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

Staphylococcus aureus Panton-Valentine Leukocidin Contributes to Inflammation and Muscle Tissue Injury

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) threatens public health worldwide, and epidemiologic data suggest that the Panton-Valentine Leukocidin (PVL) expressed by most CA-MRSA strains could contribute to severe human infections, particularly in young and immunocompetent hosts. PVL is proposed to induce cytolysis or apoptosis of phagocytes. However, recent comparisons of isogenic CA-MRSA strains with or without PVL have revealed no differences in human PMN cytolytic activity. Furthermore, many of the mouse studies performed to date have failed to demonstrate a virulence role for PVL, thereby provoking the question: does PVL have a mechanistic role in human infection? In this report, we evaluated the contribution of PVL to severe skin and soft tissue infection. We generated PVL mutants in CA-MRSA strains isolated from patients with necrotizing fasciitis and used these tools to evaluate the pathogenic role of PVL in vivo. In a model of necrotizing soft tissue infection, we found PVL caused significant damage of muscle but not the skin. Muscle injury was linked to induction of pro-inflammatory chemokines KC, MIP-2, and RANTES, and recruitment of neutrophils. Tissue damage was most prominent in young mice and in those strains of mice that more effectively cleared S. aureus, and was not significant in older mice and mouse strains that had a more limited immune response to the pathogen. PVL mediated injury could be blocked by pretreatment with anti-PVL antibodies. Our data provide new insights into CA-MRSA pathogenesis, epidemiology and therapeutics. PVL could contribute to the increased incidence of myositis in CA-MRSA infection, and the toxin could mediate tissue injury by mechanisms other than direct killing of phagocytes

Experimental evaluation of the dosimetric impact of intrafraction prostate rotation using film measurement with a 6DoF robotic arm.

PurposeTumor motion during radiotherapy can cause a reduction in target dose coverage and an increase in healthy tissue exposure. Tumor motion is not strictly translational and often exhibits complex six degree-of-freedom (6DoF) translational and rotational motion. Although the dosimetric impact of prostate tumor translational motion is well investigated, the dosimetric impact of 6DoF motion has only been studied with simulations or dose reconstruction. This study aims to experimentally quantify the dose error caused by 6DoF motion. The experiment was designed to test the hypothesis that 6DoF motion would cause larger dose errors than translational motion alone through gamma analyses of two-dimensional film measurements.MethodsFour patient-measured intrafraction prostate motion traces and four VMAT 7.25 Gy/Fx SBRT treatment plans were selected for the experiment. The traces represented typical motion patterns, including small-angle rotations (6°). Gafchromic film was placed inside a custom-designed phantom, held by a high-precision 6DoF robotic arm for dose measurements in the coronal plane during treatment delivery. For each combination of the motion trace and treatment plan, two film measurements were made, one with 6DoF motion and the other with the three-dimensional (3D) translation components of the same trace. A gamma pass rate criteria of 2% relative dose/2 mm distance-to-agreement was used in this study and evaluated for each measurement with respect to the static reference film. Two test thresholds, 90% and 50% of the reference dose, were applied to investigate the difference in dose coverage for the PTV region and surrounding areas, respectively. The hypothesis was tested using a Wilcoxon signed-rank test.ResultsFor each of the 16 plan and motion trace pairs, a reduction in the gamma pass rate was observed for 6DoF motion compared with 3D translational motion. With 90% gamma-test threshold, the reduction was 5.8% ± 7.1% (P ConclusionFor the first time, the dosimetric impact of intrafraction prostate rotation during SBRT treatment was measured experimentally. The experimental results support the hypothesis that 6DoF tumor motion causes higher dose error than translation motion alone

Characterization of the Intel RealSense D415 Stereo Depth Camera for Motion-Corrected CT Imaging

A combination of non-contrast CT (NCCT) and CT Perfusion (CTP) imaging is the most common regime for evaluation of acute ischemic stroke patients. CTP-based image analysis is known to be compromised by patient head motion. However, there is currently no technique to compensate for intra-frame head motion during CTP acquisition. In this work, we investigated the feasibility of using the small form factor Intel RealSense D415 stereo depth camera to obtain accurate head pose estimates for intra-frame motion correction in CTP. First, we quantitatively evaluated head movement in a cohort of 72 acute stroke cases. Then we characterized the performance of the Intel D415 against ground-truth robotic motion and the clinically validated OptiTrack marker-based motion tracking system. The results showed that head motion during CTP imaging of acute stroke of patients is extremely common, with around 50% of patients moving > 5 mm and 1 deg and around 20% moving 10-100 mm and rotating 3-20 deg. The pose accuracy of the Intel for controlled robotic motion was approximately 5 mm and 2 deg. For translations and rotations, respectively. For human head motion using the OptiTrack as ground truth, the accuracy was approximately 4 mm (except for lateral motion) and 1.25 deg, respectively. Although poorer than what is needed clinically, there is a lot of potential to optimize performance and potentially achieve an accuracy consistently around 1 mm and 1 deg

Rigid motion correction of dual opposed planar projections in single photon imaging

International audienceAwake and/or freely moving small animal single photon emission imaging allows the continuous study of molecules exhibiting slow kinetics without the need to restrain or anaesthetise the animals. Estimating motion free projections in freely moving small animal planar imaging can be considered as a limited angle tomography problem, except that we wish to estimate the 2D planar projections rather than the 3D volume, where the angular sampling in all three axes depends on the rotational motion of the animal. In this study, we hypothesise that the motion corrected planar projections estimated by reconstructing an estimate of the 3D volume using an iterative motion compensating reconstruction algorithm and integrating it along the projection path, will closely match the true, motion-less, planar distribution regardless of the object motion. We tested this hypothesis for the case of rigid motion using Monte-Carlo simulations and experimental phantom data based on a dual opposed detector system, where object motion was modelled with 6 degrees of freedom. In addition, we investigated the quantitative accuracy of the regional activity extracted from the geometric mean of opposing motion corrected planar projections. Results showed that it is feasible to estimate qualitatively accurate motion-corrected projections for a wide range of motions around all 3 axes. Errors in the geometric mean estimates of regional activity were relatively small and within 10% of expected true values. In addition, quantitative regional errors were dependent on the observed motion, as well as on the surrounding activity of overlapping organs. We conclude that both qualitatively and quantitatively accurate motion-free projections of the tracer distribution in a rigidly moving object can be estimated from dual opposed detectors using a correction approach within an iterative reconstruction framework and we expect this approach can be extended to the case of non-rigid motion

Immunocytochemical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy

The protein product of the bcl-2 gene is thought to be involved in inhibition of apoptosis; it may therefore be important in the modulation of hormonal/anti-hormonal responsiveness exhibited by tumours. This study immunocytochemically investigates (i) relationships between bcl-2 protein expression in primary breast cancers and other markers of prognostic and therapeutic value and (ii) associations of the bcl-2 protein with breast cancer responsiveness to endocrine therapy. The bcl-2 protein was found within the tumour epithelial cell cytoplasm of 32/46 breast cancer specimens; inter-patient staining was heterogeneous. Immunostaining for steroid hormone receptors was strongly associated with that for the bcl-2 protein, and it is thus possible that this protein, like progesterone receptor, is under oestrogen regulation via oestrogen receptor. The protein was inversely related to 2 markers of endocrine insensitivity, epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein, while no associations were observed with either transforming growth factor (TGF)-alpha or Ki-67 proliferative status. A highly significant relationship was observed between response to endocrine therapy and the presence of bcl-2 protein. Indeed, bcl-2 immunostaining proved to be a more accurate predictor of response than oestrogen receptor status. Patients with elevated bcl-2 immunostaining (particularly those who co-expressed high oestrogen receptor levels) appeared to derive the greatest benefit from endocrine therapy. Our results are paradoxical since it was expected that the bcl-2 protein would counteract the tumour inhibitory effects of endocrine therapies as it is thought to prevent programmed cell death