Non-contact strain determination of cell traction effects

Irreversible tissue damage leading to organ failure is a common health problem in today's world. Regenerating these damaged tissues with the help of scaffolds is the solution offered by tissue engineering. In cases where the extra-cellular matrix (ECM) is to be replaced by an artificial substrate (scaffold) or matrix, cellular traction forces (CTF) are exerted by the cells on the scaffold surface. An ideal scaffold should exhibit mechanical characteristics similar to those of the ECM it is intended to replace. In other words, the capacity of a scaffold to withstand deformation should be comparable to that of a natural ECM. And with knowledge of those forces and deformations the properties of the scaffolds may be inferred. Digital Image Correlation (DIC), a non-contact image analysis technique enables us to measure point to point deformation of the scaffold by comparing a sequence of images captured during the process of scaffold deformation. This review discusses the methodology involved and implementation of DIC to measure displacements and strain.Irreversible tissue damage leading to organ failure is a common health problem in today's world. Regenerating these damaged tissues with the help of scaffolds is the solution offered by tissue engineering. In cases where the extra-cellular matrix (ECM) is to be replaced by an artificial substrate (scaffold) or matrix, cellular traction forces (CTF) are exerted by the cells on the scaffold surface. An ideal scaffold should exhibit mechanical characteristics similar to those of the ECM it is intended to replace. In other words, the capacity of a scaffold to withstand deformation should be comparable to that of a natural ECM. And with knowledge of those forces and deformations the properties of the scaffolds may be inferred. Digital Image Correlation (DIC), a non-contact image analysis technique enables us to measure point to point deformation of the scaffold by comparing a sequence of images captured during the process of scaffold deformation. This review discusses the methodology involved and implementation of DIC to measure displacements and strain

Use of Multicomponent Non-Rigid Registration to Improve Alignment of Serial Oncological PET/CT Studies

Non-rigid registration of serial head and neck FDG PET/CT images from a combined scanner can be problematic. Registration techniques typically rely on similarity measures calculated from voxel intensity values; CT-CT registration is superior to PET-PET registration due to the higher quality of anatomical information present in this modality. However, when metal artefacts from dental fillings are present in a pair of CT images, a nonrigid registration will incorrectly attempt to register the two artefacts together since they are strong features compared to the features that represent the actual anatomy. This leads to localised registration errors in the deformation field in the vicinity of the artefacts. Our objective was to develop a registration technique which overcomes these limitations by using combined information from both modalities. To study the effect of artefacts on registration, metal artefacts were simulated with one CT image rotated by a small angle in the sagittal plane. Image pairs containing these simulated artifacts were then registered to evaluate the resulting errors. To improve the registration in the vicinity where there were artefacts, intensity information from the PET images was incorporated using several techniques. A well-established B-splines based non-rigid registration code was reworked to allow multicomponent registration. A similarity measure with four possible weighted components relating to the ways in which the CT and PET information can be combined to drive the registration of a pair of these dual-valued images was employed. Several registration methods based on using this multicomponent similarity measure were implemented with the goal of effectively registering the images containing the simulated artifacts. A method was also developed to swap control point displacements from the PET-derived transformation in the vicinity of the artefact. This method yielded the best result on the simulated images and was evaluated on images where actual dental artifacts were present

Quantification of tumour heterogenity in MRI

Cancer is the leading cause of death that touches us all, either directly or indirectly. It is estimated that the number of newly diagnosed cases in the Netherlands will increase to 123,000 by the year 2020. General Dutch statistics are similar to those in the UK, i.e. over the last ten years, the age-standardised incidence rate1 has stabilised at around 355 females and 415 males per 100,000. Figure 1 shows the cancer incidence per gender. In the UK, the rise in lifetime risk of cancer is more than one in three and depends on many factors, including age, lifestyle and genetic makeup

Improving Quantification in Lung PET/CT for the Evaluation of Disease Progression and Treatment Effectiveness

Positron Emission Tomography (PET) allows imaging of functional processes in vivo by measuring the distribution of an administered radiotracer. Whilst one of its main uses is directed towards lung cancer, there is an increased interest in diffuse lung diseases, for which the incidences rise every year, mainly due to environmental reasons and population ageing. However, PET acquisitions in the lung are particularly challenging due to several effects, including the inevitable cardiac and respiratory motion and the loss of spatial resolution due to low density, causing increased positron range. This thesis will focus on Idiopathic Pulmonary Fibrosis (IPF), a disease whose aetiology is poorly understood while patient survival is limited to a few years only. Contrary to lung tumours, this diffuse lung disease modifies the lung architecture more globally. The changes result in small structures with varying densities. Previous work has developed data analysis techniques addressing some of the challenges of imaging patients with IPF. However, robust reconstruction techniques are still necessary to obtain quantitative measures for such data, where it should be beneficial to exploit recent advances in PET scanner hardware such as Time of Flight (TOF) and respiratory motion monitoring. Firstly, positron range in the lung will be discussed, evaluating its effect in density-varying media, such as fibrotic lung. Secondly, the general effect of using incorrect attenuation data in lung PET reconstructions will be assessed. The study will compare TOF and non-TOF reconstructions and quantify the local and global artefacts created by data inconsistencies and respiratory motion. Then, motion compensation will be addressed by proposing a method which takes into account the changes of density and activity in the lungs during the respiration, via the estimation of the volume changes using the deformation fields. The method is evaluated on late time frame PET acquisitions using ¹⁸F-FDG where the radiotracer distribution has stabilised. It is then used as the basis for a method for motion compensation of the early time frames (starting with the administration of the radiotracer), leading to a technique that could be used for motion compensation of kinetic measures. Preliminary results are provided for kinetic parameters extracted from short dynamic data using ¹⁸F-FDG

Symmetric Biomechanically Guided Prone-to-Supine Breast Image Registration

Prone-to-supine breast image registration has potential application in the fields of surgical and radiotherapy planning, image guided interventions, and multi-modal cancer diagnosis, staging, and therapy response prediction. However, breast image registration of three dimensional images acquired in different patient positions is a challenging problem, due to large deformations induced to the soft breast tissue caused by the change in gravity loading. We present a symmetric, biomechanical simulation based registration framework which aligns the images in a central, virtually unloaded configuration. The breast tissue is modelled as a neo-Hookean material and gravity is considered as the main source of deformation in the original images. In addition to gravity, our framework successively applies image derived forces directly into the unloading simulation in place of a subsequent image registration step. This results in a biomechanically constrained deformation. Using a finite difference scheme avoids an explicit meshing step and enables simulations to be performed directly in the image space. The explicit time integration scheme allows the motion at the interface between chest and breast to be constrained along the chest wall. The feasibility and accuracy of the approach presented here was assessed by measuring the target registration error (TRE) using a numerical phantom with known ground truth deformations, nine clinical prone MRI and supine CT image pairs, one clinical prone-supine CT image pair and four prone-supine MRI image pairs. The registration reduced the mean TRE for the numerical phantom experiment from initially 19.3 to 0.9 mm and the combined mean TRE for all fourteen clinical data sets from 69.7 to 5.6 mm

Computational ultrasound tissue characterisation for brain tumour resection

In brain tumour resection, it is vital to know where critical neurovascular structuresand tumours are located to minimise surgical injuries and cancer recurrence. Theaim of this thesis was to improve intraoperative guidance during brain tumourresection by integrating both ultrasound standard imaging and elastography in thesurgical workflow. Brain tumour resection requires surgeons to identify the tumourboundaries to preserve healthy brain tissue and prevent cancer recurrence. Thisthesis proposes to use ultrasound elastography in combination with conventionalultrasound B-mode imaging to better characterise tumour tissue during surgery.Ultrasound elastography comprises a set of techniques that measure tissue stiffness,which is a known biomarker of brain tumours. The objectives of the researchreported in this thesis are to implement novel learning-based methods for ultrasoundelastography and to integrate them in an image-guided intervention framework.Accurate and real-time intraoperative estimation of tissue elasticity can guide towardsbetter delineation of brain tumours and improve the outcome of neurosurgery. We firstinvestigated current challenges in quasi-static elastography, which evaluates tissuedeformation (strain) by estimating the displacement between successive ultrasoundframes, acquired before and after applying manual compression. Recent approachesin ultrasound elastography have demonstrated that convolutional neural networkscan capture ultrasound high-frequency content and produce accurate strain estimates.We proposed a new unsupervised deep learning method for strain prediction, wherethe training of the network is driven by a regularised cost function, composed of asimilarity metric and a regularisation term that preserves displacement continuityby directly optimising the strain smoothness. We further improved the accuracy of our method by proposing a recurrent network architecture with convolutional long-short-term memory decoder blocks to improve displacement estimation and spatio-temporal continuity between time series ultrasound frames. We then demonstrateinitial results towards extending our ultrasound displacement estimation method toshear wave elastography, which provides a quantitative estimation of tissue stiffness.Furthermore, this thesis describes the development of an open-source image-guidedintervention platform, specifically designed to combine intra-operative ultrasoundimaging with a neuronavigation system and perform real-time ultrasound tissuecharacterisation. The integration was conducted using commercial hardware andvalidated on an anatomical phantom. Finally, preliminary results on the feasibilityand safety of the use of a novel intraoperative ultrasound probe designed for pituitarysurgery are presented. Prior to the clinical assessment of our image-guided platform,the ability of the ultrasound probe to be used alongside standard surgical equipmentwas demonstrated in 5 pituitary cases