Samaneh Nobakht1, Nils Forkert2, Sean Nestor3, Sandra Black4, and Phillip Barber5
1Medical Sciences, University of Calgary, Calgary, AB, Canada, 2Radiology, University of Calgary, Calgary, AB, Canada, 3Psychiatry, University of Toronto, Toronto, ON, Canada, 4Medicine, Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 5Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
Synopsis
The hippocampus atrophy rate (volumetric loss per year) might be a good
biomarker for predicting disease progression. However, hippocampus atrophy rate
assessment requires accurate delineation of the structure from longitudinal
scans. In this work, we propose an automatic approach based on convolutional
neural network (CNN) for robust and reliable hippocampus segmentation.
Therefore, the CNN was pre-trained using weakly annotated T1-weighted MRI
datasets and fine-tuned using fully-annotated datasets. Leave-one-out cross
validation revealed that the proposed method leads to robust and reproducible
segmentation results with an average Dice coefficient of 0.89.
Introduction
The
hippocampus is responsible for episodic memory and learning. Several
studies have reported volumetric loss of this structure in
Alzheimer’s disease (AD) patients, which is the most common form of
late life dementia [1]. The hippocampus atrophy rate (volumetric loss
per year) might be a good biomarker for predicting disease
progression [2]. However, hippocampus atrophy rate assessment
requires accurate delineation of the structure from longitudinal
scans. While manual segmentation is tedious, current automatic
techniques are often not robust enough to detect small volumetric
changes over time [3][4][5][6]. In this work, we propose an automatic
approach based on convolutional neural network (CNN) initially
proposed by [7][8] for robust and reliable hippocampus segmentation.Methods
Two
different datasets, a weakly annotated and fully annotated dataset,
were used for the development and evaluation of the proposed method
inspired by [9].
The
weakly annotated dataset comprises of 250 T1-weighted MRI images from
patients with AD, stroke, mild cognitive impairment, dementia, and
healthy subjects. These datasets were weakly annotated (segmented)
using a simple automatic approach. Briefly described, this technique
performs an atlas-based segmentation of the hippocampus and
subsequent post-processing using a k-means clustering approach (Fig.
1).
The
second dataset used in this work as the fully annotated dataset
includes 50 T1-weighted MRI images from patients with AD, mild
cognitive impairment, and healthy subjects, which were manually
segmented by an expert [10].
The
two datasets were pre-processed in the same fashion (Fig. 2) prior to
training and testing of the CNN by normalizing the intensity values
to zero mean and unary variance values. After this, the MNI brain
atlas was non-linearly registered to each dataset using NiftyReg
[11]. The probabilistic map of the hippocampus from the
Harvard-Oxford subcortical structural atlas was deformed to the
patient space using the transformation resulting from non-linear
registration and used to define a bounding box encompassing all
voxels with a positive hippocampus probability and including an
additional small safety margin.
Figure
3 shows the architecture of the CNN, which comprises of four
convolutional hidden layers subsequent max pooling layer and a
sigmoid activation function. The CNN was first pre-trained using the
weakly annotated data, whereas the training and testing was
restricted to the bounding box in all cases. The main idea of the
pre-training is to coarsely optimize the network parameters using a
large dataset. After this, the fully annotated datasets were used for
fine-tuning of the network parameters in the same fashion.Results
Leave-one-out
cross validation using the fully annotated datasets was used for
evaluation of the proposed method. The Dice similarity metric was
used as a quantitative overlap measurement for segmentation quality
assessment. Dice values close to 1.0 indicate a good consensus.
Overall,
leave-one-out cross validation using pre-training with weakly
annotated data followed by fully annotated data resulted in an
average Dice coefficient of 0.89±0.015, indicating a very high consensus.
Compared to this, training and testing of the CNN using only the
fully annotated dataset without any pre-training resulted in an
average Dice coefficient of 0.84±0.02, which clearly shows the benefit of
pre-training the CNN with weakly annotated datasets.
The
good quantitative results can also be confirmed visually (Fig. 4).
Here, it can be seen that the proposed method is capable of
differentiating the hippocampus from other surrounding brain regions
such as the amygdala, cerebrospinal fluid, and white matter.Discussion
Overall,
the first results of the proposed hippocampus segmentation method
using a deep convolutional neural network are very promising and in
the top range of previously described results.
The
typical drawback of deep neural networks requiring a large database
for robust training was overcome in this work by using weakly
annotated data for pre-training, prior to fine-tuning the parameters
of the network using fully annotated datasets. Our results clearly
show the benefit of pre-training using weakly annotated datasets.
Another
major benefit of the proposed method is its simplicity as it only
requires an atlas registration and subsequent application of the CNN.
Although training of a CNN can be time-consuming, the application of
a trained network is usually quite fast, especially if only applied
to a small VOI, so that the proposed segmentation method is also
fast. Future research will include further optimization of the CNN
architecture parameters (e.g. number of hidden layers) as well as
validation using test-retest datasets.Conclusion
The
proposed technique leads to robust and accurate hippocampus
segmentations from patients with various diseases such as AD, stroke,
mild cognitive impairment, dementia, as well as healthy individuals
and can, therefore, be used in future to determine hippocampus
atrophy rates in longitudinal scans.Acknowledgements
No acknowledgement found.References
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