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Objective. Dose-rate effects in Gamma Knife radiosurgery treatments can lead to varying biologically effective dose (BED) levels for the same physical dose. The non-convex BED model depends on the delivery sequence and creates a non-trivial treatment planning problem. We investigate the feasibility of employing inverse planning methods to generate treatment plans exhibiting desirable BED characteristics using the per iso-centre beam-on times and delivery sequence. Approach. We implement two dedicated optimisation algorithms. One approach relies on mixed-integer linear programming (MILP) using a purposely developed convex underestimator for the BED to mitigate local minima issues at the cost of computational complexity. The second approach (local optimisation) is faster and potentially usable in a clinical setting but more prone to local minima issues. It sequentially executes the beam-on time (quasi-Newton method) and sequence optimisation (local search algorithm). We investigate the trade-off between time to convergence and solution quality by evaluating the resulting treatment plans' objective function values and clinical parameters. We also study the treatment time dependence of the initial and optimised plans using BED 95 (BED delivered to 95% of the target volume) values. Main results. When optimising the beam-on times and delivery sequence, the local optimisation approach converges several orders of magnitude faster than the MILP approach (minutes versus hours-days) while typically reaching within 1.2% (0.02-2.08%) of the final objective function value. The quality parameters of the resulting treatment plans show no meaningful difference between the local and MILP optimisation approaches. The presented optimisation approaches remove the treatment time dependence observed in the original treatment plans, and the chosen objectives successfully promote more conformal treatments. Significance. We demonstrate the feasibility of using an inverse planning approach within a reasonable time frame to ensure BED-based objectives are achieved across varying treatment times and highlight the prospect of further improvements in treatment plan quality., (Creative Commons Attribution license.)

Here we describe methods for creating tissue-mimicking ultrasound phantoms based on patient anatomy using a soft material called gel wax. To recreate acoustically realistic tissue properties, two additives to gel wax were considered: paraffin wax to increase acoustic attenuation, and solid glass spheres to increase backscattering. The frequency dependence of ultrasound attenuation was well described with a power law over the measured range of 3-10 MHz. With the addition of paraffin wax in concentrations of 0 to 8 w/w%, attenuation varied from 0.72 to 2.91 dB cm -1 at 3 MHz and from 6.84 to 26.63 dB cm -1 at 10 MHz. With solid glass sphere concentrations in the range of 0.025-0.9 w/w%, acoustic backscattering consistent with a wide range of ultrasonic appearances was achieved. Native gel wax maintained its integrity during compressive deformations up to 60%; its Young's modulus was 17.4  ±  1.4 kPa. The gel wax with additives was shaped by melting and pouring it into 3D printed moulds. Three different phantoms were constructed: a nerve and vessel phantom for peripheral nerve blocks, a heart atrium phantom, and a placental phantom for minimally-invasive fetal interventions. In the first, nerves and vessels were represented as hyperechoic and hypoechoic tubular structures, respectively, in a homogeneous background. The second phantom comprised atria derived from an MRI scan of a patient with an intervening septum and adjoining vena cavae. The third comprised the chorionic surface of a placenta with superficial fetal vessels derived from an image of a post-partum human placenta. Gel wax is a material with widely tuneable ultrasound properties and mechanical characteristics that are well suited for creating patient-specific ultrasound phantoms in several clinical disciplines.

To tackle the problem of magnetic resonance imaging (MRI)-only radiotherapy treatment planning (RTP), we propose a multi-atlas information propagation scheme that jointly segments organs and generates pseudo x-ray computed tomography (CT) data from structural MR images (T1-weighted and T2-weighted). As the performance of the method strongly depends on the quality of the atlas database composed of multiple sets of aligned MR, CT and segmented images, we also propose a robust way of registering atlas MR and CT images, which combines structure-guided registration, and CT and MR image synthesis. We first evaluated the proposed framework in terms of segmentation and CT synthesis accuracy on 15 subjects with prostate cancer. The segmentations obtained with the proposed method were compared using the Dice score coefficient (DSC) to the manual segmentations. Mean DSCs of 0.73, 0.90, 0.77 and 0.90 were obtained for the prostate, bladder, rectum and femur heads, respectively. The mean absolute error (MAE) and the mean error (ME) were computed between the reference CTs (non-rigidly aligned to the MRs) and the pseudo CTs generated with the proposed method. The MAE was on average [Formula: see text] HU and the ME [Formula: see text] HU. We then performed a dosimetric evaluation by re-calculating plans on the pseudo CTs and comparing them to the plans optimised on the reference CTs. We compared the cumulative dose volume histograms (DVH) obtained for the pseudo CTs to the DVH obtained for the reference CTs in the planning target volume (PTV) located in the prostate, and in the organs at risk at different DVH points. We obtained average differences of [Formula: see text] in the PTV for [Formula: see text], and between [Formula: see text] and 0.05% in the PTV, bladder, rectum and femur heads for D mean and [Formula: see text]. Overall, we demonstrate that the proposed framework is able to automatically generate accurate pseudo CT images and segmentations in the pelvic region, potentially bypassing the need for CT scan for accurate RTP.

Patient motion due to respiration can lead to artefacts and blurring in positron emission tomography (PET) images, in addition to quantification errors. The integration of PET with magnetic resonance (MR) imaging in PET-MR scanners provides complementary clinical information, and allows the use of high spatial resolution and high contrast MR images to monitor and correct motion-corrupted PET data. In this paper we build on previous work to form a methodology for respiratory motion correction of PET data, and show it can improve PET image quality whilst having minimal impact on clinical PET-MR protocols. We introduce a joint PET-MR motion model, using only 1 min per PET bed position of simultaneously acquired PET and MR data to provide a respiratory motion correspondence model that captures inter-cycle and intra-cycle breathing variations. In the model setup, 2D multi-slice MR provides the dynamic imaging component, and PET data, via low spatial resolution framing and principal component analysis, provides the model surrogate. We evaluate different motion models (1D and 2D linear, and 1D and 2D polynomial) by computing model-fit and model-prediction errors on dynamic MR images on a data set of 45 patients. Finally we apply the motion model methodology to 5 clinical PET-MR oncology patient datasets. Qualitative PET reconstruction improvements and artefact reduction are assessed with visual analysis, and quantitative improvements are calculated using standardised uptake value (SUV(peak) and SUV(max)) changes in avid lesions. We demonstrate the capability of a joint PET-MR motion model to predict respiratory motion by showing significantly improved image quality of PET data acquired before the motion model data. The method can be used to incorporate motion into the reconstruction of any length of PET acquisition, with only 1 min of extra scan time, and with no external hardware required.

This work is an extension of our recent work on joint activity reconstruction/motion estimation (JRM) from positron emission tomography (PET) data. We performed JRM by maximization of the penalized log-likelihood in which the probabilistic model assumes that the same motion field affects both the activity distribution and the attenuation map. Our previous results showed that JRM can successfully reconstruct the activity distribution when the attenuation map is misaligned with the PET data, but converges slowly due to the significant cross-talk in the likelihood. In this paper, we utilize time-of-flight PET for JRM and demonstrate that the convergence speed is significantly improved compared to JRM with conventional PET data.

In this paper we propose a segmented magnetic resonance imaging (MRI) prior-based maximum penalized likelihood deconvolution technique for positron emission tomography (PET) images. The model assumes the existence of activity classes that behave like a hidden Markov random field (MRF) driven by the segmented MRI. We utilize a mean field approximation to compute the likelihood of the MRF. We tested our method on both simulated and clinical data (brain PET) and compared our results with PET images corrected with the re-blurred Van Cittert (VC) algorithm, the simplified Guven (SG) algorithm and the region-based voxel-wise (RBV) technique. We demonstrated our algorithm outperforms the VC algorithm and outperforms SG and RBV corrections when the segmented MRI is inconsistent (e.g. mis-segmentation, lesions, etc) with the PET image.

In this study, we aim to reconstruct single-photon emission computed tomography images using anatomical information from magnetic resonance imaging as a priori knowledge about the activity distribution. The trade-off between anatomical and emission data is one of the main concerns for such studies. In this work, we propose an anatomically driven anisotropic diffusion filter (ADADF) as a penalized maximum likelihood expectation maximization optimization framework. The ADADF method has improved edge-preserving denoising characteristics compared to other smoothing penalty terms based on quadratic and non-quadratic functions. The proposed method has an important ability to retain information which is absent in the anatomy. To make our approach more stable to the noise-edge classification problem, robust statistics have been employed. Comparison of the ADADF method is performed with a successful anatomically driven technique, namely, the Bowsher prior (BP). Quantitative assessment using simulated and clinical neuroreceptor volumetric data show the advantage of the ADADF over the BP. For the modelled data, the overall image resolution, the contrast, the signal-to-noise ratio and the ability to preserve important features in the data are all improved by using the proposed method. For clinical data, the contrast in the region of interest is significantly improved using the ADADF compared to the BP, while successfully eliminating noise.

Physically realistic simulations for large breast deformation are of great interest for many medical applications such as cancer diagnosis, image registration, surgical planning and image-guided surgery. To support fast, large deformation simulations of breasts in clinical settings, we proposed a patient-specific biomechanical modelling framework for breasts, based on an open-source graphics processing unit-based, explicit, dynamic, nonlinear finite element (FE) solver. A semi-automatic segmentation method for tissue classification, integrated with a fully automated FE mesh generation approach, was implemented for quick patient-specific FE model generation. To solve the difficulty in determining material parameters of soft tissues in vivo for FE simulations, a novel method for breast modelling, with a simultaneous material model parameter optimization for soft tissues in vivo, was also proposed. The optimized deformation prediction was obtained through iteratively updating material model parameters to maximize the image similarity between the FE-predicted MR image and the experimentally acquired MR image of a breast. The proposed method was validated and tested by simulating and analysing breast deformation experiments under plate compression. Its prediction accuracy was evaluated by calculating landmark displacement errors. The results showed that both the heterogeneity and the anisotropy of soft tissues were essential in predicting large breast deformations under plate compression. As a generalized method, the proposed process can be used for fast deformation analyses of soft tissues in medical image analyses and surgical simulations.

Respiratory motion can vary dramatically between the planning stage and the different fractions of radiotherapy treatment. Motion predictions used when constructing the radiotherapy plan may be unsuitable for later fractions of treatment. This paper presents a methodology for constructing patient-specific respiratory motion models and uses these models to evaluate and analyse the inter-fraction variations in the respiratory motion. The internal respiratory motion is determined from the deformable registration of Cine CT data and related to a respiratory surrogate signal derived from 3D skin surface data. Three different models for relating the internal motion to the surrogate signal have been investigated in this work. Data were acquired from six lung cancer patients. Two full datasets were acquired for each patient, one before the course of radiotherapy treatment and one at the end (approximately 6 weeks later). Separate models were built for each dataset. All models could accurately predict the respiratory motion in the same dataset, but had large errors when predicting the motion in the other dataset. Analysis of the inter-fraction variations revealed that most variations were spatially varying base-line shifts, but changes to the anatomy and the motion trajectories were also observed.

A novel method for automated curved planar reformation (CPR) of magnetic resonance (MR) images of the spine is presented. The CPR images, generated by a transformation from image-based to spine-based coordinate system, follow the structural shape of the spine and allow the whole course of the curved anatomy to be viewed in individual cross-sections. The three-dimensional (3D) spine curve and the axial vertebral rotation, which determine the transformation, are described by polynomial functions. The 3D spine curve passes through the centres of vertebral bodies, while the axial vertebral rotation determines the rotation of vertebrae around the axis of the spinal column. The optimal polynomial parameters are obtained by a robust refinement of the initial estimates of the centres of vertebral bodies and axial vertebral rotation. The optimization framework is based on the automatic image analysis of MR spine images that exploits some basic anatomical properties of the spine. The method was evaluated on 21 MR images from 12 patients and the results provided a good description of spine anatomy, with mean errors of 2.5 mm and 1.7 degrees for the position of the 3D spine curve and axial rotation of vertebrae, respectively. The generated CPR images are independent of the position of the patient in the scanner while comprising both anatomical and geometrical properties of the spine.

The accurate segmentation of the articular cartilages from magnetic resonance (MR) images of the knee is important for clinical studies and drug trials into conditions like osteoarthritis. Currently, segmentations are obtained using time-consuming manual or semi-automatic algorithms which have high inter- and intra-observer variabilities. This paper presents an important step towards obtaining automatic and accurate segmentations of the cartilages, namely an approach to automatically segment the bones and extract the bone-cartilage interfaces (BCI) in the knee. The segmentation is performed using three-dimensional active shape models, which are initialized using an affine registration to an atlas. The BCI are then extracted using image information and prior knowledge about the likelihood of each point belonging to the interface. The accuracy and robustness of the approach was experimentally validated using an MR database of fat suppressed spoiled gradient recall images. The (femur, tibia, patella) bone segmentation had a median Dice similarity coefficient of (0.96, 0.96, 0.89) and an average point-to-surface error of 0.16 mm on the BCI. The extracted BCI had a median surface overlap of 0.94 with the real interface, demonstrating its usefulness for subsequent cartilage segmentation or quantitative analysis.