On-board Robotic Multi-pinhole SPECT System for Region-of-interest (ROI) Imaging

On-board image guidance, such as cone-beam CT (CBCT) and kV/MV 2D imaging, is essential in many radiation therapy procedures, such as intensity modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT). These imaging techniques provide predominantly anatomical information for treatment planning and target localization. Recently, studies have shown that treatment planning based on functional and molecular information about the tumor and surrounding tissue could potentially improve the effectiveness of radiation therapy. However, current on-board imaging systems are limited in their functional and molecular imaging capability. Single Photon Emission Computed Tomography (SPECT) is a candidate to achieve on-board functional and molecular imaging. Traditional SPECT systems typically take 20 minutes or more for a scan, which is too long for on-board imaging. A robotic multi-pinhole SPECT system was proposed in this dissertation to provide shorter imaging time by using a robotic arm to maneuver the multi-pinhole SPECT system around the patient in position for radiation therapy.

A 49-pinhole collimated SPECT detector and its shielding were designed and simulated in this work using the computer-aided design (CAD) software. The trajectories of robotic arm about the patient, treatment table and gantry in the radiation therapy room and several detector assemblies such as parallel holes, single pinhole and 49 pinholes collimated detector were investigated. The rail mounted system was designed to enable a full range of detector positions and orientations to various crucial treatment sites including head and torso, while avoiding collision with linear accelerator (LINAC), patient table and patient.

An alignment method was developed in this work to calibrate the on-board robotic SPECT to the LINAC coordinate frame and to the coordinate frames of other on-board imaging systems such as CBCT. This alignment method utilizes line sources and one pinhole projection of these line sources. The model consists of multiple alignment parameters which maps line sources in 3-dimensional (3D) space to their 2-dimensional (2D) projections on the SPECT detector. Computer-simulation studies and experimental evaluations were performed as a function of number of line sources, Radon transform accuracy, finite line-source width, intrinsic camera resolution, Poisson noise and acquisition geometry. In computer-simulation studies, when there was no error in determining angles (α) and offsets (ρ) of the measured projections, the six alignment parameters (3 translational and 3 rotational) were estimated perfectly using three line sources. When angles (α) and offsets (ρ) were provided by Radon transform, the estimation accuracy was reduced. The estimation error was associated with rounding errors of Radon transform, finite line-source width, Poisson noise, number of line sources, intrinsic camera resolution and detector acquisition geometry. The estimation accuracy was significantly improved by using 4 line sources rather than 3 and also by using thinner line-source projections (obtained by better intrinsic detector resolution). With 5 line sources, median errors were 0.2 mm for the detector translations, 0.7 mm for the detector radius of rotation, and less than 0.5° for detector rotation, tilt and twist. In experimental evaluations, average errors relative to a different, independent registration technique were about 1.8 mm for detector translations, 1.1 mm for the detector radius of rotation (ROR), 0.5° and 0.4° for detector rotation and tilt, respectively, and 1.2° for detector twist.

Simulation studies were performed to investigate the improvement of imaging sensitivity and accuracy of hot sphere localization for breast imaging of patients in prone position. A 3D XCAT phantom was simulated in the prone position with nine hot spheres of 10 mm diameter added in the left breast. A no-treatment-table case and two commercial prone breast boards, 7 and 24 cm thick, were simulated. Different pinhole focal lengths were assessed for root-mean-square-error (RMSE). The pinhole focal lengths resulting in the lowest RMSE values were 12 cm, 18 cm and 21 cm for no table, thin board, and thick board, respectively. In both no table and thin board cases, all 9 hot spheres were easily visualized above background with 4-minute scans utilizing the 49-pinhole SPECT system while seven of nine hot spheres were visible with the thick board. In comparison with parallel-hole system, our 49-pinhole system shows reduction in noise and bias under these simulation cases. These results correspond to smaller radii of rotation for no-table case and thinner prone board. Similarly, localization accuracy with the 49-pinhole system was significantly better than with the parallel-hole system for both the thin and thick prone boards. Median localization errors for the 49-pinhole system with the thin board were less than 3 mm for 5 of 9 hot spheres, and less than 6 mm for the other 4 hot spheres. Median localization errors of 49-pinhole system with the thick board were less than 4 mm for 5 of 9 hot spheres, and less than 8 mm for the other 4 hot spheres.

Besides prone breast imaging, respiratory-gated region-of-interest (ROI) imaging of lung tumor was also investigated. A simulation study was conducted on the potential of multi-pinhole, region-of-interest (ROI) SPECT to alleviate noise effects associated with respiratory-gated SPECT imaging of the thorax. Two 4D XCAT digital phantoms were constructed, with either a 10 mm or 20 mm diameter tumor added in the right lung. The maximum diaphragm motion was 2 cm (for 10 mm tumor) or 4 cm (for 20 mm tumor) in superior-inferior direction and 1.2 cm in anterior-posterior direction. Projections were simulated with a 4-minute acquisition time (40 seconds per each of 6 gates) using either the ROI SPECT system (49-pinhole) or reference single and dual conventional broad cross-section, parallel-hole collimated SPECT. The SPECT images were reconstructed using OSEM with up to 6 iterations. Images were evaluated as a function of gate by profiles, noise versus bias curves, and a numerical observer performing a forced-choice localization task. Even for the 20 mm tumor, the 49-pinhole imaging ROI was found sufficient to encompass fully usual clinical ranges of diaphragm motion. Averaged over the 6 gates, noise at iteration 6 of 49-pinhole ROI imaging (10.9 µCi/ml) was approximately comparable to noise at iteration 2 of the two dual and single parallel-hole, broad cross-section systems (12.4 µCi/ml and 13.8 µCi/ml, respectively). Corresponding biases were much lower for the 49-pinhole ROI system (3.8 µCi/ml), versus 6.2 µCi/ml and 6.5 µCi/ml for the dual and single parallel-hole systems, respectively. Median localization errors averaged over 6 gates, for the 10 mm and 20 mm tumors respectively, were 1.6 mm and 0.5 mm using the ROI imaging system and 6.6 mm and 2.3 mm using the dual parallel-hole, broad cross-section system. The results demonstrate substantially improved imaging via ROI methods. One important application may be gated imaging of patients in position for radiation therapy.

A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150-L110 robot). An imaging study was performed with a phantom (PET CT PhantomTM), which includes 5 spheres of 10, 13, 17, 22 and 28 mm in diameter. The phantom was placed on a flat-top couch. SPECT projections were acquired with a parallel-hole collimator and a single-pinhole collimator both without background in the phantom, and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180 degrees and 228 degrees respectively. The pinhole detector viewed a 14.7 cm-diameter common volume which encompassed the 28 mm and 22 mm spheres. The common volume for parallel-hole was a 20.8-cm-diameter cylinder which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the flat-top table while avoiding collision with the table and maintaining the closest possible proximity to the common volume. For image reconstruction, detector trajectories were described by radius-of-rotation and detector rotation angle θ. These reconstruction parameters were obtained from the robot base and tool coordinates. The robotic SPECT system was able to maneuver the parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector to center-of-rotation (COR) distance. In no background case, all five spheres were visible in the reconstructed parallel-hole and pinhole images. In with background case, three spheres of 17, 22 and 28 mm diameter were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameter) were readily observed in the pinhole ROI imaging.

In conclusion, the proposed on-board robotic SPECT can be aligned to LINAC/CBCT with a single pinhole projection of the line-source phantom. Alignment parameters can be estimated using one pinhole projection of line sources. This alignment method may be important for multi-pinhole SPECT, where relative pinhole alignment may vary during rotation. For single pinhole and multi-pinhole SPECT imaging onboard radiation therapy machines, the method could provide alignment of SPECT coordinates with those of CBCT and the LINAC. In simulation studies of prone breast imaging and respiratory-gated lung imaging, the 49-pinhole detector showed better tumor contrast recovery and localization in a 4-minute scan compared to parallel-hole detector. On-board SPECT could be achieved by a robot maneuvering a SPECT detector about patients in position for radiation therapy on a flat-top couch. The robot inherent coordinate frames could be an effective means to estimate detector pose for use in SPECT image reconstruction.

Frontal eye field neurons assess visual stability across saccades.

The image on the retina may move because the eyes move, or because something in the visual scene moves. The brain is not fooled by this ambiguity. Even as we make saccades, we are able to detect whether visual objects remain stable or move. Here we test whether this ability to assess visual stability across saccades is present at the single-neuron level in the frontal eye field (FEF), an area that receives both visual input and information about imminent saccades. Our hypothesis was that neurons in the FEF report whether a visual stimulus remains stable or moves as a saccade is made. Monkeys made saccades in the presence of a visual stimulus outside of the receptive field. In some trials, the stimulus remained stable, but in other trials, it moved during the saccade. In every trial, the stimulus occupied the center of the receptive field after the saccade, thus evoking a reafferent visual response. We found that many FEF neurons signaled, in the strength and timing of their reafferent response, whether the stimulus had remained stable or moved. Reafferent responses were tuned for the amount of stimulus translation, and, in accordance with human psychophysics, tuning was better (more prevalent, stronger, and quicker) for stimuli that moved perpendicular, rather than parallel, to the saccade. Tuning was sometimes present as well for nonspatial transaccadic changes (in color, size, or both). Our results indicate that FEF neurons evaluate visual stability during saccades and may be general purpose detectors of transaccadic visual change.

In vivo small animal micro-CT using nanoparticle contrast agents.

Computed tomography (CT) is one of the most valuable modalities for in vivo imaging because it is fast, high-resolution, cost-effective, and non-invasive. Moreover, CT is heavily used not only in the clinic (for both diagnostics and treatment planning) but also in preclinical research as micro-CT. Although CT is inherently effective for lung and bone imaging, soft tissue imaging requires the use of contrast agents. For small animal micro-CT, nanoparticle contrast agents are used in order to avoid rapid renal clearance. A variety of nanoparticles have been used for micro-CT imaging, but the majority of research has focused on the use of iodine-containing nanoparticles and gold nanoparticles. Both nanoparticle types can act as highly effective blood pool contrast agents or can be targeted using a wide variety of targeting mechanisms. CT imaging can be further enhanced by adding spectral capabilities to separate multiple co-injected nanoparticles in vivo. Spectral CT, using both energy-integrating and energy-resolving detectors, has been used with multiple contrast agents to enable functional and molecular imaging. This review focuses on new developments for in vivo small animal micro-CT using novel nanoparticle probes applied in preclinical research.

New data inversion formulae in confocal scanning microscopy

Whereas the resolving power of an ordinary optical microscope is determined by the classical Rayleigh distance, significant super-resolution, i.e. resolution improvement beyond that Rayleigh limit, has been achieved by confocal scanning light microscopy. Furthermore is has been shown that the resolution of a confocal scanning microscope can still be significantly enhanced by measuring, for each scanning position, the full diffraction image by means of an array of detectors and by inverting these data to recover the value of the object at the focus. We discuss the associated inverse problem and show how to generalize the data inversion procedure by allowing, for reconstructing the object at a given point, to make use also of the diffraction images recorded at other scanning positions. This leads us to a whole family of generalized inversion formulae, which contains as special cases some previously known formulae. We also show how these exact inversion formulae can be implemented in practice.

Gamma-rays from heavy minimal dark matter

Motivated by the Minimal Dark Matter scenario, we consider the annihilation into gamma rays of candidates in the fermionic 5-plet and scalar 7-plet representations of SU(2)L, taking into account both the Sommerfeld effect and the internal bremsstrahlung. Assuming the Einasto profile, we show that present measurements of the Galactic Center by the H.E.S.S. instrument exclude the 5-plet and 7-plet as the dominant form of dark matter for masses between 1 TeV and 20 TeV, in particular, the 5-plet mass leading to the observed dark matter density via thermal freeze-out. We also discuss prospects for the upcoming Cherenkov Telescope Array, which will be able to probe even heavier dark matter masses, including the scenario where the scalar 7-plet is thermally produced.

Direction repulsion goes global

When viewing two superimposed, translating sets of dots moving in different directions, one overestimates the direction difference. This phenomenon of direction repulsion is thought to be driven by inhibitory interactions between directionally tuned motion detectors [1, 2]. However, there is disagreement on where this occurs — at early stages of motion processing [1, 3], or at the later, global motion-processing stage following “pooling” of these measures [4–6]. These two stages of motion pro - cessing have been identified as occurring in area V1 and the human homolog of macaque MT/V5, respectively[7, 8]. We designed experiments in which local and global predictions of repulsion are pitted against one another. Our stimuli contained a target set of dots, moving at a uniform speed, superimposed on a “mixed-speed” distractor set. Because the perceived speed of a mixed-speed stimulus is equal to the dots’ average speed [9], a global-processing account of direction repulsion predicts that repulsion magnitude induced by a mixed-speed distractor will be indistinguishable from that induced by a single-speed distractor moving at the same mean speed. This is exactly what we found. These results provide compelling evidence that global-motion interactions play a major role in driving direction repulsion.

Wide Variation in Adenoma Detection Rates at Screening Flexible Sigmoidoscopy

Background & Aims: Wide between-center variation in adenoma detection rates (ADRs) was observed in the U.K. Flexible Sigmoidoscopy Screening Trial (overall, 12.1%; range, 8.6%-15.9%; P <0.0001). The aim of this study was to determine whether the observed differences could be attributed to varying performance by endoscopists, to examine the effect of experience on performance, and to identify an attainable, standard ADR to which endoscopists could aspire. 

Methods: Thirteen medical endoscopists, one per trial center, each performed about 3000 examinations (200 per month) using the same equipment and protocol. Overall and monthly ADRs were compared using multivariable logistic regression. 

Results: Differences in ADRs were not explained by patient characteristics, incidence of colorectal cancer in the local population, or the endoscopists' medical specialty or previous experience. Average ADRs increased significantly with screening experience (up to 400 examinations). Endoscopists were classified as higher, intermediate, or lower adenoma detectors, and performance levels were maintained over time. Higher detectors had ADRs of 15% overall (men, 20%; women, 10%) and also detected more adenomas per case (higher/lower detectors, 21.7/10.4 adenomas per :100 examinations). 

Conclusions: The differences in ADRs were due to variation in performance of the endoscopists. Long-term follow-up will determine whether this variation is clinically important. We suggest that the standards in higher detecting centers should be achievable by all endoscopists screening unscreened populations aged older than 55 years. Endoscopists should aim to stay above the lower 95% confidence interval band for 200 examinations (10% overall; 5% in women, 15% in men).

Experimentally realizable characterizations of continuous- variable Gaussian states

Measures of entanglement, fidelity, and purity are basic yardsticks in quantum-information processing. We propose how to implement these measures using linear devices and homodyne detectors for continuous-variable Gaussian states. In particular, the test of entanglement becomes simple with some prior knowledge that is relevant to current experiments.

Conditional production of superpositions of coherent states with inefficient photon detection

It is shown that a linear superposition of two macroscopically distinguishable optical coherent states can be generated using a single photon source and simple all-optical operations. Weak squeezing on a single photon, beam mixing with an auxiliary coherent state, and photon detecting with imperfect threshold detectors are enough to generate a coherent state superposition in a free propagating optical field with a large coherent amplitude (alpha>2) and high fidelity (F>0.99). In contrast to all previous schemes to generate such a state, our scheme does not need photon number resolving measurements nor Kerr-type nonlinear interactions. Furthermore, it is robust to detection inefficiency and exhibits some resilience to photon production inefficiency.

A new device for the study of electron-ion interactions: The Belfast EBIT

An electron beam ion trap ( EBIT) has been designed and is currently under construction for use in atomic physics experiments at the Queen's University, Belfast. In contrast to traditional EBITs where pairs of superconducting magnets are used, a pair of permanent magnets will be used to compress the electron beam. The permanent magnets have been designed in conjunction with bespoke vacuum ports to give unprecedented access for photon detection. Furthermore, the bespoke vacuum ports facillitate a versatile, reconfigurable trap structure able to accommodate various in-situ detectors and in-line charged particle analysers. Although the machine will have somewhat lower specifications than many existing EBITs in terms of beam current density, it is hoped that the unique features will facilitate a number of hitherto impossible studies involving interactions between electrons and highly charged ions. In this article the new machine's design is outlined along with some suggestions of the type of process to be studied once the construction is completed.

Germanium MOS Capacitors with Hafnium Dioxide and Silicon Dioxide Dielectrics

Germanium (Ge) does not grow a suitable oxide for MOS devices. The Ge/dielectric interface is of prime importance to the operation of photo-detectors and scaled MOSTs. Therefore there is a requirement for deposited or bonded dielectric materials. MOS capacitors have been formed on germanium substrates with three different dielectric materials. Firstly, a thermally grown and bonded silicon dioxide (SiO2) layer, secondly, SiO2 deposited by atmospheric pressure CVD ‘silox’, and thirdly a hafnium oxide (HfO2) high-k dielectric deposited by atomic layer deposition (ALD). Ge wafers used were p-type 1 0 0 2 O cm. C–V measurements have been made on all three types of capacitors to assess the interface quality. ALD HfO2 and silox both display acceptable C–V characteristics. Threshold voltage and maximum and minimum capacitance values closely match expected values found through calculation. However, the bonded SiO2 has non-ideal C–V characteristics, revealing the presence of a high density of interface states. A H2/N2 post metal anneal has a detrimental effect on C–V characteristics of HfO2 and silox dielectrics, causing a shift in the threshold voltage and rise in the minimum capacitance value. In the case of hafnium dioxide, capacitor properties can be improved by performing a plasma nitridation of the Ge surface prior to dielectric deposition.

The 2003 November 14 occultation by Titan of TYC 1343-1865-1

We observed a stellar occultation by Titan on 2003 November 14 from La Palma Observatory using ULTRACAM with three Sloan filters: u, g, and i (358, 487, and 758 nm, respectively). The occultation probed latitudes 2°?S and 1°?N during immersion and emersion, respectively. A prominent central flash was present in only the i filter, indicating wavelength-dependent atmospheric extinction. We inverted the light curves to obtain six lower-limit temperature profiles between 335 and 485 km (0.04 and 0.003 mb) altitude. The i profiles agreed with the temperature measured by the Huygens Atmospheric Structure Instrument [Fulchignoni, M., and 43 colleagues, 2005. Nature 438, 785 791] above 415 km (0.01 mb). The profiles obtained from different wavelength filters systematically diverge as altitude decreases, which implies significant extinction in the light curves. Applying an extinction model [Elliot, J.L., Young, L.A., 1992. Astron. J. 103, 991 1015] gave the altitudes of line of sight optical depth equal to unity: 396±7 and 401±20 km (u immersion and emersion); 354±7 and 387±7 km (g immersion and emersion); and 336±5 and 318±4 km (i immersion and emersion). Further analysis showed that the optical depth follows a power law in wavelength with index 1.3±0.2. We present a new method for determining temperature from scintillation spikes in the occulting body's atmosphere. Temperatures derived with this method are equal to or warmer than those measured by the Huygens Atmospheric Structure Instrument. Using the highly structured, three-peaked central flash, we confirmed the shape of Titan's middle atmosphere using a model originally derived for a previous Titan occultation [Hubbard, W.B., and 45 colleagues, 1993. Astron. Astrophys. 269, 541 563].

Seasonal patterns in activity and habitat use by bats (Pipistrellus spp. and Nyctalus leisleri) in Northern Ireland, determined using a driven transect

The seasonal activity of Leisler's bat Nyctalus leisleri and pipistrelle bats Pipistrellus spp. with respect to minimum bat numbers and habitat use were investigated in County Down, Northern Ireland using a driven transect from April 1998 to October 1998. Data were collected in lowland farmland near Belfast, Northern Ireland using two BatBox III bat detectors tuned to detect both species and species groups simultaneously. The number of bats/km increased during April, May and June, peaking in July and tailed off after this period. The main peak in July is assumed to reflect the occurrence of newly volant young. An increase in the number of pipistrelle social calls during August and September probably represented mating activity. Bat activity correlated with temperature in both N. leisleri and Pipistrellus spp., although bat numbers were independent of temperature after the middle of June. There was significant variation in habitat use by pipistrelle bats along roads over the study period. Pipistrelle bats were observed in greater numbers in areas of tree-line, cut hedge (

Polarization studies of radiative electron capture into highly-charged uranium ions

Recent advances in the development of 2D microstrip detectors open up new possibilities for hard x-ray spectroscopy, in particular for polarization studies. These detectors make ideal Compton polarimeters, which enable us to study precisely the polarization of hard x-rays. Here, we present recent results from measurements of Radiative Electron Capture into the K-shell of highly-charged uranium ions. The experiments were performed with a novel 2D Si(Li) Compton polarimeter at the Experimental Storage Ring at GSI. Stored and cooled beams of U91+ and U92+ ions, with kinetic energies of 43 MeV/u and 96 MeV/u respectively, were crossed with a hydrogen gasjet. The preliminary data analysis shows x-rays from the K-REC process, emitted perpendicularly to the ion beam, to be strongly linearly polarized.

A new approach for the detection of ethylene using silica-supported palladium complexes

The coordination of olefins to square-planar Pd(II) and Pt(II) complexes containing 2,9-dimethylphenanthroline (L1) often involves a change of color associated with a change of geometry at the metal center. In order to obtain suitable colorimetric detectors for ethylene gas, a series of new Pd(II) and Pt(II) compounds with a range of 2,9-disubstituted phenanthroline ligands [2,9-di-n-butyl-1,10-phenanthroline (L-2), 2,9-di-s-butyl-1,10-phenanthroline (L3), 2,9-diphenyl-1,10-phenanthroline (L4), and 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (bathocuproine, L5)] have been prepared and their reactivity toward ethylene investigated both in solution and after depositing the detector compounds on a variety of solid supports. The Pd(II) complex [PdCl2(L2)] supported on silica undergoes a clear color change upon exposure to ethylene, while remaining stable toward air and water, and forms the basis for new simple colorimetric detectors with potential applications in ethylene pipe-leak detection and the monitoring of fruit ripening. Encouragingly, the detector is able to discriminate between fruit at different stages of ripening. The response of the detector to other volatiles was also examined, and specific color changes were also observed upon exposure to aromatic acetylenes. The crystal structures of four new derivatives, including the ethylene-Pt(II) complex [PtCl2(C2H4)(L2)], are also described.