Regional cerebral blood flow in dogs with congenital extrahepatic portosystemic shunts before surgery and six months after successful closure.

Previous studies both in humans and dogs with chronic liver diseases have shown that regional cerebral brain flow (rCBF) is altered. The current study aimed to assess abnormalities in rCBF in dogs with congenital extrahepatic portosystemic shunts (cEHPSS), both at diagnosis and after successful surgical attenuation. Furthermore, the influence of age at diagnosis, severity of hepatic encephalopathy (HE) and type of cEHPSS on rCBF were explored as a base for future research. Single photon emission computed tomography (SPECT) with 99mtechnetium-hexamethylpropylene amine oxime tracer was performed before surgical attenuation and six months postoperatively. Twenty-four dogs with cEHPSS had SPECT at time of diagnosis and 13 dogs with a confirmed closed cEHPSS had a second SPECT six months postoperatively. At diagnosis, dogs with cEHPSS had an altered rCBF distribution compared to healthy dogs. This altered rCBF distribution seemed to be most apparent in dogs ≥ one year and in dogs with overt HE at diagnosis. Six months postoperatively, only the rCBF distribution in the subcortical region decreased compared to pre-operatively. In conclusion, all dogs with cEHPSS had altered rCBF which did not seem to normalize completely six months after successful surgical attenuation. Dogs diagnosed at an older age seemed to have more distinct abnormalities in rCBF compared to younger dogs.

Localization of cerebral hypoperfusion in dogs with refractory and non-refractory epilepsy using [99mTc] ethyl cysteinate dimer and single photon emission computed tomography.

To evaluate the localization of functional deficit area in epileptogenic zones of the brain in seven refractory and seven non-refractory epilepsy dogs using technetium 99m labeled with ethyl cysteinate dimer and interictal single photon emission computed tomography [99mTc-ECD SPECT] co-registration with Magnetic Resonance Imaging (MRI). Regions showing perfusion deficits in the SPECT images were analyzed by using the standard semiquantitative evaluation method to compare the level of cortical perfusion to the maximum number of counts within the cerebellum (max C), considered the area of reference. This study showed that SPECT imaging revealed abnormalities in several regions of the brain in both epilepsy groups. The refractory epilepsy dogs showed more frequency area of hypoperfusion in temporal lobe than non-refractory group with not statistically significance (P=0.28). The result suggests the lesion in temporal might be relevance with refractory epilepsy in canine patients.

Changes in canine cerebral perfusion after accelerated high frequency repetitive transcranial magnetic stimulation (HF-rTMS): A proof of concept study.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for several neuropsychiatric disorders in human beings, but the neurobiological effects of rTMS in dogs have not been investigated to date. A proof of concept study was designed to evaluate the effect of rTMS on cerebral perfusion, measured with single photon emission computed tomography (SPECT), in dogs. An accelerated high frequency (aHF)-rTMS (20Hz) protocol was applied to the canine left frontal cortex. To accurately target this area, eight dogs underwent a 3 Tesla magnetic resonance imaging (MRI) scan before stimulation. The left frontal cortex was subjected to five consecutive aHF-rTMS sessions with a figure-of-eight coil designed for human beings at an intensity of 110% of the motor threshold. The dogs underwent 99mTc-d,1 hexamethylpropylene amine oxime (HMPAO) SPECT scans 1 week prior to and 1day after the stimulations. Perfusion indices (PIs) were determined semi-quantitatively; aHF-rTMS resulted in significantly increased PIs in the left frontal cortex and the subcortical region, whereas no significant differences were noted for the other regions. Behaviour was not influenced by the stimulation sessions. As has been observed in human beings, aHF-rTMS applied to the left frontal cortex alters regional cerebral perfusion in dogs.

Regional cerebral blood flow assessed by single photon emission computed tomography (SPECT) in dogs with congenital portosystemic shunt and hepatic encephalopathy.

Regional cerebral blood flow (rCBF) in eight dogs with congenital portosystemic shunt (PSS) and hepatic encephalopathy (HE) was compared with rCBF in eight healthy control dogs using single photon emission computed tomography (SPECT) with a 99mtechnetium-hexamethylpropylene amine oxime (99mTc-HMPAO) tracer. SPECT scans were abnormal in all PSS dogs. Compared to the control group, rCBF in PSS dogs was significantly decreased in the temporal lobes and increased in the subcortical (thalamic and striatal) area. Brain perfusion imaging alterations observed in the dogs with PSS and HE are similar to those in human patients with HE. These findings suggest that dogs with HE and PSS have altered perfusion of mainly the subcortical and the temporal regions of the brain.

Fast iterative reconstruction for helical pinhole SPECT imaging.

Pinhole SPECT for small animal has become a routine procedure in many applications of molecular biology and pharmaceutical development. There is an increasing demand in the whole body imaging of lab animals. A simple and direct solution is to scan the object along a helical trajectory, similar to a helical CT scan. The corresponding acquisition time can be greatly reduced, while the over-lapping and gap between consecutive bed positions can be avoided. However, helical pinhole SPECT inevitably leads to the tremendous increase in computational complexity when the iterative reconstruction algorithms are applied. We suggest a novel voxel-driven (VD) system model which can be integrated with geometric symmetries from helical trajectory for fast iterative image reconstruction. Such a model construction can also achieve faster calculation and lower storage requirement of the system matrix. Due to the independence among various symmetries, it permits parallel coding to further boost computation efficiency of forward/backward projection. From phantom study, the results also indicate that the proposed VD model can adequately model the helical pinhole SPECT scanner with manageable storage size of system matrix and clinically acceptable computation loading of reconstruction.

Imaging technologies and basic considerations for welfare of laboratory rodents.

Imaging technologies are regularly used in biomedical research to study processes in living animals in a noninvasive manner. But imaging procedures can affect animal physiology, and the need to anesthetize animals for imaging entails potential health risks. In addition, certain imaging modalities require the use of ionizing radiation or the administration of contrast agents or imaging biomarkers, which also have consequences for animal physiology. Finally, procedures associated with imaging, such as animal preparation (e.g., fasting, premedication) and blood sampling, can also affect physiology and animal welfare. Here, the authors review the imaging modalities commonly used for rodents in biomedical research and their associated considerations for animal welfare.

Quarter-millimeter-resolution molecular mouse imaging with U-SPECT⁺.

Limited spatial resolution of preclinical positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has slowed down applications of molecular imaging in small animals. Here we present the latest-generation U-SPECT system (U-SPECT⁺, MILabs, Utrecht, the Netherlands) enabling radionuclide imaging of mice with quarter-millimeter resolution. The system was equipped with the newest high-resolution collimator with 0.25 mm diameter circular pinholes. It was calibrated with technetium-99 m point source measurements from which the system matrix was calculated. Images were reconstructed using pixel-based ordered subset expectation maximization (OSEM). Various phantoms and mouse SPECT scans were acquired. The reconstructed spatial resolution (the smallest visible capillary diameter in a hot-rod resolution phantom) was 0.25 mm. Knee joint images show tiny structures such as the femur epicondyle sulcus, as well as a clear separation between cortical and trabecular bone structures. In addition, time-activity curves of the lumbar spine illustrated that tracer dynamics in tiny tissue amounts could be measured. U-SPECT⁺ allows discrimination between molecular concentrations in adjacent volumes of as small as 0.015 µL, which is significantly better than can be imaged by any existing SPECT or PET system. This increase in the level of detail makes it more and more attractive to replace ex vivo methods and allows monitoring biological processes in tiny parts of organs in vivo.

PET and SPECT imaging in veterinary medicine.

Veterinarians have gained increasing access to positron emission tomography (PET and PET/CT) imaging facilities, allowing them to use this powerful molecular imaging technique for clinical and research applications. SPECT is currently being used more in Europe than in the United States and has been shown to be useful in veterinary oncology and in the evaluation of orthopedic diseases. SPECT brain perfusion and receptor imaging is used to investigate behavioral disorders in animals that have interesting similarities to human psychiatric disorders. This article provides an overview of the potential applications of PET and SPECT. The use of commercially available and investigational PET radiopharmaceuticals in the management of veterinary disease has been discussed. To date, most of the work in this field has utilized the commercially available PET tracer, (18)F-fluorodeoxyglucose for oncologic imaging. Normal biodistribution studies in several companion animal species (cats, dogs, and birds) have been published to assist in lesion detection and interpretation for veterinary radiologists and clinicians. Studies evaluating other (18)F-labeled tracers for research applications are underway at several institutions and companion animal models of human diseases are being increasingly recognized for their value in biomarker and therapy development. Although PET and SPECT technologies are in their infancy for clinical veterinary medicine, increasing access to and interest in these applications and other molecular imaging techniques has led to a greater knowledge and collective body of expertise for veterinarians worldwide. Initiation and fostering of physician-veterinarian collaborations are key components to the forward movement of this field.

Normal regional distribution of cerebral blood flow in dogs: comparison between (99m) Tc-ethylcysteinate dimer and (99m) Tc- hexamethylpropylene amine oxime single photon emission computed tomography.

Functional imaging provides important insights into canine brain pathologies such as behavioral problems. Two (99m) Tc-labeled single photon emission computed tomography (SPECT) cerebral blood flow tracers-ethylcysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO)-are commonly used in human medicine and have been used previously in dogs but intrasubject comparison of both tracers in dogs is lacking. Therefore, this study investigated whether regional distribution differences between both tracers occur in dogs as is reported in humans. Eight beagles underwent two SPECT examinations first with (99m) Tc-ECD and followed by (99m) Tc-HMPAO. SPECT scanning was performed with a triple head gamma camera equipped with ultrahigh resolution parallel hole collimators. Images were reconstructed using filtered backprojection with a Butterworth filter. Emission data were fitted to a template permitting semiquantification using predefined regions or volumes of interest (VOIs). For each VOI, perfusion indices were calculated by normalizing the regional counts per voxel to total brain counts per voxel. The obtained perfusion indices for each region for both tracers were compared with a paired Student's T-test. Significant (P < 0.05) regional differences were seen in the subcortical region and the cerebellum. Both tracers can be used to visualize regional cerebral blood flow in dogs, however, due to the observed regional differences, they are not entirely interchangeable.

The use of the HiSPECT bone scan in canine flexor enthesopathy and coronoid pathology.

In this study the use of the high resolution Micro-Single Photon Emission Tomography (HiSPECT) system with a radioactive bonemarker, (99m)Tc-oxidronate, was evaluated in dogs with coronoid pathology and/or flexor enthesopathy. Sixty-five elbows of 34 dogs were included. CT and HiSPECT were performed on all elbows, arthroscopy on 59. Tracer uptake in 8 anatomical regions was graded according to two models. Increased activity in the medial epicondylar region was associated with flexor pathology on CT (P=0.0002) and arthroscopy (P<0.0001) and increased uptake in the medial coronoid (P<0.0001) and the medial condylar area (P<0.013) with coronoid pathology. Uptake in the remaining areas was not associated with both pathologies. In conclusion, the improved resolution of the HiSPECT system allows identification of increased tracer uptake in the anatomical regions involved in coronoid pathology and flexor enthesopathy. This modality may improve the diagnostic potential of the bone scan in canine elbow disease.

High-resolution micro-SPECT to evaluate the regional brain perfusion in the adult Beagle dog.

Conventional Single Photon Emission Computed Tomography (SPECT) precludes a detailed evaluation of the subcortical region. Micro-SPECT (µ-SPECT) has a higher resolution, but has not been used to evaluate the dog's brain until now. In this study, µ-SPECT of the brain was evaluated in 10 Beagle dogs. Magnetic Resonance Imaging (MRI) of the brain was used to draw a new region map containing 19 volumes of interest (VOIs). Semi-quantitative analysis of the µ-SPECT data was performed and the regional cerebral perfusion was represented by the perfusion indices (PIs). The highest perfusion was found in the parietal cortex and the lowest in the piriform cortex. An asymmetry toward the left hemisphere in general and a regional asymmetry in the frontal, temporal and parietal cortex were found. This study shows that functional imaging of the canine brain is possible using µ-SPECT and it describes the normal regional brain perfusion in the adult Beagle dog.

Regional brain perfusion in 12 cats measured with technetium-99m-ethyl cysteinate dimer pinhole single photon emission computed tomography (SPECT).

With the use of perfusion tracers, in vivo examination of the regional cerebral blood flow in cats can be performed with single photon emission computed tomography (SPECT). Reliable perfusion data of normal, healthy cats are necessary for future clinical studies or other research use. Therefore, this dataset of the regional perfusion pattern of the normal feline brain was created. Twelve cats were used in this study. Technetium-99m-ethyl cysteinate dimer ((99m)Tc-ECD) was injected intravenously and the acquisition, using a triple head gamma camera equipped with three multi-pinhole collimators (pinhole SPECT), was started 40 mins after tracer administration under general anaesthesia. Nineteen regions of interest were defined using 7T magnetic resonance images of the feline brain and a topographical atlas. Regional counts were normalised to the counts of two reference regions: the total brain and the cerebellum. The highest tracer uptake was noticed in the subcortical structures, and the lowest in the frontal cortex and the cerebellum. Also left-right asymmetry in the temporal cortex and a rostrocaudal gradient of 5% were observed.

Development of a pixelated GSO gamma camera system with tungsten parallel hole collimator for single photon imaging.

PURPOSE: In small animal imaging using a single photon emitting radionuclide, a high resolution gamma camera is required. Recently, position sensitive photomultiplier tubes (PSPMTs) with high quantum efficiency have been developed. By combining these with nonhygroscopic scintillators with a relatively low light output, a high resolution gamma camera can become useful for low energy gamma photons. Therefore, the authors developed a gamma camera by combining a pixelated Ce-doped Gd(2)SiO(5) (GSO) block with a high quantum efficiency PSPMT. METHODS: GSO was selected for the scintillator, because it is not hygroscopic and does not contain any natural radioactivity. An array of 1.9 mm × 1.9 mm × 7 mm individual GSO crystal elements was constructed. These GSOs were combined with a 0.1-mm thick reflector to form a 22 × 22 matrix and optically coupled to a high quantum efficiency PSPMT (H8500C-100 MOD8). The GSO gamma camera was encased in a tungsten gamma-ray shield with tungsten pixelated parallel hole collimator, and the basic performance was measured for Co-57 gamma photons (122 keV). RESULTS: In a two-dimensional position histogram, all pixels were clearly resolved. The energy resolution was ∼15% FWHM. With the 20-mm thick tungsten pixelated collimator, the spatial resolution was 4.4-mm FWHM 40 mm from the collimator surface, and the sensitivity was ∼0.05%. Phantom and small animal images were successfully obtained with our developed gamma camera. CONCLUSIONS: These results confirmed that the developed pixelated GSO gamma camera has potential as an effective instrument for low energy gamma photon imaging.

Effects of medetomidine and ketamine on the regional cerebral blood flow in cats: a SPECT study.

Brain perfusion can be investigated using single photon emission computed tomography (SPECT) and the intravenous injection of (99m)technetium ethyl cysteinate dimer ((99m)Tc-ECD). However, sedation using medetomidine, an α(2)-agonist, or anaesthesia using medetomidine and ketamine, an N-methyl-d-aspartate-(NMDA)-antagonist, may be required for SPECT studies in cats but can affect the regional cerebral blood flow (rCBF). The effects of medetomidine, with or without ketamine, on regional brain perfusion were therefore investigated in six cats under three conditions. Injection of tracer occurred before sedation or anaesthesia (condition A), following intramuscular (IM) sedation with medetomidine (condition M) or after IM anaesthesia with medetomidine and ketamine (condition MK). Medetomidine and medetomidine with ketamine caused a significantly higher total tracer uptake in all brain regions. Semi-quantification of brain perfusion gave lower perfusion indices in several sub-cortical regions in conditions M and MK, compared to A. Left-right differences were observed in the temporal cortex (A), the temporal, parietal cortex and the thalamus (M) and the frontal cortex (MK). A significantly higher perfusion index in the sub-cortical regions, compared to the whole cortex, was only present in condition A. This study showed that caution is needed when quantifying brain perfusion indices when using sedative or anaesthetic agents that may affect rCBF.

Development of a variable-radius pinhole SPECT system with a portable gamma camera.

OBJECTIVE: To develop a small-animal SPECT system using a low cost commercial portable gamma camera equipped with a pinhole collimator, a continuous scintillation crystal and a position-sensitive photomultiplier tube. MATERIAL AND METHODS: The gamma camera was attached to a variable radius system, which enabled us to optimize sensitivity and resolution by adjusting the radius of rotation to the size of the object. To investigate the capability of the SPECT system for small animal imaging, the dependence of resolution and calibration parameters on radius was assessed and acquisitions of small phantoms and mice were carried out. RESULTS: Resolution values, ranging from 1.0mm for a radius of 21.4mm and 1.4mm for a radius of 37.2mm were obtained, thereby justifying the interest of a variable radius SPECT system. CONCLUSIONS: The image quality of phantoms and animals were satisfactory, thus confirming the usefulness of the system for small animal SPECT imaging.

Radiography, 99mTc-HDP, and 111In labeled vitamin B12 SPECT of canine osteosarcoma: a comparative study.

The objective of this article was to compare radiography, planar bone scintigraphy, and single-photon emission computed tomography (SPECT) to determine the size of osteosarcomas in long bones of dogs. Ten dogs with osteosarcoma in six radii, two humeri, one tibia, and one ulna were evaluated. Macroslides, mediolateral radiographs, planar scintigrams, and sagittal images from SPECT scans were used to obtain measurements. On the scintigraphic images, the edges of the tumor were established using the activity profile imaging tool. The radiographic magnification was factored. The mean percentage of tumor size overestimation was 9.29% on mediolateral radiographs, 5.35% on planar scintigrams, and 33.25% on SPECT images. The correlation coefficient adjusted for sample size was significantly higher (P<0.01) for technetium 99m ((99m)Tc) hydroxyethylene diphosphonate (HDP) (75.5%) and radiography (61.3%) compared with indium 111-vitamin B(12) (28.3%). The correlation coefficient for (99m)Tc-HDP was higher than that obtained for radiographs; however, statistical difference between the two variables was not demonstrated (P>0.05). (99m)Tc bone scan is a good estimator of intramedullary size of osteosarcoma in long bones when the activity profile tool to determine the margin of the tumor is used.

Carbon tube electrodes for electrocardiography-gated cardiac multimodality imaging in mice.

This report describes a simple design of noninvasive carbon tube electrodes that facilitates electrocardiography (ECG) in mice during cardiac multimodality preclinical imaging. Both forepaws and the left hindpaw, covered by conductive gel, of mice were placed into the openings of small carbon tubes. Cardiac ECG-gated single-photon emission CT, X-ray CT, and MRI were tested (n = 60) in 20 mice. For all applications, electrodes were used in a warmed multimodality imaging cell. A heart rate of 563 ± 48 bpm was recorded from anesthetized mice regardless of the imaging technique used, with acquisition times ranging from 1 to 2 h.

The effect of medetomidine on the regional cerebral blood flow in dogs measured using Technetium-99m-Ethyl Cysteinate Dimer SPECT.

Sedatives and anaesthetics are known to cause changes in the regional cerebral blood flow. In dogs intramuscular sedation with medetomidine, a potent sedative frequently used in veterinary medicine, is sometimes indicated prior to intravenous injection of (99m)Technetium-Ethyl Cysteinate Dimer ((99m)Tc-ECD) in brain perfusion studies using Single Photon Emission Computed Tomography (SPECT). Based on the knowledge of the distribution of alpha(2)-receptors in the brain, we hypothesized altered regional brain perfusion in dogs receiving medetomidine prior to (99m)Tc-ECD. Two conditions were compared in 10 dogs; tracer injection before and after intramuscular sedation with medetomidine. In our study, medetomidine caused a significantly higher tracer uptake in all brain regions. Semi-quantification of brain perfusion rendered a lower perfusion index in the subcortical region and an imbalance between left and right cortical perfusion induced by medetomidine. This study shows that caution is needed when quantifying the brain perfusion indices under medetomidine sedation.

Recognition of anatomical predilection sites in canine elbow pathology on bone scans using micro-single photon emission tomography.

The limited resolution of planar bone scintigraphy precludes exact anatomical localisation within a joint. Micro-single photon emission tomography (µ-SPECT) has a much higher resolution, and in this study the use of µ-SPECT in the evaluation of the canine elbow joint and fusion with structural imaging data were tested. Twelve elbows of seven normal dogs were included. µ-SPECT was performed with a conventional triple head gamma camera adapted with three multi-pinhole collimators (HiSPECT). Radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) were performed on all elbows and data from CT and MRI were fused to the HiSPECT data using dedicated software. Different important anatomical regions could be recognised on the HiSPECT images. The improved resolution of the HiSPECT system allowed better differentiation of the anatomical areas in the elbow joint. Two case studies were included to demonstrate the potential of this methodology. Fusion software facilitated the use of combined structural and functional information.