Showing papers in "Physics in Medicine and Biology in 2010"

The Virtual Family—development of surface-based anatomical models of two adults and two children for dosimetric simulations

Abstract: The objective of this study was to develop anatomically correct whole body human models of an adult male (34 years old), an adult female (26 years old) and two children (an 11-year-old girl and a six-year-old boy) for the optimized evaluation of electromagnetic exposure. These four models are referred to as the Virtual Family. They are based on high resolution magnetic resonance (MR) images of healthy volunteers. More than 80 different tissue types were distinguished during the segmentation. To improve the accuracy and the effectiveness of the segmentation, a novel semi-automated tool was used to analyze and segment the data. All tissues and organs were reconstructed as three-dimensional (3D) unstructured triangulated surface objects, yielding high precision images of individual features of the body. This greatly enhances the meshing flexibility and the accuracy with respect to thin tissue layers and small organs in comparison with the traditional voxel-based representation of anatomical models. Conformal computational techniques were also applied. The techniques and tools developed in this study can be used to more effectively develop future models and further improve the accuracy of the models for various applications. For research purposes, the four models are provided for free to the scientific community.

Polymer gel dosimetry

Abstract: Polymer gel dosimeters are fabricated from radiation sensitive chemicals which, upon irradiation, polymerize as a function of the absorbed radiation dose. These gel dosimeters, with the capacity to uniquely record the radiation dose distribution in three-dimensions (3D), have specific advantages when compared to one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters, such as film. These advantages are particularly significant in dosimetry situations where steep dose gradients exist such as in intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters also have specific advantages for brachytherapy dosimetry. Potential dosimetry applications include those for low-energy x-rays, high-linear energy transfer (LET) and proton therapy, radionuclide and boron capture neutron therapy dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with properties that may be modified depending on the application. The 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound. The fundamental science underpinning polymer gel dosimetry is reviewed along with the various evaluation techniques. Clinical dosimetry applications of polymer gel dosimetry are also presented.

Evaluation of sparse-view reconstruction from flat-panel-detector cone-beam CT.

Abstract: Flat-panel-detector x-ray cone-beam computed tomography (CBCT) is used in a rapidly increasing host of imaging applications, including image-guided surgery and radiotherapy. The purpose of the work is to investigate and evaluate image reconstruction from data collected at projection views significantly fewer than what is used in current CBCT imaging. Specifically, we carried out imaging experiments using a bench-top CBCT system that was designed to mimic imaging conditions in image-guided surgery and radiotherapy; we applied an image reconstruction algorithm based on constrained total-variation (TV)-minimization to data acquired with sparsely sampled view-angles and conducted extensive evaluation of algorithm performance. Results of the evaluation studies demonstrate that, depending upon scanning conditions and imaging tasks, algorithms based on constrained TV-minimization can reconstruct images of potential utility from a small fraction of the data used in typical, current CBCT applications. A practical implication of the study is that the optimization of algorithm design and implementation can be exploited for considerably reducing imaging effort and radiation dose in CBCT.

Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma.

Abstract: The purpose of this study is to test the hypothesis that gold nanoparticle (AuNP, nanogold)-enhanced radiation therapy (nanogold radiation therapy, NRT) is efficacious when treating the radiation resistant and highly aggressive mouse head and neck squamous cell carcinoma model, SCCVII, and to identify parameters influencing the efficacy of NRT. Subcutaneous (sc) SCCVII leg tumors in mice were irradiated with x-rays at the Brookhaven National Laboratory (BNL) National Synchrotron Light Source (NSLS) with and without prior intravenous (iv) administration of AuNPs. Variables studied included radiation dose, beam energy, temporal fractionation and hyperthermia. AuNP-mediated NRT was shown to be effective for the sc SCCVII model. AuNPs were more effective at 42 Gy than at 30 Gy (both at 68 keV median beam energy) compared to controls without gold. Similarly, at 157 keV median beam energy, 50.6 Gy NRT was more effective than 44 Gy NRT. At the same radiation dose ( approximately 42 Gy), 68 keV was more effective than 157 keV. Hyperthermia and radiation therapy (RT) were synergistic and AuNPs enhanced this synergy, thereby further reducing TCD50 s (tumor control dose 50%) and increasing long-term survivals. It is concluded that gold nanoparticles enhance the radiation therapy of a radioresistant mouse squamous cell carcinoma. The data show that radiation dose, energy and hyperthermia influence efficacy and better define the potential utility of gold nanoparticles for cancer x-ray therapy.

Validation of a new grid-based Boltzmann equation solver for dose calculation in radiotherapy with photon beams

Abstract: A new grid-based Boltzmann equation solver, Acuros, was developed specifically for performing accurate and rapid radiotherapy dose calculations. In this study we benchmarked its performance against Monte Carlo for 6 and 18 MV photon beams in heterogeneous media. Acuros solves the coupled Boltzmann transport equations for neutral and charged particles on a locally adaptive Cartesian grid. The Acuros solver is an optimized rewrite of the general purpose Attila software, and for comparable accuracy levels, it is roughly an order of magnitude faster than Attila. Comparisons were made between Monte Carlo (EGSnrc) and Acuros for 6 and 18 MV photon beams impinging on a slab phantom comprising tissue, bone and lung materials. To provide an accurate reference solution, Monte Carlo simulations were run to a tight statistical uncertainty (sigma approximately 0.1%) and fine resolution (1-2 mm). Acuros results were output on a 2 mm cubic voxel grid encompassing the entire phantom. Comparisons were also made for a breast treatment plan on an anthropomorphic phantom. For the slab phantom in regions where the dose exceeded 10% of the maximum dose, agreement between Acuros and Monte Carlo was within 2% of the local dose or 1 mm distance to agreement. For the breast case, agreement was within 2% of local dose or 2 mm distance to agreement in 99.9% of voxels where the dose exceeded 10% of the prescription dose. Elsewhere, in low dose regions, agreement for all cases was within 1% of the maximum dose. Since all Acuros calculations required less than 5 min on a dual-core two-processor workstation, it is efficient enough for routine clinical use. Additionally, since Acuros calculation times are only weakly dependent on the number of beams, Acuros may ideally be suited to arc therapies, where current clinical algorithms may incur long calculation times.

The UF family of reference hybrid phantoms for computational radiation dosimetry

Abstract: Computational human phantoms are computer models used to obtain dose distributions within the human body exposed to internal or external radiation sources. In addition, they are increasingly used to develop detector efficiencies for in vivo whole-body counters. Two classes of computational human phantoms have been widely utilized for dosimetry calculation: stylized and voxel phantoms that describe human anatomy through mathematical surface equations and 3D voxel matrices, respectively. Stylized phantoms are flexible in that changes to organ position and shape are possible given avoidance of region overlap, while voxel phantoms are typically fixed to a given patient anatomy, yet can be proportionally scaled to match individuals of larger or smaller stature, but of equivalent organ anatomy. Voxel phantoms provide much better anatomical realism as compared to stylized phantoms which are intrinsically limited by mathematical surface equations. To address the drawbacks of these phantoms, hybrid phantoms based on non-uniform rational B-spline (NURBS) surfaces have been introduced wherein anthropomorphic flexibility and anatomic realism are both preserved. Researchers at the University of Florida have introduced a series of hybrid phantoms representing the ICRP Publication 89 reference newborn, 15 year, and adult male and female. In this study, six additional phantoms are added to the UF family of hybrid phantoms-those of the reference 1 year, 5 year and 10 year child. Head and torso CT images of patients whose ages were close to the targeted ages were obtained under approved protocols. Major organs and tissues were segmented from these images using an image processing software, 3D-DOCTOR. NURBS and polygon mesh surfaces were then used to model individual organs and tissues after importing the segmented organ models to the 3D NURBS modeling software, Rhinoceros. The phantoms were matched to four reference datasets: (1) standard anthropometric data, (2) reference organ masses from ICRP Publication 89, (3) reference elemental compositions provided in ICRP 89 as well as ICRU Report 46, and (4) reference data on the alimentary tract organs given in ICRP Publications 89 and 100. Various adjustments and refinements to the organ systems of the previously described newborn, 15 year and adult phantoms are also presented. The UF series of hybrid phantoms retain the non-uniform scalability of stylized phantoms while maintaining the anatomical realism of patient-specific voxel phantoms with respect to organ shape, depth and inter-organ distance. While the final versions of these phantoms are in a voxelized format for radiation transport simulation, their primary format is given as NURBS and polygon mesh surfaces, thus permitting one to sculpt non-reference phantoms using the reference phantoms as an anatomic template.

Predicting the efficacy of radiotherapy in individual glioblastoma patients in vivo: a mathematical modeling approach

Abstract: Glioblastoma multiforme (GBM) is the most malignant form of primary brain tumors known as gliomas. They proliferate and invade extensively and yield short life expectancies despite aggressive treatment. Response to treatment is usually measured in terms of the survival of groups of patients treated similarly, but this statistical approach misses the subgroups that may have responded to or may have been injured by treatment. Such statistics offer scant reassurance to individual patients who have suffered through these treatments. Furthermore, current imaging-based treatment response metrics in individual patients ignore patient-specific differences in tumor growth kinetics, which have been shown to vary widely across patients even within the same histological diagnosis and, unfortunately, these metrics have shown only minimal success in predicting patient outcome. We consider nine newly diagnosed GBM patients receiving diagnostic biopsy followed by standard-of-care external beam radiation therapy (XRT). We present and apply a patient-specific, biologically based mathematical model for glioma growth that quantifies response to XRT in individual patients in vivo. The mathematical model uses net rates of proliferation and migration of malignant tumor cells to characterize the tumor's growth and invasion along with the linear-quadratic model for the response to radiation therapy. Using only routinely available pre-treatment MRIs to inform the patient-specific bio-mathematical model simulations, we find that radiation response in these patients, quantified by both clinical and model-generated measures, could have been predicted prior to treatment with high accuracy. Specifically, we find that the net proliferation rate is correlated with the radiation response parameter (r = 0.89, p = 0.0007), resulting in a predictive relationship that is tested with a leave-one-out cross-validation technique. This relationship predicts the tumor size post-therapy to within inter-observer tumor volume uncertainty. The results of this study suggest that a mathematical model can create a virtual in silico tumor with the same growth kinetics as a particular patient and can not only predict treatment response in individual patients in vivo but also provide a basis for evaluation of response in each patient to any given therapy.

Implementation and evaluation of various demons deformable image registration algorithms on a GPU

Abstract: Online adaptive radiation therapy (ART) promises the ability to deliver an optimal treatment in response to daily patient anatomic variation. A major technical barrier for the clinical implementation of online ART is the requirement of rapid image segmentation. Deformable image registration (DIR) has been used as an automated segmentation method to transfer tumor/organ contours from the planning image to daily images. However, the current computational time of DIR is insufficient for online ART. In this work, this issue is addressed by using computer graphics processing units (GPUs). A gray-scale-based DIR algorithm called demons and five of its variants were implemented on GPUs using the compute unified device architecture (CUDA) programming environment. The spatial accuracy of these algorithms was evaluated over five sets of pulmonary 4D CT images with an average size of 256 × 256 × 100 and more than 1100 expert-determined landmark point pairs each. For all the testing scenarios presented in this paper, the GPU-based DIR computation required around 7 to 11 s to yield an average 3D error ranging from 1.5 to 1.8 mm. It is interesting to find out that the original passive force demons algorithms outperform subsequently proposed variants based on the combination of accuracy, efficiency and ease of implementation.

Four-dimensional deformable image registration using trajectory modeling.

Abstract: A four-dimensional deformable image registration (4D DIR) algorithm, referred to as 4D local trajectory modeling (4DLTM), is presented and applied to thoracic 4D computed tomography (4DCT) image sets. The theoretical framework on which this algorithm is built exploits the incremental continuity present in 4DCT component images to calculate a dense set of parameterized voxel trajectories through space as functions of time. The spatial accuracy of the 4DLTM algorithm is compared with an alternative registration approach in which component phase to phase (CPP) DIR is utilized to determine the full displacement between maximum inhale and exhale images. A publically available DIR reference database (http://www.dir-lab.com) is utilized for the spatial accuracy assessment. The database consists of ten 4DCT image sets and corresponding manually identified landmark points between the maximum phases. A subset of points are propagated through the expiratory 4DCT component images. Cubic polynomials were found to provide sufficient flexibility and spatial accuracy for describing the point trajectories through the expiratory phases. The resulting average spatial error between the maximum phases was 1.25 mm for the 4DLTM and 1.44 mm for the CPP. The 4DLTM method captures the long-range motion between 4DCT extremes with high spatial accuracy.

Theoretical variance analysis of single- and dual-energy computed tomography methods for calculating proton stopping power ratios of biological tissues.

Abstract: We discovered an empirical relationship between the logarithm of mean excitation energy (ln Im) and the effective atomic number (EAN) of human tissues, which allows for computing patient-specific proton stopping power ratios (SPRs) using dual-energy CT (DECT) imaging. The accuracy of the DECT method was evaluated for 'standard' human tissues as well as their variance. The DECT method was compared to the existing standard clinical practice-a procedure introduced by Schneider et al at the Paul Scherrer Institute (the stoichiometric calibration method). In this simulation study, SPRs were derived from calculated CT numbers of known material compositions, rather than from measurement. For standard human tissues, both methods achieved good accuracy with the root-mean-square (RMS) error well below 1%. For human tissues with small perturbations from standard human tissue compositions, the DECT method was shown to be less sensitive than the stoichiometric calibration method. The RMS error remained below 1% for most cases using the DECT method, which implies that the DECT method might be more suitable for measuring patient-specific tissue compositions to improve the accuracy of treatment planning for charged particle therapy. In this study, the effects of CT imaging artifacts due to the beam hardening effect, scatter, noise, patient movement, etc were not analyzed. The true potential of the DECT method achieved in theoretical conditions may not be fully achievable in clinical settings. Further research and development may be needed to take advantage of the DECT method to characterize individual human tissues.

Treatment planning for a scanned carbon beam with a modified microdosimetric kinetic model.

Abstract: We describe a method to calculate the relative biological effectiveness in mixed radiation fields of therapeutic ion beams based on the modified microdosimetric kinetic model (modified MKM). In addition, we show the procedure for integrating the modified MKM into a treatment planning system for a scanned carbon beam. With this procedure, the model is fully integrated into our research version of the treatment planning system. To account for the change in radiosensitivity of a cell line, we measured one of the three MKM parameters from a single survival curve of the current cells and used the parameter in biological optimization. Irradiation of human salivary gland tumor cells was performed with a scanned carbon beam in the Heavy Ion Medical Accelerator in Chiba (HIMAC), and we then compared the measured depth-survival curve with the modified MKM predicted survival curve. Good agreement between the two curves proves that the proposed method is a candidate for calculating the biological effects in treatment planning for ion irradiation.

LaBr3:Ce and SiPMs for time-of-flight PET: achieving 100 ps coincidence resolving time

Abstract: 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.

In vivo transcranial cavitation threshold detection during ultrasound-induced blood-brain barrier opening in mice

Abstract: The in vivo cavitation response associated with blood-brain barrier (BBB) opening as induced by transcranial focused ultrasound (FUS) in conjunction with microbubbles was studied in order to better identify the underlying mechanism in its noninvasive application. A cylindrically focused hydrophone, confocal with the FUS transducer, was used as a passive cavitation detector (PCD) to identify the threshold of inertial cavitation (IC) in the presence of Definity® microbubbles (mean diameter range: 1.1-3.3 µm, Lantheus Medical Imaging, MA, USA). A vessel phantom was first used to determine the reliability of the PCD prior to in vivo use. A cerebral blood vessel was simulated by generating a cylindrical channel of 610 µm in diameter inside a polyacrylamide gel and by saturating its volume with microbubbles. The microbubbles were sonicated through an excised mouse skull. Second, the same PCD setup was employed for in vivo noninvasive (i.e. transdermal and transcranial) cavitation detection during BBB opening. After the intravenous administration of Definity® microbubbles, pulsed FUS was applied (frequency: 1.525 or 1.5 MHz, peak-rarefactional pressure: 0.15-0.60 MPa, duty cycle: 20%, PRF: 10 Hz, duration: 1 min with a 30 s interval) to the right hippocampus of twenty-six (n = 26) mice in vivo through intact scalp and skull. T1 and T2-weighted MR images were used to verify the BBB opening. A spectrogram was generated at each pressure in order to detect the IC onset and duration. The threshold of BBB opening was found to be at a 0.30 MPa peak-rarefactional pressure in vivo. Both the phantom and in vivo studies indicated that the IC pressure threshold had a peak-rarefactional amplitude of 0.45 MPa. This indicated that BBB opening may not require IC at or near the threshold. Histological analysis showed that BBB opening could be induced without any cellular damage at 0.30 and 0.45 MPa. In conclusion, the cavitation response could be detected without craniotomy in mice and IC may not be required for BBB opening at relatively low pressures.

Quantitative x-ray dark-field computed tomography

Abstract: The basic principles of x-ray image formation in radiology have remained essentially unchanged since Rontgen first discovered x-rays over a hundred years ago. The conventional approach relies on x-ray attenuation as the sole source of contrast and draws exclusively on ray or geometrical optics to describe and interpret image formation. Phase-contrast or coherent scatter imaging techniques, which can be understood using wave optics rather than ray optics, offer ways to augment or complement the conventional approach by incorporating the wave-optical interaction of x-rays with the specimen. With a recently developed approach based on x-ray optical gratings, advanced phase-contrast and dark-field scatter imaging modalities are now in reach for routine medical imaging and non-destructive testing applications. To quantitatively assess the new potential of particularly the grating-based dark-field imaging modality, we here introduce a mathematical formalism together with a material-dependent parameter, the so-called linear diffusion coefficient and show that this description can yield quantitative dark-field computed tomography (QDFCT) images of experimental test phantoms.

Enhancement of cell radiation sensitivity by pegylated gold nanoparticles

Abstract: Biocompatible Au nanoparticles with surfaces modified by PEG (polyethylene glycol) were developed in view of possible applications for the enhancement of radiotherapy. Such nanoparticles exhibit preferential deposition at tumor sites due to the enhanced permeation and retention (EPR) effect. Here, we systematically studied their effects on EMT-6 and CT26 cell survival rates during irradiation for a dose up to 10 Gy with a commercial biological irradiator (E(average) = 73 keV), a Cu-Kalpha(1) x-ray source (8.048 keV), a monochromatized synchrotron source (6.5 keV), a radio-oncology linear accelerator (6 MeV) and a proton source (3 MeV). The percentage of surviving cells after irradiation was found to decrease by approximately 2-45% in the presence of PEG-Au nanoparticles ([Au] = 400, 500 or 1000 microM). The cell survival rates decreased as a function of the dose for all sources and nanoparticle concentrations. These results could open the way to more effective cancer irradiation therapies by using nanoparticles with optimized surface treatment. Difficulties in applying MTT assays were also brought to light, showing that this approach is not suitable for radiobiology.

A soft-threshold filtering approach for reconstruction from a limited number of projections

Abstract: In the medical imaging field, discrete gradient transform (DGT) is widely used as a sparsifying operator to define the total variation (TV) Recently, TV minimization has become a hot topic in image reconstruction and is usually implemented using the steepest descent method (SDM) Since TV minimization with the SDM takes a long computational time, here we construct a pseudo-inverse of the DGT and adapt a soft-threshold filtering algorithm, whose convergence and efficiency have been theoretically proven Also, we construct a pseudo-inverse of the discrete difference transform (DDT) and design an algorithm for L1 minimization of the total difference These two methods are evaluated in numerical simulation The results demonstrate the merits of the proposed techniques

Noise and signal properties in PSF-based fully 3D PET image reconstruction: an experimental evaluation

Abstract: The addition of accurate system modeling in PET image reconstruction results in images with distinct noise texture and characteristics. In particular, the incorporation of point spread functions (PSF) into the system model has been shown to visually reduce image noise, but the noise properties have not been thoroughly studied. This work offers a systematic evaluation of noise and signal properties in different combinations of reconstruction methods and parameters. We evaluate two fully 3D PET reconstruction algorithms: (1) OSEM with exact scanner line of response modeled (OSEM+LOR), (2) OSEM with line of response and a measured point spread function incorporated (OSEM+LOR+PSF), in combination with the effects of four post-reconstruction filtering parameters and 1-10 iterations, representing a range of clinically acceptable settings. We used a modified NEMA image quality (IQ) phantom, which was filled with 68Ge and consisted of six hot spheres of different sizes with a target/background ratio of 4:1. The phantom was scanned 50 times in 3D mode on a clinical system to provide independent noise realizations. Data were reconstructed with OSEM+LOR and OSEM+LOR+PSF using different reconstruction parameters, and our implementations of the algorithms match the vendor's product algorithms. With access to multiple realizations, background noise characteristics were quantified with four metrics. Image roughness and the standard deviation image measured the pixel-to-pixel variation; background variability and ensemble noise quantified the region-to-region variation. Image roughness is the image noise perceived when viewing an individual image. At matched iterations, the addition of PSF leads to images with less noise defined as image roughness (reduced by 35% for unfiltered data) and as the standard deviation image, while it has no effect on background variability or ensemble noise. In terms of signal to noise performance, PSF-based reconstruction has a 7% improvement in contrast recovery at matched ensemble noise levels and 20% improvement of quantitation SNR in unfiltered data. In addition, the relations between different metrics are studied. A linear correlation is observed between background variability and ensemble noise for all different combinations of reconstruction methods and parameters, suggesting that background variability is a reasonable surrogate for ensemble noise when multiple realizations of scans are not available.

Accuracy of out-of-field dose calculations by a commercial treatment planning system

Abstract: The dosimetric accuracy of treatment planning systems (TPSs) decreases for locations outside the treatment field borders. However, the true accuracy of specific TPSs for locations beyond the treatment field borders is not well documented. Our objective was to quantify the accuracy of out-of-field dose predicted by the commercially available Eclipse version 8.6 TPS (Varian Medical Systems, Palo Alto, CA) for a clinical treatment delivered on a Varian Clinac 2100. We calculated (in the TPS) and determined (with thermoluminescent dosimeters) doses at a total of 238 points of measurement (with distance from the field edge ranging from 3.75 to 11.25 cm). Our comparisons determined that the Eclipse TPS underestimated out-of-field doses by an average of 40% over the range of distances examined. As the distance from the treatment field increased, the TPS underestimated the dose with increasing magnitude--up to 55% at 11.25 cm from the treatment field border. These data confirm that accuracy beyond the treatment border is inadequate, and out-of-field data from TPSs should be used only with a clear understanding of this limitation. Studies that require accurate out-of-field dose should use other dose reconstruction methods, such as direct measurements or Monte Carlo calculations.

Improved scatter correction using adaptive scatter kernel superposition

Abstract: Accurate scatter correction is required to produce high-quality reconstructions of x-ray cone-beam computed tomography (CBCT) scans. This paper describes new scatter kernel superposition (SKS) algorithms for deconvolving scatter from projection data. The algorithms are designed to improve upon the conventional approach whose accuracy is limited by the use of symmetric kernels that characterize the scatter properties of uniform slabs. To model scatter transport in more realistic objects, nonstationary kernels, whose shapes adapt to local thickness variations in the projection data, are proposed. Two methods are introduced: (1) adaptive scatter kernel superposition (ASKS) requiring spatial domain convolutions and (2) fast adaptive scatter kernel superposition (fASKS) where, through a linearity approximation, convolution is efficiently performed in Fourier space. The conventional SKS algorithm, ASKS, and fASKS, were tested with Monte Carlo simulations and with phantom data acquired on a table-top CBCT system matching the Varian On-Board Imager (OBI). All three models accounted for scatter point-spread broadening due to object thickening, object edge effects, detector scatter properties and an anti-scatter grid. Hounsfield unit (HU) errors in reconstructions of a large pelvis phantom with a measured maximum scatter-to-primary ratio over 200% were reduced from -90 ± 58 HU (mean ± standard deviation) with no scatter correction to 53 ± 82 HU with SKS, to 19 ± 25 HU with fASKS and to 13 ± 21 HU with ASKS. HU accuracies and measured contrast were similarly improved in reconstructions of a body-sized elliptical Catphan phantom. The results show that the adaptive SKS methods offer significant advantages over the conventional scatter deconvolution technique.

Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers.

Abstract: In this paper, we showed that Cerenkov radiation (CR) escaping from the surface of small living animals injected with (18)F-FDG can be detected with optical imaging techniques. (18)F decays by emitting positrons with a maximum energy of 0.635 MeV; such positrons, when travelling into tissues faster than the speed of light in the same medium, are responsible of CR emission. A detailed model of the CR spectrum considering the positron energy spectrum was developed in order to quantify the amount of light emission. The results presented in this work were obtained using a commercial optical imager equipped with charged coupled detectors (CCD). Our data open the door to optical imaging (OI) in vivo of the glucose metabolism, at least in pre-clinical research. We found that the heart and bladder can be clearly identified in the animal body reflecting the accumulation of the (18)F-FDG. Moreover, we describe two different methods based on the spectral analysis of the CR that can be used to estimate the depth of the source inside the animal. We conclude that (18)F-FDG can be employed as it is as a bimodal tracer for positron emission tomography (PET) and OI techniques. Our results are encouraging, suggesting that it could be possible to apply the proposed approach not only to beta(+) but also to pure beta(-) emitters.

A study on repainting strategies for treating moderately moving targets with proton pencil beam scanning at the new Gantry 2 at PSI.

Abstract: Treating moving targets using a scanning gantry for proton therapy is a promising but very challenging, not yet clinically demonstrated treatment modality. The interference of organ motion with the sequence of the beam delivery produces uncontrolled dose inhomogeneities within the target. One promising approach to overcome this difficulty is to increase the speed of scanning in order to apply the dose repeatedly (so-called repainting). To obtain sufficiently high scanning speeds a new, technologically improved gantry-Gantry 2-has been designed and is currently under construction at PSI. As there are many possible repainting strategies, the way repainting will be implemented on Gantry 2 will depend on the result of a careful analysis of the various treatment delivery strategies available. To achieve this aim, and prior to the start of experimental work with Gantry 2, simulations of dose distribution errors due to organ motion under various beam delivery strategies were investigated. The effects of motion on the dose distribution were studied for moderate motion amplitudes (5 mm) for spherical target volumes in a homogeneous medium and with homogeneous dose. In total over 200,000 dose distributions have been simulated and analyzed and selected results are discussed. From the obtained results we are confident to be able to treat moderately moving targets on Gantry 2 using repainted pencil-beam spot scanning. Continuous line scanning seems to be the most elegant solution; it provides higher repainting rates and produces superior results but is probably more difficult to realize. For larger motion amplitudes, continuous line scanning still shows good results, but we plan anyways to use a gating system for these cases, not only to reduce the inhomogeneity within the target volume but also to reduce safety margins.

Ventilation from four-dimensional computed tomography: density versus Jacobian methods.

Abstract: Two calculation methods to produce ventilation images from four-dimensional computed tomography (4DCT) acquired without added contrast have been reported. We reported a method to obtain ventilation images using deformable image registration (DIR) and the underlying CT density information. A second method performs the ventilation image calculation from the DIR result alone, using the Jacobian determinant of the deformation field to estimate the local volume changes resulting from ventilation. For each of these two approaches, there are variations on their implementation. In this study, two implementations of the Jacobian-based methodology are evaluated, as well as a single density change-based model for calculating the physiologic specific ventilation from 4DCT. In clinical practice, (99m)Tc-labeled aerosol single photon emission computed tomography (SPECT) is the standard method used to obtain ventilation images in patients. In this study, the distributions of ventilation obtained from the CT-based ventilation image calculation methods are compared with those obtained from the clinical standard SPECT ventilation imaging. Seven patients with 4DCT imaging and standard (99m)Tc-labeled aerosol SPECT/CT ventilation imaging obtained on the same day as part of a prospective validation study were selected. The results of this work demonstrate the equivalence of the Jacobian-based methodologies for quantifying the specific ventilation on a voxel scale. Additionally, we found that both Jacobian- and density-change-based methods correlate well with global measurements of the resting tidal volume. Finally, correlation with the clinical SPECT was assessed using the Dice similarity coefficient, which showed statistically higher (p-value < 10(-4)) correlation between density-change-based specific ventilation and the clinical reference than did either Jacobian-based implementation.

Photon-counting spectral computed tomography using silicon strip detectors: a feasibility study

Abstract: 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

Weighted iterative reconstruction for magnetic particle imaging

Abstract: Magnetic particle imaging (MPI) is a new imaging technique capable of imaging the distribution of superparamagnetic particles at high spatial and temporal resolution. For the reconstruction of the particle distribution, a system of linear equations has to be solved. The mathematical solution to this linear system can be obtained using a least-squares approach. In this paper, it is shown that the quality of the least-squares solution can be improved by incorporating a weighting matrix using the reciprocal of the matrix-row energy as weights. A further benefit of this weighting is that iterative algorithms, such as the conjugate gradient method, converge rapidly yielding the same image quality as obtained by singular value decomposition in only a few iterations. Thus, the weighting strategy in combination with the conjugate gradient method improves the image quality and substantially shortens the reconstruction time. The performance of weighting strategy and reconstruction algorithms is assessed with experimental data of a 2D MPI scanner.

RBE of low energy electrons and photons.

Abstract: Relative biological effectiveness (RBE) compares the severity of damage induced by a radiation under test at a dose D relative to the reference radiation D(x) for the same biological endpoint. RBE is an important parameter in estimation of risk from exposure to ionizing radiation (IR). The present work provides a review of the recently published data and the knowledge of the RBE of low energy electrons and photons. The review presents RBE values derived from experimental data and model calculations including cell inactivation, chromosome aberration, cell transformation, micronuclei formation and induction of double-strand breaks. Biophysical models, including physical features of radiation track, and microdosimetry parameters are presented, analysed and compared with experimental data. The biological effects of low energy electrons and photons are of particular interest in radiation biology as these are strongly absorbed in micrometer and sub-micrometer layers of tissue. RBE values not only depend on the electron and photon energies but also on the irradiation condition, cell type and experimental conditions.

Dosimetry for ion beam radiotherapy.

Abstract: Recently, ion beam radiotherapy (including protons as well as heavier ions) gained considerable interest. Although ion beam radiotherapy requires dose prescription in terms of iso-effective dose (referring to an iso-effective photon dose), absorbed dose is still required as an operative quantity to control beam delivery, to characterize the beam dosimetrically and to verify dose delivery. This paper reviews current methods and standards to determine absorbed dose to water in ion beam radiotherapy, including (i) the detectors used to measure absorbed dose, (ii) dosimetry under reference conditions and (iii) dosimetry under non-reference conditions. Due to the LET dependence of the response of films and solid-state detectors, dosimetric measurements are mostly based on ion chambers. While a primary standard for ion beam radiotherapy still remains to be established, ion chamber dosimetry under reference conditions is based on similar protocols as for photons and electrons although the involved uncertainty is larger than for photon beams. For non-reference conditions, dose measurements in tissue-equivalent materials may also be necessary. Regarding the atomic numbers of the composites of tissue-equivalent phantoms, special requirements have to be fulfilled for ion beams. Methods for calibrating the beam monitor depend on whether passive or active beam delivery techniques are used. QA measurements are comparable to conventional radiotherapy; however, dose verification is usually single field rather than treatment plan based. Dose verification for active beam delivery techniques requires the use of multi-channel dosimetry systems to check the compliance of measured and calculated dose for a representative sample of measurement points. Although methods for ion beam dosimetry have been established, there is still room for developments. This includes improvement of the dosimetric accuracy as well as development of more efficient measurement techniques.

Terahertz imaging applied to cancer diagnosis.

Abstract: We report on terahertz (THz) time-domain spectroscopy imaging of 10 microm thick histological sections. The sections are prepared according to standard pathological procedures and deposited on a quartz window for measurements in reflection geometry. Simultaneous acquisition of visible images enables registration of THz images and thus the use of digital pathology tools to investigate the links between the underlying cellular structure and specific THz information. An analytic model taking into account the polarization of the THz beam, its incidence angle, the beam shift between the reference and sample pulses as well as multiple reflections within the sample is employed to determine the frequency-dependent complex refractive index. Spectral images are produced through segmentation of the extracted refractive index data using clustering methods. Comparisons of visible and THz images demonstrate spectral differences not only between tumor and healthy tissues but also within tumors. Further visualization using principal component analysis suggests different mechanisms as to the origin of image contrast.

Age-dependent tissue-specific exposure of cell phone users

Abstract: 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.

X-ray fluorescence computed tomography (XFCT) imaging of gold nanoparticle-loaded objects using 110 kVp x-rays

Abstract: A conventional x-ray fluorescence computed tomography (XFCT) technique requires monochromatic synchrotron x-rays to simultaneously determine the spatial distribution and concentration of various elements such as metals in a sample. However, the synchrotron-based XFCT technique appears to be unsuitable for in vivo imaging under a typical laboratory setting. In this study we demonstrated, for the first time to our knowledge, the possibility of performing XFCT imaging of a small animal-sized object containing gold nanoparticles (GNPs) at relatively low concentrations using polychromatic diagnostic energy range x-rays. Specifically, we created a phantom made of polymethyl methacrylate plastic containing two cylindrical columns filled with saline solution at 1 and 2 wt% GNPs, respectively, mimicking tumors/organs within a small animal. XFCT scanning of the phantom was then performed using microfocus 110 kVp x-ray beam and cadmium telluride (CdTe) x-ray detector under a pencil beam geometry after proper filtering of the x-ray beam and collimation of the detector. The reconstructed images clearly identified the locations of the two GNP-filled columns with different contrast levels directly proportional to gold concentration levels. On the other hand, the current pencil-beam implementation of XFCT is not yet practical for routine in vivo imaging tasks with GNPs, especially in terms of scanning time. Nevertheless, with the use of multiple detectors and a limited number of projections, it may still be used to image some objects smaller than the current phantom size. The current investigation suggests several modification strategies of the current XFCT setup, such as the adoption of the quasi-monochromatic cone/fan x-ray beam and XFCT-specific spatial filters or pinhole detector collimators, in order to establish the ultimate feasibility of a bench-top XFCT system for GNP-based preclinical molecular imaging applications.

On developing B-spline registration algorithms for multi-core processors

Abstract: Spline-based deformable registration methods are quite popular within the medical-imaging community due to their flexibility and robustness. However, they require a large amount of computing time to obtain adequate results. This paper makes two contributions towards accelerating B-spline-based registration. First, we propose a grid-alignment scheme and associated data structures that greatly reduce the complexity of the registration algorithm. Based on this grid-alignment scheme, we then develop highly data parallel designs for B-spline registration within the stream-processing model, suitable for implementation on multi-core processors such as graphics processing units (GPUs). Particular attention is focused on an optimal method for performing analytic gradient computations in a data parallel fashion. CPU and GPU versions are validated for execution time and registration quality. Performance results on large images show that our GPU algorithm achieves a speedup of 15 times over the single-threaded CPU implementation whereas our multi-core CPU algorithm achieves a speedup of 8 times over the single-threaded implementation. The CPU and GPU versions achieve near-identical registration quality in terms of RMS differences between the generated vector fields.