DEEPMIR: A DEEP neural network for differential detection of cerebral Microbleeds and IRon deposits in MRI

Lobar cerebral microbleeds (CMBs) and localized non-hemorrhage iron deposits in the basal ganglia have been associated with brain aging, vascular disease and neurodegenerative disorders. Particularly, CMBs are small lesions and require multiple neuroimaging modalities for accurate detection. Quantitative susceptibility mapping (QSM) derived from in vivo magnetic resonance imaging (MRI) is necessary to differentiate between iron content and mineralization. We set out to develop a deep learning-based segmentation method suitable for segmenting both CMBs and iron deposits. We included a convenience sample of 24 participants from the MESA cohort and used T2-weighted images, susceptibility weighted imaging (SWI), and QSM to segment the two types of lesions. We developed a protocol for simultaneous manual annotation of CMBs and non-hemorrhage iron deposits in the basal ganglia. This manual annotation was then used to train a deep convolution neural network (CNN). Specifically, we adapted the U-Net model with a higher number of resolution layers to be able to detect small lesions such as CMBs from standard resolution MRI. We tested different combinations of the three modalities to determine the most informative data sources for the detection tasks. In the detection of CMBs using single class and multiclass models, we achieved an average sensitivity and precision of between 0.84-0.88 and 0.40-0.59, respectively. The same framework detected non-hemorrhage iron deposits with an average sensitivity and precision of about 0.75-0.81 and 0.62-0.75, respectively. Our results showed that deep learning could automate the detection of small vessel disease lesions and including multimodal MR data (particularly QSM) can improve the detection of CMB and non-hemorrhage iron deposits with sensitivity and precision that is compatible with use in large-scale research studies

Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration: A united approach

Item does not contain fulltextCerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE)

Assessment of Post-Treatment Imaging Changes Following Radiotherapy using Magnetic Susceptibility Techniques

Radiation therapy (RT) is a common treatment for brain neoplasms and is used alone or in combination with other therapies. The use of RT has been found to be successful in controlling tumors and extending the overall survival of patients; however, there are many unanswered questions regarding radiotherapy effects in the normal brain surrounding or infiltrated by tumor. Changes to the vascular and parenchyma have been documented, and more recently inflammatory mechanisms have been postulated to play a role in radiation injury. Traditional imaging techniques used within the clinic (CT and MRI) are often lacking in their ability to differentiate between recurrent tumor, transient treatment effects, or radiation necrosis. The primary goal of this thesis is to demonstrate an MRI acquisition method that has been shown to be sensitive to deoxygenated blood and iron content as a potential biomarker of radiation effect on the normal brain. Specifically, post-processing techniques are used to determine the applicability of qualitative images such as Susceptibility-Weighted Imaging (SWI) and quantitative methods such as Quantitative Susceptibility Mapping (QSM) and apparent traverse relaxation (R2*) using the same sequence. These methods are potential surrogate markers for vascular changes and neuroinflammatory components that could predict sub-acute and long-term radiation effects. Within this thesis, R2* is shown to be a promising marker for the prediction of radiation necrosis, whereas SWI and QSM are shown to be excellent modalities for detecting longterm effects such as microbleeds. Additionally, R2 * is shown to be a potentially useful technique in identifying post-imaging treatment changes (pseudoprogression) following chemoradiotherapy for malignant glioma. Finally, the use of this non-contrast method shows promise for integration within a clinical setting and the potential for expansion to multicenter clinical trials

Development of Deep Learning Methods for Magnetic Resonance Phase Imaging of Neurological Disease

Magnetic resonance imaging (MRI) is a high-resolution, non-invasive medical imaging modality that is widely used in human brain. In recent years, susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM) have been proposed to utilize MR phase signal to generate contrast from tissue magnetic susceptibility and even quantify the property. On the other hand, deep learning, especially deep convolutional neural networks (DCNNs), have achieved state-of-the-art performances in numerous computer vision tasks and gained significant attention in the field of medical imaging in the recent years. This dissertation combined the idea of deep learning with the two MR phase imaging methods. To combined deep learning with SWI, we designed and trained a 3D deep residual network that can distinguish false positive detected candidates from cerebral microbleeds (CMBs) and built an automatic CMB detection pipeline with high performance. We further confirmed the generalizability of this deep learning-based pipeline using multiple dataset with different scan parameters and pathologies and provided lessons for application and generalization of generic deep learning based medical imaging methods.To combine deep learning with QSM, we developed a 3D U-Net based network that learns to perform dipole inversion from gold standard QSM acquired from data with multiple orientation. The model was further improved with adversarial training strategy and achieved significantly lower reconstruction error than traditional QSM algorithms. In addition, we also performed various background removal and dipole inversion algorithms on both brain tumor patients and healthy volunteers to study and compare their performances. The results could provide guidance on future application of QSM in different scenarios

A finite element model of cerebral vascular injury for predicting microbleeds location

Finite Element (FE) models of brain mechanics have improved our understanding of the brain response to rapid mechanical loads that produce traumatic brain injuries. However, these models have rarely incorporated vasculature, which limits their ability to predict the response of vessels to head impacts. To address this shortcoming, here we used high-resolution MRI scans to map the venous system anatomy at a submillimetre resolution. We then used this map to develop an FE model of veins and incorporated it in an anatomically detailed FE model of the brain. The model prediction of brain displacement at different locations was compared to controlled experiments on post-mortem human subject heads, yielding over 3,100 displacement curve comparisons, which showed fair to excellent correlation between them. We then used the model to predict the distribution of axial strains and strain rates in the veins of a rugby player who had small blood deposits in his white matter, known as microbleeds, after sustaining a head collision. We hypothesised that the distribution of axial strain and strain rate in veins can predict the pattern of microbleeds. We reconstructed the head collision using video footage and multi-body dynamics modelling and used the predicted head accelerations to load the FE model of vascular injury. The model predicted large axial strains in veins where microbleeds were detected. A region of interest analysis using white matter tracts showed that the tract group with microbleeds had 95th percentile peak axial strain and strain rate of 0.197 and 64.9 s−1 respectively, which were significantly larger than those of the group of tracts without microbleeds (0.163 and 57.0 s−1). This study does not derive a threshold for the onset of microbleeds as it investigated a single case, but it provides evidence for a link between strain and strain rate applied to veins during head impacts and structural damage and allows for future work to generate threshold values. Moreover, our results suggest that the FE model has the potential to be used to predict intracranial vascular injuries after TBI, providing a more objective tool for TBI assessment and improving protection against it

Characterizing and revealing biomarkers on patients with Cerebral Amyloid Angiopathy using artificial intelligence

Dissertação de mestrado em BioinformáticaCerebral Amyloid Angiopathy is a cerebrovascular disorder resulting from the deposition of an amyloidogenic protein in small and medium sized cortical and leptomeningeal vessels. A primary cause of spontaneous intracerebral haemorrhages, it manifests predominantly in the elder population. Although CAA is a common neuropathological finding on itself, it is also known to frequently occur in conjunction with Alzheimer’s disease, being sometimes misdiagnosed. Currently, CAA diagnosis is generally conducted by post-mortem examination or, in live patients by the examination of an evacuated hematoma or brain biopsy samples, which are typically unavailable. Therefore, a reliable and non-invasive method for diagnosing CAA would facilitate the clinical decision making and accelerate the clinical intervention. The main goal of this dissertation is to study the application of Machine Learning (ML) to reveal possible biomarkers to aid the diagnosis and early medical intervention, and better understand the disease. Therefore, three scenarios were tested: Classification of four neurodegenerative diseases with annotation data obtained from visual rating scores, age and gender; Classification of the diseases with radiomic data derived from the patient’s MRI; and a combination of the previous experiments. The results show that the application of Artificial intelligence in the medical field brings advantages to support the physicians in the decision making process and, at some point, make a correct prediction of the disease label. Although the results are satisfactory, there are still improvements to be done. For instance, image segmentation of cerebral lesions or brain regions and additional clinical information of the patients would be of value.Angiopatia Amiloide Cerebral (AAC) é uma doença vascular cerebral resultante da deposição de matéria amiloide. Principal causa de hemorragias cerebral espontâneas, a AAC manifesta se predominantemente na população idosa. Embora a AAC seja uma doença que por si só tem um grande impacto no grupo etário referido, ocorre em simultâneo com inúmeras outras doenças neurodegenerativas, como a doença de Alzheimer. Atualmente, o diagnóstico de AAC realiza-se quer em post-mortem, quer em pacientes vivos. No entanto, o diagnóstico em vida é conseguido por meio de biópsias de tecidos cerebrais, sendo um método invasivo, o que dificulta a intervenção clínica. Deste modo, torna-se imperativa a procura de alternativas fiáveis e não invasivas em vida para auxiliar o diagnóstico da doença e permitir a melhoria da qualidade de vida do paciente. Perante os progressos na área da tecnologia e medicina, esta dissertação propõe o estudo da aplicação de algoritmos de Machine Learning (ML) para revelar possíveis biomarcadores para auxiliar o diagnóstico e permitir uma intervenção precoce. Deste modo, foram testados três cenários distintos: a classificação de quatro doenças neurodegenerativas com dados anotados obtidos a partir de métricas visuais de avaliação da atrofia, idade e sexo; a classificação das doenças com dados gerados a partir de métodos radiómicos; e uma combinação das duas abordagens anteriores. Neste documento apresenta-se e discute-se os resultados obtidos com a aplicação de quatro diferentes algoritmos de ML que visam a deteção automática da doença associada à imagem testada. Adicionalmente, é feita uma análise crítica de quais as características mais relevantes que levaram à tomada de decisão por parte do algoritmo. Os resultados demonstram que através de aplicação de metodologias automáticas é possível o auxílio ao diagnostico médico por especialistas e, no limite, a realização de diagnostico automático com elevada precisão. Finalmente, são apresentadas possíveis alternativas de trabalho futuro para que os resultados possam ser aperfeiçoados, como por exemplo, a segmentação das regiões de interesse, i.e., identificação das lesões, aquando da anotação por especialistas. Mediante a inclusão dessa segmentação, uma vez que será mais especifica, os resultados serão, por sua vez, aprimorados

Automated Detection of Candidate Subjects With Cerebral Microbleeds Using Machine Learning

Cerebral microbleeds (CMBs) appear as small, circular, well defined hypointense lesions of a few mm in size on T2*-weighted gradient recalled echo (T2*-GRE) images and appear enhanced on susceptibility weighted images (SWI). Due to their small size, contrast variations and other mimics (e.g., blood vessels), CMBs are highly challenging to detect automatically. In large datasets (e.g., the UK Biobank dataset), exhaustively labelling CMBs manually is difficult and time consuming. Hence it would be useful to preselect candidate CMB subjects in order to focus on those for manual labelling, which is essential for training and testing automated CMB detection tools on these datasets. In this work, we aim to detect CMB candidate subjects from a larger dataset, UK Biobank, using a machine learning-based, computationally light pipeline. For our evaluation, we used 3 different datasets, with different intensity characteristics, acquired with different scanners. They include the UK Biobank dataset and two clinical datasets with different pathological conditions. We developed and evaluated our pipelines on different types of images, consisting of SWI or GRE images. We also used the UK Biobank dataset to compare our approach with alternative CMB preselection methods using non-imaging factors and/or imaging data. Finally, we evaluated the pipeline's generalisability across datasets. Our method provided subject-level detection accuracy > 80% on all the datasets (within-dataset results), and showed good generalisability across datasets, providing a consistent accuracy of over 80%, even when evaluated across different modalities