Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson's disease and healthy controls.

PURPOSE: Diagnosing Parkinson's disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls. METHODS: Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated. RESULTS: FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques. CONCLUSION: FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity.

Detection of cortical thickness correlates of cognitive performance: Reliability across MRI scan sessions, scanners, and field strengths.

In normal humans, relationships between cognitive test performance and cortical structure have received little study, in part, because of the paucity of tools for measuring cortical structure. Computational morphometric methods have recently been developed that enable the measurement of cortical thickness from MRI data, but little data exist on their reliability. We undertook this study to evaluate the reliability of an automated cortical thickness measurement method to detect correlates of interest between thickness and cognitive task performance. Fifteen healthy older participants were scanned four times at 2-week intervals on three different scanner platforms. The four MRI data sets were initially treated independently to investigate the reliability of the spatial localization of findings from exploratory whole-cortex analyses of cortical thickness-cognitive performance correlates. Next, the first data set was used to define cortical ROIs based on the exploratory results that were then applied to the remaining three data sets to determine whether the relationships between cognitive performance and regional cortical thickness were comparable across different scanner platforms and field strengths. Verbal memory performance was associated with medial temporal cortical thickness, while visuomotor speed/set shifting was associated with lateral parietal cortical thickness. These effects were highly reliable - in terms of both spatial localization and magnitude of absolute cortical thickness measurements - across the four scan sessions. Brain-behavior relationships between regional cortical thickness and cognitive task performance can be reliably identified using an automated data analysis system, suggesting that these measures may be useful as imaging biomarkers of disease or performance ability in multicenter studies in which MRI data are pooled.

Cerebral activation related to implicit sequence learning in a Double Serial Reaction Time task.

Using functional magnetic resonance imaging (fMRI), we examined the distribution of cerebral activations related to implicitly learning a series of fixed stimulus-response combinations. In a novel - bimanual - variant of the Serial Reaction Time task (SRT), simultaneous finger movements of the two hands were made in response to pairs of visual stimuli that were presented in a fixed order (Double SRT). Paired stimulus presentation prevented explicit sequence knowledge occurring during task practice, which implied that a dual task paradigm could be avoided. Extensive prescanning training on randomly ordered stimulus pairs allowed us to focus on the acquisition of implicit sequence knowledge. Activation specifically related to the acquisition of fixed sequence knowledge was highly significant in the right ventrolateral prefrontal cortex. The medial prefrontal and right ventral premotor cortex were more indirectly related with such procedural learning. We conclude that this set of activations reflects a stage of implicit sequence learning constituted by components of (i) spatial working memory (right ventral prefrontal cortex), (ii) response monitoring and selection (medial prefrontal cortex), and (iii) facilitated linkage of visuospatial cues to compatible responses (right ventral premotor). Comparing the random-order stimulus-response actions with fixed sequences showed activations in dorsal premotor and posterior parietal cortices, consistent with a dorsal pathway dominance in real-time visuomotor control. The relative long time during which performance improves in the DoSRT provides an opportunity for future study of various stages in both general skill and fixed sequence learning.

Corticostriatal covariance patterns of 6-[18F]fluoro-L-dopa and [18F]fluorodeoxyglucose PET in Parkinson's disease.

6-[18F]fluoro-L-dopa (FDOPA) is a common presynaptic dopaminergic tracer used in examinations by positron emission tomography (PET) for patients with Parkinson's disease (PD). The distinct metabolic covariance pattern in the uptake of [18F]fluorodeoxyglucose (FDG) can also be used to investigate PD pathology. Although the two tracers are widely used in PD research and clinical assessment, no thorough comparative studies of the tracers have been made. In this study, 25 PD patients were examined with FDOPA and FDG to investigate relationships and clinical correlates of metabolic and monoaminergic function in the Parkinsonian brain. A VOI (volume-of-interest) analysis was achieved by 3D spatial normalisation and fixed VOI-sets. The hemisphere ipsi- and contralateral to the predominant symptoms of PD was identified in each data set, and data across subjects were related using that laterality, rather than body side. Regional covariance patterns for FDOPA and FDG were derived from principal component analysis (PCA). The results demonstrated hemispheric asymmetries and sex-differences in the striatal FDOPA uptake, which were not seen with FDG. In addition, the PCA analysis identified a positive relationship between a major component in FDOPA uptake (associated with the striatal uptake) and an FDG component, which had positive loadings in the thalamus and the cerebellum. The subject scores for these components correlated positively, and both had a negative association with the clinical severity of the disease. The specific extrastriatal FDG covariance pattern contained the thalamus and the cerebellum, components of the previously reported PD related pattern, but not the striatum. The network correlated with both the severity of clinical symptoms of PD and the severity of nigrostriatal dopaminergic hypofunction. The results indicate that FDG PET, when combined with multivariate network analysis at group-level, can be used as an indicator of PD severity.

Comparison of FP-CIT SPECT with F-DOPA PET in patients with de novo and advanced Parkinson's disease.

PURPOSE: Diagnosis of Parkinson's disease (PD) can be difficult. F-DOPA PET is able to quantify striatal dopa decarboxylase activity and storage capacity of F-dopamine, but is expensive and not generally available. FP-CIT binds to the dopamine transporter, and FP-CIT SPECT is cheaper and more widely available, but has a lower resolution. The aim of this study was to compare these two methods in the same patients with different stages of PD to assess their power in demonstrating deficits of the striatal dopaminergic system. METHODS: Thirteen patients with de novo PD and 17 patients with advanced PD underwent FP-CIT SPECT and static F-DOPA PET. After data transfer to standard stereotactic space, a template with regions of interest was used to sample values of the caudate, putamen and an occipital reference region. The outcome value was striato-occipital ratios. Patients were clinically examined in the "off state" (UPDRS-III and H&Y stage). RESULTS: Good correlations were found between striatal F-DOPA uptake and striatal FP-CIT uptake (r = 0.78) and between putaminal F-DOPA uptake and putaminal FP-CIT uptake (r = 0.84, both p < 0.0001). Both striatal uptake of FP-CIT and that of F-DOPA correlated moderately with H&Y stage (rho = -0.52 for both techniques), UPDRS-III (rho = -0.38 for F-DOPA; rho = -0.45 for FP-CIT) and disease duration (rho = -0.59 for F-DOPA; rho = -0.49 for FP-CIT, all p < 0.05). CONCLUSION: FP-CIT values correlate well with F-DOPA values. Both methods correlate moderately with motor scores and are equally able to distinguish patients with advanced PD from patients with de novo PD.

Assessment of methylphenidate-induced changes in binding of continuously infused [(11)C]-raclopride in healthy human subjects: correlation with subjective effects.

RATIONALE: The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders. It has been shown that information on endogenous dopamine (DA) release can be obtained noninvasively by combining positron emission tomography with a dopaminergic challenge. This approach is based on the assumption that an injected radiolabeled ligand competes with the neurotransmitter for the same receptor. Increases in DA release will therefore result in a decreased binding of the radioligand. OBJECTIVES: We investigated the effect of the DA reuptake blocker methylphenidate (MP) on the binding of the D(2) receptor ligand [(11)C]-raclopride (RAC). METHODS: The effect of a 0.25 mg/kg intravenous dose of MP was studied in six healthy volunteers. RAC was administered as a bolus followed by constant infusion, and subjective effects were assessed using verbal rating scales. RESULTS: Control scans without MP administration showed that the mean RAC binding reached stable values approximately 30 min after start of the infusion. MP administration induced a 24% decrease in RAC binding in the total striatum. Correlations were found between the MP-induced change in euphoria and the percent change in binding potential (DeltaBP) in the dorsal striatum and between baseline anxiety and DeltaBP in the dorsal and middle striatum. We also found a negative correlation between baseline BP in the dorsal striatum and change in euphoria. CONCLUSIONS: Our results comply with previous findings, indicating the feasibility of the bolus infusion design combined with a relatively low MP dose to study dopaminergic (dys)function.

Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease.

Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the product of age and CAG repeat length (p < 0.0005). Dopamine D2 receptor availability measured by RAC-BP seems the most sensitive indicator of early neuronal impairment in PMC.

Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation.

OBJECTIVES: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. METHODS: In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. RESULTS: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen. CONCLUSIONS: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.

Mapping brain structure and personality in late adulthood.

Cerebral gray matter (GM) volume decreases in normal aging with a parallel increase in intracranial cerebrospinal fluid (CSF) volume. There is considerable interindividual variation in these changes, and the consequences of age-related GM shrinkage and CSF expansion are unclear. The present study examined whether late adulthood brain structural differences are related to differences in temperament and character. Personality structures of 42 healthy aged adults (mean age 60 years) were examined together with global and regional GM, CSF, and white matter (WM) volumes calculated from structural magnetic resonance images using voxel-based morphometry (VBM). A positive relationship was seen between GM volume at the border of the temporal, parietal, and frontal cortices, and self-transcendence, a character personality trait that reflects mature creativity and spiritualism. The relationship remained significant after a conservative correction for multiple comparisons and it was seen both using uncorrected raw values and after a correction for the effects of age and sex. The results suggest that high self-transcendence, which has adaptive advantages in the later part of life, is associated with relatively greater temporal cortical GM volumes.

PET neuroimaging and mutations in the DJ-1 gene.

Mutations in the DJ-1 gene lead to autosomal recessive early-onset parkinsonism. We performed F-DOPA and FDG PET neuroimaging in two parkinsonism patients homozygous for DJ-1 mutations, three relatives heterozygous for a DJ-1 mutation and one non-carrier, all from the originally described kindred from The Netherlands. Their characteristics were compared to those of typical Parkinson's disease patients and healthy controls. Both parkinsonism patients had reduced F-DOPA uptake concordant with typical Parkinson's disease. In the, clinically unaffected, heterozygous relatives, F-DOPA metabolism was unremarkable, thus not suggesting a dosage effect of the DJ-1 gene.

Cerebral activation related to skills practice in a double serial reaction time task: striatal involvement in random-order sequence learning.

We used functional Magnetic Resonance Imaging (fMRI) to examine the distribution of cerebral activation related to prolonged skill practice. In a bimanual variant of the Serial Reaction Time Task (SRT), simultaneous finger movements of the two hands were made in response to randomly ordered pairs of visual stimuli (Double SRT, DoSRT). Extended practice by a week of daily performance resulted in gradual decrease of reaction times, associated with an increased involvement of the ventral putamen and globus pallidus, reaching statistical significance only on the left side (Statistical Parametric Mapping, SPM99). This increase was complementary to a decrease of cortical activations. The striatal activation after training on random order stimuli indicates that the striatum is not exclusively involved in sequence learning. This extended function implies a role in the acquisition of basic visuomotor skills that includes the specific selection of the appropriate muscles in response to independent stimuli.

Pharmacological and PET studies in patient's with Parkinson's disease and a short duration-motor response: implications in the pathophysiology of motor complications.

Patients with Parkinson's disease (PD) and levodopa-induced motor complications experience a short-duration response (SDR) to levodopa which can be considered the basis of motor fluctuations. The SDR is characterized by reduced response duration, increased magnitude of the response and reduced latency to the peak effect. A short latency and a high magnitude are the most salient pharmacological features of the SDR. Its pathophysiology is not totally understood. The pharmacological characteristics of the motor response to apomorphine and their relationship with 6-[(18)F]fluoro-L-dopa (FDOPA) and [(11)C]raclopride (RACLO) uptake were studied in 9 patients with PD. Latency to peak effect was positively correlated with putaminal FDOPA uptake (p<0.05) and negatively correlated with RACLO uptake (P<0.05). A trend towards significance (p:0.06) between magnitude of the response and FDOPA uptake was found which were negatively correlated. Levodopa-induced dyskinesias were negatively correlated with FDOPA uptake (p<0.05) and a trend towards significance (positive correlation) with RACLO uptake was observed (p:0.07). These results suggest that both pre and postsynaptic mechanisms are involved in the origin of the SDR.

Development of an inexpensive, low attenuation styrofoam primate chair for use in a PET scanner.

Pharmacokinetic modelling of radiotracers for positron emission tomography (PET) imaging of neuroreceptors can be performed with time-activity data for brain and blood. We aimed to develop an alternative to withdrawal of arterial blood samples for acquisition of a blood curve. A supportive primate chair was constructed out of styrofoam and fixed to the head portion of the bed of a PET scanner. A lightly anaesthetised rhesus monkey was positioned in the chair in a sitting position and injected with the radiotracer. The styrofoam chair provided sufficient support for the monkey. The presence of the chair in the PET scanner caused negligible attenuation of radiation, allowing simultaneous acquisition of dynamic data from the subject's brain and heart. We conclude that a styrofoam primate chair is an ideal tool to measure blood and brain data from a rhesus monkey with PET. Invasiveness to the animal is reduced, as well as experimenter time.

Evidence of enhancement of spatial attention during inhibition of a visuo-motor response.

A visuo-motor task was used as the setting for a study into inhibition in six healthy volunteers using fMRI. The task involved responding to colored stimuli, which appeared at random positions in the left and right visual field, with the corresponding hand. The volunteers were asked to respond to green colored stimuli ("go" response) and to inhibit responses to red stimuli ("no-go" response). The task was presented in a block design with blocks of three types; only "go" trials, a pseudo-random mixture of "go" and "no-go" tasks ("go/no-go" block), and "visual control." ANCOVA analysis of the fMRI data was performed within the framework of SPM99. Increased activation in the go vs visual control comparison was found in the bilateral motor and medial premotor cortices associated with the action of the button press response, as well as parietal regions attending to the task of identifying the visual field. The go/no-go vs visual control comparison showed a similar pattern, plus additional prefrontal areas that have previously been shown to be associated with inhibition. The direct comparison of the go and go/no-go blocks highlighted large differences not only in the prefrontal cortices, associated with inhibition, but also particularly in the right parietal cortex. We interpret the increased parietal activation, during inhibition, as representing a heightened spatial attention required for the correct execution of the inhibition task.

Whole body [O-15]water pharmacokinetics measured in blood.

A simple pharmacokinetic model to explain the time course of [O-15] water in human whole blood after bolus injection is described. The model has been derived from measurements in twelve healthy volunteers who were measured repeatedly, resulting in 67 datasets, made in the context of PET blood flow studies. In contrast to traditional volume of distribution estimates of total body water (TBW) which rely on measurements after many hours, the model and data provide insights into the fast uptake components in the distribution of water in the body. Data fitting shows that the volume of distribution of fast exchanging tissues is 21 l. TBW was calculated to be 37 l. Monte Carlo simulation showed that the expected inaccuracy of determination of parameters due to unsystematic sources in the measurement data was around 5% for most parameters. Our data show that water extraction to tissue is somewhat higher than would be predicted from the tabulated values, probably because skeletal blood flow is sensitive to physiological status and environmental conditions. The study provides valuable reference data on the distribution and kinetics of water in man. Using the parameters and model from this study, reference input time-activity curves can be calculated, e.g. for the Monte Carlo study of error propagation in PET studies.

Familial parkinsonism with synuclein pathology: clinical and PET studies of A30P mutation carriers.

BACKGROUND: The authors identified the second known mutation in the alpha-synuclein(SNCA) gene, an alanine-to-proline exchange in amino acid position 30 (A30P), that cosegregates with the disease in one German family with autosomal dominantly inherited parkinsonism (ADP). The authors studied carriers of the A30P mutation to compare the phenotype of this mutation with idiopathic PD (IPD) and to assess nigrostriatal dopaminergic function in symptomatic and preclinical mutation carriers. METHODS: The pedigree of the A30P family spans five generations with five affected individuals. The authors performed detailed neurologic examinations followed by mutation analysis in 11 living individuals. In three mutation carriers, two individuals with definite PD and one person at risk for PD, they used L-[18]F-fluoro-3,4-dihydroxyphenylalanine (F-DOPA), [11]C-raclopride (RAC), and [18]F-fluorodeoxyglucose (FDG) PET to investigate presynaptic dopaminergic function, dopamine D2 receptors, and cerebral energy metabolism. The authors studied the cognitive functions of carriers of the A30P mutation using neuropsychological screening. RESULTS: PET studies revealed striatal presynaptic dopaminergic alterations consistent with sporadic IPD in two affected family members and no evidence for nigrostriatal dopaminergic dysfunction in one presymptomatic mutation carrier. Neuropsychological testing in four mutation carriers provided evidence for cognitive impairment as a frequent and early symptom of the A30P mutation; this is also supported by regional cerebral energy metabolism alterations in the clinically presymptomatic subject. CONCLUSIONS: The phenotype of the A30P mutation in the SNCA gene is similar to that of sporadic IPD, including a high variability of the age at disease onset, ranging from 54 to 76 years. The follow-up of presymptomatic carriers of the A30P mutation may give insight into preclinical disease stages and early manifestations of PD.

Disturbed functional brain interactions underlying deficient tactile object discrimination in Parkinson's disease.

Somatosensory discrimination of cuboid objects was studied in a group of healthy volunteers and patients with Parkinson's disease using regional cerebral blood flow (rCBF) measurements obtained with positron emission tomography (PET) and 15O labeled water [H2 15O]. A 6-[18F]-fluoro-L-dopa (FDOPA) PET scan demonstrated that the patients may be grouped into those with normal and those with abnormally lowA FDOPA uptake in the caudate nucleus. The categorical group comparisons revealed that task-induced rCBF increases were deficient in bilateral motor and sensory cortical areas in the Parkinson patients. Moreover, deficient rCBF increases were evident in the mesial and right dorsolateral prefrontal cortex for patients in a more advanced disease state, who showed low FDOPA uptake in the caudate nucleus. A principal component analysis (PCA), performed on the rCBF data, identified three patterns (principal components, PCs) that differentiated patients from normals. The first PC represented a right-hemisphere dominant, bilateral group of brain areas known to be involved in tactile exploration. A second PC reflected a cortical-subcortical pattern of functional interactions, comprising cortical areas important for working memory processes. The third group-differentiating PC revealed a pattern of functional interactions involving bilateral temporo-parieto-occipital association cortices, which was consistent with a hypothesized supramodal network necessary for object discrimination. In an additional subgroup analysis, greater expression of the third PC pattern predicted greater caudate FDOPA uptake in patients. Our neuroimaging data revealed a disturbance of distinct patterns of brain functional interactions related to the sensorimotor deficit in Parkinson's disease and to deficits of cognitive information processing deficits in the more advanced stage of Parkinson's disease.

Imaging brain tumor proliferative activity with [124I]iododeoxyuridine.

Iododeoxyuridine (IUdR) uptake and retention was imaged by positron emission tomography (PET) at 0-48 min and 24 h after administration of 28.0-64.4 MBq (0.76-1.74 mCi) of [124I]IUdR in 20 patients with brain tumors, including meningiomas and gliomas. The PET images were directly compared with gadolinium contrast-enhanced or T2-weighted magnetic resonance images. Estimates for IUdR-DNA incorporation in tumor tissue (Ki) required pharmacokinetic modeling and fitting of the 0-48 min dynamically acquired data to correct the 24-h image data for residual, nonincorporated radioactivity that did not clear from the tissue during the 24-h period after IUdR injection. Standard uptake values (SUVs) and tumor:brain activity ratios (Tm:Br) were also calculated from the 24-h image data. The Ki, SUV, and Tm/Br values were related to tumor type and grade, tumor labeling index, and survival after the PET scan. The plasma half-life of [124I]IUdR was short (2-3 min), and the arterial plasma input function was similar between patients (48 +/- 12 SUV*min). Plasma clearance of the major radiolabeled metabolite ([124I]iodide) varied somewhat between patients and was markedly prolonged in one patient with renal insufficiency. It was apparent from our analysis that a sizable fraction (15-93%) of residual nonincorporated radioactivity (largely [124I]iodide) remained in the tumors after the 24-h washout period, and this fraction varied between the different tumor groups. Because the SUV and Tm:Br ratio values reflect both IUdR-DNA incorporated and exchangeable nonincorporated radioactivity, any residual nonincorporated radioactivity will amplify their values and distort their significance and interpretation. This was particularly apparent in the meningioma and glioblastoma multiforme groups of tumors. Mean tumor Ki values ranged between 0.5 +/- 0.9 (meningiomas) and 3.9 +/- 2.3 microl/min/g (peak value for glioblastoma multiforme, GBM). Comparable SUV and Tm:Br values at 24 h ranged from 0.13 +/- 0.03 to 0.29 +/- 0.19 and from 2.0 +/- 0.6 to 6.1 +/- 1.5 for meningiomas and peak GBMs, respectively. Thus, the range of values was much greater for Ki (approximately 8-fold) compared with that for SUV (approximately 2.2-fold) and Tm:Br (approximately 3-fold). The expected relationships between Ki, SUV, and Tm:Br and other measures of tumor proliferation (tumor type and grade, labeling index, and patient survival) were observed. However, greater image specificity and significance of the SUV and Tm:Br values would be obtained by achieving greater washout and clearance of the exchangeable fraction of residual (background) radioactivity in the tumors, i.e., by increased hydration and urinary clearance and possibly by imaging later than 24 h after [124I]IUdR administration.

Variance in parametric images: direct estimation from parametric projections.

Recent work has shown that it is possible to apply linear kinetic models to dynamic projection data in PET in order to calculate parameter projections. These can subsequently be back-projected to form parametric images--maps of parameters of physiological interest. Critical to the application of these maps, to test for significant changes between normal and pathophysiology, is an assessment of the statistical uncertainty. In this context, parametric images also include simple integral images from, e.g., [O-15]-water used to calculate statistical parametric maps (SPMs). This paper revisits the concept of parameter projections and presents a more general formulation of the parameter projection derivation as well as a method to estimate parameter variance in projection space, showing which analysis methods (models) can be used. Using simulated pharmacokinetic image data we show that a method based on an analysis in projection space inherently calculates the mathematically rigorous pixel variance. This results in an estimation which is as accurate as either estimating variance in image space during model fitting, or estimation by comparison across sets of parametric images--as might be done between individuals in a group pharmacokinetic PET study. The method based on projections has, however, a higher computational efficiency, and is also shown to be more precise, as reflected in smooth variance distribution images when compared to the other methods.

Kinetic modeling of 52Fe/52mMn-citrate at the blood-brain barrier by positron emission tomography.

The kinetics of iron at the blood-brain barrier of the monkey were studied in vivo using positron emission tomography (PET) and the tracer 52Fe/52mMn-citrate. 52mMn is the beta(+)-emitting daughter nuclide of 52Fe and therefore contributes to the observed signal and background in the PET images and may influence the quantification of physiological relevant iron parameters. The kinetics of pure (52m)Mn-citrate at the blood-brain barrier of the monkey were studied experimentally, and the analysis of the data with a reasonable compartment model led to equal efflux and influx parameters for Mn (1.35 +/- 0.3 x 10(-2) min(-1)). By using complexes between Mn and diethylenetriaminepentaacetic acid, the validity of the proposed model could be confirmed. To describe the observed kinetics of 52Fe/(52m)Mn-citrate, the manganese model was coupled to an iron model, which finally allowed the quantification of two iron-specific parameters: an input rate into global brain tissue of 7.15 +/- 2.6 x 10(-4) min(-1) and a time delay of roughly 24 min to account for the observed activities. The simpler linearization procedure has been proposed and could be applied to all our data sets and is able to replace the complicated nonlinear iron/manganese tracer kinetic model neglecting any influence of manganese on the analysis.