure initiated by an increase in cardiac output. This may be due to interference with the autonomic control of the heart and/or by alteration of the relative capacitance of the vascular system.

Progress in cerebrovascular disease: local cerebral blood flow by xenon enhanced CT.

A noninvasive technique for measuring local cerebral blood flow (LCBF) by xenon enhanced x-ray transmission computed tomography (CT) has been developed an reported quite extensively in recent years. In this method, nonradioactive xenon gas in inhaled and the temporal changes in radiographic enhancement produced by the inhalation are measured by sequential computed tomography. Time dependent xenon concentrations within various tissue segments in the brain are used to derive both local partition coefficient (lambda) and LCBF. An assessment of this method reveals that although it provides functional mapping of blood flow with excellent anatomic specificity, there are distinct limitations. The assumptions underlying this methodology are examined and problems associated with various potential applications of this technique are discussed.

Side effects of xenon inhalation.

Short- and long-term side effects during and after inhalation of premixed xenon oxygen (28-47%) from 12 studies are reported. While all but one subject tolerated xenon inhalation without ill effects, that individual did experience unpleasantly severe dysesthesias and a brief period of unresponsiveness. We believe that further human studies with xenon inhalation should be conducted to explore possible early indicators for reduced tolerance of xenon by certain individuals.

Measurement of cerebral blood flow during xenon inhalation as measured by the microspheres method.

Measurements of cerebral blood flow (CBF) were performed using the microsphere technique in non-human primates (baboons) to assess the effect of non-radioactive xenon gas inhalation on CBF. Blood flows in small tissue volumes (approximately 1 cm3) were directly measured before and during the inhalation of xenon/oxygen gas mixtures. The results of these studies demonstrated that when inhaled in relatively high concentrations, xenon gas does increase CBF, but the changes are more global than tissue-specific. The problems and limitations of such evaluations are discussed.

Dynamic heterogeneity of cerebral hypoperfusion after prolonged cardiac arrest in dogs measured by the stable xenon/CT technique: a preliminary study

After prolonged cardiac arrest and reperfusion, global cerebral blood flow (gCBF) is decreased to about 50% normal for many hours. Measurement of gCBF does not reveal regional variation of flow or permit testing of hypotheses involving multifocal no-flow or low-flow areas. We employed the noninvasive stable Xenon-enhanced Computerized Tomography (Xe/CT) local CBF (LCBF) method for use in dogs before and after ventricular fibrillation (VF) cardiac arrest of 10 min. This was followed by external cardiopulmonary resuscitation (CPR) and control of cardiovascular pulmonary variables to 7 h postarrest. In a sham (no arrest) experiment, the three CT levels studied showed normal regional heterogeneity of LCBF values, all between 10 and 75 ml/100 cm3 per min for white matter and 20 and 130 ml/100 cm3 per min for gray matter. In four preliminary CPR experiments, the expected global hyperemia at 15 min after arrest, was followed by hypoperfusion with gCBF reduced to about 50% control and increased heterogeneity of LCBF. Trickle flow areas (LCBF less than 10 ml/100 cm3 per min) not present prearrest, were interspersed among regions of low, normal, or even high flow. Regions of 125-500 mm3 with trickle flow or higher flows, in different areas at different times, involving deep and superficial structures migrated and persisted to 6 h, with gCBF remaining low. These preliminary results suggest: no initial no-reflow foci (less than 10 ml/100 cm3 per min) larger than 125 mm3 persisting through the initial global hyperemic phase; delayed multifocal hypoperfusion more severe than suggested by gCBF measurements; and trickle flow areas caused by dynamic factors.

Selective lenticulostriate occlusion in the primate. A highly focal cerebral ischemia model.

A highly reliable model for the study of focal cerebral ischemia has been developed using a retro-orbital approach to occlude the lateral lenticulostriate arteries of the baboon. An infarction of the caudate, putamen and the anterior limb of the internal capsule has consistently been produced. Reliability has been attained because the anatomical variations of the lenticulostriate arteries of each animal can be fully appraised, permitting selective vessel occlusion. A well-defined clinical and radiographic lesion has also resulted from this procedure which was clinically well tolerated by all animals. Selective lenticulostriate occlusion provides a new approach to the study of focal cerebral ischemia in the sub-human primate, and serves for the evaluation of proposed therapies for treatment of focal cerebral ischemia.

Xenon-enhanced computed tomography compared with [14C] iodoantipyrine for normal and low cerebral blood flow states in baboons

The correlation between the acute, invasive diffusible [14C]iodoantipyrine technique for cerebral blood flow and the noninvasive xenon-enhanced computed tomographic method has been assessed by simultaneous measurements in the baboon. Blood flows in small tissue volumes (about 0.125 cm3) were directly compared in normal and low flow states. These studies demonstrate a statistically significant association between the two methods (p less than 0.001). Similar correlations were obtained by both the Kendall (tau) and the Spearman (r) methods (r = 0.67 to 0.92, n greater than or equal to 19 for each study). The problems and limitations of such correlations are discussed.

Simultaneous measurements of cerebral blood flow by the xenon/CT method and the microsphere method. A comparison

Simultaneous measurements of cerebral blood flow have been performed in baboons to assess the correlation between the acute and invasive nondiffusible microsphere technique and the noninvasive xenon-enhanced CT method. Blood flows in small tissue volumes (approximately 1 cm3) were directly compared. The results of these studies demonstrate a statistically significant association between the two methods (P less than .001). Similar correlations were obtained by both the Kendall tau (tau) and the Spearman (r) methods. The problems and limitations of such correlations are discussed.

The capacity for computed tomography diagnosis of cerebral infarction. An experimental study in the nonhuman primate.

The characteristic serial CT scan appearance of cerebral infarction created by embolization of the middle cerebral artery in the nonhuman primate (10 baboons) is defined. The earliest CT changes are noted by 12 to 24 hours and include generalized ventricular enlargement and a focal region of decreased absorption in the opercula-basal ganglia region. The area of diminished brain absorption is better circumscribed and of lower attenuation coefficient with increasing chronicity. Distinct hydrocephalus, unilateral exophthalmos and ventricular displacement occurred with increased intracranial pressure. Little additional diagnostic information was obtained via intravenous enhancement and care should be taken as mild enhancement may obscure an area of abnormality.