Registration of magnetic resonance and ultrasound images for guiding prostate cancer interventions

Prostate cancer is a major international health problem with a large and rising incidence in many parts of the world. Transrectal ultrasound (TRUS) imaging is used routinely to guide surgical procedures, such as needle biopsy and a number of minimally-invasive therapies, but its limited ability to visualise prostate cancer is widely recognised. Magnetic resonance (MR) imaging techniques, on the other hand, have recently been developed that can provide clinically useful diagnostic information. Registration (or alignment) of MR and TRUS images during TRUS-guided surgical interventions potentially provides a cost-effective approach to augment TRUS images with clinically useful, MR-derived information (for example, tumour location, shape and size). This thesis describes a deformable image registration framework that enables automatic and/or semi-automatic alignment of MR and 3D TRUS images of the prostate gland. The method combines two technical developments in the field: First, a method for constructing patient-specific statistical shape models of prostate motion/deformation, based on learning from finite element simulations of gland motion using geometric data from a preoperative MR image, is proposed. Second, a novel “model-to-image” registration framework is developed to register this statistical shape model automatically to an intraoperative TRUS image. This registration approach is implemented using a novel model-to-image vector alignment (MIVA) algorithm, which maximises the likelihood of a particular instance of a statistical shape model given a voxel-intensity-based feature vector that represents an estimate of the surface normal vectors at the boundary of the organ in question. Using real patient data, the MR-TRUS registration accuracy of the new algorithm is validated using intra-prostatic anatomical landmarks. A rigorous and extensive validation analysis is also provided for assessing the image registration experiments. The final target registration error after performing 100 MR–TRUS registrations for each patient have a median of 2.40 mm, meaning that over 93% registrations may successfully hit the target representing a clinically significant lesion. The implemented registration algorithms took less than 30 seconds and 2 minutes for manually defined point- and normal vector features, respectively. The thesis concludes with a summary of potential applications and future research directions

Biomechanical Modeling and Inverse Problem Based Elasticity Imaging for Prostate Cancer Diagnosis

Early detection of prostate cancer plays an important role in successful prostate cancer treatment. This requires screening the prostate periodically after the age of 50. If screening tests lead to prostate cancer suspicion, prostate needle biopsy is administered which is still considered as the clinical gold standard for prostate cancer diagnosis. Given that needle biopsy is invasive and is associated with issues including discomfort and infection, it is desirable to develop a prostate cancer diagnosis system that has high sensitivity and specificity for early detection with a potential to improve needle biopsy outcome. Given the complexity and variability of prostate cancer pathologies, many research groups have been pursuing multi-parametric imaging approach as no single modality imaging technique has proven to be adequate. While imaging additional tissue properties increases the chance of reliable prostate cancer detection and diagnosis, selecting an additional property needs to be done carefully by considering clinical acceptability and cost. Clinical acceptability entails ease with respect to both operating by the radiologist and patient comfort. In this work, effective tissue biomechanics based diagnostic techniques are proposed for prostate cancer assessment with the aim of early detection and minimizing the numbers of prostate biopsies. The techniques take advantage of the low cost, widely available and well established TRUS imaging method. The proposed techniques include novel elastography methods which were formulated based on an inverse finite element frame work. Conventional finite element analysis is known to have high computational complexity, hence computation time demanding. This renders the proposed elastography methods not suitable for real-time applications. To address this issue, an accelerated finite element method was proposed which proved to be suitable for prostate elasticity reconstruction. In this method, accurate finite element analysis of a large number of prostates undergoing TRUS probe loadings was performed. Geometry input and displacement and stress fields output obtained from the analysis were used to train a neural network mapping function to be used for elastopgraphy imaging of prostate cancer patients. The last part of the research presented in this thesis tackles an issue with the current 3D TRUS prostate needle biopsy. Current 3D TRUS prostate needle biopsy systems require registering preoperative 3D TRUS to intra-operative 2D TRUS images. Such image registration is time-consuming while its real-time implementation is yet to be developed. To bypass this registration step, concept of a robotic system was proposed which can reliably determine the preoperative TRUS probe position relative to the prostate to place at the same position relative to the prostate intra-operatively. For this purpose, a contact pressure feedback system is proposed to ensure similar prostate deformation during 3D and 2D image acquisition in order to bypass the registration step

Image Guided Robots for Urology

This dissertation addresses the development of medical image-guided robots and their applications in urology. Image-guided robots integrate medical image information with robotic precision to assist the planning and execution of the image-guided interventions. Robots guided by two different image modalities, ultrasound and MR image, were developed. Ultrasound image-guided robots manipulate an ultrasound probe and a needle-guide that are calibrated with respect to the robot for image-guided targeting. A method for calibration was developed and verified through the image-guided targeting experiments. Robotic manipulation of the calibrated probe allows acquisition of image slices at precise location, which can be combined to generate a 3D ultrasound image. Software for 3D ultrasound image acquisition, processing, and segmentation was developed as a part of the image-guided robot system. The feasibility of several image-guided intervention procedures using the ultrasound image-guided robot system was tested. The robot was used in a clinical trial of intraoperative transrectal ultrasound (TRUS) guided prostatectomy. The accuracy of TRUS-guided prostate biopsy using the robot was evaluated in a comparative study versus the classic human operation of the probe. Robot controlled palpation and image processing methods were developed for ultrasound elastography imaging of the prostate. An ultrasound to CT image-fusion method using the robot as a common reference was developed for percutaneous access of the kidney. MRI-guided robots were developed for transrectal and transperineal prostate biopsy. Extensive in-vitro tests were performed to ensure MRI compatibility and image-guided accuracy of the robots. The transrectal robot was evaluated in an animal study and the transperineal robot is undergoing a clinical trial. The collection of methods and algorithms presented in this dissertation can contribute to the development of image-guided robots that may provide less invasive and more precise interventions in urology, interventional radiology, and other fields

Accumulating delivered dose to the rectum to improve toxicity prediction in prostate radiotherapy

Accumulating delivered dose to the rectum to improve toxicity prediction in prostate radiotherapy Leila E. A. Shelley Gastrointestinal (GI) toxicity is a clinical issue suffered by up to 22% of prostate cancer radiotherapy patients. However, the relationship between radiation dose and toxicity is generally poorly understood. In prostate radiotherapy, the rectum is a dose-limiting structure to which treatment planning dose constraints are applied to minimise the risk of toxicity. Current normal tissue complication probability (NTCP) models are based on planned dose data and do not consider the effects of organ motion on true delivered dose. The VoxTox research programme has developed automated solutions for segmentation and dose calculation of the rectum for prostate cancer patients being treated with helical TomoTherapy. Daily image guidance scans, acquired primarily for the purposes of positional verification, are exploited by extracting quantitative information to facilitate the calculation of daily delivered and total accumulated dose to the rectum. Prospectively collected toxicity data at 2 years post-treatment were available for 295 patients across two separate cohorts. In this thesis, the hypothesis being tested is that delivered dose is a better predictor of rectal toxicity than planned dose in prostate radiotherapy. The research has successfully demonstrated, for the first time, that delivered dose produces stronger associations with rectal bleeding and proctitis than planned dose. Analysis was performed using dose surface maps (DSMs) of the rectal wall, allowing spatial aspects of dose to be retained during accumulation. A subsequent analysis on a separate cohort also found stronger links between delivered dose and GI toxicity, stool frequency, and bowel bother, in addition to rectal bleeding and proctitis. Biomechanical finite element (FE) modelling was introduced to provide a more anatomically plausible tool for dose accumulation and allowed more accurate tracking of dose at the voxel level. A sensitivity analysis was conducted which explored the effect of simulated rectal motion on dose, and corresponding change in NTCP. For VoxTox patient dose-toxicity analysis, further dose parameterisation approaches were explored in order to consider the increased resolution of information available. Voxel-based rectal subregions at risk (SRRs) were identified using geometric and statistical approaches. In general, discriminative power improved with FE modelling for both planned and accumulated delivered dose, and associations between accumulated dose and toxicity were strengthened by voxel-based subregion analysis. Multivariate NTCP models were constructed for 12 different toxicity endpoints based on planned and accumulated dose parameters. Model performance was compared between analysis approaches, and models were tested on a validation dataset. In general, FE-based dose models performed best, although the optimal dose parameter selected within the model varied with toxicity endpoint. Overall, results suggest that there is an advantage to incorporating delivered dose into NTCP modelling. However, the differences between planned and accumulated dose can be subtle. Meaningful parameterisation of accumulated dose needs careful consideration, as traditional methods for quantifying planned dose may not be directly transferable. Voxel-based analysis techniques are recommended in order to accurately preserve and register spatial dose information, and have been shown to improve the strength of dose-toxicity associations. Further research into quantifying voxel level dose distributions is encouraged. It is anticipated that the novel scientific contributions presented within this thesis will prove valuable for future development of clinical decision-making tools for adaptive radiotherapy, with the ultimate aim of reducing the incidence of radiation-induced toxicity for prostate cancer radiotherapy patients.Personal funding was provided by the WD Armstrong Trust. The VoxTox Research Programme was funded by Cancer Research UK

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Development and Evaluation of an Actuator System based on Centrifugal Force for Magnetic Resonance Elastography

Magnetic resonance elastography (MRE) serves as an important diagnostic tool. It represents one of numerous approaches to monitor tissue stiffness. The most fundamental challenges that MRE face are posed by two linking factors: Constructing a mechanical device that induces tissue motion to the depth of interest and meaningfully resolving said movement in the complex magnetic resonance imaging (MRI) signal. This work aims to address these challenges by improving the quantification of tissue stiffness through the development of a new actuation system for MRE. Firstly, a 3D printed pneumatic turbine vibrator was developed to induce sinusoidal mechanical waves. It used an eccentrically rotating mass generating a centrifugal force in the turbine. Contrary to conventionally used acoustic pressure drivers, the pneumatic turbine was capable of producing wave amplitudes in the range of appropriate shear waves in human tissue - especially at higher frequencies due to the centrifugal force increasing quadratically in relation to the rotational frequency. A technical assessment showed that the turbine generated vibrations in the range of 30 Hz to 150 Hz. The extent of artifacts caused by the materials brought into the field of view was restricted to the proximity of the actuator. It did not affect image quality in the region of interest. The turbine was MR-safe and an in-house certification according to §3 MPG was conducted, which enabled in-house clinical in vivo studies. The actuation system was additionally extended to a dual turbine actuator in order to investigate if the attenuation of shear waves could be further compensated by using two wave sources. Secondly, a motion encoding sequence was developed to meaningfully encode the tissue motion in the MRI signal. It was a spin-echo echo-planar-imaging sequence (SE-EPI) and contained a motion encoding gradient (MEG) adjustable for actuation frequencies ranging from 40 Hz to 120 Hz. To accurately reconstruct the wave velocities, i.e tissue elasticity, a trigger was implemented that synchronized the motion encoding sequence to the mechanical waves. Thirdly, the actuator system was evaluated regarding its performance for MRE image acquisition in a clinical MRI scanner. Silicone-based tissue elasticity mimicking phantoms were developed as test objects with known elasticity. Their shear moduli were in the range of 1.47 kPa to 7.29 kPa, which corresponds to the range of human soft tissue elasticities. A prostate phantom and an anthropomorphic abdominal phantom were manufactured. MR images were acquired with the SE-EPI sequence and were sufficient in terms of signal to noise ration (liver: SNR = 71.5) and contrast to noise ratio (liver: CNR = 16.5). The phantoms may also be used for multi-modal imaging; besides MRI, computed tomography (liver: 106+/-6 HU) and ultrasound imaging by adding scatter particles is feasible. The actuator did not interfere with the imaging procedure and could be integrated into existing clinic equipment. Three actuation set-ups were evaluated: a single, a large surface and a dual source actuation. For each, the strength of the MEG was varied from 5 mT/m to 20 mT/m for actuation frequencies ranging from 50 Hz to 80 Hz. The dual source actuation demonstrated a more uniform penetration of a larger volume of interest, especially in the peripheral region of the abdominal phantom. The obtained elasticity maps showed elasticity values (liver: 1.12+/-0.16 kPa, filling material: 4.37+/-0.52 kPa) in accordance to the results obtained by rheometric testing of the silicone samples. Additionally, an in vivo MRE examination was conducted, which served as a proof-of-principle for the successful implementation of the first developed MRE actuator system in our clinic. For both liver and prostate MRE, the actuator was well tolerated by the volunteer. Since the developed actuation technique is non-invasive, its incorporation into routine MRI protocols will facilitate patient acceptance, while its short additional set-up time will also increase clinical acceptance. MRE is a unique technique for the identification of various pathologies and the quantification of the shear modulus has the potential to become a further independent parameter for MRI diagnostics in a variety of clinical applications