Computer tomographic (CT) scans are used to correct for tissue inhomogeneities in radiotherapy treatment planning. In order to guarantee a precise treatment, it is important to obtain the relationship between CT Hounsfield units and electron densities (or proton stopping powers for proton radiotherapy), which is the basic input for radiotherapy planning systems which consider tissue heterogeneities. A method is described to determine improved CT calibrations for biological tissue (a stoichiometric calibration) based on measurements using tissue equivalent materials. The precision of this stoichiometric calibration and the more usual tissue substitute calibration is determined by a comparison of calculated proton radiographic images based on these calibrations and measured radiographs of a biological sample. It has been found that the stoichiometric calibration is more precise than the tissue substitute calibration.

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In this paper we present the pencil beam dose model used for treatment planning at the PSI proton gantry, the only system presently applying proton therapy with a beam scanning technique. The scope of the paper is to give a general overview on the various components of the dose model, on the related measurements and on the practical parametrization of the results. The physical model estimates from first physical principles absolute dose normalized to the number of incident protons. The proton beam flux is measured in practice by plane-parallel ionization chambers (ICs) normalized to protons via Faraday-cup measurements. It is therefore possible to predict and deliver absolute dose directly from this model without other means. The dose predicted in this way agrees very well with the results obtained with ICs calibrated in a cobalt beam. Emphasis is given in this paper to the characterization of nuclear interaction effects, which play a significant role in the model and are the major source of uncertainty in the direct estimation of the absolute dose. Nuclear interactions attenuate the primary proton flux, they modify the shape of the depth-dose curve and produce a faint beam halo of secondary dose around the primary proton pencil beam in water. A very simple beam halo model has been developed and used at PSI to eliminate the systematic dependences of the dose observed as a function of the size of the target volume. We show typical results for the relative (using a CCD system) and absolute (using calibrated ICs) dosimetry, routinely applied for the verification of patient plans. With the dose model including the nuclear beam halo we can predict quite precisely the dose directly from treatment planning without renormalization measurements, independently of the dose, shape and size of the dose fields. This applies also to the complex non-homogeneous dose distributions required for the delivery of range-intensity-modulated proton therapy, a novel therapy technique developed at PSI.

Protons are an interesting modality for radiotherapy because of their well defined range and favourable depth dose characteristics. On the other hand, these same characteristics lead to added uncertainties in their delivery. This is particularly the case at the distal end of proton dose distributions, where the dose gradient can be extremely steep. In practice however, this gradient is rarely used to spare critical normal tissues due to such worries about its exact position in the patient. Reasons for this uncertainty are inaccuracies and non-uniqueness of the calibration from CT Hounsfield units to proton stopping powers, imaging artefacts (e.g. due to metal implants) and anatomical changes of the patient during treatment. In order to improve the precision of proton therapy therefore, it would be extremely desirable to verify proton range in vivo, either prior to, during, or after therapy. In this review, we describe and compare state-of-the art in vivo proton range verification methods currently being proposed, developed or clinically implemented.

The new proton therapy facility is being assembled at the Paul Scherrer Institute (PSI). The beam delivered by the PSI sector cyclotron can be split and brought into a new hall where it is degraded from 590 MeV down to an energy in the range of 85-270 MeV. A new beam line following the degrader is used to clean the low-energetic beam in phase space and momentum band. The analyzed beam is then injected into a compact isocentric gantry, where it is applied to the patient using a new dynamic treatment modality, the so-called spot-scanning technique. This technique will permit full three-dimensional conformation of the dose to the target volume to be realized in a routine way without the need for individualized patient hardware like collimators and compensators. By combining the scanning of the focused pencil beam within the beam optics of the gantry and by mounting the patient table eccentrically on the gantry, the diameter of the rotating structure has been reduced to only 4 m. In the article the degrees of freedom available on the gantry to apply the beam to the patient (with two rotations for head treatments) are also discussed. The devices for the positioning of the patient on the gantry (x rays and proton radiography) and outside the treatment room (the patient transporter system and the modified mechanics of the computer tomograph unit) are briefly presented. The status of the facility and first experimental results are introduced for later reference.

The effects of calculational uncertainties on 3D and distal edge tracking (DET) intensity modulated proton therapy (IMPT) treatment plans have been investigated. Dose calculation uncertainties have been assessed by comparing analytical and Monte Carlo dose calculations, and potential range uncertainties by recalculating plans with all CT values modified by +/-3%. Analysis of the volume of PTV agreeing to within +/-3% between the two calculations shows that the 3D approach provides significantly improved agreement (87.1 versus 80.3% of points for the 3D and DET approaches, respectively). For the DET approach, doses in the CTV have also been found to globally change by 5% as a result of 3% changes in CT value. When varying the intra-field gradients of the plans a similar trend is seen, but with the more complex plans also being found to be more sensitive to both uncertainties. In conclusion, the DET approach has been found to be relatively sensitive to the calculational errors investigated here. In contrast, the 3D approach appears to be quite robust, unless strong internal gradients are present. Nevertheless, the routine use of uncertainty analysis is advised when assessing all forms of IMPT plans.

Simple tools for studying the effects of inter-fraction and inter-field motions on intensity modulated proton therapy (IMPT) plans have been developed, and have been applied to both 3D and distal edge tracking (DET) IMPT plans. For the inter-fraction motion, we have investigated the effects of misaligned density heterogeneities, whereas for the inter-field motion analysis, the effects of field misalignment on the plans have been assessed. Inter-fraction motion problems have been analysed using density differentiated error (DDE) distributions, which specifically show the additional problems resulting from misaligned density heterogeneities for proton plans. Likewise, for inter-field motion, we present methods for calculating motion differentiated error (MDE) distributions. DDE and MDE analysis of all plans demonstrate that the 3D approach is generally more robust to both inter-fraction and inter-field motions than the DET approach, but that strong in-field dose gradients can also adversely affect a plan's robustness. An important additional conclusion is that, for certain IMPT plans, even inter-fraction errors cannot necessarily be compensated for by the use of a simple PTV margins, implying that more sophisticated tools need to be developed for uncertainty management and assessment for IMPT treatments at the treatment planning level.

This paper describes a method for 4D imaging, which is used to study respiratory organ motion, a key problem in various treatments. Whilst the commonly used imaging methods rely on simplified breathing patterns to acquire one breathing cycle, the proposed method was developed to study irregularities in organ motion during free breathing over tens of minutes. The method does not assume a constant breathing depth or even strict periodicity and does not depend on an external respiratory signal. Time-resolved 3D image sequences were reconstructed by retrospective stacking of dynamic 2D images using internal image-based sorting. The generic method is demonstrated for the liver and for the lung. Quantitative evaluations of the volume consistency show the advantages over one-dimensional measurements for image sorting. Dense deformation fields describing the respiratory motion were estimated from the reconstructed volumes using non-rigid 3D registration. All obtained motion fields showed variations in the range of minutes such as drifts and deformations, which changed both the exhalation position of the liver and the breathing pattern. The obtained motion data are used in proton therapy planning to evaluate dose delivery methodologies with respect to their motion sensitivity. Besides this application, the new possibilities of studying respiratory motion are valuable for other applications such as the evaluation of gating techniques with respect to residual motion.