High resolution BrainPET combined with simultaneous MRI.

UNLABELLED: After the successful clinical introduction of PET/CT, a novel hybrid imaging technology combining PET with the versatile attributes of MRI is emerging. At the Forschungszentrum Jülich, one of four prototypes available worldwide combining a commercial 3T MRI with a newly developed BrainPET insert has been installed, allowing simultaneous data acquisition with PET and MRI. The BrainPET is equipped with LSO crystals of 2.5 mm width and Avalanche photodiodes (APD) as readout electronics. Here we report on some performance characteristics obtained by phantom studies and also on the initial BrainPET studies on various patients as compared with a conventional HR+ PET-only scanner. MATERIAL, METHODS: The radiotracers [18F]-fluoro-ethyl-tyrosine (FET), [11C]-flumazenil and [18F]-FP-CIT were applied. RESULTS: Comparing the PET data obtained with the BrainPET to those of the HR+ scanner demonstrated the high image quality and the superior resolution capability of the BrainPET. Furthermore, it is shown that various MR images of excellent quality could be acquired simultaneously with BrainPET scans without any relevant artefacts. DISCUSSION, CONCLUSION: Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.

The influence of filtered back-projection and iterative reconstruction on partial volume correction in PET.

AIM: We assess the influence of the reconstruction algorithms [OS-EM for the iterative one vs. a filtered back-projection in Fourier space (DiFT)] on partial volume correction in PET employing a fully 3D 3-compartment MR based PV-correction algorithm. The gray matter voxels in the PET image -- after removal of the white matter and cerebrospinal fluid contribution -- are corrected voxel-by-voxel using the image resolution. MATERIAL, METHODS: Phantom measurements and one healthy human brain FDG study were carried out. For the OSEM reconstruction, a combination of iteration steps and subset numbers (It/Sub) was used, whereby in case of no-convergence the image resolution had to be fitted. The RESULTS from the DiFT reconstruction were equivalent to those obtained from the OSEM reconstruction with 10/32 combination for objects with widespread activity concentration. For the sphere phantom, the mean recovery based on the actual values achieved 99.2% +/- 1.8 for all spheres and all reconstruction modes and It/sub combinations (except for 2/8). In case of the Hoffman 3D brain phantom the mean recovery of the cortical regions was 101% +/- 1.2 (the increase based on the uncorrected values: 35.5% +/- 1.5), while the subcortical regions reached a mean recovery of 80% with an increase of 43.9% +/- 2.5. For the human data, an increase of the metabolized values of several cortical regions ranged between 42% and 48% independent from the reconstruction mode. CONCLUSIONS: Our data show that the 3-compartment fully 3-D MR based PV-correction is sensitive to the choice of reconstruction algorithms and to the parameter choice. They indicate that despite improved spatial resolution, the use of the iterative reconstruction algorithm for PV-correction results in similar recovery factors when compared to a correction using DiFT reconstruction, insofar the image resolution values are fitted at the It/Sub combinations.

Quantitation of regional cerebral blood flow with 15O-butanol and positron emission tomography in humans.

We describe the implementation and validation of a combined dynamic-autoradiographic approach for measuring the regional cerebral blood flow (rCBF) with 15O-butanol. From arterial blood data sampled at a rate of 1 s and list mode data of the cerebral radioactivity accumulated over 100 s, the time shift between blood and tissue curves, the dispersion constant DC, the partition coefficient p, and the CBF were estimated by least squares fitting. Using the fit results, a pixel-by-pixel parametrization of rCBF was computed for a single 40-s (autoradiographic) 15O-butanol uptake image. The mean global CBF found in 27 healthy subjects was 49 +/- 8 ml 100 g-1 min-1. Gray and white matter rCBF were 83 +/- 20 and 16 +/- 3 ml 100 g-1 min-1, respectively, with a corresponding partition coefficient p of 0.77 +/- 0.18 and 0.77 +/- 0.29 ml/g in both compartments. The quantitative images resulted in a significantly higher gray matter rCBF than the autoradiographic images.

The influence of plasma glucose levels on fluorine-18-fluorodeoxyglucose uptake in bronchial carcinomas.

PET studies with 2-18F-fluorodeoxyglucose (FDG) were carried out in 15 patients with bronchial carcinomas, first under fasting conditions and then 2 days later during intravenous infusion of a 20% glucose solution which raised the plasma glucose level from 84.6 +/- 14.7 to 168.3 +/- 23.6 mg/100 ml (n = 15, p < 0.001). Tumor metabolism was quantified by the dose absorption ratio (DAR) of FDG uptake [DAR = tissue concentration/(injected dose/body weight)] and also by the rate of glucose consumption (MR) as measured by the Patlak graphical approach in 12 patients. The DAR decreased from 5.07 +/- 1.89 under fasting conditions to 2.84 +/- 0.97 (-41.8% +/- 15%, n = 15, p < 0.001) during glucose infusion, while the MR remained constant (4.71 +/- 2.38 mg/100 ml/min versus 4.96 +/- 2.46 mg/100 ml/min, n = 12, ns). Correction of the DAR data by plasma glucose level eliminated the significant difference between the fasting and glucose load [4.24 +/- 1.59 versus 4.70 +/- 1.45 (n = 15, ns)], but considerable changes in individual patients remained. These data indicate that the DAR of FDG uptake in bronchial carcinomas is influenced significantly by plasma glucose levels. Dynamic quantification of glucose metabolism using the Patlak approach is less dependent on the plasma glucose level and appears advantageous when high reproducibility is needed.

Expectation maximization reconstruction of positron emission tomography images using anatomical magnetic resonance information.

Using statistical methods the reconstruction of positron emission tomography (PET) images can be improved by high-resolution anatomical information obtained from magnetic resonance (MR) images. We implemented two approaches that utilize MR data for PET reconstruction. The anatomical MR information is modeled as a priori distribution of the PET image and combined with the distribution of the measured PET data to generate the a posteriori function from which the expectation maximization (EM)-type algorithm with a maximum a posteriori (MAP) estimator is derived. One algorithm (Markov-GEM) uses a Gibbs function to model interactions between neighboring pixels within the anatomical regions. The other (Gauss-EM) applies a Gauss function with the same mean for all pixels in a given anatomical region. A basic assumption of these methods is that the radioactivity is homogeneously distributed inside anatomical regions. Simulated and phantom data are investigated under the following aspects: count density, object size, missing anatomical information, and misregistration of the anatomical information. Compared with the maximum likelihood-expectation maximization (ML-EM) algorithm the results of both algorithms show a large reduction of noise with a better delineation of borders. Of the two algorithms tested, the Gauss-EM method is superior in noise reduction (up to 50%). Regarding incorrect a priori information the Gauss-EM algorithm is very sensitive, whereas the Markov-GEM algorithm proved to be stable with a small change of recovery coefficients between 0.5 and 3%.

Markov random field segmentation of brain MR images.

We describe a fully-automatic three-dimensional (3-D)-segmentation technique for brain magnetic resonance (MR) images. By means of Markov random fields (MRF's) the segmentation algorithm captures three features that are of special importance for MR images, i.e., nonparametric distributions of tissue intensities, neighborhood correlations, and signal inhomogeneities. Detailed simulations and real MR images demonstrate the performance of the segmentation algorithm. In particular, the impact of noise, inhomogeneity, smoothing, and structure thickness are analyzed quantitatively. Even single-echo MR images are well classified into gray matter, white matter, cerebrospinal fluid, scalp-bone, and background. A simulated annealing and an iterated conditional modes implementation are presented.

Compensatory mechanisms in patients with asymptomatic carotid artery occlusion.

Twelve patients with asymptomatic occlusion of one (n = 8) or both (n = 4) internal carotid arteries were examined by positron emission tomography (PET) and transcranial Doppler ultrasound. PET measurements included the determination of the regional cerebral blood flow (rCBF), oxygen extraction ratio (rOER), cerebral metabolic rate of oxygen (rCMRO2), and cerebral metabolic rate of glucose consumption (rCMRGlc). Transcranial Doppler ultrasound (TCD) was used to determine the pathways and efficacy of collateralization via the circle of Willis and included spectrum analysis of flow velocities within the middle and anterior cerebral arteries as well as vasoreactivity tests. In correspondence with ultrasound evidence of a haemodynamically effective intracranial collateral circulation no significant differences between patients and controls were observed for rOER, rCMRO2 and rCMRGlc, but rCBF was globally reduced. Furthermore, in all patients with unilateral carotid occlusion PET excluded side asymmetries of any parameter studied. In contrast, flow velocity parameters measured by TCD were significantly reduced ipsilateral and significantly increased contralateral to the carotid obstruction. Vasodilative capacities, however, remained preserved even in the territory of the occluded carotid system. These data indicate that patients with asymptomatic carotid occlusion compensate by haemodynamic and not by metabolic mechanisms in contrast to symptomatic patients.

Early effects of intra-arterial chemotherapy in patients with brain tumours studied with PET: preliminary results.

In ten patients with malignant gliomas the regional cerebral metabolic rate for glucose (rCMRGlc) was studied with positron emission tomography (PET) using 2-18F-deoxyglucose (18FDG) before and within 1 to 7 days after intra-arterial chemotherapy with the nitrosourea derivative ACNU (iaACNU). Three patients were studied before and after two iaACNU courses and one patients before and after three iaACNU courses. The early effects of iaACNU on tumour rCMRGlc were highly variable and appeared to be more pronounced after the first course of iaACNU than in later iaACNU courses, i.e. more pronounced in untreated patients. Although there was no clear correlation between the change of rCMRGlc following the first course of iaACNU and the clinical outcome in this small group of patients, the patient with the most pronounced decrease of tumour metabolism (-16.5%) after the first course of iaACNU exhibited full tumour remission for 12 months, while the patient with the most pronounced increase of tumour metabolism (+65%) after the first course of iaACNU developed rapid tumour progression. The first results indicate that early effects of intra-arterial chemotherapy may be observed with 18FDG PET, especially following the first course of iACNU. Further studies are needed to evaluate the predictive value of such studies for therapy response.

Acute S-ketamine application does not alter cerebral [18F]altanserin binding: a pilot PET study in humans.

Modeling short-term psychotic states with subanaesthetic doses of ketamine provides substantial experimental evidence in support of the glutamate hypothesis of schizophrenia. Ketamine exerts its pharmacological effects both directly via interactions with glutamate receptors and indirectly by stimulating presynaptic release of endogenous serotonin (5-HT). The aim of this feasibility study was to examine whether acute ketamine-induced 5-HT release interferes with the binding of the 5-HT(2A) receptor (5-HT(2A)R) radioligand [(18)F]altanserin and positron emission tomography (PET). Two subjects treated with ketamine and one subject treated with placebo underwent [(18)F]altanserin PET at distribution equilibrium conditions. Robust physiological, psychopathological and cognitive effects were present at ketamine plasma concentrations exceeding 100 microg/l during >70 min. Notwithstanding, we observed stable radioligand binding (changes +/-95% CI of -1.0 +/- 1.6% and +4.1 +/- 1.8% versus -1.2 +/- 2.6%) in large cortical regions presenting high basal uptake of both, [(18)F]altanserin and ketamine. Marginal decreases of 4% of radioligand binding were observed in the frontal lobe, and 8% in a posteriorily specified frontomesial subregion. This finding is not compatible with a specific radioligand displacement from 5-HT(2A)R which should occur proportionally throughout the whole brain. Instead, the spatial pattern of these minor reductions was congruent with ketamine-induced increases in cerebral blood flow observed in a previous study using [(15)O]butanol PET. This may caused by accelerated clearance of unspecifically bound [(18)F]altanserin from cerebral tissue with increased perfusion. In conclusion, this study suggests that [(18)F]altanserin PET is not sensitive to acute neurotransmitter fluctuations under ketamine. Advantageously, the stability of [(18)F]altanserin PET towards acute influences is a prerequisite for its future use to detect sub-acute and chronic effects of ketamine.

Effects of varying physical parameters of a PET system on the accuracy of radioactivity quantitation in vivo.

The accuracy of quantitation of radioactivity by positron emission tomography (PET) is dependent on design parameters which differ among the PET-cameras in use today. Using a high resolution PET camera (Scanditronix PC 4096-15WB) we have simulated various of these parametric design differences such as xy- and z-resolution, slice thickness, methods of scatter and attenuation correction. The quantitation of actual patient data differed by up to 40% for both static and dynamic data when single parameters were varied to fit cameras of preexisting and recent design. For example, we found that cortical FDG data are 15% lower for 11 mm image resolution than for 5.5 mm image resolution, and striatal uptake of a D2-receptor-ligand decreases by 25% when the slice thickness is 14 mm instead of 7 mm. In general, the errors due to the single effects studied here are expected to be cumulative, leading to an even greater discrepancy in the overall performance of older PET cameras when compared to those of recent design.

Performance characteristics of an eight-ring whole body PET scanner.

The technical characteristics of the multislice whole-body positron emission tomographic scanner (model PC4096-15WB Scanditronix) and its performance parameters are described. Spatial resolution at the center of the field of view was found to be 4.9 mm in-plane and 4.6 mm (cross slices) and 6.0 mm (direct slices) in the axial direction. The sensitivity for true and scattered coincidences is approximately 5,000 cps for direct slices and 7,100 cps for cross slices. At an activity concentration of 37 kBq/ml the system deadtime was approximately 5%. By measuring a uniform phantom with a cold cylindrical insert (5.0 cm diameter), the scatter fraction was found to be approximately 5%. The mean global uniformity over all 15 slices was 6.5%, whereas the local uniformity was found to be 4.3%. No systematic nonuniformities were observed. Finally, various methods for attenuation correction (transmission scan, contour finding, ellipse) were utilized to test their effects on the resulting reconstructed images.

Influence of some instrumental parameters on the determination of quantitative data using the PET scanner PC4096-15WB.

In order to evaluate the influence of physical and instrumental limitations of the PET technique on metabolic data, various parameters have been tested. The measurements were done with a whole body PET scanner PC4096-15WB. The dependence on the transaxial resolution of reconstruction filter cut off frequency alpha c was investigated. The high resolution (4.8 mm at r = 0 in the field of view) and the low scatter fraction (less than 5%) of this system yields a higher grey/white matter ratio (3.8:1) than that found with older scanners (2:1). The use of a rotating pin source allows transmission scans to be performed after tracer administration with an error of less than 5%.

Changed pattern of regional glucose metabolism during yoga meditative relaxation.

Using positron emission tomography (PET), measurements of the regional cerebral metabolic rate of glucose (rCMRGlc) are able to delineate cerebral metabolic responses to external or mental stimulation. In order to examine possible changes of brain metabolism due to Yoga meditation PET scans were performed in 8 members of a Yoga meditation group during the normal control state (C) and Yoga meditative relaxation (YMR). Whereas there were intraindividual changes of the total CMRGlc, the alterations were not significant for intergroup comparison; specific focal changes or changes in the interhemispheric differences in metabolism were also not seen; however the ratios of frontal vs. occipital rCMRGlc were significantly elevated (p less than 0.05) during YMR. These altered ratios were caused by a slight increase of frontal rCMRGlc and a more pronounced reduction in primary and secondary visual centers. These data indicate a holistic behavior of the brain metabolism during the time of altered state of consciousness during YMR.

Imaging dopamine D4 receptors in the living primate brain: a positron emission tomography study using the novel D1/D4 antagonist [11C]SDZ GLC 756.

The dopamine D4 receptor has lately attracted interest since it has been hypothesized to be involved in the pathogenesis and pharmacotherapy of neuropsychiatric diseases. The present study provides first in vivo evidence of dopamine D4 receptors in primate brain using a [11C]benzo[g]quinoline, the novel radioligand [11C]SDZ GLC 756 ([11C]GLC: in vitro dissociation constants at human receptor clones [nM]: 1.10 at D1; 0.40 at D2; 25 at D3; 0.18 at D4.2; 6.03 at D5). Dynamic positron emission tomography scans were performed on healthy baboons (Papio hamadryas, n = 3). Specific receptor binding (SB) was calculated for striatum and neocortex (frontal, temporal, parietal, and occipital) based on the differences between the regional and the cerebellar concentration of [11C]. Blockade of D1 and D5 receptors by SCH23390 (1.7 pmol/kg) diminished SB in the striatum by 55 +/- 4% (mean +/- standard deviation, P < 0.05) and in the frontal cortex by 13 +/- 8% (P < 0.05) when compared to SB in the unblocked state (SB(D1-D5)). In the presence of the dopamine antagonists SCH23390 (1.7 micromol/kg) and raclopride (5.7 pmol/kg)--which mask the D1, D2, D3, and D5 subtypes--SB of [11C]GLC to D4 receptors (SB(D4)) was demonstrated in the striatum and all cortical regions of interest. In the striatum, the ratio of SB(D4)/SB(D1-D5) was 0.13 +/- 0.07. In the neocortex, SB(D4)/SB(D1-D5) was notably higher (0.77 +/- 0.29; mean of all cortical regions of interest). The widespread distribution of dopamine D4 receptors suggests a basic functional role of this receptor subtype in the modulation of cortical and subcortical neuronal activity.