Medical imaging of the heart :quantitative analysis of three-dimensional echocardiographic images

PhD ThesisAccurate, reproducible determination of cardiac chamber volume, especially left ventricular (LV) volume, is important for clinical assessment, risk stratification, selection of therapy, and serial monitoring of patients with cardiovascular disease. Echocardiography is the most widely used imaging modality in the clinical diagnosis of left ventricular function abnormalities. In the last 15 years, developments in real time three-dimensional echocardiography (RT3DE) have achieved superior accuracy and reproducibility compared with conventional two-dimensional echocardiography (2DE) for measurement of left ventricular volume and function. However, RT3DE suffers from the limitations inherent to the ultrasonic imaging modality and the cost of increased effort of data handling and image analysis. There were two aims of this research project. Firstly, it aimed to develop different new semi-automated algorithms for LV endocardial surface delineation, LV volume and EF quantification from clinical RT3DE images. Secondly, through assessing and comparing the performance of these algorithms in the aspects of accuracy and reproducibility, this project aimed to investigate what factors in real time 3D echo images influenced the performance of each algorithm, so that advantages and drawbacks of 3D echo images can be better understood. The basic structure of the content of this thesis is as follows: Chapter 1 introduces the background and the aims of this project. Chapter 2 describes the development of the new semi-automated algorithms. Chapter 3 to Chapter 6 presents the four studies designed to assess and compare the accuracy and reproducibility of each algorithm. These studies were the balloon phantom study, the tissue-mimicking phantom study, the clinical cardiac magnetic resonance images study and the clinical contrast enhanced 3D stress echo images study. Chapter 7 summarises all these studies, draws conclusions, and describes future work. In conclusion, it has been shown that the semi-automated algorithms can measure LV volume and EF quantitatively in clinical 3D echo images. To achieve better accuracy and reproducibility, 3D echo images should be analysed from all three dimensions

Neuropsychiatric symptoms and brain dopamine transporter imaging in Parkinson's disease

Parkinson’s disease (PD) is a common neurodegenerative movement disorder. The motor symptoms of PD are linked to the degeneration of dopaminergic neurons of the substantia nigra, which leads to dopamine depletion in the striatum. Non-motor symptoms (NMSs), such as depression, hallucinations and impulse control disorders (ICDs), are important manifestations of PD. The role of dopamine in the pathophysiology of these symptoms is less clear. This thesis investigated NMSs in PD and their association with brain dopamine function using dopamine transporter (DAT) single-photon emission computed tomography (SPECT) imaging. Furthermore, factors that predict the DAT imaging outcome were investigated. The results suggest that ICDs of PD are associated with multiple other psychiatric symptoms. Furthermore, an older age, longer motor symptom duration and asymmetric motor symptoms are associated with an abnormal DAT imaging outcome. The results also demonstrate that lower DAT binding in the limbic striatum is associated with the development of hallucinations in PD. Finally, although PD patients suffer from multiple NMSs, the total burden of these symptoms does not differentiate PD patients from parkinsonism patients with normal DAT binding. The results demonstrate that the total NMS burden is not a specific manifestation for Parkinson’s disease and is unrelated to brain dopamine function. Clinical factors, such as patient age, motor symptom duration and motor symptom asymmetry, may be useful for selecting which patients should undergo DAT SPECT imaging. Moreover, DAT imaging may be useful in predicting subsequent NMS manifestations, such as visual hallucinations; however, further studies are required.Neuropsykiatriset oireet ja aivojen dopamiinitransportterikuvantaminen parkinsonin taudissa Parkinsonin tauti on yleinen neurodegeneratiivinen liikehäiriö. Parkinsonin taudin motoristen oireiden ajatellaan johtuvan keskiaivojen mustatumakkeen dopaminergisten hermosolujen tuhoutumisesta. Motoristen oireiden lisäksi ei-motoriset oireet, kuten masennus, hallusinaatiot ja impulssikontrollihäiriöt, ovat tärkeitä Parkinsonin taudin ilmentymiä. Dopamiinin merkitys Parkinsonin taudin ei-motoristen oireiden patofysiologiassa on vielä epäselvä. Tässä väitöskirjassa tutkittiin Parkinsonin taudin ei-motorisia oireita sekä niiden yhteyttä aivojen dopamiinitoimintaan käyttäen aivojen dopamiinitransportterien yksifotoniemissiotomografiakuvausta. Lisäksi tutkittiin kliinisiä tekijöitä, jotka ennustavat dopamiinitransportterikuvauksen tulosta. Tämän tutkimuksen kohteina olleilla henkilöillä Parkinsonin taudin impulssikontrollihäiriöt esiintyivät usein yhdessä muiden psykiatristen oireiden kanssa. Epänormaaliin löydökseen dopamiinitransportterikuvauksessa liittyivät korkea ikä, pitkä motoristen oireiden kesto sekä epäsymmetriset oireet. Tulokset osoittavat myös, että aivojen alentunut dopamiinitransportterisitoutuminen limbisessä aivojuoviossa liittyy Parkinsonin tautia sairastavilla hallusinaatioiden kehittymiseen. Lisäksi, vaikka Parkinsonin tautia sairastavat potilaat kärsivät monista ei-motorisista oireista, näiden oireiden kokonaismäärä ei näyttäisi erottavan Parkinsonin tautia sairastavia potilaita niistä potilaista, joilla esiintyy parkinsonismia mutta joiden aivojen dopamiinitransportterisitoutuminen on normaalia. Tulokset osoittavat, että ei-motoristen oireiden kokonaismäärä ei ole spesifinen ilmentymä Parkinsonin taudille, eikä se liity aivojen dopamiinitoimintaan. Kliiniset tekijät, kuten potilaan ikä, oireiden kesto ja motoristen oireiden epäsymmetria, voivat olla avuksi, kun valitaan tutkittaviksi potilaita, jotka hyötyvät aivojen dopamiinitransportterikuvauksesta. Vaikka aihetta on tutkittava vielä lisää, tulosten perusteella dopamiinitransportterikuvaus voi olla hyödyksi, kun ennustetaan ei-motoristen oireiden, kuten hallusinaatioiden, kehittymisiä Parkinson-potilailla

Fast widefield techniques for fluorescence and phase endomicroscopy

Thesis (Ph.D.)--Boston UniversityEndomicroscopy is a recent development in biomedical optics which gives researchers and physicians microscope-resolution views of intact tissue to complement macroscopic visualization during endoscopy screening. This thesis presents HiLo endomicroscopy and oblique back-illumination endomicroscopy, fast widefield imaging techniques with fluorescence and phase contrast, respectively. Fluorescence imaging in thick tissue is often hampered by strong out-of-focus background signal. Laser scanning confocal endomicroscopy has been developed for optically-sectioned imaging free from background, but reliance on mechanical scanning fundamentally limits the frame rate and represents significant complexity and expense. HiLo is a fast, simple, widefield fluorescence imaging technique which rejects out-of-focus background signal without the need for scanning. It works by acquiring two images of the sample under uniform and structured illumination and synthesizing an optically sectioned result with real-time image processing. Oblique back-illumination microscopy (OBM) is a label-free technique which allows, for the first time, phase gradient imaging of sub-surface morphology in thick scattering tissue with a reflection geometry. OBM works by back-illuminating the sample with the oblique diffuse reflectance from light delivered via off-axis optical fibers. The use of two diametrically opposed illumination fibers allows simultaneous and independent measurement of phase gradients and absorption contrast. Video-rate single-exposure operation using wavelength multiplexing is demonstrated

MRI-Based Attenuation Correction in Emission Computed Tomography

The hybridization of magnetic resonance imaging (MRI) with positron emission tomography (PET) or single photon emission computed tomography (SPECT) enables the collection of an assortment of biological data in spatial and temporal register. However, both PET and SPECT are subject to photon attenuation, a process that degrades image quality and precludes quantification. To correct for the effects of attenuation, the spatial distribution of linear attenuation coefficients (μ-coefficients) within and about the patient must be available. Unfortunately, extracting μ-coefficients from MRI is non-trivial. In this thesis, I explore the problem of MRI-based attenuation correction (AC) in emission tomography. In particular, I began by asking whether MRI-based AC would be more reliable in PET or in SPECT. To this end, I implemented an MRI-based AC algorithm relying on image segmentation and applied it to phantom and canine emission data. The subsequent analysis revealed that MRI-based AC performed better in SPECT than PET, which is interesting since AC is more challenging in SPECT than PET. Given this result, I endeavoured to improve MRI-based AC in PET. One problem that required addressing was that the lungs yield very little signal in MRI, making it difficult to infer their μ-coefficients. By using a pulse sequence capable of visualizing lung parenchyma, I established a linear relationship between MRI signal and the lungs’ μ-coefficients. I showed that applying this mapping on a voxel-by-voxel basis improved quantification in PET reconstructions compared to conventional MRI-based AC techniques. Finally, I envisaged that a framework for MRI-based AC methods would potentiate further improvements. Accordingly, I identified three ways an MRI can be converted to μ-coefficients: 1) segmentation, wherein the MRI is divided into tissue types and each is assigned an μ-coefficient, 2) registration, wherein a template of μ-coefficients is aligned with the MRI, and 3) mapping, wherein a function maps MRI voxels to μ-coefficients. I constructed an algorithm for each method and catalogued their strengths and weaknesses. I concluded that a combination of approaches is desirable for MRI-based AC. Specifically, segmentation is appropriate for air, fat, and water, mapping is appropriate for lung, and registration is appropriate for bone

Neurological and Mental Disorders

Mental disorders can result from disruption of neuronal circuitry, damage to the neuronal and non-neuronal cells, altered circuitry in the different regions of the brain and any changes in the permeability of the blood brain barrier. Early identification of these impairments through investigative means could help to improve the outcome for many brain and behaviour disease states.The chapters in this book describe how these abnormalities can lead to neurological and mental diseases such as ADHD (Attention Deficit Hyperactivity Disorder), anxiety disorders, Alzheimer’s disease and personality and eating disorders. Psycho-social traumas, especially during childhood, increase the incidence of amnesia and transient global amnesia, leading to the temporary inability to create new memories.Early detection of these disorders could benefit many complex diseases such as schizophrenia and depression

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Support for total hip replacement surgery: Structures modeling, Gait Data Analysis and Report system

For the treatment of advanced damages of hip joints, Total Hip Arthroplasty is well proven. Due to the different mechanical properties of the prosthesis material and the bone tissue, a partial unloading of the periprosthetic bone occurs. The bone cement causes reduction in bone density as a result of removal of normal stress from the bone, leading to weakening of the bone in that area and the fracture risk increases. Bone loss is identified as one of the main reasons for loosening of the stem. Otherwise, thanks to the press-fit of the non-cemented stem achieved by surgery, the bone layers immediately adjacent to the stem are preloaded, thus encouraged growing, and the bone getting stronger. The non-cemented stem would be the better choice for every patient, but the question remains if the femur can handle the press- fitting surgery. This studies aim to develop a monitoring techniques based on Gait analysis and bone density changes to assess patient recovery after Total Hip Arthroplasty. Furthermore, to validate computational processes based on 3D modeling and Finite Element Methods for optimizing decision making in the operation process and selecting the suited surgical procedure. A vision could be minimizing risk of periprosthetic fracture during and after surgery. Patients: The sample presents 11 patients receiving cemented implant and 13 for the uncemented. Patients are grouped by type of implant. Three checkpoints were considered: before, after operation and one year later. CT scans, gaitrite and kinepro measurements have been realized. Main outcome measures: Fracture risk probability is higher in bone with low bone mineral density; therefore bones are more fragile in elderly people. BMD is indeed one parameter considered among all the observations. Periprosthetic fracture of the femur is a rare but complex complication of THA, and requires demanding surgery. As such, they result in considerable morbidity and dysfunction. Thus, tests of force reaction have been accomplished to support surgeons during the prosthesis fitting. Identification of risk factors for fracture will improve preoperative counseling and aid primary prevention. To assess eventual improvements or find out trends respecting the implant used, gait data have been collected and compared with muscles mass modeling