Performance Evaluation of the GE eXplore CT 120 Micro-CT for Various Scanning Protocols

Poster (2012, November 03)

The aim of this study was to evaluate the performance of the General Electric (GE) eXplore CT 120 micro-CT using the same methodology and image quality assurance vmCT phantom developed for the GE eXplore ... [more ▼]

The aim of this study was to evaluate the performance of the General Electric (GE) eXplore CT 120 micro-CT using the same methodology and image quality assurance vmCT phantom developed for the GE eXplore Ultra. In addition, Quality assurance in Radiology and Medicine (QRM) low contrast and bar pattern phantoms were used. The phantoms were imaged using the six protocols regularly used in our laboratory (Fast scan 220 (P1) or 360 (P2): 70 kV, 32 mA, 220 or 360 views; Soft tissue fast scan (P3): 70 kV, 50 mA, 220 views, Soft tissue step & shoot (P4): 80 kV, 32 mA, 220 views; Low Noise (P5): 100 kV, 50 mA, 720 views and In Vivo Bone scan (P6): 100 kV, 50 mA, 360 views). Data were reconstructed with an isotropic voxel size of 100 µm (50 µm when protocol detector-binning was reduced to 2x2). The MTF obtained with the slanted edge and coil methods agreed very well. A 10% modulation transfer function (MTF) was observed in the range 3.6-4.8 mm-1 (P1&2 = 4.2; P3&4 = 4.8; P5 = 3.6 and P6 = 3.8), corresponding to 95-138 µm resolutions. The smallest bars visually observed on the QRM pattern phantom image were 100 µm. The geometric accuracy was better than 0.1%. A highly linear (R2 > 0.999) relationship between measured and expected CT numbers for both the CT number accuracy and linearity sections of the phantom was observed with a voltage dependent slope. A cupping effect was observed on the uniform slices. This effect was clearly highlighted by the uniformity-to-noise ratio (P1 = 0.58, P2&3&4 = 0.75, P5 = 1.35 and P6 = 2.74) especially for the low-noise protocols P5 and P6. The best low contrast discrimination was observed for P2 and P5 protocols. In conclusion the eXplore CT 120 achieved a resolution in the range 95-138 µm. It was found to be linear and geometrically accurate. The major difference between the protocols was the noise level which limits the detectability of low contrasts. [less ▲]

CHARACTERIZATION OF A NOVEL RADIOTRACER TARGETING SYNAPTIC VESICLE PROTEIN 2A (SV2A)

Poster (2012, September)

Synaptic vesicle protein 2A (SV2A) has been identified as the binding site of the antiepileptic levetiracetam (Keppra) [1]. SV2 proteins are critical for proper nervous system function and have been ... [more ▼]

Synaptic vesicle protein 2A (SV2A) has been identified as the binding site of the antiepileptic levetiracetam (Keppra) [1]. SV2 proteins are critical for proper nervous system function and have been demonstrated to be involved in vesicle trafficking. Their implication in epilepsy makes them an interesting therapeutic target, and the widespread distribution of SV2A in particular may provide an opportunity to develop a PET-based measure of neuronal function in brain diseases. [18F]UCB-H is a fluorine-18 radiolabelled PET imaging agent with a nanomolar affinity for the human SV2A protein. Preclinical PET studies in rodents were carried out using male SD rats, imaged under isoflurane anaesthesia in a Siemens Concorde Focus 120 microPET scanner. Arterial input function was measured using an arteriovenous shunt method and beta microprobe system. [18F]UCB-H was injected IV (3.8 ± 0.54 mCi bolus, specific activity 8.5 ± 0.86 Ci/Emol immediately after synthesis) and dynamic PET data acquired in list mode for 90 min. Images were reconstructed using filtered back projection with correction for all physical effects except scatter. These scans revealed high uptake of [18F]UCB-H in brain and spinal cord, matching the expected homogeneous distribution of SV2A in the rodent brain [2]. Notably, the kinetics of [18F]UCB-H uptake in the brain were fast, peaking at up to 30 % ID/cm3 before a rapid decline. Metabolism of [18F]UCB-H in vivo followed a typical pattern of rapid initial metabolism followed by a reducing rate of metabolism over time, with less than 20% of the activity in plasma attributable to the parent compound after 30 minutes, and was highly reproducible between subjects. One major metabolite was identified. The uptake of [18F]UCB-H in the brain over time was well fitted by a classical 1-tissue compartment model. Mean parameter estimates (mean ± SD, n=7, whole brain VOI) were K1: 3.58 ± 0.65 ml/cm3/min, k2: 0.21 ± 0.03 min-1, Vt: 17.21 ± 2.52 ml/cm3. Uptake of [18F]UCB-H was blocked by pretreatment with brivaracetam (21 mg/kg IV, 10 min prior to [18F]UCB-H), a recently described high affinity SV2A ligand with a 20-fold higher affinity for SV2A than levetiracetam [3]. In contrast, pretreatment with ucb-100230-1, a diastereoisomer of brivaracetam with 3200-fold lower affinity for SV2A [3], had no clear effect of the brain uptake of [18F]UCB-H. Our results indicate that [18F]UCB-H is a suitable radiotracer for the quantification of SV2A proteins in vivo and for estimating target occupancy of drugs targeting SV2A. This is the first PET tracer for in vivo quantification of SV2A. The necessary steps for implementation of [18F]UCB-H production under GMP conditions have been completed and first in human studies are planned. References [1] Lynch, B.A. et al. (2004) PNAS 101(26):9861-6. [2] Janz, R. & Sudhof, T.C. (1999) Neuroscience 94(4):1279-1290.[3] Gillard, M. et al. (2011) Eur J Pharmacol 664:36-44. [less ▲]

Small animal imaging with human PET

Poster (2012, September)

PET studies provide valuable information in the assessment of animal models for human diseases. MicroPET systems provide the high resolution needed to explore small organs but suffer from a reduced axial ... [more ▼]

PET studies provide valuable information in the assessment of animal models for human diseases. MicroPET systems provide the high resolution needed to explore small organs but suffer from a reduced axial FOV. Multiple bed positions are then used to obtain whole body scans resulting in increased scan time and incomplete dynamic data. In contrast, human PET systems have larger axial FOV but a lower resolution. In this study, an image-based model of the scanner spatial response function combined with a 3D-OSEM reconstruction algorithm were used to improve spatial resolution of the Siemens ECAT EXACT HR+ PET scanner. A stationary double Gaussian model [1] of the ECAT EXACT HR+ point spread function was derived from 18F point source measurements performed at different radial and axial locations in the scanner FOV. This model was used in a 3D-OSEM reconstruction (3D-OSEM-RM). Sinograms were normalized and attenuation and scatter corrected using the Siemens ECAT tools before reconstruction. Both NEMA NU 2-1994 performance phantoms and NEMA NU4-2008 image quality phantom mimicking small animals were used to evaluate the accuracy of corrections for physical effects and the overall image quality. A 50 min dynamic FDG rat study was conducted on the ECAT HR+ and reconstructed with 3D-OSEM-RM. The images were used to compute the metabolic rate of glucose (MRglu) in multiple brain structures. These images were also visually compared to the static image obtained with a FOCUS 120 microPET immediately after the HR+ dynamic scan. The standard deviations of the two Gaussians used to model the transaxial (axial) resolution in a central FOV of 5 cm radius were σ1 = 1.6 (2.75) mm and σ2 = 3.66 (4.16) mm, and the ratio of the weights between the first and second Gaussians was ρ = 0.2 (0.7). Image uniformity and accuracy of scatter and attenuation corrections, evaluated following NEMA NU 2-1994, were found to be very similar between 3D-OSEM, 3D-OSEM-RM, 2D- and 3D-FBP reconstructed images. When using the NEMA NU4-2008 image quality phantom a significant increase of the hot rod recovery coefficient was observed. This effect was rod size dependent and amounted to 17-35% for the 3D-OSEM-RM compared to the 3D-OSEM and to 35-62% compared to the FBP reconstructions. Nevertheless the values obtained with 3D-OSEM-RM were around 20-35% lower than those obtained with the FOCUS 120 microPET scanner. Most of the small brain structures observed on microPET images were also visible on the images obtained with the HR+ scanner and 3D-OSEM-RM. Rat cerebral MRglu values calculated on 3D-OSEM-RM images were in the range of published values [2] (e.g. whole brain = 25.34 μmol/min/100g). Using an approximate model of the ECAT EXACT HR+ spatial response in 3D-OSEM resulted in sufficient image quality for dynamic whole body scans of small rodents, despite the large FOV, and resulted in improved contrast compared to images generated using the built-in software. This methodology will be applied for future small animal dosimetry and modeling studies in our laboratory. [1] Comtat et al. IEEE Nucl Sci Symp Conf Record. pp. 4120-4123 (2008) [2] Schiffer et al. J Nucl Med 48:277-287 (2007) [less ▲]

PET In Conscious Rodents - Quantification of Stress During The Training Process

Poster (2012, September)

Recently several methods for performing PET studies in conscious rodents have been developed [1-3]. These methods have the potential to greatly improve the translational nature of PET studies in rodents ... [more ▼]

Recently several methods for performing PET studies in conscious rodents have been developed [1-3]. These methods have the potential to greatly improve the translational nature of PET studies in rodents. One of the most easily implemented methods is the training of a rat to tolerate head fixation in a restraining device. Training consists of intervals of restraint over several days. However, the stress induced by this training procedure has not been quantified in detail. Limited changes in plasma corticosterone have been reported, but this data may be confounded by sample timing and baseline levels. An implantable telemetry system (Telemetry Research) was used to remotely measure blood pressure, heart rate and core temperature during training. Transmitters were implanted in the abdominal cavity under isoflurane anesthesia, with the blood pressure sensor fixed in the abdominal aorta. Training was started after a recovery period of at least 1 week. Training consisted of a 5 min period of acclimatization in the cage containing the restraining device, followed by increasing durations of restraint in the device on subsequent training days (15, 30, 45, 60, 90 min). Telemetry data was acquired from 5 min prior to acclimatization to 60 minutes post-training. In this initial pilot study, a single rat was trained, without head fixation, for 4 consecutive days and again on day 7. All reported values are mean ± SEM across the five training days. In the home cage, prior to acclimatization, baseline heart rate (HR) was 294 ± 15 bpm. During the acclimatization period, HR was elevated to 411 ± 7 bpm. Immediately after starting training, HR was 419 ± 16 bpm. During the training period HR showed a tendency to decrease, with raised periods at undefined intervals. After return to the home cage, HR remained elevated for 15-20 min before returning to a value (313 ± 9 bpm) close to baseline. A similar pattern was seen in blood pressure (mean; BP). Baseline BP was 76 ± 7 mmHg, increasing to 94 ± 9 mmHg during acclimatization. After commencing training, a peak in BP was reached at 102 ± 8 mmHg. After the 15-20 min recovery interval, BP returned to a baseline of 77 ± 9 mmHg. The HR and BP responses to acclimatization and to the training protocol persisted throughout all training days, with the main noticeable difference being the number of bouts of increased HR, which increased with training duration. Core body temperature (baseline: 37.45 ± 0.21 °C) increased during restraint training, with a subsequent post-training peak (38.21 ± 0.03 °C). Measurement of core temp is complicated during longer training sessions by the need to charge the transmitter. This early data indicates that stress induced by the training procedure for conscious PET persists after several days of training. In subsequent studies the head will be fixed and the effect of the training on plasma corticosterone and central glucose metabolism (using [18F]FDG) will be examined. [1] Momosaki et al. (2004) Synapse 54:207–213 [2] Wyss et al. (2009) NeuroImage 48:339–347 [3] Itoh et al. (2009) J Nucl Med 50:749–756 [less ▲]

X-ray Dose Quantification for Various Scanning Protocols with the GE eXplore 120 micro-CT

Poster (2012)