Optimization of 99m Tc whole-body SPECT/CT image quality: A phantom study.

PURPOSE: Investigate the impact of acquisition time and reconstruction parameters on single-photon emission computed tomography/computed tomography (SPECT/CT) image quality with the ultimate aim of finding the shortest possible acquisition time for clinical whole-body SPECT/CT (WB-SPECT/CT) while maintaining image quality METHODS: The National Electrical Manufacturers Association (NEMA) image quality measurements were performed on a SPECT/CT imaging system using a NEMA International Electrotechnical Commission (IEC) phantom with spherical inserts of varying diameter (10-37 mm), filled with 99m Tc in activity sphere-to-background concentration ratio of 8.5:1. A gated acquisition was acquired and binned data were summed to simulate acquisitions of 15, 8, and 3 s per projection angle. Images were reconstructed on a Hermes (HERMES Medical Solutions AB, Stockholm, Sweden) workstation using eight subsets and between 4 and 24 iterations of the three-dimensional (3D) ordered subset expectation maximization (OSEM) algorithm. Reconstructed images were post-smoothed with 3D Gaussian filter ranging from 0 to 12 mm full-width at half maximum (FWHM). Contrast recovery, background variability, and contrast-to-noise ratio were evaluated RESULTS: As expected, the spheres were more clearly defined as acquisition time and count statistics improved. The optimal iteration number and Gaussian filter were determined from the contrast recovery convergence and level of noise. Convergence of contrast recovery was observed at eight iterations while 12 iterations yielded stabilized values at all acquisition times. In addition, it was observed that applying 3D Gaussian filter of 8-12 mm FWHM suppressed the noise and mitigated Gibbs artifacts. Background variability was larger for small spheres than larger spheres and the noise decreased when acquisition time became longer. A contrast-to-noise ratio >5 was reached for the two smallest spheres of 10 and 13 mm at acquisition times of 8 s CONCLUSION: Optimized reconstruction parameters preserved image quality with reduce acquisition time in present study. This study suggests an optimal protocol for clinical 99m Tc SPECT/CT can be reached at 8 s per projection angle, with data reconstructed using 12 iterations and eight subset of the 3D OSEM algorithm and 8 mm Gaussian post-filter.

Open-field PET: Simultaneous brain functional imaging and behavioural response measurements in freely moving small animals.

A comprehensive understanding of how the brain responds to a changing environment requires techniques capable of recording functional outputs at the whole-brain level in response to external stimuli. Positron emission tomography (PET) is an exquisitely sensitive technique for imaging brain function but the need for anaesthesia to avoid motion artefacts precludes concurrent behavioural response studies. Here, we report a technique that combines motion-compensated PET with a robotically-controlled animal enclosure to enable simultaneous brain imaging and behavioural recordings in unrestrained small animals. The technique was used to measure in vivo displacement of [11C]raclopride from dopamine D2 receptors (D2R) concurrently with changes in the behaviour of awake, freely moving rats following administration of unlabelled raclopride or amphetamine. The timing and magnitude of [11C]raclopride displacement from D2R were reliably estimated and, in the case of amphetamine, these changes coincided with a marked increase in stereotyped behaviours and hyper-locomotion. The technique, therefore, allows simultaneous measurement of changes in brain function and behavioural responses to external stimuli in conscious unrestrained animals, giving rise to important applications in behavioural neuroscience.

Synthesis and in vitro evaluation of fluorine-18 benzimidazole sulfones as CB2 PET-radioligands.

Cannabinoid type 2 receptor (CB2) is up-regulated on activated microglial cells and can potentially be used as a biomarker for PET-imaging of neuroinflammation. In this study the synthesis and pharmacological evaluation of novel fluorinated pyridyl and ethyl sulfone analogues of 2-(tert-butyl)-5-((2-fluoropyridin-4-yl)sulfonyl)-1-(2-methylpentyl)-1H-benzo[d]imidazole (rac-1a) are described. In general, the ligands showed low nanomolar potency (CB2 EC50 < 10 nM) and excellent selectivity over the CB1 subtype (>10 000×). Selected ligands 1d, 1e, 1g and 3l showing high CB2 binding affinity (Ki < 10 nM) were radiolabelled with fluorine-18 from chloropyridyl and alkyl tosylate precursors with good to high isolated radioactive yields (25-44%, non-decay corrected, at the end of synthesis). CB2-specific binding of the radioligand candidates [18F]-1d and [18F]-3l was assessed on rat spleen cryosections using in vitro autoradiography. The results warrant further in vivo evaluation of the tracer candidates as prospective CB2 PET-imaging agents.

Dosimetric impact of breast density in breast tomosynthesis: A comparative study.

A radiation dose survey has been undertaken involving 256 patients to investigate the dosimetric impact of breast tomosynthesis screening by employing different breast densities estimated by the Dance model, 50-50 breast model, and patient-specific density software: Volpara. Mean glandular dose (MGD) based on the Dance model provided the most realistic dose estimate with an average difference of -3.3 ± 4.8% from the patient-specific estimation. Average differences of -8.2 ± 6.5% and -7.3 ± 4.7% were observed for the 50-50 breast model and console MGD, respectively. We conclude that the Dance model should be used for dose calculations in radiation dose surveys and establishing diagnostic reference levels (DRL).

Responsiveness of quantitative cartilage measures over one year in knee osteoarthritis: comparison of radiography and MRI assessments.

PURPOSE: To directly compare the responsiveness of quantitative imaging measures of disease progression in knee osteoarthritis (OA). In the medial compartment of the knee comparison was made between: 1) radiographic joint space narrowing (JSN); 2) global quantitative magnetic resonance imaging (qMRI) of cartilage volume; 3) regional qMRI of cartilage thickness; and 4) regional analysis using an ordered value (OV) methodology. MATERIALS AND METHODS: 3T MRI and weight-bearing radiography of the knees were performed at baseline and 1-year timepoints in 23 subjects (mean age 63 years) with symptomatic knee OA. Standardized response means (SRM) were calculated for each measure. Statistical analysis to determine significance of change between timepoints was performed with a two-tailed Student's t-test (JSN, global, regional analysis) and nonparametric Mann-Whitney test (ordered values). RESULTS: At 1 year, global cartilage volume losses of 2.3% (SRM -0.44) in the medial tibia and 6.9% in the medial femur (SRM -0.74) were recorded. SRM for JSN was -0.46. Regional analysis revealed largest reductions in cartilage thickness in the external (SRM -0.84) weight-bearing subregion of the medial femur and in the posterior subregion of the medial tibia (SRM -0.79). OV analysis in the medial compartment revealed areas of cartilage thinning (four ranked OV) and cartilage thickening (two ranked OV). CONCLUSION: The MRI OV approach proved to be a superior analysis tool for detecting changes in cartilage morphology over a 1-year period. Radiographically defined JSN was found to be the least responsive measurement method of knee OA disease progression.

Use of 3T MRI and an unspoiled 3D fast gradient echo sequence for porcine knee cartilage volumetry: preliminary findings.

PURPOSE: To assess the utility of knee cartilage volumetry using an unspoiled fat-suppressed 3D fast gradient echo (FGRE) sequence at 3T. MATERIALS AND METHODS: Sagittal magnetic resonance (MR) images were obtained with an unspoiled fat-suppressed 3D FGRE sequence in eight porcine knees. Manual segmentation was used to derive the cartilage volume. This volume was compared to a volume measurement of cartilage scraping specimens obtained by water displacement. Imaging was repeated five times in four of the knees to assess interscan volume measurement reproducibility and calculate precision error. A single 3D dataset was manually segmented five times at weekly intervals to assess intraobserver volume measurement reproducibility. RESULTS: Total cartilage volume obtained from MRI and water displacement correlated well (r = 0.75). The interscan reproducibility of total volume measurements, expressed as the coefficient of variation (CV), was 4.2%, and the precision error (root mean square [RMS] CV) was 4.1%. The CV of intraobserver estimates of total cartilage volume by MRI was 3.6%. CONCLUSION: Interscan reproducibility of quantification of total cartilage volume and reproducibility of the manual segmentation technique were both high (>95%). Accurate and reproducible cartilage volumetry can be obtained by using a clinical unspoiled fat-suppressed 3D FGRE acquired at 3T MRI.

Reduction of scan duration and radiation dose in cerebral CT perfusion imaging of acute stroke using a recurrent neural network.

Objective. Cerebral CT perfusion (CTP) imaging is most commonly used to diagnose acute ischaemic stroke and support treatment decisions. Shortening CTP scan duration is desirable to reduce the accumulated radiation dose and the risk of patient head movement. In this study, we present a novel application of a stochastic adversarial video prediction approach to reduce CTP imaging acquisition time.Approach. A variational autoencoder and generative adversarial network (VAE-GAN) were implemented in a recurrent framework in three scenarios: to predict the last 8 (24 s), 13 (31.5 s) and 18 (39 s) image frames of the CTP acquisition from the first 25 (36 s), 20 (28.5 s) and 15 (21 s) acquired frames, respectively. The model was trained using 65 stroke cases and tested on 10 unseen cases. Predicted frames were assessed against ground-truth in terms of image quality and haemodynamic maps, bolus shape characteristics and volumetric analysis of lesions.Main results. In all three prediction scenarios, the mean percentage error between the area, full-width-at-half-maximum and maximum enhancement of the predicted and ground-truth bolus curve was less than 4 ± 4%. The best peak signal-to-noise ratio and structural similarity of predicted haemodynamic maps was obtained for cerebral blood volume followed (in order) by cerebral blood flow, mean transit time and time to peak. For the 3 prediction scenarios, average volumetric error of the lesion was overestimated by 7%-15%, 11%-28% and 7%-22% for the infarct, penumbra and hypo-perfused regions, respectively, and the corresponding spatial agreement for these regions was 67%-76%, 76%-86% and 83%-92%.Significance. This study suggests that a recurrent VAE-GAN could potentially be used to predict a portion of CTP frames from truncated acquisitions, preserving the majority of clinical content in the images, and potentially reducing the scan duration and radiation dose simultaneously by 65% and 54.5%, respectively.

Synthesis and Preclinical Evaluation of Fluorinated 5-Azaindoles as CB2 PET Radioligands.

Several classes of cannabinoid receptor type 2 radioligands have been evaluated for imaging of neuroinflammation, with successful clinical translation yet to take place. Here we describe the synthesis of fluorinated 5-azaindoles and pharmacological characterization and in vivo evaluation of 18F-radiolabeled analogues. [18F]2 (hCB2 Ki = 96.5 nM) and [18F]9 (hCB2 Ki = 7.7 nM) were prepared using Cu-mediated 18F-fluorination with non-decay-corrected radiochemical yields of 15 ± 6% and 18 ± 2% over 85 and 80 min, respectively, with high radiochemical purities (>97%) and molar activities (140-416 GBq/µmol). In PET imaging studies in rats, both [18F]2 and [18F]9 demonstrated specific binding in CB2-rich spleen after pretreatment with CB2-specific GW405833. Moreover, [18F]9 exhibited higher brain uptake at later time points in a murine model of neuroinflammation compared with a healthy control group. The results suggest further evaluation of azaindole based CB2 radioligands is warranted in other neuroinflammation models.

Transition to Fast Whole-Body SPECT/CT Bone Imaging: An Assessment of Image Quality.

OBJECTIVE: To investigate the impact of reduced SPECT acquisition time on reconstructed image quality for diagnostic purposes. METHOD: Data from five patients referred for a routine bone SPECT/CT using the standard multi-bed SPECT/CT protocol were reviewed. The acquisition time was 900 s using gating technique; SPECT date was resampled into reduced data sets of 480 s, 450 s, 360 s and 180 s acquisition duration per bed position. Each acquisition time was reconstructed using a fixed number of subsets (8 subsets) and 4, 8, 12, and 16 iterations, followed by a post-reconstruction 3D Gaussian filter of 8 mm FWHM. Two Nuclear Medicine physicians analysed all images independently to score image quality, noise and diagnostic confidence based on a pre-defined 4-point scale. RESULTS: Our result showed that the most frequently selected categories for 480 s and 450 s images were good image quality, average noise and fair confidence, particularly at lower iteration numbers 4 and 8. For the shortened acquisition time of 360 s and 180 s, statistical significance was observed in most reconstructed images compared with 900 s. CONCLUSION: The SPECT/CT can significantly shorten the acquisition time with maintained image quality, noise and diagnostic confidence. Therefore, acquiring data over 480 s and 450 s is feasible for WB-SPECT/CT bone scans to provide an optimal balance between acquisition time and image quality.

Inferring CT perfusion parameters and uncertainties using a Bayesian approach.

BACKGROUND: Computed tomography perfusion imaging is commonly used for the rapid assessment of patients presenting with symptoms of acute stroke. Maps of perfusion parameters, such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) derived from the perfusion scan data, provide crucial information for stroke diagnosis and treatment decisions. Most CT scanners use singular value decomposition (SVD)-based methods to calculate these parameters. However, some known problems are associated with conventional methods. METHODS: In this work, we propose a Bayesian inference algorithm, which can derive both the perfusion parameters and their uncertainties. We apply the variational technique to the inference, which then becomes an expectation-maximization problem. The probability distribution (with Gaussian mean and variance) of each estimated parameter can be obtained, and the coefficient of variation is used to indicate the uncertainty. We perform evaluations using both simulations and patient studies. RESULTS: In a simulation, we show that the proposed method has much less bias than conventional methods. Then, in separate simulations, we apply the proposed method to evaluate the impacts of various scan conditions, i.e., with different frame intervals, truncated measurement, or motion, on the parameter estimate. In one patient study, the method produced CBF and MTT maps indicating an ischemic lesion consistent with the radiologist's report. In a second patient study affected by patient movement, we showed the feasibility of applying the proposed method to motion corrected data. CONCLUSIONS: The proposed method can be used to evaluate confidence in parameter estimation and the scan protocol design. More clinical evaluation is required to fully test the proposed method.

Motion estimation and correction in SPECT, PET and CT.

Patient motion impacts single photon emission computed tomography (SPECT), positron emission tomography (PET) and x-ray computed tomography (CT) by giving rise to projection data inconsistencies that can manifest as reconstruction artifacts, thereby degrading image quality and compromising accurate image interpretation and quantification. Methods to estimate and correct for patient motion in SPECT, PET and CT have attracted considerable research effort over several decades. The aims of this effort have been two-fold: to estimate relevant motion fields characterizing the various forms of voluntary and involuntary motion; and to apply these motion fields within a modified reconstruction framework to obtain motion-corrected images. The aims of this review are to outline the motion problem in medical imaging and to critically review published methods for estimating and correcting for the relevant motion fields in clinical and preclinical SPECT, PET and CT. Despite many similarities in how motion is handled between these modalities, utility and applications vary based on differences in temporal and spatial resolution. Technical feasibility has been demonstrated in each modality for both rigid and non-rigid motion but clinical feasibility remains an important target. There is considerable scope for further developments in motion estimation and correction, and particularly in data-driven methods that will aid clinical utility. State-of-the-art deep learning methods may have a unique role to play in this context.

A motion correction approach for oral and maxillofacial cone-beam CT imaging.

Patient movement affects image quality in oral and maxillofacial cone-beam computed tomography imaging. While many efforts are made to minimize the possibility of motion during a scan, relatively little attention has been given to motion correction after acquisition. We propose a novel method which can improve the image quality after an oral and maxillofacial scan. The proposed method is based on our previous work and is a retrospective motion estimation and motion compensation (ME/MC) approach that iteratively estimates and compensates for rigid pose change over time. During motion estimation, image update and motion update are performed alternately in a multi-resolution scheme to obtain the motion. We propose use of a feature-based motion update and patch-based image update in the iterative estimation process, to alleviate the effect of limited scan field of view on estimation. During motion compensation, a fine-resolution image reconstruction was performed with compensation for the estimated motion. The proposed ME/MC method was evaluated with simulations, phantom and patient studies. Two experts in dentomaxillofacial radiology assessed the diagnostic importance of the resulting motion artifact suppression. The quality of the reconstructed images was improved after motion compensation, and most of the image artifacts were eliminated. Quantitative analysis by comparison to a reference image and by calculation of a sharpness metric agreed with the qualitative observation. The results are promising, and further evaluation is required to assess the clinical value of the proposed method.

Head movement during cerebral CT perfusion imaging of acute ischaemic stroke: Characterisation and correlation with patient baseline features.

PURPOSE: To quantitatively characterise head motion prevalence and severity and to identify patient-based risk factors for motion during cerebral CT perfusion (CTP) imaging of acute ischaemic stroke. METHODS: The head motion of 80 stroke patients undergoing CTP imaging was classified retrospectively into four categories of severity. Each motion category was then characterised quantitatively based on the average head movement with respect to the first frame for all studies. Statistical testing and principal component analysis (PCA) were then used to identify and analyse the relationship between motion severity and patient baseline features. RESULTS: 46/80 (58%) of patients showed negligible motion, 19/80 (24%) mild-to-moderate motion, and 15/80 (19%) considerable-to-extreme motion sufficient to affect diagnostic/therapeutic accuracy even with correction. The most prevalent movement was "nodding" with maximal translation/rotation in the sagittal/axial planes. There was a tendency for motion to worsen as scan proceeded and for faster motion to occur in the first 15 s. Statistical analyses showed that greater stroke severity (National Institutes of Health Stroke Scale (NIHSS)), older patient age and shorter time from stroke onset were predictive of increased head movement (p < 0.05 Kruskal-Wallis). Using PCA, the combination of NIHSS and patient age was found to be highly predictive of head movement (p < 0.001). CONCLUSIONS: Quantitative methods were developed to characterise CTP studies impacted by motion and to anticipate patients at-risk of motion. NIHSS, age, and time from stroke onset function as good predictors of motion likelihood and could potentially be used pre-emptively in CTP scanning of acute stroke.

Efficient radiation dose reduction in whole-brain CT perfusion imaging using a 3D GAN: performance and clinical feasibility.

Dose reduction in cerebral CT perfusion (CTP) imaging is desirable but is accompanied by an increase in noise that can compromise the image quality and the accuracy of image-based haemodynamic modelling used for clinical decision support in acute ischaemic stroke. The few reported methods aimed at denoising low-dose CTP images lack practicality by considering only small sections of the brain or being computationally expensive. Moreover, the prediction of infarct and penumbra size and location-the chief means of decision support for treatment options-from denoised data has not been explored using these approaches. In this work, we present the first application of a 3D generative adversarial network (3D GAN) for predicting normal-dose CTP data from low-dose CTP data. Feasibility of the approach was tested using real data from 30 acute ischaemic stroke patients in conjunction with low dose simulation. The 3D GAN model was applied to 643voxel patches extracted from two different configurations of the CTP data-frame-based and stacked. The method led to whole-brain denoised data being generated for haemodynamic modelling within 90 s. Accuracy of the method was evaluated using standard image quality metrics and the extent to which the clinical content and lesion characteristics of the denoised CTP data were preserved. Results showed an average improvement of 5.15-5.32 dB PSNR and 0.025-0.033 structural similarity index (SSIM) for CTP images and 2.66-3.95 dB PSNR and 0.036-0.067 SSIM for functional maps at 50% and 25% of normal dose using GAN model in conjunction with a stacked data regime for image synthesis. Consequently, the average lesion volumetric error reduced significantly (p-value <0.05) by 18%-29% and dice coefficient improved significantly by 15%-22%. We conclude that GAN-based denoising is a promising practical approach for reducing radiation dose in CTP studies and improving lesion characterisation.

Quantitative PET in the 2020s: a roadmap.

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice.

Anaesthetic-dependent changes in gene expression following acute and chronic exposure in the rodent brain.

Anaesthesia has been predicted to affect gene expression of the memory-related regions of the brain including the primary visual cortex. It is also believed that anaesthesia causes inflammation of neural tissues, increasing elderly patients' chances of developing precursor lesions that lead to Alzheimer's disease and other neurodegeneration related diseases. We have analyzed the expression of over 22,000 genes and 129,800 transcripts using oligonucleotide microarrays to examine the brain expression profiles in Sprague Dawley rats following exposure to acute or chronic doses of the anaesthetics isoflurane, ketamine and propofol. Here we report for the first time molecular and genomic data on the effect on the rodent brain of chronic and acute exposure to isoflurane, ketamine and propofol. Our screen identified multiple genes that responded to all three anaesthetics. Although some of the genes were previously known to be anaesthesia responsive, we have for the most part identified novel genes involved in the acute and chronic rodent brain response to different anaesthesia treatments. The latter may be useful candidate genes in the search to elucidate the molecular pathways mediating anaesthetic effects in the brain and may allow us to identify mechanisms by which anaesthetics could impact on neurodegeneration.

A scheme for PET data normalization in event-based motion correction.

Line of response (LOR) rebinning is an event-based motion-correction technique for positron emission tomography (PET) imaging that has been shown to compensate effectively for rigid motion. It involves the spatial transformation of LORs to compensate for motion during the scan, as measured by a motion tracking system. Each motion-corrected event is then recorded in the sinogram bin corresponding to the transformed LOR. It has been shown previously that the corrected event must be normalized using a normalization factor derived from the original LOR, that is, based on the pair of detectors involved in the original coincidence event. In general, due to data compression strategies (mashing), sinogram bins record events detected on multiple LORs. The number of LORs associated with a sinogram bin determines the relative contribution of each LOR. This paper provides a thorough treatment of event-based normalization during motion correction of PET data using LOR rebinning. We demonstrate theoretically and experimentally that normalization of the corrected event during LOR rebinning should account for the number of LORs contributing to the sinogram bin into which the motion-corrected event is binned. Failure to account for this factor may cause artifactual slice-to-slice count variations in the transverse slices and visible horizontal stripe artifacts in the coronal and sagittal slices of the reconstructed images. The theory and implementation of normalization in conjunction with the LOR rebinning technique is described in detail, and experimental verification of the proposed normalization method in phantom studies is presented.

Direct Estimation of Voxel-Wise Neurotransmitter Response Maps From Dynamic PET Data.

Computational methods, such as the linear parametric neurotransmitter PET (lp-ntPET) method, have been developed to characterize the transient changes in radiotracer kinetics in the target tissue during endogenous neurotransmitter release. In this paper, we describe and evaluate a parametric reconstruction algorithm that uses an expectation maximization framework, along with the lp-ntPET model, to estimate the endogenous neurotransmitter response to stimuli directly from the measured PET data. Computer simulations showed that the proposed direct reconstruction method offers improved accuracy and precision for the estimated timing parameters of the neurotransmitter response at the voxel level ( td=1±2 min, for activation onset bias and standard deviation) compared with conventional post reconstruction modeling ( td=4±7 min). In addition, we applied the proposed direct parameter estimation methodology to a [11C]raclopride displacement study of an awake rat and generated parametric maps illustrating the magnitude of ligand displacement from striatum. Although the estimated parametric maps of activation magnitude obtained from both direct and post reconstruction methodologies suffered from false positive activations, the proposed direct reconstruction framework offered more reliable parametric maps when the activation onset parameter was constrained.

DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization.

UNLABELLED: The translocator protein (18 kDa) (TSPO), formerly known as the peripheral benzodiazepine receptor, is dramatically upregulated under pathologic conditions. Activated microglia are the main cell type expressing the TSPO at sites of central nervous system pathology. Radioligands for the TSPO can therefore measure active disease in the brain. This article details the synthesis, radiofluorination, and pharmacologic evaluation of a new TSPO-specific pyrazolopyrimidine, DPA-714. METHODS: The affinity of DPA-714 for the TSPO was measured in rat kidney membranes with (3)H-PK11195. The in vitro functional activity of DPA-714 was measured in a steroidogenic assay in which the ability of DPA-714 to increase pregnenolone synthesis was measured with rat C6 glioma cells. The radiofluorination of DPA-714 was achieved by nucleophilic (18)F-fluoride displacement of the tosylate precursor. (18)F-DPA-714 was assessed in rats harboring unilateral quinolinic acid (QA) lesions. In addition, pretreatment experiments were performed with PK11195 (5 mg/kg), DPA-714 (1 mg/kg), and DPA-713 (1 mg/kg). The in vivo binding and biodistribution of (18)F-DPA-714 were determined in a baboon with PET. Experiments involving presaturation with PK11195 (1.5 mg/kg) and displacement with DPA-714 (1 mg/kg) were conducted to evaluate the specificity of radioligand binding. RESULTS: In vitro binding studies revealed that DPA-714 displayed a high affinity for the TSPO (dissociation constant, 7.0 nM). DPA-714 stimulated pregnenolone synthesis at levels 80% above the baseline. (18)F-DPA-714 was prepared at a 16% radiochemical yield and a specific activity of 270 GBq/mumol. In rats harboring unilateral QA lesions, an 8-fold-higher level of uptake of (18)F-DPA-714 was observed in the ipsilateral striatum than in the contralateral striatum. Uptake in the ipsilateral striatum was shown to be selective because it was inhibited to the level in the contralateral striatum in the presence of PK11195, nonlabeled DPA-714, or DPA-713. PET studies demonstrated rapid penetration and good retention of (18)F-DPA-714 in the baboon brain. Pretreatment with PK11195 effectively inhibited the uptake of (18)F-DPA-714 in the whole brain, indicating its selective binding to the TSPO. The injection of nonlabeled DPA-714 20 min after the injection of (18)F-DPA-714 resulted in radioligand washout, demonstrating the reversibility of (18)F-DPA-714 binding. CONCLUSION: (18)F-DPA-714 is a specific radioligand for the TSPO, displaying promising in vivo properties and thus warranting further investigation.

An event-driven motion correction method for neurological PET studies of awake laboratory animals.

PURPOSE: The purpose of the study is to investigate the feasibility of an event driven motion correction method for neurological microPET imaging of small laboratory animals in the fully awake state. PROCEDURES: A motion tracking technique was developed using an optical motion tracking system and light (<1g) printed targets. This was interfaced to a microPET scanner. Recorded spatial transformations were applied in software to list mode events to create a motion-corrected sinogram. Motion correction was evaluated in microPET studies, in which a conscious animal was simulated by a phantom that was moved during data acquisition. RESULTS: The motion-affected scan was severely distorted compared with a reference scan of the stationary phantom. Motion correction yielded a nearly distortion-free reconstruction and a marked reduction in mean squared error. CONCLUSIONS: This work is an important step towards motion tracking and motion correction in neurological studies of awake animals in the small animal PET imaging environment.