Matthias E. Bellemann

Performance evaluation of the whole-body PET scanner ECAT EXACT HR/sup +/ following the IEC standard

The performance parameters of the whole-body PET scanner ECAT EXACT HR/sup +/ (CTI/Siemens, Knoxville, TN) were determined following the standard proposed by the International Electrotechnical Commission (IEC). The tests were expanded by some measurements concerning the accuracy of the correction algorithms and the geometric fidelity of the reconstructed images. The scanner consists of 32 rings, each with 576 BGO detectors (4.05/spl times/4.39/spl times/30 mm/sup 3/), covering an axial field-of-view of 15.5 cm and a patient port of 56.2 cm. The transaxial FWHM determined by a Gaussian fit in the 2D (3D) mode is 4.5 (4.3) mm at the center. It increases to 8.9 (8.3) mm radially and to 5.8 (5.2) mm tangentially at a radial distance of r=20 cm. The average axial resolution varies between 4.9 (4.1) mm FWHM at the center and 8.8 (8.1) mm at r=20 cm. The system sensitivity for unscattered true events is 5.85 (26.4) cps/Bq/ml (measured with a 20 cm cylinder). The 50% dead-time losses were reached for a true event count rate (including scatter) of 286 (500) kcps at an activity concentration of 74 (25) kBq/ml. The system scatter fraction is 0.24 (0.35). With the exception of the 3D attenuation correction algorithm, all correction algorithms work reliably. The results reveal that the ECAT EXACT HR/sup +/ has a good and nearly isotropic spatial resolution. Due to the small detector elements, however, it has a low slice sensitivity which is a limiting factor for image quality.

MR imaging of fat-containing tissues : valuation of two quantitative imaging techniques in comparison with localized proton spectroscopy

Since lipid protons, consisting mainly of triacylglycerols (TAG), are rather mobile, magnetic resonance imaging (MRI) is ideally suited for the examination of fat-containing tissues such as bone marrow. In contrast to water protons, however, lipid protons are chemically distinct and give rise to at least eight resonance peaks with different T1 and T2 relaxation times in the 1H spectrum. This is why the characterization of fat-containing tissues by quantitative MRI is much more difficult than that of most other tissues. In our study we wanted to examine the accuracy and the potential of a 1H chemical shift imaging (CSI) technique and a multiple spin-echo imaging (MSEI) technique. A stimulated-echo (STEAM) sequence for spatially localized proton spectroscopy was used as the reference method. In the first part of this paper, we describe quantitative imaging experiments which were performed to assess the accuracy of the fat-water separation according to the Dixon method and the bi-exponential decomposition of the MSEI data. For that purpose, we used a two-compartment phantom filled with either an aqueous Gd-DTPA solution and vegetable oil or with two different aqueous Gd-DTPA solutions, respectively. The analysis of the 1H CSI data revealed that the presence of non-methylen protons in neutral fats leads to a slight under-estimation (of about 15%) of the relative fat fraction. The error is described theoretically and verified quantitatively by STEAM measurements. The bi-exponential analysis of the transverse relaxation data, on the other hand, yields reliable T2 values if the relative proton density of both components is higher than 15%. IN the second part of our investigation, the same techniques were applied to acquire data from the subcutaneous fatty tissue, the femoral head, and the lumbar vertebrae of three healthy volunteers. In the bone marrow spectra, only two broad resonances could be resolved; they were superpositions of diverse molecular groups with different T1 and T2 relaxation times. In these cases, localized proton spectroscopy does not provide additional information with respect to 1H CSI. The MSEI data of the three examined fat containing tissue regions were adequately fitted by a bi-exponential function despite the fact that there were much more chemically distinct protons present in fatty tissues.

A novel method for real-time magnetic marker monitoring in the gastrointestinal tract

In internal medicine, a simple method for the functional examination of the gastrointestinal tract without the risk of radiation exposure is required. We describe a novel principle based on the monitoring of magnetic markers which meets these demands. Our method employs a special permanent magnet which is repeatedly aligned by a vertically oriented pulsed magnetic field. Due to this alignment, the marker position can be derived from the stray field components measured by commercial field sensors. Our method was evaluated by means of a 3D intestinal phantom. The monitoring procedure yielded the time course of the marker position as a 3D plot either in real-time or as a time-lapse movie. The spatial resolution, expressed by the mean square deviation, was better than 10 mm and is thus sufficiently high to distinguish between adjacent loops of the gut. The temporal resolution, i.e. the minimum time between two successive measurements, was about 1 s. The presented method has very moderate technical demands and allows us to monitor magnetic markers in real-time. The technique may be useful with respect to functional examination of the gastrointestinal tract. In pharmaceutical research, our method offers the opportunity for remote drug release at any position of the gut.

Functional magnetic resonance imaging of category-specific cortical activation: evidence for semantic maps

Functional magnetic resonance imaging (fMRI) was used to examine the pattern of cortical activity during a picture naming task. Subjects (n=12) had to covertly name either animals or furniture items. Functional scanning was performed using a conventional 1.5-Tesla whole-body MRI system. Images obtained during naming the two categories were compared using a non-parametric test. The study revealed evidence for domain-specific lexical regions in left middle, right middle and inferior frontal areas, as well as in superior and middle temporal areas. The results corroborate neuropsychological data and demonstrate directly and non-invasively in human volunteers that semantic representations in frontal and temporal areas are, to some degree, localized and possibly implemented as multiple maps. A completely distributed storage of semantic information is rendered unlikely.

Assessment of the biodistribution and metabolism of 5-fluorouracil as monitored by 18F PET and 19F MRI: A comparative animal study

The effective clinical use of the anticancer drug 5-fluorouracil (5-FU) requires the non-invasive assessment of its transport and metabolism, particularly in the tumor and the liver, where the drug is catabolized to alpha-fluoro-beta-alanine (FBAL). In this study, the potentials and limitations of dynamic 18F PET and metabolic 19F MRI examinations for noninvasive 5-FU monitoring were investigated in ACI and Buffalo rats with transplanted MH3924A and TC5123 Morris hepatomas, respectively. Selective 5-[19F]FU and [19F]FBAL MR images were acquired 5 and 70 min after 5-FU injection using a CHESS MRI sequence. After administration of 5-[18F]FU, the kinetics of the regional 5-[18F]FU uptake were measured by dynamic PET scanning over 120 min. To allow a comparison between PET and MRI data, standardized uptake values (SUV) were computed at the same points in time. The TC5123 hepatoma showed a significantly (p < 0.002) higher mean SUV at 5 and 70 min post-5-FU injection than the MH3924A cell lines, whereas there were no significant differences between the mean SUV measured in the liver of both animal populations. In contrast to the PET data, no significant differences in the mean 5-[19F]FU and [19F]FBAL MR signal values in the tumor of both models were observed. The MR images, however, yielded the additional information that 5-FU is converted to FBAL only in the liver and not in the hepatomas.

Uncoupling of 2-fluoro-2-deoxyglucose transport and phosphorylation in rat hepatoma during gene therapy with HSV thymidine kinase

This animal study investigates the application of positron emission tomography (PET) with tracers of tumour metabolism for monitoring suicide gene therapy with herpes simplex virus thymidine kinase (HSVtk). After transplantation of HSVtk-expressing Morris hepatoma cells into ACI rats, dynamic PET measurements of 18F-labeled 2-fluoro-2-deoxyglucose (FDG) uptake were performed in animals 2 days (n = 7) and 4 days (n = 5) after the onset of therapy with 100 mg ganciclovir (GCV)/kg body weight as well as after administration of sodium chloride (n = 8). The arterial FDG plasma concentration was measured dynamically in an extracorporeal loop and the rate constants for FDG transport (K1, k2) and FDG phosphorylation (k3) were calculated using a three-compartment model modified for heterogeneous tissues. Also, quantification using the metabolic rate of FDG turnover and the standardized uptake value (SUV) was done. Furthermore, the thymidine incor- poration into the tumour DNA was determined after i.v. administration of 3H-thymidine. An uncoupling of FDG transport and phosphorylation was found with enhanced K1 and k2 values and a normal k3 after 2 days of GCV treatment. The increase in FDG transport normalized after 4 days whereas the phosphorylation rate k3 increased. Quantification using the metabolic rate or the SUV showed congruent but less sensitive results compared with the modeling approach. The thymidine incorporation into the DNA of the tumours declined to 10.5% of the controls after 4 days of GCV treatment. The data indicate that PET with 18FDG and 11C-thymidine may be applied for monitoring of gene therapy with the HSVtk/GCV suicide system. Increased transport rates are evidence of stress reactions early after therapy. The measurement of thymidine incorporation into the tumour DNA can be used as an indicator of therapy efficacy.

Functional MR imaging of the prefrontal cortex: specific activation in a working memory task.

Functional magnetic resonance imaging was used to identify cortical regions activated by a working memory task involving letter detection. Twenty four normal subjects were scanned with a conventional 1.5-T magnet while performing one of two tasks: In the activation task, subjects responded by pressing a button whenever any presented letter was the same as the second last in the sequence. In the control condition, subjects had to respond to a single predefined letter without memory update requirements. The activation task and the control condition were identical with regard to perceptual input and motor output. They were different only regarding the task demand. Movement artifacts were minimized in a two way strategy and eight subjects were excluded from further analysis. Functional MR data from the remaining 16 subjects were analyzed on the basis of anatomical regions-of-interest which were manually defined in each subject. The engagement of working memory produced significant activation in the dorsolateral prefrontal cortex (Brodmanns areas 9, 10, 46, and 47) in both hemispheres. Results demonstrate the applicability of the paradigm within a clinical MRI setup and corroborate previous findings of non-lateralized dorsolateral prefrontal activation during continuous context updating and active maintenance.

Iterative reconstruction of PET images using a high-overrelaxation single-projection algorithm

An iterative image reconstruction procedure is described which is able to calculate high-precision images within eight iterative steps. High initial overrelaxation parameters are used which drop down towards about one during continuing iteration. The parameters are determined pragmatically, postulating-maximum gain of image quality during a sequence of iterative steps. Results with simulated and measured data show that parameters derived from one data set may be widely used for other data sets. The acceleration of iterative reconstruction achieved by the estimation of optimum overrelaxation parameters is important for large data sets, especially for fully 3D reconstruction.

Noninvasive determination of the arterial input function of an anticancer drug from dynamic PET scans using the population approach

For the application of a kinetic model to PET data, it is generally necessary to obtain the arterial input function (AIF). It was the aim of the present study to introduce a method suitable for the determination of the AIF of a substance that undergoes biochemical transformation from noisy PET data: the population approach. F-18 labeled 5-fluorouracil (5-[18F]FU) was administered i.v. to eight patients suffering from liver metastases of colorectal carcinoma. Radioactivity concentrations in liver and aorta were dynamically measured with PET over 120 min. Pharmacokinetic analysis was carried out by applying a five-compartment model to individual activity-time data for the eight patients or to the mean activity-time data among the eight patients. The mean values of all parameters describing 5-FU transport and catabolism, i.e., volumes of distribution and clearances, as well as interindividual coefficients of variation (CV) were calculated according to both approaches. With our model, we were able to separate the concentration-time course of 5-FU in plasma, i.e., the AIF, from that of its major catabolite alpha-fluoro-beta-alanine (FBAL). As far as the mean parameter estimates are concerned, the differences between both approaches are not significant. For the liver data, the CVs are almost the same for both approaches. For the parameters concerning the aorta, however, there is a decrease in the CVs by using the population approach. For example, the CV of the central distribution volume of 5-FU was 30% for the individual approach and 18% for the population approach. With the population approach, it is possible to determine the AIF of drugs that undergo metabolic conversion, such as anticancer drugs, from the abdominal aorta visualized on PET images. The population approach helps to overcome noise in individual data. Since no measurements are needed in addition to the PET examination, the suggested method helps to reduce risk and pain for the patients as well as cost and thus facilitates large scale patient studies.

Functional MR imaging of semantic information processing and learning-related effects using psychometrically controlled stimulation paradigms.

Functional magnetic resonance imaging (fMRI), in conjunction with carefully designed, psychometrically optimized stimulation procedures, was used to investigate the relation between brain activation and the processing of word associations. A semantic discrimination task of word-pair similarity was performed by normal subjects (n = 17) within a clinical 1.5-Tesla whole-body MRI system. A color similarity task of psychometrically equivalent difficulty, as indicated by behavioral data acquired online during fMRI, served as active control condition. Comparisons between tasks dramatically improved results compared to comparisons between task and resting condition. The language paradigm selectively activated left frontal and left fronto-temporal areas. Cortical activation during the semantic task decreased significantly over three runs of the same word list and was paralleled by decreased reaction times. No such changes were observed in the active control condition indicating selective learning of the language task only. When combined with psychological activation schemes and the acquisition of behavioral data, fMRI represents a powerful tool for the study of brain-behavior interaction.