Showing papers in "Physics in Medicine and Biology in 2003"

Digital x-ray tomosynthesis: current state of the art and clinical potential

Abstract: Digital x-ray tomosynthesis is a technique for producing slice images using conventional x-ray systems. It is a refinement of conventional geometric tomography, which has been known since the 1930s. In conventional geometric tomography, the x-ray tube and image receptor move in synchrony on opposite sides of the patient to produce a plane of structures in sharp focus at the plane containing the fulcrum of the motion; all other structures above and below the fulcrum plane are blurred and thus less visible in the resulting image. Tomosynthesis improves upon conventional geometric tomography in that it allows an arbitrary number of in-focus planes to be generated retrospectively from a sequence of projection radiographs that are acquired during a single motion of the x-ray tube. By shifting and adding these projection radiographs, specific planes may be reconstructed. This topical review describes the various reconstruction algorithms used to produce tomosynthesis images, as well as approaches used to minimize the residual blur from out-of-plane structures. Historical background and mathematical details are given for the various approaches described. Approaches for optimizing the tomosynthesis image are given. Applications of tomosynthesis to various clinical tasks, including angiography, chest imaging, mammography, dental imaging and orthopaedic imaging, are also described.

The magnetic lead field theorem in the quasi-static approximation and its use for magnetoencephalography forward calculation in realistic volume conductors.

Abstract: The equation for the magnetic lead field for a given magnetoencephalography (MEG) channel is well known for arbitrary frequencies omega but is not directly applicable to MEG in the quasi-static approximation. In this paper we derive an equation for omega = 0 starting from the very definition of the lead field instead of using Helmholtz's reciprocity theorems. The results are (a) the transpose of the conductivity times the lead field is divergence-free, and (b) the lead field differs from the one in any other volume conductor by a gradient of a scalar function. Consequently, for a piecewise homogeneous and isotropic volume conductor, the lead field is always tangential at the outermost surface. Based on this theoretical result, we formulated a simple and fast method for the MEG forward calculation for one shell of arbitrary shape: we correct the corresponding lead field for a spherical volume conductor by a superposition of basis functions, gradients of harmonic functions constructed here from spherical harmonics, with coefficients fitted to the boundary conditions. The algorithm was tested for a prolate spheroid of realistic shape for which the analytical solution is known. For high order in the expansion, we found the solutions to be essentially exact and for reasonable accuracies much fewer multiplications are needed than in typical implementations of the boundary element methods. The generalization to more shells is straightforward.

Acquiring a four-dimensional computed tomography dataset using an external respiratory signal.

Abstract: Four-dimensional (4D) methods strive to achieve highly conformal radiotherapy, particularly for lung and breast tumours, in the presence of respiratory-induced motion of tumours and normal tissues. Four-dimensional radiotherapy accounts for respiratory motion during imaging, planning and radiation delivery, and requires a 4D CT image in which the internal anatomy motion as a function of the respiratory cycle can be quantified. The aims of our research were (a) to develop a method to acquire 4D CT images from a spiral CT scan using an external respiratory signal and (b) to examine the potential utility of 4D CT imaging. A commercially available respiratory motion monitoring system provided an 'external' tracking signal of the patient's breathing. Simultaneous recording of a TTL 'X-Ray ON' signal from the CT scanner indicated the start time of CT image acquisition, thus facilitating time stamping of all subsequent images. An over-sampled spiral CT scan was acquired using a pitch of 0.5 and scanner rotation time of 1.5 s. Each image from such a scan was sorted into an image bin that corresponded with the phase of the respiratory cycle in which the image was acquired. The complete set of such image bins accumulated over a respiratory cycle constitutes a 4D CT dataset. Four-dimensional CT datasets of a mechanical oscillator phantom and a patient undergoing lung radiotherapy were acquired. Motion artefacts were significantly reduced in the images in the 4D CT dataset compared to the three-dimensional (3D) images, for which respiratory motion was not accounted. Accounting for respiratory motion using 4D CT imaging is feasible and yields images with less distortion than 3D images. 4D images also contain respiratory motion information not available in a 3D CT image.

Monte Carlo modelling of external radiotherapy photon beams.

Abstract: An essential requirement for successful radiation therapy is that the discrepancies between dose distributions calculated at the treatment planning stage and those delivered to the patient are minimized. An important component in the treatment planning process is the accurate calculation of dose distributions. The most accurate way to do this is by Monte Carlo calculation of particle transport, first in the geometry of the external or internal source followed by tracking the transport and energy deposition in the tissues of interest. Additionally, Monte Carlo simulations allow one to investigate the influence of source components on beams of a particular type and their contaminant particles. Since the mid 1990s, there has been an enormous increase in Monte Carlo studies dealing specifically with the subject of the present review, i.e., external photon beam Monte Carlo calculations, aided by the advent of new codes and fast computers. The foundations for this work were laid from the late 1970s until the early 1990s. In this paper we will review the progress made in this field over the last 25 years. The review will be focused mainly on Monte Carlo modelling of linear accelerator treatment heads but sections will also be devoted to kilovoltage x-ray units and 60Co teletherapy sources.

Determination of complex refractive index of polystyrene microspheres from 370 to 1610 nm

Abstract: We introduce an inverse method for determining simultaneously the real and imaginary refractive indices of microspheres based on integrating sphere measurements of diffuse reflectance and transmittance, and Monte Carlo modelling in conjunction with the Mie theory. The results for polystyrene microspheres suspended in water are presented.

Measuring the elastic modulus of ex vivo small tissue samples

Abstract: Over the past decade, several methods have been proposed to image tissue elasticity based on imaging methods collectively called elastography. While progress in developing these systems has been rapid, the basic understanding of tissue properties to interpret elastography images is generally lacking. To address this limitation, we developed a system to measure the Young's modulus of small soft tissue specimens. This system was designed to accommodate biological soft tissue constraints such as sample size, geometry imperfection and heterogeneity. The measurement technique consists of indenting an unconfined small block of tissue while measuring the resulting force. We show that the measured force-displacement slope of such a geometry can be transformed to the tissue Young's modulus via a conversion factor related to the sample's geometry and boundary conditions using finite element analysis. We also demonstrate another measurement technique for tissue elasticity based on quasi-static magnetic resonance elastography in which a tissue specimen encased in a gelatine-agarose block undergoes cyclical compression with resulting displacements measured using a phase contrast MRI technique. The tissue Young's modulus is then reconstructed from the measured displacements using an inversion technique. Finally, preliminary elasticity measurement results of various breast tissues are presented and discussed.

An experimental investigation on intra-fractional organ motion effects in lung IMRT treatments

Abstract: Respiration-induced tumour motion can potentially compromise the use of intensity-modulated radiotherapy (IMRT) as a dose escalation tool for lung tumour treatment. We have experimentally investigated the intra-fractional orga nm otion effects in lung IMRT treatments delivered by multi-leaf collimator (MLC). An in-house made motor-driven platform, which moves sinusoidally with an amplitude of 1 cm and a period of 4 s, was used to mimic tumour motion. Tumour motion was simulated along cranial-caudal direction while MLC leaves moved across the patient from left to right, as in most clinical cases. The dose to a point near the centre of the tumour mass was measured according to geometric and dosimetri cp arameters from two five-field lung IMRT plans. For each field, measurement was done for two dose rates (300 and 500 MU min −1 ), three MLC delivery modes (sliding window, step-and-shoot with 10 and 20 intensity levels) and eight equally spaced starting phases of tumour motion. The dose to the measurement point delivered from all five field sw as derived for both a single fraction and 30 fractions by randomly sampling from measured dose values of each field at different initial phases. It was found that the mean dose to a moving tumour differs slightly (<2–3%) from that to a static tumour. The variation in breathing phase at the start of dose delivery results in a maximum variation around the mean dose of greater than 30% for one field. The full width at half maximum for the probability distribution of the point dose is up to 8% for all five fields in a single fraction, bu tl ess than 1–2% after 30 fractions. In general, lower dose rate can reduce the motion-caused dose variation and therefore might be preferable for lung IMRT when no motion mitigation techniques are used. From the two IMRT cases we studied where tumour motion is perpendicular to MLC leaf motion, the dose variation was found to be insensitive to the MLC delivery mode. (Some figures in this article are in colour only in the electronic version)

Medical applications of synchrotron radiation.

Abstract: The medical imaging and therapeutic technologies that are based on the use of radiation are reviewed briefly, with special emphasis on the recent developments of synchrotron radiation (SR) methods. New results have been achieved in all of these areas since the last comprehensive reviews were written in this field. This topical review is intended to make the latest possible results and complete set of references available. The different contrast mechanisms in imaging by x-rays are described. The applications range from whole-body imaging to studies of atomic and molecular structures. The SR imaging applications include coronary angiography, bronchography, mammography, computed tomography, x-ray microscopy and imaging by scattering. The therapy applications include photon activation therapy and microbeam radiation therapy.

MicroPET II: design, development and initial performance of an improved microPET scanner for small-animal imaging

Abstract: MicroPET II is a second-generation animal PET scanner designed for high-resolution imaging of small laboratory rodents. The system consists of 90 scintillation detector modules arrange di nt hree contiguous axial rings with ar in gd iameter of 16.0 cm and an axial length of 4.9 cm. Each detector module consists of a 14 × 14 array of lutetium oxyorthosilicate (LSO) crystals coupled to a multi-channel photomultiplier tube (MC-PMT) through a coherent optical fibre bundle. Each LSO crystal element measures 0.975 mm × 0.975 mm in cross section by 12.5 mm in length. A barium sulphate reflector material was used between LSO elements leading to a detector pitch of 1.15 mm in both axial and transverse directions. Fused optical fibre bundles were made from 90 µ md iameter glass fibres with a numerical aperture of 0.56. Interstitial extramural absorber was added between the fibres to reduce optical cross talk .A charge-division readout circuit was implemented on printed circuit boards to decode the 196 crystals in each array from the outputs of the 64 anode signals of the MC-PMT. Electronics from Concorde Microsystems Inc. (Knoxville, TN) were used for signa la mplification, digitization, event qualification, coincidence processing an dd atacapture. Coincidence data were passed to a host PC that recorded events in list mode. Following acquisition, data were sorted into sinograms and reconstructed using Fourier rebinning and filtered backprojection algorithms. Basic evaluation of the system has been completed. The absolute sensitivity of the microPET II scanner was 2.26% at This work was originally conducted at UCLA, Crump Institute for Molecular Imaging, and was continued and completed at UC Davis, Department of Biomedical Engineering.

Synchronized moving aperture radiation therapy (SMART): average tumour trajectory for lung patients.

Abstract: Synchronized moving aperture radiation therapy (SMART) is a new technique for treating mobile tumours under development at Massachusetts General Hospital (MGH). The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator (DMLC) with the tumour motion induced by respiration. SMART is based on the concept of the average tumour trajectory (ATT) exhibited by a tumour during respiration. During the treatment simulation stage, tumour motion is measured and the ATT is derived. Then, the original IMRT MLC leaf sequence is modified using the ATT to compensate for tumour motion. During treatment, the tumour motion is monitored. The treatment starts when leaf motion and tumour motion are synchronized at a specific breathing phase. The treatment will halt when the tumour drifts away from the ATT and will resume when the synchronization between tumour motion and radiation beam is re-established. In this paper, we present a method to derive the ATT from measured tumour trajectory data. We also investigate the validity of the ATT concept for lung tumours during normal breathing. The lung tumour trajectory data were acquired during actual radiotherapy sessions using a real-time tumour-tracking system. SMART treatment is simulated by assuming that the radiation beam follows the derived ATT and the tumour follows the measured trajectory. In simulation, the treatment starts at exhale phase. The duty cycle of SMART delivery was calculated for various treatment times and gating thresholds, as well as for various exhale phases where the treatment begins. The simulation results show that in the case of free breathing, for 4 out of 11 lung datasets with tumour motion greater than 1 cm from peak to peak, the error in tumour tracking can be controlled to within a couple of millimetres while maintaining a reasonable delivery efficiency. That is to say, without any breath coaching/control, the ATT is a valid concept for some lung tumours. However, to make SMART an efficient technique in general, it is found that breath coaching techniques are required.

Multiple-image radiography

Abstract: Conventional radiography produces a single image of an object by measuring the attenuation of an x-ray beam passing through it When imaging weakly absorbing tissues, x-ray attenuation may be a suboptimal signature of diseaserelated information In this paper we describe a new phase-sensitive imaging method, called multiple-image radiography (MIR), which is an improvement on a prior technique called diffraction-enhanced imaging (DEI) This paper elaborates on our initial presentation of the idea in Wernick et al (2002 Proc Int SympBiomedImaging pp 129–32) MIR simultaneously produces several images from a set of measurements made with a single x-ray beam Specifically, MIR yields three images depicting separately the effects of refraction, ultrasmall-angle scatter and attenuation by the object All three images have good contrast, in part because they are virtually immune from degradation due to scatter at higher angles MIR also yields a very comprehensive object description, consisting of the angular intensity spectrum of a transmitted x-ray beam at every image pixel, within a narrow angular range Our experiments are based on data acquired using a synchrotron light source; however, in preparation for more practical implementations using conventional x-ray sources, we develop and evaluate algorithms designed for Poisson noise, which is characteristic of photon-limited imaging The results suggest that MIR is capable of operating at low photon count levels, therefore the method

All about FAX: a Female Adult voXel phantom for Monte Carlo calculation in radiation protection dosimetry

Abstract: The MAX (Male Adult voXel) phantom has been developed from existing segmented images of a male adult body, in order to achieve a representation as close as possible to the anatomical properties of the reference adult male specified by the ICRP. The study describes the adjustments of the soft-tissue organ masses, a new dosimetric model for the skin, a new model for skeletal dosimetry and a computational exposure model based on coupling the MAX phantom with the EGS4 Monte Carlo code. Conversion coefficients between equivalent dose to the red bone marrow as well as effective MAX dose and air-kerma free in air for external photon irradiation from the front and from the back, respectively, are presented and compared with similar data from other human phantoms.

MRI-guided gas bubble enhanced ultrasound heating in in vivo rabbit thigh.

Abstract: In this study, we propose a focused ultrasound surgery protocol that induces and then uses gas bubbles at the focus to enhance the ultrasound absorption and ultimately create larger lesions in vivo. MRI and ultrasound visualization and monitoring methods for this heating method are also investigated. Larger lesions created with a carefully monitored single ultrasound exposure could greatly improve the speed of tumour coagulation with focused ultrasound. All experiments were performed under MRI (clinical, 1.5 T) guidance with one of two eight-sector, spherically curved piezoelectric transducers. The transducer, either a 1.1 or 1.7 MHz array, was driven by a multi-channel RF driving system. The transducer was mounted in an MRI-compatible manual positioning system and the rabbit was situated on top of the system. An ultrasound detector ring was fixed with the therapy transducer to monitor gas bubble activity during treatment. Focused ultrasound surgery exposures were delivered to the thighs of seven New Zealand while rabbits. The experimental, gas-bubble-enhanced heating exposures consisted of a high amplitude 300 acoustic watt, half second pulse followed by a 7 W, 14 W or 21 W continuous wave exposure for 19.5 s. The respective control sonications were 20 s exposures of 14 W, 21 W and 28 W. During the exposures, MR thermometry was obtained from the temperature dependency of the proton resonance frequency shift. MRT2-enhanced imaging was used to evaluate the resulting lesions. Specific metrics were used to evaluate the differences between the gas-bubble-enhanced exposures and their respective control sonications: temperatures with respect to time and space, lesion size and shape, and their agreement with thermal dose predictions. The bubble-enhanced exposures showed a faster temperature rise within the first 4 s and higher overall temperatures than the sonications without bubble formation. The spatial temperature maps and the thermal dose maps derived from the MRI thermometry closely correlated with the resulting lesion as examined by T2-weighted imaging. The lesions created with the gas-bubble-enhanced heating exposures were 2-3 times larger by volume, consistently more spherical in shape and closer to the transducer than the control exposures. The study demonstrates that gas bubbles can reliably be used to create significantly larger lesions in vivo. MRI thermometry techniques were successfully used to monitor the thermal effects mediated by the bubble-enhanced exposures.

The design and implementation of a motion correction scheme for neurological PET.

Abstract: A method is described to monitor the motion of the head during neurological positron emission tomography (PET) acquisitions and to correct the data post acquisition for the recorded motion prior to image reconstruction. The technique uses an optical tracking system, Polaris™, to accurately monitor the position of the head during the PET acquisition. The PET data are acquired in list mode where the events are written directly to disk during acquisition. The motion tracking information is aligned to the PET data using a sequence of pseudo-random numbers, which are inserted into the time tags in the list mode event stream through the gating input interface on the tomograph. The position of the head is monitored during the transmission acquisition, and it is assumed that there is minimal head motion during this measurement. Each event, prompt and delayed, in the list mode event stream is corrected for motion and transformed into the transmission space. For a given line of response, normalization, including corrections for detector efficiency, geometry and crystal interference and dead time are applied prior to motion correction and rebinning in the sinogram. A series of phantom experiments were performed to confirm the accuracy of the method: (a) a point source located in three discrete axial positions in the tomograph field of view, 0 mm, 10 mm and 20 mm from a reference point, (b) a multi-line source phantom rotated in both discrete and gradual rotations through ±5° and ±15°, including a vertical and horizontal movement in the plane. For both phantom experiments images were reconstructed for both the fixed and motion corrected data. Measurements for resolution, full width at half maximum (FWHM) and full width at tenth maximum (FWTM), were calculated from these images and a comparison made between the fixed and motion corrected datasets. From the point source measurements, the FWHM at each axial position was 7.1 mm in the horizontal direction, and increasing from 4.7 mm at the 0 mm position, to 4.8 mm, 20 mm offset, in the vertical direction. The results from the multi-line source phantom with ±5° rotations showed a maximum degradation in FWHM, when compared with the stationary phantom, of 0.6 mm, in the horizontal direction, and 0.3 mm in the vertical direction. The corresponding values for the larger rotation, ±15°, were 0.7 mm and 1.1 mm, respectively. The performance of the method was confirmed with a Hoffman brain phantom moved continuously, and a clinical acquisition using [11C]raclopride (normal volunteer). A visual comparison of both the motion and non-motion corrected images of the Hoffman brain phantom clearly demonstrated the efficacy of the method. A sample time-activity curve extracted from the clinical study showed irregularities prior to motion correction, which were removed after correction. A method has been developed to accurately monitor the motion of the head during a neurological PET acquisition, and correct for this motion prior to image reconstruction. The method has been demonstrated to be accurate and does not add significantly to either the acquisition or the subsequent data processing.

High power transcranial beam steering for ultrasonic brain therapy.

Abstract: A sparse phased array is specially designed for non-invasive ultrasound transskull brain therapy. The array is made of 200 single elements corresponding to a new generation of high power transducers developed in collaboration with Imasonic (Besancon, France). Each element has a surface of 0.5 cm2 and works at 0.9 MHz central frequency with a maximum 20 W cm(-2) intensity on the transducer surface. In order to optimize the steering capabilities of the array, several transducer distributions on a spherical surface are simulated: hexagonal, annular and quasi-random distributions. Using a quasi-random distribution significantly reduces the grating lobes. Furthermore, the simulations show the capability of the quasi-random array to electronically move the focal spot in the vicinity of the geometrical focus (up to +/- 15 mm). Based on the simulation study, the array is constructed and tested. The skull aberrations are corrected by using a time reversal mirror with amplitude correction achieved thanks to an implantable hydrophone, and a sharp focus is obtained through a human skull. Several lesions are induced in fresh liver and brain samples through human skulls, demonstrating the accuracy and the steering capabilities of the system.

Conductivity and current density image reconstruction using harmonic Bz algorithm in magnetic resonance electrical impedance tomography

Abstract: Magnetic resonance electrical impedance tomography (MREIT) is to provide cross-sectional images of the conductivity distribution sigma of a subject. While injecting current into the subject, we measure one component Bz of the induced magnetic flux density B = (Bx, By, Bz) using an MRI scanner. Based on the relation between (inverted delta)2 Bz and inverted delta sigma, the harmonic Bz algorithm reconstructs an image of sigma using the measured Bz data from multiple imaging slices. After we obtain sigma, we can reconstruct images of current density distributions for any given current injection method. Following the description of the harmonic Bz algorithm, this paper presents reconstructed conductivity and current density images from computer simulations and phantom experiments using four recessed electrodes injecting six different currents of 26 mA. For experimental results, we used a three-dimensional saline phantom with two polyacrylamide objects inside. We used our 0.3 T (tesla) experimental MRI scanner to measure the induced Bz. Using the harmonic Bz algorithm, we could reconstruct conductivity and current density images with 82 x 82 pixels. The pixel size was 0.6 x 0.6 mm2. The relative L2 errors of the reconstructed images were between 13.8 and 21.5% when the signal-to-noise ratio (SNR) of the corresponding MR magnitude images was about 30. The results suggest that in vitro and in vivo experimental studies with animal subjects are feasible. Further studies are requested to reduce the amount of injection current down to less than 1 mA for human subjects.

Poly(vinyl alcohol) gels for use as tissue phantoms in photoacoustic mammography

Abstract: Materials for solid photoacoustic breast phantoms, based on poly(vinyl alcohol) hydrogels, are presented. Phantoms intended for use in photoacoustics must possess both optical and acoustic properties of tissue. To realize the optical properties of tissue, one approach was to optimize the number of freezing and thawing cycles of aqueous poly(vinyl alcohol) solutions, a procedure which increases the turbidity of the gel while rigidifying it. The second approach concentrated on forming a clear matrix of the rigid poly(vinyl alcohol) gel without any scattering, so that appropriate amounts of optical scatterers could be added at the time of formation, to tune the optical properties as per requirement. The relevant optical and acoustic properties of such samples were measured to be close to the average properties of human breast tissue. Tumour simulating gel samples of suitable absorption coefficient were created by adding appropriate quantities of dye at the time of formation; the samples were then cut into spheres. A breast phantom embedded with such 'tumours' was developed for studying the applicability of photoacoustics in mammography.

Leaf sequencing algorithms for segmented multileaf collimation.

Abstract: The delivery of intensity-modulated radiation therapy (IMRT) with a multileaf collimator (MLC) requires the conversion of a radiation fluence map into a leaf sequence file that controls the movement of the MLC during radiation delivery. It is imperative that the fluence map delivered using the leaf sequence file is as close as possible to the fluence map generated by the dose optimization algorithm, while satisfying hardware constraints of the delivery system. Optimization of the leaf sequencing algorithm has been the subject of several recent investigations. In this work, we present a systematic study of the optimization of leaf sequencing algorithms for segmental multileaf collimator beam delivery and provide rigorous mathematical proofs of optimized leaf sequence settings in terms of monitor unit (MU) efficiency under most common leaf movement constraints that include minimum leaf separation constraint and leaf interdigitation constraint. Our analytical analysis shows that leaf sequencing based on unidirectional movement of the MLC leaves is as MU efficient as bidirectional movement of the MLC leaves.

A novel linear programming approach to fluence map optimization for intensity modulated radiation therapy treatment planning.

Abstract: We present a novel linear programming (LP) based approach for efficiently solving the intensity modulated radiation therapy (IMRT) fluence-map optimization (FMO) problem to global optimality. Our model overcomes the apparent limitations of a linear-programming approach by approximating any convex objective function by a piecewise linear convex function. This approach allows us to retain the flexibility offered by general convex objective functions, while allowing us to formulate the FMO problem as a LP problem. In addition, a novel type of partial-volume constraint that bounds the tail averages of the differential dose-volume histograms of structures is imposed while retaining linearity as an alternative approach to improve dose homogeneity in the target volumes, and to attempt to spare as many critical structures as possible. The goal of this work is to develop a very rapid global optimization approach that finds high quality dose distributions. Implementation of this model has demonstrated excellent results. We found globally optimal solutions for eight 7-beam head-and-neck cases in less than 3 min of computational time on a single processor personal computer without the use of partial-volume constraints. Adding such constraints increased the running times by a factor of 2-3, but improved the sparing of critical structures. All cases demonstrated excellent target coverage (> 95%), target homogeneity (< 10% overdosing and < 7% underdosing) and organ sparing using at least one of the two models.

Accuracy assessment protocols for electromagnetic tracking systems

Abstract: Electromagnetic tracking systems have found increasing use in medical applications during the last few years. As with most non-trivial spatial measurement systems, the complex determination of positions and orientations from their underlying raw sensor measurements results in complicated, non-uniform error distributions over the specified measurement volume. This makes it difficult to unambiguously determine accuracy and performance assessments that allow users to judge the suitability of these systems for their particular needs. Various assessment protocols generally emphasize different measurement aspects that typically arise in clinical use. This can easily lead to inconclusive or even contradictory conclusions. We examine some of the major issues involved and discuss three useful calibration protocols. The measurement accuracy of a system can be described in terms of its 'trueness' and its 'precision'. Often, the two are strongly coupled and cannot be easily determined independently. We present a method that allows the two to be disentangled, so that the resultant trueness properly represents the systematic, non-reducible part of the measurement error, and the resultant precision (or repeatability) represents only the statistical, reducible part. Although the discussion is given largely within the context of electromagnetic tracking systems, many of the results are applicable to measurement systems in general.

Can the cerebral metabolic rate of oxygen be estimated with near-infrared spectroscopy?

Abstract: We have measured the changes in oxy-haemoglobin and deoxy-haemoglobin in the adult human brain during a brief finger tapping exercise using near-infrared spectroscopy (NIRS). The cerebral metabolic rate of oxygen (CMRO2) can be estimated from these NIRS data provided certain model assumptions. The change in CMRO2 is related to changes in the total haemoglobin concentration, deoxy-haemoglobin concentration and blood flow. As NIRS does not provide a measure of dynamic changes in blood flow during brain activation, we relied on aW indkessel model that relates dynamic blood volume and flow changes, which has been used previously for estimating CMRO2 from functional magnetic resonance imaging (fMRI) data. Because of the partial volume effect we are unable to quantify the absolute changes in the local brain haemoglobin concentrations with NIRS and thus are unable to obtain an estimate of the absolute CMRO2 change. An absolute estimate is also confounded by uncertainty in the flow–volume relationship. However, the ratio of the flow change to the CMRO2 change is relatively insensitive to these uncertainties. Fo rt he finger tapping task, we estimate a most probable flow–consumption ratio ranging from 1.5 to 3 in agreement with previous findings presented in the literature, although we cannot exclude the possibility that there is no CMRO2 change. The large range in the ratio arises from the large number of model parameters that must be estimated from the data. A more precise estimate of the flow–consumption ratio will require better estimates of the model parameters or flow information, as can be provided by combining NIRS with fMRI.

Exact helical reconstruction using native cone-beam geometries

Abstract: This paper is about helical cone-beam reconstruction using the exact filtered backprojection formula recently suggested by Katsevich (2002a Phys. Med. Biol. 47 2583-97). We investigate how to efficiently and accurately implement Katsevich's formula for direct reconstruction from helical cone-beam data measured in two native geometries. The first geometry is the curved detector geometry of third-generation multi-slice CT scanners, and the second geometry is the flat detector geometry of C-arms systems and of most industrial cone-beam CT scanners. For each of these two geometries, we determine processing steps to be applied to the measured data such that the final outcome is an implementation of the Katsevich formula. These steps are first described using continuous-form equations, disregarding the finite detector resolution and the source position sampling. Next, techniques are presented for implementation of these steps with finite data sampling. The performance of these techniques is illustrated for the curved detector geometry of third-generation CT scanners, with 32, 64 and 128 detector rows. In each case, resolution and noise measurements are given along with reconstructions of the FORBILD thorax phantom.

Inverse planning for intensity-modulated arc therapy using direct aperture optimization.

Abstract: Intensity-modulated arc therapy (IMAT) is a radiation therapy delivery technique that combines gantry rotation with dynamic multi-leaf collimation (MLC). With IMAT, the benefits of rotational IMRT can be realized using a conventional linear accelerator and a conventional MLC. Thus far, the advantages of IMAT have gone largely unrealized due to the lack of robust automated planning tools capable of producing efficient IMAT treatment plans. This work describes an inverse treatment planning algorithm, called 'direct aperture optimization' (DAO) that can be used to generate inverse treatment plans for IMAT. In contrast to traditional inverse planning techniques where the relative weights of a series of pencil beams are optimized, DAO optimizes the leaf positions and weights of the apertures in the plan. This technique allows any delivery constraints to be enforced during the optimization, eliminating the need for a leaf-sequencing step. It is this feature that enables DAO to easily create inverse plans for IMAT. To illustrate the feasibility of DAO applied to IMAT, several cases are presented, including a cylindrical phantom, a head and neck patient and a prostate patient.

Specificity of noninvasive blood glucose sensing using optical coherence tomography technique: a pilot study

Abstract: Noninvasive monitoring of blood glucose concentration in diabetic patients would significantly reduce complications and mortality associated with this disease. In this paper, we experimentally and theoretically studied specificity of noninvasive blood glucose monitoring with the optical coherence tomography (OCT) technique. OCT images and signals were obtained from skin of Yucatan micropigs and New Zealand rabbits. Obtained results demonstrate that: (1) several body osmolytes may change the refractive index mismatch between the interstitial fluid (ISF) and scattering centres in tissue, however the effect of the glucose is approximately one to two orders of magnitude higher; (2) an increase of the ISF glucose concentration in the physiological range (3-30 mM) may decrease the scattering coefficient by 0.22% mM(-1) due to cell volume change; (3) stability of the OCT signal slope is dependent on tissue heterogeneity and motion artefacts; and (4) moderate skin temperature fluctuations (+/- 1 degree C) do not decrease accuracy and specificity of the OCT-based glucose sensor, however substantial skin heating or cooling (several degrees C) significantly change the OCT signal slope. These results suggest that the OCT technique may provide blood glucose concentration monitoring with sufficient specificity under normal physiological conditions.

A three-dimensional breast software phantom for mammography simulation

Abstract: This paper presents a methodology for three-dimensional (3D) computer modelling of the breast, using a combination of 3D geometrical primitives and voxel matrices that can be further subjected to simulated x-ray imaging, to produce synthetic mammograms. The breast phantom is a composite model of the breast and includes the breast surface, the duct system and terminal ductal lobular units, Cooper's ligaments, the pectoral muscle, the 3D mammographic background and breast abnormalities. A second analytical x-ray matter interaction modelling module is used to generate synthetic images from monoenergetic fan beams. Mammographic images of various synthesized breast models differing in size, shape and composition were produced. A preliminary qualitative assessment performed by three radiologists and a quantitative evaluation study using fractal and grey-level histogram analysis were conducted. A comparative study of extracted features with published data has also been performed. The evaluation results indicated good correlation of characteristics between synthetic and actual radiographs. Applications foreseen are not only in the area of breast imaging experimentation but also in education and training.

A functionalized THz sensor for marker-free DNA analysis

Abstract: We report on a novel resonant THz sensor for the label-free analysis of DNA molecules. The sensor allows the direct detection of DNA-probe molecules at functionalized electrodes via hybridization. Subsequent time resolved photoconductive sampling of the THz transmission identifies the binding state between probe and target DNA. Integrating neighbouring sensors on a chip, this technique can be extended to a parallel analysis of multiple DNA sequences. A clearly readable sensor response is obtained with less then 40 fmol of 20-mer single-stranded DNA molecules, indicating at least a sevenfold sensitivity increase compared to previous approaches.

Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera.

Abstract: A novel image-intensified charge-coupled device (ICCD) imaging system has been developed to perform 3D fluorescence tomographic imaging in the frequency-domain using near-infrared contrast agents. The imager is unique since it (i) employs a large tissue-mimicking phantom, which is shaped and sized to resemble a female breast and part of the extended chest-wall region, and (ii) enables rapid data acquisition in the frequency-domain by using a gain-modulated ICCD camera. Diffusion model predictions are compared to experimental measurements using two different referencing schemes under two different experimental conditions of perfect and imperfect uptake of fluorescent agent into a target. From these experimental measurements, three-dimensional images of fluorescent absorption were reconstructed using a computationally efficient variant of the approximate extended Kalman filter algorithm. The current work represents the first time that 3D fluorescence-enhanced optical tomographic reconstructions have been achieved from experimental measurements of the time-dependent light propagation on a clinically relevant breast-shaped tissue phantom using a gain-modulated ICCD camera.

On biologically conformal boost dose optimization

Abstract: A method is described that allows the inclusion of biological imaging data in the optimization of intensity-modulated radiotherapy to produce dose boosts that conform with target subvolumes of potentially reduced radiosensitivity. The biological image (e.g. PET, fMRI, etc) is transformed into a dose efficiency distribution using a piecewise linear calibration function with a prescribed maximum boost factor. Instead of dose alone, the cost function of the optimization algorithm depends on the product of the physical dose times dose efficiency. An example case of a base-of-tongue tumour which was imaged with the hypoxia tracer fluoro-misonidazole is presented, showing the excellent capability of IMRT to produce dose distributions that conform to spatially variable dose prescriptions.

Statistical inversion for medical x-ray tomography with few radiographs: I. General theory

Abstract: In x-ray tomography, the structure of a three-dimensional body is reconstructed from a collection of projection images of the body. Medical CT imaging does this using an extensive set of projections from all around the body. However, in many practical imaging situations only a small number of truncated projections are available from a limited angle of view. Three-dimensional imaging using such data is complicated for two reasons: (i) typically, sparse projection data do not contain sufficient information to completely describe the 3D body, and (ii) traditional CT reconstruction algorithms, such as filtered backprojection, do not work well when applied to few irregularly spaced projections. Concerning (i), existing results about the information content of sparse projection data are reviewed and discussed. Concerning (ii), it is shown how Bayesian inversion methods can be used to incorporate a priori information into the reconstruction method, leading to improved image quality over traditional methods. Based on the discussion, a low-dose three-dimensional x-ray imaging modality is described.

Influence of fragment reaction of relativistic heavy charged particles on heavy-ion radiotherapy

Abstract: The production of projectile fragments is one of the most important, but not yet perfectly understood, problems to be considered when planning for the utilization of high-energy heavy charged particles for radiotherapy. This paper reports our investigation of the fragments' fluence and linear energy transfer (LET) spectra produced from various incident ions using an experimental approach to reveal these physical qualities of the beams. Polymethyl methacrylate, as a substitute for the human body, was used as a target. A deltaE-E counter telescope with a plastic scintillator and a BGO scintillator made it possible to identify the species of fragments based on differences of various elements. By combining a gas-flow proportional counter with a counter telescope system, LET spectra as well as fluence spectra of the fragments were derived for each element down from the primary particles to hydrogen. Among them, the information on hydrogen and helium fragments was derived for the first time. The result revealed that the number of light fragments, such as hydrogen and helium, became larger than the number of primaries in the vicinity of the range end. However, the greater part of the dose delivered to a cell was still governed by the primaries. The calculated result of a simulation used for heavy-ion radiotherapy indicated room for improving the reaction model.