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

The 18 kDa Translocator Protein (Peripheral Benzodiazepine Receptor) Expression in the Bone of Normal, Osteoprotegerin or Low Calcium Diet Treated Mice

The presence of the translocator protein (TSPO), previously named as the mitochondrial or peripheral benzodiazepine receptor, in bone cells was studied in vitro and in situ using RT-qPCR, and receptor autoradiography using the selective TSPO ligand PK11195

Pompe disease diagnosis and management guideline

ACMG standards and guidelines are designed primarily as an educational resource for physicians and other health care providers to help them provide quality medical genetic services. Adherence to these standards and guidelines does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. in determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from these standards and guidelines.Duke Univ, Med Ctr, Durham, NC 27706 USAOregon Hlth Sci Univ, Portland, OR 97201 USANYU, Sch Med, New York, NY USAUniv Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32611 USAIndiana Univ, Bloomington, in 47405 USAUniv Miami, Miller Sch Med, Coral Gables, FL 33124 USAHarvard Univ, Childrens Hosp, Sch Med, Cambridge, MA 02138 USAUniversidade Federal de São Paulo, São Paulo, BrazilColumbia Univ, New York, NY 10027 USANYU, Bellevue Hosp, Sch Med, New York, NY USAColumbia Univ, Med Ctr, New York, NY 10027 USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Ligands for peripheral benzodiazepine binding sites in glial cells

Within the diseased brain, glial cells and in particular, microglia, express a multimeric protein complex termed bperipheral benzodiazepine binding sites (PBBS)Q or bperipheral benzodiazepine receptor (PBR)Q. The expression of the PBBS is dependent on the functional state of the cell and in glial cells is triggered by a wide range of activating stimuli. In the healthy brain, the PBBS are nearly absent with the notable exception of the choroid plexus, ependymal layer, perivascular cells, central canal, possibly certain nuclei in the brainstem and layers in the cerebellum where a constitutive presence of the PBBS is found. Likewise, areas that due to the absence of the blood-brain barrier contain more active glial cells, such as the pituitary gland, or the area postrema at floor of the 4th ventricle show a degree of constitutive expression. The tight correlation of the parenchymal de novo expression of the PBBS with the presence of activated glial cells, that in turn are usually only found in tissue affected by progressive disease, establishes the PBBS as a generic marker for the detection and measurement of active disease processes in the brain. Specific radioligands of the PBBS for use in positron emission tomography (PET) may thus provide a sensitive in vivo index of neuropathological activity. Whilst prototype ligands for the PBBS are available, future research needs to focus on the development of new ligands with improved pharmacodynamic properties and the ability to discriminate between the different, still insufficiently understood functional states of the peripheral benzodiazepine receptor complex

Markerless motion estimation for motion-compensated clinical brain imaging

Motion-compensated brain imaging can dramatically reduce the artifacts and quantitative degradation associated with voluntary and involuntary subject head motion during positron emission tomography (PET), single photon emission computed tomography (SPECT) and computed tomography (CT). However, motion-compensated imaging protocols are not in widespread clinical use for these modalities. A key reason for this seems to be the lack of a practical motion tracking technology that allows for smooth and reliable integration of motion-compensated imaging protocols in the clinical setting. We seek to address this problem by investigating the feasibility of a highly versatile optical motion tracking method for PET, SPECT and CT geometries. The method requires no attached markers, relying exclusively on the detection and matching of distinctive facial features. We studied the accuracy of this method in 16 volunteers in a mock imaging scenario by comparing the estimated motion with an accurate marker-based method used in applications such as image guided surgery. A range of techniques to optimize performance of the method were also studied. Our results show that the markerless motion tracking method is highly accurate (<2 mm discrepancy against a benchmarking system) on an ethnically diverse range of subjects and, moreover, exhibits lower jitter and estimation of motion over a greater range than some marker-based methods. Our optimization tests indicate that the basic pose estimation algorithm is very robust but generally benefits from rudimentary background masking. Further marginal gains in accuracy can be achieved by accounting for non-rigid motion of features. Efficiency gains can be achieved by capping the number of features used for pose estimation provided that these features adequately sample the range of head motion encountered in the study. These proof-of-principle data suggest that markerless motion tracking is amenable to motion-compensated brain imaging and holds good promise for a practical implementation in clinical PET, SPECT and CT systems

A normalization scheme for LOR-based motion correction in PET

Line of response (LOR) rebinning has been demonstrated to be an effective motion correction method for positron emission tomography (PET) imaging. In LOR rebinning, normalization of each motion-corrected event is needed before it is placed into its new sinogram bin. In general, due to data compression strategies the sinogram bincorresponding to the transformed LOR will receive contributionsfrom multiple LORs. This paper demonstrates that normalization of the corrected event must account for the relative change in its contribution to the corresponding sinogram bins before and after transformation. Failure to account for this factor may cause slice-to-slice count variations of transverse slices and visible horizontal stripe artifacts in the coronal and sagittal slices of the reconstructed images

An optical tracking system for motion correction in small animal PET

Imaging conscious animals in small animal positron emission tomography (PET) presents a significant challenge, and some form of motion compensation will normally be necessary. In this work, a commercial optical motion tracker called the Micron Tracker has been adapted to the microPET system for this purpose. We evaluated marker size limits, performed a spatial calibration for the devices, developed a synchronization method, and carried out a phantom study involving multiple, discrete 3D movements to test key components of the motion tracking system. We have demonstrated that small and lightweight markers (approx. 15mm x 18mm) are feasible with this system for 3D motion tracking, Calibration accuracy was 0.46mm RMS.Synchronization of the data streams was achieved with a precision of approximately 20ms. Moreover, a marked reduction in motion artifacts was demonstrated in the phantom study. The techniques and results presented here demonstrate the feasibility of adapting the Micron Tracker to the microPET environment for motion tracking of small laboratory animals. There is scope to improve on limitations in synchronization and further optimize marker design to achieve better pose accuracy and precision

Refraction-compensated motion tracking of unrestrained animals in PET

Stereo optical motion tracking has been shown to be a feasible and accurate way of measuring head pose in PET studies of minimally-restrained awake animals. It may be convenient and/or necessary to contain the animal within a transparent enclosure to perform such studies. However, the presence of transparent interfaces introduces refraction error in the motion tracking. Here, we extend previous work looking at the refraction error in individual target points to error in ensembles of target points representing a rigid marker for pose estimation. We used our previously validated simulation technique to look at the effect of refraction on absolute and relative pose measurements as a function of the marker size. We show that for sufficiently small markers ( 50 mm) the error in absolute pose is a shift equivalent to the triangulation error. For movements (relative pose measurements) the error depends on the shift in each pose. By simulating refraction effects in real rat head tracking data and using these data for motion correction, we demonstrate quantitative errors of 10% in a motion-corrected image. In situations with more severe refraction conditions, the necessity to correct pose errors is likely to be greater.4 page(s