Nuno C. Ferreira

RPC-PET: a new very high resolution PET technology

In this paper, we present experimental and simulated results from a first prototype of a positron emission tomography (PET) system based on the resistive plate chamber (RPC) technology-a gaseous particle detector developed for high energy physics. The prototype is aimed at validating the expectations, derived from simulations, of a system with submillimeter spatial image resolution and no parallax error, which may be useful for the imaging of small animals. By imaging a point-like 22Na source in the transaxial plane, an intrinsic spatial resolution of 0.52 mm FWHM was demonstrated for a system diameter of 60 mm, validating positron range simulations by other authors. A corresponding image spatial resolution of 0.51 mm FWHM was obtained using the standard algorithm of filtered backprojection (FBP) and 0.31 mm FWHM after reconstruction by an ML-EM type algorithm. An optimized complete system was simulated to evaluate sensitivity and system count rate performance for the imaging of mice, suggesting a sensitivity up to 2.1% at the center of the field of view and a peak noise equivalent count rate (NECR) up to 320 Kcps for a total activity of 88 MBq in the phantom

A hybrid scatter correction for 3D PET based on an estimation of the distribution of unscattered coincidences : implementation on the ECAT EXACT HR+

We implemented a hybrid scatter-correction method for 3D PET that combines two scatter-correction methods in a complementary way. The implemented scheme uses a method based on the discrimination of the energy of events (the estimation of trues method (ETM)) and an auxiliary method (the single scatter simulation method (SSS1) or the convolution–subtraction method (CONV)) in an attempt to increase the accuracy of the correction over a wider range of acquisitions. The ETM takes into account the scatter from outside the field-of-view (FOV), which is not estimated with the auxiliary method. On the other hand, the auxiliary method accounts for events that have scattered with small angles, which have an energy that cannot be discriminated from that of unscattered events using the ETM. The ETM uses the data acquired in an upper energy window above the photopeak (550–650 keV) to obtain a noisy estimate of the unscattered events in the standard window (350–650 keV). Our implementation uses the auxiliary method to correct the residual scatter in the upper window. After appropriate scaling, the upper window data are subtracted from the total coincidences acquired in the standard window, resulting in the final scatter estimate, after smoothing. In this work we compare the hybrid method with the corrections used by default in the 2D and 3D modes of the ECAT EXACT HR+ using phantom measurements. Generally, the contrast was better with the hybrid method, although the relative errors of quantification were similar. We conclude that hybrid techniques such as the one implemented in this work can provide an accurate, general-purpose and practical way to correct the scatter in 3D PET, taking into account the scatter from outside the FOV.

Whole-Body Single-Bed Time-of-Flight RPC-PET: Simulation of Axial and Planar Sensitivities With NEMA and Anthropomorphic Phantoms

A single-bed, whole-body positron emission tomograph based on resistive plate chambers has been proposed (RPC-PET). An RPC-PET system with an axial field-of-view (AFOV) of 2.4 m has been shown in simulation to have higher system sensitivity using the NEMA NU2-1994 protocol than commercial PET scanners. However, that protocol does not correlate directly with lesion detectability. The latter is better correlated with the planar (slice) sensitivity, obtained with a NEMA NU2-2001 line-source phantom. After validation with published data for the GE Advance, Siemens TruePoint and TrueV, we study by simulation their axial sensitivity profiles, comparing results with RPC-PET. Planar sensitivities indicate that RPC-PET is expected to outperform 16-cm (22-cm) AFOV scanners by a factor 5.8 (3.0) for 70-cm-long scans. For 1.5-m scans (head to mid-legs), the sensitivity gain increases to 11.7 (6.7). Yet, PET systems with large AFOV provide larger coverage but also larger attenuation in the object. We studied these competing effects with both spherical- and line-sources immersed in a 27-cm-diameter water cylinder. For 1.5-m-long scans, the planar sensitivity drops one order of magnitude in all scanners, with RPC-PET outperforming 16-cm (22-cm) AFOV scanners by a factor 9.2 (5.3) without considering the TOF benefit. A gain in the effective sensitivity is expected with TOF iterative reconstruction. Finally, object scatter in an anthropomorphic phantom is similar for RPC-PET and modern, scintillator-based scanners, although RPC-PET benefits further if its TOF information is utilized to exclude scatter events occurring outside the anthropomorphic phantom.

The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ

Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon‐γ (IFN‐γ). Mycobacterium avium‐infected mice lacking IFN‐γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine‐18‐fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN‐γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN‐γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN‐γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN‐γ is responsible for the Warburg effect observed in organs infected with M. avium.

Assessment of 3-D PET quantitation: influence of out of the field of view radioactive sources and of attenuating media

Using the Utah scatter phantom with media of different densities and activity proportions, the authors tested the accuracy of quantitation in the two-dimensional (2-D) and three-dimensional (3-D) modes of acquisition of the ECAT EXACT HR+ tomograph. The influence of radioactive sources outside the field of view (FOV) was also investigated, using different bed positions. The authors measured the activities in regions of interest drawn in the reconstructed images and compared the means through several planes versus the activities expected from well counter measurements. The 3-D scatter correction algorithm successfully restored the activity concentration in the various chambers of the phantom, with relative errors between -10.4 and +12.0%, slightly larger than those observed in 2-D (-8.6 to +5.6%) but similar to values when no activity was out of the FOV (between +4.0 and +4.6%). The activity out of the FOV increased the relative errors and introduced nonuniformities along the axial direction. The attenuation coefficient of the different materials also influenced the results: negative activity values were observed for high attenuation coefficient regions of the 3-D scatter corrected images.

Influence of malfunctioning block detectors on the calculation of single detector efficiencies in PET

The authors studied the artifacts generated by the application of methods of crystal efficiency calculation based on the fan-sum, to situations of high variability of efficiency, namely the cases of a ring with defective blocks and acquisitions using narrow energy windows. The authors propose two efficiency calculation methods to reduce these artifacts: one method discriminates the crystals with an efficiency very different from the average, and then uses a modification of the fan-sum to estimate the efficiency; the other method calculates iteratively the fan-sum of each crystal, weighted by the efficiencies of the opposed detectors. The effect of using an off-center uniform cylinder is also discussed, since it influences the performance of the algorithms. The proposed algorithms are compared with the more conventional fan-sum method and with an algorithm used in commercial tomograph, using measurements and simulations. The results show a significant reduction of the efficiency estimation errors, in severe situations where detectors in a ring have very different detection efficiency.

Iterative crystal efficiency calculation in fully 3-D PET

The calculation of the intrinsic efficiency of individual crystals is one of the steps needed to obtain accurate images of the radioisotope distribution in positron emission tomography (PET). These efficiencies can be computed by comparing the number of coincidence counts obtained when the crystals are equally illuminated by the same source. However, because the number of coincidence counts acquired for one crystal also depends on the efficiency of the other crystals in coincidence, most methods of crystal efficiency calculation need to assume that the influence of the other crystals is negligible. If there are large crystal efficiency variations, this approximation may lead to systematic errors. The authors have recently implemented an iterative method for a single ring of detectors that does not rely on this assumption. Here, they describe a fully three dimensional (3-D) iterative method that better exploits the sensitivity of the tomograph and allows reduced acquisition times or the use of narrow energy windows. They compare the performance of the iterative method (single-ring and extended to fully 3-D) with noniterative techniques for different acquisition times of a uniform cylinder. Two different energy windows were used to assess the performance of each method with different levels of variations of crystal efficiency. The results showed that the iterative methods are more accurate when large efficiency variations exist and that only the fully 3-D methods provided good efficiency estimates with very low duration scans. The authors, thus, conclude that iterative fully 3-D methods provide the best estimations and can be used in a larger range of situations than can the other methods tested.

Cardiac lymphatic dynamics after ischemia and reperfusion—experimental model

ABSTRACT. The aim of the present study was to investigate the lymphatic cardiac circulation in an experimental model of ischemia plus reperfusion in mongrel dogs (Canis familiaris L). As radiotracer we used 0.2-0.25 ml (111 MBq) of 99mTc-Re2S7 colloid (+/-10 microm), injected subcapsullary below the second diagonal of the descending anterior ligated coronary artery with a special needle. A gamma-camera/Starport + DecStation were used for data acquisition. Four experimental groups with five animals each were established: G I = controls; G II = immediately after acute myocardial infarction (AMI); G III = late infarction (5 days after AMI); G IV = ischemia (90 min) + reperfusion. Four regions of interest (ROIs) were chosen: injection area (ZA), above (ZB), near right (ZD), and far right (ZC) from ZA. Mean disappearance times in ZA and dynamic parameters in the other ROIs were determined from activity/time curves drawn in each area, using homemade software. The results obtained seem to indicate that the methodology is appropriate to a detailed study of lymphatic drainage in pathological situations in animal models.

GABA deficiency in NF1 A multimodal [11C]-flumazenil and spectroscopy study

Objective: To provide a comprehensive investigation of the γ-aminobutyric acid (GABA) system in patients with neurofibromatosis type 1 (NF1) that allows understanding the nature of the GABA imbalance in humans at pre- and postsynaptic levels. Methods: In this cross-sectional study, we employed multimodal imaging and spectroscopy measures to investigate GABA type A (GABAA) receptor binding, using [11C]-flumazenil PET, and GABA concentration, using magnetic resonance spectroscopy (MRS). Fourteen adult patients with NF1 and 13 matched controls were included in the study. MRS was performed in the occipital cortex and in a frontal region centered in the functionally localized frontal eye fields. PET and MRS acquisitions were performed in the same day. Results: Patients with NF1 have reduced concentration of GABA+ in the occipital cortex (p = 0.004) and frontal eye fields (p = 0.026). PET results showed decreased binding of GABAA receptors in patients in the parieto-occipital cortex, midbrain, and thalamus, which are not explained by decreased gray matter levels. Conclusions: Abnormalities in the GABA system in NF1 involve both GABA concentration and GABAA receptor density suggestive of neurodevelopmental synaptopathy with both pre- and postsynaptic involvement.

Synthesis of a new 18F labeled porphyrin for potential application in positron emission tomography. In vivo imaging and cellular uptake

Herein we report, for the first time, the development, labeling optimization and preliminary biodistribution studies of an [18F] radiolabeled meso-tetraphenylporphyrin. After synthesis and characterization of the “cold” fluorinated porphyrin, the conditions have been transferred to an automated radiochemistry module and the desired 5-(2-[18F]fluoroethoxyphenyl)-10,15,20-triphenylporphyrin was prepared in a radiochemical purity >95%. Moreover, data regarding the uptake into human bladder tumor cells and the radiotracer biodistribution after C57BL/6 mice injection are also presented. The maximum cellular uptake was reached at 45 min and was of 2.5%.