Table of contents

Volumetric modulated arc therapy (VMAT) offers a challenge to classical dosimetry protocols as the beams are dynamic in orientation and aperture shape and may include small apertures. The aim of this paper is to apply a formalism to VMAT beams that has recently been published by the International Atomic Energy Agency (IAEA) working party to improve the dosimetry for small and non-standard fields. We investigated three possible fields and assessed their suitability as plan class specific reference (pcsr) fields. The factors in the new dosimetry formalism were investigated: the conversion of dose to water from the conventional reference field to the pcsr and then from the pcsr to a treatment plan, using a PTW semiflex chamber, two Farmer chambers and an electron diode. Finally, the dose was compared for Alanine, the new formalism and calculated using Pinnacle³ (Philips Radiation Oncology Systems) for two typical clinical VMAT beams. Correction factors between the reference field and the pcsr determined with Alanine range from 0.1% to 2.3% for the three pcsr fields. Dose to water measured using the calibrated ionization chambers is less than 2% different to the dose calculated by Pinnacle³. VMAT planning and delivery procedures have been successfully implemented and a new dosimetry protocol has been investigated for this new technique. Calibration factors for pcsr fields are found to be up to 2.3% different when using the new formalism, compared to using a standard dosimetry protocol. Using the calibration factors determined in the pcsr fields, the ionization chambers and electron diode agree to within 1% with Alanine dosimetry for two clinical VMAT plans. Good agreements between calculations and measurements are found for these two plans when the new formalism is used.

We developed a maximum a posterior (MAP) reconstruction method for positron emission tomography (PET) image reconstruction incorporating magnetic resonance (MR) image information, with the joint entropy between the PET and MR image features serving as the regularization constraint. A non-parametric method was used to estimate the joint probability density of the PET and MR images. Using realistically simulated PET and MR human brain phantoms, the quantitative performance of the proposed algorithm was investigated. Incorporation of the anatomic information via this technique, after parameter optimization, was seen to dramatically improve the noise versus bias tradeoff in every region of interest, compared to the result from using conventional MAP reconstruction. In particular, hot lesions in the FDG PET image, which had no anatomical correspondence in the MR image, also had improved contrast versus noise tradeoff.

Corrections were made to figures 3, 4 and 6, and to the second paragraph of section 3.1 on 13 November 2009. The corrected electronic version is identical to the print version.

Raman spectroscopy is a powerful tool for studying biochemical changes in the human body. We describe a miniature, confocal fibre optic probe intended to fit within the instrument channel of a standard medical endoscope. This probe has been optimized for the study of the carcinogenesis process of oesophageal malignancy. The optical design and fabrication of this probe is described including the anisotropic wet etching technique used to make silicon motherboards and jigs. Example spectra of PTFE reference samples are shown. Spectra with acquisition times as low as 2 s from resected oesophageal tissue are presented showing identifiable biochemical changes from various pathologies.

The problem of fluorescence diffuse optical tomography consists in localizing fluorescent markers from near-infrared light measurements. Among the different available acquisition modalities, the time-resolved modality is expected to provide measurements of richer information content. To extract this information, the moments of the time-resolved measurements are often considered. In this paper, a theoretical analysis of the moments of the forward problem in fluorescence diffuse optical tomography is proposed for the infinite medium geometry. The moments are expressed as a function of the source, detector and markers positions as well as the optical properties of the medium and markers. Here, for the first time, an analytical expression holding for any moments order is mathematically derived. In addition, analytical expressions of the mean, variance and covariance of the moments in the presence of noise are given. These expressions are used to demonstrate the increasing sensitivity of moments to noise. Finally, the newly derived expressions are illustrated by means of sensitivity maps. The physical interpretation of the analytical formulae in conjunction with their map representations could provide new insights into the analysis of the information content provided by moments.

This paper addresses the inverse problem of time-resolved (fluorescence) diffuse optical tomography from temporal moments of the measurements. A methodology that enables one to provide fairly comparable reconstructions is presented. The proposed reconstruction methodology is applied to infinite medium synthetic phantoms in the transmission geometry. Reconstructions are performed for moment orders increasing from 0 to 3. The reconstruction quality is shown to be increasing when higher moment orders are added. However, the value of the highest useful moments order strongly depends on the number of photons that can be acquired. In particular, it can be considered that the benefit of using higher order moments vanishes when fewer than 10⁸ photons are detected. The evolution of the reconstruction quality with respect to the optical properties of the medium and fluorescence lifetime is also shown.

We have investigated a method to individualize the planning target volume (PTV) for deformable targets in radiotherapy by combining a computer tomography (CT) scan with multiple cone beam (CB)CT scans. All combinations of the CT and up to five initial CBCTs were considered. To exclude translational motion, the clinical target volumes (CTVs) in the CBCTs were matched to the CTV in the CT. PTVs investigated were the unions, the intersections and all other structures defined by a volume with a constant CTV location frequency. The method was investigated for three bladder cancer patients with a CT and 20–27 CBCTs. Reliable alternatives to a standard PTV required use of at least four scans for planning. The CTV unions of four or five scans gave similar results when considering the fraction of individual repeat scan CTVs they volumetrically covered to at least 99%. For patient 1, 64% of the repeat scan CTVs were covered by these unions and for patient 2, 86% were covered. Further, the PTVs defined by the volume occupied by the CTV in all except one of the four or five planning scans seemed clinically feasible. On average, 52% of the repeat CBCT CTVs for patient 1 and 64% for patient 2 were covered to minimum 99% of their total volume. For patient 3, the method failed due to poor volume control of the bladder. The suggested PTVs could, with considerably improved conformity, complement the standard PTV.

External beam radiation treatment for patients with cervical cancer is hindered by the relatively large motion of the target volume. A hybrid MRI-accelerator system makes it possible to acquire online MR images during treatment in order to correct for motion and deformation. To fully benefit from such a system, online delineation of the target volumes is necessary. The aim of this study is to investigate the accuracy of rigid, non-rigid and semi-automatic registrations of MR images for interfractional contour propagation in patients with cervical cancer. Registration using mutual information was performed on both bony anatomy and soft tissue. A B-spline transform was used for the non-rigid method. Semi-automatic registration was implemented with a point set registration algorithm on a small set of manual landmarks. Online registration was simulated by application of each method to four weekly MRI scans for each of 33 cervical cancer patients. Evaluation was performed by distance analysis with respect to manual delineations. The results show that soft-tissue registration significantly (P < 0.001) improves the accuracy of contour propagation compared to registration based on bony anatomy. A combination of user-assisted and non-rigid registration provides the best results with a median error of 3.2 mm (1.4–9.9 mm) compared to 5.9 mm (1.7–19.7 mm) with bone registration (P < 0.001) and 3.4 mm (1.3–19.1 mm) with non-rigid registration (P = 0.01). In a clinical setting, the benefit may be further increased when outliers can be removed by visual inspection of the online images. We conclude that for external beam radiation treatment of cervical cancer, online MRI imaging will allow target localization based on soft tissue visualization, which provides a significantly higher accuracy than localization based on bony anatomy. The use of limited user input to guide the registration increases overall accuracy. Additional non-rigid registration further reduces the propagation error and negates errors caused by small observer variations.

The routine use of electronic portal imaging devices (EPIDs) as dosimeters for radiotherapy quality assurance is complicated by the non-water equivalence of the EPID's dose response. A commercial EPID modified to a direct-detection configuration was previously demonstrated to provide water-equivalent dose response with d_max solid water build-up and 10 cm solid water backscatter. Clinical implementation of the direct EPID (dEPID) requires a design that maintains the water-equivalent dose response, can be incorporated onto existing EPID support arms and maintains sufficient image quality for clinical imaging. This study investigated the dEPID dose response with different configurations of build-up and backscatter using varying thickness of solid water and copper. Field size output factors and beam profiles measured with the dEPID were compared with ionization chamber measurements of dose in water for both 6 MV and 18 MV. The dEPID configured with d_max solid water build-up and no backscatter (except for the support arm) was within 1.5% of dose in water data for both energies. The dEPID was maintained in this configuration for clinical dosimetry and image quality studies. Close agreement between the dEPID and treatment planning system was obtained for an IMRT field with 98.4% of pixels within the field meeting a gamma criterion of 3% and 3 mm. The reduced sensitivity of the dEPID resulted in a poorer image quality based on quantitative (contrast-to-noise ratio) and qualitative (anthropomorphic phantom) studies. However, clinically useful images were obtained with the dEPID using typical treatment field doses. The dEPID is a water-equivalent dosimeter that can be implemented with minimal modifications to the standard commercial EPID design. The proposed dEPID design greatly simplifies the verification of IMRT dose delivery.

The purpose of this study was to evaluate the reproducibility of visual feedback-guided breath-hold using a machine vision system with a charge-coupled device camera and a monocular head-mounted display. Sixteen patients with lung tumors who were treated with stereotactic radiotherapy were enrolled. A machine vision system with a charge-coupled device camera was used for monitoring respiration. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. The patients could control their breathing so that the breathing waveform would fall between the upper and lower threshold lines. Planning and treatment were performed under visual feedback-guided expiratory breath-hold. Electronic portal images were obtained during treatment. The range of cranial–caudal motion of the tumor location during each single breath-hold was calculated as the intra-breath-hold (intra-BH) variability. The maximum displacement between the two to five averaged tumor locations of each single breath-hold was calculated as the inter-breath-hold (inter-BH) variability. All 16 patients tolerated the visual feedback-guided breath-hold maneuvers well. The intra- and inter-BH variability of all patients was 1.5 ± 0.6 mm and 1.2 ± 0.5 mm, respectively. A visual feedback-guided breath-hold technique using the machine vision system is feasible with good breath-hold reproducibility.

The aim of this study was to evaluate the effectiveness and efficiency in inverse IMRT planning of one-step optimization with the step-and-shoot (SS) technique as compared to traditional two-step optimization using the sliding windows (SW) technique. The Pinnacle IMRT TPS allows both one-step and two-step approaches. The same beam setup for five head-and-neck tumor patients and dose–volume constraints were applied for all optimization methods. Two-step plans were produced converting the ideal fluence with or without a smoothing filter into the SW sequence. One-step plans, based on direct machine parameter optimization (DMPO), had the maximum number of segments per beam set at 8, 10, 12, producing a directly deliverable sequence. Moreover, the plans were generated whether a split-beam was used or not. Total monitor units (MUs), overall treatment time, cost function and dose–volume histograms (DVHs) were estimated for each plan. PTV conformality and homogeneity indexes and normal tissue complication probability (NTCP) that are the basis for improving therapeutic gain, as well as non-tumor integral dose (NTID), were evaluated. A two-sided t-test was used to compare quantitative variables. All plans showed similar target coverage. Compared to two-step SW optimization, the DMPO-SS plans resulted in lower MUs (20%), NTID (4%) as well as NTCP values. Differences of about 15–20% in the treatment delivery time were registered. DMPO generates less complex plans with identical PTV coverage, providing lower NTCP and NTID, which is expected to reduce the risk of secondary cancer. It is an effective and efficient method and, if available, it should be favored over the two-step IMRT planning.

Several methods can be used to achieve multi-criteria optimization of radiation therapy treatment planning, which strive for Pareto-optimality. The property of the solution being Pareto optimal is desired, because it guarantees that no criteria can be improved without deteriorating another criteria. The most widely used methods are the weighted-sum method, in which the different treatment objectives are weighted, and constrained optimization methods, in which treatment goals are set and the algorithm has to find the best plan fulfilling these goals. The constrained method used in this paper, the 2pc (2-phase -constraint) method is based on the -constraint method, which generates Pareto-optimal solutions. Both approaches are uniquely related to each other. In this paper, we will show that it is possible to switch from the constrained method to the weighted-sum method by using the Lagrange multipliers from the constrained optimization problem, and vice versa by setting the appropriate constraints. In general, the theory presented in this paper can be useful in cases where a new situation is slightly different from the original situation, e.g. in online treatment planning, with deformations of the volumes of interest, or in automated treatment planning, where changes to the automated plan have to be made. An example of the latter is given where the planner is not satisfied with the result from the constrained method and wishes to decrease the dose in a structure. By using the Lagrange multipliers, a weighted-sum optimization problem is constructed, which generates a Pareto-optimal solution in the neighbourhood of the original plan, but fulfills the new treatment objectives.

Previously, we have found that the build-up dose from abutting narrow electron beams formed with unfocussed electron multi-leaf collimator (eMLC) steal leaves was higher than with the respective open field. To investigate more closely the effect of leaf material and shape on dose in the build-up region, straight, round (radius 1.5 cm) and leaf ends with a different front face angle of α (leaf front face pointing towards the beam axis at an angle of 90 − α) made of steel, brass and tungsten were modelled using the BEAMnrc code. Based on a treatment head simulation of a Varian 2100 C/D linac, depth–dose curves and profiles in water were calculated for narrow 6, 12 and 20 MeV eMLC beams (width 1.0 cm, length 10 cm) at source-to-surface distances (SSD) of 102 and 105 cm. The effects of leaf material and front face angle were evaluated based on electron fluence, angle and energy spectra. With a leaf front face angle of 15°, the dose in the build-up region of the 6 MeV field varied between 91 and 100%, while for straight and round leaf shapes the dose varied between 89 and 100%. The variation was between 94 and 100% for 12 and 20 MeV. For abutting narrow 6 MeV fields with total field size 5 × 10 cm², the build-up doses at 5 mm depth for the face angle 15° and straight and round leaf shapes were 96% and 86% (SSD 102 cm) and 89% and 85% (SSD 105 cm). With higher energies, the effect of eMLC leaf shape on dose at 5 mm was slight (3–4% units with 12 MeV) and marginal with 20 MeV. The fluence, energy and angle spectra for total and leaf scattered electrons were practically the same for different leaf materials with 6 MeV. With high energies, the spectra for tungsten were more peaked due to lower leaf transmission. Compared with straight leaf ends, the face angle of 15° and round leaf ends led to a 1 mm (for 6 MeV) and between 1 and 5 mm (12 and 20 MeV at a SSD of 105 cm) decrease of therapeutic range and increase of the field size, respectively. However, profile flatness was better for abutting 6 MeV beams with round (2.5%) and face angle 15° leaves (3.0%) compared to straight leaf shape (5.2%). The eMLC leaves with a face angle of 15° resulted in a marked increase in the build-up dose for the single narrow eMLC beam and thus in the dose in the build-up region from matched abutting fields.

In the present study, we investigate the relationship between the mass-averaged specific absorption rate (SAR) and temperature elevation in anatomically based Japanese head models due to the dipole antenna. A homogeneous cubical model is also used as a basis for the investigation. The frequency region considered is from 1 to 6 GHz. We focused on the averaging mass of SAR, which maximizes the correlation with local temperature elevation. An averaged SAR over 10 g was found to reasonably correlate with local temperature elevation even for frequencies from 3 to 6 GHz. The dominant factor influencing the correlation between mass-averaged SAR and temperature elevation is suggested to be the thermal diffusion length in biological tissue, together with the penetration depth of radio-frequency waves. The correlation of local temperature elevation to mass-averaged SAR is largely influenced by the blood perfusion rate, while at most 10% or less is due to the pinna, model inhomogeneity and the antenna position relative to the head model.

The relative size and relaxation of the invisible pool of bound spins (T_1b) underlying magnetization transfer (MT) was quantified in eight subjects in vivo at 1.5 T from progressive saturation experiments using repetitive MT pulses. The evolution of the binary spin–bath was sampled by increasing the repetition period from 8 to 200 ms. Single-shot echo-planar images at TE = 50 ms were evaluated in the central white matter. Three models were fitted: the general solution, and with constraints of equal relaxation and T_1b = 1 s for the invisible pool. The general solution of unconstrained T_1b provided a significantly better fit, indicating fast-to-intermediate exchange. The bound pool fraction was 17 ± 4%, the relaxation times T_1f = 1.6 ± 0.2 s for free water and T_1b = 171 ± 22 ms for the bound pool. The constrained models did not differ from each other, since here T_1b was similar to the observed T₁ of 1.1 ± 0.1 s. They underestimate the bound pool fraction and its relaxation. Thus, the standard assumption of continuous-wave MT models may underestimate the relaxation via the bound pool by more than a factor of five.

Studies which take into account the anisotropy of tissue dielectric properties for the numerical assessment of induced currents from low-frequency magnetic fields are scarce. In the present study, we compare the induced currents in two anatomical models, using the impedance method. In the first model, we assume that all tissues have isotropic conductivity, whereas in the second one, we assume anisotropic conductivity for the skeletal muscle. Results show that tissue anisotropy should be taken into account when investigating the exposure to low-frequency magnetic fields, because it leads to higher induced current values.

In vivo optical imaging instruments are generally devoted to the acquisition of light coming from fluorescence or bioluminescence processes. Recently, an instrument was conceived with radioisotopic detection capabilities (Kodak in Vivo Multispectral System F) based on the conversion of x-rays from the phosphorus screen. The goal of this work is to demonstrate that an optical imager (IVIS 200, Xenogen Corp., Alameda, USA), designed for in vivo acquisitions of small animals in bioluminescent and fluorescent modalities, can even be employed to detect signals due to radioactive tracers. Our system is based on scintillator crystals for the conversion of high-energy rays and a collimator. No hardware modifications are required. Crystals alone permit the acquisition of photons coming from an in vivo 20 g nude mouse injected with a solution of methyl diphosphonate technetium 99 metastable (Tc99m-MDP). With scintillator crystals and collimators, a set of measurements aimed to fully characterize the system resolution was carried out. More precisely, system point spread function and modulation transfer function were measured at different source depths. Results show that system resolution is always better than 1.3 mm when the source depth is less than 10 mm. The resolution of the images obtained with radioactive tracers is comparable with the resolution achievable with dedicated techniques. Moreover, it is possible to detect both optical and nuclear tracers or bi-modal tracers with only one instrument.