A statistical investigation of normal regional intra-subject heterogeneity of brain metabolism and perfusion by F-18 FDG and O-15 H(2)O PET imaging

BACKGROUND: The definite evaluation of the regional cerebral heterogeneity using perfusion and metabolism by a single modality of PET imaging has not been well addressed. Thus a statistical analysis of voxel variables from identical brain regions on metabolic and perfusion PET images was carried out to determine characteristics of the regional heterogeneity of F-18 FDG and O-15 H(2)O cerebral uptake in normal subjects. METHODS: Fourteen normal subjects with normal CT and/or MRI and physical examination including MMSE were scanned by both F-18 FDG and O-15 H(2)O PET within same day with head-holder and facemask. The images were co-registered and each individual voxel counts (Q) were normalized by the gloabl maximal voxel counts (M) as R = Q/M. The voxel counts were also converted to z-score map by z = (Q - mean)/SD. Twelve pairs of ROIs (24 total) were systematically placed on the z-score map at cortical locations 15-degree apart and identically for metabolism and perfusion. Inter- and intra-subject correlation coefficients (r) were computed, both globally and hemispherically, from metabolism and perfusion: between regions for the same tracer and between tracers for the same region. Moments of means and histograms were computed globally along with asymmetric indices as their hemispherical differences. RESULTS: Statistical investigations verified with data showed that, for a given scan, correlation analyses are expectedly alike regardless of variables (Q, R, z) used. The varieties of correlation (r's) of normal subjects, showing symmetry, were mostly around 0.8 and with coefficient of variations near 10%. Analyses of histograms showed non-Gaussian behavior (skew = -0.3 and kurtosis = 0.4) of metabolism on average, in contrast to near Gaussian perfusion. CONCLUSION: The co-registered cerebral metabolism and perfusion z maps demonstrated regional heterogeneity but with attractively low coefficient of variations in the correlation markers

Study of multispectral convolution scatter correction in high resolution PET

PET images acquired with a high resolution scanner based on arrays of small discrete detectors are obtained at the cost of low sensitivity and increased detector scatter. It has been postulated that these limitations can be overcome by using enlarged discrimination windows to include more low energy events and by developing more efficient energy-dependent methods to correct for scatter. In this work, we investigate one such method based on the frame-by-frame scatter correction of multispectral data. Images acquired in the conventional, broad and multispectral window modes were processed by the stationary and nonstationary consecutive convolution scatter correction methods. Broad and multispectral window acquisition with a low energy threshold of 129 keV improved system sensitivity by up to 75% relative to conventional window with a ~350 keV threshold. The degradation of image quality due to the added scatter events can almost be fully recovered by the subtraction-restoration scatter correction. The multispectral method was found to be more sensitive to the nonstationarity of scatter and its performance was not as good as that of the broad window. It is concluded that new scatter degradation models and correction methods need to be established to fully take advantage of multispectral data.Anglai

Study of multispectral frame-by-frame convolution scatter correction in high resolution PET

High resolution PET scanners based on small individual detectors have a low sensitivity resulting from increased inter-detector scatter. It has been postulated that this limitation can be overcome by using enlarged discrimination windows to include more low-energy events and by developing more efficient energy-dependent methods to correct for scatter. In this work, we investigate one such method based on the frame-by-frame scatter correction of multispectral data. Images acquired in the conventional (344-658 keV), broad (129-658 keV) and multispectral (129-658 keV) window modes were processed by stationary and nonstationary convolution-restoration scatter correction methods. Broad and multispectral window acquisition improved counting efficiency relative to the conventional window. The degradation of image quality due to added scatter can be mostly recovered by the subtraction-restoration scatter correction. However, the multispectral frame-by-frame method was found to be more sensitive to the effects of the nonstationary scatter response functions and its performance was not as good as that of the broad window. It is concluded that more sophisticated scatter degradation models and correction methods need to be established to take full advantage of multispectral data

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 simplified blood sampling scheme in FDG-PET studies

Quantitative measurement of brain glucose metabolism with positron emission tomography (PET) and fluorodeoxyglucose (FDG) involves arterial blood sampling to estimate the delivery of radioactivity to the brain. Usually, for an intra-venous bolus injection of 30 sec duration, an optimal manual sampling requires more than 25 blood samples since a frequency of 1 sample every 5 sec or less is necessary to determine the peak activity in arterial plasma during the first 2 minutes after injection. In the present 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 as well as the fitted input curves, the regional cerebral metabolic rate for glucose (rCMRGlc) was estimated in 32 cerebral regions of interest (ROIs) in 20 normal volunteers. Metabolic values were obtained by both the autoradiographic method (ARG) and the kinetic analysis of dynamic data (DYN). 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 about 1% in ARG and 2% in DYN studies. This input curve fitting technique which was not dependent on the peak time occurrence, allowed an accurate determination of the input curve shape from reduced sampling schemes.Anglai

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