Showing papers in "Physics in Medicine and Biology in 2004"

GATE : a simulation toolkit for PET and SPECT

Abstract: Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

The use of gold nanoparticles to enhance radiotherapy in mice.

Abstract: Mice bearing subcutaneous EMT-6 mammary carcinomas received a single intravenous injection of 1.9 nm diameter gold particles (up to 2.7 g Au/kg body weight), which elevated concentrations of gold to 7 mg Au/g in tumours. Tumour-to-normal-tissue gold concentration ratios remained approximately 8:1 during several minutes of 250 kVp x-ray therapy. One-year survival was 86% versus 20% with x-rays alone and 0% with gold alone. The increase in tumours safely ablated was dependent on the amount of gold injected. The gold nanoparticles were apparently non-toxic to mice and were largely cleared from the body through the kidneys. This novel use of small gold nanoparticles permitted achievement of the high metal content in tumours necessary for significant high-Z radioenhancement.

Development of realistic high-resolution whole-body voxel models of Japanese adult males and females of average height and weight, and application of models to radio-frequency electromagnetic-field dosimetry

Abstract: With advances in computer performance, the use of high-resolution voxel models of the entire human body has become more frequent in numerical dosimetries of electromagnetic waves. Using magnetic resonance imaging, we have developed realistic high-resolution whole-body voxel models for Japanese adult males and females of average height and weight. The developed models consist of cubic voxels of 2 mm on each side; the models are segmented into 51 anatomic regions. The adult female model is the first of its kind in the world and both are the first Asian voxel models (representing average Japanese) that enable numerical evaluation of electromagnetic dosimetry at high frequencies of up to 3 GHz. In this paper, we will also describe the basic SAR characteristics of the developed models for the VHF/UHF bands, calculated using the finite-difference time-domain method.

Distance-driven projection and backprojection in three dimensions

Abstract: Projection and backprojection are operations that arise frequently in tomographic imaging. Recently, we proposed a new method for projection and backprojection, which we call distance-driven, and that offers low arithmetic cost and a highly sequential memory access pattern. Furthermore, distance-driven projection and backprojection avoid several artefact-inducing approximations characteristic of some other methods. We have previously demonstrated the application of this method to parallel and fan beam geometries. In this paper, we extend the distance-driven framework to three dimensions and demonstrate its application to cone beam reconstruction. We also present experimental results to demonstrate the computational performance, the artefact characteristics and the noise-resolution characteristics of the distance-driven method in three dimensions.

Acquiring 4D thoracic CT scans using a multislice helical method

Abstract: Respiratory motion degrades anatomic position reproducibility during imaging, necessitates larger margins during radiotherapy planning and causes errors during radiation delivery. Computed tomography (CT) scans acquired synchronously with the respiratory signal can be used to reconstruct 4D CT scans, which can be employed for 4D treatment planning to explicitly account for respiratory motion. The aim of this research was to develop, test and clinically implement a method to acquire 4D thoracic CT scans using a multislice helical method. A commercial position-monitoring system used for respiratory-gated radiotherapy was interfaced with a third generation multislice scanner. 4D cardiac reconstruction methods were modified to allow 4D thoracic CT acquisition. The technique was tested on a phantom under different conditions: stationary, periodic motion and non-periodic motion. 4D CT was also implemented for a lung cancer patient with audio-visual breathing coaching. For all cases, 4D CT images were successfully acquired from eight discrete breathing phases, however, some limitations of the system in terms of respiration reproducibility and breathing period relative to scanner settings were evident. Lung mass for the 4D CT patient scan was reproducible to within 2.1% over the eight phases, though the lung volume changed by 20% between end inspiration and end expiration (870 cm3). 4D CT can be used for 4D radiotherapy, respiration-gated radiotherapy, 'slow' CT acquisition and tumour motion studies.

Poly(vinyl alcohol) cryogel phantoms for use in ultrasound and MR imaging

Abstract: Poly(vinyl alcohol) cryogel, PVA-C, is presented as a tissue-mimicking material, suitable for application in magnetic resonance (MR) imaging and ultrasound imaging. A 10% by weight poly(vinyl alcohol) in water solution was used to form PVA-C, which is solidified through a freeze-thaw process. The number of freeze-thaw cycles affects the properties of the material. The ultrasound and MR imaging characteristics were investigated using cylindrical samples of PVA-C. The speed of sound was found to range from 1520 to 1540 m s(-1), and the attenuation coefficients were in the range of 0.075-0.28 dB (cm MHz)(-1). T1 and T2 relaxation values were found to be 718-1034 ms and 108-175 ms, respectively. We also present applications of this material in an anthropomorphic brain phantom, a multi-volume stenosed vessel phantom and breast biopsy phantoms. Some suggestions are made for how best to handle this material in the phantom design and development process.

In vivo study of human skin using pulsed terahertz radiation

Abstract: Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumours tend to have different water content from normal tissue, a likely contrast mechanism is variation in water content. Thus, we have previously devised a finite difference time-domain (FDTD) model which is able to closely simulate the interaction of THz radiation with water. In this work we investigate the interaction of THz radiation with normal human skin on the forearm and palm of the hand in vivo. We conduct the first ever systematic in vivo study of the response of THz radiation to normal skin. We take in vivo reflection measurements of normal skin on the forearm and palm of the hand of 20 volunteers. We compare individual examples of THz responses with the mean response for the areas of skin under investigation. Using the in vivo data, we demonstrate that the FDTD model can be applied to biological tissue. In particular, we successfully simulate the interaction of THz radiation with the volar forearm. Understanding the interaction of THz radiation with normal skin will form a step towards developing improved imaging algorithms for diagnostic detection of skin cancer and other tissue disorders using THz radiation.

Prediction of respiratory tumour motion for real-time image-guided radiotherapy

Abstract: Image guidance in radiotherapy and extracranial radiosurgery offers the potential for precise radiation dose delivery to a moving tumour. Recent work has demonstrated how to locate and track the position of a tumour in real-time using diagnostic x-ray imaging to find implanted radio-opaque markers. However, the delivery of a treatment plan through gating or beam tracking requires adequate consideration of treatment system latencies, including image acquisition, image processing, communication delays, control system processing, inductance within the motor, mechanical damping, etc. Furthermore, the imaging dose given over long radiosurgery procedures or multiple radiotherapy fractions may not be insignificant, which means that we must reduce the sampling rate of the imaging system. This study evaluates various predictive models for reducing tumour localization errors when a real-time tumour-tracking system targets a moving tumour at a slow imaging rate and with large system latencies. We consider 14 lung tumour cases where the peak-to-peak motion is greater than 8 mm, and compare the localization error using linear prediction, neural network prediction and Kalman filtering, against a system which uses no prediction. To evaluate prediction accuracy for use in beam tracking, we compute the root mean squared error between predicted and actual 3D motion. We found that by using prediction, root mean squared error is improved for all latencies and all imaging rates evaluated. To evaluate prediction accuracy for use in gated treatment, we present a new metric that compares a gating control signal based on predicted motion against the best possible gating control signal. We found that using prediction improves gated treatment accuracy for systems that have latencies of 200 ms or greater, and for systems that have imaging rates of 10 Hz or slower.

Exact image reconstruction on PI-lines from minimum data in helical cone-beam CT.

Abstract: The development of accurate and efficient algorithms for image reconstruction from helical cone-beam projections remains a subject of active research. In the last few years, a number of quasi-exact and exact algorithms have been developed. Among them, the Katsevich algorithms are of filtered backprojection type and thus possess computational advantages over other existing exact algorithms. In this work, we propose an alternative approach to reconstructing exactly an image from helical cone-beam projections. Based on this approach, we develop an algorithm that requires less data than do the existing quasi-exact and exact algorithms, including the Katsevich algorithms. Our proposed algorithm is also of filtered backprojection type with one-dimensional filtering performed along a PI-line in image space. Therefore, it is (at least) computationally as efficient as the Katsevich algorithms. We have performed a preliminary numerical study to demonstrate and validate the proposed algorithm using computer-simulation data. The implication of the proposed approach and algorithm appears to be significant in that they can naturally address the long object problem as well as the super-short scan problem and, most importantly, in that they provide the opportunity to reconstruct images within any selected region of interest from minimum data, allowing the use of detector with a reduced size, the selection of a minimum number of rotation angles and thus the reduction of radiation dose delivered to the imaged subject.

A two-step Hilbert transform method for 2D image reconstruction.

Abstract: The paper describes a new accurate two-dimensional (2D) image reconstruction method consisting of two steps. In the first step, the backprojected image is formed after taking the derivative of the parallel projection data. In the second step, a Hilbert filtering is applied along certain lines in the differentiated backprojection (DBP) image. Formulae for performing the DBP step in fanbeam geometry are also presented. The advantage of this two-step Hilbert transform approach is that in certain situations, regions of interest (ROIs) can be reconstructed from truncated projection data. Simulation results are presented that illustrate very similar reconstructed image quality using the new method compared to standard filtered backprojection, and that show the capability to correctly handle truncated projections. In particular, a simulation is presented of a wide patient whose projections are truncated laterally yet for which highly accurate ROI reconstruction is obtained.

Medical phase contrast x-ray imaging: current status and future prospects.

Abstract: The exploitation of phase contrast appears to offer the tantalising possibility of creating the biggest change in medical x-ray imaging since the invention of computed tomography. A considerable number of experiments performed by researchers across four continents have produced some extraordinary images. These images have demonstrated greatly enhanced contrast over conventional methods revealing soft tissue discrimination at micron scale resolutions. Contrast improvements can be achieved at doses rather less than those required by conventional x-ray imaging. The use of synchrotrons has revealed the possibilities offered by these techniques but unfortunately the application of these ideas in a clinical context requires that technology be pushed to its limits in a number of areas including x-ray sources, optics and detectors. The current state of the art is reviewed.

In vivo molecular and genomic imaging: new challenges for imaging physics.

Abstract: The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field.

Extending the linear–quadratic model for large fraction doses pertinent to stereotactic radiotherapy

Abstract: Ongoing clinical trials designed to explore the use of extracranial stereotactic radiosurgery (ESR) for different tumour sites use large doses per fraction (15, 20, 30 Gy or even larger). The question of whether the linear-quadratic (LQ) model is appropriate to describe radiation response for such large fraction doses has been raised and has not been answered definitively. It has been proposed that mechanism-based models, such as the lethal-potentially lethal (LPL) model, could be more appropriate for such large fraction/acute doses. However, such models are not well characterized with clinical data and they are generally not easy to use. The purpose of this work is to modify the LQ model to more accurately describe radiation response for high fraction/acute doses. A new parameter is introduced in the modified LQ (MLQ) model. The new parameter introduced is characterized based both on in vitro cell survival data of several human tumour cell lines and in vivo animal iso-effect curves. The MLQ model produces a better fit to the iso-effect data than the LQ model. For a high single dose irradiation, the prediction of the MLQ is consistent with that from the LPL model. Unlike the LPL model, the MLQ model retains the simplicity of the LQ model and uses the well-characterized alpha and beta parameters. This work indicates that the standard LQ model can lead to erroneous results when used to calculate iso-effects with large fraction doses, such as those used for ESR. We present a solution to this problem.

Comment on the modified Beer–Lambert law for scattering media

Abstract: We present a concise overview of the modified Beer-Lambert law, which has been extensively used in the literature of near-infrared spectroscopy (NIRS) of scattering media. In particular, we discuss one form of the modified Beer-Lambert law that is commonly found in the literature and that is not strictly correct. However, this incorrect form of the modified Beer-Lambert law still leads to the correct expression for the changes in the continuous wave optical signal associated with changes in the absorption coefficient of the investigated medium. Here we propose a notation for the modified Beer-Lambert law that keeps the typical form commonly found in the literature without introducing any incorrect assumptions.

Fast free-form deformable registration via calculus of variations.

Abstract: In this paper, we present a fully automatic, fast and accurate deformable registration technique. This technique deals with free-form deformation. It minimizes an energy functional that combines both similarity and smoothness measures. By using calculus of variations, the minimization problem was represented as a set of nonlinear elliptic partial differential equations (PDEs). A Gauss-Seidel finite difference scheme is used to iteratively solve the PDE. The registration is refined by a multi-resolution approach. The whole process is fully automatic. It takes less than 3 min to register two three-dimensional (3D) image sets of size 256 x 256 x 61 using a single 933 MHz personal computer. Extensive experiments are presented. These experiments include simulations, phantom studies and clinical image studies. Experimental results show that our model and algorithm are suited for registration of temporal images of a deformable body. The registration of inspiration and expiration phases of the lung images shows that the method is able to deal with large deformations. When applied to the daily CT images of a prostate patient, the results show that registration based on iterative refinement of displacement field is appropriate to describe the local deformations in the prostate and the rectum. Similarity measures improved significantly after the registration. The target application of this paper is for radiotherapy treatment planning and evaluation that incorporates internal organ deformation throughout the course of radiation therapy. The registration method could also be equally applied in diagnostic radiology.

Integrating a MRI scanner with a 6 MV radiotherapy accelerator: dose deposition in a transverse magnetic field

Abstract: Integrating magnetic resonance imaging (MRI) functionality with a radiotherapy accelerator can facilitate on-line, soft-tissue based, position verification. A technical feasibility study, in collaboration with Elekta Oncology Systems and Philips Medical Systems, led to the preliminary design specifications of a MRI accelerator. Basically the design is a 6 MV accelerator rotating around a 1.5 T MRI system. Several technical issues and the clinical rational are currently under investigation. The aim of this paper is to determine the impact of the transverse 1.5 T magnetic field on the dose deposition. Monte Carlo simulations were used to calculate the dose deposition kernel in the presence of 1.5 T. This kernel in turn was used to determine the dose deposition for larger fields. Also simulations and measurements were done in the presence of 1.1 T. The pencil beam dose deposition is asymmetric. For larger fields the asymmetry persists but decreases. For the latter the distance to dose maximum is reduced by approximately 5 mm, the penumbra is increased by approximately 1 mm, and the 50% isodose line is shifted approximately 1 mm. The dose deposition in the presence of 1.5 T is affected, but the effect can be taken into account in a conventional treatment planning procedure. The impact of the altered dose deposition for clinical IMRT treatments is the topic of further research.

Reduction of ring artefacts in high resolution micro-CT reconstructions

Abstract: High resolution micro-CT images are often corrupted by ring artefacts, prohibiting quantitative analysis and hampering post processing. Removing or at least significantly reducing such artefacts is indispensable. However, since micro-CT systems are pushed to the extremes in the quest for the ultimate spatial resolution, ring artefacts can hardly be avoided. Moreover, as opposed to clinical CT systems, conventional correction schemes such as flat-field correction do not lead to satisfactory results. Therefore, in this note a simple but efficient and fast post processing method is proposed that effectively reduces ring artefacts in reconstructed μ-CT images.

Design and simulation of a high-resolution stationary SPECT system for small animals

Abstract: Exciting new SPECT systems can be created by combining pinhole imaging with compact high-resolution gamma cameras. These new systems are able to solve the problem of the limited sensitivity-resolution trade-off that hampers contemporary small animal SPECT. The design presented here (U-SPECT-III) uses a set of detectors placed in a polygonal configuration and a cylindrical collimator that contains 135 pinholes arranged in nine rings. Each ring contains 15 gold pinhole apertures that focus on the centre of the cylinder. A non-overlapping projection is acquired via each pinhole. Consequently, when a mouse brain is placed in the central field-of-view, each voxel in the cerebrum can be observed via 130 to 135 different pinholes simultaneously. A method for high-resolution scintillation detection is described that eliminates the depth-of-interaction problem encountered with pinhole cameras, and is expected to provide intrinsic detector resolutions better than 150 ?m. By means of simulations U-SPECT-III is compared to a simulated dual pinhole SPECT (DP-SPECT) system with a pixelated array consisting of 2.0 ? 2.0 mm NaI crystals. Analytic calculations indicate that the proposed U-SPECT-III system yields an almost four times higher linear and about sixty times higher volumetric system resolution than DP-SPECT, when the systems are compared at matching system sensitivity. In addition, it should be possible to achieve a 15 up to 30 times higher sensitivity with U-SPECT-III when the systems are compared at equal resolution. Simulated images of a digital mouse-brain phantom show much more detail with U-SPECT-III than with DP-SPECT. In a resolution phantom, 0.3 mm diameter cold rods are clearly visible with U-SPECT-III, whereas with DP-SPECT the smallest visible rods are about 0.6?0.8 mm. Furthermore, with U-SPECT-III, the image deformations outside the central plane of reconstruction that hamper conventional pinhole SPECT are strongly suppressed. Simulation results indicate that future pinhole SPECT systems are likely to bring about significant improvements in radio-molecular imaging of small animals.

Multiple-bandwidth photoacoustic tomography

Abstract: Photoacoustic tomography, also referred to as optoacoustic tomography, employs short laser pulses to generate ultrasonic waves in biological tissues. The reconstructed images can be characterized by the convolution of the structure of samples, the laser pulse and the impulse response of the ultrasonic transducer used for detection. Although the laser-induced ultrasonic waves cover a wide spectral range, a single transducer can receive only part of the spectrum because of its limited bandwidth. To systematically analyse this problem, we constructed a photoacoustic tomographic system that uses multiple ultrasonic transducers simultaneously, each at a different central frequency. The photoacoustic images associated with the different transducers were compared and analysed. The system was tested by imaging both mouse brains and phantom samples. The vascular vessels in the brain were revealed by all of the transducers, but the image resolutions differed. The higher frequency detectors provided better image resolution while the lower frequency detectors delineated the major structural traits with a higher signal–noise ratio.

A method to measure the hyperelastic parameters of ex vivo breast tissue samples

Abstract: Over the past decade, there has been increasing interest in modelling soft tissue deformation. This topic has several biomedical applications ranging from medical imaging to robotic assisted telesurgery. In these applications, tissue deformation can be very large due to low tissue stiffness and lack of physical constraints. As a result, deformation modelling of such organs often requires a treatment, which reflects nonlinear behaviour. While computational techniques such as nonlinear finite element methods are well developed, the required intrinsic nonlinear mechanical parameters of soft tissues that are critical to develop reliable tissue deformation models are not well known. To address this issue, we developed a system to measure the hyperelastic parameters of small ex vivo tissue samples. This measurement technique consists of indenting an unconfined small block of tissue using a computer controlled loading system while measuring the resulting indentation force. The nonlinear tissue force-displacement response is used to calculate the hyperelastic parameters via an appropriate inversion technique. This technique is based on a nonlinear least squares formulation that uses a nonlinear finite element model as the direct problem solver. The features of the system are demonstrated with two samples of breast tissue and typical hyperelastic results are presented.

A phenomenological model for the relative biological effectiveness in therapeutic proton beams.

Abstract: To study the effects of a variable relative biological effectiveness (RBE) in inverse treatment planning for proton therapy, fast methods for three-dimensional RBE calculations are required. We therefore propose a simple phenomenological model for the RBE in therapeutic proton beams. It describes the RBE as a function of the dose, the linear energy transfer (LET) and tissue specific parameters. Published experimental results for the dependence of the parameters alpha and beta from the linear-quadratic model on the dose averaged LET were evaluated. Using a linear function for alpha(LET) in the relevant LET region below 30 keV per micrometre and a constant beta, a simple formula for the RBE could be derived. The new model was able to reproduce the basic dependences of RBE on dose and LET, and the RBE values agreed well with experimental results. The model was also applied to spread-out Bragg peaks (SOBP), where the main effects of a variable RBE are an increase of the RBE along the SOBP plateau, and a shift in depth of the distal falloff. The new method allows fast RBE estimations and has therefore potential applications in iterative treatment planning for proton therapy.

An ultrasound-driven needle-insertion robot for percutaneous cholecystostomy

Abstract: A real-time ultrasound-guided needle-insertion medical robot for percutaneous cholecystostomy has been developed. Image-guided interventions have become widely accepted because they are consistent with minimal invasiveness. However, organ or abnormality displacement due to involuntary patient motion may undesirably affect the intervention. The proposed instrument uses intraoperative images and modifies the needle path in real time by using a novel ultrasonic image segmentation technique. In phantom and volunteer experiments, the needle path updating time was 130 and 301 ms per cycle, respectively. In animal experiments, the needle could be placed accurately in the target.

Weighted FBP—a simple approximate 3D FBP algorithm for multislice spiral CT with good dose usage for arbitrary pitch

Abstract: A new 3D reconstruction scheme, weighted filtered backprojection (WFBP) for multirow spiral CT based on an extension of the two-dimensional SMPR algorithm is described and results are presented. In contrast to other 3D algorithms available, the algorithm makes use of all available data for all pitch values. The algorithm is a FBP algorithm: linear convolution of the parallel data along the row direction followed by a 3D backprojection. Data usage for arbitrary pitch values is maintained through a weighting scheme which takes into account redundant data. If proper row weighting is applied, the image quality is superior to the image quality of the SMPR algorithm.

Photoacoustic imaging with deconvolution algorithm

Abstract: The impulse response of the ultrasonic transducer used for detection is crucial for photoacoustic imaging with high resolution. We demonstrate a reconstruction method that allows the optical absorption distribution of a sample to be reconstructed without knowing the impulse response of the ultrasonic transducer. A convolution relationship between photoacoustic signals measured by an ultrasound transducer and optical absorption distribution is developed. Based on this theory, the projection of the optical absorption distribution of a sample can be obtained directly by deconvolving the recorded PA signal originating from a point source out of that from the sample. And a modified filtered back projection algorithm is used to reconstruct the optical absorption distribution. We constructed a photoacoustic imaging system to validate the reconstruction method and the experimental results demonstrated that the reconstructed images agreed well with the original phantom samples. The spatial resolution of the system reaches 0.3 mm.

Three-dimensional cellular-level imaging using full-field optical coherence tomography.

Abstract: An ultrahigh-resolution full-field optical coherence tomography (OCT) system has been developed for cellular-level imaging of biological media. The system is based on a Linnik interference microscope illuminated with a tungsten halogen lamp, associated with a high-resolution CCD camera. En face tomographic images are produced in real time, with the best spatial resolution ever achieved in OCT (0.7 µm × 0.9 µm, axial × transverse). A shot-noise limited detection sensitivity of 80 dB can be reached with an acquisition time per image of 1 s. Images of animal ophthalmic biopsies and vegetal tissues are shown.

Transversal phase resolved polarization sensitive optical coherence tomography

Abstract: We present a novel optical coherence tomography (OCT) method to measure backscattered intensity and birefringence properties (retardation and fast axis orientation) and apply it to imaging of human ocular tissue. The method is based on a Mach Zehnder interferometer, on transversal scanning, and on a polarization sensitive two-channel detection. A highly stable carrier frequency is generated by acousto-optic modulators (AOMs). This allows a phase sensitive demodulation by the lock-in technique. Since the recording of individual interference fringes is avoided by this method the amount of data to be recorded and processed is considerably reduced. We demonstrate this method on human cornea and anterior chamber angle and present, to the best of our knowledge, the first OCT images of retardation and fast axis orientation of the anterior chamber angle region in vivo.

Viscoelastic characterization of in vitro canine tissue.

Abstract: Mechanical properties of biological tissues are of interest for assessing the performance of elastographic methods that evaluate the stiffness characteristics of tissue. The mechanical properties of interest include the frequency-dependent complex moduli, storage and loss moduli of tissues. Determination of the mechanical properties of biological tissues is often limited by proper geometry of the sample, as well as homogeneity of the stress–strain relationship. Measurements were performed on in vitro canine liver tissue specimens, over a frequency range from 0.1 to 400 Hz. Tests were conducted using an EnduraTEC ELF 3200, a dynamic testing system for determining the mechanical properties of materials. Both normal tissues and thermal lesions prepared by radio frequency ablation were tested. Experiments were conducted by uniaxially compressing tissue samples using Plexiglas platens larger than the specimens and measuring the load response. The resulting moduli spectra were then fit to a modified Kelvin–Voigt model, called the Kelvin–Voigt fractional derivative model. The data agree well with the model and in comparing the results from the normal tissue with that of the thermal lesions, the concept of a complex modulus contrast is introduced and its applications to elastography are discussed.

Integrated radiotherapy imaging system (IRIS): design considerations of tumour tracking with linac gantry-mounted diagnostic x-ray systems with flat-panel detectors

Abstract: The design of an integrated radiotherapy imaging system (IRIS), consisting of gantry mounted diagnostic (kV) x-ray tubes and fast read-out flat-panel amorphous-silicon detectors, has been studied. The system is meant to be capable of three main functions: radiographs for three-dimensional (3D) patient set-up, cone-beam CT and real-time tumour/marker tracking. The goal of the current study is to determine whether one source/panel pair is sufficient for real-time tumour/marker tracking and, if two are needed, the optimal position of each relative to other components and the isocentre. A single gantry-mounted source/imager pair is certainly capable of the first two of the three functions listed above and may also be useful for the third, if combined with prior knowledge of the target's trajectory. This would be necessary because only motion in two dimensions is visible with a single imager/source system. However, with previously collected information about the trajectory, the third coordinate may be derived from the other two with sufficient accuracy to facilitate tracking. This deduction of the third coordinate can only be made if the 3D tumour/marker trajectory is consistent from fraction to fraction. The feasibility of tumour tracking with one source/imager pair has been theoretically examined here using measured lung marker trajectory data for seven patients from multiple treatment fractions. The patients' selection criteria include minimum mean amplitudes of the tumour motions greater than 1 cm peak-to-peak. The marker trajectory for each patient was modelled using the first fraction data. Then for the rest of the data, marker positions were derived from the imager projections at various gantry angles and compared with the measured tumour positions. Our results show that, due to the three dimensionality and irregular trajectory characteristics of tumour motion, on a fraction-to-fraction basis, a 'monoscopic' system (single source/imager) is inadequate for consistent real-time tumour tracking, even with prior knowledge. We found that, among the seven patients studied with peak-to-peak marker motion greater than 1 cm, five cases have mean localization errors greater than 2 mm and two have mean errors greater than 3 mm. Because of this uncertainty associated with a monoscopic system, two source/imager pairs are necessary for robust 3D target localization. Dual orthogonal x-ray source/imager pairs mounted on the linac gantry are chosen for the IRIS. We further studied the placement of the x-ray sources/panel based on the geometric specifications of the Varian 21EX Clinac. The best configuration minimizes the localization error while maintaining a large field of view and avoiding collisions with the floor/ceiling or couch.

A unifying framework for multi-criteria fluence map optimization models.

Abstract: Models for finding treatment plans for intensity modulated radiation therapy are usually based on a number of structure-based treatment plan evaluation criteria, which are often conflicting. Rather than formulating a model that a priori quantifies the trade-offs between these criteria, we consider a multi-criteria optimization approach that aims at finding the so-called undominated treatment plans. We present a unifying framework for studying multi-criteria optimization problems for treatment planning that establishes conditions under which treatment plan evaluation criteria can be transformed into convex criteria while preserving the set of undominated treatment plans. Such transformations are identified for many of the criteria that have been proposed to date, establishing equivalences between these criteria. In addition, it is shown that the use of a nonconvex criterion can often be avoided by transformation to an equivalent convex criterion. In particular, we show that models employing criteria such as tumour control probability, normal tissue complication probability, probability of uncomplicated tumour control, as well as sigmoidal transformations of (generalized) equivalent uniform dose are equivalent to models formulated in terms of separable voxel-based criteria that penalize dose in individual voxels.

Climate change, ozone depletion and the impact on ultraviolet exposure of human skin.

Abstract: For 30 years there has been concern that anthropogenic damage to the Earth's stratospheric ozone layer will lead to an increase of solar ultraviolet (UV) radiation reaching the Earth's surface, with a consequent adverse impact on human health, especially to the skin. More recently, there has been an increased awareness of the interactions between ozone depletion and climate change (global warming), which could also impact on human exposure to terrestrial UV. The most serious effect of changing UV exposure of human skin is the potential rise in incidence of skin cancers. Risk estimates of this disease associated with ozone depletion suggest that an additional peak incidence of 5000 cases of skin cancer per year in the UK would occur around the mid-part of this century. Climate change, which is predicted to lead to an increased frequency of extreme temperature events and high summer temperatures, will become more frequent in the UK. This could impact on human UV exposure by encouraging people to spend more time in the sun. Whilst future social trends remain uncertain, it is likely that over this century behaviour associated with climate change, rather than ozone depletion, will be the largest determinant of sun exposure, and consequent impact on skin cancer, of the UK population.