Segmentation of perivascular spaces in 7 T MR image using auto-context model with orientation-normalized features

Quantitative study of perivascular spaces (PVSs) in brain magnetic resonance (MR) images is important for understanding the brain lymphatic system and its relationship with neurological diseases. One of major challenges is the accurate extraction of PVSs that have very thin tubular structures with various directions in three-dimensional (3D) MR images. In this paper, we propose a learning-based PVS segmentation method to address this challenge. Specifically, we first determine a region of interest (ROI) by using the anatomical brain structure and the vesselness information derived from eigenvalues of image derivatives. Then, in the ROI, we extract a number of randomized Haar features which are normalized with respect to the principal directions of the underlying image derivatives. The classifier is trained by the random forest model that can effectively learn both discriminative features and classifier parameters to maximize the information gain. Finally, a sequential learning strategy is used to further enforce various contextual patterns around the thin tubular structures into the classifier. For evaluation, we apply our proposed method to the 7T brain MR images scanned from 17 healthy subjects aged from 25 to 37. The performance is measured by voxel-wise segmentation accuracy, cluster- wise classification accuracy, and similarity of geometric properties, such as volume, length, and diameter distributions between the predicted and the true PVSs. Moreover, the accuracies are also evaluated on the simulation images with motion artifacts and lacunes to demonstrate the potential of our method in segmenting PVSs from elderly and patient populations. The experimental results show that our proposed method outperforms all existing PVS segmentation methods

Automatic quantification of perivascular spaces in T2-weighted images at 7 T MRI

Perivascular spaces (PVS) are believed to be involved in brain waste disposal. PVS are associated with cerebral small vessel disease. At higher field strengths more PVS can be observed, challenging manual assessment. We developed a method to automatically detect and quantify PVS. A machine learning approach identified PVS in an automatically positioned ROI in the centrum semiovale (CSO), based on -resolution T2-weighted TSE scans. Next, 3D PVS tracking was performed in 50 subjects (mean age 62.9 years (range 27–78), 19 male), and quantitative measures were extracted. Maps of PVS density, length, and tortuosity were created. Manual PVS annotations were available to train and validate the automatic method. Good correlation was found between the automatic and manual PVS count: ICC (absolute/consistency) is 0.64/0.75, and Dice similarity coefficient (DSC) is 0.61. The automatic method counts fewer PVS than the manual count, because it ignores the smallest PVS (length <2 mm). For 20 subjects manual PVS annotations of a second observer were available. Compared with the correlation between the automatic and manual PVS, higher inter-observer ICC was observed (0.85/0.88), but DSC was lower (0.49 in 4 persons). Longer PVS are observed posterior in the CSO compared with anterior in the CSO. Higher PVS tortuosity are observed in the center of the CSO compared with the periphery of the CSO. Our fully automatic method can detect PVS in a 2D slab in the CSO, and extract quantitative PVS parameters by performing 3D tracking. This method enables automated quantitative analysis of PVS

3D Regression Neural Network for the Quantification of Enlarged Perivascular Spaces in Brain MRI

Enlarged perivascular spaces (EPVS) in the brain are an emerging imaging marker for cerebral small vessel disease, and have been shown to be related to increased risk of various neurological diseases, including stroke and dementia. Automatic quantification of EPVS would greatly help to advance research into its etiology and its potential as a risk indicator of disease. We propose a convolutional network regression method to quantify the extent of EPVS in the basal ganglia from 3D brain MRI. We first segment the basal ganglia and subsequently apply a 3D convolutional regression network designed for small object detection within this region of interest. The network takes an image as input, and outputs a quantification score of EPVS. The network has significantly more convolution operations than pooling ones and no final activation, allowing it to span the space of real numbers. We validated our approach using a dataset of 2000 brain MRI scans scored visually. Experiments with varying sizes of training and test sets showed that a good performance can be achieved with a training set of only 200 scans. With a training set of 1000 scans, the intraclass correlation coefficient (ICC) between our scoring method and the expert's visual score was 0.74. Our method outperforms by a large margin - more than 0.10 - four more conventional automated approaches based on intensities, scale-invariant feature transform, and random forest. We show that the network learns the structures of interest and investigate the influence of hyper-parameters on the performance. We also evaluate the reproducibility of our network using a set of 60 subjects scanned twice (scan-rescan reproducibility). On this set our network achieves an ICC of 0.93, while the intrarater agreement reaches 0.80. Furthermore, the automatic EPVS scoring correlates similarly to age as visual scoring

Influence of threshold selection and image sequence in in-vivo segmentation of enlarged perivascular spaces

BACKGROUND: Growing interest surrounds perivascular spaces (PVS) as a clinical biomarker of brain dysfunction given their association with cerebrovascular risk factors and disease. Neuroimaging techniques allowing quick and reliable quantification are being developed, but, in practice, they require optimisation as their limits of validity are usually unspecified.NEW METHOD: We evaluate modifications and alternatives to a state-of-the-art (SOTA) PVS segmentation method that uses a vesselness filter to enhance PVS discrimination, followed by thresholding of its response, applied to brain magnetic resonance images (MRI) from patients with sporadic small vessel disease acquired at 3 T.RESULTS: The method is robust against inter-observer differences in threshold selection, but separate thresholds for each region of interest (i.e., basal ganglia, centrum semiovale, and midbrain) are required. Noise needs to be assessed prior to selecting these thresholds, as effect of noise and imaging artefacts can be mitigated with a careful optimisation of these thresholds. PVS segmentation from T1-weighted images alone, misses small PVS, therefore, underestimates PVS count, may overestimate individual PVS volume especially in the basal ganglia, and is susceptible to the inclusion of calcified vessels and mineral deposits. Visual analyses indicated the incomplete and fragmented detection of long and thin PVS as the primary cause of errors, with the Frangi filter coping better than the Jerman filter.COMPARISON WITH EXISTING METHODS: Limits of validity to a SOTA PVS segmentation method applied to 3 T MRI with confounding pathology are given.CONCLUSIONS: Evidence presented reinforces the STRIVE-2 recommendation of using T2-weighted images for PVS assessment wherever possible. The Frangi filter is recommended for PVS segmentation from MRI, offering robust output against variations in threshold selection and pathology presentation.</p

Segmentation of perivascular spaces in 7 T MR image using auto-context model with orientation-normalized features

Quantitative study of perivascular spaces (PVSs) in brain magnetic resonance (MR) images is important for understanding the brain lymphatic system and its relationship with neurological diseases. One of major challenges is the accurate extraction of PVSs that have very thin tubular structures with various directions in three-dimensional (3D) MR images. In this paper, we propose a learning-based PVS segmentation method to address this challenge. Specifically, we first determine a region of interest (ROI) by using the anatomical brain structure and the vesselness information derived from eigenvalues of image derivatives. Then, in the ROI, we extract a number of randomized Haar features which are normalized with respect to the principal directions of the underlying image derivatives. The classifier is trained by the random forest model that can effectively learn both discriminative features and classifier parameters to maximize the information gain. Finally, a sequential learning strategy is used to further enforce various contextual patterns around the thin tubular structures into the classifier. For evaluation, we apply our proposed method to the 7T brain MR images scanned from 17 healthy subjects aged from 25 to 37. The performance is measured by voxel-wise segmentation accuracy, cluster- wise classification accuracy, and similarity of geometric properties, such as volume, length, and diameter distributions between the predicted and the true PVSs. Moreover, the accuracies are also evaluated on the simulation images with motion artifacts and lacunes to demonstrate the potential of our method in segmenting PVSs from elderly and patient populations. The experimental results show that our proposed method outperforms all existing PVS segmentation methods

3D regression neural network for the quantification of enlarged perivascular spaces in brain MRI

Enlarged perivascular spaces (EPVS) in the brain are an emerging imaging marker for cerebral small vessel disease, and have been shown to be related to increased risk of various neurological diseases, including stroke and dementia. Automated quantification of EPVS would greatly help to advance research into its etiology and its potential as a risk indicator of disease. We propose a convolutional network regression method to quantify the extent of EPVS in the basal ganglia from 3D brain MRI. We first segment the basal ganglia and subsequently apply a 3D convolutional regression network designed for small object detection within this region of interest. The network takes an image as input, and outputs a quantification score of EPVS. The network has significantly more convolution operations than pooling ones and no final activation, allowing it to span the space of real numbers. We validated our approach using a dataset of 2000 brain MRI scans scored visually. Experiments with varying sizes of training and test sets showed that a good performance can be achieved with a training set of only 200 scans. With a training set of 1000 scans, the intraclass correlation coefficient (ICC) between our scoring method and the expert's visual score was 0.74. Our method outperforms by a large margin - more than 0.10 - four more conventional automated approaches based on intensities, scale-invariant feature transform, and random forest. We show that the network learns the structures of interest and investigate the influence of hyper-parameters on the performance. We also evaluate the reproducibility of our network using a set of 60 subjects scanned twice (scan-rescan reproducibility). On this set our network achieves an ICC of 0.93, while the intrarater agreement reaches 0.80. Furthermore, the automated EPVS scoring correlates similarly to age as visual scoring

Artificial Intelligence with Light Supervision: Application to Neuroimaging

Recent developments in artificial intelligence research have resulted in tremendous success in computer vision, natural language processing and medical imaging tasks, often reaching human or superhuman performance. In this thesis, I further developed artificial intelligence methods based on convolutional neural networks with a special focus on the automated analysis of brain magnetic resonance imaging scans (MRI). I showed that efficient artificial intelligence systems can be created using only minimal supervision, by reducing the quantity and quality of annotations used for training. I applied those methods to the automated assessment of the burden of enlarged perivascular spaces, brain structural changes that may be related to dementia, stroke, mult

Cerebrovascular dysfunction in cerebral small vessel disease

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