Neuroradiological assessment of brain structure and function and its implication in the pathogenesis of West syndrome.

Neuroimaging studies with magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning have contributed significantly to our understanding of West syndrome. Cortical dysplastic lesions are the most common abnormalities seen with MRI in infants with spasms, but other structural lesions are also detected occasionally. An underlying cortical dysplasia may not be apparent until myelination has advanced in the brain and poor gray-white matter differentiation becomes observable. Many cortical dysplastic lesions can only be detected using PET scanning of glucose metabolism or gamma-aminobutyric acid(A) (GABA(A)) receptor binding. The MRI and PET findings, together with neurophysiological observations, strongly suggest that infantile spasms are initiated as cortical epileptic discharges that, during a 'critical' developmental period, may undergo secondary generalization in an age-dependent mechanism to emerge as spasms. The onset of spasms often coincides with the functional maturation of cerebral cortex. Based on data from glucose metabolism PET scanning as well as electrophysiological and neurochemical findings on infants with spasms, we have postulated that the offending lesion is a focal or diffuse cortical abnormality which, at a critical stage of maturation, causes abnormal functional interactions with brainstem raphe nuclei which project widely throughout the brain. Raphe-cortical projections could mediate the hypsarrhythmic changes seen on EEG. The prominent serotonergic raphe-striatal pathway and descending spinal pathways may be responsible for secondary generalization of the cortical discharges to result in the relatively symmetric spasms. It is likely that additional factors (e.g. genetic) play a role in the manifestation of the age-specific electroclinical features of West syndrome. Recently developed PET tracers can be used to detect epileptogenic brain regions and also to investigate developmental abnormalities of serotonergic (using the tracer alpha[(11)C]methyl-L-tryptophan) and GABAergic (using [(11)C]flumazenil) neurotransmitter systems. These systems are implicated in epileptogenesis, and their involvement in the pathophysiology of West syndrome can be further addressed by future functional neuroimaging studies.

Assessment of skeletal muscle ventricle tissue blood flow using positron emission tomography.

In this pilot study, we assessed the feasibility of using positron emission tomography (PET) imaging for in vivo measurement of skeletal muscle ventricle (SMV) tissue blood flow. In 4 dogs, with SMVs prepared from their latissimus dorsi muscle, we quantified SMV tissue blood flow by PET and related it to the tissue flow measured by radiolabeled microspheres under similar physiologic conditions. The tissue blood flow was estimated in SMVs wrapped around a mandrel (not in circulation) at rest and during SMV stimulation (30 and 90 contraction-cycles/min). SMV tissue perfusion was heterogeneous, especially during SMV contraction. Furthermore, there was a linear relationship between SMV tissue flows estimated by PET and those measured by microspheres. We conclude that in vivo imaging of SMV is feasible by PET. Quantification of SMV tissue blood flow by PET has promise as a means of assessing changes in blood flow, but further technical progress needs to be made before absolute flows can be reliably measured.

Statistical parametric mapping: assessment of application in children.

SPM is a powerful technique for the comparison of functional imaging data sets among groups of patients. While this technique has been widely applied in studies of adults, it has rarely been applied to studies of children, due in part to the lack of validation of the spatial normalization procedure in children of different ages. In order to determine if spatial normalization of FDG PET images using SPM96 to an adult template can be successfully applied in children, we applied PET-derived transformation parameters to coregistered MRI images. We then compared contours of spatially normalized MRI images obtained from 13 children with epilepsy (ages 2-14 years, mean 7.6 +/- 3.9 years) with those derived from 17 adult controls (mean age 27.6 +/- 4.5 years). Contours of spatially normalized MRI image volumes derived from the pediatric group were more variable than those obtained from adult controls. The average deviation from the mean adult contour was age-dependent and decreased with age (average deviation (mm) = 2.22 (mm) - 0.021 (mm/year) x years, r = 0.70, P < 0.001). Separate SPM analyses were performed for children less than 6 years (N1 = 6) and for children between 6 and 14 years of age (N2 = 7). SPM analyses performed in both pediatric groups showed significant regions of hypometabolism in locations consistent with their epileptic foci. SPM analyses in the younger group also showed significant artifacts. Therefore, the error associated with spatial normalization of pediatric brains to an adult template in children less than 6 years of age precludes the application of statistical parametric mapping in this age group. Although the error in the spatial normalization procedure for children ages 6 to 14 years is higher than in adults, it appears that this error does not result in artifacts in the SPM analysis. Furthermore, in contrast our previous studies showing large age-related changes in the absolute glucose metabolic rate at puberty, the SPM analysis showed children over 6 years of age appear to display the same pattern of glucose utilization as adults. However, small differences in the pattern of glucose utilization which might occur during late childhood and adolescence may not have been detected due to the sample size.

Assessment of diagnostic performance of quantitative flow measurements in normal subjects and patients with angiographically documented coronary artery disease by means of nitrogen-13 ammonia and positron emission tomography.

OBJECTIVES: Regional myocardial blood flow (MBF) and flow reserve measurements using nitrogen-13 (N-13) ammonia positron emission tomography (PET) were compared with quantitative coronary angiography to determine their utility in the detection of significant coronary artery disease (CAD). BACKGROUND: Dynamic PET protocols using N-13 ammonia allow regional quantification of MBF and flow reserve. To establish the diagnostic performance of this method, the sensitivity and specificity must be known for varying decision thresholds. METHODS: MBF and flow reserve for three coronary territories were determined in 20 normal subjects and 31 patients with angiographically documented CAD by means of dynamic PET and a three-compartment model for N-13 ammonia kinetics. Ten normal subjects defined the normal mean and SD of MBF and flow reserve, and 10 normal subjects were compared with patients. PET flow obtained in the territory with the most severe stenosis in each patient was correlated with the angiographic assessment of the stenosis (severity > or = 50%, > or = 70%, > or = 90%). Receiver operating characteristic (ROC) curve analysis was performed for 1.5, 2.0, 2.5, 3.0 and 4.0 SD of flow abnormalities. RESULTS: MBF and flow reserve values from the normal subjects and from territories with documented stenoses > or = 50% were significantly different (p < 0.05). A significant difference was found between normal subjects and angiographically normal territories of patients with CAD. High diagnostic accuracy and sensitivity, with moderately high specificity, were demonstrated for detection of all stenoses. CONCLUSIONS: Quantification of myocardial perfusion using dynamic PET and N-13 ammonia provides a high performance level for the detection and localization of CAD. The specificity of dynamic PET was excellent in patients with a low likelihood of CAD, whereas an abnormal flow reserve in angiographically normal territories was postulated to represent early functional abnormalities of vascular reactivity.

Carbon-11 hydroxyephedrine with positron emission tomography for serial assessment of cardiac adrenergic neuronal function after acute myocardial infarction in humans.

OBJECTIVES: The purpose of this study was to assess the extent and reversibility of neuronal abnormalities in patients with an acute myocardial infarction. BACKGROUND: Previous experimental studies have described ischemic injury to sympathetic neurons exceeding the area of myocardial necrosis. Carbon-11 (C-11) hydroxyephedrine (HED) is a norepinephrine analogue that can be used for the noninvasive evaluation of neuronal integrity using positron emission tomography. METHODS: We studied 14 volunteers and 16 patients experiencing a first acute myocardial infarction. Positron emission tomographic imaging was used to quantitatively compare regional perfusion, as assessed with nitrogen-13 ammonia, with myocardial retention of C-11 hydroxyephedrine early after myocardial infarction as well as > 6 months after the acute event. RESULTS: C-11 hydroxyephedrine and flow images demonstrated homogeneous tracer retention in volunteers but were abnormal in all patients. C-11 hydroxyephedrine abnormalities were more extensive than those for blood flow assessed by semiquantitative polar map analysis (31 +/- 15% vs. 17 +/- 17% left ventricle; p < 0.05), particularly in five patients with non-Q wave infarction (31 +/- 11% vs. 3.5 +/- 2.5% left ventricle; p = 0.008). Eleven patients with Q wave infarction had matched defects (28 +/- 17% vs. 21 +/- 17% left ventricle; p = NS). C-11 hydroxyephedrine tissue retention fraction was quantified in three tissue zones: zone 1 (abnormal rest flow) had retention fraction 0.037 +/- 0.022-min; zone 2 (normal rest flow but decreased carbon-11 hydroxyephedrine retention) had retention fraction 0.068 +/- .034-min, and zone 3 (normal flow and carbon-11 hydroxyephedrine retention) had retention fraction 0.087 +/- 0.041-min (p = 0.0004). Follow-up studies at 8 +/- 3 months in eight patients revealed no change in extent of abnormalities or absolute tissue tracer retention in infarct and peri-infarct territories. CONCLUSIONS: The results of abnormal regional sympathetic innervation in patients with infarction confirm previous experimental data and suggest persistent neuronal damage in infarct and peri-infarct territories, without evidence of reinnervation of reversibly injured myocardium.

Assessment of myocardial perfusion by positron emission tomography.

Positron emission tomography (PET) represents an advanced imaging technology for the noninvasive evaluation of regional myocardial blood flow. Several blood flow tracers are available, including cyclotron-produced radiopharmaceuticals such as [15O]H2O and [13N]NH3 and generator-produced rubidium-82 ([82Rb]-) and copper-62 ([62Cu]-) pyruvaldehyde-bis-(N-4-methylthiosemicarbazone) (PTSM). 82Rb and [13N]NH3 are the most commonly employed tracers for the qualitative evaluation of regional myocardial perfusion. Their use allows the accurate detection of coronary artery disease in combination with pharmacologic stress. Initial comparative studies with thallium-201 (201Tl) single-photon emission computed tomography (SPECT) have shown that PET has a higher diagnostic accuracy. Beyond improved diagnostic performance, the quantitative flow measurements provided by PET represent an important advance in nuclear cardiology. The radiopharmaceuticals [15O]H2O and [13N]NH3 have been applied for the noninvasive determination of regional coronary reserve. Quantification of blood flow based on tracer kinetic modeling yields blood flow values in close agreement with determinations provided by invasive procedures. The noninvasive quantification of blood flow provides a useful research and clinical tool for the objective assessment of therapeutic interventions as well as pathophysiologic alterations of regional myocardial blood flow in various cardiac diseases.