[Diagnostic evaluation of the breast using PET: optimization of data acquisition and postprocessing]. / Mammadiagnostik mit PET: Optimierung der Datenakquisition und -nachverarbeitung.

PURPOSE: Development and evaluation of an optimized protocol for PET examinations of the female breast with 2-F-18-fluoro-2-deoxyglucose (F-18-FDG). METHODS: All PET measurements were performed with a whole-body PET system (ECAT EXACT HR+). In order to examine the women with the breasts freely pendant, a special extension for the patient table made of carbon layer composite was designed. After data acquisition in the 3D modus, emission data were sorted into 2D sinograms using the Fourier rebinning algorithm and reconstructed by means of an ultra-fast iterative 2D algorithm (HOSP). The reconstructed emission scans were superimposed onto the corresponding transmission images. The protocol presented was evaluated in examinations on 6 women with breast lesions after the administration of 150-220 MBq F-18-FDG. From two adjacent bed positions, emission and transmission data were acquired over periods of 20 min and 10 min, respectively. For comparison, dynamic magnetic resonance (MR) image series were acquired with a whole-body MR system (MAGNETOM SP 4000) using a double-breast coil. RESULTS AND CONCLUSION: Using the designed extension of the patient table, it was possible to examine corpulent women despite the limited patient port of the PET system in the prone position with the breasts freely pendant. Alongside a reduction in motion artifacts, this positioning also offers the possibility of making a direct comparison between PET and MR images. Despite the fact that the amount of F-18-FDG applied to the patient was markedly reduced, the combination of 3D data acquisition and iterative image reconstruction resulted in excellent quality of the emission scans. By super-positioning of iteratively reconstructed emission and transmission scans, anatomical localization of breast lesions visualized on the emission scans could be improved. The postprocessing of the PET data described was completed in 60 min, this meaning that the presented concept can readily be employed in clinical practice.

[Reduction of radiation exposure in PET examinations by data acquisition in the 3D mode]. / Reduktion der Strahlenexposition bei PET-Untersuchungen durch Datenakquisition im 3D-Modus.

AIM: Modern volume PET systems offer the possibility to measure without the shadowing effect of interplane septa (2D mode) and thus to detect coincident events between detectors on distant rings (3D mode). It was the aim of the present paper to characterize the count rate behaviour of a latest-generation whole-body PET system in the 2D and 3D mode as well as to discuss the consequences for the radiation hygiene of PET examinations with 2-[F-18]-fluoro-2-deoxyglucose (18-F-FDG). METHODS: All experiments were performed with the PET system ECAT EXACT HR+. For 2D data acquisition, a collimator of thin tungsten septa was positioned in the field-of-view. The count rate behaviour of the scanner was evaluated in the 2D and 3D mode over a wide range of F-18 activity concentrations following the NEMA protocol. Moreover, PET images of the EEC whole-body phantom with different inserts were acquired in the 2D and 3D mode over a period of 15 min each. For the 3D measurement, the activity concentrations of the F-18 solution were only half of those used for the 2D measurement. RESULTS: For the circular NEMA phantom (phi = 19.4 cm, length = 19.0 cm), we observed an increase of the system sensitivity in the 3D mode by a factor of about 5 with respect to the 2D mode (27.7 vs. 5.7 cps/Bq/ml). The evaluation of the activity distributions of the EEC phantom reconstructed from the 3D data set revealed a superior image quality compared to the corresponding 2D images despite the fact that the activity concentrations were only half as high. CONCLUSIONS: By using the 3D data acquisition mode, it is possible to markedly reduce the amount of activity to be applied to the patient and nevertheless to improve image quality. In our experience, it is sufficient to administer an activity of 150-200 MBq for whole-body examinations with F-18-FDG, which results in an effective equivalent dose of 3 or 4 mSv, respectively.

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 incorporation 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.

[Investigation of the signal-to-noise ratio on a state-of-the-art PET system: measurements with the EEC whole-body phantom]. / Untersuchung des Signal-zu-Rausch-Verhältnisses an einem modernen PET-System: Messungen am EEC-Ganzkörperphantom.

AIM: The spatial resolution of PET scanners can be improved by using smaller detector elements. This approach, however, results in poorer counting statistics of the reconstructed images. Therefore, the aim of this study was to investigate the influence of different acquisition parameters on the signal-to-noise ratio (SNR) and thus to optimize PET image quality. METHODS: The experiments were performed with the latest-generation whole-body PET system (ECAT Exact HR+, Siemens/CTI) using the standard 2D and 3D data acquisition parameters recommended by the manufacturer. The EEC whole-body phantom with different inserts was used to simulate patient examinations of the thorax. Emission and transmission scans were acquired with varying numbers of events and at different settings of the lower level energy discriminator. The influence of the number of counts on the SNR was parameterized using a simple model function. RESULTS: For count rates frequently encountered in clinical PET studies, the emission scan has a stronger influence on the SNR in the reconstructed image than the transmission scan. The SNR can be improved by using a higher setting of the lower energy level provided that the total number of counts is kept constant. Based on the established model function, the relative duration of the emission scan with respect to the total acquisition time was optimized, yielding a value of about 75% for both the 2D and 3D mode. CONCLUSION: The presented phenomenological approach can readily be employed to optimize the SNR and thus the quality of PET images acquired at different scanners or with different examination protocols.

[Optimization of PET image quality by means of 3D data acquisition and iterative image reconstruction]. / Optimierung der Bildqualität von PET-Aufnahmen durch 3D-Datenakquisition und iterative Bildrekonstruction.

PURPOSE: In the recent past, several algorithms have been developed in order to transform 3D sinograms acquired at volume PET systems into 2D data sets. These methods offer the possibility to combine the high sensitivity of the 3D measurement with the advantages of iterative 2D image reconstruction. The purpose of our study was the assessment of this approach by using phantom measurements and patient examinations. METHODS: The experiments were performed at the latest-generation whole-body PET system ECAT EXACT HR+. For 2D data acquisition, a collimator of thin tungsten septa was positioned in the field-of-view. Prior to image reconstruction, the measured 3D data were sorted into 2D sinograms by suing the Fourier rebinning (FORE) algorithm developed by M. Defrise. The standard filtered backprojection (FBP) method and an optimized ML/EM algorithm with overrelaxation for accelerated convergence were employed for image reconstruction. The spatial resolution of both methods as well as the convergence and noise properties of the ML/EM algorithm were studied in phantom measurements. Furthermore, patient data were acquired in the 2D mode as well as in the 3D mode and reconstructed with both techniques. RESULTS: At the same spatial resolution, the ML/EM-reconstructed images showed fewer and less prominent artefacts than the FBP-reconstructed images. The resulting improved detail conspicuously was achieved for the data acquired in the 2D mode as well as in the 3D mode. The best image quality was obtained by iterative 2D reconstruction of 3D data sets which were previously rebinned into 2D sinograms with help of the FORE algorithm. The phantom measurements revealed that 50 iteration steps with the optimized ML/EM algorithm were sufficient to keep the relative quantitation error below 5%. CONCLUSION: Our measurements show that the image quality in 3D PET can be improved by using iterative reconstruction techniques. The concept of 3D data acquisition and combining the FORE algorithm with 2D ML/EM reconstruction can readily be employed in clinical practice since the computation time is not considerably longer than that in iterative reconstruction of true 2D data.

Performance evaluation of a whole-body PET scanner using the NEMA protocol. National Electrical Manufacturers Association.

UNLABELLED: This study evaluates the performance of the newly developed high-resolution whole-body PET scanner ECAT EXACT HR+. METHODS: The scanner consists of four rings of 72 bismuth germanate block detectors each, covering an axial field of view of 15.5 cm with a patient port of 56.2 cm. A single block detector is divided into an 8 x 8 matrix, giving a total of 32 rings with 576 detectors each. The dimensions of a single detector element are 4.39 x 4.05 x 30 mm3. The scanner is equipped with extendable tungsten septa for two-dimensional two-dimensional measurements, as well as with three 68Ge line sources for transmission scans and daily quality control. The spatial resolution, scatter fraction, count rate, sensitivity, uniformity and accuracy of the implemented correction algorithms were evaluated after the National Electrical Manufacturers Association protocol using the standard acquisition parameters. RESULTS: The transaxial resolution in the two-dimensional mode is 4.3 mm (4.4 mm) in the center and increases to 4.7 mm (4.8 mm) tangential and to 8.3 mm (8.0 mm) radial at a distance of r = 20 cm from the center. The axial slice width measured in the two-dimensional mode varies between 4.2 and 6.6 mm FWHM over the transaxial field of view. In the three-dimensional mode the average axial resolution varies between 4.1 mm FWHM in the center and 7.8 mm at r = 20 cm. The scatter fraction is 17.1% (32.5%) for a lower energy discriminator level of 350 keV. The maximum true event count rate of 263 (345) kcps was measured at an activity concentration of 142 (26.9) kBq/ml. The total system sensitivity for true events is 5.7 (27.7) cps/Bq/ml. From the uniformity measurements, we obtained a volume variance of 3.9% (5.0%) and a system variance of 1.6% (1.7%). The implemented three-dimensional scatter correction algorithm reveals very favorable properties, whereas the three-dimensional attenuation correction yields slightly inaccurate results in low- and high-density regions. CONCLUSION: The ECAT EXACT HR+ has an excellent, nearly isotropic spatial resolution, which is advantageous for brain and small animal studies. While the relatively low slice sensitivity may hamper the capability for performing fast dynamic two-dimensional studies, the scanner offers a sufficient sensitivity and count rate capacity for fully three-dimensional whole-body imaging.

Use of scanner characteristics in iterative image reconstruction for high-resolution positron emission tomography studies of small animals.

The purpose of this work was to improve of the spatial resolution of a whole-body positron emission tomography (PET) system for experimental studies of small animals by incorporation of scanner characteristics into the process of iterative image reconstruction. The image-forming characteristics of the PET camera were characterized by a spatially variant line-spread function (LSF), which was determined from 49 activated copper-64 line sources positioned over a field of view (FOV) of 21.0 cm. This information was used to model the image degradation process. During the course of iterative image reconstruction, the forward projection of the estimated image was blurred with the LSF at each iteration step before the estimated projections were compared with the measured projections. The imaging characteristics of the high-resolution algorithm were investigated in phantom experiments. Moreover, imaging studies of a rat and two nude mice were performed to evaluate the imaging properties of our approach in vivo. The spatial resolution of the scanner perpendicular to the direction of projection could be approximated by a one-dimensional Gaussian-shaped LSF with a full-width at half-maximum increasing from 6.5 mm at the centre to 6.7 mm at a radial distance of 10.5 cm. The incorporation of this blurring kernel into the iteration formula resulted in a significantly improved spatial resolution of about 3.9 mm over the examined FOV. As demonstrated by the phantom and the animal experiments, the high-resolution algorithm not only led to a better contrast resolution in the reconstructed emission scans but also improved the accuracy for quantitating activity concentrations in small tissue structures without leading to an amplification of image noise or image mottle. The presented data-handling strategy incorporates the image restoration step directly into the process of algebraic image reconstruction and obviates the need for ill-conditioned "deconvolution" procedures to be performed on the projections or on the reconstructed image. In our experience, the proposed algorithm is of special interest in experimental studies of small animals.

FDG uptake, tumor proliferation and expression of glycolysis associated genes in animal tumor models.

To determine the influence of tumor cell proliferation and changes in the genetic program in malignant cells on the fluorodeoxyglucose (FDG) uptake we performed PET studies in several animal tumors: spontaneous mammary fibroadenoma, chemically-induced mammary adenocarcinoma and Dunning prostate adenocarcinoma. The expression of the glucose transporter (GLUT1) and of hexokinase (Hk) was measured using 32P-labeled cDNA probes and densitometry. Furthermore the proliferative activity was determined with one-dimensional flow cytometry. The FDG uptake and the proliferation parameters were not correlated. The normalized amounts of GLUT and Hk mRNA were lower in spontaneous fibroadenomas and prostate tumors than in chemically induced mammary. The FDG uptake was correlated to GLUT1 expression with r = 0.83 and to Hk expression with r = 0.77. Multiple regression analysis revealed a relation of FDG uptake to GLUT1 and HK with r = 0.87. Our results show that the FDG uptake in our study was related not to differences in proliferation, but rather to differences in the transcription of glycolysis associated genes.

[Eye involvement in leprosy. A study in Togo, West Africa]. / Augenbeteiligung bei Lepra. Eine Studie in Togo/Westafrika.

It is well known that ocular changes occur in leprosy, but data on their frequency differ very considerably (0.8-100%). Two groups of lepers in Togo were examined: first, 206 lepers who had had the disease for approximately 10 years and a second group (101) patients who had been suffering from it for approximately 24 years and had severe mutilations. It became apparent that sooner or later all lepers suffer from ocular complications. The following symptoms were found: loss of the eyebrows in 40.8% (42.6%), loss of the eyelashes in 29.6% (34.6%), lagophthalmos caused by involvement of the 7th cranial nerve in 21.4% (31.7%), corneal changes in 34.5% (49.5%), uveitis in 5.8% (19.8%), atrophy of the optic nerve in 12.6% (11.9%) and cataract in 21.8% (12.8%). The duration of the disease, the type of leprosy and the time when treatment was started are obviously the main factors associated with ocular changes in leprosy.

Isolation of antigen from Litomosoides carinii macrofilariae detecting serum antibodies due to Onchocerca volvulus.

Crude aqueous Litomosoides carinii adult worm extract was used as antigen for the detection of antibodies in sera from African patients with proven onchocerciasis (n = 45) resident in rural endemic areas of Togo and Sierra Leone. In 71% of cases this extract was found to produce 1 to 5 precipitation arcs in immunoelectrophoresis. Using a crude aqueous extract from adult Onchocerca volvulus, precipitation tests were positive in 75% of cases. The complexity of the L. carinii crude extract was shown by PAG-disc electrophoresis, PAG-electrofocusing, immunoelectrophoresis and crossed immunoelectrophoresis with the appropriate rabbit-antiserum. An antigen detecting onchocercal antibodies was isolated by two step preparative flat bed electrofocusing in granulated gel (PEGG). The antigen (pI 6.55, molecular weight 55 to 60 kd as estimated by SDS-PAG electrophoresis) was very suitable for antibody demonstration in double diffusion test and immunoelectrophoresis. Preliminary controls for specificity were performed by diffusing the antigen against sera from human and animal helminthoses including filarial infections. In contrast to the crude L. carinii extract no reaction was observed with sera from helminthic infections others than filariasis.

[Eye damage as a result of long-term malaria prophylaxis with chloroquine (author's transl)]. / Augenschäden bei Langzeitprophylaxe der Malaria mit Chloroquin.

Several authors have reported corneal and retinal changes occurring during high-dosage application of chloroquine for the treatment of some internal and dermatological diseases (300-500 mg of the base daily). The critical limit seems to be application of a total of 100 g of the base of chloroquine. In malaria prophylaxis (300 mg of the base weekly) it will take six-and-a-half years to reach this limit. In the few reports (27 cases) of ocular damage following malaria prophylaxis, a hyperdosage became evident. People living for prolonged periods of time in areas where malaria is endemic should have regular ophthalmological examinations and the administration of chloroquine should be stopped at the slightest sign of ocular damage.

[Aetiology and therapy of Mooren's ulcer (author's transl)]. / Ulcus rodens (Mooren)--Aspekte der Atiologie, des Verlaufs und der Therapie.

A report is given of 34 cases of Ulcus rodens of the eye (Mooren), which were examined and treaded during a period of five years in Togo, West Africa. The cases were divided into two groups according to the development of the disease. In fourteen cases the progress of the disease was arrested by local treatment (described individually for each eye), and by simultaneous treatment of the Helminthosis (Ascaris lumbricoides and Ankylostoma duodenale), from which the patients were also suffering. It seems likely that Ulcus rodens is caused by an antigen-antibody reaction to Helminth toxins.

[Astigmatism - a cause for misinterpretation of x-ray photographs (author's transl)]. / Der Astigmatismus als Fehlerquelle zur Beurteilung von Röntgenbildern

With increasing age a corneal, inverse astigmatism may develop, leading to an unequal projection upon the retina depending on the different angles of view. Fine details, like fissures in a X-ray photograph, will only be recognized in turning the photograph for 90 degrees.