Table of contents

The aim of this study was to investigate and quantify two biomarkers for radiation exposure (dicentrics and γ-H2AX foci) in human lymphocytes after CT scans in the presence of an iodinated contrast agent. Blood samples from a healthy donor were exposed to CT scans in the absence or presence of iotrolan 300 at iodine concentrations of 5 or 50 mg ml⁻¹ blood. The samples were exposed to 0.025, 0.05, 0.1 and 1 Gy in a tissue equivalent body phantom. Chromosome aberration scoring and automated microscopic analysis of γ-H2AX foci were performed in parts of the same samples. The theoretical physical dose enhancement factor (DEF) was calculated on the basis of the mass energy-absorption coefficients of iodine and blood and the photon energy spectrum of the CT tube. No significant differences in the yields of dicentrics and γ-H2AX foci were observed in the absence or presence of 5 mg iodine ml⁻¹ blood up to 0.1 Gy, whereas at 1 Gy the yields were elevated for both biomarkers. At an iodine concentration of 50 mg ml⁻¹ serving as a positive control, a biological DEF of 9.5 ± 1.4 and 2.3 ± 0.5 was determined for dicentrics and γ-H2AX foci, respectively. A physical DEF of 1.56 and 6.30 was calculated for 5 and 50 mg iodine ml⁻¹, respectively. Thus, it can be concluded that in the diagnostic dose range (radiation and contrast dose), no relevant biological dose-enhancing effect could be detected, whereas a clear biological dose-enhancing effect could be found for a contrast dose well outside the diagnostic CT range for the complete radiation dose range with both methods.

Quantitative contrast-enhanced mammography, based on a dual-energy approach, aims to extract quantitative and temporal information of the tumour enhancement after administration of iodinated vascular contrast media. Simulations using analytical expressions and optimization of critical parameters essential for the development of quantitative contrast-enhanced mammography are presented. The procedure has been experimentally evaluated using a tissue-equivalent phantom and an amorphous silicon active matrix flat panel imager. The x-ray beams were produced by a tungsten target tube and spectrally shaped using readily available materials. Measurement of iodine projected thickness in mg cm⁻² has been performed. The effect of beam hardening does not introduce nonlinearities in the measurement of iodine projected thickness for values of thicknesses found in clinical investigations. However, scattered radiation introduces significant deviations from slope equal to unity when compared with the actual iodine projected thickness. Scatter correction before the analysis of the dual-energy images provides accurate iodine projected thickness measurements. At 10% of the exposure used in clinical mammography, signal-to-noise ratios in excess of 5 were achieved for iodine projected thicknesses less than 3 mg cm⁻² within a 4 cm thick phantom. For the extraction of temporal information, a limited number of low-dose images were used with the phantom incorporating a flow of iodinated contrast medium. The results suggest that spatial and temporal information of iodinated contrast media can be used to indirectly measure the tumour microvessel density and determine its uptake and washout from breast tumours. The proposed method can significantly improve tumour detection in dense breasts. Its application to perform in situ x-ray biopsy and assessment of the oncolytic effect of anticancer agents is foreseeable.

Proton radiotherapy represents a potential major advance in cancer therapy. Most current proton beams are spread out to cover the tumor using passive scattering and collimation, resulting in an extra whole-body high-energy neutron dose, primarily from proton interactions with the final collimator. There is considerable uncertainty as to the carcinogenic potential of low doses of high-energy neutrons, and thus we investigate whether this neutron dose can be significantly reduced without major modifications to passively scattered proton beam lines. Our goal is to optimize the design features of a patient-specific collimator or pre-collimator/collimator assembly. There are a number of often contradictory design features, in terms of geometry and material, involved in an optimal design. For example, plastic or hybrid plastic/metal collimators have a number of advantages. We quantify these design issues, and investigate the practical balances that can be achieved to significantly reduce the neutron dose without major alterations to the beamline design or function. Given that the majority of proton therapy treatments, at least for the next few years, will use passive scattering techniques, reducing the associated neutron-related risks by simple modifications of the collimator assembly design is a desirable goal.

EEG source analysis is a valuable tool for brain functionality research and for diagnosing neurological disorders, such as epilepsy. It requires a geometrical representation of the human head or a head model, which is often modeled as an isotropic conductor. However, it is known that some brain tissues, such as the skull or white matter, have an anisotropic conductivity. Many studies reported that the anisotropic conductivities have an influence on the calculated electrode potentials. However, few studies have assessed the influence of anisotropic conductivities on the dipole estimations. In this study, we want to determine the dipole estimation errors due to not taking into account the anisotropic conductivities of the skull and/or brain tissues. Therefore, head models are constructed with the same geometry, but with an anisotropically conducting skull and/or brain tissue compartment. These head models are used in simulation studies where the dipole location and orientation error is calculated due to neglecting anisotropic conductivities of the skull and brain tissue. Results show that not taking into account the anisotropic conductivities of the skull yields a dipole location error between 2 and 25 mm, with an average of 10 mm. When the anisotropic conductivities of the brain tissues are neglected, the dipole location error ranges between 0 and 5 mm. In this case, the average dipole location error was 2.3 mm. In all simulations, the dipole orientation error was smaller than 10°. We can conclude that the anisotropic conductivities of the skull have to be incorporated to improve the accuracy of EEG source analysis. The results of the simulation, as presented here, also suggest that incorporation of the anisotropic conductivities of brain tissues is not necessary. However, more studies are needed to confirm these suggestions.

We investigate some generalizations of the most likely path formalism developed for proton-computed tomography. The stochastic path of a proton inside a homogeneous medium is replaced by a deterministic smooth path that maximizes the probability of the proton passing through the points on this curve, given measured entrance and exit parameters for each individual proton. We study various factors that influence this curve and the associated error envelopes. These factors are the influence of the energy loss, a logarithmic correction factor in the small angle Coulomb scattering and the importance of path length versus material thickness. We develop a method for further constraining the possible proton paths by including energy information in the derivation of the most likely path, utilizing an infinite-dimensional constrained functional analysis method. It is shown that while there is an additional uncertainty on the most likely path that is difficult to determine experimentally, the associated error envelopes are smaller, resulting in possibly slightly improved spatial resolution for proton-computed tomography.

Diffraction-enhanced imaging (DEI) is an x-ray-based medical imaging modality that, when used in tomography mode (DECT), can generate a three-dimensional map of both the apparent absorption coefficient and the out-of-plane gradient of the index of refraction of the sample. DECT is known to have contrast gains over monochromatic synchrotron radiation CT (SRCT) for soft tissue structures. The goal of this experiment was to compare contrast-to-noise ratio (CNR) and resolution in images of human trabecular bone acquired using SRCT with images acquired using DECT. All images were acquired at the National Synchrotron Light Source (Upton, NY, USA) at beamline X15 A at an x-ray energy of 40 keV and the silicon [3 3 3] reflection. SRCT, apparent absorption DECT and refraction DECT slice images of the trabecular bone were created. The apparent absorption DECT images have significantly higher spatial resolution and CNR than the corresponding SRCT images. Thus, DECT will prove to be a useful tool for imaging applications in which high contrast and high spatial resolution are required for both soft tissue features and bone.

Silicon diodes have good spatial resolution, which makes them advantageous over ionization chambers for dosimetry in fields with high dose gradients. However, silicon diodes overrespond to low-energy photons, that are more abundant in scatter which increase with large fields and larger depths. We present a cavity-theory-based model for a general response function for silicon detectors at arbitrary positions within photon fields. The model uses photon and electron spectra calculated from fluence pencil kernels. The incident photons are treated according to their energy through a bipartition of the primary beam photon spectrum into low- and high-energy components. Primary electrons from the high-energy component are treated according to Spencer–Attix cavity theory. Low-energy primary photons together with all scattered photons are treated according to large cavity theory supplemented with an energy-dependent factor K(E) to compensate for energy variations in the electron equilibrium. The depth variation of the response for an unshielded silicon detector has been calculated for 5 × 5 cm², 10 × 10 cm² and 20 × 20 cm² fields in 6 and 15 MV beams and compared with measurements showing that our model calculates response factors with deviations less than 0.6%. An alternative method is also proposed, where we show that one can use a correlation with the scatter factor to determine the detector response of silicon diodes with an error of less than 3% in 6 MV and 15 MV photon beams.

Three widely used Monte Carlo systems were benchmarked against recently published measurements of the angular distribution of 13 MeV and 20 MeV electrons scattered from foils of different atomic numbers and thicknesses. Source and geometry were simulated in detail to calculate electron fluence profiles 118.2 cm from the exit window. Results were compared to the measured fluence profiles and the characteristic angle where the fluence drops to 1/e of its maximum value. EGSnrc and PENELOPE results, on average, agreed with measurement within 1 standard deviation experimental uncertainty, with EGSnrc estimating slightly lower scatter than measurement and PENELOPE slightly higher scatter. Geant4.9.2 overestimated the characteristic angle for the lower atomic number foils by as much as 10%. Retuning of the scatter distributions in Geant4 led to a much better agreement with measurement, close to that achieved with the other codes. The 3% differences from measurement seen with all codes for at least some of the foils would result in clinically significant errors in the fluence profiles (2%/4 mm), given accurate knowledge of the electron source and treatment head geometry used in radiotherapy. Further improvement in simulation accuracy is needed to achieve 1%/1 mm agreement with measurement for the full range of beam energies, foil atomic number and thickness used in radiotherapy. EGSnrc would achieve this accuracy with an increase in thickness of the mylar sheets in the monitor chamber, PENELOPE with a decrease in thickness.

Lung tumors move during breathing depending on the patient's patho-physiological condition and orientation, thereby compromising the accurate deposition of the radiation dose during radiotherapy. In this paper, we present and validate a computer-based simulation framework to calculate the delivered dose to a 3D moving tumor and its surrounding normal tissues. The computer-based simulation framework models a 3D volumetric lung tumor and its surrounding tissues, simulates the tumor motion during a simulated dose delivery both as a self-reproducible motion and a random motion using the dose extracted from a treatment plan, and predicts the amount and location of radiation doses deposited. A radiation treatment plan of a small lung tumor (1–3 cm diameter) was developed in a commercial planning system (iPlan software, BrainLab, Munich, Germany) to simulate the radiation dose delivered. The dose for each radiation field was extracted from the software. The tumor motion was simulated for varying values of its rate, amplitude and direction within a single breath as well as from one breath to another. Such variations represent the variations in tumor motion induced by breathing variations. During the simulation of dose delivery, the dose on the target was summed to generate the real-time dose to the tumor for each beam independently. The simulation results show that the dose accumulated on the tumor varies significantly with both the tumor size and the tumor's motion rate, amplitude and direction. For a given tumor motion rate, amplitude and direction, the smaller the tumor size the smaller is the percentage of the radiation dose accumulated. The simulation results are validated by comparing the center plane of the 3D tumor with 2D film dosimetry measurements using a programmable 4D motion phantom moving in a self-reproducible pattern. The results also show the real-time capability of the framework at 40 discrete tumor motion steps per breath, which is higher than the number of four-dimensional computed tomography (CT) steps (approximately 20) during a single breath. The real-time capability enables the framework to be coupled with real-time tumor monitoring systems such as implanted fiducials for computing the dose delivered in real time during the treatment.

For radionuclide therapy, individual patient pharmacokinetics can be measured in three dimensions by sequential SPECT imaging. Accurate registration of the time series of images is central for voxel-based calculations of the residence time and absorbed dose. In this work, rigid and non-rigid methods are evaluated for registration of 6–7 SPECT/CT images acquired over a week, in anatomical regions from the head-and-neck region down to the pelvis. A method for calculation of the absorbed dose, including a voxel mass determination from the CT images, is also described. Registration of the SPECT/CT images is based on a CT-derived spatial transformation. Evaluation is focused on the CT registration accuracy, and on its impact on values of residence time and absorbed dose. According to the CT evaluation, the non-rigid method produces a more accurate registration than the rigid one. For images of the residence time and absorbed dose, registration produces a sharpening of the images. For volumes-of-interest, the differences between rigid and non-rigid results are generally small. However, the non-rigid method is more consistent for regions where non-rigid patient movements are likely, such as in the head–neck–shoulder region.

Amyloid-β plaques are an Alzheimer's disease biomarker which present unique challenges for near-infrared fluorescence tomography because of size (<50 µm diameter) and distribution. We used high-resolution simulations of fluorescence in a digital Alzheimer's disease mouse model to investigate the optimal fluorophore and imaging parameters for near-infrared fluorescence tomography of amyloid plaques. Fluorescence was simulated for amyloid-targeted probes with emission at 630 and 800 nm, plaque-to-background ratios from 1–1000, amyloid burden from 0–10%, and for transmission and reflection measurement geometries. Fluorophores with high plaque-to-background contrast ratios and 800 nm emission performed significantly better than current amyloid imaging probes. We tested idealized fluorophores in transmission and full-angle tomographic measurement schemes (900 source–detector pairs), with and without anatomical priors. Transmission reconstructions demonstrated strong linear correlation with increasing amyloid burden, but underestimated fluorescence yield and suffered from localization artifacts. Full-angle measurements did not improve upon the transmission reconstruction qualitatively or in semi-quantitative measures of accuracy; anatomical and initial-value priors did improve reconstruction localization and accuracy for both transmission and full-angle schemes. Region-based reconstructions, in which the unknowns were reduced to a few distinct anatomical regions, produced highly accurate yield estimates for cortex, hippocampus and brain regions, even with a reduced number of measurements (144 source–detector pairs).

Endothelial dysfunction is considered to be a key factor in the development of atherosclerosis, and the measurement of flow-mediated vasodilation (FMD) in brachial and other conduit arteries has become a common method to assess the status of endothelial function in vivo. Based on the direct relationship between the FMD response and local shear stress on the conduit brachial artery endothelium, we hypothesize that measuring relevant changes in the brachial wall strain tensor would provide a non-invasive tool for assessing vascular mechanics during post-occlusion reactive hyperemia. Direct measurement of the wall strain tensor due to FMD has not yet been reported in the literature. In this work, a noninvasive direct ultrasound-based strain tensor measuring (STM) technique is presented to assess changes in the mechanical parameters of the vascular wall during post-occlusion reactive hyperemia and/or FMD, including local velocities and displacements, diameter change, local strain tensor and strain rates. The STM technique utilizes sequences of B-mode ultrasound images as its input with no extra hardware requirement, and its algorithm starts with segmenting a region of interest within the artery and providing the acquisition parameters. Then a block matching technique based on speckle tracking is employed to measure the frame-to-frame local velocities. Displacements, diameter change, local strain tensor and strain rates are then calculated by integrating or differentiating velocity components. The accuracy of the STM algorithm was assessed in vitro using phantom studies, where an average error of 7% was reported using different displacement ranging from 100 µm to 1000 µm. Furthermore, in vivo studies using human subjects were performed to test the STM algorithm during pre- and post-occlusion. Good correlations (|r| >0.5, P < 0.05) were found between the post-occlusion responses of diameter change and local wall strains. Results indicate the validity and versatility of the STM algorithm and describe how parameters other than the diameter change are sensitive to reactive hyperemia following occlusion. This work suggests that parameters such as local strains and strain rates within the arterial wall are promising metrics for the assessment of endothelial function, which can then be used for accurate assessment of atherosclerosis. In summary, this study describes a simple and computationally efficient algorithm that can be integrated with ultrasound machines for vascular research. Moreover, it suggests that monitoring the local strain and strain rates of the brachial artery wall can replace or augment the measurement of arterial diameter in FMD studies.

This study is to evaluate the dose calculation accuracy using Varian's cone-beam CT (CBCT) for pelvic adaptive radiotherapy. We first calibrated the Hounsfield Unit (HU) to electron density (ED) for CBCT using a mini CT QC phantom embedded into an IMRT QA phantom. We then used a Catphan 500 with an annulus around it to check the calibration. The combined CT QC and IMRT phantom provided correct HU calibration, but not Catphan with an annulus. For the latter, not only was the Teflon an incorrect substitute for bone, but the inserts were also too small to provide correct HUs for air and bone. For the former, three different scan ranges (6 cm, 12 cm and 20.8 cm) were used to investigate the HU dependence on the amount of scatter. To evaluate the dose calculation accuracy, CBCT and plan-CT for a pelvic phantom were acquired and registered. The single field plan, 3D conformal and IMRT plans were created on both CT sets. Without inhomogeneity correction, the two CT generated nearly the same plan. With inhomogeneity correction, the dosimetric difference between the two CT was mainly from the HU calibration difference. The dosimetric difference for 6 MV was found to be the largest for the single lateral field plan (maximum 6.7%), less for the 3D conformal plan (maximum 3.3%) and the least for the IMRT plan (maximum 2.5%). Differences for 18 MV were generally 1–2% less. For a single lateral field, calibration with 20.8 cm achieved the minimum dosimetric difference. For 3D and IMRT plans, calibration with a 12 cm range resulted in better accuracy. Because Catphan is the standard QA phantom for the on-board imager (OBI) device, we specifically recommend not using it for the HU calibration of CBCT.

Cone-beam computed tomography (CBCT) is used for patient alignment before treatment and is ideal for use in adaptive radiotherapy to account for tumor shrinkage, organ deformation and weight loss. However, CBCT images are prone to artifacts such as streaking and cupping effects, reducing image quality and CT number accuracy. Our goal was to determine the optimum combination of cone-beam imaging options to increase the accuracy of image CT numbers. Several phantoms with and without inserts of known relative electron densities were imaged using the Varian on-board imaging system. It was found that CT numbers are most influenced by the selection of field-of-view and are dependent on object size and filter type. Image acquisition in half-fan mode consistently produced more accurate CT numbers, regardless of phantom size. Values measured using full-fan mode can differ by up to 7% from planning CT values. No differences were found between CT numbers of all phantom images with low and standard dose modes.

In this work we have developed a simulation tool, based on the PENELOPE code, to study the response of MOSFET devices to irradiation with high-energy photons. The energy deposited in the extremely thin silicon dioxide layer has been calculated. To reduce the statistical uncertainties, an ant colony algorithm has been implemented to drive the application of splitting and Russian roulette as variance reduction techniques. In this way, the uncertainty has been reduced by a factor of ∼5, while the efficiency is increased by a factor of above 20. As an application, we have studied the dependence of the response of the pMOS transistor 3N163, used as a dosimeter, with the incidence angle of the radiation for three common photons sources used in radiotherapy: a ⁶⁰Co Theratron-780 and the 6 and 18 MV beams produced by a Mevatron KDS LINAC. Experimental and simulated results have been obtained for gantry angles of 0^o, 15^o, 30^o, 45^o, 60^o and 75^o. The agreement obtained has permitted validation of the simulation tool. We have studied how to reduce the angular dependence of the MOSFET response by using an additional encapsulation made of brass in the case of the two LINAC qualities considered.

A solid dynamic phantom with tissue-like optical properties is presented, which contains seven discrete targets impregnated with thermochromic pigment located at different depths from the surface. Changes in absorption are obtained in response to localized heating of the targets, simulating haemodynamic changes occurring in the brain and other tissues. The depth sensitivity of a continuous wave optical topography system was assessed successfully using the phantom. Images of the targets have been reconstructed using a spatially variant regularization, and the determined spatial localization in the depth direction is shown to be accurate within an uncertainty of about 3 mm down to a depth of about 30 mm.

Online adaptive radiation therapy (ART) is an attractive concept that promises the ability to deliver an optimal treatment in response to the inter-fraction variability in patient anatomy. However, it has yet to be realized due to technical limitations. Fast dose deposit coefficient calculation is a critical component of the online planning process that is required for plan optimization of intensity-modulated radiation therapy (IMRT). Computer graphics processing units (GPUs) are well suited to provide the requisite fast performance for the data-parallel nature of dose calculation. In this work, we develop a dose calculation engine based on a finite-size pencil beam (FSPB) algorithm and a GPU parallel computing framework. The developed framework can accommodate any FSPB model. We test our implementation in the case of a water phantom and the case of a prostate cancer patient with varying beamlet and voxel sizes. All testing scenarios achieved speedup ranging from 200 to 400 times when using a NVIDIA Tesla C1060 card in comparison with a 2.27 GHz Intel Xeon CPU. The computational time for calculating dose deposition coefficients for a nine-field prostate IMRT plan with this new framework is less than 1 s. This indicates that the GPU-based FSPB algorithm is well suited for online re-planning for adaptive radiotherapy.

One approach to multi-criteria IMRT planning is to automatically calculate a data set of Pareto-optimal plans for a given planning problem in a first phase, and then interactively explore the solution space and decide on the clinically best treatment plan in a second phase. The challenge of computing the plan data set is to ensure that all clinically meaningful plans are covered and that as many clinically irrelevant plans as possible are excluded to keep computation times within reasonable limits. In this work, we focus on the approximation of the clinically relevant part of the Pareto surface, the process that constitutes the first phase. It is possible that two plans on the Pareto surface have a small, clinically insignificant difference in one criterion and a significant difference in another criterion. For such cases, only the plan that is clinically clearly superior should be included into the data set. To achieve this during the Pareto surface approximation, we propose to introduce bounds that restrict the relative quality between plans, the so-called trade-off bounds. We show how to integrate these trade-off bounds into the approximation scheme and study their effects. The proposed scheme is applied to two artificial cases and one clinical case of a paraspinal tumor. For all cases, the quality of the Pareto surface approximation is measured with respect to the number of computed plans, and the range of values occurring in the approximation for different criteria is compared. Through enforcing trade-off bounds, the scheme disregards clinically irrelevant plans during the approximation. Thereby, the number of plans necessary to achieve a good approximation quality can be significantly reduced. Thus, trade-off bounds are an effective tool to focus the planning and to reduce computation time.

In many medical treatments oscillating (non-equilibrium) bubbles appear. They can be the result of high-intensity-focused ultrasound, laser treatments or shock wave lithotripsy for example. The physics of such oscillating bubbles is often not very well understood. This is especially so if the bubbles are oscillating near (soft) bio-materials. It is well known that bubbles oscillating near (hard) materials have a tendency to form a high speed jet directed towards the material during the collapse phase of the bubble. It is equally well studied that bubbles near a free interface (air) tend to collapse with a jet directed away from this interface. If the interface is neither 'free' nor 'hard', such as often occurs in bio-materials, the resulting flow physics can be very complex. Yet, in many bio-applications, it is crucial to know in which direction the jet will go (if there is a jet at all). Some applications require a jet towards the tissue, for example to destroy it. For other applications, damage due to impacting jets is to be prevented at all cost. This paper tries to address some of the physics involved in these treatments by using a numerical method, the boundary element method (BEM), to study the dynamics of such bubbles near several bio-materials. In the present work, the behaviour of a bubble placed in a water-like medium near various bio-materials (modelled as elastic fluids) is investigated. It is found that its behaviour depends on the material properties (Young's modulus, Poisson ratio and density) of the bio-material. For soft bio-materials (fat, skin, brain and muscle), the bubble tends to split into smaller bubbles. In certain cases, the resulting bubbles develop opposing jets. For hard bio-materials (cornea, cartilage and bone), the bubble collapses towards the interface with high speed jets (between 100 and about 250 m s⁻¹). A summary graph is provided identifying the combined effects of the dimensionless elasticity (κ) and density ratio (α) of the elastic materials which will result in a nearby oscillating bubble jetting towards, splitting or jetting away from the elastic material interface. Since the phenomenon of a bubble jetting away from an elastic material as it collapses has not been reported before in the literature, experiments were performed to validate the numerical observation. A bubble is created in a heavy fluid (hydrofluoroether (HFE)) using a laser pulse. The bubble collapses near the elastic material polydimethylsiloxane (PDMS). The experimental results obtained are compared with the corresponding simulation. The simulation provides spatial and temporal details about the bubble dynamics beyond experimental limits and can therefore be considered as a very useful tool to get a better understanding of the physics involved.

This paper describes an LED-based optically stimulated luminescence (OSL) system for dose profile measurements using OSL detector strips and investigates its performance in x-ray computed tomography (CT) dosimetry. To compensate for the energy response of the Al₂O₃:C OSL detectors, which have an effective atomic number of 11.28, field-specific energy correction factors were determined using two methods: (a) comparing the OSL profiles with ionization chamber point measurements (0.3 cm³ ionization chamber) and (b) comparing the OSL profiles integrated over a 100 mm length with 100 mm long pencil ionization chamber measurements. These correction factors were obtained for the CT body and head phantoms, central and peripheral positions and three x-ray tube potential differences (100 kVp, 120 kVp and 140 kVp). The OSL dose profiles corrected by the energy dependence agreed with the ionization chamber point measurements over the entire length of the phantom (300 mm). For 120 kVp x-ray tube potential difference, the CTDI₁₀₀ values calculated using the OSL dose profiles corrected for the energy dependence and those obtained from an independent measurement with a 100 mm long pencil ionization chamber also agreed within ±5%.

In the liver, the efficacy of radiofrequency or high-intensity focused ultrasound (HIFU) ablation is impaired by blood perfusion. This can be overcome by hepatic inflow occlusion. Here we report the in vivo evaluation of ablations performed in the liver using a surgical toroidal HIFU device used during an open procedure with and without hepatic inflow occlusion. The HIFU device was composed of 256 toroidal-shaped emitters working at 3 MHz and an integrated ultrasound imaging probe working at 7.5 MHz. Using an intermittent Pringle maneuver (IPM), thermal ablations were created in three pigs with hepatic inflow occlusion (IPM group) and in three pigs with normal perfusion (NoIPM group). The ablations were studied on sonograms, macroscopically and microscopically 14 days after the treatment. In the NoIPM group, the average coagulated volume obtained after a 40 s exposure was 7.4 ± 3.8 cm³ (2.2–16.6). In the IPM group, the average ablated volume was 6.3 ± 2.9 cm³ (2.6–12.1). There was no significant difference between the two groups in terms of ablated volume (p = 0.25), diameter (p = 0.37) or depth (p = 0.61). Therefore, a toroidal-shaped HIFU device allows treatment in the liver that can be considered as independent from hepatic inflow occlusion.

We develop a statistical line of response (LOR) estimator of the three-dimensional interaction positions of a pair of annihilation photons in a PET detector module with depth of interaction capability. The three-dimensional points of interaction of a coincidence pair of photons within the detector module are estimated by calculation of an expectation of the points of interaction conditioned on the signals measured by the photosensors. This conditional expectation is computed from estimates of the probability density function of the light collection process and a model of the kinetics of photon interactions in the detector module. Our algorithm is capable of handling coincidences where each annihilation photon interacts any number of times within the detector module before being completely absorbed or escaping. In the case of multiple interactions, our algorithm estimates the position of the first interaction for each of the coincidence photons. This LOR estimation algorithm is developed for a high-resolution PET detector capable of providing depth-of-interaction information. Depth of interaction is measured by tailoring the light shared between two adjacent detector elements. These light-sharing crystal pairs are referred to as dMiCE and are being developed in our lab. Each detector element in the prototype system has a 2 × 2 mm² cross section and is directly coupled to a micro-pixel avalanche photodiode (MAPD). In this set-up, the distribution of the ratio of light shared between two adjacent detector elements can be expressed as a function of the depth of interaction. Monte Carlo experiments are performed using our LOR estimation algorithm and compared with Anger logic. We show that our LOR estimation algorithm provides a significant improvement over Anger logic under a variety of parameters.

Diffuse optical imaging is a non-invasive technique that uses near-infrared light to measure changes in brain activity through an array of sensors placed on the surface of the head. Compared to functional MRI, optical imaging has the advantage of being portable while offering the ability to record functional changes in both oxy- and deoxy-hemoglobin within the brain at a high temporal resolution. However, the reconstruction of accurate spatial images of brain activity from optical measurements represents an ill-posed and underdetermined problem that requires regularization. These reconstructions benefit from incorporating prior information about the underlying spatial structure and function of the brain. In this work, we describe a novel image reconstruction approach which uses surface-based wavelets derived from structural MRI to incorporate high-resolution anatomical and structural prior information about the brain. This surface-based approach is used to approximate brain activation patterns through the reconstruction and presentation of topographical (two-dimensional) maps of brain activation directly onto the folded surface of the cortex. The set of wavelet coefficients is directly estimated by a truncated singular-value decomposition based pseudo-inversion of the wavelet projection of the optical forward model. We use a reconstruction metric based on Shannon entropy which quantifies the sparse loading of the wavelet coefficients and is used to determine the optimal truncation and regularization of this inverse model. In this work, examples of the performance of this model are illustrated for several cases of numerical simulation and experimental data with comparison to functional magnetic resonance imaging.

Transport phenomena of platelets and white blood cells (WBCs) are fundamental to the processes of vascular disease and thrombosis. Unfortunately, the dilute volume occupied by these cells is not amenable to fluid-continuum modeling, and yet the cell count is large enough that modeling each individual cell is impractical for most applications. The most feasible option is to treat them as dilute species governed by convection and diffusion; however, this is further complicated by the role of the red blood cell (RBC) phase on the transport of these cells. We therefore propose an extended convection–diffusion (ECD) model based on the diffusive balance of a fictitious field potential, Ψ, that accounts for the gradients of both the dilute phase and the local hematocrit. The ECD model was applied to the flow of blood in a tube and between parallel plates in which a profile for the RBC concentration field was imposed and the resulting platelet concentration field predicted. Compared to prevailing enhanced-diffusion models that dispersed the platelet concentration field, the ECD model was able to simulate a near-wall platelet excess, as observed experimentally. The extension of the ECD model depends only on the ability to prescribe the hematocrit distribution, and therefore may be applied to a wide variety of geometries to investigate platelet-mediated vascular disease and device-related thrombosis.

The application of steady-state-free-precession (SSFP) techniques at 3 T systems is still limited by their sensitivity to magnetic field inhomogeneities. Especially during imaging of the heart, the arising signal voids and distortions in the myocardium currently often limit the diagnostic value of the resulting images. Dedicated shim systems providing higher order shimming capabilities have been applied to improve the field homogeneity across the heart. In this study, the potential benefit of applying a cardiac phase-specific shim (CPSS) was investigated. The cardiac phase dependence of the magnetic field distortions over the heart was assessed and the potential gain in field homogeneity by CPSS was evaluated. CPSS was successfully applied in volunteers and yielded significant improvement in the main magnetic field homogeneity over the entire cardiac cycle.

We studied through Monte Carlo simulation in Geant4 the absorbed fractions for photons, characterized by energies ranging from 10 keV to 1000 keV, which can be emitted by gamma radionuclides uniformly distributed in ellipsoidal volumes of soft tissue. The same analytical relationship between absorbed fraction and the 'generalized radius' as introduced in a previous paper was found, and the dependence of its parameters ρ₀ and s on photon energy is discussed and fitted by suitably chosen parametric functions. As a consequence, the absorbed fraction for photons in the 10–1000 keV energy range can be calculated for all volumes and for every ellipsoidal shape of practical interest. Such results can be a useful complement for the dosimetry of beta- and gamma-emitting radionuclides during internal radiotherapy or gamma emitters employed in diagnostic nuclear medicine.

A major difficulty in conformal lung cancer radiotherapy is respiratory organ motion, which may cause clinically significant targeting errors. Respiratory-gated radiotherapy allows for more precise delivery of prescribed radiation dose to the tumor, while minimizing normal tissue complications. Gating based on external surrogates is limited by its lack of accuracy, while gating based on implanted fiducial markers is limited primarily by the risk of pneumothorax due to marker implantation. Techniques for fluoroscopic gating without implanted fiducial markers (markerless gating) have been developed. These techniques usually require a training fluoroscopic image dataset with marked tumor positions in the images, which limits their clinical implementation. To remove this requirement, this study presents a markerless fluoroscopic gating algorithm based on 4DCT templates. To generate gating signals, we explored the application of three similarity measures or scores between fluoroscopic images and the reference 4DCT template: un-normalized cross-correlation (CC), normalized cross-correlation (NCC) and normalized mutual information (NMI), as well as average intensity (AI) of the region of interest (ROI) in the fluoroscopic images. Performance was evaluated using fluoroscopic and 4DCT data from three lung cancer patients. On average, gating based on CC achieves the highest treatment accuracy given the same efficiency, with a high target coverage (average between 91.9% and 98.6%) for a wide range of nominal duty cycles (20–50%). AI works well for two patients out of three, but failed for the third patient due to interference from the heart. Gating based on NCC and NMI usually failed below 50% nominal duty cycle. Based on this preliminary study with three patients, we found that the proposed CC-based gating algorithm can generate accurate and robust gating signals when using 4DCT reference template. However, this observation is based on results obtained from a very limited dataset, and further investigation on a larger patient population has to be done before its clinical implementation.

In our work, analysis and comparisons for water were made to the data of Kosanetzky et al (1987). The references to Narten (1970) in sections 4.4 and 5.1, including table 4 and figures 6 and 7, were in error and should be replaced by references to Kosanetzky it et al (1987).