Table of contents

Intensity-modulated arc therapy (IMAT) was proposed by Yu (1995 Phys. Med. Biol.40 1435–49) as an alternative to tomotherapy. Over more than a decade, much progress has been made. The advantages and limitations of the IMAT technique have also been better understood. In recent years, single-arc forms of IMAT have emerged and become commercially adopted. The leading example is the volumetric-modulated arc therapy (VMAT), a single-arc form of IMAT that delivers apertures of varying weights with a single-arc rotation that uses dose-rate variation of the treatment machine. With commercial implementation of VMAT, wide clinical adoption has quickly taken root. However, there remains a lack of general understanding for the planning of such arc treatments, as well as what delivery limitations and compromises are made. Commercial promotion and competition add further confusion for the end users. It is therefore necessary to provide a summary of this technology and some guidelines on its clinical implementation. The purpose of this review is to provide a summary of the works from the radiotherapy community that led to wide clinical adoption, and point out the issues that still remain, providing some perspective on its further developments. Because there has been vast experience in IMRT using multiple intensity-modulated fields, comparisons between IMAT and IMRT are also made in the review within the areas of planning, delivery and quality assurance.

Magnetic resonance imaging (MRI) relaxation times provide indirect estimates of tissue O₂ for monitoring tumour oxygenation. This study provides insight into mechanisms underlying longitudinal (R₁ = 1/T₁) and transverse effective (R₂* = 1/T₂*) relaxation rate changes during inhalation of 100% O₂ and 3%, 6% and 9% CO₂ (balanced O₂) in a rabbit tumour model. Quantitative R₁, R₂*, and dynamic contrast-enhanced (DCE) imaging was performed in six rabbits 12–23 days following implantation of VX2 carcinoma cells in the quadricep muscle. Invasive measurements of tissue partial pressure of O₂ (pO₂) and perfusion were also performed, which revealed elevated pO₂ levels in all tumour regions for all hyperoxic gases compared to baseline (air) and reduced perfusion for carbogen. During 100% O₂ breathing, an R₁ increase and R₂* decrease consistent with elevated pO₂ were observed within tumours. DCE-derived blood flow was weakly correlated with R₁ changes from air to 100% O₂. Further addition of CO₂ (carbogen) did not introduce considerable changes in MR relaxation rates, but a trend towards higher R₁ relative to breathing 100% O₂ was observed, while R₂* changes were inconsistent. This observation supports the predominance of dissolved O₂ on R₁ sensitivity and demonstrates the value of R₁ over R₂* for tissue oxygenation measures.

In prostate radiation therapy, inter-fractional organ motion/deformation has posed significant challenges on reliable daily dose delivery. To correct for this issue, off-line re-optimization and online re-positioning have been used clinically. In this paper, we propose an adaptive images guided radiation therapy (AIGRT) scheme that combines these two correction methods in an anatomy-driven fashion. The AIGRT process first tries to find a best plan for the daily target from a plan pool, which consists of the original CT plan and all previous re-optimized plans. If successful, the selected plan is used for daily treatment with translational shifts. Otherwise, the AIGRT invokes the re-optimization process of the CT plan for the anatomy of the day, which is afterward added to the plan pool as a candidate for future fractions. The AIGRT scheme is evaluated by comparisons with daily re-optimization and online re-positioning techniques based on daily target coverage, organs at risk (OAR) sparing and implementation efficiency. Simulated treatment courses for 18 patients with re-optimization alone, re-positioning alone and AIGRT shows that AIGRT offers reliable daily target coverage that is highly comparable to daily re-optimization and significantly improves from re-positioning. AIGRT is also seen to provide improved OAR sparing compared to re-positioning. Apart from dosimetric benefits, AIGRT in addition offers an efficient scheme to integrate re-optimization to current re-positioning-based IGRT workflow.

This work develops imaging protocols for improved dose readout of a Fricke-xylenol orange-gelatin (FXG) gel-filled 1 L polyethylene terephthalate (PETE) jar dosimeter using a commercial Vista^TM cone-beam optical computed tomography (CT) scanner from Modus Medical Devices Inc. (London, ON, Canada). To ensure good management of light source–detector stability, it was determined that (a) a minimum of 2 h warm-up time is necessary prior to dosimeter scanning, (b) the light source should be kept on until the completion of the last data scan except for the minimum amount of time required to acquire dark field images, and (c) the optional Vista software projection image normalization routine should be used in image reconstruction. The institution of dosimeter scan time and temperature control was strongly indicated from the experiments. A standard post-irradiation wait time of 30 min measured to within ±30 s was established to minimize the measurement uncertainties due to dosimeter development and diffusion. To alleviate thermochromic behavior leading to inaccurate dose readout, holding bath warm up and pre-scan temperature adjustment procedures were developed to control dosimeter temperature to within ±0.2 °C. The possibility of stray light minimizing protocols was also investigated and deemed to be unnecessary. The largest significant sources of stray light in the system were identified as being due to angled scatter from the dosimeter gelatin matrix and refraction from the jar wall interfaces. It was concluded that these phenomena would be better addressed through dosimeter modification and an inter-jar dose-to-attenuation calibration methodology, rather than by setting additional imaging protocols.

An independent assessment of the dose delivery in ion therapy can be performed using positron emission tomography (PET). For that a distribution of positron emitters which appear as the result of interaction between ions of the therapeutic beam and the irradiated tissue is measured during or after the irradiation. Three concepts for PET monitoring implemented in various therapy facilities are considered in this paper. The in-beam PET concept relies on the PET measurement performed simultaneously to the irradiation by means of a PET scanner which is completely integrated into the irradiation site. The in-room PET concept allows measurement immediately after irradiation by a standalone PET scanner which is installed very close to the irradiation site. In the off-line PET scenario the measurement is performed by means of a standalone PET/CT scanner 10–30 min after the irradiation. These three concepts were evaluated according to image quality criteria, integration costs, and their influence onto the workflow of radiotherapy. In-beam PET showed the best performance. However, the integration costs were estimated as very high for this modality. Moreover, the performance of in-beam PET depends heavily on type and duty cycle of the accelerator. The in-room PET is proposed for planned therapy facilities as a good compromise between the quality of measured data and integration efforts. For facilities which are close to the nuclear medicine departments off-line PET can be suggested under several circumstances.

Respiratory and cardiac motions induce displacement and deformation of the tumor volumes in various internal organs. To accommodate this undesired movement and other errors, physicians incorporate a large margin around the tumor to delineate the planning target volume, so that the clinical target volume receives the prescribed radiation dose under any scenario. Consequently, a large volume of healthy tissue is irradiated and sometimes it is difficult to spare critical organs adjacent to the tumor. In this study we have proposed a novel approach to the 4D active tracking and dynamic delivery incorporating the tumor motion prediction technique. This method has been applied to the two commercially available robotic treatment couches. The proposed algorithm can predict the tumor position and the robotic systems are able to continuously track the tumor during radiation dose delivery. Therefore a precise dose is given to a moving target while the dose to the nearby critical organs is reduced to improve the patient treatment outcome. The efficacy of the proposed method has been investigated by extensive computer simulation. The tumor tracking method is simulated for two couches: HexaPOD robotic couch and ELEKTA Precise Table. The comparison results have been presented in this paper. In order to assess the clinical significance, dosimetric effects of the proposed method have been analyzed.

Performance of a treatment planning system is an essential factor in making sophisticated plans. The dose calculation is a major time-consuming process in planning operations. The standard algorithm for proton dose calculations is the pencil beam algorithm which produces relatively accurate results, but is time consuming. In order to shorten the computational time, we have developed a GPU (graphics processing unit)-based pencil beam algorithm. We have implemented this algorithm and calculated dose distributions in the case of a water phantom. The results were compared to those obtained by a traditional method with respect to the computational time and discrepancy between the two methods. The new algorithm shows 5–20 times faster performance using the NVIDIA GeForce GTX 480 card in comparison with the Intel Core-i7 920 processor. The maximum discrepancy of the dose distribution is within 0.2%. Our results show that GPUs are effective for proton dose calculations.

The aim of this work was to investigate the potential effect of sweat gland ducts (SGD) on specific absorption rate (SAR) and temperature distributions during mm-wave irradiation. High resolution electromagnetic and bio-heat transfer models of human skin with SGD were developed using a commercially available simulation software package (SEMCAD X™). The skin model consisted of a 30 µm stratum corneum, 350 µm epidermis and papillary dermis (EPD) and 1000 µm dermis. Five SGD of 60 µm radius and 300 µm height were embedded linearly with 370 µm separation. A WR-10 waveguide positioned 20 µm from the skin surface and delivering 94 GHz electromagnetic radiation was included in the model. Saline conductivity was assigned inside SGD. SAR and temperatures were computed with and without SGD. Despite their small scale, SAR was significantly higher within SGD than in the EPD without SGD. Without SGD, SAR and temperature maxima were in the dermis near EPD. With SGD, SAR maximum was inside SGD while temperature maximum moved to the EPD/stratum-corneum junction. Since the EPD participates actively in perception, the effect of SGD should be taken into account in nociceptive studies involving mm-waves. This research represents a significant step towards higher spatial resolution numerical modelling of the skin and shows that microstructures can play a significant role in mm-wave absorption and induced temperature distributions.

In this paper we describe a method to non-rigidly co-register a 2D slice sequence from real-time 3D echocardiography with a 2D cardiovascular MR image sequence. This is challenging because the imaging modalities have different spatial and temporal resolution. Non-rigid registration is required for accurate alignment due to imprecision of cardiac gating and natural motion variations between cardiac cycles. In our approach the deformation field between the imaging modalities is decoupled into temporal and spatial components. First, temporal alignment is performed to establish temporal correspondence between a real-time 3D echocardiography frame and a cardiovascular MR frame. Spatial alignment is then performed using an adaptive non-rigid registration algorithm based on local phase mutual information on each temporally aligned image pair. Experiments on seven volunteer datasets are reported. Evaluation of registration errors based on expert-identified landmarks shows that the spatio-temporal registration algorithm gives a mean registration error of 3.56 ± 0.49 and 3.54 ± 0.27 mm for the short and long axis sequences, respectively.

A broad-beam-delivery system for radiotherapy with protons or ions often employs multiple collimators and a range-compensating filter, which offer complex and potentially useful beam customization. It is however difficult for conventional pencil-beam algorithms to deal with fine structures of these devices due to beam-size growth during transport. This study aims to avoid the difficulty with a novel computational model. The pencil beams are initially defined at the range-compensating filter with angular-acceptance correction for upstream collimation followed by stopping and scattering. They are individually transported with possible splitting near the aperture edge of a downstream collimator to form a sharp field edge. The dose distribution for a carbon-ion beam was calculated and compared with existing experimental data. The penumbra sizes of various collimator edges agreed between them to a submillimeter level. This beam-customization model will be used in the greater framework of the pencil-beam splitting algorithm for accurate and efficient patient dose calculation.

In order (i) to evaluate the dose uncertainty of the mouthpiece in daily use during intensity-modulated radiotherapy of patients with head and neck cancer, and (ii) to present a system for in vivo dosimetry of the oral mucosa, we equipped the mouthpiece with alanine dosimeter probes for in vivo dosimetry. The aim was to determine the dose uncertainty caused by the daily positioning of the mouthpiece during dynamic treatment techniques. During IMRT radiotherapy of patients with head and neck cancer, the doses accumulated next to the mucosa were measured in five patients and compared to the dose calculated by the treatment planning system. The comparison of the applied and measured dose for each measurement point showed in six of the eight alanine probe positions a good agreement within the given relative combined standard uncertainty of less than 4.5% for a accumulated dose of 30 Gy and less than 4.6% for an accumulated dose of 8 Gy, respectively. In two of the eight alanine probe positions the applied and measured doses differed by 7.7% and 8.2% from each other. The dominant contribution to the overall uncertainty for the in vivo measurements was the positioning of the dosimeter probes in the patient's body and their corresponding localization in the CT data as well as the inaccuracy of the available algorithm for dose distribution calculation at the low-density material/soft tissue interface between the mouthpiece and the mucosa. Regarding our results, we refrain from the use of a mouthpiece during dynamic treatments such as IMRT.

An external surrogate-based respiratory gating technique is a useful method to reduce target margins for the treatment of a moving lung tumor. The success of this technique relies on a good correlation between the motion of the external markers and the internal tumor as well as the repeatability of the respiratory motion. In gated lung stereotactic body radiation therapy (SBRT), the treatment time for each fraction could exceed 30 min due to large fractional dose. Tumor motion may experience pattern changes such as baseline shift during such extended treatment time. The purpose of this study is to analyze tumor motion traces in actual treatment situations and to evaluate the effect of the target baseline shift in gated lung SBRT treatment. Real-time motion data for both the external markers and tumors from 51 lung SBRT treatments with Cyberknife Synchrony technology were analyzed in this study. The treatment time is typically greater than 30 min. The baseline shift was calculated with a rolling average window equivalent to ∼20 s and subtracted from that at the beginning. The magnitude of the baseline shift and its relationship with treatment time were investigated. Phase gating simulation was retrospectively performed on 12 carefully selected treatments with respiratory amplitude larger than 5 mm and regular phases. A customized gating window was defined for each individual treatment. It was found that the baseline shifts are specific to each patient and each fraction. Statistical analysis revealed that more than 69% treatments exhibited increased baseline shifts with the lapse of treatment time. The magnitude of the baseline shift could reach 5.3 mm during a 30 min treatment. Gating simulation showed that tumor excursion was caused mainly by the uncertainties in phase gating simulation and baseline shift, the latter being the primary factor. With a 5 mm gating window, 2 out of 12 treatments in the study group showed significant tumor excursion. Baseline shifts alone could cause up to 20% of tumor excursion outside the gating window. It is concluded that baseline shifts may increase with the treatment time and are more likely to act as a time-dependent systematic error. For phase-based gated lung SBRT, a baseline shift may be one of the major sources of targeting error during treatment.

We present a method of correcting self-scatter and crosstalk effects in simultaneous technetium-99m/thallium-201 stress/rest myocardial perfusion (single photon emission computed tomography) SPECT scans. The method, which is in essence a hybrid between the triple energy window method and scatter modelling, is based on a model of spatial and spectral distribution of projection counts in several selected energy windows. The parameters of the model are determined from measurements of thin rod sources in air when no in-object scatter or attenuation effects are present. The model equations are solved using the iterative maximum likelihood expectation maximization algorithm in the projection space to find estimates of the primary photopeak counts of both radionuclides. The method has been developed particularly for a novel dedicated cardiac camera based on CdZnTe pixellated detectors, although it can also be adapted to a conventional scintillator camera. The method has been validated in anthropomorphic phantom experiments. Significant improvement in defect contrast has been observed with only moderate increase in image noise. The application of the method to patient data is illustrated.

There has recently been increased interest in developing tensor data processing methods for the new medical imaging modality referred to as diffusion tensor magnetic resonance imaging (DT-MRI). This paper proposes a method for interpolating the primary vector fields from human cardiac DT-MRI, with the particularity of achieving interpolation and denoising simultaneously. The method consists of localizing the noise-corrupted vectors using the local statistical properties of vector fields, removing the noise-corrupted vectors and reconstructing them by using the thin plate spline (TPS) model, and finally applying global TPS interpolation to increase the resolution in the spatial domain. Experiments on 17 human hearts show that the proposed method allows us to obtain higher resolution while reducing noise, preserving details and improving direction coherence (DC) of vector fields as well as fiber tracking. Moreover, the proposed method perfectly reconstructs azimuth and elevation angle maps.

The γ-index dose comparison tool has been widely used to compare dose distributions in cancer radiotherapy. The accurate calculation of γ-index requires an exhaustive search of the closest Euclidean distance in the high-resolution dose-distance space. This is a computational intensive task when dealing with 3D dose distributions. In this work, we combine a geometric method (Ju et al 2008 Med. Phys.35 879–87) with a radial pre-sorting technique (Wendling et al 2007 Med. Phys.34 1647–54) and implement them on computer graphics processing units (GPUs). The developed GPU-based γ-index computational tool is evaluated on eight pairs of IMRT dose distributions. The γ-index calculations can be finished within a few seconds for all 3D testing cases on one single NVIDIA Tesla C1060 card, achieving 45–75× speedup compared to CPU computations conducted on an Intel Xeon 2.27 GHz processor. We further investigated the effect of various factors on both CPU and GPU computation time. The strategy of pre-sorting voxels based on their dose difference values speeds up the GPU calculation by about 2.7–5.5 times. For n-dimensional dose distributions, γ-index calculation time on CPU is proportional to the summation of γⁿ over all voxels, while that on GPU is affected by γⁿ distributions and is approximately proportional to the γⁿ summation over all voxels. We found that increasing the resolution of dose distributions leads to a quadratic increase of computation time on CPU, while less-than-quadratic increase on GPU. The values of dose difference and distance-to-agreement criteria also have an impact on γ-index calculation time.

Fluorescence tomography (FT) reconstructs the three-dimensional (3D) fluorescent reporter probe distribution inside biological tissue. These probes target molecules of biological function, e.g. cell surface receptors or enzymes, and emit fluorescence light upon illumination with an external light source. The fluorescence light is detected on the tissue surface and a source reconstruction algorithm based on the simplified spherical harmonics (SP_N) equations calculates the unknown 3D probe distribution inside tissue. While current FT approaches require multiple external sources at a defined wavelength range, the proposed FT method uses only a white light source with tunable wavelength selection for fluorescence stimulation and further exploits the spectral dependence of tissue absorption for the purpose of 3D tomographic reconstruction. We will show the feasibility of the proposed hyperspectral excitation-resolved fluorescence tomography method with experimental data. In addition, we will demonstrate the performance and limitations of such a method under ideal and controlled conditions by means of a digital mouse model and synthetic measurement data. Moreover, we will address issues regarding the required amount of wavelength intervals for fluorescent source reconstruction. We will explore the impact of assumed spatially uniform and nonuniform optical parameter maps on the accuracy of the fluorescence source reconstruction. Last, we propose a spectral re-scaling method for overcoming the observed limitations in reconstructing accurate source distributions in optically non-uniform tissue when assuming only uniform optical property maps for the source reconstruction process.

Some current investigations based on small animal models are dedicated to functional cerebral imaging. They represent a fundamental tool to understand the mechanisms involved in neurodegenerative diseases. In the radiopharmaceutical development approach, the main challenge is to measure the radioactivity distribution in the brain of a subject with good temporal and spatial resolutions. Classical SPECT systems mainly use parallel hole or pinhole collimators. In this paper we investigate the use of a rotating slat collimator system for small animal brain imaging. The proposed prototype consists of a 64-channel multi-anode photomultiplier tube (H8804, Hamamatsu Corp.) coupled to a YAP:Ce crystal highly segmented into 32 strips of 0.575 × 18.4 × 10 mm³. The parameters of the rotating slat collimator are optimized using GATE Monte Carlo simulations. The performance of the proposed prototype in terms of spatial resolution, detection efficiency and signal-to-noise ratio is compared to that obtained with a gamma camera equipped with a parallel hole collimator. Preliminary experimental results demonstrate that a spatial resolution of 1.54 mm can be achieved with a detection efficiency of 0.012% for a source located at 20 mm, corresponding to the position of the brain in the prototype field of view.

We have produced an optically clear, close to water-equivalent gel that is radio-fluorogenic, i.e. fluoresces in UV light after exposure to high-energy radiation. Its potential as a 2D and 3D dosimetric medium is demonstrated by fixed fluorescent images of the cross-section, track and intersection of collimated (10 × 10 or 5 × 5 mm²) 205 kVp x-ray beams. The images, produced by doses on the order of 10 Gy, are formed instantaneously and can be digitally recorded and scanned with a spatial resolution on the order of 0.1 mm. No loss of spatial resolution occurs on standing under ambient conditions for at least 3 days.

Dimethyl sulfoxide (DMSO) can effectively form a glassy matrix necessary for dynamic nuclear polarization (DNP) experiments. We tested the effects of ¹³C enrichment in DMSO on DNP of [1-¹³C]pyruvate doped with trityl radical OX063Me. We found that the polarization build-up time τ of pyruvate in ¹³C-labeled DMSO glassing solution is twice as fast as the unenriched DMSO while the nuclear magnetic resonance enhancement was unchanged. This indicates that ¹³C–¹³C spin diffusion is a limiting factor in the kinetics of DNP in this system, but it has a minimal effect on the absolute value of polarization achievable for the target.