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Background Bronchoscopy serves as direct visualisation of the airway. Virtual bronchoscopy provides similar visual information using a non-invasive imaging procedure(s). Early and accurate image-guided diagnosis requires the possible highest performance, which might be approximated by combining anatomical and functional imaging. This communication describes an advanced functional virtual bronchoscopic (fVB) method based on the registration of PET images to high-resolution diagnostic CT images instead of low-dose CT images of lower resolution obtained from PET/CT scans. PET/CT and diagnostic CT data were collected from 22 oncological patients to develop a computer-aided high-precision fVB. Registration of segmented images was performed using elastix. Results For virtual bronchoscopy, we used an in-house developed segmentation method. The quality of low- and high-dose CT image registrations was characterised by expert’s scoring the spatial distance of manually paired corresponding points and by eight voxel intensity-based (dis)similarity parameters. The distribution of (dis)similarity parameter correlating best with anatomic scoring was bootstrapped, and 95% confidence intervals were calculated separately for acceptable and insufficient registrations. We showed that mutual information (MI) of the eight investigated (dis)similarity parameters displayed the closest correlation with the anatomy-based distance metrics used to characterise the quality of image registrations. The 95% confidence intervals of the bootstrapped MI distribution were [0.15, 0.22] and [0.28, 0.37] for insufficient and acceptable registrations, respectively. In case of any new patient, a calculated MI value of registered low- and high-dose CT image pair within the [0.28, 0.37] or the [0.15, 0.22] interval would suggest acceptance or rejection, respectively, serving as an aid for the radiologist. Conclusion A computer-aided solution was proposed in order to reduce reliance on radiologist’s contribution for the approval of acceptable image registrations.

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One of the current research objectives of medical imaging is to determine the prognostic value of tumor textures and related numerical values. In PET/CT studies the diagnostic and prognostic values of specific texture parameters were confirmed at several tumor types (lung, prostate, cervix, colon, head and neck). However, the results are often contradictory, various publications find different texture parameters useful for the same tumor type. The reason for the contradictions is partly methodological, since the definition and the calculation of texture data is a multi-step process. Such steps include scan protocol, image reconstruction, tumor segmentation, re-sampling the voxel values and the form of texture algorithms. Recent publications show that by harmonizing these steps, the prognostic power and reliability of the texture features can be improved. The most optimal way of harmonization would be a special phantom application that could simulate inhomogeneous distributions typical for tumor tissues, with high reproducibility.

Background Long-term survival of xenogeneic transplanted cells in adults requires strong immunosuppression and/or encapsulation of the cells to achieve peripheral transplant tolerance. Purpose The aim of our project was to seed decellularized tissue engineered heart valves (TEHV) with xenogeneic (porcine) mesenchymal stem cells (pMSCs) transfected transiently (Lipofectamine) with a positron emission tomography (PET)-reporter gene (pMSC-PETr), followed by implantation as pulmonary valve replacement into sheep without immunosuppression. The fate of the seeded pMSC-PETr was tracked via serial in-vivo non-invasive PET-computed tomography (PET-CT). Methods Static cultivation of TEHV scaffold led to successful ingrowth of the pMSC-PETr. For enabling quantitative assessment of viable pMSC-PETr in the TEHV scaffold after in vivo implantation, vials containing 5x104, 2x105, and 4x105 pMSC-PETr were in vitro mixed with the [18F]-FHBG PET tracer for 1 hr, then the non-bound tracer was washed out and vials were in vitro PET-CT imaged, giving reference values. TEHV-pMSC-PETr were then implanted percutaneously into the pulmonary valve position of sheep (n=4) under general anesthesia, while an additional sheep with no valve implantation served as a control. Ten mCi of [18F]-FHBGPET radiotracer was produced for each procedure and serial PET-CT imaging of the sheep was performed at 3 hr, 24 hr, 2 or 3 weeks, and 5 and 6 months after valve implantation. The study followed the Principles of laboratory animal care. Results PET-CT of vials containing increasing number of pMSC-PETr showed dose-dependent tracer uptake in the transfected cells in vitro (Figure). PET-CT images of the sheep 3 hr after implantation of the TEHV-pMSC-PETr showed a clear signal of transfected cells, with a mean estimated number of viable pMSC-PETr of 5.18±1.19x106. No meaningful decrease of the amount of living cells occurred at 24 hr or 2 or 3 weeks. Interestingly, 5- and 6-month follow-up PET-CT images showed clear in vivo and in vitro (after explantation) PET signals of the pMSC-PETr on TEHV, indicating spontaneous stable transfection of the PET reporter plasmid (insertional mutagenesis). Histology confirmed the survival of the pMSC-PETr at 5 and 6-month after xenogeneic transplantation. Merged immunohistochemistry and fluorescence imaging of anti-pig SLA I and anti-sheep MHC I antibodies and PET-reporter gene (HSV1-tk) suggested in vivo inter-species lateral jump gene transfer between pig MSCs and host sheep cells. Figure 1 Conclusions This is the first report on serial non-invasive in vivo tracking of long-term survival of xenogeneic pMSCs-PETr seeded on TEHVs and percutaneously implanted into the pulmonary position of sheep. Long-term follow-up revealed spontaneous stable transfection of the plasmid PET-reporter gene, which suggests the risk of insertional mutagenesis induced by the plasmid (transposon), and PET-reporter gene shuttle from xenogeneic pig MSCs to sheep cells. Acknowledgement/Funding LifeValve EU project (grant number: 242008)

Quantifying tumour heterogeneity from [

The aim of this study is to support medical experts to be able to make an order among large number of automatic registration. The experts could tackle with the most problematic cases due to the inaccuracy of automatic registration procedure in the vicinity of the bronchus to help virtual bronchoscopy (VB) systems. Functional images (e.g. PET) can be projected on the relevant part of the organ that is examined in VB systems. We collected cases where the difference between the time of low-dose (ldCT) and diagnostic CT (hdCT) was less than one year. Altogether 22 anonymous ldCT and hdCT studies were selected in this study. Based on the literature, a potential candidate for image registration was elastix. We applied a specific in-house developed application for image preprocessing, before the elastix registration. We tried to resolve the goodness of the entire registration process by visual judgment combining it with special numerical features. Numerical data include the mutual information, standardized mutual information, Kullback-Leibler entropy, cross correlation, L1norm, L2norm square. We found satisfying correlation between mutual information and visual judgment in the close vicintiy of airtree. We calculated confident intervals for MI of acceptable and rejected registrations about the mean values of it by bootstraping method: [0.27, 0.36], [0.13, 0.19].

[EN] To find structural differences between brain metastases of lung and breast cancer, computing their heterogeneity parameters by means of both 2D and 3D texture analysis (TA). Patients with 58 brain metastases from breast (26) and lung cancer (32) were examined by MR imaging. Brain lesions were manually delineated by 2D ROIs on the slices of contrast-enhanced T1-weighted (CET1) images, and local binary patterns (LBP) maps were created from each region. Histogram-based (minimum, maximum, mean, standard deviation, and variance), and co-occurrence matrix-based (contrast, correlation, energy, entropy, and homogeneity) 2D, weighted average of the 2D slices, and true 3D TA were obtained on the CET1 images and LBP maps. For LBP maps and 2D TA contrast, correlation, energy, and homogeneity were identified as statistically different heterogeneity parameters (SDHPs) between lung and breast metastasis. The weighted 3D TA identified entropy as an additional SDHP. Only two texture indexes (TI) were significantly different with true 3D TA: entropy and energy. All these TIs discriminated between the two tumor types significantly by ROC analysis. For the CET1 images there was no SDHP at all by 3D TA. Our results indicate that the used textural analysis methods may help with discriminating between brain metastases of different primary tumors., This work was supported in part by the Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds under Grant BFU2015-64380-C2-2-R, by the "Richter Gedeon Talentum Alapitvany" and by the Campus Hungary Mobility Program. Andres Larroza was funded by the Spanish Ministerio de Educacion, Cultura y Deporte (MECD) under Grant FPU12/01140. The authors also thank to the continuous help of Dr. Joaquin Gavila from Fundacion IVO

OBJECTIVE Wall motion abnormalities during acute ST-segment elevation myocardial infarction (STEMI) and the improvement after recanalization depend on the conditions of the coronary occlusion. METHODS Fifty-seven patients with first-ever STEMI due to one-artery occlusion, treated with primary PCI, were evaluated. Area at risk and left ventricular wall motion abnormalities were localized with coronary angiography and echocardiography and then compared in relation to the time elapsed from the onset of symptoms at the time of infarction and at 3 months. Left ventricular diameters and ejection fractions were evaluated in relation to the ischemic time. RESULTS Three hundred forty-one affected left ventricular segments were detected with angiography, while echocardiography showed 206 segments with motion abnormality. No correlation was found between the regional wall motion index in the area at risk and the time elapsed from the beginning of symptoms. However, the improvement in wall motion abnormalities at the follow-up was dependent on the ischemic time (r=-0.29, p

Excel2Genie, a simple and user-friendly Microsoft Excel interface, has been developed to the Genie-2000 Spectroscopic Software of Canberra Industries. This Excel application can directly control Canberra Multichannel Analyzer (MCA), process the acquired data and visualize them. Combination of Genie-2000 with Excel2Genie results in remarkably increased flexibility and a possibility to carry out repetitive data acquisitions even with changing parameters and more sophisticated analysis. The developed software package comprises three worksheets: display parameters and results of data acquisition, data analysis and mathematical operations carried out on the measured gamma spectra. At the same time it also allows control of these processes. Excel2Genie is freely available to assist gamma spectrum measurements and data evaluation by the interested Canberra users. With access to the Visual Basic Application (VBA) source code of this application users are enabled to modify the developed interface according to their intentions.

Quantifying tumour heterogeneity from [18F]FDG-PET images promises benefits for treatment selection of cancer patients. Here, the calculation of texture parameters mandates an initial discretization step (binning) to reduce the number of intensity levels. Typically, three types of discrimination methods are used: lesion relative resampling (LRR) with fixed bin number, lesion absolute resampling (LAR) and absolute resampling (AR) with fixed bin widths. We investigated the effects of varying bin widths or bin number using 27 commonly cited local and regional texture indices (TIs) applied on lung tumour volumes. The data set were extracted from 58 lung cancer patients, with three different and robust tumour segmentation methods. In our cohort, the variations of the mean value as the function of the bin widths were similar for TIs calculated with LAR and AR quantification. The TI histograms calculated by LRR method showed distinct behaviour and its numerical values substantially effected by the selected bin number. The correlations of the AR and LAR based TIs demonstrated no principal differences between these methods. However, no correlation was found for the interrelationship between the TIs calculated by LRR and LAR (or AR) discretization method. Visual classification of the texture was also performed for each lesion. This classification analysis revealed that the parameters show statistically significant correlation with the visual score, if LAR or AR discretization method is considered, in contrast to LRR. Moreover, all the resulted tendencies were similar regardless the segmentation methods and the type of textural features involved in this work.

Whole Body PET scans are typically performed as a series of image sets acquired at discrete axial positions to cover most or all of the body. The acquisition time at each axial position is typically kept fixed for all positions although the total imaging time is typically adjusted according to the patient's weight. Because of the varying amount of attenuation for different sections of the body, it is expected that the image Signal-to-Noise (S/N) will vary accordingly. The aim of this work is to investigate the possibility of varying the acquisition time at different sections of the body such that the image S/N is kept relatively constant for all slices. To estimate the acquisition times for the different sections of the body we propose to use the attenuation correction (AC) sinogram generated from the CT scan that is acquired prior to the PET scan. Both simulations and phantom measurements of different diameter cylinders with activity distributions were performed. The image noise was estimated in every pixel from multiple replicate image sets. The image noise was compared to the average AC factors through the center of each body slice. A simple polynomial function was found for both the simulations and the phantom measurement images to accurately describe the image noise as a function of AC factors. These results indicate that the noise properties of whole body images can be made more uniform axially by adjusting the acquisition time according to the amount of attenuation. Instead of using a fixed scan time per bed position, the acquisition time can be reduced in areas of lower attenuation and increased in more absorbing sections of the body. Since there is a strong correlation of the image noise and the AC factors, the relative acquisition times can be quickly calculated using a simple functional relationship.

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) forin vivofollow-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 that18FDG,18F-FLT,18FAZA, and11C-methionine are suitable PET tracers for the diagnosis andin vivofollow-up of the efficacy of tumor chemotherapy in both Pgp+and Pgp−human tumor xenografts by miniPET.

Textural analysis might give new insights into the quantitative characterization of metabolically active tumors. More than thirty textural parameters have been investigated in former F18-FDG studies already. The purpose of the paper is to declare basic requirements as a selection strategy to identify the most appropriate heterogeneity parameters to measure textural features. Our predefined requirements were: a reliable heterogeneity parameter has to be volume independent, reproducible, and suitable for expressing quantitatively the degree of heterogeneity. Based on this criteria, we compared various suggested measures of homogeneity. A homogeneous cylindrical phantom was measured on three different PET/CT scanners using the commonly used protocol. In addition, a custom-made inhomogeneous tumor insert placed into the NEMA image quality phantom was imaged with a set of acquisition times and several different reconstruction protocols. PET data of 65 patients with proven lung lesions were retrospectively analyzed as well. Four heterogeneity parameters out of 27 were found as the most attractive ones to characterize the textural properties of metabolically active tumors in FDG PET images. These four parameters included Entropy, Contrast, Correlation, and Coefficient of Variation. These parameters were independent of delineated tumor volume (bigger than 25-30 ml), provided reproducible values (relative standard deviation< 10%), and showed high sensitivity to changes in heterogeneity. Phantom measurements are a viable way to test the reliability of heterogeneity parameters that would be of interest to nuclear imaging clinicians.

The aim of the study is to demonstrate the diagnostic and geographical distribution of the domestic PET/CT examinations financed by the OEP based on the data from the waiting list of the past 4 years. The analysis of the demonstrated data can support the rational usage of PET/CT examination contingents in the domestic oncological attendance, which has growing importance. PET examinations with oncological aims have started in Debrecen more than 10 years ago. In 2005 already 1500 PET examinations have been carried out. According to the governmental regulation accepted in 2006, OEP ensures the financing of the three PET/CT centers until 2012, which means 12,000 examinations in 2012. However, the number of domestic oncological patients requiring PET/CT examinations can reach the number of 20,000-30,000 patients. The study summarizes the number of patients who applied for PET/CT examinations for the first time and later again between 2006 and 2010, based on the data of the waiting list, and the change of the patient assigning diagnosis and the number of examinations carried out with 18F-FDG and with 11C-methionine. The study demonstrates the number of examinations by counties which characterize the population's access to PET/CT. The assigning diagnosis in 2007 was already widespread and focused on problems. After the regulation came in to force in 2008 the possibilities significantly decreased. Clinical cases which were efficiently examined with PET/CT earlier were left out from the indication list. The distribution by county is uneven, although the number of examinations increases year by year. The number of repeated examinations increases as well. As a conclusion, the annual PET/CT examination contingents are constantly exploited. This might seem sufficient, because the method has not become a part of the oncological routine in all counties. Although the current indication list includes the most frequent oncological cases requiring PET/CT, the abandoning of the less frequent ones narrowed the professional latitude, which is disadvantageous for the patients suffering from such diseases. The radiopharmacon supply of PET/CT centers is inadequate thus they cannot provide modern oncological diagnostic attendance in case of frequent types of cancer (such as prostate). In the long run the growing number of repeated PET/CT examinations built in the oncological professional protocol has to be taken into account.

Background— Porcine bone marrow-derived mesenchymal stem cells (MSCs) were stably transfected with a lentiviral vector for transgene expression of the trifusion protein renilla luciferase, red fluorescent protein and herpes simplex truncated thymidine kinase (LV-RL-RFP-tTK; positron emission tomography [PET] reporter gene) for in vivo noninvasive tracking of the intramyocardially delivered MSC fate. Methods and Results— A closed-chest, reperfused myocardial infarction was created in farm pigs. Sixteen days after myocardial infarction, LV-RL-RFP-tTK-MSCs were injected intramyocardially using electromechanical mapping guidance in the infarct border zone (n=7). PET-computed tomographic metabolic and perfusion imaging was performed after an intravenous injection of 10 mCi [18F]-FHBG and 13N-ammonia PET at 30�2 hours and 7 days after LV-RL-RFP-tTK-MSC treatment. Fusion imaging of the [18F]-FHBG PET-computed tomography with MRI was used to determine the myocardial location of the injected LV-RL-RFP-tTK-MSCs. Seven days after injections, [18F]-FHBG PET showed a decreased cardiac uptake with a mild increased pericardial and pleura uptake in the treated animals, which was confirmed by the measurement of luciferase activity. At 10 days, infarct size by MRI in the LV-RL-RFP-tTK-MSC-treated animals was smaller than controls (n=7) (23.3�1.5% versus 30.2�3.5%, P Conclusions— Reporter gene imaging enables the tracking of the persistence of viable LV-RL-RFP-tTK-MSC in the peri-infarcted porcine myocardium at 10 days after delivery using clinical PET scanners.

Iterative reconstruction methods are commonly used to obtain images with high resolution and good signal-to-noise ratio in nuclear imaging. The aim of this work was to develop a scalable, fast, cluster based, fully 3-D iterative image reconstruction package for our small animal PET camera, the miniPET. The reconstruction package is developed to determine the 3-D radioactivity distribution from list mode type of data sets and it can also simulate noise-free projections of digital phantoms. We separated the system matrix generation and the fully 3-D iterative reconstruction process. As the detector geometry is fixed for a given camera, the system matrix describing this geometry is calculated only once and used for every image reconstruction, making the process much faster. The Poisson and the random noise sensitivity of the ML-EM iterative algorithm were studied for our small animal PET system with the help of the simulation and reconstruction tool. The reconstruction tool has also been tested with data collected by the miniPET from a line and a cylinder shaped phantom and also a rat.

UNLABELLED 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.

The aim was to elucidate whether aneurysmal subarachnoid hemorrhage (SAH)-induced vasospasm induces changes of regional glucose uptake in surgically treated, asymptomatic cases.(18)FDG uptake (standardized uptake value, SUV) was analysed with PET in eight surgically treated aneurismal patients with a mean middle cerebral artery flow velocity120 cm/seconds measured with transcranial Doppler ultrasound. Data were compared with a healthy control group using Statistical Parametric Mapping (SPM99b).Six of the eight patients had no focal neurological signs. The inhomogeneous bilateral increase in SUV (p0.0001) was asymmetrical, with an almost 70% larger volume on the operated side. Reduced glucose uptake was found in the frontal and temporobasal regions of the two patients with neurological deficits (p0.0001); the affected volume was 40% larger on the operated side.SAH-induced vasospasm results in widespread increase of glucose uptake-probably reflecting increased glycolysis. This was earlier than neurological focal signs appear. Decreased glucose uptake can be detected in severe cases of vasospasm reflected by neurological deficit. Although the changes are more prominent where surgery had taken place our results suggest that not only the surgery, but also subarachnoid blood might have resulted in our findings.

AIM To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells. METHODS The accumulations of different P-gp substrates, including rhodamine 123, daunorubicin and [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the tumor-diagnostic tracers (11)C-choline and 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) were measured in the same cell lines. The P-gp expression and function were demonstrated by flow-cytometry. RESULTS The (18)FDG measurements revealed that the glucose metabolic rate was significantly higher (p

A new type of experimental technique to investigate the depth- of-interaction (DOI) dependence in small scintillator elements designed for high-resolution animal PET is tested. An Oxford-type nucle ...

Adenosine receptors are widely distributed in mammalian tissues and have been possibly involved through transmembrane potential changes in cell function regulation. The effect of A 1 and A 2 A adenosine receptor ligands on transmembrane potential measured with flow cytometry and potassium conductance measured by the patch-clamp technique was investigated in DDT1 MF-2 smooth muscle cells. The A 1 adenosine-receptor agonist CPA (50 nM) and the A 2 A adenosine-receptor agonist CGS 21680 (50 nM) elicited a rapid and maintained increase and decrease in the potassium conductance, respectively, and a concomitant hyperpolarization and depolarization of the membrane, respectively. These effects were eliminated by subtype-selective adenosine receptor antagonists (DPCPX, CSC, ZM 241385, all 1 μM). The ligand induced membrane potential changes were reversible. Based on these detected membrane potential changes along with the published voltage dependence of the adenylyl cyclase, the regulation of cAMP production by A 1 - and A 2 A -receptor activation is suggested to be mediated through the induced early hyperpolarization and depolarization. The interaction between the effects of these receptor subtypes allows for a complex regulation mechanism.

The aim of the study is to review the new tomographic imaging technologies which enable to investigate the metabolic activity of the human body. Accordingly, we overview the current promising methodology in the field of PET and SPECT, but we will also mention interesting applications at the area of MRI and CT.A tanulmány célja a metabolikus aktivitás vizsgálatára alkalmas olyan újabb technikai megoldások áttekintése, amelyek tomografikus (3D) leképezésen alapulnak. Így elsõsorban a PET- és a SPECT-vizsgálatok kapcsán említünk meg újdonságokat, de ismertetni fogunk ígéretes lehetõségeket az MRI és a CT területérõl is.

Deriving quantitative measures from the medical imaging methods is a key issue for the optimal oncologic therapy, when the anatomical abnormalities and changes of the metabolic state of the tissues need to be characterized. In order to improve the effectiveness of the therapy, the results of medical imaging procedures should be comparable after two or more consecutive scans. There are several tomographic imaging applications (CT, MRI, SPECT and PET), but in this work we will focus on the quantitative capability of PET, because this method provides the most versatile possibilities for quantifying the resulting images.Az optimális onkológiai terápia kidolgozásához és a hatékonyságának leméréséhez fontos, hogy az anatómiai elváltozásokat és a sejtszintû metabolizmus megváltozását az orvosi képalkotásban is minél több esetben lehessen kvantitatívan jellemezni. Minél inkább törekedni kell arra, hogy a képalkotás eredményei összehasonlíthatóak legyenek a két vagy akár több egymást idõben követõ leképezés után. Ebben a munkában a tomográfiai módszerek (CT, MRI, SPECT és PET) közül fõleg a funkcionális információt szolgáltató PET kapcsán számolunk be az aktuális lehetõségekrõl, mert jelenleg ez a technika rendelkezik a legsokoldalúbb kvantitálási képességgel.

Strictly finite-range (SFR) potentials are exactly zero beyond their finite range. Single-particle energies and densities as well as S-matrix pole trajectories are studied in a few SFR potentials suited for the description of neutrons interacting with light and heavy nuclei. The SFR potentials considered are the standard cut-off Woods--Saxon (CWS) potentials and two potentials approaching zero smoothly: the SV potential introduced by Salamon and Vertse and the SS potential of Sahu and Sahu. The parameters of these latter were set so that the potentials may be similar to the CWS shape. The range of the SV and SS potentials scales with the cube root of the mass number of the core like the nuclear radius itself. For light nuclei a single term of the SV potential (with a single parameter) is enough for a good description of the neutron-nucleus interaction. The trajectories are compared with a bench-mark for which the starting points (belonging to potential depth zero) can be determined independently. Even the CWS potential is found to conform to this bench-mark if the range is identified with the cutoff radius. For the CWS potentials some trajectories show irregular shapes, while for the SV and SS potentials all trajectories behave regularly., 14 figs

2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) is a tumor diagnostic radiotracer of great importance in both diagnosing primary and metastatic tumors and in monitoring the efficacy of the treatment. P-glycoprotein (Pgp) is an active transporter that is often expressed in various malignancies either intrinsically or appears later upon disease progression or in response to chemotherapy. Several authors reported that the accumulation of (18)FDG in P-glycoprotein (Pgp) expressing cancer cells (Pgp(+)) and tumors is different from the accumulation of the tracer in Pgp nonexpressing (Pgp(-)) ones, therefore we investigated whether (18)FDG is a substrate or modulator of Pgp pump. Rhodamine 123 (R123) accumulation experiments and ATPase assay were used to detect whether (18)FDG is substrate for Pgp. The accumulation and efflux kinetics of (18)FDG were examined in two different human gynecologic (A2780/A2780AD and KB-3-1/KB-V1) and a mouse fibroblast (3T3 and 3T3MDR1) Pgp(+) and Pgp(-) cancer cell line pairs both in cell suspension and monolayer cultures. We found that (18)FDG and its derivatives did not affect either the R123 accumulation in Pgp(+) cells or the basal and the substrate stimulated ATPase activity of Pgp supporting that they are not substrates or modulators of the pump. Measuring the accumulation and efflux kinetics of (18)FDG in different Pgp(+) and Pgp(-) cell line pairs, we have found that the Pgp(+) cells exhibited significantly higher (p⩽0.01) (18)FDG accumulation and slightly faster (18)FDG efflux kinetics compared to their Pgp(-) counterparts. The above data support the idea that expression of Pgp may increase the energy demand of cells resulting in higher (18)FDG accumulation and faster efflux. We concluded that (18)FDG and its metabolites are not substrates of Pgp.

Background Membrane potential changes in cells from the human lymphoid B cell line, JY, evoked by increasing cell density in culture were investigated, as data published on other cell types are controversial. An attempt was also made to clear the underlying mechanism. Methods Nonadherent JY cells were isolated from high-density plateau-phase cultures (type A cells), medium-density log-phase cultures (type B cells), and low-density lag-phase cultures (type C cells). They were analyzed for transmembrane potential, intracellular free concentration of potassium and sodium, membrane permeability for monovalent cations, cell cycle distribution by measuring DNA content, and glucose uptake. Results C type cells proved to be relatively depolarized (−41 ± 3 mV) and cells obtained from the highest density cultures hyperpolarized (−60 ± 3 mV). Intracellular concentrations ([K]i = 92–97 mM and [Na]i = 34–35 mM) were almost identical for each type of cell. The sodium/potassium permeability constant ratio in the A and C type of cells was 0.047 and 0.094, respectively. High-density culture conditions resulted in a pronounced G1-phase arrest. Conclusions Differences in the membrane potential values induced by high-density culture conditions were maintained by changes in the membrane permeability for the monovalent cations. Cytometry 41:186-192,2000. © 2000 Wiley-Liss, Inc.

To prove the general applicability of a recently published flow cytometric method to determine the membrane potentials of cells on the absolute (mV) scale, the validity of the premises involved were analyzed individually. Experimental evidence was given for bis-oxonol, the applied membrane potential indicator being a Nernstian dye. The results of special measurements proved that extracellular dye concentrations were not affected by cellular dye uptake under the applied experimental conditions and that the dye content of the suspending medium did not contribute directly to the measured cellular fluorescence. A direct, membrane-potential-independent contribution of the extracellular dye to cellular fluorescence was also found to be negligible, as membrane potential values of the same type of cells evaluated from measurements in the presence of different extracellular oxonol concentrations were very close to each other. The transmembrane potential of B lymphoid JY cells was measured by the method as a function of cell density in the tissue culture. Cells isolated during the log phase of growth displayed a –40±4 mV membrane potential. At a high density of the culture (plateau phase), a significant increase of the membrane potential to –61±3 mV was observed and a medium value of –47±3.5 mV was measured at an intermediate density of the cells. Our observation indicates that nonadherent cells can also be hyperpolarized when optimal growth conditions are terminated.

Cold or warm adaptation usually results in changes of the cellular parameters of poikilothermic animals. However, no data are available about the changes in cellular parameters of sperm samples from cold or warm adapted animals. Here the effects of warm and cold adaptation on the spermation of common carp ( Cyprinus carpio L.) and the changes in the characteristics of the individual sperm cells are described. Measurements were carried out on semen samples from 10 warm adapted and 10 cold adapted animals. The sperm cells from the cold adapted animals had a higher intracellular pH (7.4±0.1) than those from the warm adapted ones (7.1±0.1). The pH of the seminal plasma of the cold adapted animals (8.6±0.2) was also higher than that of the warm adapted animals (8.3±0.1). The concentration of spermatozoa in the semen of cold adapted animals was about half that for the warm adapted animals (0.7±0.1×10 10 vs. 1.4±0.2×10 10 cells/ml). The Na + concentration of the seminal plasma of the cold adapted animals (83±12 mM) was higher, while the K + concentration in these samples (64±11 mM) was lower than the corresponding data for the warm adapted animals (63±10 mM and 87±16 mM, respectively). All of these differences proved to be significant at 5% level of significance using the Student's t -test. In contrast, there was no significant difference between the intracellular free K + concentrations in the spermatozoa from cold and warm adapted animals (58±8 mM vs. 60±7 mM). The ion compositions and concentrations of the blood sera of cold and warm adapted animals were similar. Also, the motile fraction and duration of motility of the spermatozoa from cold and warm adapted animals were identical. An increase by 0.2 pH unit occurred in the intracellular pH during hypoosmotic shock induced motility of sperm cells from the cold and warm adapted animals. This pH increase could be blocked by the Na + /H + exchange inhibitor amiloride in a concentration of 100 μM. Based on the kinetics of the processes involved and on additional experimental evidence it is suggested that the hypoosmotic shock induced immediate hyperpolarization of the sperm under usual spawning conditions. Thus, it may be a regulatory step in the motility activation of common carp sperm but not in the relatively slowly occurring intracellular alkalinization.

2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) is a tumor diagnostic radiotracer of great importance in both diagnosing primary and metastatic tumors and in monitoring the efficacy of the treatment. P-glycoprotein (Pgp) is an active transporter that is often expressed in various malignancies either intrinsically or appears later upon disease progression or in response to chemotherapy. Several authors reported that the accumulation of (18)FDG in P-glycoprotein (Pgp) expressing cancer cells (Pgp(+)) and tumors is different from the accumulation of the tracer in Pgp nonexpressing (Pgp(-)) ones, therefore we investigated whether (18)FDG is a substrate or modulator of Pgp pump. Rhodamine 123 (R123) accumulation experiments and ATPase assay were used to detect whether (18)FDG is substrate for Pgp. The accumulation and efflux kinetics of (18)FDG were examined in two different human gynecologic (A2780/A2780AD and KB-3-1/KB-V1) and a mouse fibroblast (3T3 and 3T3MDR1) Pgp(+) and Pgp(-) cancer cell line pairs both in cell suspension and monolayer cultures. We found that (18)FDG and its derivatives did not affect either the R123 accumulation in Pgp(+) cells or the basal and the substrate stimulated ATPase activity of Pgp supporting that they are not substrates or modulators of the pump. Measuring the accumulation and efflux kinetics of (18)FDG in different Pgp(+) and Pgp(-) cell line pairs, we have found that the Pgp(+) cells exhibited significantly higher (p⩽0.01) (18)FDG accumulation and slightly faster (18)FDG efflux kinetics compared to their Pgp(-) counterparts. The above data support the idea that expression of Pgp may increase the energy demand of cells resulting in higher (18)FDG accumulation and faster efflux. We concluded that (18)FDG and its metabolites are not substrates of Pgp.

The relationship between metabolic disorders and the distribution of fat in different body regions is not clearly understood in humans. The aim of this study was to develop a suitable method for assessing the regional distribution of fat deposits and their metabolic effects in dogs. Twenty-five dogs were subjected to computed tomographic (CT) imaging and blood sampling in order to characterise their metabolic status. The different fat areas were measured on a cross-sectional scan, and the animals’ metabolic status was evaluated by measuring fasting glucose, insulin and leptin levels. The volume of visceral adipose tissue is the main determinant of leptin levels. The correlation of visceral fat volume and leptin concentration was found to be independent of insulin levels or the degree of insulin resistance. There was a positive correlation between the visceral to subcutaneous fat volume ratio and serum insulin concentration, and a similar trend was observed in the relationship of fat ratio and insulin resistance. The distribution of body fat essentially influences the metabolic parameters in dogs, but the effects of adiposity differ between humans and dogs. The findings can facilitate a possible extrapolation of results from animal studies to humans with regard to the metabolic consequences of different obesity types.

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.

This paper presents results of the performance of a small animal PET system (MiniPET-II) installed at our Institute. MiniPET-II is a full ring camera that includes 12 detector modules in a single ring comprised of 1.27×1.27×12 mm 3 LYSO scintillator crystals. The axial field of view and the inner ring diameter are 48 mm and 211 mm, respectively. The goal of this study was to determine the NEMA-NU4 performance parameters of the scanner. In addition, we also investigated how the calculated parameters depend on the coincidence time window ( τ =2, 3 and 4 ns) and the low threshold settings of the energy window ( E lt =250, 350 and 450 keV). Independent measurements supported optimization of the effective system radius and the coincidence time window of the system. We found that the optimal coincidence time window and low threshold energy window are 3 ns and 350 keV, respectively. The spatial resolution was close to 1.2 mm in the center of the FOV with an increase of 17% at the radial edge. The maximum value of the absolute sensitivity was 1.37% for a point source. Count rate tests resulted in peak values for the noise equivalent count rate (NEC) curve and scatter fraction of 14.2 kcps (at 36 MBq) and 27.7%, respectively, using the rat phantom. Numerical values of the same parameters obtained for the mouse phantom were 55.1 kcps (at 38.8 MBq) and 12.3%, respectively. The recovery coefficients of the image quality phantom ranged from 0.1 to 0.87. Altering the τ and E lt resulted in substantial changes in the NEC peak and the sensitivity while the effect on the image quality was negligible. The spatial resolution proved to be, as expected, independent of the τ and E lt . The calculated optimal effective system radius (resulting in the best image quality) was 109 mm. Although the NEC peak parameters do not compare favorably with those of other small animal scanners, it can be concluded that under normal counting situations the MiniPET-II imaging capability assures remarkably good image quality, sensitivity and spatial resolution.

The osmolality and composition of fish seminal plasma usually suppress sperm motility in the testis and sperm duct. Change in the osmolality of the environment at spawning activates flagellar motion of the sperm tail. The effect of inhibitors of anion and cation channels on active motion was investigated by a microscopic motility test. While sodium channel inhibitors (amiloride and tetrodotoxin) as well as anion channel inhibitors (DIDS and ethacrynic acid) did not affect motility, potassium channel inhibitors (4-AP, quinine, veratrine, verapamil) decreased the duration of flagellar motion or abolished motility completely. Potassium channel inhibitors exerted an effect on sperm motility depending on the dose and length of incubation. The voltage-activated K+ blocker 4-aminopiridine proved to be the most potent inhibitor. Its effect was completely reversible, indicating that the functional state of potassium channels is essential to the activation mechanism of sperm. Intracellular pH of the spermatozoa was measured by a fluorescent flow cytometric technique. Hypo-osmotic shock induced intracellular alkalinization of carp sperm. Increase in pHi was 0.15 pH units. In the presence of 4-AP the measured amplitude and kinetics of the pHi change was the same as in the absence of this inhibitor, arguing against a regulatory role of intracellular pH change.

The concept of implementing Positron Emission Tomography and Magnetic Resonance Imaging in a dual modality imaging system gained high scientific importance recently. SiPM photo detectors became a solution for operation in high magnetic fields instead of the conventional photomultipliers. The method of Anger logics in the SiPM readout of pixelated scintillator crystals would produce significant noise in the readout signals, while single channel readout for each crystal pixel would not be cost effective. Another solution could be defined if we sum the SiPM signals for each row and column and an appropriate algorithm may select the X and Y coordinates of the original position of the scintillation source. It is expected that the highest signal related row and column would indicate correct position. The scope of this work was to calculate the optimal light distribution for different SiPM and scintillator matrix geometries, that would result in the greatest signal difference between the primary and adjacent readout channels and therefore would perform the best reliable selection of the relevant row and column indices.

In the last decade both the number of powerful CT scanners and the number of patient investigations increased with a consequent increase of the patient radiation dose. There are large dose variations (more than 10 fold) among individual CT centers and it remains true if they include the same model of CT scanners. The aim of this study was to compare the patient effective dose (De) during the CT examinations from different manufacturer models presuming the same acquisition protocol and using the imPACT patient organ and effective dose calculator program. The following manufacturers and models were selected in the program: GE (LightSpeed Ultra, LightSpeed 16, LightSpeed Pro 16, LightSpeed VCT), Philips (Brilliance 16, Brilliance 16 Power, Big Bore, Brilliance 64/40) and the Siemens (Emotion 6, Sensation 16, Sensation 16 Straton, Sensation 64, Definition AS). Head and body scans were defined for all cases altering tube voltages, while dose calculations were normalized to 100 mAs X-ray exposure. It was found that in body investigations the calculated De for the GE scans were higher by 20% comparing to Siemens and Philips related values. For the head examinations the differences were larger by almost 55%. We also demonstrated that a power relationship can be found between the De and the tube voltage with the exponent of 3.02±0.14 kV-1 and 2.68±0.14 kV-1 for the body and the head scans respectively. It can be concluded that the patient effective dose could be different in CT examinations using distinct CT scanners but defining the same acquisition protocol. Considering the patient dose, this also means that the scan protocols cannot be transferred between different models without specific investigation.

We report on the development of an evaluation detector module built for our miniPET -3 small animal PET scanner. The module is based on an LySO scintillation matrix exactly matching that used in miniPET-II (so that the performance of the two PET scanners is easier to compare), followed by a Silicon Photomultiplier (SiPM) matrix array. The front-end electronics is designed to be modular, so that different readout concepts can be evaluated and prototype-tested. The readout electronics is based on a system-on-module with Spartan-6 FPGA and Gigabit Ethernet connectivity. Different SiPM readout concepts were tested using the module, and based on the evaluation results one was selected for implementation and testing.

In positron emission tomography (PET), photon scattering inside the body causes significant blurring and quantification error in the reconstructed images. To solve this problem we have developed Monte Carlo (MC) based 3D PET reconstruction algorithms implemented on the Graphics Processing Unit (GPU). Our implementation takes multiple Compton scattering into account without any significant additional cost. The performance of the scatter correction is evaluated using GATE simulation as well as by comparing reconstruction results of Tera-Tomo to the reference reconstruction implementation of the Philips Gemini TOF PET which applies attenuation correction and single scatter simulation (SSS) for scatter correction. The comparative reconstruction results are based on the NEMA NU2-2007 image quality phantom.

The factors determining the position resolution of continuous crystal based position sensitive scintillation gamma detectors are discussed. The key factors are the position functions which give the relation between the coordinates of the point of interaction (POI) and the responses of the photodetectors reading out of the scintillator. The physical phenomena limiting the position resolution are the statistical fluctuation of the detected photons and the electronic noise. For the standard deviation of the POI coordinates simple relations are deduced. It has been established that the contributions of both the statistical fluctuation and the noise to the standard deviation of the POI coordinates are inversely proportional to the square root of the detected photon numbers and the measure of these contributions can be characterised with the position resolution coefficients deduced from the position functions. A detailed discussion of the effect of the scintillator and photodetector characteristics is also given. As an example, calculations for the resolution coefficients in the case of the solid angle method with a chosen scintillator photodetector arrangement are given. The results show that the resolution coefficients as a function of the POI coordinates vary in a wide range. With realistic practical data and using almost the largest value for the resolution coefficients similar or better position resolution can be reached with continuous crystal than with a pixellated one.

We carried out spectrofluorimetric and flow cytometric measurements to investigate the effect of hypo-osmotic shock on cell membranes of common carp sperm. The time course of the permeability of the sperm cell membrane, as monitored by DNA-related propidium iodide (PI) fluorescence, was followed for 30 min after dilution of semen in hypo-osmotic environments of different ionic strengths. Spectrofluorimetric measurements indicated a continuous increase in the total PI emission intensity of a sperm suspension. Cell-by-cell flow cytometric measurements suggested that the permeability changes were of the all-or-none type. The permeabilized fraction of cells in the individual samples was time and osmolality dependent. The number and percentage of cells in which DNA was stained by PI increased gradually over time and reached a steady-state plateau value after 5-15 min. This equilibrium fraction of cells with a PI-permeable cytoplasmic membrane displayed an inverse relationship with the osmolality of the diluent, having a near 100% value for fresh water and distilled water. Dilution of sperm in hypo-osmotic medium brought about a fast decrease in the forward light-scattering signal on a short time scale compared to the pre-steady-state time of the permeabilization. With the addition of extracellular Ca2+ (1.8 mM), restoration of the light scattering signal was observed. Permeabilization of the membrane and restoration of light scattering were not coincident in time. We propose a two-dimensional reorganization of the lipid structure as the underlying mechanism of the latter process.

The examination of small animals using high resolution in-vivo imaging methods is a crucial tool in pharmaceutical research projects. These type of studies frequently require the measurement of very low activity lesions in a background region or high activity body parts for instance in case of dynamic investigations. To suffice these demands, two independent qualities of the PET scanner need to be appropriate, the low count detectability and the count rate performance. In our study we investigated the detectability of the low level activity area using our LYSO based small animal PET camera. The minimum detectable activity (MDA) was evaluated by the Currie equation and by taking into account the scanner recovery coefficient for different source diameters. We used two different water fillable cylindrical phantoms, the radius and the length of the cylinders are 15 mm and 50 mm, respectively. The phantom I includes five teflon (water density) rods with different diameter (0.5, 1.5, 2.5, 4, 6.5 mm). The phantom II includes tree glass rods with diameter of 0.5 mm. Filling the same F18 activity concentration to the rods of phantom I., the background (cylinder) region we injected C11 activity. This way we could examine different target to background ratios (T/B) simply. We found that the MDA depends on the actual background level and the size of the object. We also found that only the RC corrected MDA∗ values and related points correspond to the real detectability (visibility). The smallest rod (diameter = 0.5 mm) could not be imaged by our mini PET scanner with the activity range we used in this study.

The aim of the study is to demonstrate the diagnostic and geographical distribution of the domestic PET/CT examinations financed by the OEP based on the data from the waiting list of the past 4 years. The analysis of the demonstrated data can support the rational usage of PET/CT examination contingents in the domestic oncological attendance, which has growing importance. PET examinations with oncological aims have started in Debrecen more than 10 years ago. In 2005 already 1500 PET examinations have been carried out. According to the governmental regulation accepted in 2006, OEP ensures the financing of the three PET/CT centers until 2012, which means 12,000 examinations in 2012. However, the number of domestic oncological patients requiring PET/CT examinations can reach the number of 20,000-30,000 patients. The study summarizes the number of patients who applied for PET/CT examinations for the first time and later again between 2006 and 2010, based on the data of the waiting list, and the change of the patient assigning diagnosis and the number of examinations carried out with 18F-FDG and with 11C-methionine. The study demonstrates the number of examinations by counties which characterize the population's access to PET/CT. The assigning diagnosis in 2007 was already widespread and focused on problems. After the regulation came in to force in 2008 the possibilities significantly decreased. Clinical cases which were efficiently examined with PET/CT earlier were left out from the indication list. The distribution by county is uneven, although the number of examinations increases year by year. The number of repeated examinations increases as well. As a conclusion, the annual PET/CT examination contingents are constantly exploited. This might seem sufficient, because the method has not become a part of the oncological routine in all counties. Although the current indication list includes the most frequent oncological cases requiring PET/CT, the abandoning of the less frequent ones narrowed the professional latitude, which is disadvantageous for the patients suffering from such diseases. The radiopharmacon supply of PET/CT centers is inadequate thus they cannot provide modern oncological diagnostic attendance in case of frequent types of cancer (such as prostate). In the long run the growing number of repeated PET/CT examinations built in the oncological professional protocol has to be taken into account.

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.