The gap between predicted brain age using magnetic resonance imaging (MRI) and chronological age may serve as a biomarker for early-stage neurodegeneration. However, owing to the lack of large longitudinal studies, it has been challenging to validate this link. We aimed to investigate the utility of such a gap as a risk biomarker for incident dementia using a deep learning approach for predicting brain age based on MRI-derived gray matter (GM). We built a convolutional neural network (CNN) model to predict brain age trained on 3,688 dementia-free participants of the Rotterdam Study (mean age 66 ± 11 y, 55% women). Logistic regressions and Cox proportional hazards were used to assess the association of the age gap with incident dementia, adjusted for age, sex, intracranial volume, GM volume, hippocampal volume, white matter hyperintensities, years of education, and APOE e4 allele carriership. Additionally, we computed the attention maps, which shows which regions are important for age prediction. Logistic regression and Cox proportional hazard models showed that the age gap was significantly related to incident dementia (odds ratio [OR] = 1.11 and 95% confidence intervals [CI] = 1.05-1.16; hazard ratio [HR] = 1.11, and 95% CI = 1.06-1.15, respectively). Attention maps indicated that GM density around the amygdala and hippocampi primarily drove the age estimation. We showed that the gap between predicted and chronological brain age is a biomarker, complimentary to those that are known, associated with risk of dementia, and could possibly be used for early-stage dementia risk screening. deep learning | dementia | age prediction | magnetic resonance imaging | voxel-based morphometry T he human brain continuously changes throughout the entire lifespan. These changes partially reflect a normal aging process and are not necessarily pathological (1). However, neurodegenerative diseases, including dementia, also affect brain structure and function (2, 3). Therefore, a better understanding and modeling of normal brain aging can help to disentangle these two processes and improve the detection of early-stage neurodegeneration.Age prediction models based on brain MRI are a popular trend in neuroscience (4-7). The difference between predicted and chronological age is thought to serve as an important biomarker reflecting pathological processes in the brain. Several recent studies showed the relation between accelerated brain aging and various disorders, such as Alzheimer's disease (8), schizophrenia, epilepsy, or diabetes (7,9,10).In recent years, CNNs have become the methodology of choice for analyzing medical images. These models are able to learn complex relations between input data and desired outcomes. Recent studies (11, 12) were able to demonstrate that CNN models can be successfully applied in brain MRI-based age prediction (5, 6).Although cross-sectional studies have suggested that the gap between predicted and chronological age may serve as a biomarker for dementia diagnosis, it remains unclear whether this is also t...

The scarcity of labeled data often limits the application of supervised deep learning techniques for medical image segmentation. This has motivated the development of semi-supervised techniques that learn from a mixture of labeled and unlabeled images. In this paper, we propose a novel semi-supervised method that, in addition to supervised learning on labeled training images, learns to predict segmentations consistent under a given class of transformations on both labeled and unlabeled images. More specifically, in this work we explore learning equivariance to elastic deformations. We implement this through: 1) a Siamese architecture with two identical branches, each of which receives a differently transformed image, and 2) a composite loss function with a supervised segmentation loss term and an unsupervised term that encourages segmentation consistency between the predictions of the two branches. We evaluate the method on a public dataset of chest radiographs with segmentations of anatomical structures using 5-fold crossvalidation. The proposed method reaches significantly higher segmentation accuracy compared to supervised learning. This is due to learning transformation consistency on both labeled and unlabeled images, with the latter contributing the most. We achieve the performance comparable to state-of-the-art chest X-ray segmentation methods while using substantially fewer labeled images.

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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.

Abstract. We propose a novel convolutional neural network for lesion detection from weak labels. Only a single, global label per image -the lesion count -is needed for training. We train a regression network with a fully convolutional architecture combined with a global pooling layer to aggregate the 3D output into a scalar indicating the lesion count. When testing on unseen images, we first run the network to estimate the number of lesions. Then we remove the global pooling layer to compute localization maps of the size of the input image. We evaluate the proposed network on the detection of enlarged perivascular spaces in the basal ganglia in MRI. Our method achieves a sensitivity of 62% with on average 1.5 false positives per image. Compared with four other approaches based on intensity thresholding, saliency and class maps, our method has a 20% higher sensitivity.

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