Imaging Techniques in Large Animals

Imaging techniques in large animals bridges the gap between preclinical and clinical research.  The same scanners can be used for large laboratory animals and for human beings and, with few  modifications, the same scanning protocols can also be used. Therefore, knowledge obtained from imaging  techniques in animal research can readily be used in humans. Similarly, medical hypotheses and problems  from clinical experience with humans can often be tested and studied in large animals. Imaging techniques  create either anatomical images (Computerized Tomography, CT or Magnetic Resonance Imaging, MRI) or  functional images of the body (Positron Emission Tomography, PET). While X-ray radiation is used to get  a cross-sectional CT image of the body, MRI involves the use of a magnetic field that forces the hydrogen  cellular nuclei to align in different positions. PET utilizes radiation emitted from the animal after injection  of radioactive tracers. The most commonly used large animals in imaging research are dogs, sheep, goats,  pigs and nonhuman primates. These laboratory animals have large organs and blood volumes that allow  repeated blood sampling, which is needed in most PET studies, while blood sampling is unnecessary for  CT and MRI imaging. Large animals are outbreed, and so many animals are typically needed in each study,  due to marked individual variation. That situation is unfavourable, because imaging studies of large animals  are expensive and time consuming. Except for nonhuman primates, large animals must be anaesthetised for  scanning procedures, and this may influence the experiments.

PET Neuroimaging in Pigs

Current interest in studying molecular processes as they occur in the living brain has accelerated the use of laboratory animals for neuroimaging of novel radiolabelled compounds. In particular, positron emission tomography (PET) has contributed to the development of radiolabelled compounds for assessing molecular processes in the living brain. The dynamics of PET typically require a relatively large organ size and blood supply in order to properly evaluate radioligand binding kinetics. To fulfil these requirements, pigs have often been used in such studies. Today, much is known about the metabolism, neurotransmission and molecular binding properties of the living porcine brain, and most findings support similarities between neuronal mechanisms in pigs and humans. Here, we review 10-years of PET findings on neuromolecular processes in the living porcine brain and, whenever possible, we relate PET findings in pigs to those obtained in humans

Estimating Discard Mortality in Commercial Fisheries without Fish Dying:A 3R Challenge

SIMPLE SUMMARY: Due to the implementation of a landing obligation in fisheries in the European Union (EU), with an exemption for species with “high survival”, discard survival studies (henceforth DSSs) have become one of the most politically prioritized fisheries research areas in European fisheries. In contrast to most fisheries science research areas, DSSs are embedded by the EUs animal research welfare directive. This is a challenge, and there has not been any focus on how to implement animal welfare (AW) regulations experimentally in DSSs. This paper focuses on AW regulations in relation to conducting DSSs, but the outreach is much broader. We investigate experimental procedures by bringing in relevant examples, using the output results, and relating this information to relevant AW guidelines and regulations by focusing on implementing 3R principles. ABSTRACT: Globally, it is estimated that around 10% of the fish that are caught are discarded. This is considered to be a wasteful human marine activity since these fish are often dead or dying. To reduce the high discard rates of commercial fisheries, the European Union (E.U.) has enacted a landing obligation that includes the ability to exempt “species for which scientific evidence demonstrates high survival rates”. Therefore, discard survival studies (henceforth DSSs) have become one of the most politically prioritized fisheries research areas in European fisheries. International expert groups have produced guidance reports to promote best practices and to harmonize the methodologies. Nevertheless, there has not been any focus on how to implement animal welfare (AW) regulations experimentally. Discard survival studies are “frontrunners” in fisheries science research areas that are embedded by animal research welfare requirements and are expected to be more restrictive in the future because of an increased public focus on fish welfare. This paper focuses on AW regulations in relation to conducting DSSs, but the outreach is much broader. We investigate experimental procedures by bringing in relevant examples, using output results, and relating this information to relevant AW guidelines and regulations by focusing on implementing 3R principles

Type of Anesthesia Influences Positron Emission Tomography Measurements of Dopamine D2/3 Receptor Binding in the Rat Brain

Rats are often anesthetized prior to positron emission tomography (PET) brain imaging in order to prevent head movements. Anesthesia can be administered by inhalation agents, such as isoflurane (Forene), or injection mixtures, such as fentanyl-fluanisone-midazolam (Hypnorm-Dormicum). Unfortunately, anesthesia affects a variety of physiological variables, including those in the brain. The aim of this study was to compare the effects of inhalation and injection anesthesia on the binding potential of the dopaminergic D2/3 tracer [11C]raclopride used for PET brain imaging in human and animal studies. Male Lewis rats were assigned to either inhalation (isoflurane; N=4) or injection (fentanyl-fluanisone-midazolam; N=5) anesthesia. Isoflurane was given continuously, and fentanyl-fluanisone-midazolam was supplemented every 30-60 minutes when the tail reflex was positive. Catheters were surgically placed in femoral arteries and veins for blood sampling and tracer injection. After a short attenuation scan, the rats were PET scanned for 90 minutes after injection of [11C]raclopride. We found that rats anesthetized with isoflurane had double the binding potential in the striatum compared with fentanyl-fluanisone-midazolam anesthetized rats. Our results are in agreement with other studies showing that anesthesia may have a major influence on brain imaging studies involving tracer kinetics in rats

Blood lactate and glucose concentrations in the femoral artery and three different veins during anaesthesia of healthy laboratory pigs

Blood lactate is a parameter used for monitoring pigs during prolonged anaesthesia. Here we compared blood lactate and glucose concentrations in nine anaesthetised laboratory pigs. Seventeen of the samples originated from a liver project and 15 from a kidney project. Mean and standard deviations of arterial blood lactate and glucose were compared with values for portal, renal and femoral veins by using paired Student’s t-test, paired Wilcoxon test as well as Spearman rank-order correlation. The study showed that lactate concentration was constant whether measured in blood from the femoral artery, portal vein, renal vein or femoral vein. The study showed that the origin of the blood sampled is not important and that changes in blood lactate concentration are likely to be the same throughout the cardiovascular system in healthy pigs

Radiotracers for Bone Marrow Infection Imaging

Introduction: Radiotracers are widely used in medical imaging, using techniques of gamma-camera imaging (scintigraphy and SPECT) or positron emission tomography (PET). In bone marrow infection, there is no single routine test available that can detect infection with sufficiently high diagnostic accuracy. Here, we review radiotracers used for imaging of bone marrow infection, also known as osteomyelitis, with a focus on why these molecules are relevant for the task, based on their physiological uptake mechanisms. The review comprises [(67)Ga]Ga-citrate, radiolabelled leukocytes, radiolabelled nanocolloids (bone marrow) and radiolabelled phosphonates (bone structure), and [(18)F]FDG as established radiotracers for bone marrow infection imaging. Tracers that are under development or testing for this purpose include [(68)Ga]Ga-citrate, [(18)F]FDG, [(18)F]FDS and other non-glucose sugar analogues, [(15)O]water, [(11)C]methionine, [(11)C]donepezil, [(99m)Tc]Tc-IL-8, [(68)Ga]Ga-Siglec-9, phage-display selected peptides, and the antimicrobial peptide [(99m)Tc]Tc-UBI(29-41) or [(68)Ga]Ga-NOTA-UBI(29-41). Conclusion: Molecular radiotracers allow studies of physiological processes such as infection. None of the reviewed molecules are ideal for the imaging of infections, whether bone marrow or otherwise, but each can give information about a separate aspect such as physiology or biochemistry. Knowledge of uptake mechanisms, pitfalls, and challenges is useful in both the use and development of medically relevant radioactive tracers

Monitoring variables affecting positron emission tomography measurements of cerebral blood flow in anaesthetized pigs

Abstract Background Positron emission tomography (PET) imaging of anaesthetized pig brains is a useful tool in neuroscience. Stable cerebral blood flow (CBF) is essential for PET, since variations can affect the distribution of several radiotracers. However, the effect of physiological factors regulating CBF is unresolved and therefore knowledge of optimal anaesthesia and monitoring of pigs in PET studies is sparse. The aim of this study was therefore to determine if and how physiological variables and the duration of anaesthesia affected CBF as measured by PET using [15O]-water in isoflurane–N2O anaesthetized domestic female pigs. First, we examined how physiological monitoring parameters were associated with CBF, and which parameters should be monitored and if possible kept constant, during studies where a stable CBF is important. Secondly, we examined how the duration of anaesthesia affected CBF and the monitoring parameters. Results No significant statistical correlations were found between CBF and the nine monitoring variables. However, we found that arterial carbon dioxide tension (PaCO2) and body temperature were important predictors of CBF that should be observed and kept constant. In addition, we found that long-duration anaesthesia was significantly correlated with high heart rate, low arterial oxygen tension, and high body temperature, but not with CBF. Conclusions The findings indicate that PaCO2 and body temperature are crucial for maintaining stable levels of CBF and thus optimizing PET imaging of molecular mechanisms in the brain of anaesthetized pigs. Therefore, as a minimum these two variables should be monitored and kept constant. Furthermore, the duration of anaesthesia should be kept constant to avoid variations in monitoring variables