Roger Fulton

The design and implementation of a motion correction scheme for neurological PET

A method is described to monitor the motion of the head during neurological positron emission tomography (PET) acquisitions and to correct the data post acquisition for the recorded motion prior to image reconstruction. The technique uses an optical tracking system, Polaris, to accurately monitor the position of the head during the PET acquisition. The PET data are acquired in list mode where the events are written directly to disk during acquisition. The motion tracking information is aligned to the PET data using a sequence of pseudo-random numbers, which are inserted into the time tags in the list mode event stream through the gating input interface on the tomograph. The position of the head is monitored during the transmission acquisition, and it is assumed that there is minimal head motion during this measurement. Each event, prompt and delayed, in the list mode event stream is corrected for motion and transformed into the transmission space. For a given line of response, normalization, including corrections for detector efficiency, geometry and crystal interference and dead time are applied prior to motion correction and rebinning in the sinogram. A series of phantom experiments were performed to confirm the accuracy of the method: (a) a point source located in three discrete axial positions in the tomograph field of view, 0 mm, 10 mm and 20 mm from a reference point, (b) a multi-line source phantom rotated in both discrete and gradual rotations through +/- 5 degrees and +/- 15 degrees, including a vertical and horizontal movement in the plane. For both phantom experiments images were reconstructed for both the fixed and motion corrected data. Measurements for resolution, full width at half maximum (FWHM) and full width at tenth maximum (FWTM), were calculated from these images and a comparison made between the fixedand motion corrected datasets. From the point source measurements, the FWHM at each axial position was 7.1 mm in the horizontal direction, and increasing from 4.7 mm at the 0 mm position, to 4.8 mm, 20 mm offset, in the vertical direction. The results from the multi-line source phantom with +/- 5 degrees rotations showed a maximum degradation in FWHM, when compared with the stationary phantom, of 0.6 mm, in the horizontal direction, and 0.3 mm in the vertical direction. The corresponding values for the larger rotation, +/- 15 degrees, were 0.7 mm and 1.1 mm, respectively. The performance of the method was confirmed with a Hoffman brain phantom moved continuously, and a clinical acquisition using [11C]raclopride (normal volunteer). A visual comparison of both the motion and non-motion corrected images of the Hoffman brain phantom clearly demonstrated the efficacy of the method. A sample time-activity curve extracted from the clinical study showed irregularities prior to motion correction, which were removed after correction. A method has been developed to accurately monitor the motion of the head during a neurological PET acquisition, and correct for this motion prior to image reconstruction. The method has been demonstrated to be accurate and does not add significantly to either the acquisition or the subsequent data processing.

Correction for head movements in positron emission tomography using an optical motion tracking system

Methods capable of correcting for head motion in all six degrees of freedom have been proposed for positron emission tomography (PET) brain imaging but not yet demonstrated in human studies. These methods rely on the accurate measurement of head motion in relation to the reconstruction coordinate frame. We present methodology for the direct calibration of an optical motion-tracking system to the reconstruction coordinate frame using paired coordinate measurements obtained simultaneously from a PET scanner and tracking system. We also describe the implementation of motion correction, based on the multiple acquisition frame method originally described by Picard and Thompson (1997), using data provided by the motion tracking system. Effective compensation for multiple six-degree-of-freedom movements is demonstrated in dynamic PET scans of the Hoffman brain phantom and a normal volunteer. We conclude that reduced distortion and improved quantitative accuracy can be achieved with this method in PET brain studies degraded by head movements.

DPA-714, a New Translocator Protein–Specific Ligand: Synthesis, Radiofluorination, and Pharmacologic Characterization

The translocator protein (18 kDa) (TSPO), formerly known as the peripheral benzodiazepine receptor, is dramatically upregulated under pathologic conditions. Activated microglia are the main cell type expressing the TSPO at sites of central nervous system pathology. Radioligands for the TSPO can therefore measure active disease in the brain. This article details the synthesis, radiofluorination, and pharmacologic evaluation of a new TSPO-specific pyrazolopyrimidine, DPA-714. Methods: The affinity of DPA-714 for the TSPO was measured in rat kidney membranes with 3H-PK11195. The in vitro functional activity of DPA-714 was measured in a steroidogenic assay in which the ability of DPA-714 to increase pregnenolone synthesis was measured with rat C6 glioma cells. The radiofluorination of DPA-714 was achieved by nucleophilic 18F-fluoride displacement of the tosylate precursor. 18F-DPA-714 was assessed in rats harboring unilateral quinolinic acid (QA) lesions. In addition, pretreatment experiments were performed with PK11195 (5 mg/kg), DPA-714 (1 mg/kg), and DPA-713 (1 mg/kg). The in vivo binding and biodistribution of 18F-DPA-714 were determined in a baboon with PET. Experiments involving presaturation with PK11195 (1.5 mg/kg) and displacement with DPA-714 (1 mg/kg) were conducted to evaluate the specificity of radioligand binding. Results: In vitro binding studies revealed that DPA-714 displayed a high affinity for the TSPO (dissociation constant, 7.0 nM). DPA-714 stimulated pregnenolone synthesis at levels 80% above the baseline. 18F-DPA-714 was prepared at a 16% radiochemical yield and a specific activity of 270 GBq/μmol. In rats harboring unilateral QA lesions, an 8-fold-higher level of uptake of 18F-DPA-714 was observed in the ipsilateral striatum than in the contralateral striatum. Uptake in the ipsilateral striatum was shown to be selective because it was inhibited to the level in the contralateral striatum in the presence of PK11195, nonlabeled DPA-714, or DPA-713. PET studies demonstrated rapid penetration and good retention of 18F-DPA-714 in the baboon brain. Pretreatment with PK11195 effectively inhibited the uptake of 18F-DPA-714 in the whole brain, indicating its selective binding to the TSPO. The injection of nonlabeled DPA-714 20 min after the injection of 18F-DPA-714 resulted in radioligand washout, demonstrating the reversibility of 18F-DPA-714 binding. Conclusion: 18F-DPA-714 is a specific radioligand for the TSPO, displaying promising in vivo properties and thus warranting further investigation.

Evaluation of two population-based input functions for quantitative neurological FDG PET studies

The conventional measurement of the regional cerebral metabolic rate of glucose (rCMRGlc) with fluorodeoxyglucose (FDG) and positron emission tomography (PET) requires arterial or arterialised-venous (a–v) blood sampling at frequent intervals to obtain the plasma input function (IF). We evaluated the accuracy of rCMRGlc measurements using population-based IFs that were calibrated with two a–v blood samples. Population-based IFs were derived from: (1) the average of a–v IFs from 26 patients (Standard IF) and (2) a published model of FDG plasma concentration (Feng IF). Values for rCMRGlc calculated from the population-based IFs were compared with values obtained with IFs derived from frequent a–v blood sampling in 20 non-diabetic and six diabetic patients. Values for rCMRGlc calculated with the different IFs were highly correlated for both patient groups (r≥0.992) and root mean square residuals about the regression line were less than 0.24 mg/min/100 g. The Feng IF tended to underestimate high rCMRGlc. Both population-based IFs simplify the measurement of rCMRGlc with minimal loss in accuracy and require only two a–v blood samples for calibration. The reduced blood sampling requirements markedly reduce radiation exposure to the blood sampler.

Content-based retrieval of dynamic PET functional images

The recent information explosion has led to a massively increased demand for multimedia data storage in integrated database systems. Content-based retrieval is an important alternative and complement to traditional keyword-based searching for multimedia data and can greatly enhance information management. However, current content-based image retrieval techniques have some deficiencies when applied in the biomedical functional imaging domain. In this paper, we presented a prototype design for a content-based functional image retrieval database system for dynamic positron emission tomography (PET). The system supports efficient content-based retrieval based on physiological kinetic features and reduces image storage requirements. This design makes it possible to maintain a large number of patient data sets online and to rapidly retrieve dynamic functional image sequences for the interpretation and generation of physiological parametric images, and offers potential advantages in medical image data management and telemedicine, as well as providing possible opportunities in the statistical and comparative analysis of functional image data.

Feasibility of stereo-infrared tracking to monitor patient motion during cardiac SPECT imaging

Patient motion during cardiac SPECT imaging can cause diagnostic imaging artifacts. We investigated the feasibility of monitoring patient motion using the Polaris motion-tracking system. This system uses passive infrared reflection from small spheres to provide real-time position data with vendor stated 0.35 mm accuracy and 0.2 mm repeatability. In our configuration, the Polaris system views through the SPECT gantry toward the patients head. List-mode event data were temporally synchronized with motion-tracking data utilizing a modified LabVIEW virtual instrument that we have employed in previous optical motion-tracking investigations. Calibration of SPECT to Polaris coordinates was achieved by determining the transformation matrix necessary to align the position of four reflecting spheres as seen by Polaris, with the location of Tc-99m activity placed inside the sphere mounts as determined in SPECT reconstructions. We have successfully tracked targets placed on volunteers in simulated imaging positions on the table of our SPECT system. We obtained excellent correlation (R/sup 2/>0.998) between the change in location of the targets as measured by our SPECT system and the Polaris. We have also obtained excellent agreement between the recordings of the respiratory motion of four targets attached to an elastic band wrapped around the abdomen of volunteers and from a pneumatic bellows. We used the axial motion of point sources as determined by the Polaris to correct the motion in SPECT image acquisitions yielding virtually identical point source full-width at half-maximum and full-width at tenth-maximum values, and profiled maximum heart wall counts of cardiac phantom images, compared to the reconstructions with no motion.

A practical 3D tomographic method for correcting patient head motion in clinical SPECT

Patient motion during brain SPECT studies can degrade resolution and introduce distortion. The authors have developed a correction method which incorporates a motion tracking system to monitor the position and orientation of the patients head during acquisition. Correction is achieved by spatially repositioning projections according to measured head movements and reconstructing these projections with a fully three-dimensional (3D) algorithm. The method has been evaluated in SPECT studies of the Hoffman 3D brain phantom performed on a triple head camera with fan beam collimation. Movements were applied to the phantom and recorded by a head tracker during SPECT acquisition. Fully 3D reconstruction was performed using the motion data provided by the tracker. Correction accuracy was assessed by comparing the corrected and uncorrected studies with a motion free study, visually and by calculating mean squared error (MSE). In all studies, motion correction reduced distortion and improved MSE by a factor of 2 or more. It is concluded that this method can compensate for head motion under clinical SPECT imaging conditions.

Real-time 3D motion tracking for small animal brain PET.

High-resolution positron emission tomography (PET) imaging of conscious, unrestrained laboratory animals presents many challenges. Some form of motion correction will normally be necessary to avoid motion artefacts in the reconstruction. The aim of the current work was to develop and evaluate a motion tracking system potentially suitable for use in small animal PET. This system is based on the commercially available stereo-optical MicronTracker S60 which we have integrated with a Siemens Focus-220 microPET scanner. We present measured performance limits of the tracker and the technical details of our implementation, including calibration and synchronization of the system. A phantom study demonstrating motion tracking and correction was also performed. The system can be calibrated with sub-millimetre accuracy, and small lightweight markers can be constructed to provide accurate 3D motion data. A marked reduction in motion artefacts was demonstrated in the phantom study. The techniques and results described here represent a step towards a practical method for rigid-body motion correction in small animal PET. There is scope to achieve further improvements in the accuracy of synchronization and pose measurements in future work.

A hybrid 3-D reconstruction/registration algorithm for correction of head motion in emission tomography

Even with head restraint, small head movements can occur during data acquisition in emission tomography that are sufficiently large to result in detectable artifacts in the final reconstruction. Direct measurement of motion can be cumbersome and difficult to implement, whereas previous attempts to use the measured projection data for correction have been limited to simple translation orthogonal to the projection. A fully three-dimensional (3-D) algorithm is proposed that estimates the patient orientation based on the projection of motion-corrupted data, with incorporation of motion information within subsequent ordered-subset expectation-maximization subiterations. Preliminary studies have been performed using a digital version of the Hoffman brain phantom. Movement was simulated by constructing a mixed set of projections in discrete positions of the phantom. The algorithm determined the phantom orientation that best matched each constructed projection with its corresponding measured projection. In the case of a simulated single movement in 24 of 64 projections, all misaligned projections were correctly identified. Incorporating data at the determined object orientation resulted in a reduction of mean square difference (MSD) between motion-corrected and motion-free reconstructions, compared to the MSD between uncorrected and motion-free reconstructions, by a factor of 1.9.

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.