Imre Lajtos

Performance test of the MiniPET-II small animal scanner according to the NEMA NU-4 standard

A full ring small animal PET camera (MiniPET-II) has been built in our institute as part of an R+D project. In this work we determined the performance parameters of the MiniPET-II scanner. The measurements and data evaluation for this purpose were based on the National Electrical Manufacturers Association (NEMA) NU-4 standards. The spatial resolution varies between 1.4 to 2.1 mm from central to 25 mm radial distances. The system sensitivity was 1.14%. The counting rate capability, expressed in noise equivalent counting rate (NEC), was shown to peak of over 55.1 kcps at 38.9 MBq using a mouse phantom. The scatter fraction with the same acquisition was 12.3%. Evaluations of image quality and quantization accuracy were also performed using the NEMA NU-4 required image-quality phantom and animal studies. The study proved that the MiniPET-II scanner has a good imaging capability and ability to perform real animal studies.

A Promising Future: Comparable Imaging Capability of MRI-Compatible Silicon Photomultiplier and Conventional Photosensor Preclinical PET Systems

We recently completed construction of a small-animal PET system—the MiniPET-3—that uses state-of-the-art silicon photomultiplier (SiPM) photosensors, making possible dual-modality imaging with MRI. In this article, we compare the MiniPET-3 with the MiniPET-2, a system with the same crystal geometry but conventional photomultiplier tubes (PMTs). Methods: The standard measurements proposed by the National Electrical Manufacturers Association NU 4 protocols were performed on both systems. These measurements included spatial resolution, system sensitivity, energy resolution, counting rate performance, scatter fraction, spillover ratio for air and water, recovery coefficient, and image uniformity. The energy windows were set to 350–650 keV on the MiniPET-2 and 360–662 keV on the MiniPET-3. Results: Spatial resolution was approximately 17% better on average for the MiniPET-3 than the MiniPET-2. The systems performed similarly in terms of peak absolute sensitivity (∼1.37%), spillover ratio for air (∼0.15), spillover ratio for water (∼0.25), and recovery coefficient (∼0.33, 0.59, 0.81, 0.89, and 0.94). Uniformity was 5.59% for the MiniPET-2 and 6.49% for the MiniPET-3. Minor differences were found in scatter fraction. With the ratlike phantom, the peak noise-equivalent counting rate was 14 kcps on the MiniPET-2 but 24 kcps on the MiniPET-3. However, with the mouselike phantom, these values were 55 and 91 kcps, respectively. The optimal coincidence time window was 6 ns for the MiniPET-2 and 8 ns for the MiniPET-3. Conclusion: Images obtained with the SiPM-based MiniPET-3 small-animal PET system are similar in quality to those obtained with the conventional PMT-based MiniPET-2.

18FDG, [18F]FLT, [18F]FAZA, and 11C-Methionine Are Suitable Tracers for the Diagnosis and In Vivo Follow-Up of the Efficacy of Chemotherapy by miniPET in Both Multidrug Resistant and Sensitive Human Gynecologic Tumor Xenografts

Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG), 11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), and [18F]fluoroazomycin-arabinofuranoside (18FAZA) for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+) and negative (Pgp−) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+ and Pgp− A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+ tumors. Our results demonstrate that 18FDG, 18F-FLT, 18FAZA, and 11C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp+ and Pgp− human tumor xenografts by miniPET.

Cold wall effect eliminating method to determine the contrast recovery coefficient for small animal PET scanners using the NEMA NU-4 image quality phantom

The contrast recovery coefficients (CRC) were evaluated for five different small animal PET scanners: GE Explore Vista, Genisys4, MiniPET-2, nanoScan PC and Siemens Inveon. The NEMA NU-4 2008 performance test with the suggested image quality phantom (NU4IQ) does not allow the determination of the CRC values for the hot regions in the phantom. This drawback of NU4IQ phantom motivated us to develop a new method for this purpose. The method includes special acquisition and reconstruction protocols using the original phantom, and results in an artificially merged image enabling the evaluation of CRC values. An advantageous feature of this method is that it stops the cold wall effect from distorting the CRC calculation. Our suggested protocol results in a set of CRC values contributing to the characterization of small animal PET scanners. GATE simulations were also performed to validate the new method and verify the evaluated CRC values. We also demonstrated that the numerical values of this parameter depend on the actual object contrast of the hot region(s) and this mainly comes from the spillover effect. This effect was also studied while analysing the background activity level around the hot rods. We revealed that the calculated background mean values depended on the target contrast in a scanner specific manner. Performing the artificially merged imaging procedure and additional simulations using the micro hollow sphere (MHS) phantom geometry, we also proved that the inactive wall around the hot spheres can have a remarkable impact on the calculated CRC. In conclusion, we have shown that the proposed artificial merging procedure and the commonly used NU4IQ phantom prescribed by the NEMA NU-4 can easily deliver reliable CRC data otherwise unavailable for the NU4IQ phantom in the conventional protocol or the MHS phantom.

The strong in vivo anti-tumor effect of the UIC2 monoclonal antibody is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity

P-glycoprotein (Pgp) extrudes a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance (MDR). The UIC2 monoclonal antibody recognizes human Pgp and inhibits its drug transport activity. However, this inhibition is partial, since UIC2 binds only to 10–40% of cell surface Pgps, while the rest becomes accessible to this antibody only in the presence of certain substrates or modulators (e.g. cyclosporine A (CsA)). The combined addition of UIC2 and 10 times lower concentrations of CsA than what is necessary for Pgp inhibition when the modulator is applied alone, decreased the EC50 of doxorubicin (DOX) in KB-V1 (Pgp+) cells in vitro almost to the level of KB-3-1 (Pgp-) cells. At the same time, UIC2 alone did not affect the EC50 value of DOX significantly. In xenotransplanted severe combined immunodeficient (SCID) mice co-treated with DOX, UIC2 and CsA, the average weight of Pgp+ tumors was only ∼10% of the untreated control and in 52% of these animals we could not detect tumors at all, while DOX treatment alone did not decrease the weight of Pgp+ tumors. These data were confirmed by visualizing the tumors in vivo by positron emission tomography (PET) based on their increased 18FDG accumulation. Unexpectedly, UIC2+DOX treatment also decreased the size of tumors compared to the DOX only treated animals, as opposed to the results of our in vitro cytotoxicity assays, suggesting that immunological factors are also involved in the antitumor effect of in vivo UIC2 treatment. Since UIC2 binding itself did not affect the viability of Pgp expressing cells, but it triggered in vitro cell killing by peripheral blood mononuclear cells (PBMCs), it is concluded that the impressive in vivo anti-tumor effect of the DOX-UIC2-CsA treatment is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity (ADCC).

Increased resting-state EEG functional connectivity in benign childhood epilepsy with centro-temporal spikes

PURPOSE To explore intrahemispheric, cortico-cortical EEG functional connectivity (EEGfC) in benign childhood epilepsy with rolandic spikes (BECTS). METHODS 21-channel EEG was recorded in 17 non-medicated BECTS children and 19 healthy controls. 180s of spike- and artifact-free activity was selected for EEGfC analysis. Correlation of Low Resolution Electromagnetic Tomography- (LORETA-) defined current source density time series were computed between two cortical areas (region of interest, ROI). Analyses were based on broad-band EEGfC results. Groups were compared by statistical parametric network (SPN) method. Statistically significant differences between group EEGfC values were emphasized at p<0.05 corrected for multiple comparison by local false discovery rate (FDR). RESULTS (1) Bilaterally increased beta EEGfC occurred in the BECTS group as compared to the controls. Greatest beta abnormality emerged between frontal and frontal, as well as frontal and temporal ROIs. (2) Locally increased EEGfC emerged in all frequency bands in the right parietal area. CONCLUSIONS Areas of increased EEGfC topographically correspond to cortical areas that, based on relevant literature, are related to speech and attention deficit in BECTS children.

Analysis of the minimum detectable activity of a small animal scanner

Studies in nuclear medicine frequently require the measurement of very low activity lesions in a background region. The detectability depends on a number of properties of the lesion (size, shape, signal amplitude), the background (quantum noise from the imaging process and anatomical variability) and the observer performance. We investigated the differences between the human and mathematical model observers. We used simulated images in this work. The simulated images were investigated by human observers (HuO) using an own software tool, testing whether these signals (lesions) are visible or not. For model observers the images were compared on the basis of the channelized Hotelling observer (CHO) using predefined channels.