Frederik Luca Sandig1,2, Julian Emmerich3,4, Edris El-Sanosy1,2, Mark Ladd1,2,3, Heinz-Peter Schlemmer1, and Sina Straub3
1Division of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Faculty of Medicine, Heidelberg University, Heidelberg, Germany, 3Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 4Faculty of Physics and Astronomy, Heidelberg University, Heidelberg, Germany
Synopsis
Multiple sclerosis is a chronic
inflammatory disease characterized by demyelination. Magnetic resonance imaging
(MRI) is an important method for diagnosis and prognosis predictions. The
ongoing study presented here shows the use of deep learning algorithms for
white and grey matter lesion segmentation in 7T MRI images. Results show high
accuracy for patients with high lesion load. Furthermore, it is demonstrated that
it is possible to train a neural net to find small cortical lesions, which can
be used as a potential biomarker.
INTRODUCTION –
Although manual segmentation of multiple sclerosis (MS) lesions is still
the gold standard, it is highly subjective and barely feasible in longitudinal
large cohort studies. Therefore,
automatic lesion segmentation has been an active research topic for more than
20 years.1 However, research has predominantly been focused on
segmenting white matter lesions. Only recently, a number of studies also
attempted to segment grey matter lesions,
which are often much smaller.2,3 Exploiting the higher resolution and
contrast-to-noise ratio achievable using a 7T magnetic resonance imaging (MRI)
scanner, small white matter, subcortical white matter, and even grey
matter lesions can be detected.4 However, to the best of our
knowledge, the use of deep learning architectures like the U-net have not yet been
used to develop automatic lesion detection in 7T data. The possibility of more
precise segmentation and localization of small cortical lesions can improve prognosis
predictions and diagnosis. As manual segmentation is time consuming, automation
of this procedure is required, in particular when the number of detectable
lesions is large. METHODS –
The study was conducted in accordance with the
Declaration of Helsinki. All subjects provided written informed consent and
institutional review board approval was received. Twenty-nine patients were
scanned on a 7T whole-body scanner (MAGNETOM 7T, Siemens Healthcare, Germany).
Some patients were scanned multiple times, and the total number of measurements
was 35. The following sequences were used: 3D multi-echo gradient echo (GRE),
3D MP2RAGE, 2D multi-echo turbo spin echo (TSE), and a pre-saturation‐based 2D turbo flash for B1 mapping (Table 1). All
sequences were registered using FSL-FLIRT and the Medical Imaging Interaction Toolkit (MITK).5,6 Brain masks were created with the
FSL Brain Extraction Tool by using the first echo of GRE.7 This
brain mask was used to create brain extracted images with FSLMaths. The B1 maps
were used to correct for the field inhomogeneities of the MP2RAGE with github.com/JosePMarques/MP2RAGE-related-scripts.
Ground truth lesion segmentations were drawn manually on the MP2RAGE
data and on the first echo of the T2-weighted turbo spin echo data in MITK.6
All lesions that included cortical gray matter were classified as cortical
lesions (CL).8,9 Both modalities were segmented separately and a
merged mask was generated from the T1 and the T2 masks that included a lesion
if there was a lesion in either of the two masks.
The data were used for training within the fully-automated nnU-net
framework, which is an improved version of the U-net architecture. 10,11
The nnU-net provides a 2D, 3D, and a Cascade U-net model. In this study, only
the 3D model was trained on the corrected MP2RAGE data, the T2-weighted data,
and on both modalities. The 35 measurements were randomly divided into training
and test sets, whereby the latter consisted of seven measurements and all
measurements of a single patient were fully contained either in the training or
in the test set. For each training set, the nnU-net was trained on a NVIDIA
P6000 GPU for about 65 hours. Ground truth lesion masks and automatically
generated lesion segmentations were evaluated using the Dice coefficient (DSC),
true positive rate (TPR), and volume difference (VD).12RESULTS –
Figure 1 illustrates the capability of the nnU-net to
segment small lesions on representative slices containing grey matter lesions
by comparing manual and automatic segmentations. The displayed slices
demonstrate CL-I on
MP2RAGE, while manual segmentations belong to the merged masks. The nnU-net
provides smooth and comprehensible segmentations.
Figure 2 shows median DSC for white and grey matter
segmentation. Values for median DSC are 0.654 for T1, 0.720 for T2, and 0.706
for T1+T2. Further evaluation metrics are listed in Table 2.
Figure 3 shows a boxplot of DSC and TPR only for the
segmentation of cortical lesions in the T1+T2 set. In M5+M6 no CL was found in
either. For the remaining data a median DSC of 0.695 and a median TPR of 0.624 were
calculated. It is worth mentioning that every CL in the test set was
leukocortical, and the volumes of cortical lesions were low (average cortical
lesion volume of 0.572ml in the test set).DISCUSSION AND CONCLUSION –
In comparison to architectures segmenting only white
matter lesions of MS patients, to be seen on the leaderboard (https://smart-stats-tools.org/lesion-challenge) of the 2015 longitudinal MS lesion segmentation
challenge, the performance in our study was similar. The DSC of the currently
best architecture has a median of 0.686. Furthermore, the same correlation
between low lesion load and poor DSC was observed. For the segmentation of
cortical lesions, our results are comparable to studies segmenting cortical MS lesions.13
However, this has to be evaluated on a larger test set with a higher number of
cortical lesions in the future. Automatic machine learning based lesion
segmentation combined with the high resolution available when using 7T MRI
could therefore help to detect a higher number of small cortical lesions. In
future, automatic lesion detection with 7T data could improve disease staging
and help explore the impact of grey matter lesions in multiple sclerosis.Acknowledgements
The nnU-net pipeline, publically available at github.com/MIC-DKFZ/nnUNet by Fabian Isensee et al., is kindly acknowledged. The
Quadro P6000 used for this research was donated by the NVIDIA Corporation.References
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