Development and validation of HRCT airway segmentation algorithms

Direct measurements of airway lumen and wall areas are potentially useful as a diagnostic tool and as an aid to understanding the pathophysiology underlying lung disease. Direct measurements can be made from images created by high resolution computer tomography (HRCT) by using computer-based algorithms to segment airways, but current validation techniques cannot adequately establish the accuracy and precision of these algorithms. A detailed review of HRCT airway segmentation algorithms was undertaken, from which three candidate algorithm designs were developed. A custom Windows-based software program was implemented to facilitate multi-modality development and validation of the segmentation algorithms. The performance of the algorithms was examined in clinical HRCT images. A centre-likelihood (CL) ray-casting algorithm was found to be the most suitable algorithm due to its speed and reliability in semi-automatic segmentation and tracking of the airway wall. Several novel refinements were demonstrated to improve the CL algorithm’s robustness in HRCT lung data. The performance of the CL algorithm was then quantified in two-dimensional simulated data to optimise customisable parameters such as edge-detection method, interpolation and number of rays. Novel correction equations to counter the effects of volume averaging and airway orientation angle were derived and demonstrated in three-dimensional simulated data. The optimal CL algorithm was validated with HRCT data using a plastic phantom and a pig lung phantom matched to micro-CT. Accuracy was found to be improved compared to previous studies using similar methods. The volume averaging correction was found to improve precision and accuracy in the plastic phantom but not in the pig lung phantom. When tested in a clinical setting the results of the optimised CL algorithm was in agreement with the results of other measures of lung function. The thesis concludes that the relative contributions of confounders of airway measurement have been quantified in simulated data and the CL algorithm’s performance has been validated in a plastic phantom as well as animal model. This validation protocol has improved the accuracy and precision of measurements made using the CL algorith

Imaging Biomarkers of Pulmonary Structure and Function

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airflow limitations resulting from airway obstruction and/or tissue destruction. The diagnosis and monitoring of these pulmonary diseases is primarily performed using spirometry, specifically the forced expiratory volume in one second (FEV1), which measures global airflow obstruction and provides no regional information of the different underlying disease pathologies. The limitations of spirometry and current therapies for lung disease patients have motivated the development of pulmonary imaging approaches, such as computed tomography (CT) and magnetic resonance imaging (MRI). Inhaled hyperpolarized noble gas MRI, specifically using helium-3 (3He) and xenon-129 (129Xe) gases, provides a way to quantify pulmonary ventilation by visualizing lung regions accessed by gas during a breath-hold, and alternatively, regions that are not accessed - coined “ventilation defects.” Despite the strong foundation and many advantages hyperpolarized 3He MRI has to offer research and patient care, clinical translation has been inhibited in part due to the cost and need for specialized equipment, including multinuclear-MR hardware and polarizers, and personnel. Accordingly, our objective was to develop and evaluate imaging biomarkers of pulmonary structure and function using MRI and CT without the use of exogenous contrast agents or specialized equipment. First, we developed and compared CT parametric response maps (PRM) with 3He MR ventilation images in measuring gas-trapping and emphysema in ex-smokers with and without COPD. We observed that in mild-moderate COPD, 3He MR ventilation abnormalities were related to PRM gas-trapping whereas in severe COPD, ventilation abnormalities correlated with both PRM gas-trapping and PRM emphysema. We then developed and compared pulmonary ventilation abnormalities derived from Fourier decomposition of free-breathing proton (1H) MRI (FDMRI) with 3He MRI in subjects with COPD and bronchiectasis. This work demonstrated that FDMRI and 3He MRI ventilation defects were strongly related in COPD, but not in bronchiectasis subjects. In COPD only, FDMRI ventilation defects were spatially related with 3He MRI ventilation defects and emphysema. Based on the FDMRI biomarkers developed in patients with COPD and bronchiectasis, we then evaluated ventilation heterogeneity in patients with severe asthma, both pre- and post-salbutamol as well as post-methacholine challenge, using FDMRI and 3He MRI. FDMRI free-breathing ventilation abnormalities were correlated with but under-estimated 3He MRI static ventilation defects. Finally, based on the previously developed free-breathing MRI approach, we developed a whole-lung free-breathing pulmonary 1H MRI technique to measure regional specific-ventilation and evaluated both asthmatics and healthy volunteers. These measurements not only provided similar information as specific-ventilation measured using plethysmography, but also information about regional ventilation defects that were correlated with 3He MRI ventilation abnormalities. These results demonstrated that whole-lung free-breathing 1H MRI biomarker of specific-ventilation may reflect ventilation heterogeneity and/or gas-trapping in asthma. These important findings indicate that imaging biomarkers of pulmonary structure and function using MRI and CT have the potential to regionally reveal the different pathologies in COPD and asthma without the use of exogenous contrast agents. The development and validation of these clinically meaningful imaging biomarkers are critically required to accelerate pulmonary imaging translation from the research workbench to being a part of the clinical workflow, with the overall goal to improve patient outcomes

Diseases of the Chest, Breast, Heart and Vessels 2019-2022

This open access book focuses on diagnostic and interventional imaging of the chest, breast, heart, and vessels. It consists of a remarkable collection of contributions authored by internationally respected experts, featuring the most recent diagnostic developments and technological advances with a highly didactical approach. The chapters are disease-oriented and cover all the relevant imaging modalities, including standard radiography, CT, nuclear medicine with PET, ultrasound and magnetic resonance imaging, as well as imaging-guided interventions. As such, it presents a comprehensive review of current knowledge on imaging of the heart and chest, as well as thoracic interventions and a selection of "hot topics". The book is intended for radiologists, however, it is also of interest to clinicians in oncology, cardiology, and pulmonology

Effect of acute and chronic pressure-threshold inspiratory muscle training on upper and lower airway function

There is evidence to suggest that inspiratory muscle training (IMT) may influence the functional properties of the muscles of the upper (UA) and lower (LA) airway. However, the nature and functional relevance of this influence is currently unclear. This thesis examined the effect of acute and chronic IMT in the context of UA and LA function. The ability of IMT to activate the UA dilator muscles, genioglossus (GG) and geniohyoid (GH), was examined using magnetic resonance imaging (MRI), as was the effect of chronic training on these muscles. In addition, the effect of acute and chronic IMT upon LA resistance (Rrs) and function was investigated in people with asthma using the Forced Oscillation Technique and conventional spirometry. For the UA, an acute bout of IMT at 60% maximal inspiratory mouth pressure (MIP) resulted in significant GG and GH activation (P < 0.001) as demonstrated by increases in the transverse relaxation time of muscle water (T2). Despite this, MRI was unable to detect any effect of chronic IMT upon UA function. For the LA, the usual increase in Rrs, following deep inhalation (DI) in people with asthma was attenuated with both single and multiple breaths against a pressure-threshold load equal to 50% MIP. However, six weeks IMT had no effect on baseline airway function or response to DI. In conclusion, an acute effect of pressure-threshold IMT upon UA and LA function was demonstrated. A strong rationale for a beneficial influence of chronic pressure-threshold IMT was therefore demonstrated. However, the data were insufficient to either reject, or accept the hypothesis that IMT exerts more than a transient influence upon UA and LA function, but insights are presented that support the need for further investigations.EThOS - Electronic Theses Online ServiceHarry BrarHaB International LtdGBUnited Kingdo