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.

Effect of ambulation following 18F-fluorodeoxyglucose injection on standing positron emission tomography of the healthy equine digit.

OBJECTIVE: Measure 18F-FDG uptake in digital tissues of healthy horses subjected to different ambulatory conditions between the time of injection and positron emission tomography (PET) scan acquisition. ANIMALS: 8 healthy adult horses. METHODS: Horses were walked (AMB) or tied in stalls (NONAMB) immediately after injection with ∼1.5 MBq/kg 18F-FDG until scan acquisition using a randomized crossover design. Steps were quantified using accelerometers. Standardized uptake values (SUV; mean and maximum) in digital tissues including the dorsal lamellae (proximal, middle, and distal), quarter lamellae (medial and lateral), and coronary band were analyzed using a mixed-effects linear regression model. RESULTS: Mean (95% CI) step count for AMB (569[484-653]) was higher than NONAMB (88[24-152]) P = <.001. The SUVmax (but not SUVmean) was increased in AMB compared with NONAMB in the proximal (2.74[2.52-2.98] vs 2.42[2.05-2.78]; P = .04) and middle (2.74[2.37-3.11] vs 2.36[2.05-2.68]; P = .03) dorsal lamellae but was not different in the distal lamellae or coronary band. In the medial quarter lamellae, both SUVmax (2.53[1.58-3.48] vs 2.07[0.81-3.33]; P = .01) and SUVmean (1.90[1.55-2.25] vs 1.49[0.91-2.06]; P = .007) were increased in AMB compared with NONAMB. The medial quarter lamellae also had lower SUVmax (P = .002) and SUVmean (P = .04) compared with the lateral quarter and lower SUVmax compared with the mid-dorsal lamellae (P = .01). CLINICAL RELEVANCE: Lamellar 18F-FDG uptake was affected by ambulatory activity mostly in the medial quarter; however, this effect was relatively small and unlikely to interfere with clinical detection of laminitis.

Establishment of a sequential dual tracer 18 F-NaF/18 F-FDG PET protocol for imaging the equine foot.

The combination of 18 F-Sodium Fluoride (18 F-NaF) and 18 F-FluoroDeoxyGlucose (18 F-FDG) for positron emission tomography (PET) imaging of the equine foot is appealing for detection of both osseous and soft tissue lesions in a single scan. As the combination of tracers could lead to a loss of information, a sequential approach, consisting in imaging with one tracer prior to injecting the second tracer, might be valuable. The goals of this prospective, methods comparison, exploratory study were to establish the order of tracer injection and timing for imaging. Six research horses were imaged under general anesthesia with 18 F-NaF PET, 18 F-FDG PET, dual 18 F-NaF/18 F-FDG PET, and CT. Proper uptake could be identified in tendon lesions as early as 10 min after 18F-FDG injection. Bone uptake was limited when 18F-NaF was injected under general anesthesia, even at 1 h after injection, when compared with 18 F-NaF injection prior to anesthesia. The sensitivity and specificity of the dual tracer scans were 0.77 (0.63 to 0.86) and 0.98 (0.96 to 0.99) respectively, to assess 18 F-NaF uptake and 0.5 (0.28 to 0.72) and 0.98 (0.95 to 0.99), respectively, for 18F-FDG uptake. These results suggest that the sequential dual tracer approach is a pertinent technique to optimize the PET data gained from a single anesthetic episode. Based on dynamics of tracer uptake, the optimal protocol consists in injecting 18F-NaF prior to anesthesia, acquire 18F-NaF data then inject 18F-FDG and start acquisition of dual tracer PET data 10 min later. This protocol should be further validated in a larger clinical study.

Comparison of skeletal scintigraphy and standing 18 F-NaF positron emission tomography for imaging of the fetlock in 33 Thoroughbred racehorses.

This retrospective, methods comparison study aimed to compare skeletal scintigraphy and 18 F-NaF positron emission tomography (PET) for the detection of abnormalities in the fetlocks of Thoroughbred racehorses. Thirty-three horses (72 limbs) imaged with both scintigraphy and 18 F-NaF PET, for investigation of lameness or poor performance related to the fetlock, were included. Seven observers, including experienced racetrack practitioners, surgery and imaging residents, and a board-certified veterinary radiologist, independently reviewed all data for evidence of increased radiopharmaceutical uptake in 10 different regions of interest. The interobserver agreement was higher for PET (Kappa-weighted (K-w) 0.73 (0.51-0.84)) (median (range)) than for scintigraphy (0.61 (0.40-0.77)) (P < 0.0001). When scintigraphy and PET were compared, the agreement was fair (K-w 0.29). More sites of increased uptake were identified using PET compared with scintigraphy. Agreement between the two modalities was higher for the palmar/plantar metacarpal/metatarsal condylar regions (K-w 0.59) than for the proximal sesamoid bones (K-w 0.25). Increased radiopharmaceutical uptake was detected in the medial proximal sesamoid bone in 6.9% and 22.2% of limbs with scintigraphy and PET, respectively. The high interobserver agreement for PET, despite the recent introduction of this technique, demonstrates the ease of clinical interpretation of PET scans. The higher number of lesions detected with PET compared with scintigraphy can be explained by the higher spatial resolution and cross-sectional nature of this modality. Study findings supported using PET in a clinical population of racehorses, in particular for the assessment of the proximal sesamoid bones.

Longitudinal monitoring of fetlock lesions in Thoroughbred racehorses using standing 18F-sodium fluoride positron emission tomography.

OBJECTIVE: To assess the repeatability of equine 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) findings, and to evaluate the ability of PET to monitor the progression of areas of increased radiopharmaceutical uptake (IRU) in the fetlocks of Thoroughbred racehorses. ANIMALS: 25 racehorses with clinical signs related to fetlock injuries. PROCEDURES: This study is a prospective, longitudinal clinical study. Twenty-five racehorses (54 fetlocks) underwent three 18F-NaF PET scans 6 weeks apart. The first 18F-NaF PET scan was performed at the start of a 12-week period of rest from racing (lay-up). Areas of IRU in the fetlock joints were quantified using maximal standardized uptake values (SUVmax) and were graded by 2 experienced observers. Statistical comparisons were made between scans to detect changes in IRU grade and SUVmax over time. RESULTS: Standing PET findings were repeatable, with 131/149 (88%) areas of IRU identified on the initial scans seen again at the 6-week follow-up scan. The palmar/plantar condyles were the sites most commonly presenting with IRU, followed by the proximal sesamoid bones. Overall, 65% of fetlocks demonstrated improvement in IRU grade during the 12-week period of rest from racing. Areas of higher IRU grade took longer to resolve than the lower graded areas. CLINICAL RELEVANCE: Standing PET findings in the racehorse fetlock were repeatable. The SUV-based grading system may be helpful when determining appropriate lay-up duration for Thoroughbred racehorses. PET may be used to monitor areas of the fetlock involved in catastrophic breakdown injuries in Thoroughbred racehorses.

Positron emission tomography: a horse in the musculoskeletal imaging race.

Positron emission tomography (PET) has established itself as a pertinent tool in equine musculoskeletal imaging in the last few years. With the ability to provide functional information regarding both bone and soft tissues, PET has found several clinical applications in horses. PET is currently used in horses as an enhanced bone scan, providing high-resolution 3-dimensional information, in particular for imaging of the racehorse fetlock. Combined with CT and MRI, PET is particularly pertinent in horses for the assessment of subchondral bone and enthesis. The development of a dedicated PET scanner to image the distal limb of horses with standing sedation led to new applications, where PET is used as a first-line advanced imaging tool, in particular for foot, fetlock, and tarsal imaging. A complimentary clinical review of when to seek advanced imaging in equine athletes can be found in the companion Currents in One Health by Garrett in the July 2022 issue of the Journal of American Veterinary Medical Association. The clinical use of PET in human medicine remains mainly focused on oncological imaging; however, numerous small-scale clinical studies have demonstrated valuable applications for musculoskeletal imaging. These include assessment of foot and ankle pain, osteoarthritis of the knee and hip, osteoporosis, response to bisphosphonates, and chronic osteomyelitis. The use of musculoskeletal PET in dogs remains quite limited, but a few studies have recently been published and clinical interest is growing. The available research data and clinical applications between horses, humans, and dogs are currently quite disparate, but all suggest great promises for earlier and more accurate clinical diagnosis, as well as better understanding of pathophysiology and response to treatment. Translating knowledge from a species to another will undoubtedly help further growth of musculoskeletal PET.

Standardized uptake values and attenuation correction in 18 F-sodium fluoride PET of the equine foot and fetlock.

Maximal standardized uptake values (SUVmax ) are commonly used for the interpretation of PET studies. Limited information regarding the SUVmax of 18 F-NaF PET in horses is currently available in the literature. The goals of this retrospective secondary analysis study were to provide reference values for 18 F-NaF SUVmax in the equine distal extremity and assess the effect of attenuation correction. Nonattenuation corrected (NAC) and CT-based attenuation corrected (CTAC) SUVmax were obtained from 19 feet and 19 fetlocks. Twenty regions of interest (ROIs) were defined for the foot and 22 for the fetlock. Areas presenting abnormal uptake were excluded. The overall NAC and CTAC SUVmax were 3.6 +/- 1.5 (mean +/- sd) and 5.0 +/- 1.8 for the feet and 2.9 +/- 1.1 and 3.8 +/- 1.4 for the fetlocks, respectively. The 3 ROIs showing the highest attenuation correction were the navicular center (83.4%), navicular flexor surface (74.9%) and distal phalanx flexor surface (81.3%), whereas attenuation correction was only 5.2% at the dorsal aspect of the proximal phalanx. Significant SUVmax differences were observed between the different ROIs (P < 0.0001), with the toe (CTAC SUVmax 7.7 +/- 3.7), dorsal (7.5 +/- 1.9) and central (6.1 +/- 2.2) ROIs of the distal phalanx being significantly higher than those of the other areas. This study demonstrates that attenuation correction affects SUVmax in the equine distal extremity and should be performed if CT data are available. However, as the maximal attenuation correction results in less than doubling the signal intensity, nonattenuation corrected images likely remain relevant for subjective clinical interpretation.

Evaluation of 18F-fluorodeoxyglucose uptake of beagle dogs for different durations of isoflurane anesthesia.

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used for tumor evaluation. In veterinary medicine, anesthesia is an essential tool during the PET scanning process. However, the changes in FDG uptake in dogs that have undergone anesthesia for a longer duration have not been studied. This study aimed to analyze the influence of isoflurane anesthesia on FDG uptake in dogs undergoing PET. A crossover design was implemented by exposing 3 groups of 6 dogs to different durations of anesthesia (60, 90, and 150 minutes). Inhalation anesthesia was maintained throughout the scanning process (30 minutes) and FDG was injected 1 hour before the start of the PET scan. The standard uptake value of FDG was obtained for the 7 gross structures (whole brain, lung, salivary gland, liver, spleen, mediastinal blood pool, and kidney cortex) as well as for the 7 intracranial structures (frontal, parietal, temporal and occipital lobes, cerebellum, brain stem, and caudal colliculus). The whole brain and intracranial structures showed significantly lower FDG uptake in dogs with a longer duration of anesthesia, whereas other gross structures did not. Our results suggest that the duration of anesthesia should be considered when evaluating the uptake of FDG by the brain.

La tomographie par émission de positrons (PET) au 18F-fluorodésoxyglucose (FDG) est utilisée pour l'évaluation des tumeurs. En médecine vétérinaire, l'anesthésie est un outil essentiel lors du processus de PET. Cependant, les modifications de l'absorption du FDG chez les chiens ayant subi une anesthésie de plus longue durée n'ont pas été étudiées. Cette étude visait à analyser l'influence de l'anesthésie à l'isoflurane sur l'absorption du FDG chez les chiens subissant une PET. Un modèle croisé a été mis en oeuvre en exposant trois groupes de six chiens à différentes durées d'anesthésie (60, 90 et 150 minutes). L'anesthésie par inhalation a été maintenue tout au long du processus de numérisation (30 minutes) et le FDG a été injecté 1 heure avant le début de la PET. La valeur d'absorption standard du FDG a été obtenue pour les sept structures macroscopiques (cerveau entier, poumon, glande salivaire, foie, rate, pool sanguin médiastinal et cortex rénal) ainsi que pour les sept structures intracrâniennes (frontale, pariétale, temporale et lobes occipitaux, cervelet, tronc cérébral et colliculus caudal). L'ensemble du cerveau et les structures intracrâniennes ont montré une absorption de FDG significativement plus faible chez les chiens avec une durée d'anesthésie plus longue, contrairement aux autres structures. Nos résultats suggèrent que la durée de l'anesthésie doit être prise en compte lors de l'évaluation de la captation du FDG par le cerveau.(Traduit par Docteur Serge Messier).

Validation of a dedicated positron emission tomography scanner for imaging of the distal limb of standing horses.

A positron emission tomography (PET) scanner, with an openable ring of detectors, was specifically designed to image the distal limb of standing horses. The goals of this prospective, preclinical, experimental, methods comparison study were to validate the safety of the scanner, assess image quality, and optimize scanning protocols. Six research horses were imaged three times (twice standing, once anesthetized) and six horses in active race training were imaged once under standing sedation. Multiple scans of both front fetlocks were obtained with different scan durations and axial fields of view. A total of 94 fetlock scans were attempted and 90 provided images of diagnostic value. Radiotracer uptake was the main factor affecting image quality, while motion did not represent a major issue. Scan duration and field of view also affected image quality. Eight specific lesions were identified on PET images from anesthetized horses and were all also independently recognized on the PET images obtained on standing horses. Maximal standardized uptake values (SUVmax) had good repeatability for the assessment of specific lesions among different scans. Three feet and six carpi were also successfully imaged. This study validated the safety and practicality of a PET scanner specifically designed to image the distal limb in standing horses. Proper preparation of horses, similar to bone scintigraphy, is important for image quality. A 4-min scan with 12 cm field of view was considered optimal for clinical fetlock imaging. Evaluation of a larger clinical population is the next step for further assessment of the clinical utility of PET imaging in horses.

NEMA NU 4-2008 performance evaluation and MR compatibility tests of an APD-based small animal PET-insert for simultaneous PET/MR imaging.

An avalanche photodiode (APD)-based small animal positron emission tomography (PET)-insert was fully evaluated for its PET performance, as well as potential influences on magnetic resonance imaging (MRI) performance. This PET-insert has an extended axial field of view (FOV) compared with the previous design to increase system sensitivity, as well as an updated cooling and temperature regulation to enable stable and reproducible PET acquisitions. The PET performance was evaluated according to the National Electrical Manufacturers Association NU4-2008 protocol. The energy and timing resolution's full width at half maximum were 16.1% and 4.7 ns, respectively. The reconstructed radial spatial resolution of the PET-insert was 1.8 mm full width at half maximum at the center FOV using filtered back projection for reconstruction and sensitivity was 3.68%. The peak noise equivalent count rates were 70 kcps for a rat-like and 350 kcps for a mouse-like phantom, respectively. Image quality phantom values and contrast recovery were comparable to state-of-the art PET-inserts and standalone systems. Regarding MR compatibility, changes in the mean signal-to-noise ratio for turbo spin echo and echo-planar imaging sequences were below 8.6%, for gradient echo sequences below 1%. Degradation of the mean homogeneity was below 2.3% for all tested sequences. The influence of the PET-insert on theB0maps was negligible and no influence on functional MRI sequences was detected. A mouse and rat imaging study demonstrated the feasibility ofin vivosimultaneous PET/MRI.

18F-FDG PET/CT image findings of a dog with adrenocortical carcinoma.

BACKGROUND: In human medicine, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been used to differentiate between benign and malignant adrenal tumors and to identify metastases. However, canine adrenocortical carcinomas identified by 18F-FDG PET/computed tomography (CT) have not been reported. CASE PRESENTATION: A 13-year-old, castrated male, Cocker Spaniel dog with severe systolic hypertension exhibited an adrenal mass approximately 3.6 cm in diameter on ultrasonography. There was no evidence of pulmonary metastasis or vascular invasion on thoracic radiography and abdominal ultrasonography, respectively. 18F-FDG PET/CT was performed to identify the characteristics of the adrenal mass and the state of metastasis. One hour after injection of 5.46 MBq/kg 18F-FDG intravenously, the peripheral region of the adrenal mass visually revealed an increased 18F-FDG uptake, which was higher than that of the liver, and the central region of the mass exhibited necrosis. The maximal standardized uptake value (SUV) of the adrenal mass was 3.24; and relative SUV, calculated by dividing the maximal SUV of the adrenal tumor by the mean SUV of the normal liver, was 5.23. Adrenocortical carcinoma was tentatively diagnosed and surgical adrenalectomy was performed. Histopathologic examination of the resected adrenal mass revealed the characteristics of an adrenocortical carcinoma. After adrenalectomy, systolic blood pressure reduced to below 150 mmHg without any medication. CONCLUSION: This is the first case report of 18F-FDG PET/CT findings in a dog with suspected adrenocortical carcinoma and may provide valuable diagnostic information for adrenocortical carcinoma in dogs.

Neuroprotective effects of minocycline and KML29, a potent inhibitor of monoacylglycerol lipase, in an experimental stroke model: a small-animal positron emission tomography study.

Hypoxia caused by ischemia induces acidosis and neuroexcitotoxicity, resulting in neuronal death in the central nervous system (CNS). Monoacylglycerol lipase (MAGL) is a modulator of 2-arachidonoylglycerol (2-AG), which is involved in retrograde inhibition of glutamate release in the endocannabinoid system. In the present study, we used positron emission tomography (PET) to monitor MAGL-positive neurons and neuroinflammation in the brains of ischemic rats. Additionally, we performed PET imaging to evaluate the neuroprotective effects of an MAGL inhibitor in an ischemic injury model. Methods: Ischemic-injury rat models were induced by intraluminal right middle cerebral artery occlusion (MCAO). PET studies of the brains of the ischemic rats were performed at several experimental time points (pre-occlusion, days 2, 4, and 7 after the MCAO surgery) using [11C]SAR127303 for MAGL and [18F]FEBMP for 18 kDa translocator protein (TSPO, a hall-mark of neuroinflammation). Medication using minocycline (a well-known neuroprotective agent) or KML29 (a potent MAGL inhibitor) was given immediately after the MCAO surgery and then daily over the subsequent three days. Results: PET imaging of the ischemic rats using [11C]SAR127303 showed an acute decline of radioactive accumulation in the ipsilateral side at two days after MCAO surgery (ratio of the area under the curve between the ipsilateral and contralateral sides: 0.49 ± 0.04 in the cortex and 0.73 ± 0.02 in the striatum). PET imaging with [18F]FEBMP, however, showed a moderate increase in accumulation of radioactivity in the ipsilateral hemisphere on day 2 (1.36 ± 0.11), and further increases on day 4 (1.72 ± 0.15) and day 7 (1.99 ± 0.06). Treatment with minocycline or KML29 eased the decline in radioactive accumulation of [11C]SAR127303 for MAGL (minocycline-treated group: 0.82 ± 0.06 in the cortex and 0.81 ± 0.05 in the striatum; KML29-treated group: 0.72 ± 0.07 in the cortex and 0.88 ± 0.04 in the striatum) and increased uptake of [18F]FEBMP for TSPO (minocycline-treated group: 1.52 ± 0.21 in the cortex and 1.56 ± 0.11 in the striatum; KML29-treated group: 1.63 ± 0.09 in the cortex and 1.50 ± 0.17 in the striatum). In MCAO rats, minocycline treatment showed a neuroprotective effect in the sensorimotor cortex suffering from severe hypoxic injury, whereas KML29 treatment saved neurons in the striatum, including bundles of myelinated axons. Conclusions: PET imaging allowed visualization of the different neuroprotective effects of minocycline and KML29, and indicated that combination pharmacotherapy using these drugs may be an effective therapy in acute ischemia.

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.

Biomarkers of non-infectious inflammatory CNS diseases in dogs - Where are we now? Part I: Meningoencephalitis of unknown origin.

Meningoencephalitides of Unknown Origin (MUO) comprises a group of non-infectious inflammatory brain conditions, which frequently cause severe neurological disease and death in dogs. Although multiple diagnostic markers have been investigated, a conclusive diagnosis, at present, essentially relies on postmortem histopathology. However, different groups of biomarkers, e.g. acute phase proteins, antibodies, cytokines, and neuro-imaging markers may prove useful in the diagnostic investigation of dogs with MUO. It appears from the current literature that acute phase proteins such as C-reactive protein are often normal in MUO, but may be useful to rule out steroid responsive meningitis-arteritis as well as other systemic inflammatory conditions. In antibody research, anti-glial fibrillary acidic protein (GFAP) may play a role, but further research is needed to establish this as a consistent marker of particularly Pug dog encephalitis. The proposed diagnostic markers often lack specificity to distinguish between the subtypes of MUO, but an increased expression of interferon-γ (IFN-γ) in necrotizing meningoencephalitis (NME) and interleukin-17 (IL-17) in granulomatous meningoencephalitis (GME) in tissue biopsies may indicate their potential as specific markers of NME and GME, respectively, suggesting further investigations of these in serum and CSF. While neuro-imaging is already an important part of the diagnostic work-up in MUO, further promising results have been shown with Positron Emission Tomography (PET) as well as proton resonance spectroscopy (1H MRS), which may be able to detect areas of necrosis and granulomas, respectively, with relatively high specificity. This review presents different groups of established and potential diagnostic markers of MUO assessing current results and future potential.

Characteristics of 18F-FDG and 18F-FDOPA PET in an 8-year-old neutered male Yorkshire Terrier dog with glioma: long-term chemotherapy using hydroxyurea plus imatinib with prednisolone and immunoreactivity for PDGFR-ß and LAT1.

An 8-year-old neutered male Yorkshire Terrier dog presented with head pressing, vestibular ataxia, neck tenderness, and no oculocephalic reflex. A demarcated lesion in the pons was identified on MRI. The patient was tentatively diagnosed with a glioma and was treated with hydroxyurea plus imatinib and prednisolone. After 30 days of therapeutic treatment, the patient showed a clear improvement in neurological signs, which lasted for 1117 days. On day 569 after the initiation of treatment, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) was performed with no significant findings on visual analysis. The average and maximal standardized uptake values (SUVs) were 1.92 and 2.29, respectively. The tumor-to-normal-tissue (T/N) ratio was 0.97. The first evidence of clinical deterioration was noticed on day 1147. On day 1155, 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (18F-FDOPA)-PET was performed. High uptake of 18F-FDOPA was observed in the intracranial lesion. The mean and maximal SUVs of the tumor were 1.59 and 2.29, respectively. The T/N ratio was 2.22. The patient was euthanized on day 1155 and histopathologic evaluations confirmed glioma (astrocytoma). This case shows that chemotherapy with hydroxyurea plus imatinib may be considered in the treatment of canine glioma. Furthermore, this is the first case describing the application of 18F-FDG and 18F-FDOPA in a dog with glioma.

A novel rabbit fixator made of a thermoplastic mask for awake imaging experiments.

This study aimed to develop and validate a novel rabbit fixator made from a thermoplastic mask for awake imaging experiments. When heated in a hot-water bath at 65-70 °C for 2-5 min, the thermoplastic mask became soft and could be molded to fit over the entire body of an anesthetized rabbit (4 ml of 3% pentobarbital sodium solution by intramuscular injection). Twenty rabbits were randomly divided into fixator (n = 10) and anesthesia (n = 10) groups. The animals' vital signs, stress hormones (cortisol and adrenaline), and subjective image quality scores for the computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) scanning were measured and compared. Phantom CT, MRI and PET studies were performed to assess the performance with and without the thermoplastic mask by using image agents at different concentrations or with different radioactivity. The respiration rate (RR), systolic blood pressure (SBP), diastolic blood pressure (DBP), peripheral capillary oxygen saturation (SpO2) and body temperature (T) decreased after anesthesia (all P < 0.05) but did not significantly decrease after fixation (all P > 0.05). The heart rate (HR), cortisol and adrenaline did not significantly decrease after either anesthesia or fixation (all P > 0.05). The subjective image quality scores for the CT and MRI images of the head, thorax, liver, kidney, intestines and pelvis and the subjective image quality scores for the PET images did not significantly differ between the two groups (all P > 0.05). For all examined organs except the muscle, 18F-FDG metabolism was lower after fixation than after anesthesia, and was almost identical of liver between two groups. The phantom study showed that the CT values, standard uptake values and MR T2 signal values did not differ significantly with or without the mask (all P > 0.05). A novel rabbit fixator created using a thermoplastic mask could be used to obtain high-quality images for different imaging modalities in an awake and near-physiological state.

Small animal PET: a review of what we have done and where we are going.

Small animal research is an essential tool in studying both pharmaceutical biodistribution and disease progression over time. Furthermore, through the rapid development ofin vivoimaging technology over the last few decades, small animal imaging (also referred to as preclinical imaging) has become a mainstay for all fields of biologic research and a center point for most preclinical cancer research. Preclinical imaging modalities include optical, MRI and MRS, microCT, small animal PET, ultrasound, and photoacoustic, each with their individual strengths. The strong points of small animal PET are its translatability to the clinic; its quantitative imaging capabilities; its whole-body imaging ability to dynamically trace functional/biochemical processes; its ability to provide useful images with only nano- to pico- molar concentrations of administered compounds; and its ability to study animals serially over time. This review paper gives an overview of the development and evolution of small animal PET imaging. It provides an overview of detector designs; system configurations; multimodality PET imaging systems; image reconstruction and analysis tools; and an overview of research and commercially available small animal PET systems. It concludes with a look toward developing technologies/methodologies that will further enhance the impact of small animal PET imaging on medical research in the future.

Temporal and anatomical distribution of 18F-flutemetamol uptake in canine brain using positron emission tomography.

BACKGROUND: Positron emission tomography (PET) is increasingly being used as an imaging modality for clinical and research applications in veterinary medicine. Amyloid PET has become a useful tool for diagnosing Alzheimer's disease (AD) in humans, by accurately identifying amyloid-beta (Aß) plaques. Cognitive dysfunction syndrome in dogs shows cognitive and pathophysiologic characteristics similar to AD. Therefore, we assessed the physiologic characteristics of uptake of 18F-flutemetamol, an Aß protein-binding PET tracer in clinical development, in normal dog brains, for distinguishing an abnormal state. Static and dynamic PET images of six adult healthy dogs were acquired after 18F-flutemetamol was administered intravenously at approximately 3.083 MBq/kg. For static images, PET data were acquired at 30, 60, and 90 min after injection. One week later, dynamic images were acquired for 120 min, from the time of tracer injection. PET data were reconstructed using an iterative technique, and corrections for attenuation and scatter were applied. Regions of interest were manually drawn over the frontal, parietal, temporal, occipital, anterior cingulate, posterior cingulate, and cerebellar cortices, cerebral white matter, midbrain, pons, and medulla oblongata. After calculating standardized uptake values with an established formula, standardized uptake value ratios (SUVRs) were obtained, using the cerebellar cortex as a reference region. RESULTS: Among the six cerebral cortical regions, the cingulate cortices and frontal lobe showed the highest SUVRs. The lowest SUVR was observed in the occipital lobe. The average values of the cortical SUVRs were 1.25, 1.26, and 1.27 at 30, 60, and 90 min post-injection, respectively. Tracer uptake on dynamic scans was rapid, peaking within 4 min post-injection. After reaching this early maximum, cerebral cortical regions showed a curve with a steep descent, whereas cerebral white matter demonstrated a curve with a slow decline, resulting in a large gap between cerebral cortical regions and white matter. CONCLUSION: This study provides normal baseline data of 18F-flutemetamol PET that can facilitate an objective diagnosis of cognitive dysfunction syndrome in dogs in future.

Higher neuron densities in the cerebral cortex and larger cerebellums may limit dive times of delphinids compared to deep-diving toothed whales.

Since the work of Tower in the 1950s, we have come to expect lower neuron density in the cerebral cortex of larger brains. We studied dolphin brains varying from 783 to 6215g. As expected, average neuron density in four areas of cortex decreased from the smallest to the largest brain. Despite having a lower neuron density than smaller dolphins, the killer whale has more gray matter and more cortical neurons than any mammal, including humans. To begin a study of non-dolphin toothed whales, we measured a 596g brain of a pygmy sperm whale and a 2004g brain of a Cuvier's beaked whale. We compared neuron density of Nissl stained cortex of these two brains with those of the dolphins. Non-dolphin brains had lower neuron densities compared to all of the dolphins, even the 6215g brain. The beaked whale and pygmy sperm whale we studied dive deeper and for much longer periods than the dolphins. For example, the beaked whale may dive for more than an hour, and the pygmy sperm whale more than a half hour. In contrast, the dolphins we studied limit dives to five or 10 minutes. Brain metabolism may be one feature limiting dolphin dives. The brain consumes an oversized share of oxygen available to the body. The most oxygen is used by the cortex and cerebellar gray matter. The dolphins have larger brains, larger cerebellums, and greater numbers of cortex neurons than would be expected given their body size. Smaller brains, smaller cerebellums and fewer cortical neurons potentially allow the beaked whale and pygmy sperm whale to dive longer and deeper than the dolphins. Although more gray matter, more neurons, and a larger cerebellum may limit dolphins to shorter, shallower dives, these features must give them some advantage. For example, they may be able to catch more elusive individual high-calorie prey in the upper ocean.