Josef Doll

Fast implementation of the single scatter simulation algorithm and its use in iterative image reconstruction of PET data

In positron emission tomography (PET), scatter correction is usually performed prior to image reconstruction using a more or less exact model of the scatter processes. These models require estimates of the true activity and object density distributions of the imaged object. The problem is that these estimates are computed from measured data and, therefore, already contain scattered events. The purpose of this work was to overcome this problem by incorporating scatter characteristics directly into the process of iterative image reconstruction. This could be achieved by an optimized implementation of the single scatter simulation (SSS) algorithm, which results in a significant speed-up of the scatter estimation procedure. The scatter simulation was then included in the forward projection step of maximum likelihood image reconstruction. The results demonstrate that this approach leads to a more exact estimation of the scatter component which cannot be obtained by a simple sequential data processing strategy.

Scatter correction in the transaxial slices of a whole-body positron emission tomograph

A procedure for scatter correction in a whole-body positron emission tomograph (PET) is presented. The method is based on measured scatter distributions of line sources. It extends the method originally developed by Bergstrom et al. (1983) for brain scanners to large objects. Scatter distributions were measured with line sources at different positions in cylindrical water containers with diameters ranging from 20 to 35 cm. The projection data were approximated by a monoexponential function, the scatter distribution function f. The parameters of this function depended on the projected distance of the source from the centre and on the diameter of the phantom. For scatter correction, the scatter distributions in emission scans were calculated by integral transformation of the measured projection data with the spatially variant scatter distribution function, and then subtracted from the measured projection data. The method was tested using cylindrical phantoms of different diameters and the EEC body phantom with arms, both with uniform activity distributions.

Measured attenuation correction methods.

Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4–5 in brain studies to 50–100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide68Ge/68Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible.

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.

Scatter suppression by using a rotating pin source in PET transmission measurements

Transmission scans used essentially for attenuation correction in whole-body studies with positron-emission tomography (PET) contain different amounts of scatter contamination, depending on the source used. It is shown by phantom studies that scatter causes spatial distortions and nonuniformities in the attenuation images, leading to errors in the attenuation correction factors. For these measurements a ring-shaped transmission source is simulated by a 6-cm-long rotating pin source containing 5 mCi of /sup 68/Ge. The measurements are performed using large phantoms filled with water. Scattered radiation is substantially suppressed by selecting only chords through the actual position of the source instead of collecting all coincident events. Improved edge delineation and homogeneity of the attenuation images are achieved. >

Development and Initial Results of a Tomographic Dual-Modality Positron/Optical Small Animal Imager

Herein, we present a novel concept for fully integrated dual-modality in vivo tomographic imaging yielding simultaneous detection of positron and optically labeled probes in small animals. The imager consists of an allocation of optical detector modules and, in radial extension, the allocation of positron emission detector modules. Laser scanning and large-field light sources are integrated to facilitate fluorescence imaging in addition to bioluminescence imaging. Each optical detector unit consists of a large-area photon sensor for light detection, a microlens array for field-of-view definition, a septum mask for cross-talk suppression, and a transferable filter for wavelength selection. To prove the working principle of the dual-modality detector system a pair of optical detectors along with a large-field excitation source was placed inside the bore of a Siemens EXACT HR+ scanner, performing simultaneous imaging. The imaging characteristics of the optical detector were evaluated experimentally using a prototypical setup with geometrical phantoms. The sensitivity of the optical detector prototype was found less than that of a reference CCD camera. We propose several ways of increasing optical detector sensitivity.

PET-Studien mit C-11-Äthanol bei der intratumoralen Therapie von hepatozellulären Karzinomen

ZusammenfassungDie Positronenemissionstomographie (PET) ermöglicht als nicht-invasive funktionelle Methode die Untersuchung von Perfusion, Stoffwechsel sowie Therapeutikawirkung bei soliden Tumoren und wurde deshalb zur Analyse der Äthanolablation von hepatozellulären Karzinomen (HCC) eingesetzt. Bei 7 Patienten (Child-A-Zirrhose) mit HCC (Tumorstadium III-IVA; Tumorgröße 3–6 cm) wurden vor einer Äthanolablation dynamische PET-Messungen mit F-18-Fluordeoxyglukose (FDG) über 60 min zur Erfassung des regionalen FDG-Stoffwechsels über dem Zielgebiet durchgeführt; 6 Tumoren (gut und mittel differenzierte HCC) zeigten eine leberäquivalente FDG-Aufnahme und waren schlecht abgrenzbar, ein Tumor (mittel differenziertes HCC) zeigte eine mäßige Stoffwechselerhöhung. Es fand sich in diesem Kollektiv kein Zusammenhang zwischen Histologie und FDG-Metabolismus. Die Untersuchung der Äthanolkinetik erfolgte während einer intratumoralen Applikation von 37–80 MBq C-11-Äthanol zusammen mit der therapeutischen Dosis von 5–10 ml unmarkiertem Äthanol über eine sonographisch positionierte Punktionsnadel. Die dynamischen PET-Messungen des C-11-Äthanoltracers wurden über 45 min durchgeführt. In 5 von 7 Tumoren wurde eine hohe intratumorale Anreicherung des Tracers nach Applikation beobachtet, die über die gesamte Meßperiode anhielt. Eine signifikante Elimination des Äthanols aus dem Tumor bzw. eine Akkumulation im umgebenden Lebergewebe fand nicht statt. In einem Fall erfolgte ein frühzeitiger Abstrom über eine Tumorvene, bei einer anderen Behandlung kam es wegen einer Fehlpositionierung der Nadel zu einer Traceraufnahme des umgebenden Lebergewebes. Die PET-Methodik eignet sich zur Untersuchung von Kinetik und Mechanismus der perkutanen intratumoralen Äthanolbehandlung und leistet damit einen Beitrag zur Validierung und Optimierung von Lokalverfahren.SummaryPositron emission tomography (PET) is a noninvasive functional method for the study of solid tumor perfusion, metabolism and interaction with different therapeutic agents. The aim of the study was the investigation of the metabolism of hepatocellular carcinomas (HCC) and the kinetics during a treatment with intratumoral ethanol by PET. The ongoing study includes seven patients with child A cirrhosis and HCC (UICC stage III-IVA; tumor size 3–6 cm). Dynamic PET studies (60 min) with 18F-fluordeoxyglucose (FDG) were performed prior to therapy to assess tumor viability. The evaluation of the FDG data demonstrated a liver-equivalent uptake in six of the tumors (well and moderately differentiated HCC), which were poorly delineated against the normal liver parenchyma. One moderately differentiated HCC showed an increased FDG metabolism, indicating no correlation between histology and metabolism. A dose of 37–80 MBq 11C-ethanol was applied together with a nonlabelled therapeutic dose of the drug via a puncture needle positioned under sonography. Five out of seven tumors demonstrated a high 11C uptake shortly after the end of the ethanol injection followed by constant 11C-ethanol concentration during the whole study period of 45 min. The PET data demonstrated no significant elimination of the 11C-ethanol from the tumor and no accumulation in the surrounding liver tissue. One case showed a decrease of the intratumoral 11C-ethanol concentration due to a punkture of a tumor vein, and in another case the surrounding liver parenchyma demonstrated significant 11C uptake in the early phase following paratumoral injection of the drug. In conclusion, PET is a useful tool for the study of the mechanism and the kinetics of percutaneous intratumoral ethanol injection of HCC.

Effects of Distorted PET Projection Data on the Reconstructed Image Using Different Reconstruction Algorithms

In a simulation study, the effects of multiplicative and additive distortions of the projection data on the reconstructed image quality and quantitation capability were investigated. Three different reconstruction algorithms were compared: (i) filtered back-projection (FBP), (ii) an iterative method with multiplicative correction term (ML-EM), and (iii) an iterative method with additive correction term (AR-AC). Distortions were uniformly applied to all projections with projection angles ranging from 72° through 108°. Multiplicative distortion factors ranged from 0.5 to 1.4, additive distortions were −30% to +30%. The reconstructed images and activity concentrations were not affected by the multiplicative distortions if ML-EM was applied, whereas additive distortions were best tolerated when FBP or AR-AC were used for image reconstruction.

Calculation of residence time distributions of intravascular radioactive tracers in fields of external registration.

Because of the physiological significance of the mean velocity of blood flow, indicator dispersion models are of special interest and posses practical relevance, if biological and extraneous variables can be altered. The variables being considered are flow characteristics of the streaming blood, tracer distribution at the entrance into the flow system, and the area in which impulses are collected to form the time-activity curve. Using a simplified version of the general convective diffusion equation (diffusion model) in which the diffusion constant D includes all propagation and mixing of the tracer, a simple numerical method can be applied. The method is used to determine influences of injection and changed regions of interest on the time-activity curve and the following parameters: appearance times, peak times, mean circulation times, and the times of the first inflection points. For this purpose, the range of D was determined in 14 patients by applying experimental data to the model. The calculations on the variables show, that the advantage of this method is its applicability to any experimental case by simply adapting the input data to the recordings.

Positron Emission Tomography with Fluorodeoxyglucose for the Evaluation of Tumor Recurrence of Thoracic Tumors

The detection of recurrent tumors of thoracic lesions has remained a difficult diagnostic challenge despite the great advances seen in computed tomography (CT) and magnetic resonance imaging (MRI). The common differential diagnostic problem of distinguishing tumor recurrence from scar or inflammatory tissue has increasingly become a difficult clinical problem. Since therapeutic approaches are available in cases of recurrences, a timely and correct diagnosis becomes of increasing importance. The morphologic evaluation of suspect regions of tumor recurrences is quite limited especially if the size of the lesion is still small. Therefore additional information in conjunction with its morphologic information is needed. Positron emission tomography (PET) using metabolically active compounds, such as flour-18 labelled deoxyglucose (FDG) allow imaging of metabolism [1]. As clinical studies to evaluate the potential use of FDG PET imaging for thoracic lesions have shown a great potential benefits [2, 3], this technique is being introduced for the evaluation of recurrent tumors. Two considerations of great importance in the evaluation of recurrent tumors by PET are changes in the metabolic state and function of lesions due to the previous therapy and secondarily due to therapeutic procedures, which may have altered the cross-sectional anatomy. A very careful correlation between the morphologic cross-sectional information obtained by CT and MRI with the functional cross-sectional information available by PET is necessary.