Open-field PET: Simultaneous brain functional imaging and behavioural response measurements in freely moving small animals.

A comprehensive understanding of how the brain responds to a changing environment requires techniques capable of recording functional outputs at the whole-brain level in response to external stimuli. Positron emission tomography (PET) is an exquisitely sensitive technique for imaging brain function but the need for anaesthesia to avoid motion artefacts precludes concurrent behavioural response studies. Here, we report a technique that combines motion-compensated PET with a robotically-controlled animal enclosure to enable simultaneous brain imaging and behavioural recordings in unrestrained small animals. The technique was used to measure in vivo displacement of [11C]raclopride from dopamine D2 receptors (D2R) concurrently with changes in the behaviour of awake, freely moving rats following administration of unlabelled raclopride or amphetamine. The timing and magnitude of [11C]raclopride displacement from D2R were reliably estimated and, in the case of amphetamine, these changes coincided with a marked increase in stereotyped behaviours and hyper-locomotion. The technique, therefore, allows simultaneous measurement of changes in brain function and behavioural responses to external stimuli in conscious unrestrained animals, giving rise to important applications in behavioural neuroscience.

A scheme for PET data normalization in event-based motion correction.

Line of response (LOR) rebinning is an event-based motion-correction technique for positron emission tomography (PET) imaging that has been shown to compensate effectively for rigid motion. It involves the spatial transformation of LORs to compensate for motion during the scan, as measured by a motion tracking system. Each motion-corrected event is then recorded in the sinogram bin corresponding to the transformed LOR. It has been shown previously that the corrected event must be normalized using a normalization factor derived from the original LOR, that is, based on the pair of detectors involved in the original coincidence event. In general, due to data compression strategies (mashing), sinogram bins record events detected on multiple LORs. The number of LORs associated with a sinogram bin determines the relative contribution of each LOR. This paper provides a thorough treatment of event-based normalization during motion correction of PET data using LOR rebinning. We demonstrate theoretically and experimentally that normalization of the corrected event during LOR rebinning should account for the number of LORs contributing to the sinogram bin into which the motion-corrected event is binned. Failure to account for this factor may cause artifactual slice-to-slice count variations in the transverse slices and visible horizontal stripe artifacts in the coronal and sagittal slices of the reconstructed images. The theory and implementation of normalization in conjunction with the LOR rebinning technique is described in detail, and experimental verification of the proposed normalization method in phantom studies is presented.

An event-driven motion correction method for neurological PET studies of awake laboratory animals.

PURPOSE: The purpose of the study is to investigate the feasibility of an event driven motion correction method for neurological microPET imaging of small laboratory animals in the fully awake state. PROCEDURES: A motion tracking technique was developed using an optical motion tracking system and light (<1g) printed targets. This was interfaced to a microPET scanner. Recorded spatial transformations were applied in software to list mode events to create a motion-corrected sinogram. Motion correction was evaluated in microPET studies, in which a conscious animal was simulated by a phantom that was moved during data acquisition. RESULTS: The motion-affected scan was severely distorted compared with a reference scan of the stationary phantom. Motion correction yielded a nearly distortion-free reconstruction and a marked reduction in mean squared error. CONCLUSIONS: This work is an important step towards motion tracking and motion correction in neurological studies of awake animals in the small animal PET imaging environment.

An investigation of the challenges in reconstructing PET images of a freely moving animal.

Imaging the brain of a freely moving small animal using positron emission tomography (PET) while simultaneously observing its behaviour is an important goal for neuroscience. While we have successfully demonstrated the use of line-of-response (LOR) rebinning to correct the head motion of confined animals, a large proportion of events may need to be discarded because they either 'miss' the detector array after transformation or fall out of the acceptance range of a sinogram. The proportion of events that would have been measured had motion not occurred, so-called 'lost events', is expected to be even larger for freely moving animals. Moreover, the data acquisition in the case of a freely moving animal is further complicated by a complex attenuation field. The aims of this study were (a) to characterise the severity of the 'lostevents' problem for the freely moving animal scenario, and(b) to investigate the relative impact of attenuation correction errors on quantitative accuracy of reconstructed images. A phantom study was performed to simulate the uncorrelated motion of a target and non-target sourcevolume. A small animal PET scanner was used to acquirelist-mode data for different sets of phantom positions. The list-mode data were processed using the standard LOR rebinning approach, and multiple frame variants of this designed to reduce discarded events. We found that LOR rebinning caused up to 86 % 'lost events', and artifacts that we attribute to incomplete projections, when applied to a freely moving target. This fraction was reduced by up to 18 % using the variant approaches, resulting in slightly reduced image artifacts. The effect of the non-target compartment on attenuation correction of the target volume was surprisingly small. However, for certain poses where the target and non-target volumes are aligned transaxially in the field-of-view, the attenuation problem becomes more complex and sophisticated correction methods will be required. We conclude that there are limitations with the LOR rebinning approach and simplified attenuation correction for freely moving animals requiring the development and validation of more sophisticated approaches.

Event-based motion correction for PET transmission measurements with a rotating point source.

Accurate attenuation correction is important for quantitative positron emission tomography (PET) studies. When performing transmission measurements using an external rotating radioactive source, object motion during the transmission scan can distort the attenuation correction factors computed as the ratio of the blank to transmission counts, and cause errors and artefacts in reconstructed PET images. In this paper we report a compensation method for rigid body motion during PET transmission measurements, in which list mode transmission data are motion corrected event-by-event, based on known motion, to ensure that all events which traverse the same path through the object are recorded on a common line of response (LOR). As a result, the motion-corrected transmission LOR may record a combination of events originally detected on different LORs. To ensure that the corresponding blank LOR records events from the same combination of contributing LORs, the list mode blank data are spatially transformed event-by-event based on the same motion information. The number of counts recorded on the resulting blank LOR is then equivalent to the number of counts that would have been recorded on the corresponding motion-corrected transmission LOR in the absence of any attenuating object. The proposed method has been verified in phantom studies with both stepwise movements and continuous motion. We found that attenuation maps derived from motion-corrected transmission and blank data agree well with those of the stationary phantom and are significantly better than uncorrected attenuation data.

Optimised motion tracking for positron emission tomography studies of brain function in awake rats.

Positron emission tomography (PET) is a non-invasive molecular imaging technique using positron-emitting radioisotopes to study functional processes within the body. High resolution PET scanners designed for imaging rodents and non-human primates are now commonplace in preclinical research. Brain imaging in this context, with motion compensation, can potentially enhance the usefulness of PET by avoiding confounds due to anaesthetic drugs and enabling freely moving animals to be imaged during normal and evoked behaviours. Due to the frequent and rapid motion exhibited by alert, awake animals, optimal motion correction requires frequently sampled pose information and precise synchronisation of these data with events in the PET coincidence data stream. Motion measurements should also be as accurate as possible to avoid degrading the excellent spatial resolution provided by state-of-the-art scanners. Here we describe and validate methods for optimised motion tracking suited to the correction of motion in awake rats. A hardware based synchronisation approach is used to achieve temporal alignment of tracker and scanner data to within 10 ms. We explored the impact of motion tracker synchronisation error, pose sampling rate, rate of motion, and marker size on motion correction accuracy. With accurate synchronisation (<100 ms error), a sampling rate of >20 Hz, and a small head marker suitable for awake animal studies, excellent motion correction results were obtained in phantom studies with a variety of continuous motion patterns, including realistic rat motion (<5% bias in mean concentration). Feasibility of the approach was also demonstrated in an awake rat study. We conclude that motion tracking parameters needed for effective motion correction in preclinical brain imaging of awake rats are achievable in the laboratory setting. This could broaden the scope of animal experiments currently possible with PET.