99 research outputs found

    Cerebrovascular dysfunction in cerebral small vessel disease

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    INTRODUCTION: Cerebral small vessel disease (SVD) is the cause of a quarter of all ischaemic strokes and is postulated to have a role in up to half of all dementias. SVD pathophysiology remains unclear but cerebrovascular dysfunction may be important. If confirmed many licensed medications have mechanisms of action targeting vascular function, potentially enabling new treatments via drug repurposing. Knowledge is limited however, as most studies assessing cerebrovascular dysfunction are small, single centre, single imaging modality studies due to the complexities in measuring cerebrovascular dysfunctions in humans. This thesis describes the development and application of imaging techniques measuring several cerebrovascular dysfunctions to investigate SVD pathophysiology and trial medications that may improve small blood vessel function in SVD. METHODS: Participants with minor ischaemic strokes were recruited to a series of studies utilising advanced MRI techniques to measure cerebrovascular dysfunction. Specifically MRI scans measured the ability of different tissues in the brain to change blood flow in response to breathing carbon dioxide (cerebrovascular reactivity; CVR) and the flow and pulsatility through the cerebral arteries, venous sinuses and CSF spaces. A single centre observational study optimised and established feasibility of the techniques and tested associations of cerebrovascular dysfunctions with clinical and imaging phenotypes. Then a randomised pilot clinical trial tested two medications’ (cilostazol and isosorbide mononitrate) ability to improve CVR and pulsatility over a period of eight weeks. The techniques were then expanded to include imaging of blood brain barrier permeability and utilised in multi-centre studies investigating cerebrovascular dysfunction in both sporadic and monogenetic SVDs. RESULTS: Imaging protocols were feasible, consistently being completed with usable data in over 85% of participants. After correcting for the effects of age, sex and systolic blood pressure, lower CVR was associated with higher white matter hyperintensity volume, Fazekas score and perivascular space counts. Lower CVR was associated with higher pulsatility of blood flow in the superior sagittal sinus and lower CSF flow stroke volume at the foramen magnum. Cilostazol and isosorbide mononitrate increased CVR in white matter. The CVR, intra-cranial flow and pulsatility techniques, alongside blood brain barrier permeability and microstructural integrity imaging were successfully employed in a multi-centre observational study. A clinical trial assessing the effects of drugs targeting blood pressure variability is nearing completion. DISCUSSION: Cerebrovascular dysfunction in SVD has been confirmed and may play a more direct role in disease pathogenesis than previously established risk factors. Advanced imaging measures assessing cerebrovascular dysfunction are feasible in multi-centre studies and trials. Identifying drugs that improve cerebrovascular dysfunction using these techniques may be useful in selecting candidates for definitive clinical trials which require large sample sizes and long follow up periods to show improvement against outcomes of stroke and dementia incidence and cognitive function

    A Review on Brain Tumor Segmentation Based on Deep Learning Methods with Federated Learning Techniques

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    Brain tumors have become a severe medical complication in recent years due to their high fatality rate. Radiologists segment the tumor manually, which is time-consuming, error-prone, and expensive. In recent years, automated segmentation based on deep learning has demonstrated promising results in solving computer vision problems such as image classification and segmentation. Brain tumor segmentation has recently become a prevalent task in medical imaging to determine the tumor location, size, and shape using automated methods. Many researchers have worked on various machine and deep learning approaches to determine the most optimal solution using the convolutional methodology. In this review paper, we discuss the most effective segmentation techniques based on the datasets that are widely used and publicly available. We also proposed a survey of federated learning methodologies to enhance global segmentation performance and ensure privacy. A comprehensive literature review is suggested after studying more than 100 papers to generalize the most recent techniques in segmentation and multi-modality information. Finally, we concentrated on unsolved problems in brain tumor segmentation and a client-based federated model training strategy. Based on this review, future researchers will understand the optimal solution path to solve these issues

    Machine Learning and Quantitative Imaging for the Management of Brain Metastasis

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    Significantly affecting patients’ clinical course and quality of life, a growing number of cancer cases are diagnosed with brain metastasis annually. Although a considerable percentage of cancer patients survive for several years if the disease is discovered at an early stage while it is still localized, when the tumour is metastasized to the brain, the median survival decreases considerably. Early detection followed by precise and effective treatment of brain metastasis may lead to improved patient survival and quality of life. A main challenge to prescribe an effective treatment regimen is the variability of tumour response to treatments, e.g., radiotherapy as a main treatment option for brain metastasis, despite similar cancer therapy, due to many patient-related factors. Stratifying patients based on their predicted response and consequently assessing their response to therapy are challenging yet crucial tasks. While risk assessment models with standard clinical attributes have been proposed for patient stratification, the imaging data acquired for these patients as a part of the standard-of-care are not computationally analyzed or directly incorporated in these models. Further, therapy response monitoring and assessment is a cumbersome task for patients with brain metastasis that requires longitudinal tumour delineation on MRI volumes before and at multiple follow-up sessions after treatment. This is aggravated by the time-sensitive nature of the disease. In an effort to address these challenges, a number of machine learning frameworks and computational techniques in areas of automatic tumour segmentation, radiotherapy outcome assessment, and therapy outcome prediction have been introduced and investigated in this dissertation. Powered by advanced machine learning algorithms, a complex attention-guided segmentation framework is introduced and investigated for segmenting brain tumours on serial MRI. The experimental results demonstrate that the proposed framework can achieve a dice score of 91.5% and 84.1% to 87.4% on the baseline and follow-up scans, respectively. This framework is then applied in a proposed system that follows standard clinical criteria based on changes in tumour size at post-treatment to assess tumour response to radiotherapy automatically. The system demonstrates a very good agreement with expert clinicians in detecting local response, with an accuracy of over 90%. Next, innovative machine-learning-based solutions are proposed and investigated for radiotherapy outcome prediction before or early after therapy, using MRI radiomic models and novel deep learning architectures that analyze treatment-planning MRI with and without standard clinical attributes. The developed models demonstrate an accuracy of up to 82.5% in predicting radiotherapy outcome before the treatment initiation. The ground-breaking machine learning platforms presented in this dissertation along with the promising results obtained in the conducted experiments are steps forward towards realizing important decision support tools for oncologists and radiologists and, can eventually, pave the way towards the personalized therapeutics paradigm for cancer patient

    Medical Image Segmentation: Thresholding and Minimum Spanning Trees

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    I bildesegmentering deles et bilde i separate objekter eller regioner. Det er et essensielt skritt i bildebehandling for Ä definere interesseomrÄder for videre behandling eller analyse. Oppdelingsprosessen reduserer kompleksiteten til et bilde for Ä forenkle analysen av attributtene oppnÄdd etter segmentering. Det forandrer representasjonen av informasjonen i det opprinnelige bildet og presenterer pikslene pÄ en mÄte som er mer meningsfull og lettere Ä forstÄ. Bildesegmentering har forskjellige anvendelser. For medisinske bilder tar segmenteringsprosessen sikte pÄ Ä trekke ut bildedatasettet for Ä identifisere omrÄder av anatomien som er relevante for en bestemt studie eller diagnose av pasienten. For eksempel kan man lokalisere berÞrte eller anormale deler av kroppen. Segmentering av oppfÞlgingsdata og baseline lesjonssegmentering er ogsÄ svÊrt viktig for Ä vurdere behandlingsresponsen. Det er forskjellige metoder som blir brukt for bildesegmentering. De kan klassifiseres basert pÄ hvordan de er formulert og hvordan segmenteringsprosessen utfÞres. Metodene inkluderer de som er baserte pÄ terskelverdier, graf-baserte, kant-baserte, klynge-baserte, modell-baserte og hybride metoder, og metoder basert pÄ maskinlÊring og dyp lÊring. Andre metoder er baserte pÄ Ä utvide, splitte og legge sammen regioner, Ä finne diskontinuiteter i randen, vannskille segmentering, aktive kontuter og graf-baserte metoder. I denne avhandlingen har vi utviklet metoder for Ä segmentere forskjellige typer medisinske bilder. Vi testet metodene pÄ datasett for hvite blodceller (WBCs) og magnetiske resonansbilder (MRI). De utviklede metodene og analysen som er utfÞrt pÄ bildedatasettet er presentert i tre artikler. I artikkel A (Paper A) foreslo vi en metode for segmentering av nukleuser og cytoplasma fra hvite blodceller. Metodene estimerer terskelen for segmentering av nukleuser automatisk basert pÄ lokale minima. Metoden segmenterer WBC-ene fÞr segmentering av cytoplasma avhengig av kompleksiteten til objektene i bildet. For bilder der WBC-ene er godt skilt fra rÞde blodlegemer (RBC), er WBC-ene segmentert ved Ä ta gjennomsnittet av nn bilder som allerede var filtrert med en terskelverdi. For bilder der RBC-er overlapper WBC-ene, er hele WBC-ene segmentert ved hjelp av enkle lineÊre iterative klynger (SLIC) og vannskillemetoder. Cytoplasmaet oppnÄs ved Ä trekke den segmenterte nukleusen fra den segmenterte WBC-en. Metoden testes pÄ to forskjellige offentlig tilgjengelige datasett, og resultatene sammenlignes med toppmoderne metoder. I artikkel B (Paper B) foreslo vi en metode for segmentering av hjernesvulster basert pÄ minste dekkende tre-konsepter (minimum spanning tree, MST). Metoden utfÞrer interaktiv segmentering basert pÄ MST. I denne artikkelen er bildet lastet inn i et interaktivt vindu for segmentering av svulsten. Fokusregion og bakgrunn skilles ved Ä klikke for Ä dele MST i to trÊr. Ett av disse trÊrne representerer fokusregionen og det andre representerer bakgrunnen. Den foreslÄtte metoden ble testet ved Ä segmentere to forskjellige 2D-hjerne T1 vektede magnetisk resonans bildedatasett. Metoden er enkel Ä implementere og resultatene indikerer at den er nÞyaktig og effektiv. I artikkel C (Paper C) foreslÄr vi en metode som behandler et 3D MRI-volum og deler det i hjernen, ikke-hjernevev og bakgrunnsegmenter. Det er en grafbasert metode som bruker MST til Ä skille 3D MRI inn i de tre regiontypene. Grafen lages av et forhÄndsbehandlet 3D MRI-volum etterfulgt av konstrueringen av MST-en. Segmenteringsprosessen gir tre merkede, sammenkoblende komponenter som omformes tilbake til 3D MRI-form. Etikettene brukes til Ä segmentere hjernen, ikke-hjernevev og bakgrunn. Metoden ble testet pÄ tre forskjellige offentlig tilgjengelige datasett og resultatene ble sammenlignet med ulike toppmoderne metoder.In image segmentation, an image is divided into separate objects or regions. It is an essential step in image processing to define areas of interest for further processing or analysis. The segmentation process reduces the complexity of an image to simplify the analysis of the attributes obtained after segmentation. It changes the representation of the information in the original image and presents the pixels in a way that is more meaningful and easier to understand. Image segmentation has various applications. For medical images, the segmentation process aims to extract the image data set to identify areas of the anatomy relevant to a particular study or diagnosis of the patient. For example, one can locate affected or abnormal parts of the body. Segmentation of follow-up data and baseline lesion segmentation is also very important to assess the treatment response. There are different methods used for image segmentation. They can be classified based on how they are formulated and how the segmentation process is performed. The methods include those based on threshold values, edge-based, cluster-based, model-based and hybrid methods, and methods based on machine learning and deep learning. Other methods are based on growing, splitting and merging regions, finding discontinuities in the edge, watershed segmentation, active contours and graph-based methods. In this thesis, we have developed methods for segmenting different types of medical images. We tested the methods on datasets for white blood cells (WBCs) and magnetic resonance images (MRI). The developed methods and the analysis performed on the image data set are presented in three articles. In Paper A we proposed a method for segmenting nuclei and cytoplasm from white blood cells. The method estimates the threshold for segmentation of nuclei automatically based on local minima. The method segments the WBCs before segmenting the cytoplasm depending on the complexity of the objects in the image. For images where the WBCs are well separated from red blood cells (RBCs), the WBCs are segmented by taking the average of nn images that were already filtered with a threshold value. For images where RBCs overlap the WBCs, the entire WBCs are segmented using simple linear iterative clustering (SLIC) and watershed methods. The cytoplasm is obtained by subtracting the segmented nucleus from the segmented WBC. The method is tested on two different publicly available datasets, and the results are compared with state of the art methods. In Paper B, we proposed a method for segmenting brain tumors based on minimum spanning tree (MST) concepts. The method performs interactive segmentation based on the MST. In this paper, the image is loaded in an interactive window for segmenting the tumor. The region of interest and the background are selected by clicking to split the MST into two trees. One of these trees represents the region of interest and the other represents the background. The proposed method was tested by segmenting two different 2D brain T1-weighted magnetic resonance image data sets. The method is simple to implement and the results indicate that it is accurate and efficient. In Paper C, we propose a method that processes a 3D MRI volume and partitions it into brain, non-brain tissues, and background segments. It is a graph-based method that uses MST to separate the 3D MRI into the brain, non-brain, and background regions. The graph is made from a preprocessed 3D MRI volume followed by constructing the MST. The segmentation process produces three labeled connected components which are reshaped back to the shape of the 3D MRI. The labels are used to segment the brain, non-brain tissues, and the background. The method was tested on three different publicly available data sets and the results were compared to different state of the art methods.Doktorgradsavhandlin

    Brainlesion: Glioma, Multiple Sclerosis, Stroke and Traumatic Brain Injuries

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    This two-volume set LNCS 12962 and 12963 constitutes the thoroughly refereed proceedings of the 7th International MICCAI Brainlesion Workshop, BrainLes 2021, as well as the RSNA-ASNR-MICCAI Brain Tumor Segmentation (BraTS) Challenge, the Federated Tumor Segmentation (FeTS) Challenge, the Cross-Modality Domain Adaptation (CrossMoDA) Challenge, and the challenge on Quantification of Uncertainties in Biomedical Image Quantification (QUBIQ). These were held jointly at the 23rd Medical Image Computing for Computer Assisted Intervention Conference, MICCAI 2020, in September 2021. The 91 revised papers presented in these volumes were selected form 151 submissions. Due to COVID-19 pandemic the conference was held virtually. This is an open access book

    Need for speed:Achieving fast image processing in acute stroke care

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    This thesis aims to investigate the use of high-performance computing (HPC) techniques in developing imaging biomarkers to support the clinical workflow of acute stroke patients. In the first part of this thesis, we evaluate different HPC technologies and how such technologies can be leveraged by different image analysis applications used in the context of acute stroke care. More specifically, we evaluated how computers with multiple computing devices can be used to accelerate medical imaging applications in Chapter 2. Chapter 3 proposes a novel data compression technique that efficiently processes CT perfusion (CTP) images in GPUs. Unfortunately, the size of CTP datasets makes data transfers to computing devices time-consuming and, therefore, unsuitable in acute situations. Chapter 4 further evaluates the algorithm's usefulness proposed in Chapter 3 with two different applications: a double threshold segmentation and a time-intensity profile similarity (TIPS) bilateral filter to reduce noise in CTP scans. Finally, Chapter 5 presents a cloud platform for deploying high-performance medical applications for acute stroke patients. In Part 2 of this thesis, Chapter 6 presents a convolutional neural network (CNN) for detecting and volumetric segmentation of subarachnoid hemorrhages (SAH) in non-contrast CT scans. Chapter 7 proposed another method based on CNNs to quantify the final infarct volumes in follow-up non-contrast CT scans from ischemic stroke patients

    False memory and delusions in Alzheimer's disease

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    Aims: This thesis aimed to investigate the relationship between memory errors and delusions in Alzheimer’s disease (AD), in order to further elucidate the mechanisms underlying delusion formation. This was achieved by undertaking narrative and systematic review of relevant literature, by exploring the relationship between performance on memory and metamemory tasks and delusions in AD patient populations and by investigating the neuroanatomical correlates of memory errors and delusions in AD patient populations. // Methods: I recruited 27 participants with and without delusions in AD and compared performance on measures of context memory, false memory and metamemory. I explored statistically significant behavioural findings further in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort of participants with AD (n = 733). I then conducted hypothesis-driven region of interest and exploratory voxel-based morphometric analyses to determine the relationship between false memory and delusions and regional brain volume in the ADNI cohort. This informed similar analyses of neuroimaging data in my own participants (n = 8). // Results: In both samples, individuals with delusions in AD had higher false recognition rates on recognition memory tasks than those without delusions. False recognition was inversely correlated with volume of medial temporal lobe, ventral visual stream and prefrontal cortex in both samples. In the ADNI sample, false recognition was also inversely correlated with anterior cingulate cortex (ACC) volume bilaterally. Participants with delusions had reduced volume of right ACC and increased volume of right parahippocampal gyrus compared to the control group. // Conclusions: These two complementary studies provide evidence of specific memory impairments associated with both delusions and a distinct pattern of brain atrophy in AD. Simple cognitive interventions can reduce false recognition rates in AD. Given the significant risks associated with antipsychotic drug treatment of delusions, exploring how these non-pharmacological interventions potentially affect psychosis symptoms in AD is an important next step

    The Role of Transient Vibration of the Skull on Concussion

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    Concussion is a traumatic brain injury usually caused by a direct or indirect blow to the head that affects brain function. The maximum mechanical impedance of the brain tissue occurs at 450±50 Hz and may be affected by the skull resonant frequencies. After an impact to the head, vibration resonance of the skull damages the underlying cortex. The skull deforms and vibrates, like a bell for 3 to 5 milliseconds, bruising the cortex. Furthermore, the deceleration forces the frontal and temporal cortex against the skull, eliminating a layer of cerebrospinal fluid. When the skull vibrates, the force spreads directly to the cortex, with no layer of cerebrospinal fluid to reflect the wave or cushion its force. To date, there is few researches investigating the effect of transient vibration of the skull. Therefore, the overall goal of the proposed research is to gain better understanding of the role of transient vibration of the skull on concussion. This goal will be achieved by addressing three research objectives. First, a MRI skull and brain segmentation automatic technique is developed. Due to bones’ weak magnetic resonance signal, MRI scans struggle with differentiating bone tissue from other structures. One of the most important components for a successful segmentation is high-quality ground truth labels. Therefore, we introduce a deep learning framework for skull segmentation purpose where the ground truth labels are created from CT imaging using the standard tessellation language (STL). Furthermore, the brain region will be important for a future work, thus, we explore a new initialization concept of the convolutional neural network (CNN) by orthogonal moments to improve brain segmentation in MRI. Second, the creation of a novel 2D and 3D Automatic Method to Align the Facial Skeleton is introduced. An important aspect for further impact analysis is the ability to precisely simulate the same point of impact on multiple bone models. To perform this task, the skull must be precisely aligned in all anatomical planes. Therefore, we introduce a 2D/3D technique to align the facial skeleton that was initially developed for automatically calculating the craniofacial symmetry midline. In the 2D version, the entire concept of using cephalometric landmarks and manual image grid alignment to construct the training dataset was introduced. Then, this concept was extended to a 3D version where coronal and transverse planes are aligned using CNN approach. As the alignment in the sagittal plane is still undefined, a new alignment based on these techniques will be created to align the sagittal plane using Frankfort plane as a framework. Finally, the resonant frequencies of multiple skulls are assessed to determine how the skull resonant frequency vibrations propagate into the brain tissue. After applying material properties and mesh to the skull, modal analysis is performed to assess the skull natural frequencies. Finally, theories will be raised regarding the relation between the skull geometry, such as shape and thickness, and vibration with brain tissue injury, which may result in concussive injury
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