Table of contents

Volume 55

Number 7, 7 April 2010

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Papers

1767

, , , and

The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

1785

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In this study, a comprehensive electron dosimetry model of newborn skeletal tissues is presented. The model is constructed using the University of Florida newborn hybrid phantom of Lee et al (2007 Phys. Med. Biol.52 3309–33), the newborn skeletal tissue model of Pafundi et al (2009 Phys. Med. Biol.54 4497–531) and the EGSnrc-based Paired Image Radiation Transport code of Shah et al (2005 J. Nucl. Med.46 344–53). Target tissues include the active bone marrow (surrogate tissue for hematopoietic stem cells), shallow marrow (surrogate tissue for osteoprogenitor cells) and unossified cartilage (surrogate tissue for chondrocytes). Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following source tissues: active marrow, trabecular bone (surfaces and volumes), cortical bone (surfaces and volumes) and cartilage. Transport results are reported as specific absorbed fractions according to the MIRD schema and are given as skeletal-averaged values in the paper with bone-specific values reported in both tabular and graphic format as electronic annexes (supplementary data). The method utilized in this work uniquely includes (1) explicit accounting for the finite size and shape of newborn ossification centers (spongiosa regions), (2) explicit accounting for active and shallow marrow dose from electron emissions in cortical bone as well as sites of unossified cartilage, (3) proper accounting of the distribution of trabecular and cortical volumes and surfaces in the newborn skeleton when considering mineral bone sources and (4) explicit consideration of the marrow cellularity changes for active marrow self-irradiation as applicable to radionuclide therapy of diseased marrow in the newborn child.

1815

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This paper presents an evaluation of two types of Geiger-mode avalanche photodiodes (G-APDs) for their potential to be used in a positron emission tomography (PET) detector. While the MPPC G-APD had only 3600 cells, the solid state photomultiplier (SSPM)-type G-APD had 8100 cells. In a single-channel G-APD/LSO setup, the energy resolution of the SSPM at 511 keV was 25%, while the of the MPPC was 13.5% (FWHM). No influences were observed while the detectors were inside a 7 T magnetic resonance (MR) scanner. A time resolution of 2.7 ns (FWHM) was measured for the LSO/SSPM and 0.9 ns for the LSO/MPPC detector setup. Although the linearity was superior for the SSPM in the single detector readout, the inferior energy and time resolution excluded them to be used for the block detector readout. All 12 × 12 LSO crystals of the block could be resolved in a crystal map using a 3 × 3 MPPC G-APD array. The time resolution of the block detector was 950 ps. While the energy spectra for the MPPC-based single-channel setup were nonlinear, they reached linearity better than 5% in the block detector. A high number of G-APD cells provide a linear signal in a single-channel detector setup, but not necessarily a good timing or due to a larger inactive surface resulting in lower photon detection efficiency. G-APDs with a low number of cells provide a good timing and and linear signals in block detector designs, where the scintillation light is shared over many G-APDs.

1833

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A fully 3D iterative image reconstruction algorithm has been developed for high-resolution PET cameras composed of pixelated scintillator crystal arrays and rotating planar detectors, based on the ordered subsets approach. The associated system matrix is precalculated with Monte Carlo methods that incorporate physical effects not included in analytical models, such as positron range effects and interaction of the incident gammas with the scintillator material. Custom Monte Carlo methodologies have been developed and optimized for modelling of system matrices for fast iterative image reconstruction adapted to specific scanner geometries, without redundant calculations. According to the methodology proposed here, only one-eighth of the voxels within two central transaxial slices need to be modelled in detail. The rest of the system matrix elements can be obtained with the aid of axial symmetries and redundancies, as well as in-plane symmetries within transaxial slices. Sparse matrix techniques for the non-zero system matrix elements are employed, allowing for fast execution of the image reconstruction process. This 3D image reconstruction scheme has been compared in terms of image quality to a 2D fast implementation of the OSEM algorithm combined with Fourier rebinning approaches. This work confirms the superiority of fully 3D OSEM in terms of spatial resolution, contrast recovery and noise reduction as compared to conventional 2D approaches based on rebinning schemes. At the same time it demonstrates that fully 3D methodologies can be efficiently applied to the image reconstruction problem for high-resolution rotational PET cameras by applying accurate pre-calculated system models and taking advantage of the system's symmetries.

1863

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Currently, high-precision delivery in stereotactic radiosurgery (SRS) is achieved via high-precision target localization and rigid patient immobilization. Rigid patient immobilization can result in, however, patient discomfort, which is exacerbated by the long duration of SRS treatments and may induce patient movement. To address this issue, we developed a new SRS technique that is aimed to minimize patient discomfort while maintaining high-precision treatment, based on a less-rigid patient immobilization combined with continuous patient motion monitoring. In this paper, we examine the feasibility of this new technique. An anthropomorphic head phantom is used to check the accuracy of a 3D surface imaging system that provides the monitoring. Volunteers are used to study patient motion inside a new type of head mold that is used for minimal immobilization. Results show that for different couch angles, the difference between the phantom positions recorded by the surface imaging system and by an infrared optical tracking system was within 1 mm in displacements and 1° in rotation. The motion detected by both systems during couch shifts is within 1 mm agreement. The average maximum volunteer head motion in the head mold during the 20 min interval in any direction was 0.7 mm (range: 0.4–1.1 mm). Patient motion due to couch motion was always less than 0.2 mm. We conclude that motion inside the minimally immobilizing head mold is small and can be accurately detected by real-time surface imaging.

1875

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In this paper, we propose identification of the morphological factors that may impact the whole-body averaged specific absorption rate (WBSAR). This study is conducted for the case of exposure to a front plane wave at a 2100 MHz frequency carrier. This study is based on the development of different regression models for estimating the WBSAR as a function of morphological factors. For this purpose, a database of 12 anatomical human models (phantoms) has been considered. Also, 18 supplementary phantoms obtained using the morphing technique were generated to build the required relation. This paper presents three models based on external morphological factors such as the body surface area, the body mass index or the body mass. These models show good results in estimating the WBSAR (<10%) for families obtained by the morphing technique, but these are still less accurate (30%) when applied to different original phantoms. This study stresses the importance of the internal morphological factors such as muscle and fat proportions in characterization of the WBSAR. The regression models are then improved using internal morphological factors with an estimation error of approximately 10% on the WBSAR. Finally, this study is suitable for establishing the statistical distribution of the WBSAR for a given population characterized by its morphology.

1889

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It was previously demonstrated that it is feasible to simultaneously perform ultrasound therapy and imaging of a coagulated lesion during treatment with an integrated transducer that is capable of high intensity focused ultrasound (HIFU) and B-mode ultrasound imaging. It was found that coded excitation and fixed notch filtering upon reception could significantly reduce interference caused by the therapeutic transducer. During HIFU sonication, the imaging signal generated with coded excitation and fixed notch filtering had a range side-lobe level of less than −40 dB, while traditional short-pulse excitation and fixed notch filtering produced a range side-lobe level of −20 dB. The shortcoming is, however, that relatively complicated electronics may be needed to utilize coded excitation in an array imaging system. It is for this reason that in this paper an adaptive noise canceling technique is proposed to improve image quality by minimizing not only the therapeutic interference, but also the remnant side-lobe 'ripples' when using the traditional short-pulse excitation. The performance of this technique was verified through simulation and experiments using a prototype integrated HIFU/imaging transducer. Although it is known that the remnant ripples are related to the notch attenuation value of the fixed notch filter, in reality, it is difficult to find the optimal notch attenuation value due to the change in targets or the media resulted from motion or different acoustic properties even during one sonication pulse. In contrast, the proposed adaptive noise canceling technique is capable of optimally minimizing both the therapeutic interference and residual ripples without such constraints. The prototype integrated HIFU/imaging transducer is composed of three rectangular elements. The 6 MHz center element is used for imaging and the outer two identical 4 MHz elements work together to transmit the HIFU beam. Two HIFU elements of 14.4 mm × 20.0 mm dimensions could increase the temperature of the soft biological tissue from 55 °C to 71 °C within 60 s. Two types of experiments for simultaneous therapy and imaging were conducted to acquire a single scan-line and B-mode image with an aluminum plate and a slice of porcine muscle, respectively. The B-mode image was obtained using the single element imaging system during HIFU beam transmission. The experimental results proved that the combination of the traditional short-pulse excitation and the adaptive noise canceling method could significantly reduce therapeutic interference and remnant ripples and thus may be a better way to implement real-time simultaneous therapy and imaging.

1903

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An observer-based contrast-detail study is performed in an effort to evaluate the limits of object detectability using a dedicated CZT-based breast SPECT imaging system under various imaging conditions. A custom geometric contrast-resolution phantom was developed that can be used for both positive ('hot') and negative contrasts ('cold'). The 3 cm long fillable tubes are arranged in six sectors having equal inner diameters ranging from 1 mm to 6 mm with plastic wall thicknesses of <0.25 mm, on a pitch of twice their inner diameters. Scans of the activity filled tubes using simple circular trajectories are obtained in a 215 mL uniform water filled cylinder, varying the rod:background concentration ratios from 10:1 to 1:10 simulating a large range of biological uptake ratios. The rod phantom is then placed inside a non-uniformly shaped 500 mL breast phantom and scans are again acquired using both simple and complex 3D trajectories for similarly varying contrasts. Summed slice and contiguous multi-slice images are evaluated by five independent readers, identifying the smallest distinguishable rod for each concentration and experimental setup. Linear and quadratic regression is used to compare the resulting contrast-detail curves. Results indicate that in a moderately low-noise 500 mL background, using the SPECT camera having 2.5 mm intrinsic pixels, the mean detectable rod was ∼3.4 mm at a 10:1 ratio, degrading to ∼5.2 mm with the 2.5:1 concentration ratio. The smallest object detail was observed using a 45° tilted trajectory acquisition. The complex 3D projected sine wave acquisition, however, had the most consistent combined intra- and inter-observer results, making it potentially the best imaging approach for consistent results.

1917

, and

In this paper we describe a method for quantitative photoacoustic tomography (qPAT) based on the photon radiative transfer equation (RTE) coupled with the Helmholtz photoacoustic wave equation. Considerable simulations and tissue-like phantom experiments are conducted to evaluate transport-based qPAT in comparison with diffusion-based qPAT. In these comparative simulations and experiments, we systematically examine the effects of the ratio of μa/μ's (absorption/reduced scattering coefficient), the anisotropy factor (g) and the imaging domain size on the transport- and diffusion-based photoacoustic image reconstruction. The results obtained show that transport-based qPAT allows for clearly more accurate recovery of the absolute absorption coefficient images of heterogeneous media over diffusion-based qPAT for all the cases examined and provides considerably improved image quality for cases where the photon diffusion approximation (DA) is invalid.

1935

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IMRT treatment planning requires consideration of two competing objectives: achieving the required amount of radiation for the planning target volume and minimizing the amount of radiation delivered to all other tissues. It is important for planners to understand the tradeoff between competing factors so that the time-consuming human interaction loop (plan–evaluate–modify) can be eliminated. Treatment-plan-surface models have been proposed as a decision support tool to aid treatment planners and clinicians in choosing between rival treatment plans in a multi-plan environment. In this paper, an empirical approach is introduced to determine the minimum number of treatment plans (minimum knowledge base) required to build accurate representations of the IMRT plan surface in order to predict organ-at-risk (OAR) dose–volume (DV) levels and complications as a function of input DV constraint settings corresponding to all involved OARs in the plan. We have tested our approach on five head and neck patients and five whole pelvis/prostate patients. Our results suggest that approximately 30 plans were sufficient to predict DV levels with less than 3% relative error in both head and neck and whole pelvis/prostate cases. In addition, approximately 30–60 plans were sufficient to predict saliva flow rate with less than 2% relative error and to classify rectal bleeding with an accuracy of 90%.

1949

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The aim of this study was to investigate temperature and thermal dose distributions of thermobrachytherapy surface applicators (TBSAs) developed for concurrent or sequential high dose rate (HDR) brachytherapy and microwave hyperthermia treatment of chest wall recurrence and other superficial diseases. A steady-state thermodynamics model coupled with the fluid dynamics of a water bolus and electromagnetic radiation of the hyperthermia applicator is used to characterize the temperature distributions achievable with TBSAs in an elliptical phantom model of the human torso. Power deposited by 915 MHz conformal microwave array (CMA) applicators is used to assess the specific absorption rate (SAR) distributions of rectangular (500 cm2) and L-shaped (875 cm2) TBSAs. The SAR distribution in tissue and fluid flow distribution inside the dual-input dual-output (DIDO) water bolus are coupled to solve the steady-state temperature and thermal dose distributions of the rectangular TBSA (R-TBSA) for superficial tumor targets extending 10–15 mm beneath the skin surface. Thermal simulations are carried out for a range of bolus inlet temperature (Tb = 38–43 °C), water flow rate (Qb = 2–4 L min−1) and tumor blood perfusion (ωb = 2–5 kg m−3 s−1) to characterize their influence on thermal dosimetry. Steady-state SAR patterns of the R- and L-TBSA demonstrate the ability to produce conformal and localized power deposition inside the tumor target sparing surrounding normal tissues and nearby critical organs. Acceptably low variation in tissue surface cooling and surface temperature homogeneity was observed for the new DIDO bolus at a 2 L min−1 water flow rate. Temperature depth profiles and thermal dose volume histograms indicate bolus inlet temperature (Tb) to be the most influential factor on thermal dosimetry. A 42 °C water bolus was observed to be the optimal choice for superficial tumors extending 10–15 mm from the surface even under significant blood perfusion. Lower bolus temperature may be chosen to reduce the thermal enhancement ratio (TER) in the most sensitive skin where maximum radiation dose is delivered and to extend the thermal enhancement of radiation dose deeper. This computational study indicates that well-localized elevation of tumor target temperature to 40–44 °C can be accomplished by large surface-conforming TBSAs using appropriate selection of coupling bolus temperature.

1971

, , and

In 123I-IBZM brain SPECT, the main interest is the activity uptake in the striatum relative to the background, and semi-quantitative techniques using regions of interest are typically used for this purpose. Uncertainties in the measured uptakes can however be a problem due to low contrasts and high noise levels. Like SPECT in general, IBZM SPECT should benefit from reconstruction methods that include model-based compensation, but it is important that image acquisition is optimized for this technique. An important factor is the choice of collimator. In this study we compare four different parallel-hole collimators for IBZM SPECT regarding overall quantitative accuracy and measured uptake ratio as a function of image noise and uncertainty. The collimators are low-energy high-resolution (LEHR), low-energy general-purpose (LEGP), extended LEGP (ELEGP) and medium-energy general-purpose (MEGP). The effect of three Butterworth post-filters with cut-off frequencies of 0.3, 0.45 and 0.6 cm−1 (power factor 8) is also studied. All raw-data projections are produced using Monte Carlo simulations. Of the investigated collimators, the one that is most sensitive to the primary photons, ELEGP, proved to be the most optimal for realistic noise levels. Butterworth post-filtering is advantageous, and the cut-off frequency 0.45 cm−1 was the best compromise in this study.

1989

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At present, in-beam positron emission tomography (PET) is the only method for in vivo and in situ range verification in ion therapy. At the GSI Helmholtzzentrum für Schwerionenforschung GmbH (GSI) Darmstadt, Germany, a unique in-beam PET installation has been operated from 1997 until the shut down of the carbon ion therapy facility in 2008. Therapeutic irradiation by means of 12C ion beams of more than 400 patients have been monitored. In this paper a first quantitative study on the accuracy of the in-beam PET method to detect range deviations between planned and applied treatment in clinically relevant situations using simulations based on clinical data is presented. Patient treatment plans were used for performing simulations of positron emitter distributions. For each patient a range difference of ± 6 mm in water was applied and compared to simulations without any changes. The comparisons were performed manually by six experienced evaluators for data of 81 patients. The number of patients required for the study was calculated using the outcome of a pilot study. The results indicate a sensitivity of (91 ± 3)% and a specificity of (96 ± 2)% for detecting an overrange, a reduced range is recognized with a sensitivity of (92 ± 3)% and a specificity of (96 ± 2)%. The positive and the negative predictive value of this method are 94% and 87%, respectively. The interobserver coefficient of variation is between 3 and 8%. The in-beam PET method demonstrated a high sensitivity and specificity for the detection of range deviations. As the range is a most indicative factor of deviations in the dose delivery, the promising results shown in this paper confirm the in-beam PET method as an appropriate tool for monitoring ion therapy.

1999

and

We show how the spectral imaging framework should be modified to account for a high fraction of Compton interactions in low Z detector materials such as silicon. Using this framework, where deposited energies differ from actual photon energies, we compare the performance of a silicon strip detector, including the influence of scatter inside the detector and charge sharing but disregarding signal pileup, with an ideal energy integrating detector. We show that although the detection efficiency for silicon rapidly drops for the acceleration voltages encountered in clinical computed tomography practice, silicon detectors could perform on a par with ideal energy integrating detectors for routine imaging tasks. The use of spectrally sensitive detectors opens up the possibility for decomposition techniques such as k-edge imaging, and we show that the proposed modification of the spectral imaging framework is beneficial for such imaging tasks.

2023

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Block-iterative image reconstruction methods, such as ordered subset expectation maximization (OSEM), are commonly used to accelerate image reconstruction. In OSEM, the speed-up factor over maximum likelihood expectation maximization (MLEM) is approximately equal to the number of subsets in which the projection data are divided. Traditionally, each subset consists of a couple of projection views, and the more subsets are used, the more the solution deviates from MLEM solutions. We found for multi-pinhole single photon emission computed tomography (SPECT) that even moderate acceleration factors in OSEM lead to inaccurate reconstructions. Therefore, we introduce pixel-based ordered subset expectation maximization (POSEM), which is based on an alternative subset choice. Pixels in each subset are spread out regularly over projections and are spatially separated as much as possible. We validated POSEM for data acquired with a focusing multi-pinhole SPECT system. Performance was compared with traditional OSEM and MLEM for a rat total body bone scan, a gated mouse myocardial perfusion scan and a Defrise phantom scan. We found that POSEM can be operated at acceleration factors that are often an order of magnitude higher than in traditional OSEM.

2035

, , and

This paper is concerned with an efficient implementation suitable for the elastography inverse problem. More precisely, the novel algorithm allows us to compute the unknown stiffness distribution in soft tissue by means of the measured displacement field by considerably reducing the numerical cost compared to previous approaches. This is realized by combining and further elaborating variational mesh adaption with a clustering technique similar to those known from digital image compression. Within the variational mesh adaption, the underlying finite element discretization is only locally refined if this leads to a considerable improvement of the numerical solution. Additionally, the numerical complexity is reduced by the aforementioned clustering technique, in which the parameters describing the stiffness of the respective soft tissue are sorted according to a predefined number of intervals. By doing so, the number of unknowns associated with the elastography inverse problem can be chosen explicitly. A positive side effect of this method is the reduction of artificial noise in the data (smoothing of the solution). The performance and the rate of convergence of the resulting numerical formulation are critically analyzed by numerical examples.

2057

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Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced. The effect of radiation on plexiform and fistulous AVM nidus vessels was simulated using this theoretical model. The similarities between vascular and electrical networks were used to construct this biomathematical AVM model and provide an accurate rendering of transnidal and intranidal hemodynamics. The response of different vessels to radiation and their obliteration probability as a function of different angiostructures were simulated and total obliteration was defined as the probability of obliteration of all possible vascular pathways. The dose response of the whole AVM is observed to depend on the vascular structure of the intra-nidus AVM. Furthermore, a plexiform AVM appears to be more prone to obliteration compared with an AVM of the same size but having more arteriovenous fistulas. Finally, a binomial model was introduced, which considers the number of crucial vessels and is able to predict the dose response behavior of AVMs with a complex vascular structure.

2069

, , , , , , , and

A fully automated, intrinsic gating algorithm for small animal cone-beam CT is described and evaluated. A parameter representing the organ motion, derived from the raw projection images, is used for both cardiac and respiratory gating. The proposed algorithm makes it possible to reconstruct motion-corrected still images as well as to generate four-dimensional (4D) datasets representing the cardiac and pulmonary anatomy of free-breathing animals without the use of electrocardiogram (ECG) or respiratory sensors. Variation analysis of projections from several rotations is used to place a region of interest (ROI) on the diaphragm. The ROI is cranially extended to include the heart. The centre of mass (COM) variation within this ROI, the filtered frequency response and the local maxima are used to derive a binary motion-gating parameter for phase-sensitive gated reconstruction. This algorithm was implemented on a flat-panel-based cone-beam CT scanner and evaluated using a moving phantom and animal scans (seven rats and eight mice). Volumes were determined using a semiautomatic segmentation. In all cases robust gating signals could be obtained. The maximum volume error in phantom studies was less than 6%. By utilizing extrinsic gating via externally placed cardiac and respiratory sensors, the functional parameters (e.g. cardiac ejection fraction) and image quality were equivalent to this current gold standard. This algorithm obviates the necessity of both gating hardware and user interaction. The simplicity of the proposed algorithm enables adoption in a wide range of small animal cone-beam CT scanners.

2087

, , and

Reducing the number of false positives (FPs) as much as possible is a challenging task for computer-aided detection (CAD) of colonic polyps. As part of a typical CAD pipeline, an accurate and robust process for segmenting initial polyp candidates (IPCs) will significantly benefit the successive FP reduction procedures, such as feature-based classification of false and true positives (TPs). In this study, we introduce an improved scheme for segmenting IPCs. It consists of two main components. One is geodesic distance-based merging, which merges suspicious patches (SPs) for IPCs. Based on the merged SPs, another component, called convex dilation, grows each SP beyond the inner surface of the colon wall to form a volume of interest (VOI) for that IPC, so that the inner border of the VOI beyond the colon inner surface could be segmented as convex, as expected. The IPC segmentation strategy was evaluated using a database of 50 patient studies, which include 100 scans at supine and prone positions with 84 polyps and masses sized from 6 to 35 mm. The presented IPC segmentation strategy (or VOI extraction method) demonstrated improvements, in terms of having no undesirably merged true polyp and providing more helpful mean and variance of the image intensities rooted from the extracted VOI for classification of the TPs and FPs, over two other VOI extraction methods (i.e. the conventional method of Nappi and Yoshida (2003 Med. Phys.30 1592–601) and our previous method (Zhu et al 2009 Cancer Manag. Res.1 1–13). At a by-polyp sensitivity of 0.90, these three methods generated the FP rate (number of FPs per scan) of 4.78 (new method), 6.37 (Nappi) and 7.01 (Zhu) respectively.

2103

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This paper presents a new algorithm for ultrasonic particle image velocimetry (Echo PIV) for improving the flow velocity measurement accuracy and efficiency in regions with high velocity gradients. The conventional Echo PIV algorithm has been modified by incorporating a multiple iterative algorithm, sub-pixel method, filter and interpolation method, and spurious vector elimination algorithm. The new algorithms' performance is assessed by analyzing simulated images with known displacements, and ultrasonic B-mode images of in vitro laminar pipe flow, rotational flow and in vivo rat carotid arterial flow. Results of the simulated images show that the new algorithm produces much smaller bias from the known displacements. For laminar flow, the new algorithm results in 1.1% deviation from the analytically derived value, and 8.8% for the conventional algorithm. The vector quality evaluation for the rotational flow imaging shows that the new algorithm produces better velocity vectors. For in vivo rat carotid arterial flow imaging, the results from the new algorithm deviate 6.6% from the Doppler-measured peak velocities averagely compared to 15% of that from the conventional algorithm. The new Echo PIV algorithm is able to effectively improve the measurement accuracy in imaging flow fields with high velocity gradients.

Notes

N167

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The clonogenic assay is the method of choice to determine cell reproductive death after in vitro irradiation treatment. Traditionally, colony quantification has been performed by manual counting, a very laborious, time-consuming and rather subjective task. In this study, we compared manual counting by two skilled investigators with automated counting using the freely available ClonoCounter program. Five human tumour cell lines were irradiated under normoxia (21% O2) or anoxia (<0.1% O2), after 24 h or 6 h anoxic preincubation. Colonies were quantified manually or using the ClonoCounter software. A positive correlation between the absolute number of colonies counted manually and automatically was shown. Though there was a general trend of underpredicting the absolute number of cell colonies when counting automatically, survival curves were very similar, and in none of the cell lines were significant differences in radiobiological parameters such as mean inactivation dose, surviving fraction at 2 Gy and oxygen enhancement ratio detected. Our results suggest that the ClonoCounter provides sufficient reliability to be implemented for counting human tumour colonies in in vitro irradiation experiments. In contrast to several previously reported computer-aided colony-counting methods, it is a freely available program, requiring only minimal instrument costs.

N179

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The use of time-of-flight (TOF) information in positron emission tomography (PET) enables significant improvement in image noise properties and, therefore, lesion detection. Silicon photomultipliers (SiPMs) are solid-state photosensors that have several advantages over photomultiplier tubes (PMTs). SiPMs are small, essentially transparent to 511 keV gamma rays and insensitive to magnetic fields. This enables novel detector designs aimed at e.g. compactness, high resolution, depth-of-interaction (DOI) correction and MRI compatibility. The goal of the present work is to study the timing performance of SiPMs in combination with LaBr3:Ce(5%), a relatively new scintillator with promising characteristics for TOF-PET. Measurements were performed with two, bare, 3 mm × 3 mm × 5 mm LaBr3:Ce(5%) crystals, each coupled to a 3 mm × 3 mm SiPM. Using a 22Na point source placed at various positions in between the two detectors, a coincidence resolving time (CRT) of ∼100 ps FWHM for 511 keV annihilation photon pairs was achieved, corresponding to a TOF positioning resolution of ∼15 mm FWHM. At the same time, pulse height spectra with well-resolved full-energy peaks were obtained. To our knowledge this is the best CRT reported for SiPM-based scintillation detectors to date. It is concluded that SiPM-based scintillation detectors can provide timing resolutions at least as good as detectors based on PMTs.