Robert Dann

Glucose Metabolic Rate Kinetic Model Parameter Determination in Humans: The Lumped Constants and Rate Constants for [18F]Fluorodeoxyglucose and [11C]Deoxyglucose

The rate constants and lumped constants (LCs) for [18F]fluorodeoxyglucose ([18F]FDG) and [11C]deoxyglucose ([11C]DG) were determined in humans for the glucose metabolic rate kinetic model used to measure local cerebral glucose consumption. The mean values (±SE) of the LCs for [18F]FDG and [11C]DG are 0.52 ± 0.028 (n = 9) and 0.56 ± 0.043 (n = 6), respectively. The mean values (±SE) of the rate constants k*1, k*2, k*3, and k*4 for [18F]FDG for gray matter are 0.095 ± 0.005, 0.125 ± 0.002, 0.069 ± 0.002, and 0.0055 ± 0.0003, respectively. The corresponding values for white matter are 0.065 ± 0.005, 0.126 ± 0.003, 0.066 ± 0.002, and 0.0054 ± 0.0006, respectively. Using these values and previously published values for the rate constants for [11C]DG, the average whole-brain metabolic rates for glucose in normal subjects measured with [18F]FDG and [11C]DG are 5.66 ± 0.37 (n = 6) and 4.99 ± 0.23 (n = 6) mg/100 g/min, respectively. These values are not significantly different (t = 1.56, p > 0.10) and agree well with reported values in the literature determined by means of the Kety-Schmidt technique.

Scintigraphic detection of acute gastrointestinal bleeding.

In induced bleeding experiments on dogs, 99mTc-sulfur colloid was a suitable agent for detecting the bleeding site in the small intestine, providing that the site was distant from the liver and spleen. Bleeding sites were detectable at rates as low as 0.1 ml/min. When induced in the sigmoid or descending colon, the site was demonstrated by scintigraphy with 99mTc-sulfur colloid. Unsatisfactory images were obtained in the esophagus and stomach, however, when 131I-ortho-iodohippurate or 99mTc-DTPA was used.

Positron emission tomography imaging of regional cerebral glucose metabolism

The (F-18) fluorodeoxyglucose (FDG) technique to measure local cerebral metabolic rate for glucose (LCMRglu) is well accepted and widely used by many institutions around the world. A large number of studies has been carried out in normal volunteers and patients with a variety of CNS disorders. Several investigators have noted that no significant age-related changes in cerebral glucose use occur with normal aging. Some important and interesting findings have been revealed following sensory, motor, visual, and auditory stimulations. Functional imaging with FDG in certain neurologic disorders has dramatically improved our understanding of their underlying pathophysiologic phenomena. Some abnormalities detected on the positron emission tomography (PET) images have no corresponding changes on either x-ray computed tomograms (XCT) or magnetic resonance images (MRI). In patients with Alzheimers disease, primary sensorimotor, visual, and cerebellar metabolic activity appears relatively preserved. In contrast, parietal, temporal, and to some degree, frontal glucose metabolism is significantly diminished even in the early stages of the disease. Patients with Huntingtons disease and those at risk of developing this disorder have a typical pattern of diminished CMRglu in the caudate nuclei and putamen. In patients with stroke, PET images with FDG have demonstrated abnormal findings earlier than either XCT or MRI and with a wider topographic distribution. FDG scans have revealed interictal zones of decreased LCMRglu in approximately 70% of patients with partial epilepsy. The location of the area of hypometabolism corresponds to the site of the epileptic focus as determined by electroencephalography and microscopic examination of the resected tissue. Ictal scans during partial seizures demonstrate areas of hypermetabolism corresponding to the sites of seizure onset and spread. Several investigators have reported relative hypofrontal CMRglu in patients with schizophrenia. In our center, FDG scans from patients with schizophrenia were successfully differentiated from those obtained in normal controls. Finally, our preliminary data (using PET, XCT, and MRI) in patients with CNS disorders indicate that MRI provides excellent delineation of the structural abnormalities. It may prove to be superior to XCT in the evaluation of certain diseases such as cerebral ischemia and infarcts, head injury, tumors, and white matter lesions. Metabolic imaging with FDG provides functional information not obtainable with either MRI or NMR spectroscopy. Therefore, PET studies will play a complementary role to the anatomic imaging in the management of patients with CNS disorders.

Evaluation of elastic matching system for anatomic (CT,MR) and functional (PET) cerebral images

To evaluate the performance of our elastic matching system, we have created a digitized atlas from the brain of a normal young man, using 135 myelin-stained sections at 700 μ.m spacing. Software was written to enter and edit regional anatomic contours, which were stacked and aligned to create a three-dimensional atlas. We then evaluated the matching system by comparing computer generated contours with expert defined contours for several subcortical structures, based on CT scans from six neurologically normal patients. The error in positioning, as defined by the distance between the centers of gravity, averaged 4.2 mm for the computer and 1.7 mm for the worst experts reading, with the computer drawn region frequently inscribed within that of the expert. Comparison was also made for each structure by determining the volume of overlap and the volumes not overlapping. On average, the computers agreement with the experts was –20% less than the agreement among the experts. This was a preliminary test of the system using only subcortical structures. The results are promising, and techniques are being implemented to overcome the current deficiencies.

Cerebral metabolism and patterned visual Stimulation: A positron emission tomographic study of the human visual cortex

We studied the impact of visual stimulation upon cerebral metabolism in normal young men using FDG-PET. Results obtained from subjects receiving patterned visual stimulation while performing an ocular fixation task were compared with results from ocular fixation alone. Visual stimulation in the macular region of either hemifield produced significant increases in metabolism of the contralateral posterior striate cortex. Visual stimulation induced highly significant asymmetries in metabolism of the prefrontal and inferior parietal cortices. Metabolic activation in extrastriate areas tended to be right-sided. These findings support the classic notion of retinotopic organization within the primary visual sensory cortex. They also indicate that the patterns of cerebral metabolism are not equivalent between the two cerebral hemispheres. This latter finding suggests that in humans the right cerebral hemisphere may be specialized for visual processing.

Ischemic lesions of the occipital cortex and optic radiations Positron emission tomography

We used 18-F-fluoro-2-deoxyglucose positron emission tomography (PET) and computed tomography (CT) to study eight patients with homonymous hemianopias or quadrantanopias due to ischemic lesions of the visual pathways. Four patients with ischemic damage to all or part of the occipital lobe had decreased glucose metabolism in the affected region. Three patients with ischemic damage limited to the optic radiations had decreased glucose metabolism in the portion of striate cortex appropriate for the visual field defect. Changes in glucose metabolism frequently occurred in the undamaged ipsilateral thalamus and visual association areas.

Cerebral blood flow with the continuous infusion of oxygen-15-labeled water

This work describes the determination of CBF in eight normal human subjects with positron emission tomographic (PET) imaging using the continuous intravenous infusion of H215O. A whole-brain CBF model is described that permits the comparison of the CBF values determined using PET with those obtained using other methods. This model includes a correction for whole-brain recovery coefficient, a correction for the underestimation of flow due to the nonlinearity of the CBF model when considering tissue that includes both gray and white matter, the use of in vitro-determined brain–blood partition coefficients for gray and white matter, and a variation of the equilibrium model that permits the arterial concentration to vary. CBF values using this method compare well with values determined previously. Regional determinations using a brain overlay atlas are presented. Radiation dosimetry for the continuous infusion of H215O is also included.

Three-Dimensional Computerized Brain Atlas For Elastic Matching: Creation And Initial Evaluation

We have previously reported the creation of software to perform elastic matching of medical images, for example, to compare an idealized atlas with a set of computer tomography (CT) images. In order to evaluate the performance of this software, we have created a digitized atlas from a young normal brain, using 135 myelin-stained sections at 700 micron spacing. Software was written in C on a Hewlett-Packard workstation to allow the entering and editing of regional anatomical contours. The 2-D contours are stacked to create a 3-D atlas that can be rotated, scaled, and resliced in the three standard imaging planes. For each patient being analyzed, an individualized atlas is created from this idealized atlas by elastically matching the atlas to the patients CT scans. Matching is achieved in two steps - global registration first, followed by deformation of the atlas to match the contours of the CT brain. This is done iteratively at coarse, medium and high resolution to achieve the best results. During this process, all regional contours are also dis-placed and deformed. We have evaluated how well the computer places these regional contours by having four experts outline several subcortical structures on the CT scans of six patients. Their degree of overlap and the variability in positioning were measured and compared with the placement of the same regions of interest by the computer. In one third of the structures there was no difference between the computer and the experts. In 18% of the regions the computer-defined region was closer to the truth than at least one of the experts. When the computer differed, it was usually by 2-3 mm in both x and y, and frequently the computer-defined region was inscribed within the experts. This is a preliminary test of the system, using only one set of elastic coefficients, one processing variant, and only subcortical structures. The results are promising and techniques are being implemented to overcome any current deficiencies. A more systematic evaluation of the entire process, exploring all the variables that affect the accuracy of elastic matching and adding cortical regions of interest, will follow in the near future. The elastic matching produces an individualized template of regions that can be super-imposed on the anatomical images. The user may then interactively modify these regions based on the observed anatomy, delete or add regions, and extract data from these user-adjusted overlays. The flexibility inherent in this approach allows data analysis with both standard and non-standard approaches, with regions defined both by the anatomy and by areas of functional activity.

Cerebral glucose consumption following verbal auditory stimulation

We studied the effect of auditory stimulation upon cerebral glucose metabolism in young normals. The stimulus consisted of a non-English discourse which was presented monaurally to 10 normal blindfolded subjects (5 left ear, 5 right); the opposite ear was plugged. Six subjects studied blindfolded and with ears plugged served as controls. Sixteen discrete homologous cortical and subcortical regions of interest were examined. Regional glucose consumption and side-to-side differences in glucose metabolism were analyzed. Monaural stimulation produced significant increases in temporal metabolism contralateral to the side of stimulation. Significant asymmetries in metabolism were found at the temporoparietal junction, inferior parietal region, insula and corpus collosum. The left frontal speech areas remained unaffected. These findings demonstrate that in man the primary auditory pathways retain a contralateral organization. Further, cerebral activation induced by non-meaningful verbal stimulation is widespread within the left temporal and parietal regions but does not impact upon the frontal speech cortices.

Regional cerebral glucose metabolism in aphemia: a case report

Local cerebral metabolism was determined in a patient suffering aphemia following cerebral infarction using the 18FDG-PET technique. The syndrome was characterized by profound ictal nonfluency with sparing of other language functions. Speech subsequently improved so that content and grammar were appropriate but mild dysprosody persisted. Conventional CT showed no lesion of the left hemisphere while PET revealed a discrete focus of hypometabolism on the left which partially resolved on serial studies. The metabolic lesion could be localized to the region of the inferior precentral gyrus and the adjacent subcortical space.