Table of contents

This paper presents a new concept to automatically detect the neighborhood in an image where deformable registration is mis-performing. Specifically, the displacement vector field (DVF) from a deformable image registration is substituted into a finite-element-based elastic framework to calculate unbalanced energy in each element. The value of the derived energy indicates the quality of the DVF in its neighborhood. The new voxel-based evaluation approach is compared with three other validation criteria: landmark measurement, a finite element approach and visual comparison, for deformable registrations performed with the optical-flow-based 'demons' algorithm as well as thin-plate spline interpolation. This analysis was performed on three pairs of prostate CT images. The results of the analysis show that the four criteria give mutually comparable quantitative assessments on the six registration instances. As an objective concept, the unbalanced energy presents no requirement on boundary constraints in its calculation, different from traditional mechanical modeling. This method is automatic, and at voxel level suitable to evaluate deformable registration in a clinical setting.

Disease-specific enhanced imaging through a targeted agent promises to improve the specificity of medical ultrasound. Nanoparticles may provide unique advantages for targeted ultrasound imaging due to their novel physical and surface properties. In this study, we examined a nanoparticle agent developed from a biodegradable polymer, polylactic acid (PLA). The nanoparticles (mean diameter = 250 nm) were surface conjugated to an anti-Her2 antibody (i.e., Herceptin) for specific binding to breast cancer cells that overexpress Her2 receptors. We examined the targeting specificity and the resultant ultrasound enhancement in Her2-positive and negative cells. Flow cytometry and confocal imaging were used to assess the nanoparticle-cell binding. Her2-positive cells demonstrated substantial staining after incubation with nanoparticle/antibody conjugates, while minimal staining was found in Her2-negative cells, indicating receptor-specific binding of the conjugated PLA nanoparticles. In high-resolution ultrasound B-mode images, the average gray scale of the Her2-positive cells was consistently and significantly higher after nanoparticle treatment (133 ± 4 in treated cells versus 109 ± 4 in control, p < 0.001, n = 5), while no difference was detected in the cells that did not overexpress the receptors (117 ± 3 in treated cells versus 118 ± 5 in control). In conclusion, the feasibility of using targeted nanoparticles to enhance ultrasonic images was demonstrated in vitro. This may be a promising approach to target cancer biomarkers for site-specific ultrasound imaging.

Infants and children are a higher risk population for radiation cancer induction compared to adults. Although some values on pediatric patient doses for cardiac procedures have been reported, data to determine reference levels are scarce, especially when compared to those available for adults in diagnostic and therapeutic procedures. The aim of this study is to make a new contribution to the scarce published data in pediatric cardiac procedures and help in the determination of future dose reference levels. This paper presents a set of patient dose values, in terms of air kerma area product (KAP) and entrance surface air kerma (ESAK), measured in a pediatric cardiac catheterization laboratory equipped with a biplane x-ray system with dynamic flat panel detectors. Cardiologists were properly trained in radiation protection. The study includes 137 patients aged between 10 days and 16 years who underwent diagnostic catheterizations or therapeutic procedures. Demographic data and technical details of the procedures were also gathered. The x-ray system was submitted to a quality control programme, including the calibration of the transmission ionization chamber. The age distribution of the patients was 47 for <1 year; 52 for 1–<5 years; 25 for 5–<10 years and 13 for 10–<16 years. Median values of KAP were 1.9, 2.9, 4.5 and 15.4 Gy cm² respectively for the four age bands. These KAP values increase by a factor of 8 when moving through the four age bands. The probability of a fatal cancer per fluoroscopically guided cardiac procedure is about 0.07%. Median values of ESAK for the four age bands were 46, 50, 56 and 163 mGy, which lie far below the threshold for deterministic effects on the skin. These dose values are lower than those published in previous papers.

Tumors, especially in the thorax and abdomen, are subject to respiratory motion, and understanding the structure of respiratory motion is a key component to the management and control of disease in these sites. We have applied statistical analysis and correlation discovery methods to analyze and mine tumor respiratory motion based on a finite state model of tumor motion. Aggregates (such as minimum, maximum, average and mean), histograms, percentages, linear regression and multi-round statistical analysis have been explored. The results have been represented in various formats, including tables, graphs and text description. Different graphs, for example scatter plots, clustered column figures, 100% stacked column figures and box-whisker plots, have been applied to highlight different aspects of the results. The internal tumor motion from 42 lung tumors, 30 of which have motion larger than 5 mm, has been analyzed. Results for both inter-patient and intra-patient motion characteristics, such as duration and travel distance patterns, are reported. New knowledge of patient-specific tumor motion characteristics have been discovered, such as expected correlations between properties. The discovered tumor motion characteristics will be utilized in different aspects of image-guided radiation treatment, including treatment planning, online tumor motion prediction and real-time radiation dose delivery.

Optimization of treatment plans in radiotherapy requires the knowledge of tumour control probability (TCP) and normal tissue complication probability (NTCP). Mathematical models may help to obtain quantitative estimates of TCP and NTCP. A single-cell-based computer simulation model is presented, which simulates tumour growth and radiation response on the basis of the response of the constituting cells. The model contains oxic, hypoxic and necrotic tumour cells as well as capillary cells which are considered as sources of a radial oxygen profile. Survival of tumour cells is calculated by the linear quadratic model including the modified response due to the local oxygen concentration. The model additionally includes cell proliferation, hypoxia-induced angiogenesis, apoptosis and resorption of inactivated tumour cells. By selecting different degrees of angiogenesis, the model allows the simulation of oxic as well as hypoxic tumours having distinctly different oxygen distributions. The simulation model showed that poorly oxygenated tumours exhibit an increased radiation tolerance. Inter-tumoural variation of radiosensitivity flattens the dose response curve. This effect is enhanced by proliferation between fractions. Intra-tumoural radiosensitivity variation does not play a significant role. The model may contribute to the mechanistic understanding of the influence of biological tumour parameters on TCP. It can in principle be validated in radiation experiments with experimental tumours.

The imaging of neural sources of magnetoencephalographic data based on distributed source models requires additional constraints on the source distribution in order to overcome ill-posedness and obtain a plausible solution. The minimum l_p norm (0 < p ⩽ 1) constraint is known to be appropriate for reconstructing focal sources distributed in several regions. A well-known recursive method for solving the l_p-norm minimization problem, for example, is the focal underdetermined system solver (FOCUSS). However, this iterative algorithm tends to give spurious sources when the noise level is high. In this study, we present an algorithm to incorporate a smoothing technique into the FOCUSS algorithm and test different smoothing kernels in a surface-based cortical source space. Simulations with cortical source patches assumed in auditory areas show that the incorporation of the smoothing procedure improves the performance of the FOCUSS algorithm, and that using the geodesic distance for constructing a smoothing kernel is a better choice than using the Euclidean one, particularly when employing a cortical source space. We also apply these methods to a real data set obtained from an auditory experiment and illustrate their applicability to realistic data by presenting the reconstructed source images localized in the superior temporal gyrus.

Intrafraction tumour (e.g. lung) motion due to breathing can, in principle, be compensated for by applying identical breathing motions to the leaves of a multileaf collimator (MLC) as intensity-modulated radiation therapy is delivered by the dynamic MLC (DMLC) technique. A difficulty arising, however, is that irradiated voxels, which are in line with a bixel at one breathing phase (at which the treatment plan has been made), may move such that they cease to be in line with that breathing bixel at another phase. This is the phenomenon of differential voxel motion and existing tracking solutions have ignored this very real problem. There is absolutely no tracking solution to the problem of compensating for differential voxel motion. However, there is a strategy that can be applied in which the leaf breathing is determined to minimize the geometrical mismatch in a least-squares sense in irradiating differentially-moving voxels. A 1D formulation in very restricted circumstances is already in the literature and has been applied to some model breathing situations which can be studied analytically. These are, however, highly artificial. This paper presents the general 2D formulation of the problem including allowing different importance factors to be applied to planning target volume and organ at risk (or most generally) each voxel. The strategy also extends the literature strategy to the situation where the number of voxels connecting to a bixel is a variable. Additionally the phenomenon of 'cross-leaf-track/channel' voxel motion is formally addressed. The general equations are presented and analytic results are given for some 1D, artificially contrived, motions based on the Lujan equations of breathing motion. Further to this, 3D clinical voxel motion data have been extracted from 4D CT measurements to both assess the magnitude of the problem of 2D motion perpendicular to the beam-delivery axis in clinical practice and also to find the 2D optimum breathing-leaf strategy. Issues relating to the practical calculation of the strategy, including effects on leaf velocity and effects of different spatial-sampling frequencies, have been investigated, and unattenuated-fluence maps have been produced showing the effects of the differential motion and tracking. It was discovered that large distances between adjacent leaf-ends could cause the tracking to fail when there was tissue motion across the leaf channels. To overcome this problem the use of 'synchronized' leaf trajectories, which ensure that adjacent leaf-ends are always close enough to each other to facilitate tracking, has also been investigated.

Minimally invasive therapies (such as radiofrequency ablation) are becoming more commonly used in the United States for the treatment of hepatocellular carcinomas and liver metastases. Unfortunately, these procedures suffer from high recurrence rates of hepatocellular carcinoma (∼34–55%) or metastases following ablation therapy. The ability to perform real-time temperature imaging while a patient is undergoing radiofrequency ablation could provide a significant reduction in these recurrence rates. In this paper, we demonstrate the feasibility of ultrasound-based temperature imaging on a tissue-mimicking phantom undergoing radiofrequency heating. Ultrasound echo signals undergo time shifts with increasing temperature, which are tracked using 2D correlation-based speckle tracking methods. Time shifts or displacements in the echo signal are accumulated, and the gradient of these time shifts are related to changes in the temperature of the tissue-mimicking phantom material using a calibration curve generated from experimental data. A tissue-mimicking phantom was developed that can undergo repeated radiofrequency heating procedures. Both sound speed and thermal expansion changes of the tissue-mimicking material were measured experimentally and utilized to generate the calibration curve relating temperature to the displacement gradient. Temperature maps were obtained, and specific regions-of-interest on the temperature maps were compared to invasive temperatures obtained using fiber-optic temperature probes at the same location. Temperature elevation during a radiofrequency ablation procedure on the phantom was successfully tracked to within ±0.5 °C.

PET-SORTEO is a Monte Carlo-based simulator that enables the fast generation of realistic PET data for the geometry of the ECAT EXACT HR+ scanner. In order to address the increasing need for simulation models of animal PET imaging systems, our aim is to adapt and configure this simulation tool for small animal PET scanners, especially for the widely distributed microPET R4 and Focus 220 systems manufactured by Siemens Preclinical Solutions. We propose a simulation model that can produce realistic rodent images in order to evaluate and optimize acquisition and reconstruction protocols. The first part of this study presents the validation of SORTEO against the geometries of the R4 and the Focus 220 systems. This validation is carried out against actual measurements performed on the R4 scanner at the Montreal Neurological Institute in Canada and on the Focus 220 system of the department of radiopharmaceuticals of the Austrian Research Center in Seibersdorf. The comparison of simulated and experimental performance measurements includes spatial resolution, energy spectra, scatter fraction and count rates. In the second part of the study, we demonstrate the ability to rapidly generate realistic whole-body radioactive distributions using the MOBY phantom and give comparative example case studies of the same rodent model simulated with PET-SORTEO for the R4 and Focus 220 systems.

Radiographic imaging of large patients is compromised by x-ray scatter. Optimization of digital x-ray imaging systems used for projection radiography requires the use of the best possible antiscatter grid. The performance of antiscatter grids used in conjunction with digital x-ray imaging systems can be characterized through measurement of the signal-to-noise ratio (SNR) improvement factor (K_SNR). The SNR improvement factor of several linear, focused antiscatter grids was determined from measurements of the fundamental primary and scatter transmission fraction measurements of the grids as well as the inherent scatter-to-primary ratio (SPR) of the x-ray beam and scatter phantom. The inherent SPR and scatter transmission fraction was measured using a graduated lead beam stop method. The K_SNR of eight grids with line rates (N) in the range 40 to 80 cm⁻¹ and ratios (r) in the range 8:1 to 15:1 was measured. All of the grids had fiber interspace material and carbon-fiber covers. The scatter phantom used was Solid Water® with thickness 10 to 50 cm, and a 30 × 30 cm² field of view was used. All measurements were acquired using a 104 kVp x-ray beam. The SPR of the non-grid imaging condition ranged from 2.55 for the 10 cm phantom to 25.9 for the 50 cm phantom. The scatter transmission fractions ranged from a low of 0.083 for the N50 r15 grid to a high of 0.22 for the N40 r8 grid and the primary transmission fractions ranged from a low of 0.69 for the N80 r15 grid to 0.76 for the N40 r8 grid. The SNR improvement factors ranged from 1.2 for the 10 cm phantom and N40 r8 grid to 2.09 for the 50 cm phantom and the best performing N50 r15, N44 r15 and N40 r14 grids.

Synchrotron stereotactic radiotherapy (SSR) is a radiotherapy technique that makes use of the interactions of monochromatic low energy x-rays with high atomic number (Z) elements. An important dose-enhancement can be obtained if the target volume has been loaded with a sufficient amount of a high-Z element, such as iodine. In this study, we compare experimental dose measurements, obtained with normoxic polymer gel (nPAG), with Monte Carlo computations. Gels were irradiated within an anthropomorphic head phantom and were read out by magnetic resonance imaging. The dose-enhancement due to the presence of iodine in the gel (iodine concentration: 5 and 10 mg ml⁻¹) was measured at two radiation energies (35 and 80 keV) and was compared to the calculated factors. nPAG dosimetry was shown to be efficient for measuring the sharp dose gradients produced by SSR. The agreement between 3D gel dosimetry and calculated dose distributions was found to be within 4% of the dose difference criterion and a distance to agreement of 2.1 mm for 80% of the voxels. Polymer gel doped with iodine exhibited higher sensitivity, in good agreement with the calculated iodine-dose enhancement. We demonstrate in this preliminary study that iodine-doped nPAG could be used for measuring in situ dose distributions for iodine-enhanced SSR treatment.

The purpose of this study is to investigate whether the method of applicator reconstruction and/or the applicator orientation influence the dose calculation to points around the applicator for brachytherapy of cervical cancer with CT-based treatment planning. A phantom, containing a fixed ring applicator set and six lead pellets representing dose points, was used. The phantom was CT scanned with the ring applicator at four different angles related to the image plane. In each scan the applicator was reconstructed by three methods: (1) direct reconstruction in each image (DR), (2) reconstruction in multiplanar reconstructed images (MPR) and (3) library plans, using pre-defined applicator geometry (LIB). The doses to the lead pellets were calculated. The relative standard deviation (SD) for all reconstruction methods was less than 3.7% in the dose points. The relative SD for the LIB method was significantly lower (p < 0.05) than for the DR and MPR methods for all but two points. All applicator orientations had similar dose calculation reproducibility. Using library plans for applicator reconstruction gives the most reproducible dose calculation. However, with restrictive guidelines for applicator reconstruction the uncertainties for all methods are low compared to other factors influencing the accuracy of brachytherapy.

Breast density (the percentage of fibroglandular tissue in the breast) has been suggested to be a useful surrogate marker for breast cancer risk. It is conventionally measured using screen–film mammographic images by a labor-intensive histogram segmentation method (HSM). We have adapted and modified the HSM for measuring breast density from raw digital mammograms acquired by full-field digital mammography. Multiple regression model analyses showed that many of the instrument parameters for acquiring the screening mammograms (e.g. breast compression thickness, radiological thickness, radiation dose, compression force, etc) and image pixel intensity statistics of the imaged breasts were strong predictors of the observed threshold values (model R² = 0.93) and %-density (R² = 0.84). The intra-class correlation coefficient of the %-density for duplicate images was estimated to be 0.80, using the regression model-derived threshold values, and 0.94 if estimated directly from the parameter estimates of the %-density prediction regression model. Therefore, with additional research, these mathematical models could be used to compute breast density objectively, automatically bypassing the HSM step, and could greatly facilitate breast cancer research studies.

Atrial fibrillation (AF) is the most frequently sustained cardiac arrhythmia affecting humans. The electrical isolation by ablation of the pulmonary veins (PVs) in the left atrium (LA) of the heart has been proven as an effective cure of AF. The ablation consists mainly in the formation of a localized circumferential thermal coagulation of the cardiac tissue surrounding the PVs. In the present numerical study, the feasibility of producing the required circumferential lesion with an endoesophageal ultrasound probe is investigated. The probe operates at 1 MHz and consists of a 2D array with enough elements (114 × 20) to steer the acoustic field electronically in a volume comparable to the LA. Realistic anatomical conditions of the thorax were considered from the segmentation of histological images of the thorax. The cardiac muscle and the blood-filled cavities in the heart were identified and considered in the sound propagation and thermal models. The influence of different conditions of the thermal sinking in the LA chamber was also studied. The circumferential ablation of the PVs was achieved by the sum of individual lesions induced with the proposed device. Different scenarios of lesion formation were considered where ultrasound exposures (1, 2, 5 and 10 s) were combined with maximal peak temperatures (60, 70 and 80 °C). The results of this numerical study allowed identifying the limits and best conditions for controlled lesion formation in the LA using the proposed device. A controlled situation for the lesion formation surrounding the PVs was obtained when the targets were located within a distance from the device in the range of 26 ± 7 mm. When combined with a maximal temperature of 70 °C and an exposure time between 5 and 10 s, this distance ensured preservation of the esophageal structures, controlled lesion formation and delivery of an acoustic intensity at the transducer surface that is compatible with existing materials. With a peak temperature of 70 °C, the device and setup presented here induced highly localized lesions with a lesion volume varying from 10 ± 4 to 18 ± 7 mm³ for an ultrasound exposure between 5 and 10 s, respectively, while the intensity varied from 26 ± 7 to 20 ± 6 W cm⁻².

In this paper we present electromagnetic (EM) analysis of the unloaded slotted-tube resonator (STR) with a circular cross section, using the finite element method (FEM) and method of moments (MoM) in two dimensions. This analysis allows the determination of the primary parameters: [L] and [C] matrices, optimization of the field homogeneity, and simulates the frequency response of S₁₁ at the RF port of the designed STR. The optimum configuration is presented, taking into account the effect of the thickness of the STR and the effect of the RF shield. As an application, we present the design results of a MRI probe using the STR and operating at 500 MHz (proton imaging at 11.74 T). The resonator has −69.37 dB minimum reflection and an unloaded quality factor (Q_o) > 500 at 500 MHz.

Nanodosimetric single-event distributions or their mean values may contribute to a better understanding of how radiation induced biological damages are produced. They may also provide means for radiation quality characterization in therapy beams. Experimental nanodosimetry is however technically challenging and Monte Carlo simulations are valuable as a complementary tool for such investigations. The dose-mean lineal energy was determined in a therapeutic p(65)+Be neutron beam and in a ⁶⁰Co γ beam using low-pressure gas detectors and the variance-covariance method. The neutron beam was simulated using the condensed history Monte Carlo codes MCNPX and SHIELD-HIT. The dose-mean lineal energy was calculated using the simulated dose and fluence spectra together with published data from track-structure simulations. A comparison between simulated and measured results revealed some systematic differences and different dependencies on the simulated object size. The results show that both experimental and theoretical approaches are needed for an accurate dosimetry in the nanometer region. In line with previously reported results, the dose-mean lineal energy determined at 10 nm was shown to be related to clinical RBE values in the neutron beam and in a simulated 175 MeV proton beam as well.

The layered–resolved microstructure and spectroscopy of mouse oral mucosa are obtained using a combination of multiphoton imaging and spectral analysis with different excitation wavelengths. In the keratinizing layer, the keratinocytes microstructure can be characterized and the keratinizing thickness can be measured. The keratin fluorescence signal can be further characterized by emission maxima at 510 nm. In the epithelium, the cellular microstructure can be quantitatively visualized with depth and the epithelium thickness can be determined by multiphoton imaging excited at 730 nm. The study also shows that the epithelial spectra excited at 810 nm, showing a combination of NADH and FAD fluorescence, can be used for the estimation of the metabolic state in epithelium. Interestingly, a second-harmonic generation (SHG) signal from DNA was observed for the first time within the epithelial layer in backscattering geometry and provides the possibility of analyzing the chromatin structure. In the stroma, the combination of multiphoton imaging and spectral analysis excited at 850 nm in tandem can obtain quantitative information regarding the biomorphology and biochemistry of stroma. Specifically, the microstructure of collagen, minor salivary glands and elastic fibers, and the optical property of the stroma can be quantitatively displayed. Overall, these results suggest that the combination of multiphoton imaging and spectral analysis with different excitation wavelengths has the potential to provide important and comprehensive information for early diagnosis of oral cancer.

Experimental methods are commonly used for patient-specific intensity-modulated radiotherapy (IMRT) verification. The purpose of this study was to investigate the accuracy and performance of independent dose calculation software (denoted as 'MUV' (monitor unit verification)) for patient-specific quality assurance (QA). 52 patients receiving step-and-shoot IMRT were considered. IMRT plans were recalculated by the treatment planning systems (TPS) in a dedicated QA phantom, in which an experimental 1D and 2D verification (0.3 cm³ ionization chamber; films) was performed. Additionally, an independent dose calculation was performed. The fluence-based algorithm of MUV accounts for collimator transmission, rounded leaf ends, tongue-and-groove effect, backscatter to the monitor chamber and scatter from the flattening filter. The dose calculation utilizes a pencil beam model based on a beam quality index. DICOM RT files from patient plans, exported from the TPS, were directly used as patient-specific input data in MUV. For composite IMRT plans, average deviations in the high dose region between ionization chamber measurements and point dose calculations performed with the TPS and MUV were 1.6 ± 1.2% and 0.5 ± 1.1% (1 S.D.). The dose deviations between MUV and TPS slightly depended on the distance from the isocentre position. For individual intensity-modulated beams (total 367), an average deviation of 1.1 ± 2.9% was determined between calculations performed with the TPS and with MUV, with maximum deviations up to 14%. However, absolute dose deviations were mostly less than 3 cGy. Based on the current results, we aim to apply a confidence limit of 3% (with respect to the prescribed dose) or 6 cGy for routine IMRT verification. For off-axis points at distances larger than 5 cm and for low dose regions, we consider 5% dose deviation or 10 cGy acceptable. The time needed for an independent calculation compares very favourably with the net time for an experimental approach. The physical effects modelled in the dose calculation software MUV allow accurate dose calculations in individual verification points. Independent calculations may be used to replace experimental dose verification once the IMRT programme is mature.

CCD (charged coupled device) and CMOS imaging technologies can be applied to thin tissue autoradiography as potential imaging alternatives to using conventional film. In this work, we compare two particular devices: a CCD operating in slow scan mode and a CMOS-based active pixel sensor, operating at near video rates. Both imaging sensors have been operated at room temperature using direct irradiation with images produced from calibrated microscales and radiolabelled tissue samples. We also compare these digital image sensor technologies with the use of conventional film. We show comparative results obtained with ¹⁴C calibrated microscales and ³⁵S radiolabelled tissue sections. We also present the first results of ³H images produced under direct irradiation of a CCD sensor operating at room temperature. Compared to film, silicon-based imaging technologies exhibit enhanced sensitivity, dynamic range and linearity.

This study investigated the relationship between the specific absorption rate and temperature elevation in an anatomically-based model named NORMAN for exposure to radio-frequency far fields in the ICNIRP guidelines (1998 Health Phys.74 494–522). The finite-difference time-domain method is used for analyzing the electromagnetic absorption and temperature elevation in NORMAN. In order to consider the variability of human thermoregulation, parameters for sweating are derived and incorporated into a conventional sweating formula. First, we investigated the effect of blood temperature variation modeling on body-core temperature. The computational results show that the modeling of blood temperature variation was the dominant factor influencing the body-core temperature. This is because the temperature in the inner tissues is elevated via the circulation of blood whose temperature was elevated due to EM absorption. Even at different frequencies, the body-core temperature elevation at an identical whole-body average specific absorption rate (SAR) was almost the same, suggesting the effectiveness of the whole-body average SAR as a measure in the ICNIRP guidelines. Next, we discussed the effect of sweating on the temperature elevation and thermal time constant of blood. The variability of temperature elevation caused by the sweating rate was found to be 30%. The blood temperature elevation at the basic restriction in the ICNIRP guidelines of 0.4 W kg⁻¹ is 0.25 °C even for a low sweating rate. The thermal time constant of blood temperature elevation was 23 min and 52 min for a man with a lower and a higher sweating rate, respectively, which is longer than the average time of the SAR in the ICNIRP guidelines. Thus, the whole-body average SAR required for blood temperature elevation of 1 °C was 4.5 W kg⁻¹ in the model of a human with the lower sweating coefficients for 60 min exposure. From a comparison of this value with the basic restriction in the ICNIRP guidelines of 0.4 W kg⁻¹, the safety factor was 11.

A new method utilizing alpha particles to treat solid tumors is presented. Tumors are treated with interstitial radioactive sources which continually release short-lived alpha emitting atoms from their surface. The atoms disperse inside the tumor, delivering a high dose through their alpha decays. We implement this scheme using thin wire sources impregnated with ²²⁴Ra, which release by recoil ²²⁰Rn, ²¹⁶Po and ²¹²Pb atoms. This work aims to demonstrate the feasibility of our method by measuring the activity patterns of the released radionuclides in experimental tumors. Sources carrying ²²⁴Ra activities in the range 10–130 kBq were used in experiments on murine squamous cell carcinoma tumors. These included gamma spectroscopy of the dissected tumors and major organs, Fuji-plate autoradiography of histological tumor sections and tissue damage detection by Hematoxylin-Eosin staining. The measurements focused on ²¹²Pb and ²¹²Bi. The ²²⁰Rn/²¹⁶Po distribution was treated theoretically using a simple diffusion model. A simplified scheme was used to convert measured ²¹²Pb activities to absorbed dose estimates. Both physical and histological measurements confirmed the formation of a 5–7 mm diameter necrotic region receiving a therapeutic alpha-particle dose around the source. The necrotic regions shape closely corresponded to the measured activity patterns. ²¹²Pb was found to leave the tumor through the blood at a rate which decreased with tumor mass. Our results suggest that the proposed method, termed DART (diffusing alpha-emitters radiation therapy), may potentially be useful for the treatment of human patients.

The use of magnetic ac susceptibility measurements of biological tissues in the quantitative determination of their particulate magnetic carrier content has been investigated. In a first step, an ad hoc series of agar dilutions of the superparamagnetic contrast agent Endorem®, used as an example of magnetic carrier, has been characterized to determine the influence of the dipolar interaction. With this result in hand, the quantitative determination of the content of a magnetic carrier in the ex vivo liver and spleen tissues of rats, to which the same compound was previously administered, has been accomplished. It is shown that, by careful interpretation of the temperature dependent out-of-phase susceptibility profiles in the cryogenic range, it is possible to discern between the magnetic contribution of the carrier and that of biomineral iron, being able to detect magnetic carrier iron concentrations of the order of 1 µg Fe g⁻¹ dry tissue. At the usual dosages in humans, necessarily small to avoid toxicity, the amount of magnetic carrier in terms of elemental iron is small compared to physiological iron. The choice of their most salient property, that is, the magnetic moment, therefore makes the quantification possible even in such a minority proportion. By analysing the magnetic dynamics, through a method that just considers the in-phase and the out-of phase components of the susceptibility at only one frequency, it has been possible to decouple the carrier concentration from eventual local aggregations, opening the possibility of investigating the degree of particle clustering at a larger observation scale compared with transmission electron microscopy, and independently of physiological iron.

Helical tomotherapy is a relatively new intensity-modulated radiation therapy (IMRT) treatment for which room shielding has to be reassessed for the following reasons. The beam-on-time needed to deliver a given target dose is increased and leads to a weekly workload of typically one order of magnitude higher than that for conventional radiation therapy. The special configuration of tomotherapy units does not allow the use of standard shielding calculation methods. A conventional linear accelerator must be shielded for primary, leakage and scatter photon radiations. For tomotherapy, primary radiation is no longer the main shielding issue since a beam stop is mounted on the gantry directly opposite the source. On the other hand, due to the longer irradiation time, the accelerator head leakage becomes a major concern. An analytical model based on geometric considerations has been developed to determine leakage radiation levels throughout the room for continuous gantry rotation. Compared to leakage radiation, scatter radiation is a minor contribution. Since tomotherapy units operate at a nominal energy of 6 MV, neutron production is negligible. This work proposes a synthetic and conservative model for calculating shielding requirements for the Hi-Art II TomoTherapy unit. Finally, the required concrete shielding thickness is given for different positions of interest.

The aim of this work was to investigate the dosimetric performance properties of the N-vinylpyrrolidone argon (VIPAR) based polymer gel as a dosimetric tool in clinical radiotherapy. VIPAR gels with a larger concentration of gelatin than the standard recipe were manufactured and irradiated up to 68 Gy using a 6 and 18 MV linear accelerator. Using MRI, the R2-dose response was recorded at different imaging sessions within a 34 day time period post-irradiation. The R2-dose response was found to be linear between 5 and 68 Gy. Although dose sensitivity did not show significant variation with time, the measured R2-dose values showed an increasing trend, which was less evident beyond 17 days. At one day post-irradiation, calculated dose standard uncertainties at 20 Gy and 56 Gy were 2.2% and 1.7%, providing a dose resolution of 0.45 Gy and 0.97 Gy, respectively. Although these values fulfilled the 2% limit of ICRU, when gels were imaged at one day post-irradiation, it was shown that the temporal evolution of the R2 values deteriorated the per cent standard uncertainty and the dose resolution by ∼57%, when imaged 17 days post-irradiation. Variation in the coagulation temperature of the gels did not impact the R2-dose sensitivity. This study has shown that the VIPAR gel has the properties of a dosimetric tool required in clinical radiotherapy, especially in applications where a wide dose dynamic range is employed. For results with the lowest per cent uncertainty and the optimum dose resolution, the dosimetry gels used in this work should be MR scanned at one day post-irradiation. Furthermore, a preliminary study on the R2-dose response of a new normoxic N-vinylpyrrolidone-based polymer gel showed that it could potentially replace the traditional VIPAR gel formulation, while preserving the wide dynamic dose response inherent to that monomer.

A theoretical study on the magnetoacoustic signal generation with magnetic induction and its applications to electrical conductivity reconstruction is conducted. An object with a concentric cylindrical geometry is located in a static magnetic field and a pulsed magnetic field. Driven by Lorentz force generated by the static magnetic field, the magnetically induced eddy current produces acoustic vibration and the propagated sound wave is received by a transducer around the object to reconstruct the corresponding electrical conductivity distribution of the object. A theory on the magnetoacoustic waveform generation for a circular symmetric model is provided as a forward problem. The explicit formulae and quantitative algorithm for the electrical conductivity reconstruction are then presented as an inverse problem. Computer simulations were conducted to test the proposed theory and assess the performance of the inverse algorithms for a multi-layer cylindrical model. The present simulation results confirm the validity of the proposed theory and suggest the feasibility of reconstructing electrical conductivity distribution based on the proposed theory on the magnetoacoustic signal generation with magnetic induction.

This work reports the results of the application of a practical method to determine the in vivo dose at the isocenter point, D_iso, of brain thorax and pelvic treatments using a transit signal S_t. The use of a stable detector for the measurement of the signal S_t (obtained by the x-ray beam transmitted through the patient) reduces many of the disadvantages associated with the use of solid-state detectors positioned on the patient as their periodic recalibration, and their positioning is time consuming. The method makes use of a set of correlation functions, obtained by the ratio between S_t and the mid-plane dose value, D_m, in standard water-equivalent phantoms, both determined along the beam central axis.

The in vivo measurement of D_iso required the determination of the water-equivalent thickness of the patient along the beam central axis by the treatment planning system that uses the electron densities supplied by calibrated Hounsfield numbers of the computed tomography scanner. This way it is, therefore, possible to compare D_iso with the stated doses, D_iso,TPS, generally used by the treatment planning system for the determination of the monitor units.

The method was applied in five Italian centers that used beams of 6 MV, 10 MV, 15 MV x-rays and ⁶⁰Co γ-rays. In particular, in four centers small ion-chambers were positioned below the patient and used for the S_t measurement. In only one center, the S_t signals were obtained directly by the central pixels of an EPID (electronic portal imaging device) equipped with commercial software that enabled its use as a stable detector.

In the four centers where an ion-chamber was positioned on the EPID, 60 pelvic treatments were followed for two fields, an anterior–posterior or a posterior–anterior irradiation and a lateral–lateral irradiation. Moreover, ten brain tumors were checked for a lateral–lateral irradiation, and five lung tumors carried out with three irradiations with different gantry angles were followed. One center used the EPID as a detector for the S_t measurement and five pelvic treatments with six fields (many with oblique incidence) were followed. These last results are reported together with those obtained in the same center during a pilot study on ten pelvic treatments carried out by four orthogonal fields.

The tolerance/action levels for every radiotherapy fraction were 4% and 5% for the brain (symmetric inhomogeneities) and thorax/pelvic (asymmetric inhomogeneities) irradiations, respectively. This way the variations between the total measured and prescribed doses at the isocenter point in five fractions were well within 2% for the brain treatment, and 4% for thorax/pelvic treatments. Only 4 out of 90 patients needed new replanning, 2 patients of which needed a new CT scan.