Extraction of Prostatic Lumina and Automated Recognition for Prostatic Calculus Image Using PCA-SVM

Identification of prostatic calculi is an important basis for determining the tissue origin. Computation-assistant diagnosis of prostatic calculi may have promising potential but is currently still less studied. We studied the extraction of prostatic lumina and automated recognition for calculus images. Extraction of lumina from prostate histology images was based on local entropy and Otsu threshold recognition using PCA-SVM and based on the texture features of prostatic calculus. The SVM classifier showed an average time 0.1432 second, an average training accuracy of 100%, an average test accuracy of 93.12%, a sensitivity of 87.74%, and a specificity of 94.82%. We concluded that the algorithm, based on texture features and PCA-SVM, can recognize the concentric structure and visualized features easily. Therefore, this method is effective for the automated recognition of prostatic calculi

Automated classification of cancer tissues using multispectral imagery

Automated classification of medical images for colorectal and prostate cancer diagnosis is a crucial tool for improving routine diagnosis decisions. Therefore, in the last few decades, there has been an increasing interest in refining and adapting machine learning algorithms to classify microscopic images of tumour biopsies. Recently, multispectral imagery has received a significant interest from the research community due to the fast-growing development of high-performance computers. This thesis investigates novel algorithms for automatic classification of colorectal and prostate cancer using multispectral imagery in order to propose a system outperforming the state-of-the-art techniques in the field. To achieve this objective, several feature extraction methods based on image texture have been investigated, analysed and evaluated. A novel texture feature for multispectral images is also constructed as an adaptation of the local binary pattern texture feature to multispectral images by expanding the pixels neighbourhood to the spectral dimension. It has the advantage of capturing the multispectral information with a limited feature vector size. This feature has demonstrated improved classification results when compared against traditional texture features. In order to further enhance the systems performance, advanced classification schemes such as bag-of-features - to better capture local information - and stacked generalisation - to select the most discriminative texture features - are explored and evaluated. Finally, the recent years have seen an accelerated and exponential rise of deep learning, boosted by the advances in hardware, and more specifically graphics processing units. Such models have demonstrated excellent results for supervised learning in multiple applications. This observation has motivated the employment in this thesis of deep neural network architectures, namely convolutional neural networks. Experiments were also carried out to evaluate and compare the performance obtained with the features extracted using convolutional neural networks with random initialisation against features extracted with pre-trained models on ImageNet dataset. The analysis of the classication accuracy achieved with deep learning models reveals that the latter outperforms the previously proposed texture extraction methods. In this thesis, the algorithms are assessed using two separate multiclass datasets: the first one consists of prostate tumour multispectral images, and the second contains multispectral images of colorectal tumours. The colorectal dataset was acquired on a wide domain of the light spectrum ranging from the visible to the infrared wavelengths. This dataset was used to demonstrate the improved results produced using infrared light as well as visible light

A robust technique for the detection and quantification of abdominal aortic calcification using dual energy X-Ray absorptiometry

Arterial calcification is a manifestation of atherosclerosis, which over the last two decades has become a recognised predictor of cardiovascular disease. Abdominal Aortic Calcification (AAC) and osteoporosis have been shown to coincide in older individuals. The accepted method of diagnosing osteoporosis is through the measurement of bone mineral density by dual energy x-ray absorptiometry (DXA). Vertebral fracture assessment (VFA) images obtained alongside BMD using DXA technology provide an inexpensive resource for AAC diagnosis. Although several simple methods have been proposed for manual semi-quantitative scoring of AAC in x-ray images in the past, these methods have limitations in terms of capturing small changes in atherosclerosis progression and are time-consuming. Several automatic approaches have been proposed to measure AAC on radiographs. However, these methods have not been related to any accepted medical AAC scoring systems and thus are not likely to be adopted easily by the medical community. In addition, there has been no attempt to apply the proposed methods to VFA images. The main focus of the research presented in this thesis is the automatic quantification of AAC in VFA images acquired in single energy mode. The thesis is divided into two main parts. In the first part, an automatic method for AAC detection and quantification in VFA images is proposed and evaluated on a large number of images. In the second part, the performance of both single and dual energy VFA imaging for the detection of uniformly distributed calcification is investigated. The automatic method for AAC detection consists of two stages. In the first stage an active appearance model was employed for the purpose of segmentaion. In the second stage, adaptive thresholding techniques were used to detect AAC, whilst automatic iii classification techniques were used to quantify the detected calcification. The performance of several classifiers were investigated, and the proposed method was evaluated against the manual AC-24 scoring method using several hundred images and two human readers. A thorough statistical analysis of the results showed that, overall, the SVM classifier gave the best results. Weighted accuracy, sensitivity, specificity assessed for 4 AAC categories were 89.2%, 78.5% and 92.3% respectively while the corresponding values for 3 AAC categories were 88.6%, 86%, 90.4%. In the second part, a study using a tissue-mimicking physical phantom is described. The phantom consists of an aluminium strip within Perspex to simulate calcification and abdominal soft tissue respectively. VFA images of different phantom configurations were acquired in single energy (SE) and dual energy (DE) modes. The minimum detectable aluminium thickness was assessed visually and related to contrast and contrast-to-noise ratio. Percentage coefficient of variation was used to quantify uniformity, repeatability and reproducibility with a Perspex width of 25 cm, the smallest thickness of aluminium that could be detected was 0.20- 0.25 mm. The initial results are promising, and the system proposed in this research can be used as an alternative method to the manual scoring system (AC-24) for a wide range of AAC. The principal conclusion from the phantom work is that under idealised imaging conditions, VFA images have the potential to be used for detecting small thicknesses of calcification with good linearity, repeatability and reproducibility in SE and DE modes for patients with a body width < 30 cm

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p\u3c0.01. Among 218 non-smokers, 130 (59%) were male, 142 (65%) were Caucasian; 60 (28%) reported SHS exposure compared to 158 (72%) with no exposure. Non-smoker adolescents with SHS exposure were compared to those without SHS exposure. There was no racial, age, or gender differences between both groups. Baseline creatinine, diastolic hypertension, C reactive protein, lipid profile, GFR and hemoglobin were not statistically different. Significantly higher protein to creatinine ratio (0.90 vs. 0.53, p\u3c0.01) was observed in those exposed to SHS compared to those not exposed. Exposed adolescents were heavier than non-exposed adolescents (85th percentile vs. 55th percentile for BMI, p\u3c 0.01). Uncontrolled casual systolic hypertension was twice as prevalent among those exposed to SHS (16%) compared to those not exposed to SHS (7%), though the difference was not statistically significant (p= 0.07). Adjusted multivariate regression analysis [OR (95% CI)] showed that increased protein to creatinine ratio [1.34 (1.03, 1.75)] and higher BMI [1.14 (1.02, 1.29)] were independently associated with exposure to SHS among non-smoker adolescents. These results reveal that among adolescents with CKD, cigarette use is low and SHS is highly prevalent. The association of smoking with hypertension and SHS with increased proteinuria suggests a possible role of these factors in CKD progression and cardiovascular outcomes