Pulmonary Nodule Classification in Lung Cancer from 3D Thoracic CT Scans Using fastai and MONAI

We construct a convolutional neural network to classify pulmonary nodules as malignant or benign in the context of lung cancer. To construct and train our model, we use our novel extension of the fastai deep learning framework to 3D medical imaging tasks, combined with the MONAI deep learning library. We train and evaluate the model using a large, openly available data set of annotated thoracic CT scans. Our model achieves a nodule classification accuracy of 92.4% and a ROC AUC of 97% when compared to a “ground truth” based on multiple human raters subjective assessment of malignancy. We further evaluate our approach by predicting patient-level diagnoses of cancer, achieving a test set accuracy of 75%. This is higher than the 70% obtained by aggregating the human raters assessments. Class activation maps are applied to investigate the features used by our classifier, enabling a rudimentary level of explainability for what is otherwise close to “black box” predictions. As the classification of structures in chest CT scans is useful across a variety of diagnostic and prognostic tasks in radiology, our approach has broad applicability. As we aimed to construct a fully reproducible system that can be compared to new proposed methods and easily be adapted and extended, the full source code of our work is available at https://github.com/MMIV-ML/Lung-CT-fastai-2020

2D and 3D U-Nets for skull stripping in a large and heterogeneous set of head MRI using fastai

Skull stripping in brain imaging is the removal of the parts of images corresponding to non-brain tissue. Fast and accurate skull stripping is a crucial step for numerous medical brain imaging applications, e.g. registration, segmentation and feature extraction, as it eases subsequent image processing steps. In this work, we propose and compare two novel skull stripping methods based on 2D and 3D convolutional neural networks trained on a large, heterogeneous collection of 2777 clinical 3D T1-weighted MRI images from 1681 healthy subjects. We investigated the performance of the models by testing them on 927 images from 324 subjects set aside from our collection of data, in addition to images from an independent, large brain imaging study: the IXI dataset (n = 556). Our models achieved mean Dice scores higher than 0:978 and Jaccard indices higher than 0:957 on all tests sets, making predictions on new unseen brain MR images in approximately 1.4s for the 3D model and 12.4s for the 2D model. A preliminary exploration of the models’ robustness to variation in the input data showed favourable results when compared to a traditional, well-established skull stripping method. With further research aimed at increasing the models’ robustness, such accurate

Correlations between measures of executive attention and cortical thickness of left posterior middle frontal gyrus - a dichotic listening study

Background: The frontal lobe has been associated to a wide range of cognitive control functions and is also vulnerable to degeneration in old age. A recent study by Thomsen and colleagues showed a difference between a young and old sample in grey matter density and activation in the left middle frontal cortex (MFC) and performance on a dichotic listening task. The present study investigated this brain behaviour association within a sample of healthy older individuals, and predicted a positive correlation between performance in a condition requiring executive attention and measures of grey matter structure of the posterior left MFC. Methods: A dichotic listening forced attention paradigm was used to measure attention control functions. Subjects were instructed to report only the left or the right ear syllable of a dichotically presented consonant-vowel syllable pair. A conflict situation appears when subjects are instructed to report the left ear stimulus, caused by the conflict with the bottom-up, stimulus-driven right ear advantage. Overcoming this processing conflict was used as a measure of executive attention. Thickness and volumes of frontal lobe regions were derived from automated segmentation of 3D magnetic resonance image acquisitions. Results: The results revealed a statistically significant positive correlation between the thickness measure of the left posterior MFC and performance on the dichotic listening measures of executive attention. Follow-up analyses showed that this correlation was only statistically significant in the subgroup that showed the typical bottom-up, stimulus-driven right ear advantage. Conclusion: The results suggest that the left MFC is a part of an executive attention network, and that the dichotic listening forced attention paradigm may be a feasible tool for assessing subtle attentional dysfunctions in older adults

2D and 3D U-Nets for skull stripping in a large and heterogeneous set of head MRI using fastai

Skull stripping in brain imaging is the removal of the parts of images corresponding to non-brain tissue. Fast and accurate skull stripping is a crucial step for numerous medical brain imaging applications, e.g. registration, segmentation and feature extraction, as it eases subsequent image processing steps. In this work, we propose and compare two novel skull stripping methods based on 2D and 3D convolutional neural networks trained on a large, heterogeneous collection of 2777 clinical 3D T1-weighted MRI images from 1681 healthy subjects. We investigated the performance of the models by testing them on 927 images from 324 subjects set aside from our collection of data, in addition to images from an independent, large brain imaging study: the IXI dataset (n = 556). Our models achieved mean Dice scores higher than 0:978 and Jaccard indices higher than 0:957 on all tests sets, making predictions on new unseen brain MR images in approximately 1.4s for the 3D model and 12.4s for the 2D model. A preliminary exploration of the models’ robustness to variation in the input data showed favourable results when compared to a traditional, well-established skull stripping method. With further research aimed at increasing the models’ robustness, such accurate and fast skull stripping methods can potentially form a useful component of brain MRI analysis pipelines.publishedVersio

Representative factor generation for the interactive visual analysis of high-dimensional data

Datasets with a large number of dimensions per data item (hundreds or more) are challenging both for computational and visual analysis. Moreover, these dimensions have different characteristics and relations that result in sub-groups and/or hierarchies over the set of dimensions. Such structures lead to heterogeneity within the dimensions. Although the consideration of these structures is crucial for the analysis, most of the available analysis methods discard the heterogeneous relations among the dimensions. In this paper, we introduce the construction and utilization of representative factors for the interactive visual analysis of structures in high-dimensional datasets. First, we present a selection of methods to investigate the sub-groups in the dimension set and associate representative factors with those groups of dimensions. Second, we introduce how these factors are included in the interactive visual analysis cycle together with the original dimensions. We then provide the steps of an analytical procedure that iteratively analyzes the datasets through the use of representative factors. We discuss how our methods improve the reliability and interpretability of the analysis process by enabling more informed selections of computational tools. Finally, we demonstrate our techniques on the analysis of brain imaging study results that are performed over a large group of subjects

Healthy kidney segmentation in the dce-mr images using a convolutional neural network and temporal signal characteristics

Quantification of renal perfusion based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) requires determination of signal intensity time courses in the region of renal parenchyma. Thus, selection of voxels representing the kidney must be accomplished with special care and constitutes one of the major technical limitations which hampers wider usage of this technique as a standard clinical routine. Manual segmentation of renal compartments—even if performed by experts—is a common source of decreased repeatability and reproducibility. In this paper, we present a processing framework for the automatic kidney segmentation in DCE-MR images. The framework consists of two stages. Firstly, kidney masks are generated using a convolutional neural network. Then, mask voxels are classified to one of three regions—cortex, medulla, and pelvis–based on DCE-MRI signal intensity time courses. The proposed approach was evaluated on a cohort of 10 healthy volunteers who underwent the DCE-MRI examination. MRI scanning was repeated on two time events within a 10-day interval. For semantic segmentation task we employed a classic U-Net architecture, whereas experiments on voxel classification were performed using three alternative algorithms—support vector machines, logistic regression and extreme gradient boosting trees, among which SVM produced the most accurate results. Both segmentation and classification steps were accomplished by a series of models, each trained separately for a given subject using the data from other participants only. The mean achieved accuracy of the whole kidney segmentation was 94% in terms of IoU coefficient. Cortex, medulla and pelvis were segmented with IoU ranging from 90 to 93% depending on the tissue and body side. The results were also validated by comparing image-derived perfusion parameters with ground truth measurements of glomerular filtration rate (GFR). The repeatability of GFR calculation, as assessed by the coefficient of variation was determined at the level of 14.5 and 17.5% for the left and right kidney, respectively and it improved relative to manual segmentation. Reproduciblity, in turn, was evaluated by measuring agreement between image-derived and iohexol-based GFR values. The estimated absolute mean differences were equal to 9.4 and 12.9 mL/min/1.73 m2 for scanning sessions 1 and 2 and the proposed automated segmentation method. The result for session 2 was comparable with manual segmentation, whereas for session 1 reproducibility in the automatic pipeline was weaker.publishedVersio

Fractional anisotropy shows differential reduction in frontal-subcortical fiber bundles - A longitudinal MRI study of 76 middle-aged and older adults

Motivated by the frontal- and white matter (WM) retrogenesis hypotheses and the assumptions that fronto-striatal circuits are especially vulnerable in normal aging, the goal of the present study was to identify fiber bundles connecting subcortical nuclei and frontal areas and obtain site-specific information about age related fractional anisotropy (FA) changes. Multimodal magnetic resonance image acquisitions [3D T1-weighted and diffusion weighted imaging (DWI)] were obtained from healthy older adults (N = 76, range 49–80 years at inclusion) at two time points, 3 years apart. A subset of the participants (N = 24) was included at a third time-point. In addition to the frontal-subcortical fibers, the anterior callosal fiber (ACF) and the corticospinal tract (CST) was investigated by its mean FA together with tract parameterization analysis. Our results demonstrated fronto-striatal structural connectivity decline (reduced FA) in normal aging with substantial inter-individual differences. The tract parameterization analysis showed that the along tract FA profiles were characterized by piece-wise differential changes along their extension rather than being uniformly affected. To the best of our knowledge, this is the first longitudinal study detecting age-related changes in frontal-subcortical WM connections in normal aging.publishedVersio

Interactive Visual Analysis of Heterogeneous Cohort Study Data

Cohort studies in medicine are conducted to enable the study of medical hypotheses in large samples. Often, a large amount of heterogeneous data is acquired from many subjects. The analysis is usually hypothesis-driven, i.e., a specific subset of such data is studied to confirm or reject specific hypotheses. In this paper, we demonstrate how we enable the interactive visual exploration and analysis of such data, helping with the generation of new hypotheses and contributing to the process of validating them. We propose a data-cube based model which handles partially overlapping data subsets during the interactive visualization. This model enables seamless integration of the heterogeneous data, as well as linking spatial and non-spatial views on these data. We implemented this model in an application prototype, and used it to analyze data acquired in the context of a cohort study on cognitive aging. We present case-study analyses of selected aspects of brain connectivity by using the prototype implementation of the presented model, to demonstrate its potential and flexibility

A new framework for assessing subject-specific whole brain circulation and perfusion using MRI-based measurements and a multi-scale continuous flow model

A large variety of severe medical conditions involve alterations in microvascular circulation. Hence, measurements or simulation of circulation and perfusion has considerable clinical value and can be used for diagnostics, evaluation of treatment efficacy, and for surgical planning. However, the accuracy of traditional tracer kinetic one-compartment models is limited due to scale dependency. As a remedy, we propose a scale invariant mathematical framework for simulating whole brain perfusion. The suggested framework is based on a segmentation of anatomical geometry down to imaging voxel resolution. Large vessels in the arterial and venous network are identified from time-of-flight (ToF) and quantitative susceptibility mapping (QSM). Macro-scale flow in the large-vessel-network is accurately modelled using the Hagen-Poiseuille equation, whereas capillary flow is treated as two-compartment porous media flow. Macro-scale flow is coupled with micro-scale flow by a spatially distributing support function in the terminal endings. Perfusion is defined as the transition of fluid from the arterial to the venous compartment. We demonstrate a whole brain simulation of tracer propagation on a realistic geometric model of the human brain, where the model comprises distinct areas of grey and white matter, as well as large vessels in the arterial and venous vascular network. Our proposed framework is an accurate and viable alternative to traditional compartment models, with high relevance for simulation of brain perfusion and also for restoration of field parameters in clinical brain perfusion applications.publishedVersio

Deep Gray Matter Demyelination Detected by Magnetization Transfer Ratio in the Cuprizone Model

Abstract In multiple sclerosis (MS), the correlation between lesion load on conventional magnetic resonance imaging (MRI) and clinical disability is weak. This clinico-radiological paradox might partly be due to the low sensitivity of conventional MRI to detect gray matter demyelination. Magnetization transfer ratio (MTR) has previously been shown to detect white matter demyelination in mice. In this study, we investigated whether MTR can detect gray matter demyelination in cuprizone exposed mice. A total of 54 female C57BL/6 mice were split into one control group () and eight cuprizone exposed groups (Ns~6). The mice were exposed to 0:2% (w/w) cuprizone for up to six weeks. MTR images were obtained at a 7 Tesla Bruker MR-scanner before cuprizone exposure, weekly for six weeks during cuprizone exposure, and once two weeks after termination of cuprizone exposure. Immunohistochemistry staining for myelin (anti-Proteolopid Protein) and oligodendrocytes (anti-Neurite Outgrowth Inhibitor Protein A) was obtained after each weekly scanning. Rates of MTR change and correlations between MTR values and histological findings were calculated in five brain regions. In the corpus callosum and the deep gray matter a significant rate of MTR value decrease was found, 0:96% per week (pv:0001) and 0:39% per week (pv:0001) respectively. The MTR values correlated to myelin loss as evaluated by immunohistochemistry (Corpus callosum: R 2~: 43, pv:0001. Deep gray matter: R 2~: 21, pv:001), but did not correlate to oligodendrocyte density. Significant results were not found in the cerebellum, the olfactory bulb or the cerebral cortex. This study shows that MTR can be used to detect demyelination in the deep gray matter, which is of particular interest for imaging of patients with MS, as deep gray matter demyelination is common in MS, and is not easily detected on conventional clinical MRI