A. Coppens

Comparison of regional cerebral blood flow and glucose metabolism in the normal brain: effect of aging

The regional cerebral blood flow (rCBF) and metabolic rate for glucose (rCMRGlc) are associated with functional activity of the neural cells. The present work reports a comparison study between rCBF and rCMRGlc in a normal population as a function of age. 10 young (25.9+/-5.6 years) and 10 old (65.4+/-6.1 years) volunteers were similarly studied at rest. In each subject, rCBF and rCMRGlc were measured in sequence, during the same session. Both rCBF and rCMRGlc values were found to decrease from young (mean rCBF=43.7 ml/100 g per min; mean rCMRGlc=40.6 micromol/100 g per min) to old age (mean rCBF=37.3 ml/100 g per min; mean rCMRGlc=35.2 micromol/100 g per min), resulting in a drop over 40 years of 14.8% (0.37%/year) and 13.3% (0.34%/year), respectively. On a regional basis, the frontal and the visual cortices were observed to have, respectively, the highest and the lowest reduction in rCBF, while, for rCMRGlc, these extremes were observed in striatum and cerebellum. Despite these differences, the ratio of rCBF to rCMRGlc was found to have a similar behavior in all brain regions for young and old subjects as shown by a correlation coefficient of 88%. This comparative study indicates a decline in rCBF and rCMRGlc values and a coupling between CBF and CMRGlc as a function of age.

Changes in occipital cortex activity in early blind humans using a sensory substitution device

The purpose of this study was to investigate the neural networks involved when using an ultrasonic echolocation device, which is a substitution prosthesis for blindness through audition. Using positron emission tomography with fluorodeoxyglucose, regional brain glucose metabolism was measured in the occipital cortex of early blind subjects and blindfolded controls who were trained to use this prosthesis. All subjects were studied under two different activation conditions: (i) during an auditory control task, (ii) using the ultrasonic echolocation device in a spatial distance and direction evaluation task. Results showed that the abnormally high metabolism already observed in early blind occipital cortex at rest [C. Veraart, A.G. De Volder, M.C. Wanet-Defalque, A. Bol, C. Michel, A.M. Goffinet, Glucose utilization in human visual cortex is, respectively elevated and decreased in early versus late blindness, Brain Res. 510 (1990) 115-121.] was also present during the control task and showed a trend to further increase during the use of the ultrasonic echolocation device. This specific difference in occipital cortex activity between the two tasks was not observed in control subjects. The metabolic recruitment of the occipital cortex in early blind subjects using a substitution prosthesis could reflect a concurrent stimulation of functional cross-modal sensory connections. Given the unfamiliarity of the task, it could be interpreted as a prolonged plasticity in the occipital cortex early deprived of visual afferences.

Cholinergic Neurotransmission Has Different Effects on Cerebral Glucose Consumption and Blood Flow in Young Normals, Aged Normals, and Alzheimer's Disease Patients

Cerebral blood flow (CBF) and glucose consumption (GC) are both tracers of brain metabolic activity used to image the human brain in vivo. To know if both tracers reacted in the same manner when brain cholinergic neurotransmission was activated, CBF and GC were measured in young normals (YN), aged normals (AN), and Alzheimers Disease patients (AD) using positron emission tomography (PET), H2 15O, and 18F-FDG. Each subject was studied twice, under placebo and physostigmine, in randomized order and blind fashion using the maximal tolerated dose of physostigmine individually determined. Under physostigmine CBF increased significantly (P = 0.0007) in posterior regions of the cerebral cortex and in the subcortical structures. Inversely, GC was decreased significantly in most regions. The largest decrease was seen in the prefrontal region of the cerebral cortex (P < 0.0001). Significant regional decreases were registered in all three groups of subjects, but were larger in AD than in controls. Looking at the absolute values of prefrontal cortex metabolism we found no correlation (r = 0.04) between the responses of CBF and GC. After normalization of the regional values for the mean we found a significant positive correlation between the responses of CBF and GC (r = 0.71, P < 0.0001). These findings suggest two components in the CBF response to physostigmine: one metabolic, depressive, and regional which follows the GC response; and one vascular, larger, diffuse, and opposite in direction to the metabolic component. These results have implications for the interpretation of CBF values as tracer of brain metabolic activity when brain cholinergic neurotransmission is manipulated.

Mediman: an object oriented programming approach for medical image analysis

Mediman is an image analysis package which has been developed to analyze quantitatively PET (positron emission tomography) data. It is object-oriented, written in C++, and based on InterViews on top of which new classes have been added. Mediman accesses data through NSF using external data representation or an import/export mechanism which avoids data duplication. Multimodality studies are organized in a database which includes images, headers, color tables, lists and objects of interest (OOIs), and history files. Stored color table parameters allow one to focus directly on the interesting portion of the dynamic range. Lists allow one to organize the image database according to modality, acquisition protocol, and time and spatial properties. OOIs are stored in absolute 3-D coordinates, allowing correlation with other coregistered imaging modalities such as magnetic resonance imaging or single photon emission computed tomography. OOIs have visualization properties and are organized into groups. Quantitative region-of-interest analysis of anatomic images consists of position, distance, and volume calculation on selected OOIs. >

Evolution of brain glucose metabolism with age in epileptic infants, children and adolescents.

During the first years of life, the human brain undergoes repetitive modifications in its anatomical, functional, and synaptic construction to reach the complex functional organization of the adult central nervous system. As an attempt to gain further insight in those maturation processes, the evolution of cerebral metabolic activity was investigated as a function of age in epileptic infants, children and adolescents. The regional cerebral metabolic rates for glucose (rCMRGlc) were measured with positron emission tomography (PET) in 60 patients aged from 6 weeks to 19 years, who were affected by complex partial epilepsy. They were scanned at rest, without premedication, in similar conditions to 20 epileptic adults and in 49 adult controls. The distribution of brain metabolic activity successively extended from sensorimotor areas and thalamus in epileptic newborns to temporo-parietal and frontal cortices and reached the adult pattern after 1 year of age. The measured rCMRGlc in the cerebral cortex, excluding the epileptic lesions, increased from low values in infants to a maximum between 4 and 12 years, before it declined to stabilize at the end of the second decade of life. Similar age-related changes in glucose metabolic rates were not observed in the adult groups. Despite the use of medications, the observed variations of rCMRGlc with age in young epileptic humans confirm those previously described in pediatric subjects. These metabolic changes are in full agreement with the current knowledge of the synaptic density evolution in the human brain.

A standardized blood sampling scheme in quantitative FDG-PET studies

Quantitative estimation of brain glucose metabolism (rCMRGlc) with positron emission tomography and fluorodeoxyglucose involves arterial blood sampling to estimate the delivery of radioactivity to the brain. Usually, for an intravenous injection of 30 s duration, an accurate input curve requires a frequency of one sample every 5 s or less to determine the peak activity in arterial plasma during the first 2 min after injection. In this work, 13 standardized sampling times were shown to be sufficient to accurately define the input curve. This standardized input curve was subsequently fitted by a polynomial function for its rising part and by spectral analysis for its decreasing part. Using the measured, the standardized, and the fitted input curves, rCMRGlc was estimated in 32 cerebral regions of interest in 20 normal volunteers. Comparison of rCMRGlc values obtained with the measured and the fitted input curves showed that both procedures gave consistent results, with a maximal relative error in mean rCMRGlc of 1% when using the autoradiographic method and 2% using kinetic analysis of dynamic data. This input-curve-fitting technique, which is not dependent on the peak time occurrence, allows an accurate determination of the input-curve shape from reduced sampling schemes.

Direct comparison between 2-dimensional and 3-dimensional PET acquisition modes for myocardial blood flow absolute quantification with O-15 water and N-13 ammonia

BACKGROUND Positron emission tomography scanners with retractable septa allow both 3-dimensional (3D) and 2-dimensional (2D) acquisition modes. The study aim was to directly compare 2D and 3D acquisition modes for the evaluation of absolute myocardial blood flow (MBF) over a wide range of flow values. METHODS AND RESULTS Instrumentation was used in 4 dogs to reduce the left circumflex artery lumen by greater than 75%. During infusion of adenosine, MBF was measured with both 2D and 3D dynamic acquisition and both oxygen 15 water and nitrogen 13 ammonia. Injected activities were 333 MBq and 111 MBq for 2D acquisition and 3D acquisition, respectively. Data were reconstructed by analytic methods, and MBF was assessed by use of an 18-segment model. MBF values ranged from 0.4 to 5.8 mL x g(-1) x min(-1) with O-15 water and from 0.3 to 3.9 mL x g(-1) x min(-1) with N-13 ammonia. No significant differences were observed in absolute MBF values obtained with the 2 acquisition modes, regardless of the flow tracer used. Two-dimensionally and three-dimensionally derived MBF values were significantly strongly correlated by use of both O-15 water (y = 0.98x + 0.18, r = 0.87, P < .001) and N-13 ammonia (y = 0.99x + 0.09, r = 0.95, P < .001). CONCLUSION Quantification of MBF in dogs with 3D positron emission tomography provides results similar to those obtained with the 2D technique, despite a lower activity being injected.

Decreased benzodiazepine receptor density in the cerebellum of early blind human subjects.

As a first approach to study the effect of early visual deprivation in the GABA-ergic inhibitory system, the distribution of benzodiazepine receptors (BZR) was accurately estimated using [11C]flumazenil ([11C]FMZ). Measurements were carried out in five subjects who became blind early in life and in five sighted control subjects. The interactions between [11C]FMZ and BZR were described using a non-linear compartmental analysis which permitted to estimate the BZR synaptic density independently of other model parameters. The distribution of BZR in the visual areas and other cortical regions of blind subjects was qualitatively and quantitatively similar to that of controls. However, the BZR density in the cerebellum was significantly lower in blind than in control subjects (P<0.01). Our findings suggest that modifications of the cerebellar neural circuitry may be concomitant to the already observed compensatory reorganization in cerebral areas of blind subjects.

Lossless compression for 3D PET

A new adaptive scheme is proposed for the lossless compression of positron emission tomography (PET) sinogram data. The algorithm uses an adaptive differential pulse code modulator (ADPCM) followed by a universal variable length coder (UVLC). Contrasting with Lempel-Ziv (LZ), which operates on a whole sinogram, UVLC operates very efficiently on short data blocks. This is a major advantage for real-time implementation. The algorithm is adaptive and codes data after some on-line estimations of the statistics inside each block. Its efficiency is tested when coding dynamic and static scans from two PET scanners and reaches asymptotically the entropy limit for long frames. For very short 3D frames, the new algorithm is twice more efficient than LZ. Since an application specific integrated circuit (ASIC) implementing a similar UVLC scheme is available today, a similar one should be able to sustain PET data lossless compression and decompression at a rate of 27 MBytes/sec. This algorithm is consequently a good candidate for the next generation of lossless compression engine. >

A flexible image smoothing and segmenting prior to parametric estimation

PET images suffer from statistical fluctuations where pixels representing the same tissue present different amplitudes, especially in short frames acquired in dynamic studies. Another difficulty is the time consuming in fitting images pixel by pixel in order to obtain parametric images. In the present work, a flexible method based on spatial and temporal pixel variance to compute parametric images is reported. For fluorodeoxyglucose and [/sup 15/O]-labeled water brain studies, a template image is obtained using: (1) summed frames, (2) thresholds to exclude background, (3) segmentation based on coefficients of variation and correlation coefficients of neighboring pixels, and (4) parameter estimation by dynamic fitting (DYN) or autoradiographic (ARG) method. Visually better images and images of parameters other than regional cerebral metabolic rates for glucose (rCMRGlc) or regional cerebral blood flow (rCBF) are obtained. For comparison, rCMRGlc and rCBF in both DYN and ARG methods estimated from segmented and usual images are compared. The maximal relative error is found to be 4% for ARG rCMRGlc, 10% for DYN rCMRGlc, and 17% for DYN rCBF, while the F-test shows no difference between values estimated from segmented and usual images. This technique allows more accurate parameter estimation in a reduced computation time.