Positron emission tomography assessment of metacarpal/metatarsal condylar fractures post surgical repair: Prospective study in 14 racehorses.

OBJECTIVES: To assess 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) findings associated with metacarpal/metatarsal condylar fractures at the time of fracture repair and through healing. STUDY DESIGN: Prospective descriptive study. ANIMALS: Fourteen Thoroughbred racehorses. METHODS: 18F-NaF PET was performed within 4 days of surgical metacarpal/metatarsal condylar fracture repair, on both the injured and contralateral limb. Follow-up PET scans were offered at 3- and 5-months post fracture repair. Areas of abnormal uptake were assessed using a previously validated grading system. RESULTS: Eight fractures were located in the parasagittal groove (PSG) (six lateral and two medial) and six fractures were located abaxial to the PSG (non-PSG) through the palmar/plantar condyle (all lateral). All horses in the latter group had uptake in the lateral palmar condyle of the contralateral limb suggestive of stress remodeling. Three horses with PSG fractures had uptake in a similar location in the contralateral limb. Horses with lateral condylar fracture only presented minimal or mild uptake in the medial condyle, which is considered atypical in the front limbs for horses in full training. Four horses developed periarticular uptake in the postoperative period suggestive of degenerative joint disease, three of these horses had persistent uptake at the fracture site. These four horses did not return to racing successfully. CONCLUSION: The findings of this study provide evidence of pre-existing lesions and specific uptake patterns in racehorses suffering from metacarpal/metatarsal condylar fractures. CLINICAL SIGNIFICANCE: PET has a possible role in the prevention, diagnosis, and postoperative monitoring of metacarpal/metatarsal condylar fractures in racehorses.

18F-sodium fluoride positron emission tomography provides pertinent additional information to computed tomography for assessment and management of tarsal pain in horses.

OBJECTIVE: To assess the value of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) for imaging the tarsus and proximal metatarsus and compare it with CT and lameness evaluation. ANIMALS: 25 horses with lameness localized to the tarsal and proximal metatarsal regions that underwent 18F-NaF PET/CT between 2016 and 2021. METHODS: 18F-NaF PET and CT images were retrospectively independently evaluated by 3 observers. Standardized uptake values (SUV) were used to characterize 18F-NaF uptake. Correlation between PET and CT findings with subjective and objective maximum (Max-D) and minimum pelvic height lameness data was estimated. RESULTS: The inter-observer Kappa-weighted value (κ) was higher for PET (κ = 0.66) than CT (κ = 0.6). CT and PET scores were fairly correlated (R = 0.49; P < 0.05). PET SUVratio (SUV of the main lesion/SUV talus) had the highest correlation with Max-D (R = 0.71; P < .05). PET and CT scores for the plantar region were significantly higher in Quarter Horses (P < .05) and showed consistently higher correlation with objective lameness data (CT plantar grade - Max-D [R = 0.6; P < .05], PET plantar grade - Max-D [R = 0.47; P = .04]) than other regions of the distal tarsal joints. Three Warmbloods presented marked uptake at the medial cochlea of the distal tibia. CLINICAL RELEVANCE: PET had a moderate correlation with CT for assessment of tarsal lesions. The degree of PET uptake can help differentiate active versus inactive lesions. Specific location of the uptake is important in determining clinical relevance.

18 Fluorine-fluorodeoxyglucose positron emission tomography for assessment of deep digital flexor tendinopathy: An exploratory study in eight horses with comparison to CT and MRI.

Lesions of the deep digital flexor tendon (DDFT) are a cause for foot lameness in horses. Positron emission tomography (PET) could provide valuable information regarding the metabolic activity of these lesions. The aims of this exploratory, prospective, methods comparison study were to assess the ability of 18 fluorine-fluorodeoxyglucose (18 F-FDG) PET to detect DDFT lesions and to compare the PET findings with CT and MRI findings. Eight horses with lameness due to pain localized to the front feet were included. Both front limbs of all horses were imaged with 18 F-FDG PET, noncontrast CT, and arterial contrast-enhanced CT; 11 limbs were also assessed using MRI. Two observers graded independently 18 F-FDG PET, noncontrast CT, arterial contrast CT, T1-weighted (T1-w) MRI, and T2-weighted (T2-w)/STIR MRI. Maximal standardized uptake values were measured. Lesions were found in seven of 16 DDFT on PET, 12 of 16 DDFT on noncontrast CT, six of 15 DDFT on arterial contrast CT, eight of 11 DDFT on T1-w MRI, and six of 11 DDFT on T2-w/STIR MRI. Positron emission tomography was in better agreement with arterial contrast CT (Kappa-weighted 0.40) and T2-w/STIR MRI (0.35) than with noncontrast CT (0.28) and T1-w MRI (0.20). Maximal standardized uptake values of lesions ranged from 1.9 to 4.6 with a median of 3.1. Chronic lesions with scar tissues identified on noncontrast CT or T1-w MRI did not have increased 18 F-FDG uptake. These results demonstrated that 18 F-FDG PET agreed more closely with modalities previously used to detect active tendon lesions, i.e. arterial contrast CT and T2-w/STIR MRI. 18 Fluorine-fluorodeoxyglucose PET can be used to identify metabolically active DDFT lesions in horses.

Invited review--Off-site PET imaging programs: challenges and opportunities.

Veterinarians are gaining interest in and access to Position Emission Tomography (PET and PET/CT) imaging for both clinical and research applications. This manuscript provides an overview of how veterinarians may approach the use of off-site PET and PET/CT scanners already in use for human medical imaging in order to gain access to this technology without direct investment in costly equipment and infrastructure. An overview of general procedures, animal transport, and radiation safety considerations is offered along with references to key regulatory statutes that may apply to the operation of PET imaging facilities in individual states.

Invited review--neuroimaging response assessment criteria for brain tumors in veterinary patients.

The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.

Accurate modeling of a DOI capable small animal PET scanner using GATE.

In this work we developed a Monte Carlo (MC) model of the Sedecal Argus pre-clinical PET scanner, using GATE (Geant4 Application for Tomographic Emission). This is a dual-ring scanner which features DOI compensation by means of two layers of detector crystals (LYSO and GSO). Geometry of detectors and sources, pulses readout and selection of coincidence events were modeled with GATE, while a separate code was developed in order to emulate the processing of digitized data (for example, customized time windows and data flow saturation), the final binning of the lines of response and to reproduce the data output format of the scanner's acquisition software. Validation of the model was performed by modeling several phantoms used in experimental measurements, in order to compare the results of the simulations. Spatial resolution, sensitivity, scatter fraction, count rates and NECR were tested. Moreover, the NEMA NU-4 phantom was modeled in order to check for the image quality yielded by the model. Noise, contrast of cold and hot regions and recovery coefficient were calculated and compared using images of the NEMA phantom acquired with our scanner. The energy spectrum of coincidence events due to the small amount of (176)Lu in LYSO crystals, which was suitably included in our model, was also compared with experimental measurements. Spatial resolution, sensitivity and scatter fraction showed an agreement within 7%. Comparison of the count rates curves resulted satisfactory, being the values within the uncertainties, in the range of activities practically used in research scans. Analysis of the NEMA phantom images also showed a good agreement between simulated and acquired data, within 9% for all the tested parameters. This work shows that basic MC modeling of this kind of system is possible using GATE as a base platform; extension through suitably written customized code allows for an adequate level of accuracy in the results. Our careful validation against experimental data confirms that the developed simulation setup is a useful tool for a wide range of research applications.

Comparison of Gallium-68 and Fluorine-18 imaging characteristics in positron emission tomography.

This review article compares PET imaging performance with Gallium-68 ((68)Ga) and Fluorine-18 ((18)F). The literature on this topic is scarce; hence in order to complete the published data, Monte Carlo calculations, as well as phantom measurements, were carried out. The qualitative and quantitative differences between (68)Ga and (18)F imaging were evaluated in terms of spatial resolution, sensitivity, contrast and activity recovery coefficients for both human PET systems and small animal PET scanners. The clinical and pre-clinical implications of these differences are discussed.

Quantitative assessment of crystal material and size on the performance of rotating dual head small animal PET scanners using Monte Carlo modeling.

In this work, among different proposed designs we have studied dual-head coincidence detectors (DHC) with pixelated crystals in order to optimize the design of detector systems of small animal PET scanners. Monte Carlo simulations and different detector components and materials, under different imaging conditions and geant 4 application for tomographic emission (GATE) were used for all simulations. Crystal length and inter material space on system performance were studied modeling several pixel sizes, ranging from 0.5 x 0.5mm² to 3.0 x 3.0mm² by increment of 0.5mm and using epoxy intermaterial with pitch of 0.1, 0.2 and 0.3mm. Three types of scintillator crystals:bismuth germinate orthosilicate, cerium-doped lutetium orthosilicate and gadolinium orthosilicate were simulated with thicknesses of 10mm and 15 mm. For all measurements a point source with the activity of 1MBq was placed at the center of field of view. The above simulation revealed that by increasing pixel size and crystal length in scintillator material of a pixelated array, sensitivity can be raised from 1% to 7%. However, spatial resolution becomes worse when pixel size increases from 0.6mm to 2.6mm. In addition, photons mispositioned events decrease from 76%to 45%. Crystal length decrease, significantly reduces the percentage of mispositioned events from 89% to 59%. Moreover increase in crystal length from 10mm to 15 mm changes sensitivity from 2% to 6% and spatial resolution from 0.6mm to 3.5mm. In conclusion, it was shown that pixel size 2mm with 10mm crystal thickness can provide the best dimensions in order to optimize system performance. These results confirmed the value of GATE Monte Carlo code, as being a useful tool for optimizing nuclear medicine imaging systems performance, for small animal PET studies.

Assessment of MR compatibility of a PET insert developed for simultaneous multiparametric PET/MR imaging on an animal system operating at 7 T.

The combination of positron emission tomography and MR in one system is currently emerging and opens up new domains in the functional examinations of living systems. This article reports on relevant influences of a positron emission tomography insert on MR imaging. The basic conditions of main magnetic field and RF field homogeneity were measured as well as image quality and signal-to-noise ratio when applying the usual MR sequence types including echo-planar techniques. Moreover, the influence of the positron emission tomography insert on the RF noise level and on RF interferences was measured by comparing results achieved with and without the positron emission tomography insert. The temporal stability of EPI imaging with and without the positron emission tomography insert was assessed. Small but significant decreases in the signal-to-noise ratio were revealed when the positron emission tomography insert was present, whereas B(0) and B(1) homogeneity as well as RF noise level were not adversely affected. A higher signal intensity drift was found for EPI imaging studies; however, this can be compensated by post processing. In summary, this study shows that positron emission tomography inserts can be designed for and used within an MR system practically, without substantially affecting the MR image quality.

Monte Carlo simulation of a GE eXplore VISTA system for quantitative small animal PET imaging.

OBJECTIVE: We aim to establish an evaluation platform for the GE eXplore VISTA small animal positron emission tomography (PET) scanner, a dual layer phoswich system, by using Monte Carlo simulation. METHODS: We developed a detection model based on the Geant4 Application for Tomographic Emission to realistically reproduce the physics of PET, the scanner configuration, and the data collecting system of an eXplore VISTA system. For verification purpose, several different physical phantoms were simulated to perform evaluation tests, including sensitivity, spatial resolution, scatter fraction, and count rate performance, which were compared with an actual scanner. After the experimental validation, our detection model was applied to assess the quantification loss in the reconstructed images associated with photon attenuation, photon scatter, and random coincidences. RESULTS: A simulated sensitivity profile as a function of 18F point source axial position was fitted to the measured results. In terms of spatial resolution, agreement was within 10-18% for the point source at various locations. The simulated and measured scatter fractions differed by less than 4.3 and 5.2% for the physical mouse and rat phantoms, respectively. The count rate performance of our model was matched by the measured results, up to the peak activity concentration of 455 kBq/ml for the mouse-sized phantom and 141 kBq/ml for the rat-sized phantom. Finally, we found that photon attenuation is the dominant physical degrading factor in quantitative analysis (> 13.4%). CONCLUSION: These results suggested that the proposed detection model is able to produce realistic data from the eXplore VISTA system with knowing the ground truth, thus facilitating its evaluation for small animal PET studies.

Validation of PET-SORTEO Monte Carlo simulations for the geometries of the MicroPET R4 and Focus 220 PET scanners.

PET-SORTEO is a Monte Carlo-based simulator that enables the fast generation of realistic PET data for the geometry of the ECAT EXACT HR+ scanner. In order to address the increasing need for simulation models of animal PET imaging systems, our aim is to adapt and configure this simulation tool for small animal PET scanners, especially for the widely distributed microPET R4 and Focus 220 systems manufactured by Siemens Preclinical Solutions. We propose a simulation model that can produce realistic rodent images in order to evaluate and optimize acquisition and reconstruction protocols. The first part of this study presents the validation of SORTEO against the geometries of the R4 and the Focus 220 systems. This validation is carried out against actual measurements performed on the R4 scanner at the Montreal Neurological Institute in Canada and on the Focus 220 system of the department of radiopharmaceuticals of the Austrian Research Center in Seibersdorf. The comparison of simulated and experimental performance measurements includes spatial resolution, energy spectra, scatter fraction and count rates. In the second part of the study, we demonstrate the ability to rapidly generate realistic whole-body radioactive distributions using the MOBY phantom and give comparative example case studies of the same rodent model simulated with PET-SORTEO for the R4 and Focus 220 systems.

Assessment of myocardial blood flow using 15O-water and 1-11C-acetate in rats with small-animal PET.

UNLABELLED: This feasibility study was undertaken to determine whether myocardial blood flow (MBF, mL/g/min) could be quantified noninvasively in small rodents using microPET and 15O-water or 1-11C-acetate. METHODS: MBF was measured in 18 healthy rats using PET and 15O-water (MBF-W) under different interventions and compared with direct measurements obtained with microspheres (MBF-M). Subsequently, MBF was estimated in 24 rats at rest using 1-11C-acetate (MBF-Ace) and compared with measurements obtained with 15O-water. Using factor analysis, images were processed to obtain 1 blood and 1 myocardial time-activity curve per tracer per study. MBF-W was calculated using a well-validated 1-compartment kinetic model. MBF-Ace was estimated using a simple 1-compartment model to estimate net tracer uptake, K1 (K1 (mL/g/min) = MBF.E; E = first-pass myocardial extraction of 1-11C-acetate) and washout (k2 (min(-1))) along with F(BM) (spillover correction) after fixing F(MM) (partial-volume correction) to values obtained from 15O-water modeling. K1 values were converted to MBF values using a first-pass myocardial extraction/flow relationship measured in rats (E = 1.0-0.74.exp(-1.13/MBF)). RESULTS: In the first study, MBF-W correlated well with MBF-M (y = 0.74x + 0.96; n = 18, r = 0.91, P < 0.0001). However, the slope was different than unity, P < 0.05). Refitting of the data after forcing the intercept to be zero resulted in a nonbias correlation between MBF-W and MBF-M (y = 0.95x + 0.0; n = 18, r = 0.86, P < 0.0001) demonstrating that the underestimation of the slope could be attributed to the overestimation of MBF-W for 2 MBF-M values lower than 1.50 mL/g/min. In the second study, MBF-Ace values correlated well with MBF-W with no underestimation of MBF (y = 0.91x + 0.35; n = 24, r = 0.87, P < 0.0001). CONCLUSION: MBF can be quantified by PET using (15)O-water or 1-11C-acetate in healthy rats. Future studies are needed to determine the accuracy of the methods in low-flow states and to develop an approach for a partial-volume correction when 1-11C-acetate is used.

Performance evaluation of the microPET focus: a third-generation microPET scanner dedicated to animal imaging.

UNLABELLED: The microPET Focus is the latest generation microPET system dedicated to high-resolution animal imaging and incorporates several changes to enhance its performance. This study evaluated the basic performance of the scanner and compared it with the Primate (P4) and Rodent (R4) models. METHODS: The system consists of 168 lutetium oxyorthosilicate (LSO) detectors arranged in 4 contiguous rings, with a 25.8-cm diameter and a 7.6-cm axial length. Each detector consists of a 12 x 12 LSO crystal array of 1.51 x 1.51 x 10.00 mm3 elements. The scintillation light is transmitted to position-sensitive photomultiplier tubes via optical fiber bundles. The system was evaluated for its energy and spatial resolutions, sensitivity, and noise equivalent counting rate. Phantoms and animals of varying sizes were scanned to evaluate its imaging capability. RESULTS: The energy resolution averages 18.5% for the entire system. Reconstructed image resolution is 1.3-mm full width at half maximum (FWHM) at the center of field of view (CFOV) and remains under 2 mm FWHM within the central 5-cm-diameter FOV in all 3 dimensions. The absolute sensitivity of the system is 3.4% at the CFOV for an energy window of 250-750 keV and a timing window of 10 ns. The noise equivalent counting-rate performance reaches 645 kcps for a mouse-size phantom using 250- to 750-keV and 6-ns settings. Emission images of a micro-Derenzo phantom demonstrate the improvement in image resolution compared with previous models. Animal studies exhibit the capability of the system in studying disease models using mouse, rat, and nonhuman primates. CONCLUSION: The Focus has significantly improved performance over the previous models in all areas evaluated. This system represents the state-of-the-art scintillator-based animal PET scanner currently available and is expected to advance the potential of small animal PET.

Small animal PET: aspects of performance assessment.

Dedicated small animal positron emission tomography (PET) systems are increasingly prevalent in industry (e.g. for preclinical drug development) and biological research. Such systems permit researchers to perform animal studies of a longitudinal design characterised by repeated measurements in single animals. With the advent of commercial systems, scanners have become readily available and increasingly popular. As a consequence, technical specifications are becoming more diverse, making scanner systems less broadly applicable. The investigator has, therefore, to make a decision regarding which type of scanner is most suitable for the intended experiments. This decision should be based on gantry characteristics and the physical performance. The first few steps have been taken towards standardisation of the assessment of performance characteristics of dedicated animal PET systems, though such assessment is not yet routinely implemented. In this review, we describe current methods of evaluation of physical performance parameters of small animal PET scanners. Effects of methodologically different approaches on the results are assessed. It is underscored that particular attention has to be paid to spatial resolution, sensitivity, scatter fraction and count rate performance. Differences in performance measurement methods are described with regard to commercially available systems, namely the Concorde MicroPET systems P4 and R4 and the quad-HIDAC. Lastly, consequences of differences in scanner performance parameters are rated with respect to applications of small animal PET.