Small Animal Brain Research Articles

Optimising rigid motion compensation for small animal brain PET imaging

Motion compensation (MC) in PET brain imaging of awake small animals is attracting increased attention in preclinical studies since it avoids the confounding effects of anaesthesia and enables behavioural tests during the scan. A popular MC technique is to use multiple external cameras to track the motion of the animal’s head, which is assumed to be represented by the motion of a marker attached to its forehead. In this study we have explored several methods to improve the experimental setup and the reconstruction procedures of this method: optimising the camera-marker separation; improving the temporal synchronisation between the motion tracker measurements and the list-mode stream; post-acquisition smoothing and interpolation of the motion data; and list-mode reconstruction with appropriately selected subsets. These techniques have been tested and verified on measurements of a moving resolution phantom and brain scans of an awake rat. The proposed techniques improved the reconstructed spatial resolution of the phantom by 27% and of the rat brain by 14%. We suggest a set of optimal parameter values to use for awake animal PET studies and discuss the relative significance of each parameter choice.

Magnetic resonance imaging of the small animal brain

Advanced imaging modalities, such as magnetic resonance imaging (MRI), are readily available to most specialist referral hospitals and also increasingly to a growing number of first-opinion/general practice veterinary hospitals. Despite...

Label-free photoacoustic tomography of whole mouse brain structures ex vivo.

Capitalizing on endogenous hemoglobin contrast, photoacoustic-computed tomography (PACT), a deep-tissue high-resolution imaging modality, has drawn increasing interest in neuroimaging. However, most existing studies are limited to functional imaging on the cortical surface and the deep brain structural imaging capability of PACT has never been demonstrated. Here, we explicitly studied the limiting factors of deep brain PACT imaging. We found that the skull distorted the acoustic signal and blood suppressed the structural contrast from other chromophores. When the two effects are mitigated, PACT can potentially provide high-resolution label-free imaging of structures in the entire mouse brain. With [Formula: see text] in-plane resolution, we can clearly identify major structures of the brain, which complements magnetic resonance microscopy for imaging small-animal brain structures. Spectral PACT studies indicate that structural contrasts mainly originate from cytochrome distribution and that the presence of lipid sharpens the image contrast; brain histology results provide further validation. The feasibility of imaging the structure of the brain in vivo is also discussed. Our results demonstrate that PACT is a promising modality for both structural and functional brain imaging.

SU‐F‐T‐673: Effects of Cardiac Induced Brain Pulsations On Proton Minibeams

Purpose:To quantify the dosimetric impact of internal motion within the brain on spatially modulated proton minibeam radiation therapy (pMRT) for small animal research.Methods:The peak‐to‐valley dose ratio (PVDR) is an essential dosimetric factor for pMRT. Motion of an animal brain caused by cardiac‐induced pulsations (CIP) can impact dose deposition. For synchrotron generated high dose rate X‐ray microbeams this effect is evaded due to the quasi‐instantaneous delivery. By comparison, pMRT potentially suffers increased spread due to lower dose rates. However, for a given dose rate it is less susceptible to beam spread than microbeams, due to the spatial modulation being an order of magnitude larger. Monte Carlo simulations in TOPAS were used to model the beam spread for a 50.5MeV pMRT beam. Motion effects were simulated for a 50mm thick brass collimator with 0.3mm slit width and 1.0mm center‐to‐center spacing in a water phantom. The maximum motion in a rat brain due to CIP has been reported to be 0.06mm. Motion was simulated with a peak amplitude in the range 0–0.2mm.Results:The impact of 0.06mm peak motion was minimal and reduced the PVDR by about 1% at a depth of 10mm. For 0.2mm peak motion the PVDR was reduced by 16% at a depth of 10mm.Conclusion:For the pMRT beam the magnitude of cardiac‐induced brain motion has minimal impact on the PVDR for the investigated collimator geometry. For more narrow beams the effect is likely to be larger. This indicates that delivery of pMRT to small animal brains should not be affected considerably by beamlines with linac compatible dose rates.

An improved approach to align and embed multiple brain samples in a gelatin-based matrix for simultaneous histological processing

BackgroundPreparation and processing of free-floating histological sections involve a series of steps. The amount of labor, particularly sectioning and mounting, quickly multiplies as the number of samples increases. Embedding tissue samples in a flexible matrix allows simultaneous handling of multiple samples and preserves the integrity of the tissue during histological processing. However, aligning multiple asymmetrical samples, for example small-animal brains, in a particular orientation requires skillful arrangement and securing of the samples by pinning onto a solid surface. Consequently, costly technical services offered by contract research organizations are often sought. New methodAn improved approach to align and embed multiple whole or half rodent brain samples into a gelatin-based matrix is described. Using a template specifically designed to form arrayed mouse brain-shaped cavities, a ⿿receiving matrix⿿ is prepared. Inserting brain samples directly into the cavities allows the samples to be effortlessly positioned into a uniform orientation and embedded in a block of matrix. ResultsMultiple mouse brains were arrayed in a uniform orientation in a gelatin matrix block with ease using the receiving matrix. The gelatin-embedded brains were simultaneously sectioned and stained, and effortlessly mounted onto glass slides. Comparison with existing methodsThe improved approach allowed multiple whole or half mouse brains to be easily arrayed without pinning the samples onto a solid surface and prevented damages or shifting of the samples during embedding. ConclusionsThe new approach to array multiple brain samples provides a simple way to prepare gelatin-embedded whole or half brain arrays of commercial quality.

Design considerations for a C-shaped PET system, dedicated to small animal brain imaging, using GATE Monte Carlo simulations

Commercial clinical and preclinical PET scanners rely on the full cylindrical geometry for whole body scans as well as for dedicated organs. In this study we propose the construction of a low cost dual-head C-shaped PET system dedicated for small animal brain imaging. Monte Carlo simulation studies were performed using GATE toolkit to evaluate the optimum design in terms of sensitivity, distortions in the FOV and spatial resolution. The PET model is based on SiPMs and BGO pixelated arrays. Four different configurations with C- angle 0°, 15°, 30° and 45° within the modules, were considered. Geometrical phantoms were used for the evaluation process. STIR software, extended by an efficient multi-threaded ray tracing technique, was used for the image reconstruction. The algorithm automatically adjusts the size of the FOV according to the shape of the detector's geometry. The results showed improvement in sensitivity of ∼15% in case of 45° C-angle compared to the 0° case. The spatial resolution was found 2 mm for 45° C-angle.

Attenuation correction for freely moving small animal brain PET studies based on a virtual scanner geometry

Attenuation correction in positron emission tomography brain imaging of freely moving animals is a very challenging problem since the torso of the animal is often within the field of view and introduces a non negligible attenuating factor that can degrade the quantitative accuracy of the reconstructed images. In the context of unrestrained small animal imaging, estimation of the attenuation correction factors without the need for a transmission scan is highly desirable. An attractive approach that avoids the need for a transmission scan involves the generation of the hull of the animal’s head based on the reconstructed motion corrected emission images. However, this approach ignores the attenuation introduced by the animal’s torso. In this work, we propose a virtual scanner geometry which moves in synchrony with the animal’s head and discriminates between those events that traversed only the animal’s head (and therefore can be accurately compensated for attenuation) and those that might have also traversed the animal’s torso. For each recorded pose of the animal’s head a new virtual scanner geometry is defined and therefore a new system matrix must be calculated leading to a time-varying system matrix. This new approach was evaluated on phantom data acquired on the microPET Focus 220 scanner using a custom-made phantom and step-wise motion. Results showed that when the animal’s torso is within the FOV and not appropriately accounted for during attenuation correction it can lead to bias of up to 10% . Attenuation correction was more accurate when the virtual scanner was employed leading to improved quantitative estimates (bias < 2%), without the need to account for the attenuation introduced by the extraneous compartment. Although the proposed method requires increased computational resources, it can provide a reliable approach towards quantitatively accurate attenuation correction for freely moving animal studies.

Thermal and Mechanical Analysis of Novel Transcranial Magnetic Stimulation Coil for Mice

Transcranial magnetic stimulation (TMS) has potential to treat various neurological disorders noninvasively and safely. There has been significant work on coil designs for use on the human brain; however, there are fewer reports on the coil design for small animal brains, such as mice. Such work is essential to validate TMS treatment procedures on animals prior to clinical trials. We report thermal and mechanical analysis of a new small-animal coil system designed to produce focused electric fields resulting in more selective deep-brain stimulation. Thermal and magnetic force analyses conducted at experimental TMS operating conditions are used to determine the mechanical stability of the new coil system. Low magnetic linear attraction and rotational forces suggest mechanical stability of the coil. Small temperature increase over a simulated 60 s TMS therapy session indicates that the coil system operates within safe temperature limits. This coil configuration can be used on mice to stimulate selective regions of the brain to study various neurological disorders, such as Parkinson's disease.

Diffeomorphic registration with self-adaptive spatial regularization for the segmentation of non-human primate brains.

Cerebral aging has been linked to structural and functional changes in the brain throughout life. Here, we study the marmoset, a small non-human primate, in order to get insights into the mechanisms of brain aging in normal and pathological conditions. Imaging the brain of small animals with techniques such as MRI, quickly becomes a challenging task when compared with human brain imaging. Very often, a simple pre-processing step such as brain extraction cannot be achieved with classical tools. In this paper, we propose a diffeomorphic registration algorithm, which makes use of learned constraints to propagate the manual segmentation of a marmoset brain template to other MR images of marmoset brains. The main methological contribution of our paper is to explore a new strategy to automatically tune the spatial regularization of the deformations. Results show that we obtain a robust segmentation of the brain, even for images with a low contrast.

Differentiating BOLD and non-BOLD signals in fMRI time series from anesthetized rats using multi-echo EPI at 11.7T

The study of spontaneous brain activity using fMRI is central to mapping brain networks. However, current fMRI methodology has limitations in the study of small animal brain organization using ultra-high field fMRI experiments, as imaging artifacts are difficult to control and the relationship between classical neuroanatomy and spontaneous functional BOLD activity is not fully established. Challenges are especially prevalent during the fMRI study of individual rodent brains, which could be instrumental to studies of disease progression and pharmacology. A recent advance in fMRI methodology enables unbiased, accurate, and comprehensive identification of functional BOLD signals by interfacing multi-echo (ME) fMRI acquisition, NMR signal decay analysis, and independent components analysis (ICA), in a procedure called ME-ICA. Here we present a pilot study on the suitability of ME-ICA for ultra high field animal fMRI studies of spontaneous brain activity under anesthesia. ME-ICA applied to 11.7T fMRI data of rats first showed robust performance in automatic high dimensionality estimation and ICA decomposition, similar to that previously reported for 3.0T human data. ME sequence optimization for 11.7T indicated that 3 echoes, 0.5mm isotropic voxel size and TR=3s was adequate for sensitive and specific BOLD signal acquisition. Next, in seeking optimal inhaled isoflurane anesthesia dosage, we report that progressive increase in anesthesia goes with concomitant decrease in statistical complexity of “global” functional activity, as measured by the number of BOLD components, or degrees of freedom (DOF). Finally, BOLD functional connectivity maps for individual rodents at the component level show that spontaneous BOLD activity follows classical neuroanatomy, and seed-based analysis shows plausible cortical–cortical and cortical–subcortical functional interactions.

Dynamic changes in the distribution and time course of blood–brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia

Electron paramagnetic resonance (EPR) imaging using nitroxides as redox-sensitive probes is a powerful, noninvasive method that can be used under various physiological conditions to visualize changes in redox status that result from oxidative damage. Two blood–brain barrier-permeative nitroxides, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy (MCP), have been widely used as redox-sensitive probes in the brains of small animals, but their in vivo distribution and properties have not yet been analyzed in detail. In this study, a custom-made continuous-wave three-dimensional (3D) EPR imager was used to obtain 3D EPR images of mouse heads using MCP or HMP. This EPR imager made it possible to take 3D EPR images reconstructed from data from 181 projections acquired every 60s. Using this improved EPR imager and magnetic resonance imaging, the distribution and reduction time courses of HMP and MCP were examined in mouse heads. EPR images of living mice revealed that HMP and MCP have different distributions and different time courses for entering the brain. Based on the pharmacokinetics of the reduction reactions of HMP and MCP in the mouse head, the half-lives of HMP and MCP were clearly and accurately mapped pixel by pixel. An ischemic mouse model was prepared, and the half-life of MCP was mapped in the mouse head. Compared to the half-life in control mice, the half-life of MCP in the ischemic model mouse brain was significantly increased, suggesting a shift in the redox balance. This in vivo EPR imaging method using BBB-permeative MCP is a useful noninvasive method for assessing changes in the redox status in mouse brains under oxidative stress.

WE-G-BRE-01: A High Power Nanotube X-Ray Microbeam Irradiator for Preclinical Brain Tumor Treatment

Purpose: Microbeam radiation therapy (MRT) is a new type of cancer treatment undergoing studies at various synchrotron facilities. The principle of MRT is using arrays of microscopically small, low-energy X-radiation for the treatment of various radio-resistant, deep-seated tumors. Our motivation is to develop a compact and inexpensive image guided MRT irradiator to use in the research lab setting. After a successful initial demonstration, here we report a second generation carbon nanotube (CNT) cathode based MRT tube, capable of producing multiple microbeam lines with an anticipated dose rate of 11 Gy/min per line. Methods: The system uses multiple line CNT source arrays to generate multiple focal lines on the anode. The increase in dose-rate, compared to our first generation system, is achieved by increasing the operating voltage from 160 kVp to 225kVp, adding multiple simultaneous focal lines on the anode, and a more efficient cooling mechanism using a 6kW oil-cooled anode. Results: This work will present the design and development process, challenges and solutions to meeting operating specifications, and the final design of the tube and collimator, along with optimization and stabilization of its use. A detailed characterization of its capabilities will be included with a comprehensive measurement of its X-ray focal line dimensions, an evaluation of its collimator alignment and microbeam dimensions, and phantom-based quantification of its dosimetric output. Conclusion: The development of a second generation, compact, multiple line MRT device using carbon nanotube (CNT) cathode based X-ray technology and a novel oil cooled anode design is presented here. With this new source, we are capable of delivering a total microbeam radiation dose comparable to the low end of the synchrotron based MRT systems for small animal brain tumor models.

Abnormal metabolic connectivity in the pilocarpine-induced epilepsy rat model: A multiscale network analysis based on persistent homology

Temporal lobe epilepsy is associated with dysfunctional brain networks. Here we investigated metabolic connectivity in the pilocarpine-induced epilepsy rat model and applied a new multiscale framework to the analysis of metabolic networks of small-animal brains. [18F]fluorodeoxyglucose PET was acquired in pilocarpine-induced chronic epilepsy rats and controls to yield interregional metabolic correlation by inter-subject manner. When interregional correlation of epilepsy rats and controls was compared directly, the epilepsy rats showed reduced connectivity involving the left amygdala and left entorhinal cortex. When regional graph properties were calculated to characterize abnormal nodes in the epileptic brain network, the epilepsy rats showed reduced nodal and local efficiencies in the left amygdala. Then, a new multiscale framework, persistent brain network homology, was used to examine metabolic connectivity with a threshold-free approach and the difference between two networks was analyzed using single linkage distances (SLDs) of all pairwise nodes. We found a tendency for longer SLDs between the left insula/left amygdala and bilateral cortical/subcortical structures in the epilepsy rats. Persistent brain network homology analysis as well as interregional correlation study implied the abnormal left limbic–paralimbic–neocortical network in the pilocarpine-induced epilepsy rat models. In conclusion, we found a globally disrupted network in the epileptic brain in rats, particularly in the limbic and paralimbic structures by direct comparison, graph properties and multiscale network analysis. These results demonstrate that the multiscale and threshold-free network analysis can be used to find the network abnormality in small-animal brains as a preclinical research.

Towards a reproducible protocol for repetitive and semi-quantitative rat brain imaging with 18 F-FDG: Exemplified in a memantine pharmacological challenge

The standard uptake value (SUV), commonly used to quantify 18F-FluoroDeoxyGlucose (FDG) uptake in small animal brain PET imaging, is affected by many factors. In this study the influence of fasting times, inter-scan duration and repetitive scanning on the variability of different SUV measures is investigated. Additionally it is demonstrated that these variables could adversely influence the outcome of a pharmacological challenge when not accounted for.Naive Sprague–Dawley rats (n=20) were randomly divided into five different fasting groups (no fasting up to 24h of fasting). SUV brain uptake values were reproducible in naive animals when a fasting period of at least 12h is used and for shorter fasting periods SUV values need to be corrected for the glucose level. Additionally, a separate animal group (n=6) was sufficiently fasted for 16h and in a longitudinal setting being scanned six times in three weeks. Especially with short inter-scan durations, increasing glucose levels were found over time which was attributed to increased stress due to repeated food deprivation, altered food intake or scan manipulations. As a result, even with controlled and sufficient fasting, blood glucose levels should be taken into account for data quantification. Strikingly, even the brain activation effects of an NMDA-antagonist challenge with memantine could not be detected in experiments with a short inter-scan duration if glucose levels were not taken into account.Correcting for glucose levels decreases the inter- and intra-animal variability for rat brain imaging. SUV corrected for glucose levels yields the lowest inter-animal variation. However, if the body weight changes significantly, as in a long experiment, quantification based on the glucose corrected percentage injected dose (and not SUV) is recommendable as this yields the lowest intra-animal variation.

Photoacoustic imaging of brain cortex in rhesus macaques

Functional detection in the brain by photoacoustic (PA) imaging has been an area of interest because of its potential to overcome the limitation of the current available techniques. Both small and large animal brains have been studied by PA imaging. Functional detection in primate brains is particularly of interest because of the similarity between non-human primate brain and human brain and the potential for relevance to a wide range of conditions such as stroke and Parkinson's disease. In this presentation, we show the application of PA imaging technique in detecting functional changes in primary motor cortex of awake rhesus monkeys. Strong increases in PA signal amplitude during forelimb movement indicate an increase in activity in primary motor cortex. The results demonstrate that PA imaging can reliably detect primary motor cortex activation associated with forelimb movement in rhesus macaques. The potentials of PA imaging on clinical human brain imaging will also be discussed.

Manganese-enhanced magnetic resonance imaging investigation of the interferon-α model of depression in rats

Therapeutic effects of interferon-α (IFN-α) are known to be associated with CNS toxicity in humans, and in particular with depression symptoms. Animal models of IFN-α-induced depression (sickness behaviour) have been developed in rodents using various preparations, dosing schedules or routes of administrations. In this work, Manganese Enhanced MRI (MEMRI) has been applied to investigate an experimental model of sickness behaviour induced by administration of IFN-α in rats. IFN-α (3.105 U/kg), or vehicle, was daily administered i.p., for 7days in rats (n=20 IFN-α treated and n=20 controls). After treatment, animals were assigned to behavioural (n=10 treated, n=10 control) or MRI (n=10 treated and n=10 control) studies. Animals assigned to the MRI study received two repeated i.p. injections of MnCl2, before image acquisition. Images were acquired at 4.7T using T1 mapping for determination of Mn concentration in brain. After co-registration of T1 maps to a digital brain atlas, differences between brains of treated and untreated animals were assessed pixel-to-pixel by statistical analysis.Behavioural tests showed alterations in freezing and struggling parameters, as expected in an experimental model of sickness behaviour. MRI showed a well defined brain region, mainly contained in the visual cortex, in which Mn uptake was significantly lower in treated than in control animals, indicating probably altered functionality. No significant difference was detected in other brain regions. In addition, a statistically significant decrease in the volume of the pituitary gland, paralleled by a slight increase in its Mn content, was detected in treated animals. MEMRI provides both morphological and functional information in the brain of small laboratory animals and can constitute a valuable tool in the investigation of experimental models of psychiatric diseases.

Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system--MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was "printed" using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A passing rate of 99% was measured in areas of above 40% of the prescription dose. The final inverse treatment plan was comprised of 43 beams ranging from 5 to 12.5 mm in diameter (2.5 mm size increments are available up to 15 mm in diameter collimation). Using the Xsight Spine Tracking module, the CyberKnife system could not reliably identify and track the tiny mouse spine; however, the CyberKnife system could identify and track the fiducial markers on the 3D mold.In vivo positional accuracy analysis using the 3D mold generated a mean error of 1.41 mm ± 0.73 mm when fiducial markers were used for position tracking. Analysis of the dissected brain confirmed the ability to target the correct brain volume. With the use of a stereotactic body mold with fiducial markers, microCT imaging, and resolution down-sampling, the CyberKnife system can successfully perform small-animal radiotherapy studies.

Optical imaging of phantoms from real data by an approximately globally convergent inverse algorithm

A numerical method for an inverse problem for an elliptic equation with the running source at multiple positions is presented. This algorithm does not rely on a good first guess for the solution. The so-called ‘approximate global convergence’ property of this method is shown here. The performance of the algorithm is verified on real data for Diffusion Optical Tomography. Direct applications are in near-infrared laser imaging technology for stroke detection in brains of small animals.

Multispectral Opto-acoustic Tomography (MSOT) of the Brain and Glioblastoma Characterization

Brain research depends strongly on imaging for assessing function and disease in vivo. We examine herein multispectral opto-acoustic tomography (MSOT), a novel technology for high-resolution molecular imaging deep inside tissues. MSOT illuminates tissue with light pulses at multiple wavelengths and detects the acoustic waves generated by the thermoelastic expansion of the environment surrounding absorbing molecules. Using spectral unmixing analysis of the data collected, MSOT can then differentiate the spectral signatures of oxygenated and deoxygenated hemoglobin and of photo-absorbing agents and quantify their concentration. By being able to detect absorbing molecules up to centimeters deep in the tissue it represents an ideal modality for small animal brain imaging, simultaneously providing anatomical, hemodynamic, functional, and molecular information. In this work we examine the capacity of MSOT in cross-sectional brain imaging of mice. We find unprecedented optical imaging performance in cross-sectional visualization of anatomical and physiological parameters of the mouse brain. For example, the potential of MSOT to characterize ischemic brain areas was demonstrated through the use of a carbon dioxide challenge. In addition, indocyanine green (ICG) was injected intravenously, and the kinetics of uptake and clearance in the vasculature of the brain was visualized in real-time. We further found that multiparameter, multispectral imaging of the growth of U87 tumor cells injected into the brain could be visualized through the intact mouse head, for example through visualization of deoxygenated hemoglobin in the growing tumor. We also demonstrate how MSOT offers several compelling features for brain research and allows time-dependent detection and quantification of brain parameters that are not available using other imaging methods without invasive procedures.

Scanning rats on the high resolution research tomograph (HRRT): A comparison study with a dedicated micro‐PET

The Siemens ECAT high resolution research tomograph (HRRT) is a dedicated human brain PET camera with a 6% absolute sensitivity and a (2.3 mm)(3) spatial resolution, improving to (1.8 mm)(3) when point spread function (PSF) modeling algorithms are used. These values are very close to those of dedicated small animal PET cameras such as the Siemens microPET FOCUS 120 (F120). The larger axial and transaxial field of view of the HRRT compared to the F120 allows, in principle, for simultaneous imaging of several rodents thus potentially reducing scanning costs and time. This study investigates the feasibility of using the HRRT for quantitative small animal brain studies. We compare, in terms of magnitude, reproducibility, and asymmetry, the nondisplaceable tissue input binding potentials (BP(ND)) in the striata obtained from [(11)C]methylphenidate scans of the same rats imaged on both the F120 and the HRRT. The animal studies are complemented by a phantom study aimed at investigating noise properties relevant to the size of typical regions of interest used in rat brain image analysis. (i) The BP(ND) values obtained from HRRT data are lower than those obtained on the F120 by 38% when PSF modeling is not used, while they are 7% higher with PSF modeling. (ii) The within animal reproducibility on the HRRT is 18% without PSF modeling, worse than the 6% reproducibility on the F120, and is even further degraded to a value of 27% with the use of PSF modeling. (iii) The asymmetry between the left and right striatum in healthy rats worsens from 4.7% in the F120 images to 7.8% in the HRRT images reconstructed without PSF modeling, and is even worse with a value of 14.8% when PSF modeling is used. (iv) Overshooting artifacts and clumpiness in the noise structure of the HRRT images reconstructed with PSF modeling are clearly visible. The spatial resolution achieved on the HRRT without the use of resolution recovery techniques is not sufficient to allow for reliable quantitative small animal brain imaging. While PSF modeling in the reconstruction of the HRRT images in principle improves the resolution close to the level of the F120, it also introduces small scale nonuniformity artifacts and overshooting artifacts which preclude reliable quantitative small animal brain imaging on the HRRT.