Advancing Pancreas Segmentation in Multi-protocol MRI Volumes using Hausdorff-Sine Loss Function

Computing pancreatic morphology in 3D radiological scans could provide significant insight about a medical condition. However, segmenting the pancreas in magnetic resonance imaging (MRI) remains challenging due to high inter-patient variability. Also, the resolution and speed of MRI scanning present artefacts that blur the pancreas bound- aries between overlapping anatomical structures. This paper proposes a dual-stage automatic segmentation method: 1) a deep neural network is trained to address the problem of vague organ boundaries in high class-imbalanced data. This network integrates a novel loss function to rigorously optimise boundary delineation using the modified Hausdorff metric and a sinusoidal component; 2) Given a test MRI volume, the output of the trained network predicts a sequence of targeted 2D pan- creas classes that are reconstructed as a volumetric binary mask. An energy-minimisation approach fuses a learned digital contrast model to suppress the intensities of non-pancreas classes, which, combined with the binary volume performs a refined segmentation in 3D while reveal- ing dense boundary detail. Experiments are performed on two diverse MRI datasets containing 180 and 120 scans, in which the proposed ap- proach achieves a mean Dice score of 84.1 ± 4.6% and 85.7 ± 2.3%, respectively. This approach is statistically stable and outperforms state- of-the-art methods on MRI

Automatic Pancreas Segmentation and 3D Reconstruction for Morphological Feature Extraction in Medical Image Analysis

The development of highly accurate, quantitative automatic medical image segmentation techniques, in comparison to manual techniques, remains a constant challenge for medical image analysis. In particular, segmenting the pancreas from an abdominal scan presents additional difficulties: this particular organ has very high anatomical variability, and a full inspection is problematic due to the location of the pancreas behind the stomach. Therefore, accurate, automatic pancreas segmentation can consequently yield quantitative morphological measures such as volume and curvature, supporting biomedical research to establish the severity and progression of a condition, such as type 2 diabetes mellitus. Furthermore, it can also guide subject stratification after diagnosis or before clinical trials, and help shed additional light on detecting early signs of pancreatic cancer. This PhD thesis delivers a novel approach for automatic, accurate quantitative pancreas segmentation in mostly but not exclusively Magnetic Resonance Imaging (MRI), by harnessing the advantages of machine learning and classical image processing in computer vision. The proposed approach is evaluated on two MRI datasets containing 216 and 132 image volumes, achieving a mean Dice similarity coefficient (DSC) of 84:1 4:6% and 85:7 2:3% respectively. In order to demonstrate the universality of the approach, a dataset containing 82 Computer Tomography (CT) image volumes is also evaluated and achieves mean DSC of 83:1 5:3%. The proposed approach delivers a contribution to computer science (computer vision) in medical image analysis, reporting better quantitative pancreas segmentation results in comparison to other state-of-the-art techniques, and also captures detailed pancreas boundaries as verified by two independent experts in radiology and radiography. The contributions’ impact can support the usage of computational methods in biomedical research with a clinical translation; for example, the pancreas volume provides a prognostic biomarker about the severity of type 2 diabetes mellitus. Furthermore, a generalisation of the proposed segmentation approach successfully extends to other anatomical structures, including the kidneys, liver and iliopsoas muscles using different MRI sequences. Thus, the proposed approach can incorporate into the development of a computational tool to support radiological interpretations of MRI scans obtained using different sequences by providing a “second opinion”, help reduce possible misdiagnosis, and consequently, provide enhanced guidance towards targeted treatment planning

Automated Measurement of Pancreatic Fat and Iron Concentration Using Multi-Echo and T1-Weghted MRI Data

We present an automated method for estimation of proton density fat fraction and iron concentration in the pancreas using both structural and quantitative imaging data present in the UK Biobank abdominal MRI acquisition protocol. Our method relies on automatic segmentation of 3D T1-weighted MRI data using a convolutional neural network and extracting the location of the multi-echo slice through the segmented volume. We finally estimate the fat and iron content in the pancreas using the extracted segmentation as a mask on the multi-echo data. Our segmentation model achieves a mean dice similarity coefficient of 0.842±0.071 on unseen data, which is comparable to the current state of the art for 3D segmentation of the pancreas. The proposed method is efficient and robust and enables an enhanced analysis of spatial distribution of proton density fat fraction and iron concentration over the current practice of manually placing regions of interest on often ambiguous multi-echo data

Cultivate Quantitative Magnetic Resonance Imaging Methods to Measure Markers of Health and Translate to Large Scale Cohort Studies

Magnetic Resonance Imaging (MRI) is an indispensable tool in healthcare and research, with a growing demand for its services. The appeal of MRI stems from its non-ionizing radiation nature, ability to generate high-resolution images of internal organs and structures without invasive procedures, and capacity to provide quantitative assessments of tissue properties such as ectopic fat, body composition, and organ volume. All without long term side effects. Nine published papers are submitted which show the cultivation of quantitative measures of ectopic fat within the liver and pancreas using MRI, and the process of validating whole-body composition and organ volume measurements. All these techniques have been translated into large-scale studies to improve health measurements in large population cohorts. Translating this work into large-scale studies, including the use of artificial intelligence, is included. Additionally, an evaluation accompanies these published studies, appraising the evolution of these quantitative MRI techniques from the conception to their application in large cohort studies. Finally, this appraisal provides a summary of future work on crowdsourcing of ground truth training data to facilitate its use in wider applications of artificial intelligence.In conclusion, this body of work presents a portfolio of evidence to fulfil the requirements of a PhD by published works at the University of Salford

Eigenloss: Combined PCA-Based Loss Function for Polyp Segmentation

Colorectal cancer is one of the leading cancer death causes worldwide, but its early diagnosis highly improves the survival rates. The success of deep learning has also benefited this clinical field. When training a deep learning model, it is optimized based on the selected loss function. In this work, we consider two networks (U-Net and LinkNet) and two backbones (VGG-16 and Densnet121). We analyzed the influence of seven loss functions and used a principal component analysis (PCA) to determine whether the PCA-based decomposition allows for the defining of the coefficients of a non-redundant primal loss function that can outperform the individual loss functions and different linear combinations. The eigenloss is defined as a linear combination of the individual losses using the elements of the eigenvector as coefficients. Empirical results show that the proposed eigenloss improves the general performance of individual loss functions and outperforms other linear combinations when Linknet is used, showing potential for its application in polyp segmentation problems

Quantitative Magnetic Resonance Imaging Techniques for the Measurement of Organ Fat and Body Composition - Validation and Initial Clinical Utility

Ectopic fat is defined by excess deposition of triglycerides in non-adipose tissues that normally contain only small amounts of fat. Measuring the distribution of ectopic fat is important for understanding the pathogenesis of diseases such as obesity and type 2 diabetes mellitus (T2DM) and understanding variation in treatment response amongst patients. Body composition (the proportion of fat and lean mass in the body) is thought to influence both the development of T2DM and outcomes for treatments such as weight-loss surgery. It can also affect clinical outcomes in chronic diseases and malignancy. Quantitative magnetic resonance imaging (qMRI) enables objective measurements of tissue characteristics to be made directly from acquired data. In this thesis, a qMRI protocol based on chemical shift-encoded (CSE)-MRI, specifically the derived proton density fat fraction (PDFF) measurements, was validated against phantoms, and in volunteers and patients with obesity. A new, semi-automated tool for measurement of body composition from CSE-MRI images was developed and validated. CSE-MRI was used to quantify ectopic organ fat depots and body composition in diseases including obesity, T2DM and cancer. Specifically, differences in organ fat between patients with and without remission of T2DM after bariatric surgery was explored. Body composition was investigated in T2DM remission and it was also compared between patients with colorectal and lung cancer undergoing whole body MRI staging. Data from the pilot phase of a study investigating a new duodenal surfacing procedural treatment for T2DM (Revita-2) is presented, demonstrating the utility of hepatic fat content measured using PDFF as an endpoint in an international, multi-centre clinical trial. Finally, I describe the development of a novel technique for quantification of bone mineral density (BMD) using CSE-MRI techniques. The methodology and tools described in this thesis could be used to measure ectopic fat and body composition in future studies and have the potential for integration into clinical care pathways

[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)

Life Sciences Program Tasks and Bibliography for FY 1997

This document includes information on all peer reviewed projects funded by the Office of Life and Microgravity Sciences and Applications, Life Sciences Division during fiscal year 1997. This document will be published annually and made available to scientists in the space life sciences field both as a hard copy and as an interactive internet web page

NOTIFICATION !!!

All the content of this special edition is retrieved from the conference proceedings published by the European Scientific Institute, ESI. http://eujournal.org/index.php/esj/pages/view/books The European Scientific Journal, ESJ, after approval from the publisher re publishes the papers in a Special edition