Showing papers in "Physics in Medicine and Biology in 2001"
TL;DR: Applications of image registration include combining images of the same subject from different modalities, aligning temporal sequences of images to compensate for motion of the subject between scans, image guidance during interventions and aligning images from multiple subjects in cohort studies.
Abstract: Radiological images are increasingly being used in healthcare and medical research. There is, consequently, widespread interest in accurately relating information in the different images for diagnosis, treatment and basic science. This article reviews registration techniques used to solve this problem, and describes the wide variety of applications to which these techniques are applied. Applications of image registration include combining images of the same subject from different modalities, aligning temporal sequences of images to compensate for motion of the subject between scans, image guidance during interventions and aligning images from multiple subjects in cohort studies. Current registration algorithms can, in many cases, automatically register images that are related by a rigid body transformation (i.e. where tissue deformation can be ignored). There has also been substantial progress in non-rigid registration algorithms that can compensate for tissue deformation, or align images from different subjects. Nevertheless many registration problems remain unsolved, and this is likely to continue to be an active field of research in the future.
2,166 citations
TL;DR: A review article describes the developments of a number of 3D ultrasound imaging systems using mechanical, free-hand and 2D array scanning techniques and the sources of errors in the reconstruction techniques as well as formulae relating design specification to geometric errors.
Abstract: Ultrasound is an inexpensive and widely used imaging modality for the diagnosis and staging of a number of diseases. In the past two decades, it has benefited from major advances in technology and has become an indispensable imaging modality, due to its flexibility and non-invasive character. In the last decade, research investigators and commercial companies have further advanced ultrasound imaging with the development of 3D ultrasound. This new imaging approach is rapidly achieving widespread use with numerous applications. The major reason for the increase in the use of 3D ultrasound is related to the limitations of 2D viewing of 3D anatomy, using conventional ultrasound. This occurs because: (a) Conventional ultrasound images are 2D, yet the anatomy is 3D, hence the diagnostician must integrate multiple images in his mind. This practice is inefficient, and may lead to variability and incorrect diagnoses. (b) The 2D ultrasound image represents a thin plane at some arbitrary angle in the body. It is difficult to localize the image plane and reproduce it at a later time for follow-up studies. In this review article we describe how 3D ultrasound imaging overcomes these limitations. Specifically, we describe the developments of a number of 3D ultrasound imaging systems using mechanical, free-hand and 2D array scanning techniques. Reconstruction and viewing methods of the 3D images are described with specific examples. Since 3D ultrasound is used to quantify the volume of organs and pathology, the sources of errors in the reconstruction techniques as well as formulae relating design specification to geometric errors are provided. Finally, methods to measure organ volume from the 3D ultrasound images and sources of errors are described.
722 citations
TL;DR: The concept and feasibility of MAX-T and the capability of the treatment machine to deliver such a treatment were investigated by performing measurements for uniform and IMRT fields using a mechanical sinusoidal oscillator to simulate target motion.
Abstract: Intrafraction motion caused by breathing requires increased treatment margins for chest and abdominal radiotherapy and may lead to `motion artefacts' in dose distributions during intensity modulated radiotherapy (IMRT). Technologies such as gated radiotherapy may significantly increase the treatment time, while breath-hold techniques may be poorly tolerated by pulmonarily compromised patients. A solution that allows reduced margins and dose distribution artefacts, without compromising delivery time, is to synchronously follow the target motion by adapting the x-ray beam using a dynamic multileaf collimator (MLC), i.e. motion adaptive x-ray therapy, or MAX-T for short. Though the target is moving with time, in the MAX-T beam view the target is static. The MAX-T method superimposes the target motion due to respiration onto the beam originally planned for delivery. Thus during beam delivery the beam is dynamically changing position with respect to the isocentre using a dynamic MLC, the leaf positions of which are dependent upon the target position. Synchronization of the MLC motion and target motion occurs using respiration gated radiotherapy equipment. The concept and feasibility of MAX-T and the capability of the treatment machine to deliver such a treatment were investigated by performing measurements for uniform and IMRT fields using a mechanical sinusoidal oscillator to simulate target motion. Target dose measurements obtained using MAX-T for a moving target were found to be equivalent to those delivered to a static target by a static beam.
561 citations
TL;DR: An important determinant of the sensitivity to detect small dose changes is shown to be the slope-to-intercept ratio of the dose-response curve, which varied from 0.08 to 0.17, comparable to hypoxic gels described earlier.
Abstract: Polymer gels whose NMR and optical properties change when irradiated offer unique advantages for measuring radiation dose distributions. To date, all acrylic polymer gel dosimeters must be manufactured, stored and irradiated in hypoxic conditions which severely limits their use and stability. A new formulation of acrylic dosimeter gel has been developed that responds well in normal atmosphere and which we have named MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper). To produce dosimeter gels, an aqueous solution of gelatin, open to the atmosphere, is mixed with methacrylic acid, copper(II) ions, ascorbic acid and hydroquinone. It is believed that the copper(II) and ascorbic acid form a complex with oxygen which (with radiolysis of water) serves as a free radical source for the initiation of the polymerization of methacrylic acid. At room air the water proton spin relaxation rate R2 in MAGIC gels is proportional to absorbed dose though the precise relationship depends on the composition of the gel and the initiating complex. For example, in the range 0-30 Gy the slope of the response of R2 versus dose at 20 MHz was 0.300, 0.519 and 0.681 s(-1) Gy(-1), respectively, when the concentration of MAA was 3, 6 and 9%. The slopes increased to 0.310, 0.567 and 0.868 s(-1) Gy(-1) at 85 MHz. An important determinant of the sensitivity to detect small dose changes is shown to be the slope-to-intercept ratio of the dose-response curve. These varied from 0.08 to 0.17, comparable to hypoxic gels described earlier. MAGIC gels can be manufactured and used much more easily than the previous formulations and can be imaged by magnetic resonance imaging or optical scanning, and thus they will likely be of considerable interest to radiation physicists.
394 citations
TL;DR: Two near-infrared diffuse optical techniques are combined to study variations of blood flow, haemoglobin concentration, and blood oxygen saturation in the functioning rat brain to demonstrate self-consistency and compare with other measurements in the literature.
Abstract: We combine two near-infrared diffuse optical techniques to study variations of blood flow, haemoglobin concentration, and blood oxygen saturation in the functioning rat brain. Diffuse correlation spectroscopy (or flowmetry) monitors changes in the cerebral blood flow, without the use of the principles of tracer clearance, by measuring the optical phase-shifts caused by moving blood cells. Near-infrared absorption spectroscopy concurrently measures tissue absorption at two wavelengths to determine haemoglobin concentration and blood oxygen saturation in this same tissue volume. This optical probe is non-invasive and was employed through the intact skull. The utility of the technique is demonstrated in vivo by measuring the temporal changes in the regional vascular dynamics of rat brain during hypercapnia. Temporal and spatial variations of cerebral blood flow, haemoglobin concentration and blood oxygen saturation during hypercapnia are compared with other measurements in the literature, and a quantitative analysis demonstrating the self-consistency of our combined observations of vascular response is presented.
320 citations
TL;DR: Images from two phantoms and three different types of laboratory animal demonstrate the advantage of the P4 system over the original prototype microPET, including its threefold improvement in sensitivity and a large axial FOV sufficient to image an entire mouse in a single bed position.
Abstract: The microPET Primate 4-ring system (P4) is an animal PET tomograph with a 7.8 cm axial extent, a 19 cm diameter transaxial field of view (FOV) and a 22 cm animal port. The system is composed of 168 detector modules, each with an 8×8 array of 2.2×2.2×10 mm3 lutetium oxyorthosilicate crystals, arranged as 32 crystal rings 26 cm in diameter. The detector crystals are coupled to a Hamamatsu R5900-C8 PS-PMT via a 10 cm long optical fibre bundle. The detectors have a timing resolution of 3.2 ns, an average energy resolution of 26%, and an average intrinsic spatial resolution of 1.75 mm. The system operates in 3D mode without inter-plane septa, acquiring data in list mode. The reconstructed image spatial resolution ranges from 1.8 mm at the centre to 3 mm at 4 cm radial offset. The tomograph has a peak system sensitivity of 2.25% at the centre of the FOV with a 250-750 keV energy window. The noise equivalent count rate peaks at 100-290 kcps for representative object sizes. Images from two phantoms and three different types of laboratory animal demonstrate the advantage of the P4 system over the original prototype microPET, including its threefold improvement in sensitivity and a large axial FOV sufficient to image an entire mouse in a single bed position.
319 citations
TL;DR: In this paper, a review of the current understanding of the interactions between terahertz radiation and biological molecules, cells and tissues is presented, showing that at frequencies below approximately 6 THz the interaction may be understood as a classical EM wave interaction, whereas at higher frequencies transitions between different molecular vibrational and rotational energy levels are more readily understood using a quantum-mechanical framework.
Abstract: Terahertz (THz) radiation occupies that region of the electromagnetic (EM) spectrum between approximately 03 and 20 THz Recent advances in methods of producing THz radiation have stimulated interest in studying the interaction between radiation and biological molecules and tissue Given that the photon energies associated with this region of the spectrum are 20 x 10(-22) to 13 x 10(-20) J, an analysis of the interactions requires an understanding of the permittivity and conductivity of the medium (which describe the bulk motions of the molecules) and the possible transitions between the molecular energy levels This paper reviews current understanding of the interactions between THz radiation and biological molecules, cells and tissues At frequencies below approximately 6 THz the interaction may be understood as a classical EM wave interaction (using the parameters of permittivity and conductivity), whereas at higher frequencies transitions between different molecular vibrational and rotational energy levels become increasingly important and are more readily understood using a quantum-mechanical framework The latter is of particular interest in using THz to probe transitions between different vibrational modes of deoxyribonucleic acid Much additional experimental work is required in order to fully understand the interactions between THz radiation and biological molecules and tissue
269 citations
TL;DR: A theoretical approach is presented to determine absorption changes in different compartments of a layered structure from distributions of times of flight of photons, and a single-distance, time-domain method is applied to in vivo measurements on the human head.
Abstract: A theoretical approach is presented to determine absorption changes in different compartments of a layered structure from distributions of times of flight of photons. In addition resulting changes in spatial profiles of time-integrated intensity and mean time of flight are calculated. The capability of a single-distance, time-domain method to determine absorption changes with depth resolution is tested on a layered phantom. We apply this method to in vivo measurements on the human head (motor stimulation, Valsalva manoeuvre) and introduce a small-sized time-domain experimental set-up suitable for bedside monitoring.
267 citations
TL;DR: A novel computational algorithm is presented, which, at least in principle, yields an exact reconstruction of the absorbing structures in three-dimensional space inside the tissue based on 2D pressure distributions captured outside at different delay times.
Abstract: In medical imaging different techniques have been developed to gain information from inside a tissue. Optoacoustics is a method to generate tomography pictures of tissue using Q-switched laser pulses. Due to thermal and pressure confinement, a short light pulse generates a pressure distribution inside tissue, which mirrors absorbing structures and can be measured outside the tissue. Using a temporal back-projection method, the pressure distribution measured on the tissue surface allows us to gain a tomography picture of the absorbing structures inside tissue. This study presents a novel computational algorithm, which, at least in principle, yields an exact reconstruction of the absorbing structures in three-dimensional space inside the tissue. The reconstruction is based on 2D pressure distributions captured outside at different delay times. The algorithm is tested in a simulation and back-projection of pressure transients of a small absorber and a single point source.
254 citations
TL;DR: The dielectric properties of ten rat tissues at six different ages were measured using an open-ended coaxial probe and a computer controlled network analyser to provide some insight into possible differences in the assessment of exposure for children and adults.
Abstract: The dielectric properties of ten rat tissues at six different ages were measured at 37 °C in the frequency range of 130 MHz to 10 GHz using an open-ended coaxial probe and a computer controlled network analyser. The results show a general decrease of the dielectric properties with age. The trend is more apparent for brain, skull and skin tissues and less noticeable for abdominal tissues. The variation in the dielectric properties with age is due to the changes in the water content and the organic composition of tissues. The percentage decrease in the dielectric properties of certain tissues in the 30 to 70 day old rats at cellular phone frequencies have been tabulated. These data provide an important input in the provision of rigorous dosimetry in lifetime-exposure animal experiments. The results provide some insight into possible differences in the assessment of exposure for children and adults.
251 citations
TL;DR: The Monte Carlo code PENELOPE has been used to simulate electron beams from a Siemens Mevatron KDS linac with nominal energies of 6, 12 and 18 MeV, and its results are compared with those of equivalent simulations with the EGS4-based user codes BEAM and DOSXYZ.
Abstract: The Monte Carlo code PENELOPE has been used to simulate electron beams from a Siemens Mevatron KDS linac with nominal energies of 6, 12 and 18 MeV. Owing to its accuracy, which stems from that of the underlying physical interaction models, PENELOPE is suitable for simulating problems of interest to the medical physics community. It includes a geometry package that allows the definition of complex quadric geometries, such as those of irradiation instruments, in a straightforward manner. Dose distributions in water simulated with PENELOPE agree well with experimental measurements using a silicon detector and a monitoring ionization chamber. Insertion of a lead slab in the incident beam at the surface of the water phantom produces sharp variations in the dose distributions, which are correctly reproduced by the simulation code. Results from PENELOPE are also compared with those of equivalent simulations with the EGS4-based user codes BEAM and DOSXYZ. Angular and energy distributions of electrons and photons in the phase-space plane (at the downstream end of the applicator) obtained from both simulation codes are similar, although significant differences do appear in some cases. These differences, however, are shown to have a negligible effect on the calculated dose distributions. Various practical aspects of the simulations, such as the calculation of statistical uncertainties and the effect of the 'latent' variance in the phase-space file, are discussed in detail.
TL;DR: This review discusses the various ways in which tissue pattern can be engineered chiefly from a biophysical standpoint and gives particular attention to regions of research and practice where the involvement of the physicist or biophysicist is of importance.
Abstract: Tissue engineering is the construction, repair or replacement of damaged or missing tissue in humans and other animals. This engineering may take place within the animal body or as tissue constructs to be made in a bioreactor for later grafting into the animal. The minimal set of materials for this are the appropriate types of cell. Usually, however, non-living substrata are used as well. These substrata may be nothing more than materials that bulk up any voids in the damaged tissue and provide the mechanical strength that has been lost when the tissue is damaged or removed. They may serve a similar pair of functions in the bioreactor. They can do much more in terms of pattern formation. The orientations and morphology of the cells, the arrangement of intercellular material as it is laid down and the relationships between different cell types in the repairing or construct tissue are all of importance, for these should resemble the correct normal tissue as closely as possible. Most of these requirements are ones involving pattern formation. This review discusses the various ways in which tissue pattern can be engineered chiefly from a biophysical standpoint. Unpatterned cells are effectively not tissue. This engineering includes the use of topography on the substrata, chemical patterning of adhesive and other cues for the cells, mechanical force application to cause cell orientation and appropriate synthetic responses and electrical fields. The review also discusses the methods used to impart the appropriate cues to and through the materials which are often biodegradable polymers. The article gives particular attention to regions of research and practice where the involvement of the physicist or biophysicist is of importance.
TL;DR: The results demonstrate conclusively that bulk susceptibility variations in the lungs during respiration cause variations inThe static magnetic field within the brain tissue and suggest that respiration effects may not necessarily be well characterized as simple additive noise and that an alternative model based on the physical origins of susceptibility variations may be more appropriate.
Abstract: Functional magnetic resonance imaging relies on detecting small changes in the signal in the presence of noise from various sources. It has been shown that periodic variations in the signal at the respiratory frequency occur in the brain and various techniques have been proposed to remove them. However, the precise mechanism by which respiration affects the fMRI signal has not yet been proven. Here, we explore the nature of respiratory signal variations and the artefacts they produce in brain images. Our results demonstrate conclusively that bulk susceptibility variations in the lungs during respiration cause variations in the static magnetic field within the brain tissue. These variations in field strength and homogeneity lead to a shift of the image and a shading of image intensity in the phase encoding direction. These artefacts, if left uncorrected, may lead to the production of spurious activations and/or decreased statistical significance of true activations in fMRI. In addition, these results suggest that respiration effects may not necessarily be well characterized as simple additive noise and that an alternative model based on the physical origins of susceptibility variations may be more appropriate.
TL;DR: The best fit of the absorption spectra measured in vivo with the spectra of the pure constituents yielded information on the percentage composition of the different tissues, and the interpretation of transport scattering spectra with Mie theory provided information on tissue structure.
Abstract: A fully automated system for time-resolved reflectance spectroscopy based on tunable mode-locked laser sources and on time-correlated single-photon counting for the detection of time-resolved reflectance data was applied to the evaluation of the optical properties of biological tissues (arm, abdomen and forehead) in vivo from 610 to 1010 nm. The scattering decreases progressively with increasing wavelength, while the absorption line shapes show the typical spectral features of the principal tissue components (haemoglobin, water and lipid), with different weights depending on the tissue type. The best fit of the absorption spectra measured in vivo with the spectra of the pure constituents yielded information on the percentage composition of the different tissues. The interpretation of transport scattering spectra with Mie theory provided information on tissue structure.
TL;DR: StO2 is not equal to any fixed weighted average of SaO2 and SvO2 unless the authors introduce an effective background tissue absorption, which may be real, an artefact caused by the application of a simplified model to a complex sample, or a combination of factors.
Abstract: The frequency-domain multiple-distance (FDMD) method is capable of measuring the absolute absorption and reduced scattering coefficients of optically turbid media. Absolute measurement of absorption at two near-infrared (NIR) wavelengths makes possible the quantitation of tissue haemoglobin concentration and tissue haemoglobin oxygen-saturation (StO2). However, errors are introduced by the uncertainties of background absorption and the dissimilarities between real tissues and the simplified mathematical model on which these measurements are based. An FDMD-based tissue instrument has been used for the monitoring of tissue haemoglobin concentration and oxygenation in the brain of newborn piglets during periods of hypoxia and hyperoxia. These tissue haemoglobin saturation values were compared with arterial saturation (SaO2) and venous saturation (SvO2) measured by blood gas analyses. A linear correlation was observed between StO2 and the average of SaO2 and SvO2. However, StO2 is not equal to any fixed weighted average of SaO2 and SvO2 unless we introduce an effective background tissue absorption. The magnitude of the background absorption was about 0.08 cm −1 at 758 nm and 0.06 cm −1 at 830 nm, and it was nearly consistent between piglets. The origin of this ‘effective’ background absorption may be real, an artefact caused by the application of a simplified model to a complex sample, or a combination of factors.
TL;DR: Dpdelta of a polyacrylamide polymer gel dosimeter is presented for customized 32-echo and standard multiple-spin-echo sequences on a clinical MRI scanner.
Abstract: In polymer gel dosimetry using magnetic resonance imaging, the uncertainty in absorbed dose is dependent on the experimental determination of T2. The concept of dose resolution (Dpdelta) of polymer gel dosimeters is developed and applied to the uncertainty in dose related to the uncertainty in T2 from a range of T4 encountered in polymer gel dosimetry. Dpdelta is defined as the minimal separation between two absorbed doses such that they may be distinguished with a given level of confidence, p. The minimum detectable dose (MDD) is Dpdelta as the dose approaches zero. Dpdelta and the minimum detectable dose both give a quantifiable indication of the likely practical limitations and usefulness of the dosimeter. Dpdelta of a polyacrylamide polymer gel dosimeter is presented for customized 32-echo and standard multiple-spin-echo sequences on a clinical MRI scanner. In evaluating uncertainties in T2, a parameter of particular significance in the pulse sequence is the echo spacing (ES). For optimal results, ES should be selected to minimize Dpdelta over a range of doses of interest in polymer gel dosimetry.
TL;DR: An iterative Bayesian reconstruction algorithm for limited view angle tomography, or ectomography, based on the three-dimensional total variation (TV) norm has been developed and has been shown to improve the perceived image quality.
Abstract: An iterative Bayesian reconstruction algorithm for limited view angle tomography, or ectomography, based on the three-dimensional total variation (TV) norm has been developed. The TV norm has been described in the literature as a method for reducing noise in two-dimensional images while preserving edges, without introducing ringing or edge artefacts. It has also been proposed as a 2D regularization function in Bayesian reconstruction, implemented in an expectation maximization algorithm (TV-EM). The TV-EM was developed for 2D single photon emission computed tomography imaging, and the algorithm is capable of smoothing noise while maintaining edges without introducing artefacts. The TV norm was extended from 2D to 3D and incorporated into an ordered subsets expectation maximization algorithm for limited view angle geometry. The algorithm, called TV3D-EM, was evaluated using a modelled point spread function and digital phantoms. Reconstructed images were compared with those reconstructed with the 2D filtered backprojection algorithm currently used in ectomography. Results show a substantial reduction in artefacts related to the limited view angle geometry, and noise levels were also improved. Perhaps most important, depth resolution was improved by at least 45%. In conclusion, the proposed algorithm has been shown to improve the perceived image quality.
Journal Article•
TL;DR: It is shown that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament and type III beta-tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy.
Abstract: Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent alpha-latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission. Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III beta-tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy. Ultrastructurally, axon terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells. These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating nerve terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.
TL;DR: The results presented in this paper represent the first simultaneous tomographic reconstruction of the internal scattering and absorbing properties of a clinical subject using purely temporal data, with additional co-registered difference images showing repeatable absorption changes at two wavelengths in response to exercise.
Abstract: A 32-channel time-resolved optical imaging instrument has been developed principally to study functional parameters of the new-born infant brain. As a prelude to studies on infants, the device and image reconstruction methodology have been evaluated on the adult human forearm. Cross-sectional images were generated using time-resolved measurements of transmitted light at two wavelengths. All data were acquired using a fully automated computer-controlled protocol. Images representing the internal scattering and absorbing properties of the arm are presented, as well as images that reveal physiological changes during a simple finger flexion exercise. The results presented in this paper represent the first simultaneous tomographic reconstruction of the internal scattering and absorbing properties of a clinical subject using purely temporal data, with additional co-registered difference images showing repeatable absorption changes at two wavelengths in response to exercise.
TL;DR: Experimental results indicate that inverse methods using appropriate cortex-based source models are almost always able to locate the active source with excellent precision, with little or no spurious activity in close or distant regions, even when two sources are simultaneously active.
Abstract: We used a real-skull phantom head to investigate the performances of representative methods for EEG source localization when considering various head models. We describe several experiments using a montage with current sources located at multiple positions and orientations inside a human skull filled with a conductive medium. The robustness of selected methods based on distributed source models is evaluated as various solutions to the forward problem (from the sphere to the finite element method) are considered. Experimental results indicate that inverse methods using appropriate cortex-based source models are almost always able to locate the active source with excellent precision, with little or no spurious activity in close or distant regions, even when two sources are simultaneously active. Superior regularization schemes for solving the inverse problem can dramatically help the estimation of sparse and focal active zones, despite significant approximation of the head geometry and the conductivity properties of the head tissues. Realistic head models are necessary, though, to fit the data with a reasonable level of residual variance.
TL;DR: Resistivity values were measured from living human brain tissue in nine patients and values for tumour tissues were dependent on the type of tumour and ranged from 2.30 to 9.70 Ohms m.
Abstract: Resistivity values were measured from living human brain tissue in nine patients. A monopolar needle electrode was used with a measurement frequency of 50 kHz. Mean values were 3.51 Ohms m for grey matter and 3.91 Ohms m for white matter. Cerebrospiral fluid had a mean value of 0.80 Ohms m. Values for tumour tissues were dependent on the type of tumour and ranged from 2.30 to 9.70 Ohms m.
TL;DR: A new OCT scanner based on a broad beam light source and a two-dimensional charge-coupled device (CCD) detector is described, showing that the non-uniform pixel sensitivity of the low-cost CCD detector used and the granularity of the diffuser screen lead to a serious ring artefact in the reconstructed images.
Abstract: Methods based on magnetic resonance imaging for the measurement of threedimensional distributions of radiation dose are highly developed. However, relatively little work has been done on optical computed tomography (OCT). This paper describes a new OCT scanner based on a broad beam light source and a two-dimensional charge-coupled device (CCD) detector. A number of key design features are discussed including the light source; the scanning tank, turntable and stepper motor control; the diffuser screen onto which images are projected and the detector. It is shown that the non-uniform pixel sensitivity of the low-cost CCD detector used and the granularity of the diffuser screen lead to a serious ring artefact in the reconstructed images. Methods are described for eliminating this. The problems arising from reflection and refraction at the walls of the gel container are explained. Optical ray-tracing simulations are presented for cylindrical containers with a variety of radii and verified experimentally. Small changes in the model parameters lead to large variations in the signal intensity observed in the projection data. The effect of imperfect containers on data quality is discussed and a method based on a ‘correction scan’ is shown to be successful in correcting many of the related image artefacts. The results of two tomography experiments are presented. In the first experiment, a radiochromic Fricke gel sample was exposed four times in different positions to a 100 kVp x-ray beam perpendicular to the plane of imaging. Images of absorbed dose with slice thickness of 140 µm were acquired, with ‘true’ in-plane resolution of 560 × 560 µm 2 at the edge of the 72 mm field of view and correspondingly higher resolution at the centre. The nominal doses measured correlated well with the known exposure times. The second experiment demonstrated the well known phenomenon of diffusion in the dosemeter gels and yielded a value of (0.12 ± 0.02) mm 2 s −1 for the
TL;DR: The clinical implementation and application of a novel treatment planning system (TPS) for scanned ion beams is described, which is in clinical use for carbon ion treatments at the German heavy ion facility (GSI).
Abstract: The clinical implementation and application of a novel treatment planning system (TPS) for scanned ion beams is described, which is in clinical use for carbon ion treatments at the German heavy ion facility (GSI) All treatment plans are evaluated on the basis of biologically effective dose distributions For therapy control, in-beam positron emission tomography (PET) and an online monitoring system for the beam intensity and position are used The absence of a gantry restricts the treatment plans to horizontal beams Most of the treatment plans consist of two nearly opposing lateral fields or sometimes orthogonal fields In only a very few cases a single beam was used For patients with very complex target volumes lateral and even distal field patching techniques were applied Additional improvements can be achieved when the patient's head is fixed in a tilted position, in order to achieve sparing of the organs at risk In order to test the stability of dose distributions in the case of patient misalignments we routinely simulate the effects of misalignments for patients with critical structures next to the target volume The uncertainties in the range calculation are taken into account by a margin around the target volume of typically 2-3 mm, which can, however, be extended if the simulation demonstrates larger deviations The novel TPS developed for scanned ion beams was introduced into clinical routine in December 1997 and was used for the treatment planning of 63 patients with head and neck tumours until July 2000 Planning strategies and methods were developed for this tumour location that facilitate the treatment of a larger number of patients with the scanned heavy ion beam in a clinical setting Further developments aim towards a simultaneous optimization of the treatment field intensities and more effective procedures for the patient set-up The results demonstrate that ion beams can be integrated into a clinical environment for treatment planning and delivery
TL;DR: This work shows that increasing the comonomer concentration increases the CT-dose sensitivity of the polymer gel dosimeter, which can be further increased by replacing gelatin with agarose, and Varying the gelatin concentration however does not significantly change the CT -dose sensitivity.
Abstract: Changes in the linear attenuation coefficient of polymer gel dosimeters post-irradiation enable the imaging of dose distributions by x-ray computed tomography (CT). Various compositions of polymer gel dosimeters manufactured from acrylamide (AA), and N,N'-methylene-bis-acrylamide (BIS) comonomers and gelatin or agarose gelling agents were investigated. This work shows that increasing the comonomer concentration increases the CT-dose sensitivity of the polymer gel dosimeter. This can be further increased by replacing gelatin with agarose. Varying the gelatin concentration however does not significantly change the CT-dose sensitivity. Among the compositions studied, dose resolution (D(delta)95%) was found to be optimal for polymer gel dosimeters comprising 5% gelatin, 3% AA, 3% BIS and 89% water.
TL;DR: For samples stored within crushed ice for up to 30 h post-mortem the wavelength dependence of optical properties of the dermis remains unchanged while the values of the parameters vary moderately due to modification of the water content of the tissue.
Abstract: The weak absorption of shortwave infrared light by skin tissues between 700 and 1500 nm offers an important window for diagnosis by optical means. The strong scattering of shortwave infrared light by the skin, however, presents a challenge to the modelling of light propagation through the skin and the understanding of skin optics. We have measured the collimated and diffuse transmittance and diffuse reflectance of porcine skin dermis samples within 30 h post-mortem. Monte Carlo simulations have been performed to inversely determine the absorption coefficient, scattering coefficient and anisotropy factor of the dermis samples in the spectral range from 900 to 1500 nm. We further analyse the sensitivity of the values of the parameters to the experimental errors and inverse calculation procedures. The state of the cellular integrity of the skin samples following optical measurements was verified using transmission electron microscopy. These results were correlated to study post-mortem effects on the in vitro optical properties of porcine dermis. We concluded that for samples stored within crushed ice for up to 30 h post-mortem the wavelength dependence of optical properties of the dermis remains unchanged while the values of the parameters vary moderately due to modification of the water content of the tissue.
TL;DR: The application of this multiobjective gradient-based algorithm to two test cases shows that a correct selection for the importance factors to multiply the individual objectives in the global objective value is not trivial and that the location and shape of the boundary region between the feasible and non-feasible solution regions are case dependent.
Abstract: A multiobjective gradient-based algorithm has been developed for the purpose of dose distribution optimization in external beam conformal radiotherapy. This algorithm is based on the concept of gathering the values of all objectives into a single value. The weighting factors of the composite objective values are varied in different steps, allowing the reconstruction of the trade-off surfaces (three or more objectives) or curves (two objectives) which define the boundary between the feasible and non-feasible domain regions. The analysis of these curves allows the decision-maker to select the solution that best fits the clinical goals. In contrast to all the other algorithms, our method provides not a single solution but a sample of solutions representing all possible clinical importance factors (weights) for the objectives used. The application of this algorithm to two test cases shows that a correct selection for the importance factors to multiply the individual objectives in the global objective value is not trivial and that the location and shape of the boundary region between the feasible and non-feasible solution regions are case dependent. Provided that the individual objective functions are analytically differentiable and that the number of objectives is the range of two to three, the computation times are acceptable for clinical use. Furthermore, the optimization for a unique combination of importance factors within the aggregate objective function is performed in less than 1 min.
TL;DR: The aim of this work was to investigate the applicability of MR-based polymer gel dosimetry to measure the absorbed dose distribution at short distance from an iridium-192 brachytherapy point source by constructing a dose-versus-distance curve by polar averaging.
Abstract: The aim of this work was to investigate the applicability of MR-based polymer gel dosimetry to measure the absorbed dose distribution at short distance from an iridium-192 brachytherapy point source. In this paper, different methodological problems that may result in significant errors in the measured dose distribution are discussed. First of all the extent to which physico-chemical mechanisms alter the dose response is discussed. The most important among these are the oxygen permeability of the catheter material and monomer-diffusion-related effects during irradiation. The effect of oxygen on the dose–R2 curve has been determined quantitatively and an oxygen map is performed using a well-defined external irradiation beam. The effect of diffusion of monomer during irradiation has been simulated. Another contribution of errors is related to magnetic susceptibility differences between the catheter and the gel during scanning the irradiated gel. The magnetic field distortion has been mapped by using both an experimental MRI technique and by simulation. Moreover, in constructing a dose-versus-distance curve by polar averaging, the sensitivity to the exact distance between source and point of measurement and to partial volume effects is illustrated. An optimization program is proposed to determine the location of the source on a sub-pixel scale.
TL;DR: BF can be measured accurately and BF, PS, BV and MTT reproducibly using the functional CT technique can be readily incorporated into existing imaging protocols to assess tumour angiogenesis.
Abstract: Functional parameters such as blood flow (BF), microvessel permeability surface area product (PS), blood volume (BV) and mean transit time (MTT) are physiological markers related to the changes associated with angiogenesis. In the current study we present a functional CT technique for the simultaneous measurement of these four functional parameters and the display of each parameter as a functional image over an entire tissue slice. New Zealand White rabbits with implanted VX2 thigh tumours were scanned using CT with contrast media injection. The ex vivo method of radioactive microspheres was used to evaluate the accuracy of BF measurements with the functional CT technique. There was a significant linear correlation (R = 0.96) between regional CT and microsphere-measured BF values, with a slope not significantly different from unity (0.98 +/- 0.02, P < 0.0001). The precision of our CT technique was determined by the repeated scanning under steady-state conditions. The precision of CT-measured BF, PS. BV and MTT was 14%, 18%, 20% and 24%, respectively. In conclusion, BF can be measured accurately and BF, PS, BV and MTT reproducibly using our functional CT technique. Functional CT can be readily incorporated into existing imaging protocols to assess tumour angiogenesis.
TL;DR: Time-resolved optical coherence tomography and still images were compared with predictions of temperature rise and damage using Monte Carlo and finite difference techniques, and predicted damage agreed with the actual blood vessel and surrounding tissue coagulation seen in images.
Abstract: Optical-thermal models that can accurately predict temperature rise and damage in blood vessels and surrounding tissue may be used to improve the treatment of vascular disorders. Verification of these models has been hampered by the lack of time- and depth-resolved experimental data. In this preliminary study, an optical coherence tomography system operating at 4-30 frames per second was used to visualize laser irradiation of cutaneous (hamster dorsal skin flap) blood vessels. An argon laser was utilized with the following parameters: pulse duration 0.1-2.0 s, spot size 0.1-1.0 mm, power 100-400 mW. Video microscopy images were obtained before and after irradiations, and optical-thermal modelling was performed on two irradiation cases. Time-resolved optical coherence tomography and still images were compared with predictions of temperature rise and damage using Monte Carlo and finite difference techniques. In general, predicted damage agreed with the actual blood vessel and surrounding tissue coagulation seen in images. However, limitations of current optical-thermal models were identified, such as the inability to model the dynamic changes in blood vessel diameter that were seen in the optical coherence tomography images.
TL;DR: It is suggested that preferential deposition of microspheres in the well-vascularized periphery of large tumours will lead to a high proportion of the tumour volume receiving a therapeutic dose, with most of the normal liver tissue being spared substantial damage.
Abstract: Radiation dose distributions arising from intrahepatic arterial infusion of 90Y microspheres have been investigated. Tissue samples from normal liver, the tumour periphery and tumour centre were taken from a patient following infusion of 3 GBq of 32 microm diameter resin microspheres labelled with 90Y as treatment for an 80 mm diameter metastatic liver tumour. The measured microsphere distributions in three dimensions were used to calculate radiation dose patterns. Although microspheres concentrated in the tumour periphery, heterogeneous doses were delivered to all tissues. Within the tumour periphery average doses ranged from 200 Gy to 600 Gy with minimum doses between 70 Gy and 190 Gy. The average and minimum doses for the tumour centre sample were 6.8 Gy and 3.7 Gy respectively. In the normal liver sample the average dose was 8.9 Gy with a minimum dose of 5 Gy. Less than 1% of the normal liver tissue volume received more than 30 Gy, the level above which complications have resulted for whole liver exposure using external beam radiotherapy. These calculations suggest that preferential deposition of microspheres in the well-vascularized periphery of large tumours will lead to a high proportion of the tumour volume receiving a therapeutic dose, with most of the normal liver tissue being spared substantial damage.