Impact of improved dead time correction on the quantification accuracy of a dedicated BrainPET scanner.

OBJECTIVE: Quantitative values derived from PET brain images are of high interest for neuroscientific applications. Insufficient DT correction (DTC) can lead to a systematic bias of the output parameters obtained by a detailed analysis of the time activity curves (TACs). The DTC method currently used for the Siemens 3T MR BrainPET insert is global, i.e., differences in DT losses between detector blocks are not considered, leading to inaccurate DTC and, consequently, to inaccurate measurements masked by a bias. However, following careful evaluation with phantom measurements, a new block-pairwise DTC method has demonstrated a higher degree of accuracy compared to the global DTC method. APPROACH: Differences between the global and the block-pairwise DTC method were studied in this work by applying several radioactive tracers. We evaluated the impact on [11C]ABP688, O-(2-[18F]fluoroethyl)-L-tyrosine (FET), and [15O]H2O TACs. RESULTS: For [11C]ABP688, a relevant bias of between -0.0034 and -0.0053 ml/ (cm3 • min) was found in all studied brain regions for the volume of distribution (VT) when using the current global DTC method. For [18F]FET-PET, differences of up to 10% were observed in the tumor-to-brain ratio (TBRmax), these differences depend on the radial distance of the maximum from the PET isocenter. For [15O]H2O, differences between +4% and -7% were observed in the GM region. Average biases of -4.58%, -3.2%, and -1.2% for the regional cerebral blood flow (CBF (K1)), the rate constant k2, and the volume of distribution VT were observed, respectively. Conversely, in the white matter region, average biases of -4.9%, -7.0%, and 3.8% were observed for CBF (K1), k2, and VT, respectively. CONCLUSION: The bias introduced by the global DTC method leads to an overestimation in the studied quantitative parameters for all applications compared to the block-pairwise method. SIGNIFICANCE: The observed differences between the two DTC methods are particularly relevant for research applications in neuroscientific studies as they affect the accuracy of quantitative Brain PET images.

Fast 3D kernel computation method for positron range correction in PET.

Objective. The positron range is a fundamental, detector-independent physical limitation to spatial resolution in positron emission tomography (PET) as it causes a significant blurring of underlying activity distribution in the reconstructed images. A major challenge for positron range correction methods is to provide accurate range kernels that inherently incorporate the generally inhomogeneous stopping power, especially at tissue boundaries. In this work, we propose a novel approach to generate accurate three-dimensional (3D) blurring kernels both in homogenous and heterogeneous media to improve PET spatial resolution.Approach. In the proposed approach, positron energy deposition was approximately tracked along straight paths, depending on the positron stopping power of the underlying material. The positron stopping power was derived from the attenuation coefficient of 511 keV gamma photons according to the available PET attenuation maps. Thus, the history of energy deposition is taken into account within the range of kernels. Special emphasis was placed on facilitating the very fast computation of the positron annihilation probability in each voxel.Results. Positron path distributions of18F in low-density polyurethane were in high agreement with Geant4 simulation at an annihilation probability larger than 10-2∼ 10-3of the maximum annihilation probability. The Geant4 simulation was further validated with measured18F depth profiles in these polyurethane phantoms. The tissue boundary of water with cortical bone and lung was correctly modeled. Residual artifacts from the numerical computations were in the range of 1%. The calculated annihilation probability in voxels shows an overall difference of less than 20% compared to the Geant4 simulation.Significance. The proposed method is expected to significantly improve spatial resolution for non-standard isotopes by providing sufficiently accurate range kernels, even in the case of significant tissue inhomogeneities.

Impact of framing scheme optimization and smoking status on binding potential analysis in dynamic PET with [11C]ABP688.

BACKGROUND: For positron emission tomography (PET) ligands, such as [11C]ABP688, to be able to provide more evidence about the glutamatergic hypothesis in schizophrenia (SZ), quantification bias during dynamic PET studies and its propagation into the estimated values of non-displaceable binding potential (BPND) must be addressed. This would enable more accurate quantification during bolus + infusion (BI) neuroreceptor studies and further our understanding of neurological diseases. Previous studies have shown BPND-related biases can often occur due to overestimated cerebellum activity (reference region). This work investigates whether an alternative framing scheme can minimize quantification biases propagated into BPND, whether confounders, such as smoking status, need to be controlled for during the study, and what the consequences for the data interpretation following analysis are. A group of healthy controls (HC) and a group of SZ patients (balanced and unbalanced number of smokers) were investigated with [11C]ABP688 and a BI protocol. Possible differences in BPND quantification as a function of smoking status were tested with constant 5 min ('Const 5 min') and constant true counts ('Const Trues') framing schemes. In order to find biomarkers for SZ, the differences in smoking effects were compared between groups. The normalized BPND and the balanced number of smokers and non-smokers for both framing schemes were evaluated. RESULTS: When applying F-tests to the 'Const 5 min' framing scheme, effect sizes (η2p) and brain regions which showed significant effects fluctuated considerably with F = 50.106 ± 54.948 (9.389 to 112.607), P-values 0.005 to < 0.001 and η2p = 0.514 ± 0.282 (0.238 to 0.801). Conversely, when the 'Const Trues' framing scheme was applied, the results showed much smaller fluctuations with F = 78.038 ± 8.975 (86.450 to 68.590), P < 0.001 for all conditions and η2p = 0.730 ± 0.017 (0.742 to 0.710), and regions with significant effects were more robustly reproduced. Further, differences, which would indicate false positive identifications between HC and SZ groups in five brain regions when using the 'Const 5 min' framing scheme, were not observed with the 'Const Trues' framing. CONCLUSIONS: Based on an [11C]ABP688 PET study in SZ patients, the results show that non-consistent BPND outcomes can be propagated by the framing scheme and that potential bias can be minimized using 'Const Trues' framing.

A detector block-pairwise dead time correction method for improved quantitation with a dedicated BrainPET scanner.

'Objective. Dead time correction (DTC) is an important factor in ensuring accurate quantification in PET measurements. This is currently often achieved using a global DTC method, i.e., an average DTC factor is computed. For PET scanners designed to image dedicated organs, e.g., those used in brain imaging or positron emission mammography (PEM), a substantial amount of the administered radioactivity is located outside of the PET field-of-view (FOV). This activity contributes to the dead time (DT) of the scintillation detectors. Moreover, the count rates of the individual scintillation detectors are potentially very inhomogeneous due to the specific irradiation of each detector, especially for combined MR/PET systems, where radiation shields cannot be applied. Approach: We have developed a block-pairwise DTC method for our Siemens 3T MR BrainPET insert by extending a previously published method that uses the delayed random coincidence count rate to estimate the DT in the individual scans and planes (i.e., scintillation pixel rings). The method was validated in decay experiments using phantoms with a homogenous activity concentration and with and without out-of-FOV activity. Based on a three-compartment phantom, we compared the accuracy and noise properties of the block-pairwise DTC and the global DTC method.Main results. The currently used global DTC led to a substantial positive bias in regions with high activity; the block-pairwise DTC resulted in substantially less bias. The noise level for the block-pairwise DTC was comparable to the global DTC and image reconstructions without any DTC. Finally, we tested the block-pairwise DTC with a data set obtained from volunteer measurements using the mGluR5 (metabotropic glutamate receptor subtype 5) antagonist [11C]ABP688. When the relative differences in activity concentrations obtained with global DTC and block-pairwise DTC for the ACC and the cerebellum GM were compared, the ratios differed by a factor of up to 1.4 at the beginning-when the first injection is administered as a bolus with high radioactivity.Significance. In this work, global DTC was shown to have the potential to introduce quantification bias, while better quantitation accuracy was achieved with the presented block-pairwise DTC method. The method can be implemented in all systems that use the delayed window technique and is particulary expected to improve the quantiation accuracy of dedicated brain PET scanners due to their geometry.'

Stereological Evidence of Non-Selective Hippocampal Neurodegeneration, IGF-1 Depletion, and Behavioral Deficit following Short Term Bilateral Adrenalectomy in Wistar Rats.

The development of animal models to study cell death in the brain is a delicate task. One of the models, that was discovered in the late eighties, is the induction of neurodegeneration through glucocorticoid withdrawal by adrenalectomy in albino rats. Such a model is one of the few noninvasive models for studying neurodegeneration. In the present study, using stereological technique and ultrastructural examination, we aimed to investigate the impact of short-term adrenalectomy (2 weeks) on different hippocampal neuronal populations in Wistar rats. In addition, the underlying mechanism(s) of degeneration in these neurons were investigated by measuring the levels of insulin-like growth factor-1 (IGF-1) and ß-nerve growth factor (ß-NGF). Moreover, we examined whether the biochemical and histological changes in the hippocampus, after short-term adrenalectomy, have an impact on the cognitive behavior of Wistar rats. Stereological counting in the hippocampus revealed significant neuronal deaths in the dentate gyrus and CA4/CA3, but not in the CA2 and CA1 areas, 7 and 14 days post adrenalectomy. The ultrastructural examinations revealed degenerated and degenerating neurons in the dentate, as well as CA4, and CA3 areas, over the course of 3, 7 and 14 days. The levels of IGF-1 were significantly decreased in the hippocampus of ADX rats 24 h post adrenalectomy, and lasted over the course of two weeks. However, ß-NGF was not affected in rats. Using a passive avoidance task, we found a cognitive deficit in the ADX compared to the SHAM operated rats over time (3, 7, and 14 days). In conclusion, both granule and pyramidal cells were degenerated in the hippocampus following short-term adrenalectomy. The early depletion of IGF-1 might play a role in hippocampal neuronal degeneration. Consequently, the loss of the hippocampal neurons after adrenalectomy leads to cognitive deficits.

Evaluation of Radiation Doses in Pediatric Patients Undergoing Conventional Chest X-ray Examination.

ABSTRACT: This work deals with the evaluation of radiation doses from chest x rays for 240 male and female pediatric patients selected randomly from four Palestinian hospitals. The patient population was divided into five age groups: Newborn, 1, 5, 10, and 15 y old. Doses were theoretically calculated by using Monte Carlo based codes: CALDOSE-X5 and PCXMC-2.0. Patients' data and type of radiographic systems used as well as exposure factors were provided by the administrations of the selected hospitals. Absorbed organ doses from AP and PA projections were evaluated for 76 pediatric patients selected from one hospital in East Jerusalem. The highest mean organ dose for these patients was 0.085 mGy to the breast in AP projection. Effective doses were estimated for the five age groups for all patients. The highest average effective dose was found for patients in the age group of 10 y and was about 0.13 mSv, while the lowest average effective dose was found for the 5-y age group, about 0.06 mSv. The mean effective dose for all investigated patients in the five age categories was about 0.08 mSv. Variations in effective doses for the same age group and x-ray examination among involved hospitals are remarkable.

Bias evaluation and reduction in 3D OP-OSEM reconstruction in dynamic equilibrium PET studies with 11C-labeled for binding potential analysis.

Iterative image reconstruction is widely used in positron emission tomography. However, it is known to contribute to quantitation bias and is particularly pronounced during dynamic studies with 11C-labeled radiotracers where count rates become low towards the end of the acquisition. As the strength of the quantitation bias depends on the counts in the reconstructed frame, it can differ from frame to frame of the acquisition. This is especially relevant in the case of neuro-receptor studies with simultaneous PET/MR when a bolus-infusion protocol is applied to allow the comparison of pre- and post-task effects. Here, count dependent changes in quantitation bias may interfere with task changes. We evaluated the impact of different framing schemes on quantitation bias and its propagation into binding potential (BP) using a phantom decay study with 11C and 3D OP-OSEM. Further, we propose a framing scheme that keeps the true counts per frame constant over the acquisition time as constant framing schemes and conventional increasing framing schemes are unlikely to achieve stable bias values during the acquisition time range. For a constant framing scheme with 5 minutes frames, the BP bias was 7.13±2.01% (10.8% to 3.8%) compared to 5.63±2.85% (7.8% to 4.0%) for conventional increasing framing schemes. Using the proposed constant true counts framing scheme, a stabilization of the BP bias was achieved at 2.56±3.92% (3.5% to 1.7%). The change in BP bias was further studied by evaluating the linear slope during the acquisition time interval. The lowest slope values were observed in the constant true counts framing scheme. The constant true counts framing scheme was effective for BP bias stabilization at relevant activity and time ranges. The mean BP bias under these conditions was 2.56±3.92%, which represents the lower limit for the detection of changes in BP during equilibrium and is especially important in the case of cognitive tasks where the expected changes are low.

PATIENT RADIATION DOSE FROM CHEST X-RAY EXAMINATIONS IN THE WEST BANK-PALESTINE.

Radiation doses to patients resulting from chest X-ray examinations were evaluated in four medical centers in the West Bank and East Jerusalem-Palestine. Absorbed organ and effective doses were calculated for a total of 428 adult male and female patients by using commercially available Monte Carlo based softwares; CALDOSE-X5 and PCXMC-2.0, and hermaphrodite mathematical adult phantoms. Patients were selected randomly from medical records in the time period from November 2014 to February 2015. A database of surveyed patients and exposure factors has been established and includes: patient's height, weight, age, gender, X-ray tube voltage, electric current (mAs), examination projection (anterior posterior (AP), posterior anterior (PA), lateral), X-ray tube filtration thickness in each X-ray equipment, anode angle, focus to skin distance and X-ray beam size. The average absorbed doses in the whole body from different projections were: 0.06, 0.07 and 0.11 mGy from AP, PA and lateral projections, respectively. The average effective dose for all surveyed patients was 0.14 mSv for all chest X-ray examinations and projections in the four investigated medical centers. The effect of projection geometry was also investigated. The average effective doses for AP, PA and lateral projections were 0.14, 0.07 and 0.22 mSv, respectively. The collective effective dose estimated for the exposed population was ~60 man-mSv.