Ernst Meyer

Oxygen Consumption of the Living Human Brain Measured after a Single Inhalation of Positron Emitting Oxygen

We measured the rate of washout of 15O-labeled water generated from labeled oxygen accumulated in brain after bolus [15O]O2 inhalation, and compared the washout with that of labeled water measured with H215O. Contrary to the original expectation, the radioactive water generated from labeled oxygen failed to leave the brain tissue at the rate predicted by exogenous water. Therefore, the use of a separately measured value for exogenous water clearance led to an error in the calculation of oxygen consumption. A new method presented in this paper eliminated the error by yielding oxygen consumption in a single oxygen study. We used time-weighted integration to estimate three parameters, including the unidirectional clearance from blood to brain (k1O2), the fractional clearance of the distribution volume in brain (k1O2), and the vascular volume correction (Vo). We showed that the clearance of oxygen from blood to brain can be estimated with acceptable precision by this new approach, and that the new method yields a reliable measure of oxygen consumption.

Cerebral [15O]Water Clearance in Humans Determined by PET: I. Theory and Normal Values

When used to measure blood flow in the brain, water leaves a residue in the vascular bed that influences the estimation of blood flow by current methods. To assess the magnitude of this influence, we developed a two-compartment model of blood flow with separate parameters for transport and vascular distribution of brain water. Maps of the water clearance, K1 into brain tissue, separated from the circulation by a measurably resistant blood–brain barrier (BBB), were generated by time-weighted integration. Depending on the validity of the assumptions underlying the two-compartment model presented here, the maps revealed a significant overestimation of the clearance of water when the vascular residue was ignored. Maps of Vo the estimate of the apparent vascular distribution volume of tracer H215O, clearly revealed major cerebral arteries. Thus, we claim that the accumulation of radioactive water in brain tissue also reflects the volume of the arterial vascular bed of the brain.

The Effect of Nimodipine on the Evolution of Human Cerebral Infarction Studied by PET

Fourteen patients were studied by positron emission tomography (PET) within 48 h of onset of a hemispheric ischemic stroke and again 7 days later. After the first set of PET scans, the patients were randomized to receive either nimodipine (n = 7) or a carrier solution (n = 7) by intravenous infusion. The infusions were maintained until the end of the second PET studies. CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), CMRO2, and CMRglc were measured each time. These metabolic and perfusion measurements were performed by standard methods. A surface map of each metabolic and perfusion measurement in the cortical mantle was generated by interpolating between the available slices. The various surface maps representing the physiological characteristics determined in the same or subsequent studies were aligned so that all data sets could be analyzed identically using an array of square regions of interest (ROIs). The functional status of each ROI was recorded at the two intervals following the cerebrovascular accident to characterize the evolution of the infarct, penumbra, and normal brain regions. We presumed the ischemic penumbra to be cortical regions in the proximity of the infarct and perfused at CBF values between 12 and 18 ml/100 g/min on the first PET scan, while densely ischemic regions had CBF of <12 nl/100 g/min and normally perfused brain >18 ml/100 g/min. In the densely ischemic zone, CBF increased more in the nimodipine-treated group than in the carrier group. As well, in this region nimodipine reversed the decline in CMRO2 noted in the carrier group, the difference in the changes being significant. In the penumbra zone, comparable trends were noted in OER and CMRO2 but the difference in the changes between the two groups did not reach statistical significance. Changes in CMRglc and CBV were comparable between the two groups in both cortical regions.

Performance evaluation of the PC-2048: a new 15-slice encoded-crystal PET scanner for neurological studies

Initial experience is reported with the Scanditronix PC 2048-15B, a 15-slice positron emission tomography (PET) system using multicrystal/multiphoto-multiplier modules to obtain high spatial resolution. Random and scattered events are reduced using an orbiting (68)Ge rod source for transmission scans by only accepting coincidence lines which intersect the instantaneous position of the source. Scatter correction of the emission data is removed with a deconvolution kernel, random and dead-time correction by the use of observed singles rates. The peak count rates are 11.7/20.0 Kcps for the direct cross slices at concentrations of 4.5/5.1 muCi/cc. respectively. Over the radial range 0-9 cm from the ring center, radial transverse resolution is 4.6-6.4 mm, aid tangential transverse resolution is 4.6-5.1 mm using a Hanning filter. Over the same range, axial resolution varies from 6.1-6.2 mm in direct slices and from 5.4-7.1 mm in cross slices. This near-isotropic resolution allows collection of image volume data with no preferred direction for signal averaging errors.

Language Localization with Activation Positron Emission Tomography Scanning

We report the first instance of the use of 3-dimensional magnetic resonance imaging anatomically correlated to positron emission tomography (PET) scanning to identify language areas in a patient with an arteriovenous malformation (AVM) in the posterior speech region. The patient was a 24-year-old right-handed woman with an angiographically proven AVM (3-4 cm) in the left mid-posterior second temporal convolution in whom a left intracarotid injection of sodium Amytal produced significant language disruption. A baseline PET cerebral blood flow study identified the AVM, and an activation PET scan performed during the reading and speaking of simple words showed increased activity in the left parastriate cortex (the second visual area), in the left posterior third frontal convolution (Brocas area), and in the left inferior and midtemporal gyri (Wernickes area). Increased activity was also noted in the right and left transverse temporal (Heschls) gyri, in the left precentral gyrus, in the left medial superior frontal gyrus (the supplementary motor area), and in the right cerebellum. We conclude that activation PET scanning is useful in the preoperative assessment of patients who harbor cerebral AVMs in classically described speech regions.

Positome II: A High Efficiency Positron Imaging Device for Dynamic Brain Studies

The performance of a new positron imaging device designed for high resolution dynamic studies on the human brain is described. This unit is the first to exploit the high photoelectric efficiency of bismuth germanate (BGO) detectors which are almost 3 times as dense as NaI. In the first 4 months of clinical use some 300 patient studies have been performed. The detector performance and design criteria are discussed. The principles of operation of the coincidence circuit and computer programs are described. Finally some clinical studies are presented to demonstrate its imaging capabilities.

Hemodynamic and metabolic effects of cerebral arteriovenous malformations studied by positron emission tomography

Seventeen patients with an intracranial arteriovenous malformation were studied with positron emission tomography. Cerebral blood flow, cerebral blood volume, oxygen extraction fraction, and glucose and oxygen metabolism were evaluated in both hemispheres, excluding the area of the malformation itself. Patients were divided into three groups according to the size of their malformation, and results obtained were compared with studies in healthy volunteers. The glucose metabolism was significantly (p less than 0.01) decreased in the ipsilateral hemisphere in all patients. The cerebral blood volume was significantly increased (p less than 0.001) ipsilaterally in the three groups, and contralaterally in patients with medium- and large-sized arteriovenous malformations. The cerebral blood volume to cerebral blood flow ration, an index of vascular mean transit time, was significantly increased (p less than 0.005) ipsilaterally in patients with medium- and large-sized malformations and contralaterally in patients with large ones. Cerebral blood flow, oxygen extraction fraction, and oxygen metabolism were within the normal range bilaterally in all three groups, but oxygen extraction fraction tended to be higher in patients with larger lesions. The lack of significant change in oxygen metabolism suggests that oxygen metabolism in cortical areas remote from the arteriovenous malformation has been maintained by compensatory hemodynamic mechanisms. These data reveal widespread metabolic and hemodynamic consequences of arteriovenous malformations and suggest that they are associated with impairment of glucose metabolism, both in ipsilateral regions remote from the lesion and in the contralateral hemisphere in patients with large lesions.

Density of perfused capillaries in living human brain during functional activation

Recent evidence has indicated that functional activation of cerebral cortex is accompanied by increases of blood flow and glucose consumption but not oxygen consumption. No explanation has been advanced for this change of the flow-metabolism couple. We formulated the hypothesis that oxygen delivery to brain tissue is diffusion-limited by the enormous hemoglobin binding, and rate-limiting for the oxygen consumption of the tissue. One prediction of this hypothesis is very low oxygen tensions in the tissue. A second prediction is the inability of oxygen consumption to increase during functional activation in the absence of recruitment of capillaries for the oxygen diffusion capacity. We designed a study to test the latter prediction by calculating the density of functioning capillaries during vibrotactile stimulation of the parietal cortex. We defined functioning capillaries as capillaries that transport glucose and therefore calculated the capillary density from the glucose diffusion capacity (K1) of the cerebral capillaries. We confirmed the presence of a partial flow-CMRglc couple (2:1) during the functional activation. Oxygen consumption did not change despite an increase of capillary density in proportion to the change of blood flow.

Increased oxygen consumption in human visual cortex: response to visual stimulation

To test whether a sufficiently complex visual stimulus causes the consumption of oxygen to rise in the human visual cortex, we used positron emission tomography (PET) to measure the cerebral metabolic rate of oxygen (CMRO2) during visual stimulation in 6 healthy normal volunteers. A yellow‐blue checkerboard, reversing its contrast at a frequency of 8 Hz, was presented for a period of 7 min, beginning 4 min before the onset of a 3‐min scan. In the baseline condition, subjects fixated a cross‐hair from 30 s before until the end of the 3‐min scan. The CMRO2 was calculated with the two‐compartment weighted integration method (1). The checkerboard minus baseline subtraction yielded statistically significant increases in CMRO2 in the primary (VI) and higher order visual cortices (V4 and V5). The significant CMRO2 increases were detected in these regions in both the group average and in each individual subject.

Cerebral [15O] Water Clearance in Humans Determined by Positron Emission Tomography: II. Vascular Responses to Vibrotactile Stimulation

When used to measure blood flow, water leaves a residue in the vascular bed, which may contribute to the calculation of increased blood flow during functional activation of brain tissue. To assess the magnitude of this contribution with the two-compartment positron emission tomography (PET) method, we mapped the water clearance (K1) of the brain as an index of cerebral blood flow (CBF) and the apparent vascular distribution of nonextracted H215O (Vo). The latter map represented mainly the cerebral arterial and arteriolar volume. We also prepared subtraction maps (ΔK1, ΔVo) of the response to vibrotactile stimulation of the fingertips of the right hand of six normal volunteers. Using magnetic resonance (MR) images of all subjects, the data were rendered into Talairachs stereotaxic coordinates and the averaged subtraction images (activation minus baseline) merged with the corresponding averaged MRI image. The ΔK1 map revealed the expected response in the primary sensory hand area; the ΔVo response was located about 13 mm more anteriorly, close to the central fissure, most likely reflecting changes of the arteries feeding the primary sensory hand area. We conclude that cerebral perfusion and cerebrovascular responses to vibrotactile stimulation may occur in disparate locations that can be identified separately by using the two-compartment method.