Impact of the size of the normal database on the performance of the specific binding ratio in dopamine transporter SPECT

Background: This study investigated the impact of the size of the normal database on the classification performance of the specific binding ratio (SBR) in dopamine transporter (DAT) SPECT with [123I]FP-CIT in different settings. Methods: The first subject sample comprised 645 subjects from the Parkinson's Progression Marker Initiative (PPMI), 207 healthy controls (HC), and 438 Parkinson's disease (PD) patients. The second sample comprised 372 patients from clinical routine patient care, 186 with non-neurodegenerative parkinsonian syndrome (PS) and 186 with neurodegenerative PS. Single-photon emission computed tomography (SPECT) images of the clinical sample were reconstructed with two different reconstruction algorithms (filtered backprojection, iterative ordered subsets expectation maximization (OSEM) reconstruction with resolution recovery). The putaminal specific binding ratio (SBR) was computed using an anatomical region of interest (ROI) predefined in standard (MNI) space in the Automated Anatomic Labeling (AAL) atlas or using hottest voxels (HV) analysis in large predefined ROIs. SBR values were transformed to z-scores using mean and standard deviation of the SBR in a normal database of varying sizes (n = 5, 10, 15,…, 50) randomly selected from the HC subjects (PPMI sample) or the patients with non-neurodegenerative PS (clinical sample). Accuracy, sensitivity, and specificity for identifying patients with PD or neurodegenerative PS were determined as performance measures using a predefined fixed cutoff on the z-score. This was repeated for 10,000 randomly selected normal databases, separately for each size of the normal database. Mean and 5th percentile of the performance measures over the 10,000 realizations were computed. Accuracy, sensitivity, and specificity when using the whole set of HC or non-neurodegenerative PS subjects as normal database were used as benchmark. Results: Mean loss of accuracy of the putamen SBR z-score was below 1% when the normal database included at least 15 subjects, independent of subject sample (PPMI or clinical), reconstruction method (filtered backprojection or OSEM), and ROI method (AAL or HV). However, the variability of the accuracy of the putamen SBR z-score decreased monotonically with increasing size of normal database and was still considerable at size 15. In order to achieve less than 5% "maximum" loss of accuracy (defined by the 5th percentile) in all settings required at least 25 to 30 subjects in the normal database. Reduction of mean and "maximum" loss of accuracy of the putamen SBR z-score by further increasing the size of the normal database was very small beyond size 40. Conclusions: The results of this study suggest that 25 to 30 is the minimum size of the normal database to reliably achieve good performance of semi-quantitative analysis in dopamine transporter (DAT) SPECT, independent of the algorithm used for image reconstruction and the ROI method used to estimate the putaminal SBR

Correction for continuous motion in small animal PET

In small animal PET imaging experiments, animals are generally required to be anaesthetized to avoid motion artifacts. However, anaesthesia can alter biochemical pathways within the brain, thus affecting the physiological parameters under investigation. The ability to image conscious animals would overcome this problem andopen up the possibility of entirely new investigational paradigms.We have previously reported a motion-correction approach for small animal PET imaging that employs motion tracking and line of response (LOR) rebinning, and successfully demonstrated its use in phantom scans with step wise motion. In this paper we investigate an improvedsynchronization method in which TTL signals output by the motion tracker are sent to the microPET gate input to trigger the insertion of gate marks in the list mode stream that indicate the times of motion tracker measurements. The method is tested in separate microPET scans of a phantom and an anaesthetized rat which were moved continuously during data acquisition. In both cases, the motion-corrected images corresponded well with the motion-free images.We also tested the effect of pose measurement rate and synchronization error on motion correction accuracy by down-sampling and temporally misaligning list mode and motion data in a phantom study. Motion correction errors were relatively large at frequencies below -10Hz and fell rapidly to a roughly constant level above 20Hz. Motion correction errors also increased rapidly with increasingsynchronization error. In practice the acceptable limits of sampling rate and synchronization error will depend on the velocity of the motion. Using the synchronization technique presented here, and an adequate pose sampling rate, it was possible to correct for continuous motion similar to that we expect to be exhibited by conscious rats during microPET imaging experiments

Whole-body biodistribution and radiation dosimetry of [18F]PR04.MZ: a new PET radiotracer for clinical management of patients with movement disorders

Purpose [18F]PR04.MZ is a new PET imaging agent for dopamine transporters, providing excellent image quality and allowing for the evaluation of patients with movement disorders such as Parkinson’s disease. The objective of this study was to evaluate the biodistribution and radiation dosimetry of [18F]PR04.MZ by serial PET imaging. Methods Six healthy subjects (n = 3 males, n = 3 females) were enrolled in this study. A series of 14 whole-body PET/CT scans were acquired until 5.5 h post-injection of 200 ± 11 MBq of [18F]PR04.MZ. After rigid co-registration, volumes of interest were outlined either on CT or PET images. Time-integrated activity coefficients were calculated for selected source organs. Organ absorbed doses, and the effective dose were calculated using IDAC-Dose 2.1. Results Physiological uptake of [18F]PR04.MZ was mainly observed in the striatum, brain, liver, gall bladder, intestine, red marrow and cortical bone. [18F]PR04.MZ was primarily excreted via hepatobiliary clearance and, to a lower extent, via renal clearance. The normalized absorbed doses were highest in gall bladder wall (32.2 ± 6.4 µGy/MBq), urinary bladder wall (27.2 ± 4.5 µGy/MBq), red marrow (26.5 ± 1.4 µGy/MBq), cortical bone surface (26.3 ± 2.5 µGy/MBq), liver (22.5 ± 1.8 µGy/MBq) and kidneys (21.8 ± 1.1 µGy/MBq). The effective dose according to ICRP 60 and 103 was 16.3 ± 1.1 and 16.6 ± 1.5 µSv/MBq, respectively. Conclusion [18F]PR04.MZ has a favourable dosimetry profile, comparable to those of other 18F-labelled PET tracers, and is suitable for larger clinical applications. Trial registration CEC SSM Oriente, Santiago, Chile, permit 20140520

Development and dosimetry of Pb-203 / Pb-212 labeled PSMA ligands – Bringing “the Lead” into PSMA-Targeting Alpha Therapy?

The development of a prostate-specific membrane antigen (PSMA)-ligand for labeling with different radioisotopes of lead and the approximation of the dosimetry of a simulated Pb-212 based alpha-therapy by using its Pb-203 imaging analogue.JRC.G.I.5-Advanced Nuclear Knowledg

Investigation of motion-corrected VOI reconstruction for freely moving small animals with microPET

We are developing an imaging system that enables the brain of a freely moving animal to be imaged with microPET while simultaneously observing its behaviour. Towards this end, we investigated the feasibility of reconstructing a motion-tracked volume of interest (VOI) in the presence of an extraneous activity compartment with unknown motion. A dual phantom study was performed to simulate movements of a freely moving animal. Both phantoms were moved through discrete positions but only one phantom (representing the head) was tracked. The multiple acquisition frames (MAF) and LOR rebinning methods were applied based on the measured motion of the tracked phantom. We also investigated alternative approaches that are hybrids of these two methods. We found that LOR rebinning causes up to 90% ‘lost events’ (events that would have been measured had motion not occurred) when applied to a freely moving target and this fraction can be significantly reduced using the hybrid approaches, resulting in improved image quality. The MAF-based motion correction yields good results but is not practical for unconstrained motion due to the assumption of no motion within each time segment. We conclude that it is feasible to reconstruct a target VOI in the presence of extraneous activity whose motion is unknown, provided the target motion is accurately tracked

Food utilisation and digestive ability of aquatic and semi-terrestrial crayfishes, Cherax destructor and Engaeus sericatus (Astacidae, Parastacidae)

Both Engaeus sericatus and Cherax destructor are omnivorous crayfishes consuming a variety of food items. Materials identified in the faeces of both E. sericatus and C. destructor consisted of mainly plant material with minor amounts of arthropod animals, algae and fungi. The morphology of the gastric mill of C. destructor suggests that it is mainly involved in crushing of food material while the gastric mill of E. sericatus appears to be better suited to cutting of food material. Given this, the gastric mill of E. sericatus may be better able to cut the cellulose and hemicellulose fibres associated with fibrous plant material. In contrast, the gastric mill of C. destructor appears to be more efficient in grinding soft materials such as animal protein and algae. Both species accumulated high amounts of lipids in their midgut glands (about 60% of the dry mass) which were dominated by triacylglycerols (81&ndash;82% of total lipids). The dominating fatty acids were 16:0, 16:1(n-7), 18:1(n-9), 18:2(n-6), and 18:3(n-3). The two latter fatty acids can only be synthesised by plants, and are thus indicative of the consumption of terrestrial plants by the crayfishes. The similarity analysis of the fatty acid patterns showed three distinct clusters of plants and each of the crayfish species. The complement of digestive enzymes, proteinases, total cellulase, endo-&beta;-1,4-glucanase, &beta;-glucosidase, laminarinase and xylanase within midgut gland suggests that both C. destructor and E. sericatus are capable of hydrolysing a variety of substrates associated with an omnivorous diet. Higher activities of total cellulase, endo-&beta;-1,4-glucanase and &beta;-glucosidase indicate that E. sericatus is better able to hydrolyse cellulose within plant material than C. destructor. In contrast to E. sericatus, higher total protease and N-acetyl-&beta;-d-glucosaminidase activity in the midgut gland of C. destructor suggests that this species is better able to digest animal materials in the form of arthropods. Differences in total cellulase and gastric mill morphology suggest that E. sericatus is more efficient at digesting plant material than C. destructor. However, the contents of faecal pellets and the fatty acid compositions seem to indicate that both species opportunistically feed on the most abundant and easily accessible food items.<br /