Table of contents

In emission tomography statistically based iterative methods can improve image quality relative to analytic image reconstruction through more accurate physical and statistical modelling of high-energy photon production and detection processes. Continued exponential improvements in computing power, coupled with the development of fast algorithms, have made routine use of iterative techniques practical, resulting in their increasing popularity in both clinical and research environments. Here we review recent progress in developing statistically based iterative techniques for emission computed tomography. We describe the different formulations of the emission image reconstruction problem and their properties. We then describe the numerical algorithms that are used for optimizing these functions and illustrate their behaviour using small scale simulations.

A new dosimeter, based on chemical vapour deposited (CVD) diamond as the active detector material, is being developed for dosimetry in radiotherapeutic beams. CVD-diamond is a very interesting material, since its atomic composition is close to that of human tissue and in principle it can be designed to introduce negligible perturbations to the radiation field and the dose distribution in the phantom due to its small size. However, non-tissue-equivalent structural components, such as electrodes, wires and encapsulation, need to be carefully selected as they may induce severe fluence perturbation and angular dependence, resulting in erroneous dose readings. By introducing metallic electrodes on the diamond crystals, interface phenomena between high- and low-atomic-number materials are created. Depending on the direction of the radiation field, an increased or decreased detector signal may be obtained. The small dimensions of the CVD-diamond layer and electrodes (around 100 µm and smaller) imply a higher sensitivity to the lack of charged-particle equilibrium and may cause severe interface phenomena. In the present study, we investigate the variation of energy deposition in the diamond detector for different photon-beam qualities, electrode materials and geometric configurations using the Monte Carlo code PENELOPE. The prototype detector was produced from a 50 µm thick CVD-diamond layer with 0.2 µm thick silver electrodes on both sides. The mean absorbed dose to the detector's active volume was modified in the presence of the electrodes by 1.7%, 2.1%, 1.5%, 0.6% and 0.9% for 1.25 MeV monoenergetic photons, a complete (i.e. shielded) ⁶⁰Co photon source spectrum and 6, 18 and 50 MV bremsstrahlung spectra, respectively. The shift in mean absorbed dose increases with increasing atomic number and thickness of the electrodes, and diminishes with increasing thickness of the diamond layer. From a dosimetric point of view, graphite would be an almost perfect electrode material. This study shows that, for the considered therapeutic beam qualities, the perturbation of the detector signal due to charge-collecting graphite electrodes of thicknesses between 0.1 and 700 µm is negligible within the calculation uncertainty of 0.2%.

The aim of the present work was to implement the kinetics of cisplatin into a previously developed tumour growth model and to simulate the combined cisplatin–radiotherapy treatment with the emphasis on time sequencing and scheduling of drug and radiation. An investigation into whether the effect of cisplatin–radiation is determined by independent cell kill or by cisplatin-produced radiosensitization was also undertaken. It was shown that cisplatin administered before radiation conferred similar tumour control to the post-radiation sequencing of the drug. The killing effect of the combined modality treatment on tumour increased with the increase in cell recruitment. Furthermore, the individual cell kill produced by the two cytotoxins led to an additive only tumour response when the treatments were given concurrently, suggesting that for a synergistic effect, cisplatin must potentiate the effect of radiation, through the radiosensitizing mechanisms addressed in the literature. It was concluded that the optimal timing of cisplatin should be close to radiation. The model showed that daily administration of cisplatin led to a 35% improvement of tumour control as compared to radiation alone, while weekly cisplatin has improved radiotherapy by only 6%.

In this study we have investigated a spatial distribution of cell growth after their irradiation using a modulated x-ray intensity pattern. An A549 human non-small cell lung cancer cell line was grown in a 6-well culture. Two of the wells were the unirradiated control wells, whilst another two wells were irradiated with a modulated x-ray intensity pattern and the third two wells were uniformly irradiated. A number of plates were incubated for various times after irradiation and stained with crystal violet. The spatial distribution of the stained cells within each well was determined by measurement of the crystal violet optical density at multiple positions in the plate using a microplate photospectrometer. The crystal violet optical density for a range of cell densities was measured for the unirradiated well and this correlated with cell viability as determined by the MTT cell viability assay. An exponential dose response curve was measured for A549 cells from the average crystal violet optical density in the uniformly irradiated well up to a dose of 30 Gy. By measuring the crystal violet optical density distribution within a well the spatial distribution of cell growth after irradiation with a modulated x-ray intensity pattern can be plotted. This method can be used for in vitro investigation into the changes in radiation response associated with treatment using intensity modulated radiation therapy (IMRT).

The purpose of this study is to extend an algorithm proposed for beam orientation optimization in classical conformal radiotherapy to intensity-modulated radiation therapy (IMRT) and to evaluate the algorithm's performance in IMRT scenarios. In addition, the effect of the candidate pool of beam orientations, in terms of beam orientation resolution and starting orientation, on the optimized beam configuration, plan quality and optimization time is also explored. The algorithm is based on the technique of mixed integer linear programming in which binary and positive float variables are employed to represent candidates for beam orientation and beamlet weights in beam intensity maps. Both beam orientations and beam intensity maps are simultaneously optimized in the algorithm with a deterministic method. Several different clinical cases were used to test the algorithm and the results show that both target coverage and critical structures sparing were significantly improved for the plans with optimized beam orientations compared to those with equi-spaced beam orientations. The calculation time was less than an hour for the cases with 36 binary variables on a PC with a Pentium IV 2.66 GHz processor. It is also found that decreasing beam orientation resolution to 10° greatly reduced the size of the candidate pool of beam orientations without significant influence on the optimized beam configuration and plan quality, while selecting different starting orientations had large influence. Our study demonstrates that the algorithm can be applied to IMRT scenarios, and better beam orientation configurations can be obtained using this algorithm. Furthermore, the optimization efficiency can be greatly increased through proper selection of beam orientation resolution and starting beam orientation while guaranteeing the optimized beam configurations and plan quality.

Absolute dose measurements with a transportable water calorimeter and ionization chambers were performed at a water depth of 20 mm in four different types of radiation fields, for a collimated ⁶⁰Co photon beam, for a collimated neutron beam with a fluence-averaged mean energy of 5.25 MeV, for collimated proton beams with mean energies of 36 MeV and 182 MeV at the measuring position, and for a ¹²C ion beam in a scanned mode with an energy per atomic mass of 430 MeV u⁻¹. The ionization chambers actually used were calibrated in units of air kerma in the photon reference field of the PTB and in units of absorbed dose to water for a Farmer-type chamber at GSI. The absorbed dose to water inferred from calorimetry was compared with the dose derived from ionometry by applying the radiation-field-dependent parameters. For neutrons, the quantities of the ICRU Report 45, for protons the quantities of the ICRU Report 59 and for the ¹²C ion beam, the recommended values of the International Atomic Energy Agency (IAEA) protocol (TRS 398) were applied. The mean values of the absolute absorbed dose to water obtained with these two independent methods agreed within the standard uncertainty (k = 1) of 1.8% for calorimetry and of 3.0% for ionometry for all types and energies of the radiation beams used in this comparison.

The frequency-dependent complex moduli of human uterine tissue have been characterized. Quantification of the modulus is required for developing uterine ultrasound elastography as a viable imaging modality for diagnosing and monitoring causes for abnormal uterine bleeding and enlargement, as well assessing the integrity of uterine and cervical tissue. The complex modulus was measured in samples from hysterectomies of 24 patients ranging in age from 31 to 79 years. Measurements were done under small compressions of either 1 or 2%, at low pre-compression values (either 1 or 2%), and over a frequency range of 0.1–100 Hz. Modulus values of cervical tissue monotonically increased from approximately 30–90 kPa over the frequency range. Normal uterine tissue possessed modulus values over the same range, while leiomyomas, or uterine fibroids, exhibited values ranging from approximately 60–220 kPa.

This paper presents a direct inversion approach for reconstructing the elastic shear modulus in soft tissue from dynamic measurements of the interior displacement field during time harmonic excitation. The tissue is assumed to obey the equations of nearly incompressible, linear, isotropic elasto-dynamics in harmonic motion. A finite element discretization of the governing equations is used as a basis, and a procedure is outlined to eliminate the need for boundary conditions in the inverse problem. The hydrostatic stress (pressure) is also reconstructed in the process, and the effect of neglecting this term in the governing equations, which is common practice, is considered. The approach does not require iterations and can be performed on sub-regions of the domain resulting in a computationally efficient method. A sensitivity study is performed to investigate the detectability of abnormal regions of different size and shear modulus contrast from the background. The algorithm is tested on simulated data on a two-dimensional domain, where the data are generated on a very fine mesh to get a near exact solution, then downsampled to a coarser mesh that is similar to the spatial discretization of actual data, and noise is added. Results showing the effect of the hydrostatic stress term and noise are presented. A reconstruction using MR measured experimental data involving a tissue-mimicking phantom is also shown to demonstrate the algorithm.

This work presents the results of a dose survey performed for paediatric patients and carried out in two large paediatric public hospitals in Rio de Janeiro city. The entrance surface dose (ESD) and the effective dose (ED) were evaluated for chest, skull, abdomen, lumbar spine, cervical spine and pelvis in antero-posterior (AP), postero-anterior (PA) and lateral (LAT) projections. For each examination, four age groups 0–1, 1–5, 5–10 and 10–15 years were studied. The DoseCal software was used to calculate these doses. Wide variations for the same type of examination and projection have been detected. These variations were evident, in Brazil, from previous work. In spite of the present results being still preliminary, they can give an idea of what paediatric ESDs are like in Brazil. Also, with respect to the entrance surface dose, some of the results are above the reference levels, which cause high ED, as well. On the other hand, the wide range of ESD reflects the disparity of radiographic techniques and demonstrates that the ALARA principle is not being applied in Brazilian hospitals and becomes a concern in terms of public health.

A simple approach for estimating the location and power of a bioluminescent point source inside tissue is reported. The strategy consists of using a diffuse reflectance image at the emission wavelength to determine the optical properties of the tissue. Following this, bioluminescence images are modelled using a single point source and the optical properties from the reflectance image, and the depth and power are iteratively adjusted to find the best agreement with the experimental image. The forward models for light propagation are based on the diffusion approximation, with appropriate boundary conditions. The method was tested using Monte Carlo simulations, Intralipid tissue-simulating phantoms and ex vivo chicken muscle. Monte Carlo data showed that depth could be recovered within 6% for depth 4–12 mm, and the corresponding relative source power within 12%. In Intralipid, the depth could be estimated within 8% for depth 4–12 mm, and the relative source power, within 20%. For ex vivo tissue samples, source depths of 4.5 and 10 mm and their relative powers were correctly identified.

No routine test exists to determine the quality of blood platelet transfusions although every year millions of patients require platelet transfusions to survive cancer chemotherapy, surgery or trauma. A new, portable dynamic light scattering instrument is described that is suitable for the measurement of turbid solutions of large particles under temperature-controlled conditions. The challenges of small sample size, short light path through the sample and accurate temperature control have been solved with a specially designed temperature-controlled sample holder for small diameter, disposable capillaries. Efficient heating and cooling is achieved with Peltier elements in direct contact with the sample capillary. Focusing optical fibres are used for light delivery and collection of scattered light. The practical use of this new technique was shown by the reproducible measurement of latex microspheres and the temperature-induced morphological changes of human blood platelets. The measured parameters for platelet transfusions are platelet size, number of platelet-derived microparticles and the response of platelets to temperature changes. This three-dimensional analysis provides a high degree of confidence for the determination of platelet quality. The experimental data are compared to a matrix and facilitate automated, unbiased quality testing.

Incorporation of polarimetric sensitivity into optical coherence tomography can provide additional image contrast when structures of interest are optically anisotropic (e.g., fibrous tissue). We present a generalized technique based on polarization-sensitive optical coherence tomography to detect changes in depth-resolved fibre orientation and thus increase image contrast in multiple-layered birefringent tissues. A high contrast B-scan image of collagen fibre orientation is shown for a porcine intervertebral disc cartilage specimen that exhibited low backscattering intensity contrast. Interfaces in the annulus fibrosus identified using depth-resolved fibre orientation allowed quantification of lamellae thickness. Moreover, the technique detects changes in fibre orientation without intense processing needed to effectively quantify tissue retardation and diattenuation.

Cardiac and respiratory motion artefacts in PET imaging have been traditionally resolved by acquiring the data in gated mode. However, gated PET images are usually characterized by high noise content due to their low photon statistics. In this paper, we present a novel 4D model for the PET imaging system, which can incorporate motion information to generate a motion-free image with all acquired data. A computer simulation and a phantom study were conducted to test the performance of this approach. The computer simulation was based on a digital phantom that was continuously scaled during data acquisition. The phantom study, on the other hand, used two spheres in a tank of water, all of which were filled with ¹⁸F water. One of the spheres was stationary while the other moved in a sinusoidal fashion to simulate tumour motion in the thorax. Data were acquired using both 4D CT and gated PET. Motion information was derived from the 4D CT images and then used in the 4D PET model. Both studies showed that this 4D PET model had a good motion-compensating capability. In the phantom study, this approach reduced quantification error of the radioactivity concentration by 95% when compared to a corresponding static acquisition, while signal-to-noise ratio was improved by 210% when compared to a corresponding gated image.

Previous studies have established the feasibility of monitoring radiofrequency (RF) ablation procedures with acoustic radiation force impulse (ARFI) imaging. However, questions remained regarding the utility of the technique in clinically realistic scenarios and at scanning depths associated with abdominal imaging in adults. We address several of these issues and detail recent progress towards the clinical relevance of the ARFI technique. Results from in vitro bovine tissues and an in vivo ovine model are presented. Additional experiments were conducted with a tissue-mimicking phantom and parallel receive tracking techniques in order to further support the clinical feasibility of the method. Thermal lesions created during RF ablation are visualized with high contrast in both in vitro and in vivo hepatic tissues, and radial lesion growth can be monitored throughout the duration of the procedure. ARFI imaging is implemented on a diagnostic ultrasonic scanner, and thus may be a convenient option to guide RF ablation procedures, particularly when electrode insertion is also performed with sonographic guidance.

Unlike conventional optimization with dose–volume (DV) constraints, multi-criteria optimization (MCO) with DV objectives provides tradeoff information which we believe is necessary for choosing better treatment plans. We show that the MCO formulation with DV objectives is better suited to convex approximation than conventional formulations with DV constraints. We provide a relaxation of the integer programming formulation which reduces the computation time for a single plan from over 5 h to about 2 min, without significantly compromising the results. We also derive a heuristic to improve on the relaxed solutions, adding only a few additional minutes of computation time. We apply these techniques to a skull based tumour case and a paraspinal tumour case. Based on a careful examination of the driving terms in the relaxed formulation and the heuristic, we argue that our techniques should apply more generally for DV objectives in multi-objective IMRT treatment planning.

In-air output ratios, S_c, were measured using miniphantoms made of PMMA (thickness 2.4–24 g cm⁻²), graphite (1.8–26.5 g cm⁻²), copper (1.6–23.3 g cm⁻²) and lead (2.3–21.6 g cm⁻²), for collimator settings of 3 × 3 to 40 × 40 cm², and x-ray energies of 6 MV and 15 MV, respectively. The effects of the miniphantom on S_c were quantified as correction factors as functions of collimator setting, material types and miniphantom thickness for each photon energy to correct the measured values. For miniphantoms with sufficient thickness to eliminate electron disequilibrium, the total correction factors can be expressed as multiplications of three factors: the attenuation correction factor, the mass energy absorption correction factor and the phantom scatter correction factor. This formalism implies that the collimator setting dependence of the correction factor is mainly caused by the energy spectrum shift. The narrow-beam attenuation coefficients in various phantom materials for different collimator settings were determined in narrow-beam geometries using a specially constructed collimator mounted on the tray holder of the accelerator. We have determined that the maximum total correction factor is approximately 1.01. For miniphantoms made of PMMA, graphite, copper and lead, at the miniphantom thickness of 10 g cm⁻², the maximum total correction factors are 1.002, 1.003, 1.005, 1.007, and 1.002, 1.003, 1.008 and 1.009 for 6 MV and 15 MV, respectively.

We have developed a novel, radiofrequency thermal therapy device designed to improve local control of large solid tumours using heat in the range 55–90°C. The device is a solenoid or helical coil designed to be loosely wound inside a tumour and excited with radiofrequency energy. Typically, we associate a uniform axially directed magnetic field with a solenoid coil, which when time varying, results in an electric field inside the coil, which lies mainly in the circumferential direction. In addition to this magnetically induced electric field, there exists a less familiar axially directed electric field inside the coil. Previous investigators have demonstrated the presence of this secondary axial electric field both experimentally and theoretically. Our design exploits the size and uniformity of these electric fields, for heating and coagulating a large tissue volume with a single applicator. The loosely wound solenoid is constructed from Nitinol, an electrically conductive shape memory alloy that permits the minimally invasive percutaneous insertion of the coil through a single cannulating delivery needle. To demonstrate the potential of this device and to determine the optimal frequency of operation, phantom tissue models and finite-element calculation models using COMSOL 3.2® were used to characterize frequency- and geometry-dependent trends in absorption rate density (ARD), which is proportional to electric field intensity. Radial and axial ARD profiles were measured, calculated and evaluated to determine the frequency and geometry best suited for producing large, homogenous coagulation volumes. Based on the trade-off between radial and axial uniformities of the ARD profiles, a 2 cm diameter coil with a 4 cm length and 1 cm pitch, operated at 27.12 MHz, produced the optimal heating pattern, as determined using tissue-mimicking phantom models.

We have developed a novel, thermal therapy device designed to improve local control of large solid tumours using heat in the range 55–90 °C. The device is a helical coil designed to be loosely wound inside a tumour and excited with radiofrequency energy at 27.12 MHz. This design exploits the size and uniformity of the electric fields generated by magnetic induction inside this solenoidal geometry for heating and coagulating a large target volume. The use of the electrically conductive shape memory alloy Nitinol for the coil and an external ground plane permit the minimally invasive percutaneous insertion of the coil through a single cannulating delivery needle. To demonstrate the feasibility of this device, phantom models and finite-element models using COMSOL 3.2® were used to characterize uniformity of the radial and axial ARD (absorption rate density) profiles of different monopolar coil geometries. COMSOL 3.2® was also used to calculate temperature profiles and distributions produced by these coils in a non-perfused tissue-mimicking domain following a 10 min heating period. ARD results showed that optimum radial and axial uniformities were achieved with a 0.75 cm pitch and 3 cm length for a 1.5 cm diameter coil, and a 1.4 cm pitch and 4.2 cm length for a 2 cm diameter coil. These coils were able to produce lesions in excised bovine liver of 4 cm × 4.5 cm and 3.5 cm × 6.5 cm, respectively. Predicted temperature profiles showed similar profile sizes and shapes in a non-perfused domain, with the absolute temperature rise determined by the source input to the coil. These results demonstrate the potential of this interstitial, monopolar induction coil device for heating large tumours using a single applicator delivered through a single needle insertion.

In Yang et al (2006 Phys. Med. Biol.51 1157–72), an exact filtered backprojection (FBP) reconstruction algorithm was proposed for cone beam tomography with saddle trajectory based on the seminal works of Pack and Noo (2005a Inverse Problems21 1105–20; 2005b 8th Int. Meeting on Fully 3D Reconstruction in Radiology and Nuclear Medicine (Salt Lake City) ed F Noo, H Kudo and L G Zeng pp 287–90). However, the artefacts due to discretization and/or sampling errors in the reconstructed images by this method were still visible, especially when the pitch is large. In this paper, two view-independent (VI) algorithms, which are similar to the FDK-type algorithms (Feldkamp et al 1984 J. Opt. Soc. Am. A 1 612–19), are proposed for planar detector geometry. The first VI algorithm involves two filtered projections and a small additional term (two-dimensional (2D) Radon transform term). One of the filtered projections is obtained by ramp filtering (as in the FDK algorithm for circular trajectory) and the other one is obtained by Hilbert transform. The 2D Radon transform term is just like the term which was first derived by Hu (1996 Scanning18 572–81) for a circular trajectory. The second VI algorithm involves only one filtered projection term, which is obtained by differentiation followed by Hilbert transform and the 2D Radon transform term. Both algorithms involve only one backprojection step with a weighting factor as in the FDK algorithm. The simulation studies show that the pixel values of the reconstructed images by the VI algorithms are more accurate than those by the original view differencing (VD) algorithm, the streak artefacts are also reduced, and their computational times are comparable to that of the original VD algorithm. We also generalize the concept of saddle trajectory and the corresponding reconstruction algorithm. The generalized algorithm is also theoretically exact, has a shift-invariant FBP structure, and does not depend on the concept of π-line.