Lefteris Livieratos

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.

Rigid-body transformation of list-mode projection data for respiratory motion correction in cardiac PET

Respiratory motion is a source of artefacts and quantification errors in cardiac imaging. Preliminary studies with retrospective respiratory gating in PET support the observation of other imaging modalities of a rigid-body motion of the heart during respiration. However, the use of gating techniques to eliminate motion may result in poor count statistics per reconstructed image. We have implemented a motion correction technique which applies rigid-body transformations on list-mode data event-by-event on the basis of a geometric model of intersection of the lines-of-response with the scanner. Pre-correction for detector efficiencies and photon attenuation before transformation are included in the process. Projection data are acquired together with physiological signal (every ms) from an inductive respiration monitor with an elasticised belt at chest level. Data are retrospectively sorted into separate respiratory gates on an off-line workstation. Transformation parameters relating the gated images, estimated by means of image registration, can be applied on the original list-mode data to obtain a single motion-corrected dataset. The accuracy of the technique was assessed with point source data and a good correlation between applied and measured transformations, estimated from the centroid of the source, was observed. The technique was applied on phantom data with simulated respiratory motion and on patient data with C/sup 15/O and /sup 18/FDG. Quantitative assessment of preliminary C/sup 15/O patient datasets showed at least 4.5% improvement in the recovery coefficient at the centre of the left ventricle.

Parametric image reconstruction using spectral analysis of PET projection data

Spectral analysis is a general modelling approach that enables calculation of parametric images from reconstructed tracer kinetic data independent of an assumed compartmental structure. We investigated the validity of applying spectral analysis directly to projection data motivated by the advantages that: (i) the number of reconstructions is reduced by an order of magnitude and (ii) iterative reconstruction becomes practical which may improve signal-to-noise ratio (SNR). A dynamic software phantom with typical 2-[11C]thymidine kinetics was used to compare projection-based and image-based methods and to assess bias-variance trade-offs using iterative expectation maximization (EM) reconstruction. We found that the two approaches are not exactly equivalent due to properties of the non-negative least-squares algorithm. However, the differences are small (< 5%) and mainly affect parameters related to early and late time points on the impulse response function (K1 and, to a lesser extent, VD). The optimal number of EM iteration was 15-30 with up to a two-fold improvement in SNR over filtered back projection. We conclude that projection-based spectral analysis with EM reconstruction yields accurate parametric images with high SNR and has potential application to a wide range of positron emission tomography ligands.

Experience with fully 3D PET and implications for future high-resolution 3D tomographs

The aim of this paper is to report on experience with 3D positron emission tomography (PET) in our institute where we have three 3D scanners, of which two operate exclusively in 3D mode (ECAT ART, EXACT 3D). Fully 3D PET requires attention to a number of factors which are not as problematic in 2D PET. Firstly, 3D tomographs designed for whole-body acquisition suffer from a large single-photon field of view, extending well beyond the coincidence field of view. Single photons from outside the coincidence field of view increase the dead time and random coincidence rates, and contribute scattered events. For brain studies, we have extended the lead side shielding at the ends of the tomograph to mitigate against these effects, and this has dramatically improved the count rate performance. This approach is not as effective for whole-body scanning. In addition, operating in 3D without septa necessitates new approaches to transmission scanning, as measurements using positron emitters such as 68Ge/68Ga have the unfavourable characteristics of high dead time and high scatter. Both of our fully 3D scanners use 137Cs for single-photon transmission measurements, although the data are treated differently. On the ECAT ART, a combination of physical and electronic collimation effectively reduces transmission scatter to acceptable levels. On the EXACT 3D physical collimation is not as readily implemented and therefore segmentation and reassignment of the histogrammed attenuation (mu) values is employed to produce unbiased attenuation correction factors in 3D. Many of the lessons learnt with these BGO (bismuth germanate) based tomographs will be applicable to the next generation of systems using faster detectors such as lutetium oxyorthosilicate (LSO).

Real-time differential tracking of human neutrophil and eosinophil migration in vivo

BACKGROUND Hitherto, in vivo studies of human granulocyte migration have been based on indiscriminate labeling of total granulocyte populations. We hypothesized that the kinetics of isolated human neutrophil and eosinophil migration through major organs in vivo are fundamentally different, with the corollary that studying unseparated populations distorts measurement of both. METHODS Blood neutrophils and eosinophils were isolated on 2 separate occasions from human volunteers by using Current Good Manufacturing Practice CD16 CliniMACS isolation, labeled with technetium 99m-hexamethylpropyleneamine oxime, and then reinfused intravenously. The kinetics of cellular efflux were imaged over 4 hours. RESULTS Neutrophils and eosinophils were isolated to a mean purity of greater than 97% and greater than 95%, respectively. Activation of neutrophils measured as an increase in their CD11b mean fluorescence intensity in whole blood and after isolation and radiolabeling was 25.98 ± 7.59 and 51.82 ± 17.44, respectively, and was not significant (P = .052), but the mean fluorescence intensity of CD69 increased significantly on eosinophils. Analysis of the scintigraphic profile of lung efflux revealed exponential clearance of eosinophils, with a mean half-life of 4.16 ± 0.11 minutes. Neutrophil efflux was at a significantly slower half-life of 13.72 ± 4.14 minutes (P = .009). The migration of neutrophils and eosinophils was significantly different in the spleen at all time points (P = .014), in the liver at 15 minutes (P = .001), and in the bone marrow at 4 hours (P = .003). CONCLUSIONS The kinetics of migration of neutrophils and eosinophils through the lung, spleen, and bone marrow of human volunteers are significantly different. Study of mixed populations might be misleading.

Investigation of the scatter contribution in single photon transmission measurements by means of Monte Carlo simulations

The fraction of detected scattered radiation in transmission measurements with a single photon transmission (SPT) source of Cesium-137 was investigated by means of Monte Carlo (MC) techniques. The scatter contamination was determined for different energy thresholds and the use of interplane septa. The simulations were validated with measurements performed at the whole-body 3D PET scanner ECAT EXACT 3D (CTI/Siemens, Knoxville, TN), which uses a SPT source. The comparison of the results from the simulations and the measurements shows good agreement. Transmission through a water-filled cylinder (o=20 cm) gave values of the scatter fraction SF of about 27% at a lower level discriminator (LLD) value of 500 keV in the center of the projection. A reduction to 17% was achieved by an increase of the LLD to 600 keV; a relative decrease of 37%. But a corresponding loss of counts by a factor of 1.5 was observed. Furthermore, simulations of the ECAT EXACT HR/sup +/ have been performed, a whale-body PET scanner which can be operated in 2D and 3D mode, but has no SPT mode yet. At a value of the LLD of 500 keV, the simulations showed a decrease of the SF in the 2D mode of 45% relative to the 3D mode for the transmission of the water-filled cylinder.

Exploiting the Metal-Chelating Properties of the Drug Cargo for In Vivo Positron Emission Tomography Imaging of Liposomal Nanomedicines

The clinical value of current and future nanomedicines can be improved by introducing patient selection strategies based on noninvasive sensitive whole-body imaging techniques such as positron emission tomography (PET). Thus, a broad method to radiolabel and track preformed nanomedicines such as liposomal drugs with PET radionuclides will have a wide impact in nanomedicine. Here, we introduce a simple and efficient PET radiolabeling method that exploits the metal-chelating properties of certain drugs (e.g., bisphosphonates such as alendronate and anthracyclines such as doxorubicin) and widely used ionophores to achieve excellent radiolabeling yields, purities, and stabilities with 89Zr, 52Mn, and 64Cu, and without the requirement of modification of the nanomedicine components. In a model of metastatic breast cancer, we demonstrate that this technique allows quantification of the biodistribution of a radiolabeled stealth liposomal nanomedicine containing alendronate that shows high uptake in primary tumors and metastatic organs. The versatility, efficiency, simplicity, and GMP compatibility of this method may enable submicrodosing imaging studies of liposomal nanomedicines containing chelating drugs in humans and may have clinical impact by facilitating the introduction of image-guided therapeutic strategies in current and future nanomedicine clinical studies.

Diagnosis of prosthetic aortic valve endocarditis with gallium-67 citrate single-photon emission computed tomography/computed tomography hybrid imaging using software registration.

Prosthetic valve endocarditis can be challenging to diagnose and is associated with high mortality rates even if recognized and managed early. We present a case of staphylococcal sepsis soon after aortic valve surgery and permanent pacemaker implantation for which conventional investigation with echocardiography and computed tomography (CT) failed to identify an infective focus. Subsequent gallium–single-photon emission CT (67Ga-SPECT) imaging with software registration of the SPECT data helped to correctly identify the prosthetic aortic value as the source of sepsis, with resolution of changes on subsequent imaging. A 70-year-old woman underwent bioprosthetic aortic valve replacement and coronary artery bypass grafting for symptomatic severe aortic stenosis and significant 2-vessel coronary disease. Her postoperative course was complicated by significant bradycardia necessitating dual-chamber permanent pacemaker implantation. She presented 3 months after surgery in a confused state, with low-grade pyrexia. The examination identified a soft systolic aortic murmur but no diastolic component, normal breath sounds, absence of cutaneous markers of endocarditis, and no evidence of …

Strategies for accurate attenuation correction with single photon transmission measurements in 3D PET

3D PET systems benefit from using single photon sources for transmission measurements as this reduces dead time and improves the photon flux, and therefore the signal-to-noise ratio, in the attenuation (CL) correction data. However, uncollimated point source measurements will include a large (/spl sim/50%) scatter component which biases the /spl mu/ values. No single approach will necessarily be able to mitigate against this for different scanning scenarios. The authors have investigated five approaches to scatter removal and/or correction using a /sup 137/Cs source for transmission data: (i) rescaling the measured data, (ii) energy window methods, (iii) restricting the polar acceptance angle (/spl theta/), (iv) collimating the source (ECAT ART only), and (v) segmentation and reassignment with expected /spl mu/ values. The results indicate that physical collimation of the ECAT ART point source and segmentation on the fixed ring EXACT 3D produce quantitatively useful data.

Comparison of 10 versus 20 min SPECT 99mTc-MDP bone scans: use of 3D-OSEM image reconstruction with distance-dependent resolution modelling.

BackgroundIterative reconstruction with system response modelling has been implemented in commercial software by manufacturers for distance-dependent resolution modelling (DRM) of the collimator physical effects. Initial experience with such algorithms also shows improvements in noise characteristics with lower dependency on counting statistics. In this study the performance of one such algorithm, the Philips Astonish, was assessed for bone single-photon emission computed tomography (SPECT) acquired at count levels reduced by half on technetium-99m methylene diphosphonate scans. MethodsFor every SPECT scan, two sets of images were generated with the aid of concurrent data acquisition: (i) a conventional scan used routinely for reporting at 20 s per projection reconstructed with filtered back-projection (FBP20 s) and (ii) a scan at 10 s per projection reconstructed with Astonish (DRM10 s). Phantom and pilot patient data were used to initially establish optimal reconstruction parameters. Subsequently, patient studies (n=28) were scored independently by two experienced observers (blinded to reconstruction method or acquisition time) for image quality based on a scale of 1–5. Observers were also asked to report the number of observed lesions in each scan. ResultsResults show that scores were better or equivalent for the vast majority of DRM10 s images compared with FBP20 s with statistically significant differences between the two methods (observer A: mean DRM10 s=4.3±0.5, mean FBP20 s=3.8±0.8, P=0.0064; observer B: mean DRM10 s=3.6±0.8, mean FBP20 s=3.1±0.9, P=0.0073). Improvements in image quality for DRM10 s were reported on 16 out of 28 scans for observer A and 15 out of 28 scans for observer B, whereas 8 out of 28 and 9 out of 28 scans received equivalent scores, respectively. The total number of lesions reported for both DRM10 s and FBP20 s was 72 for both observers showing no differences between the two methods. ConclusionThese results indicate that the use of the DRM algorithm has the potential for reducing bone SPECT acquisition times by half without compromising current levels of image quality and diagnostic value, or reduce the injected dose when radioactivity supply is limited.