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OBJECTIVE: To investigate the potential impact of polymorphism in the 3'-untranslated region (3'UTR) of the SLC6A3 gene (DAT1) on normal variation in dopamine transporter (DAT) imaging with [18F]FE-PE2I PET and [123I]FP-Cit SPECT. METHODS: Thirty-six individuals (mean age 70.4±5.4 years) with normal [18F]FE-PE2I PET and [123I]FP-Cit SPECT were genotyped for variable number of tandem repeats (VNTR) in the 3′UTR of the DAT1 gene. The DAT-availability in the caudate and putamen as measured with [18F]FE-PE2I PET and [123I]FP-Cit SPECT, as well as in the substantia nigra with [18F]FE-PE2I PET were compared between the participants carrying one or two 9-repeat alleles (i.e. 9R+10R or 9R+9R; 47%) and the participants without a 9R allele (i.e. 10R+10R or 10R+11R; 53%). Nonparametric tests, linear regression analysis and mixed model analysis were used to assess any statistical difference in measured DAT availability between the two allele groups. RESULTS: The measured DAT-availability in PET- and SPECT-imaging tended to be slightly higher in the 9R-group; however, the difference did not reach statistical significance in either the caudate or the putamen or the substantia nigra. Instead, age did have a significant effect on the DAT level (P < 0.05) notwithstanding the genotype. CONCLUSION: No significant effect of DAT1-genotype was detectable in imaging with [18F]FE-PE2I PET or [123I]FP-Cit, instead, age accounted for the normal variation in DAT-PET and DAT-SPECT.

Aim/Introduction: Quantification in PET/MRI is of importance, and its accuracy is currently limited by the MR based attenuation correction estimate. A common method for attenuation correction of the pelvic region is based on a 2-echo Dixon MRI sequence for segmentation of fat and water and does not account for bone. In this work, we evaluate a new method for attenuation correction using an algorithm based on statistical decomposition of a T2 weighted MRI scan. Materials and Methods: Substitute CT images (sCTs) were calculated from T2 weighted MRI scans with a statistical decomposition algorithm, originally developed for MRI-based radiotherapy dose-planning [1]. These sCTs benefits from having bone density information included, in addition to fat and water information. Prostate cancer patients from the PARAPLY study [2] were retrospectivelyselected, scanned with PET/MRI 11C-Acatate and CT the same day. The stand-alone CT images were transformed to the same geometry as the PET and MR images, using a non-rigid registration. CT images, generated sCT images, and the Dixonbased attenuation maps (MRAC), all in the same geometry, were together with the PET raw data used to reconstruct attenuation-corrected PET images using the PETrecon toolbox [GE Healthcare]. The two MR-based attenuation corrections were compared to the CT-based attenuation correction with root mean squared error (RMSE). Lesion analysis will also be reported. PET/MRI images were acquired on a Signa PET/MRI (GE Healthcare), and the CT images on a Brilliance Big Bore (Phillips Healthcare). The study will include 12 patients and a subset of 6 patients has been analyzed so far and is presented here. Results: Soft tissue in-between pelvic bone structures were overestimated with 13% in MRAC-PET, and the error was reduced to 5% with sCT attenuation corrected PET (sCT-PET). For the whole patient volume, an average underestimation of 6% was found in the MRAC-PET, compared to 1% for sCTPET. RMSE within the body was

Statistical modelling and intelligent data sampling in MRI and PET measurements for cancer therapy assessment

F-18-(E)-N-(3-iodoprop-2-enyl)-2 beta-carbofluoroethoxy-3 beta-(4'-methylphenyl) nortropane (F-18-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for F-18-FE-PE2I as a suitable radioligand for DAT imaging. In this study, we investigated the whole-body biodistribution and dosimetry of F-18-FE-PE2I in healthy volunteers to support its utility as a suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were performed immediately after injection followed by 4 whole-body PET/CT scans between 0.5 and 6 h after injection. Blood samples were drawn in connection with the whole-body scans, and all urine was collected until 6 h after injection. Volumes of interest were delineated around 17 organs on all images, and the areas under the time-activity curves were calculated to obtain the total number of decays in the organs. The absorbed doses to organs and the effective dose were calculated using the software IDAC. Results: The highest activity concentration was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after injection. At later time points, the highest concentration was seen in the gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the highest absorbed dose (119 mu Gy/MBq), followed by the liver (46 mu Gy/MBq). The effective dose was 23 mu Sv/MBq (range, 19-28 mu Sv/MBq), resulting in an effective dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The effective dose is within the same order of magnitude as other commonly used PET imaging agents as well as DAT agents. The reasonable effective dose, together with the previously reported favorable characteristics for DAT imaging and quantification, indicates that F-18-FE

Purpose: Attenuation correction is a requirement for quantification of the activity distribution in PET. The need to base attenuation correction on MRI instead of CT has arisen with the introduction of integrated PET/MRI systems. The aim was to describe the effect of residual gradient field nonlinearity distortions on PET attenuation correction. Methods: MRI distortions caused by gradient field nonlinearity were simulated in CT images used for attenuation correction in PET reconstructions. The simulations yielded radial distortion of up to at 15 cm from the scanner isocentre for distortion corrected images. The mean radial distortion of uncorrected images were 6.3 mm at the same distance. Reconstructions of PET data were performed using the distortion corrected images as well as the images where no correction had been applied. Results: The mean relative difference in reconstructed PET uptake intensity due to incomplete distortion correction was less than ±5%. The magnitude of this difference varied between patients and the size of the distortions remaining after distortion correction. Conclusions: Radial distortions of 2 mm at 15 cm radius from the scanner isocentre lead to PET attenuation correction errors smaller than 5%. Keeping the gradient field nonlinearity distortions below this limit can be a reasonable goal for MRI systems used for attenuation correction in PET for quantification purposes. A higher geometrical accuracy may, however, be warranted for quantification of peripheral lesions. These distortions can, e.g., be controlled at acceptance testing and subsequent quality assurance intervals.

Objective: The reference Logan plot is a tool for determining the non-displaceable binding potential for dynamic PET exams using tracers with reversible bindings. Dynamic frame protocols affect noise in PET images and short frames can lead to quantitative uncertainties and noise-induced reconstruction bias. The aim of this study was to analyze the effect of frame binning on 11C-Raclopride striatal binding potential from reference Logan analysis. Methods: 12 healthy volunteers were scanned in list mode using 11C-raclopride, and the image data were reconstructed into 9 different frame binning schemes whereof 3 clinical schemes. Reconstruction was performed with 3 different algorithms, one based on filtered back projection (FBP) and two based on ordered subset expectation maximization (OSEM); one including resolution recovery. Logan plots were used for calculating the non-displaceable binding potential. Variation in binding potential was evaluated using Students t-tests. Results: It was found that frame lengths of up to 60 s gave significantly different results compared to the reference clinical protocol for OSEM, both with and without resolution recovery (maximum deviation: 10.3 % for the 15 s protocol). For FBP, frame lengths of up to 30 s gave significantly different results with a maximum deviation of 2.8 %. The higher sampling dependence of OSEM compared to FBP is likely due to noise-dependent bias in the OSEM algorithm, most apparent at high noise levels. Conclusions: Bias related to OSEM reconstruction of high-noise data is an important factor for dynamic PET protocols. Time frames of 120 s or more generate the most stable values for the striatum binding potential with the reference Logan plot for 11C-Raclopride brain PET.

Objectives: This study applies diffusion tensor imaging (DTI) to determine differences in neuronal integrity between motor phenotypes in Parkinson's disease. Material and Methods: One hundred and twenty-two patients (47 females, mean age = 70.3 years) were included at baseline. Forty patients were tremor dominant (TD), 64 had postural imbalance and gait difficulty (PIGD), and 18 patients were indeterminate. The DTI was repeated after one, three and 5 years, including reassessment of phenotype. DTI was quantified using fractional anisotropy (FA), and mean, radial and axial diffusion. Targeted white matter involved six regions of interests (ROIs) in prefrontal cortex (PFC), the entrance to the external capsule (EEC) and lateral to the horn of the anterior ventricle (LVAH). Grey matter involved the basal ganglia. Data were analysed using mixed linear models with P < 0.05 (Bonferroni corrected) as significance threshold. Results: PIGD and Indeterminate had reduced FA and axial diffusion in PFC, EEC and LVAH compared to Tremor dominant (P < 0.05). Basal ganglia showed no differences. Post hoc analysis showed that FA correlated negatively, and mean and radial diffusion positively, to PIGD symptoms in EEC, LVAH and four ROIs in PFC (P < 0.05). Tremor symptoms showed no correlations. Patients converting to PIGD and Indeterminate had lower FA, and higher mean and radial diffusion, at baseline in EEC, LVAH and four areas in PFC compared to non-converting patients (P < 0.05). Conclusion: Degeneration in frontal white matter is connected to PIGD symptoms in Parkinson's disease and if present at an early stage, the risk for conversion to the PIGD phenotype increases.

Purpose: This work describes PETSTEP (PET Simulator of Tracers via Emission Projection): a faster and more accessible alternative to Monte Carlo (MC) simulation generating realistic PET images, for studies assessing image features and segmentation techniques. Methods: PETSTEP was implemented within Matlab as open source software. It allows generating threedimensional PET images from PET/CT data or synthetic CT and PET maps, with user-drawn lesions and user-set acquisition and reconstruction parameters. PETSTEP was used to reproduce images of the NEMA body phantom acquired on a GE Discovery 690 PET/CT scanner, and simulated with MC for the GE Discovery LS scanner, and to generate realistic Head and Neck scans. Finally the sensitivity (S) and Positive Predictive Value (PPV) of three automatic segmentation methods were compared when applied to the scanner-acquired and PETSTEP-simulated NEMA images. Results: PETSTEP produced 3D phantom and clinical images within 4 and 6 min respectively on a single core 2.7 GHz computer. PETSTEP images of the NEMA phantom had mean intensities within 2% of the scanner-acquired image for both background and largest insert, and 16% larger background Full Width at Half Maximum. Similar results were obtained when comparing PETSTEP images to MC simulated data. The S and PPV obtained with simulated phantom images were statistically significantly lower than for the original images, but led to the same conclusions with respect to the evaluated segmentation methods. Conclusions: PETSTEP allows fast simulation of synthetic images reproducing scanner-acquired PET data and shows great promise for the evaluation of PET segmentation methods.

Compartmental modeling of dynamic PET data enables quantifi- cation of tracer kinetics in vivo, through the calculated model parameters. In this study, we aimed to investigate the effect of early frame sampling and reconstruction method on pharmacokinetic parameters obtained from a 2-tissue model, in terms of bias and uncertainty (SD). Methods: The GATE Monte Carlo software was used to simulate 2 · 15 dynamic 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) brain PET studies, typical in terms of noise level and kinetic parameters. The data were reconstructed by both 3- dimensional (3D) filtered backprojection with reprojection (3DRP) and 3D ordered-subset expectation maximization (OSEM) into 6 dynamic image sets with different early frame durations of 1, 2, 4, 6, 10, and 15 s. Bias and SD were evaluated for fitted parameter estimates, calculated from regions of interest. Results: The 2-tissue-model parameter estimates K1, k2, and fraction of arterial blood in tissue depended on early frame sampling, and a sampling of 6–15 s generally minimized bias and SD. The shortest sampling of 1 s yielded a 25% and 42% larger bias than the other schemes, for 3DRP and OSEM, respectively, and a parameter uncertainty that was 10%–70% higher. The schemes from 4 to 15 s were generally not significantly different in regards to bias and SD. Typically, the reconstruction method 3DRP yielded less framesampling dependence and less uncertain results, compared with OSEM, but was on average more biased. Conclusion: Of the 6 sampling schemes investigated in this study, an early frame duration of 6–15 s generally kept both bias and uncertainty to a minimum, for both 3DRP and OSEM reconstructions. Veryshort frames of 1 s should be avoided because they typically resulted in the largest parameter bias and uncertainty. Furthermore, 3DRP may be p