Multi-dimensional local binary pattern texture descriptors and their application for medical image analysis

Texture can be broadly stated as spatial variation of image intensities. Texture analysis and classification is a well researched area for its importance to many computer vision applications. Consequently, much research has focussed on deriving powerful and efficient texture descriptors. Local binary patterns (LBP) and its variants are simple yet powerful texture descriptors. LBP features describe the texture neighbourhood of a pixel using simple comparison operators, and are often calculated based on varying neighbourhood radii to provide multi-resolution texture descriptions. A comprehensive evaluation of different LBP variants on a common benchmark dataset is missing in the literature. This thesis presents the performance for different LBP variants on texture classification and retrieval tasks. The results show that multi-scale local binary pattern variance (LBPV) gives the best performance over eight benchmarked datasets. Furthermore, improvements to the Dominant LBP (D-LBP) by ranking dominant patterns over complete training set and Compound LBP (CM-LBP) by considering 16 bits binary codes are suggested which are shown to outperform their original counterparts. The main contribution of the thesis is the introduction of multi-dimensional LBP features, which preserve the relationships between different scales by building a multi-dimensional histogram. The results on benchmarked classification and retrieval datasets clearly show that the multi-dimensional LBP (MD-LBP) improves the results compared to conventional multi-scale LBP. The same principle is applied to LBPV (MD-LBPV), again leading to improved performance. The proposed variants result in relatively large feature lengths which is addressed using three different feature length reduction techniques. Principle component analysis (PCA) is shown to give the best performance when the feature length is reduced to match that of conventional multi-scale LBP. The proposed multi-dimensional LBP variants are applied for medical image analysis application. The first application is nailfold capillary (NC) image classification. Performance of MD-LBPV on NC images is highest, whereas for second application, HEp-2 cell classification, performance of MD-LBP is highest. It is observed that the proposed texture descriptors gives improved texture classification accuracy

Microvasculopathy in SMA is driven by a reversible autonomous endothelial cell defect

Spinal muscular atrophy (SMA) is a neuromuscular disorder due to degeneration of spinal cord motor neurons caused by deficiency of the ubiquitously expressed SMN protein. Here, we present a retinal vascular defect in patients, recapitulated in SMA transgenic mice, driven by failure of angiogenesis and maturation of blood vessels. Importantly, the retinal vascular phenotype was rescued by early, systemic SMN restoration therapy in SMA mice. We also demonstrate in patients an unfavorable imbalance between endothelial injury and repair, as indicated by increased circulating endothelial cell counts and decreased endothelial progenitor cell counts in blood circulation. The cellular markers of endothelial injury were associated with disease severity and improved following SMN restoration treatment in cultured endothelial cells from patients. Finally, we demonstrated autonomous defects in angiogenesis and blood vessel formation, secondary to SMN deficiency in cultured human and mouse endothelial cells, as the underlying cellular mechanism of microvascular pathology. Our cellular and vascular biomarker findings indicate microvasculopathy as a fundamental feature of SMA. Our findings provide mechanistic insights into previously described SMA microvascular complications, and highlight the functional role of SMN in the periphery, including the vascular system, where deficiency of SMN can be addressed by systemic SMN-restoring treatment

Basic Research in Endocrinology

The first all-Russia conference with international participation “Basic Research in Endocrinology: A Modern Strategy for the Development and Technologies of Personalized Medicine” was held in Novosibirsk on 26–27 November 2020. The purpose of this conference was to disseminate the latest basic and clinical findings in the fields of etiology, clinical characteristics, and modern diagnostics and treatments of endocrine disorders among various relevant specialists. The conference was intended for practicing endocrinologists, primary care physicians, medical geneticists, pediatric endocrinologists, pediatricians, and physician–scientists. The main topics included epidemiology and pathogenesis of endocrine disorders; genomic research in endocrinology; biochemical characteristics of endocrine aberrations; immunology and immunogenetics in endocrinology; cellular technologies in endocrinology; metabolomic research in endocrinology; pharmacogenetics; basic pathomorphology; high-tech care of patients with endocrine disorders; iodine-deficiency-related, autoimmune, and oncological diseases of the thyroid; modern diagnostic and therapeutic strategies for diabetes mellitus; osteoporosis and osteopenias; polyendocrinopathies; an interdisciplinary approach to the diagnosis and treatment of obesity and metabolic syndrome; hypo- and hyperparathyroidism, vitamin D; neuroendocrine disorders; reproductive health; rehabilitation of patients with endocrine disorders; health resort and spa treatments of endocrine disorders and comorbid conditions

The development and alignment of engineered microvasculature in fibrin gel

University of Minnesota Ph.D. dissertation. Ph.D. November 2012. Major:Biomedical Engineering. Advisor: Robert T. Tranquillo. 1 computer file (PDF); iv, 301 pages, appendices A-C.The ability to engineer microvasculature would be of great utility for the tissue engineering of highly metabolic tissues such as myocardium. In addition, the alignment of such a network is critical to the success of using it to deliver oxygen to tissue cells because it provides natural inlet and outlet sides for perfusion. In this work, the ability of engineered microvessels to align with their fibrin gel matrix has been examined and a bioreactor has been designed to harness this ability and perfuse the engineered tissue. The results indicate that engineered microvasculature can be aligned via cell-induced gel compaction and that this compaction improves lumen density. Interstitial flow provided an additional increase in lumen density. A mathematical model of fluid flow through engineered microvessels and a variety of image analysis methods were also developed

Expression and regulation of monocyte chemoattractant protein-3 (MCP-3) in fibrosis

Systemic sclerosis is a multisystem connective tissue disease characterised by skin thickening and widespread, but variable, visceral fibrosis. The aetiopathogenesis is likely to involve immunological activation and microvascular dysfunction leading to excessive accumulation of extracellular matrix (ECM) with increased production of collagen type I in lesional tissues. This implies a dysregulated repair process probably as a consequence of aberrant crosstalk between fibroblasts and inflammatory cells. It has been proposed that a hierarchical cascade of soluble mediators in which initial induction of proinflammatory cytokines expressed by the inflammatory infiltrate may lead to expression of profibrotic mediators including TGFβ. A salient feature of the inflammatory response is directional migration of leucocytes into subendothelial tissues orchestrated by chemokines in a spatially and temporally-regulated multistep process. Work described in this thesis explores the expression of chemokine, monocyte chemoattractant protein-3 (MCP-3/CCL7) in SSc and in murine models for SSc: type 1 tight skin mouse (Tsk1) and a transgenic mouse strain (TβRIIΔk) in which there is fibroblast-directed disruption of TGFβ signalling. The hypothesis that crosstalk between MCP-3 and TGFβ may modulate the signalling response in the fibrotic microenvironment was also explored. Overexpression of MCP-3 was demonstrated on cDNA expression profiling and protein analysis of neonatal Tsk1 and TβRIIΔk fibroblasts. This was supported by immunohistochemical studies on dermal tissues. Similar upregulation dermal patterns of MCP-3 protein expression were observed in the early stage of diffuse cutaneous SSc. Activation of collagen reporter genes by MCP-3 in transgenic mouse fibroblasts and wildtype neonatal mouse fibroblasts harbouring proα2(Ι)collagen promoter reporter gene constructs is mediated via sequences within the proximal promoter and is partly dependent on TGFβ. This coinduction between the two factors in the fibrotic response is also demonstrated by activation of TGFβ signalling pathways by MCP-3 leading to type I collagen secretion. In addition, MCP-3 gene expression is stimulated by TGFβ. Comparison of downstream signalling pathways that regulate collagen gene activation by both cytokines confirms the central role of MAPK pathway activation in mediating the effects of both factors. An additive effect of these two agonists was demonstrated for key TGFβ-regulated genes on comparative microarray analysis. Overall, these results demonstrate that overexpression of MCP-3 is a key biochemical feature of early stage SSc and murine models of SSc, and suggest a novel role for this chemokine as a profibrotic mediator in addition to its role in regulating leucocyte recruitment. Furthermore, there is a potentially important interplay between MCP-3 and TGFβ in modulation of the signalling response in the fibrotic microenvironment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Hemodynamic responses following dynamic resistance exercise in young and older adult women

This investigation examined the effects of age, exercise and test condition on hemodynamic variables, autonomic and vascular function in relation to resistance exercise (RE). The associations among these variables were also examined. METHODS: Sixteen young (21.4+1.4 yrs) and 16 older (69.7+3.9 yrs) women performed 5- and 15- repetition maximal (RM) of knee extension RE. Continuous blood pressure (BP) and electrocardiography (ECG) data were recorded. The dependent variables are reported at pre-exercise, peak exercise and recovery period. Heart rate variability data were derived from 5- and 10-min segments before and after exercise. Resting and after arterial occlusion forearm vascular function indices and pre- and post-exercise resting forearm blood flow and forearm vascular resistance (FVR) were measured using plethysmography technique. ANOVA with repeated measures was used for statistical analysis. LSD was used where post hoc comparison required. Pearson correlation and linear regression were used to examine associations between autonomic and vascular function indices and hemodynamic parameters; alpha=0.05. RESULTS: Resistance exercise resulted in increased BP (SBP=36.6+2.2; DBP=27.4+1.6 mmHg) and HR (37.8+1.6 beat/min). This was followed by a drop in BP below pre-exercise level throughout the recovery period up to 60 minutes. The 15-RM condition resulted in higher SBP at peak exercise (15-RM: 155.7+3.7 vs. 5-RM: 142.3+3.7 mmHg) and in the early phase of recovery (local min: 15-RM=127.0+2.7 vs. 5-RM=120.4+2.6 mmHg); however, the 5-RM condition resulted in greater 1-min and 3-min post-exercise SBP recovery ratios (15-RM: 1-min=0.78+0.01; 3-min=0.76+0.01 vs. 5-RM: 1-min=0.84+0.01; 3-min=0.82+0.01). Older women had higher SBP throughout the testing period, and higher 1-min and 3-min recovery ratios (Young: 1-min=0.80+0.01; 3-min=0.78+0.01 vs. Old: 1-min=0.83+0.01; 3-min=0.80+0.01). However, the older women experienced greater drops in BP (SBP: young=-0.02+2.6 vs. old=-9.4+2.3; DBP: young=-3.5+1.8 vs. old=-9.8+1.9 mmHg) during the recovery period. FVR after RE increased above pre-exercise only in the young (p\u3c0.03). Low-frequency variations in HR were related to recovery of mean arterial pressure (young: r=0.66, p\u3c0.001; older: r=0.79; p\u3c0.001) and FVR (young: r=0.93, p=0.001; old: r=0.95; p\u3c0.001). CONCUSION: Age-group differences in post-exercise BP drop, characterized by a greater decline in BP in older adults, might be attributed to smaller increases in vascular resistance in older women

Investigating the pathological mechanism of neuropathy in POEMS syndrome

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin disorder) is a rare disease characterised by an inflammatory polyneuropathy an a monoclonal plasma cell dyscrasia. POEMS syndrome causes some of the most significant disability and mortality of any inflammatory neuropathy. The pathophysiology is unknown but recognised to be cytokine mediated, notably driven by vascular endothelial growth factor, however little is known about the other mediators at play. This thesis collates clinical data from the largest POEMS cohorti in Europe in order to study the characteristic disease features, optimise therapies and identify factors that influence outcome. Utilising our POEMS sample biobank, we carry out highly sensitive immunoassays to study the cytokines released in POEMS syndrome, and whether they correlate with disease activity. We go on to study the proteome of POEMS syndrome through mass spectrometry, to uncover the biological pathway involved and identify a number of novel, potentially pathogenic molecules. Fluid biomarkers of neuropathy in POEMS syndrome and related neuropathies are additionally explored. The development and optimisation of a homebrew immunoassay for peripherin, a peripheral nerve specific biomarker is detailed. The potential clinical utility of this biomarker is compared against that of serum neurofilament light. Finally, we attempt to model the neuropathogenesis of POEMS neuropathy in vitro using a novel human induced pleuripotent stem cell derived neuronal culture system

The association between macular pigment optical density and glare recovery time with selected macular degeneration and ocular vascular perfusion risk factors

Age-related macular degeneration (AMD) is the most common cause of severe visual impairment affecting older adults in the developed world. The pathogenesis of AMD is not fully understood. This study sought to investigate the association between macular pigment optical density (MPOD) and glare recovery time (GRT) with a selection of other confirmed and putative AMD risk factors (RF): age, gender, body mass index (BMI), calculated percentage body fat (%BF), iris colour, family history (FH) of AMD, and ocular vascular perfusion (OVP) RF: migraine, Raynaud's phenomenon (Rph) and vascular dysregulation (VDys). Interocular comparison was assessed for MPOD and GRT. The effect of ocular dominance on MPOD and GRT, and GRT repeatability was also examined. The use of GRT as a surrogate measure for MPOD was assessed. In this healthy, mixed-gender, White population no significant association was found between MPOD measured by heterochromatic flicker photometry (HFP) at 0.5° eccentricity and any AMD or OVP RF assessed by this study. No significant interocular difference in MPOD was found. No significant association was found between MPOD and ocular dominance. GRT after 30-second duration bleach using the direct ophthalmoscope was significantly and positively associated with age. No significant association was found for any other AMD or OVP RF examined, after correction for age. No significant interocular difference was found. No significant association was found with ocular dominance. GRT intra-session repeatability was good and inter-session repeatability was moderate. This method of GRT was not found to be a good surrogate measure for MPOD. This study generated three new theories: the possible association between the OVP RF migraine, Rph and VDys and AMD risk, the Müller cell (Mc) / neuroglial cell hypothesis for macular pigment, and the retinal theory for Meares-Irlen syndrome (MIS) also known as Visual Stress

Outcomes and optimal treatment of patients with Acromegaly

This thesis defines mortality in acromegaly in a modern patient cohort, elucidates underlying explanations for the increased mortality and explores the impact of treatment, focussing on somatostatin analogue therapy. Results confirm there remains a 30% increase in mortality in patients with acromegaly. Mortality was increased in patients with GH >2µg/L, but not in patients with raised IGF-I. This is the first study showing reduced survival in patients with acromegaly following pituitary radiotherapy. Somatostatin analogue therapy was shown to be efficacious and safe. I also explored factors influencing pituitary tumourigenesis by characterising mRNA levels for 11β-HSD isozymes in normal and neoplastic pituitary tissue. Results demonstrated reduced 11β-HSDl expression and 10-fold increased 11β-HSD2 expression in pituitary tumours compared with normal pituitary, resulting in reduced active glucocorticoid concentrations within the pituitary. This may diminish the antiproliferative effects of glucocorticoids, thus contributing to the process of pituitary tumourigenesis. Finally, I explored complications of pituitary adenomas by evaluating outcome in patients presenting acutely with pituitary apoplexy. Patients presenting without visual deficit or showing evidence of early improvement in visual deficit can be managed without acute neurosurgical intervention. Results of this research will undoubtedly improve the management and outcome of patients with acromegaly and pituitary tumours.EThOS - Electronic Theses Online ServiceGBUnited Kingdo