747 research outputs found
Assessment and optimisation of MRI measures of atrophy as potential markers of disease progression in multiple sclerosis
There is a need for sensitive measures of disease progression in multiple sclerosis (MS) to
monitor treatment effects and understand disease evolution. MRI measures of brain
atrophy have been proposed for this purpose. This thesis investigates a number of
measurement techniques to assess their relative ability to monitor disease progression in
clinically isolated syndromes (CIS) and early relapsing remitting MS (RRMS).
Presented, is work demonstrating that measurement techniques and MR acquisitions can
be optimised to give small but significant improvements in measurement sensitivity and
precision, which provided greater statistical power. Direct comparison of numerous
techniques demonstrated significant differences between them. Atrophy measurements
from SIENA and the BBSI (registration-based techniques) were significantly more
precise than segmentation and subtraction of brain volumes, although larger percentage
losses were observed in grey matter fraction. Ventricular enlargement (VE) gave similar
statistical power and these techniques were robust and reliable; scan-rescan measurement
error was <0.01% of brain volume for BBSI and SIENA and <0.04ml for VE.
Annual atrophy rates (using SIENA) were -0.78% in RRMS and -0.52% in CIS patients
who progressed to MS, which were significantly greater than the rate observed in controls
(-0.07%). Sample size calculations for future trials of disease-modifying treatments in
RRMS, using brain atrophy as an outcome measure, are described. For SIENA, the BBSI
and VE respectively, an estimated 123, 157 and 140 patients per treatment arm
respectively would be required to show a 30% slowing of atrophy rate over two years. In
CIS subjects brain atrophy rate was a significant prognostic factor, independent of T2
MRI lesions at baseline, for development of MS by five year follow-up. It was also the
most significant MR predictor of disability in RRMS subjects. Cognitive assessment of
RRMS patients at five year follow-up is described, and brain atrophy rate was a
significant predictor of overall cognitive performance, and more specifically, of
performance in tests of memory.
The work in this thesis has identified methods for sensitively measuring progressive brain
atrophy in MS. It has shown that brain atrophy changes in early MS are related to early
clinical evolution, providing complementary information to clinical assessment that could
be utilised to monitor disease progression
Development, Implementation and Pre-clinical Evaluation of Medical Image Computing Tools in Support of Computer-aided Diagnosis: Respiratory, Orthopedic and Cardiac Applications
Over the last decade, image processing tools have become crucial components of all clinical and research efforts involving medical imaging and associated applications. The imaging data available to the radiologists continue to increase their workload, raising the need for efficient identification and visualization of the required image data necessary for clinical assessment.
Computer-aided diagnosis (CAD) in medical imaging has evolved in response to the need for techniques that can assist the radiologists to increase throughput while reducing human error and bias without compromising the outcome of the screening, diagnosis or disease assessment. More intelligent, but simple, consistent and less time-consuming methods will become more widespread, reducing user variability, while also revealing information in a more clear, visual way.
Several routine image processing approaches, including localization, segmentation, registration, and fusion, are critical for enhancing and enabling the development of CAD techniques. However, changes in clinical workflow require significant adjustments and re-training and, despite the efforts of the academic research community to develop state-of-the-art algorithms and high-performance techniques, their footprint often hampers their clinical use.
Currently, the main challenge seems to not be the lack of tools and techniques for medical image processing, analysis, and computing, but rather the lack of clinically feasible solutions that leverage the already developed and existing tools and techniques, as well as a demonstration of the potential clinical impact of such tools. Recently, more and more efforts have been dedicated to devising new algorithms for localization, segmentation or registration, while their potential and much intended clinical use and their actual utility is dwarfed by the scientific, algorithmic and developmental novelty that only result in incremental improvements over already algorithms.
In this thesis, we propose and demonstrate the implementation and evaluation of several different methodological guidelines that ensure the development of image processing tools --- localization, segmentation and registration --- and illustrate their use across several medical imaging modalities --- X-ray, computed tomography, ultrasound and magnetic resonance imaging --- and several clinical applications:
Lung CT image registration in support for assessment of pulmonary nodule growth rate and disease progression from thoracic CT images.
Automated reconstruction of standing X-ray panoramas from multi-sector X-ray images for assessment of long limb mechanical axis and knee misalignment.
Left and right ventricle localization, segmentation, reconstruction, ejection fraction measurement from cine cardiac MRI or multi-plane trans-esophageal ultrasound images for cardiac function assessment.
When devising and evaluating our developed tools, we use clinical patient data to illustrate the inherent clinical challenges associated with highly variable imaging data that need to be addressed before potential pre-clinical validation and implementation.
In an effort to provide plausible solutions to the selected applications, the proposed methodological guidelines ensure the development of image processing tools that help achieve sufficiently reliable solutions that not only have the potential to address the clinical needs, but are sufficiently streamlined to be potentially translated into eventual clinical tools provided proper implementation.
G1: Reducing the number of degrees of freedom (DOF) of the designed tool, with a plausible example being avoiding the use of inefficient non-rigid image registration methods. This guideline addresses the risk of artificial deformation during registration and it clearly aims at reducing complexity and the number of degrees of freedom.
G2: The use of shape-based features to most efficiently represent the image content, either by using edges instead of or in addition to intensities and motion, where useful. Edges capture the most useful information in the image and can be used to identify the most important image features. As a result, this guideline ensures a more robust performance when key image information is missing.
G3: Efficient method of implementation. This guideline focuses on efficiency in terms of the minimum number of steps required and avoiding the recalculation of terms that only need to be calculated once in an iterative process. An efficient implementation leads to reduced computational effort and improved performance.
G4: Commence the workflow by establishing an optimized initialization and gradually converge toward the final acceptable result. This guideline aims to ensure reasonable outcomes in consistent ways and it avoids convergence to local minima, while gradually ensuring convergence to the global minimum solution.
These guidelines lead to the development of interactive, semi-automated or fully-automated approaches that still enable the clinicians to perform final refinements, while they reduce the overall inter- and intra-observer variability, reduce ambiguity, increase accuracy and precision, and have the potential to yield mechanisms that will aid with providing an overall more consistent diagnosis in a timely fashion
Quantitation in MRI : application to ageing and epilepsy
Multi-atlas propagation and label fusion techniques have recently been developed for segmenting
the human brain into multiple anatomical regions. In this thesis, I investigate
possible adaptations of these current state-of-the-art methods. The aim is to study ageing
on the one hand, and on the other hand temporal lobe epilepsy as an example for a
neurological disease.
Overall effects are a confounding factor in such anatomical analyses. Intracranial volume
(ICV) is often preferred to normalize for global effects as it allows to normalize for estimated
maximum brain size and is hence independent of global brain volume loss, as seen
in ageing and disease. I describe systematic differences in ICV measures obtained at 1.5T
versus 3T, and present an automated method of measuring intracranial volume, Reverse
MNI Brain Masking (RBM), based on tissue probability maps in MNI standard space. I
show that this is comparable to manual measurements and robust against field strength
differences.
Correct and robust segmentation of target brains which show gross abnormalities, such as
ventriculomegaly, is important for the study of ageing and disease. We achieved this with
incorporating tissue classification information into the image registration process. The
best results in elderly subjects, patients with TLE and healthy controls were achieved using
a new approach using multi-atlas propagation with enhanced registration (MAPER).
I then applied MAPER to the problem of automatically distinguishing patients with TLE
with (TLE-HA) and without (TLE-N) hippocampal atrophy on MRI from controls, and
determine the side of seizure onset. MAPER-derived structural volumes were used for
a classification step consisting of selecting a set of discriminatory structures and applying
support vector machine on the structural volumes as well as morphological similarity
information such as volume difference obtained with spectral analysis. Acccuracies were
91-100 %, indicating that the method might be clinically useful.
Finally, I used the methods developed in the previous chapters to investigate brain regional
volume changes across the human lifespan in over 500 healthy subjects between 20
to 90 years of age, using data from three different scanners (2x 1.5T, 1x 3T), using the IXI
database. We were able to confirm several known changes, indicating the veracity of the
method. In addition, we describe the first multi-region, whole-brain database of normal
ageing
Computational Methods for Segmentation of Multi-Modal Multi-Dimensional Cardiac Images
Segmentation of the heart structures helps compute the cardiac contractile function quantified via the systolic and diastolic volumes, ejection fraction, and myocardial mass, representing a reliable diagnostic value. Similarly, quantification of the myocardial mechanics throughout the cardiac cycle, analysis of the activation patterns in the heart via electrocardiography (ECG) signals, serve as good cardiac diagnosis indicators. Furthermore, high quality anatomical models of the heart can be used in planning and guidance of minimally invasive interventions under the assistance of image guidance.
The most crucial step for the above mentioned applications is to segment the ventricles and myocardium from the acquired cardiac image data. Although the manual delineation of the heart structures is deemed as the gold-standard approach, it requires significant time and effort, and is highly susceptible to inter- and intra-observer variability. These limitations suggest a need for fast, robust, and accurate semi- or fully-automatic segmentation algorithms. However, the complex motion and anatomy of the heart, indistinct borders due to blood flow, the presence of trabeculations, intensity inhomogeneity, and various other imaging artifacts, makes the segmentation task challenging.
In this work, we present and evaluate segmentation algorithms for multi-modal, multi-dimensional cardiac image datasets. Firstly, we segment the left ventricle (LV) blood-pool from a tri-plane 2D+time trans-esophageal (TEE) ultrasound acquisition using local phase based filtering and graph-cut technique, propagate the segmentation throughout the cardiac cycle using non-rigid registration-based motion extraction, and reconstruct the 3D LV geometry. Secondly, we segment the LV blood-pool and myocardium from an open-source 4D cardiac cine Magnetic Resonance Imaging (MRI) dataset by incorporating average atlas based shape constraint into the graph-cut framework and iterative segmentation refinement. The developed fast and robust framework is further extended to perform right ventricle (RV) blood-pool segmentation from a different open-source 4D cardiac cine MRI dataset. Next, we employ convolutional neural network based multi-task learning framework to segment the myocardium and regress its area, simultaneously, and show that segmentation based computation of the myocardial area is significantly better than that regressed directly from the network, while also being more interpretable. Finally, we impose a weak shape constraint via multi-task learning framework in a fully convolutional network and show improved segmentation performance for LV, RV and myocardium across healthy and pathological cases, as well as, in the challenging apical and basal slices in two open-source 4D cardiac cine MRI datasets.
We demonstrate the accuracy and robustness of the proposed segmentation methods by comparing the obtained results against the provided gold-standard manual segmentations, as well as with other competing segmentation methods
Automatic volumetry on MR brain images can support diagnostic decision making.
Background: Diagnostic decisions in clinical imaging currently rely almost exclusively on visual image interpretation. This can lead to uncertainty, for example in dementia disease, where some of the changes resemble those of normal ageing. We hypothesized that extracting volumetric data from patients MR brain images, relating them to reference data and presenting the results as a colour overlay on the grey scale data would aid diagnostic readers in classifying dementia disease versus normal ageing. Methods: A proof-of-concept forced-choice reader study was designed using MR brain images from 36 subjects. Images were segmented into 43 regions using an automatic atlas registration-based label propagation procedure. Seven subjects had clinically probable AD, the remaining 29 of a similar age range were used as controls. Seven of the control subject data sets were selected at random to be presented along with the seven AD datasets to two readers, who were blinded to all clinical and demographic information except age and gender. Readers were asked to review the grey scale MR images and to record their choice of diagnosis (AD or non-AD) along with their confidence in this decision. Afterwards, readers were given the option to switch on a false-colour overlay representing the relative size of the segmented structures. Colorization was based on the size rank of the test subject when compared with a reference group consisting of the 22 control subjects who were not used as review subjects. The readers were then asked to record whether and how the additional information had an impact on their diagnostic confidence. Results: The size rank colour overlays were useful in 18 of 28 diagnoses, as determined by their impact on readers diagnostic confidence. A not useful result was found in 6 of 28 cases. The impact of the additional information on diagnostic confidence was significant (p < 0.02). Conclusion: Volumetric anatomical information extracted from brain images using automatic segmentation and presented as colour overlays can support diagnostic decision making. © 2008 Heckemann et al; licensee BioMed Central Ltd.Published versio
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Characterization and modeling of the human left atrium using optical coherence tomography
With current needs to better understand the interaction between atrial tissue microstructure and atrial fibrillation dynamics, micrometer scale imaging with optical coherence tomography has significant potential to provide further insight on arrhythmia mechanisms and improve treatment guidance. However, optical coherence tomography imaging of cardiac tissue in humans is largely unexplored, and the ability of optical coherence tomography to identify the structural substrate of atrial fibrillation has not yet been investigated. Therefore, the objective of this thesis was to develop an optical coherence tomography imaging atlas of the human heart, study the utility of optical coherence tomography in providing useful features of human left atrial tissues, and develop a framework for optical coherence tomography-informed cardiac modeling that could be used to probe dynamics between electrophysiology and tissue structure.
Human left atrial tissues were comprehensively imaged by optical coherence tomography for the first time, providing an imaging atlas that can guide identification of left atrial tissue features from optical coherence tomography imaging. Optical coherence tomography image features corresponding to myofiber and collagen fiber orientation, adipose tissue, endocardial thickness and composition, and venous media were established. Varying collagen fiber distributions in the myocardial sleeves were identified within the pulmonary veins. A scheme for mapping optical coherence tomography data of dissected left atrial tissues to a three-dimensional, anatomical model of the human left atrium was also developed, enabling the mapping of distributions of imaged adipose tissue and fiber orientation to the whole left atrial geometry. These results inform future applications of structural substrate mapping in the human left atrium using optical coherence tomography-integrated catheters, as well as potential directions of ex vivo optical coherence tomography atrial imaging studies.
Additionally, we developed a workflow for creating optical mapping models of atrial tissue as informed by optical coherence tomography. Tissue geometry, fiber orientation, ablation lesion geometry, and heterogeneous tissue types were extracted from optical coherence tomography images and incorporated into tissue-specific meshes. Electrophysiological propagation was simulated and combined with photon scattering simulations to evaluate the influence of tissue-specific structure on electrical and optical mapping signals. Through tissue-specific modeling of myofiber orientation, ablation lesions, and heterogeneous tissue types, the influence of myofiber orientation on transmural activation, the relationship between fluorescent signals and lesion geometry, and the blurring of optical mapping signals in the presence of heterogeneous tissue types were investigated.
By providing a comprehensive optical coherence tomography image database of the human left atrium and a workflow for developing optical coherence tomography-informed cardiac tissue models, this work establishes the foundation for utilizing optical coherence tomography to improve the structural substrate characterization of atrial fibrillation. Future developments include analysis of optical coherence tomography imaged tissue structure with respect to clinical presentation, development of automated processing to better leverage the large amount of imaging data, enhancements and validation of the modeling scheme, and in vivo evaluation of the left atrial structural substrate through optical coherence tomography-integrated catheter
Improving patient-specific assessments of regional aortic mechanics via quantitative magnetic resonance imaging with early applications in patients at elevated risk for thoracic aortopathy
Unstable aortic aneurysms and dissections are serious cardiovascular conditions associated with high mortality. The current gold standards for assessment of stability, however, rely on simple geometric measurements, like cross-sectional area or increased diameter between follow-up scans, and fail to incorporate information about underlying aortic mechanics. Displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) has been used previously to determine heterogeneous circumferential strain patterns in the aortas of healthy volunteers. Here, I introduce technical improvements to DENSE aortic analysis and early pilot application in patients at higher risk for the development of aortopathies. Modifications to the DENSE aortic postprocessing method involving the separate spatial smoothing of the inner and outer layers of the aortic wall allowed for the preservation of radial and shear strains without impacting circumferential strain calculations. The implementation of a semiautomatic segmentation approach utilizing the intrinsic kinematic information provided by DENSE MRI reduced lengthy post-processing times while generating circumferential strain distributions with good agreement to a manually generated benchmark. Finally, a new analysis pipeline for the combined use and spatial correlation of 4D phase-contrast MRI alongside DENSE MRI to quantify both regional fluid and solid mechanics in the descending aorta is explored in a limited pilot study
Investigating Cardiac Motion Patters Using Synthetic High-Resolution 3D Cardiovascular Magnetic Resonance Images and Statistical Shape Analysis
Diagnosis of ventricular dysfunction in congenital heart disease is more and more based on medical imaging, which allows investigation of abnormal cardiac morphology and correlated abnormal function. Although analysis of 2D images represents the clinical standard, novel tools performing automatic processing of 3D images are becoming available, providing more detailed and comprehensive information than simple 2D morphometry. Among these, statistical shape analysis (SSA) allows a consistent and quantitative description of a population of complex shapes, as a way to detect novel biomarkers, ultimately improving diagnosis and pathology understanding. The aim of this study is to describe the implementation of a SSA method for the investigation of 3D left ventricular shape and motion patterns and to test it on a small sample of 4 congenital repaired aortic stenosis patients and 4 age-matched healthy volunteers to demonstrate its potential. The advantage of this method is the capability of analyzing subject-specific motion patterns separately from the individual morphology, visually and quantitatively, as a way to identify functional abnormalities related to both dynamics and shape. Specifically, we combined 3D, high-resolution whole heart data with 2D, temporal information provided by cine cardiovascular magnetic resonance images, and we used an SSA approach to analyze 3D motion per se. Preliminary results of this pilot study showed that using this method, some differences in end-diastolic and end-systolic ventricular shapes could be captured, but it was not possible to clearly separate the two cohorts based on shape information alone. However, further analyses on ventricular motion allowed to qualitatively identify differences between the two populations. Moreover, by describing shape and motion with a small number of principal components, this method offers a fully automated process to obtain visually intuitive and numerical information on cardiac shape and motion, which could be, once validated on a larger sample size, easily integrated into the clinical workflow. To conclude, in this preliminary work, we have implemented state-of-the-art automatic segmentation and SSA methods, and we have shown how they could improve our understanding of ventricular kinetics by visually and potentially quantitatively highlighting aspects that are usually not picked up by traditional approaches
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