Benoit M. Dawant

Han Liu, Michelle K. Sigona, Thomas J. Manuel et al.

Transcranial focused ultrasound (tFUS) is a therapeutic ultrasound method that focuses sound through the skull to a small region noninvasively and often under MRI guidance. CT imaging is used to estimate the acoustic properties that vary between individual skulls to enable effective focusing during tFUS procedures, exposing patients to potentially harmful radiation. A method to estimate acoustic parameters in the skull without the need for CT would be desirable. Here, we synthesized CT images from routinely acquired T1-weighted MRI by using a 3D patch-based conditional generative adversarial network (cGAN) and evaluated the performance of synthesized CT (sCT) images for treatment planning with tFUS. We compared the performance of sCT to real CT (rCT) images for tFUS planning using Kranion and simulations using the acoustic toolbox, k-Wave. Simulations were performed for 3 tFUS scenarios: 1) no aberration correction, 2) correction with phases calculated from Kranion, and 3) phase shifts calculated from time-reversal. From Kranion, skull density ratio, skull thickness, and number of active elements between rCT and sCT had Pearson's Correlation Coefficients of 0.94, 0.92, and 0.98, respectively. Among 20 targets, differences in simulated peak pressure between rCT and sCT were largest without phase correction (12.4$\pm$8.1%) and smallest with Kranion phases (7.3$\pm$6.0%). The distance between peak focal locations between rCT and sCT was less than 1.3 mm for all simulation cases. Real and synthetically generated skulls had comparable image similarity, skull measurements, and acoustic simulation metrics. Our work demonstrates the feasibility of replacing real CTs with the MR-synthesized CT for tFUS planning. Source code and a docker image with the trained model are available at https://github.com/han-liu/SynCT_TcMRgFUS

Han Liu, Yubo Fan, Zhoubing Xu et al.

Unsupervised cross-modality domain adaptation is a challenging task in medical image analysis, and it becomes more challenging when source and target domain data are collected from multiple institutions. In this paper, we present our solution to tackle the multi-institutional unsupervised domain adaptation for the crossMoDA 2023 challenge. First, we perform unpaired image translation to translate the source domain images to the target domain, where we design a dynamic network to generate synthetic target domain images with controllable, site-specific styles. Afterwards, we train a segmentation model using the synthetic images and further reduce the domain gap by self-training. Our solution achieved the 1st place during both the validation and testing phases of the challenge. The code repository is publicly available at https://github.com/MedICL-VU/crossmoda2023.

Han Liu, Yubo Fan, Hao Li et al.

Image-level domain alignment is the de facto approach for unsupervised domain adaptation, where unpaired image translation is used to minimize the domain gap. Prior studies mainly focus on the domain shift between the source and target domains, whereas the intra-domain variability remains under-explored. To address the latter, an effective strategy is to diversify the styles of the synthetic target domain data during image translation. However, previous methods typically require intra-domain variations to be pre-specified for style synthesis, which may be impractical. In this paper, we propose an exemplar-based style synthesis method named IntraStyler, which can capture diverse intra-domain styles without any prior knowledge. Specifically, IntraStyler uses an exemplar image to guide the style synthesis such that the output style matches the exemplar style. To extract the style-only features, we introduce a style encoder to learn styles discriminatively based on contrastive learning. We evaluate the proposed method on the largest public dataset for cross-modality domain adaptation, CrossMoDA 2023. Our experiments show the efficacy of our method in controllable style synthesis and the benefits of diverse synthetic data for downstream segmentation. Code is available at https://github.com/han-liu/IntraStyler.

Han Liu, Yubo Fan, Ipek Oguz et al.

Automatic segmentation of vestibular schwannoma (VS) and cochlea from magnetic resonance imaging can facilitate VS treatment planning. Unsupervised segmentation methods have shown promising results without requiring the time-consuming and laborious manual labeling process. In this paper, we present an approach for VS and cochlea segmentation in an unsupervised domain adaptation setting. Specifically, we first develop a cross-site cross-modality unpaired image translation strategy to enrich the diversity of the synthesized data. Then, we devise a rule-based offline augmentation technique to further minimize the domain gap. Lastly, we adopt a self-configuring segmentation framework empowered by self-training to obtain the final results. On the CrossMoDA 2022 validation leaderboard, our method has achieved competitive VS and cochlea segmentation performance with mean Dice scores of 0.8178 $\pm$ 0.0803 and 0.8433 $\pm$ 0.0293, respectively.

Dingjie Su, Weixiang Hong, Benoit M. Dawant et al.

We propose a novel method for establishing correspondence between two sequences of 2D images. One particular application of this technique is slice-level content navigation, where the goal is to localize specific 2D slices within a 3D volume or determine the anatomical coverage of a 3D scan based on its 2D slices. This serves as an important preprocessing step for various diagnostic tasks, as well as for automatic registration and segmentation pipelines. Our approach builds sequence correspondence by training a network to learn how to insert a slice from one sequence into the appropriate position in another. This is achieved by encoding contextual representations of each slice and modeling the insertion process using a slice-to-slice attention mechanism. We apply this method to localize manually labeled key slices in body CT scans and compare its performance to the current state-of-the-art alternative known as body part regression, which predicts anatomical position scores for individual slices. Unlike body part regression, which treats each slice independently, our method leverages contextual information from the entire sequence. Experimental results show that the insertion network reduces slice localization errors in supervised settings from 8.4 mm to 5.4 mm, demonstrating a substantial improvement in accuracy.

Navodini Wijethilake, Reuben Dorent, Marina Ivory et al.

The cross-Modality Domain Adaptation (crossMoDA) challenge series, initiated in 2021 in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), focuses on unsupervised cross-modality segmentation, learning from contrast-enhanced T1 (ceT1) and transferring to T2 MRI. The task is an extreme example of domain shift chosen to serve as a meaningful and illustrative benchmark. From a clinical application perspective, it aims to automate Vestibular Schwannoma (VS) and cochlea segmentation on T2 scans for more cost-effective VS management. Over time, the challenge objectives have evolved to enhance its clinical relevance. The challenge evolved from using single-institutional data and basic segmentation in 2021 to incorporating multi-institutional data and Koos grading in 2022, and by 2023, it included heterogeneous routine data and sub-segmentation of intra- and extra-meatal tumour components. In this work, we report the findings of the 2022 and 2023 editions and perform a retrospective analysis of the challenge progression over the years. The observations from the successive challenge contributions indicate that the number of outliers decreases with an expanding dataset. This is notable since the diversity of scanning protocols of the datasets concurrently increased. The winning approach of the 2023 edition reduced the number of outliers on the 2021 and 2022 testing data, demonstrating how increased data heterogeneity can enhance segmentation performance even on homogeneous data. However, the cochlea Dice score declined in 2023, likely due to the added complexity from tumour sub-annotations affecting overall segmentation performance. While progress is still needed for clinically acceptable VS segmentation, the plateauing performance suggests that a more challenging cross-modal task may better serve future benchmarking.

Han Liu, Michelle K. Sigona, Thomas J. Manuel et al.

Transcranial MRI-guided focused ultrasound (TcMRgFUS) is a therapeutic ultrasound method that focuses sound through the skull to a small region noninvasively under MRI guidance. It is clinically approved to thermally ablate regions of the thalamus and is being explored for other therapies, such as blood brain barrier opening and neuromodulation. To accurately target ultrasound through the skull, the transmitted waves must constructively interfere at the target region. However, heterogeneity of the sound speed, density, and ultrasound attenuation in different individuals' skulls requires patient-specific estimates of these parameters for optimal treatment planning. CT imaging is currently the gold standard for estimating acoustic properties of an individual skull during clinical procedures, but CT imaging exposes patients to radiation and increases the overall number of imaging procedures required for therapy. A method to estimate acoustic parameters in the skull without the need for CT would be desirable. Here, we synthesized CT images from routinely acquired T1-weighted MRI by using a 3D patch-based conditional generative adversarial network and evaluated the performance of synthesized CT images for treatment planning with transcranial focused ultrasound. We compared the performance of synthetic CT to real CT images using Kranion and k-Wave acoustic simulation. Our work demonstrates the feasibility of replacing real CT with the MR-synthesized CT for TcMRgFUS planning.

Han Liu, Kathryn L. Holloway, Dario J. Englot et al.

Epilepsy is the fourth most common neurological disorder and affects people of all ages worldwide. Deep Brain Stimulation (DBS) has emerged as an alternative treatment option when anti-epileptic drugs or resective surgery cannot lead to satisfactory outcomes. To facilitate the planning of the procedure and for its standardization, it is desirable to develop an algorithm to automatically localize the DBS stimulation target, i.e., Anterior Nucleus of Thalamus (ANT), which is a challenging target to plan. In this work, we perform an extensive comparative study by benchmarking various localization methods for ANT-DBS. Specifically, the methods involved in this study include traditional registration method and deep-learning-based methods including heatmap matching and differentiable spatial to numerical transform (DSNT). Our experimental results show that the deep-learning (DL)-based localization methods that are trained with pseudo labels can achieve a performance that is comparable to the inter-rater and intra-rater variability and that they are orders of magnitude faster than traditional methods.

Han Liu, Yubo Fan, Can Cui et al.

Automatic methods to segment the vestibular schwannoma (VS) tumors and the cochlea from magnetic resonance imaging (MRI) are critical to VS treatment planning. Although supervised methods have achieved satisfactory performance in VS segmentation, they require full annotations by experts, which is laborious and time-consuming. In this work, we aim to tackle the VS and cochlea segmentation problem in an unsupervised domain adaptation setting. Our proposed method leverages both the image-level domain alignment to minimize the domain divergence and semi-supervised training to further boost the performance. Furthermore, we propose to fuse the labels predicted from multiple models via noisy label correction. In the MICCAI 2021 crossMoDA challenge, our results on the final evaluation leaderboard showed that our proposed method has achieved promising segmentation performance with mean dice score of 79.9% and 82.5% and ASSD of 1.29 mm and 0.18 mm for VS tumor and cochlea, respectively. The cochlea ASSD achieved by our method has outperformed all other competing methods as well as the supervised nnU-Net.

Reuben Dorent, Aaron Kujawa, Marina Ivory et al.

Domain Adaptation (DA) has recently raised strong interests in the medical imaging community. While a large variety of DA techniques has been proposed for image segmentation, most of these techniques have been validated either on private datasets or on small publicly available datasets. Moreover, these datasets mostly addressed single-class problems. To tackle these limitations, the Cross-Modality Domain Adaptation (crossMoDA) challenge was organised in conjunction with the 24th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2021). CrossMoDA is the first large and multi-class benchmark for unsupervised cross-modality DA. The challenge's goal is to segment two key brain structures involved in the follow-up and treatment planning of vestibular schwannoma (VS): the VS and the cochleas. Currently, the diagnosis and surveillance in patients with VS are performed using contrast-enhanced T1 (ceT1) MRI. However, there is growing interest in using non-contrast sequences such as high-resolution T2 (hrT2) MRI. Therefore, we created an unsupervised cross-modality segmentation benchmark. The training set provides annotated ceT1 (N=105) and unpaired non-annotated hrT2 (N=105). The aim was to automatically perform unilateral VS and bilateral cochlea segmentation on hrT2 as provided in the testing set (N=137). A total of 16 teams submitted their algorithm for the evaluation phase. The level of performance reached by the top-performing teams is strikingly high (best median Dice - VS:88.4%; Cochleas:85.7%) and close to full supervision (median Dice - VS:92.5%; Cochleas:87.7%). All top-performing methods made use of an image-to-image translation approach to transform the source-domain images into pseudo-target-domain images. A segmentation network was then trained using these generated images and the manual annotations provided for the source image.

Han Liu, Yubo Fan, Can Cui et al.

Automatic methods to segment the vestibular schwannoma (VS) tumors and the cochlea from magnetic resonance imaging (MRI) are critical to VS treatment planning. Although supervised methods have achieved satisfactory performance in VS segmentation, they require full annotations by experts, which is laborious and time-consuming. In this work, we aim to tackle the VS and cochlea segmentation problem in an unsupervised domain adaptation setting. Our proposed method leverages both the image-level domain alignment to minimize the domain divergence and semi-supervised training to further boost the performance. Furthermore, we propose to fuse the labels predicted from multiple models via noisy label correction. Our results on the challenge validation leaderboard showed that our unsupervised method has achieved promising VS and cochlea segmentation performance with mean dice score of 0.8261 $\pm$ 0.0416; The mean dice value for the tumor is 0.8302 $\pm$ 0.0772. This is comparable to the weakly-supervised based method.

Jianing Wang, Dingjie Su, Yubo Fan et al.

We propose an atlas-based method to segment the intracochlear anatomy (ICA) in the post-implantation CT (Post-CT) images of cochlear implant (CI) recipients that preserves the point-to-point correspondence between the meshes in the atlas and the segmented volumes. To solve this problem, which is challenging because of the strong artifacts produced by the implant, we use a pair of co-trained deep networks that generate dense deformation fields (DDFs) in opposite directions. One network is tasked with registering an atlas image to the Post-CT images and the other network is tasked with registering the Post-CT images to the atlas image. The networks are trained using loss functions based on voxel-wise labels, image content, fiducial registration error, and cycle-consistency constraint. The segmentation of the ICA in the Post-CT images is subsequently obtained by transferring the predefined segmentation meshes of the ICA in the atlas image to the Post-CT images using the corresponding DDFs generated by the trained registration networks. Our model can learn the underlying geometric features of the ICA even though they are obscured by the metal artifacts. We show that our end-to-end network produces results that are comparable to the current state of the art (SOTA) that relies on a two-steps approach that first uses conditional generative adversarial networks to synthesize artifact-free images from the Post-CT images and then uses an active shape model-based method to segment the ICA in the synthetic images. Our method requires a fraction of the time needed by the SOTA, which is important for end-user acceptance.

Han Liu, Can Cui, Dario J. Englot et al.

Atlas-based methods are the standard approaches for automatic targeting of the Anterior Nucleus of the Thalamus (ANT) for Deep Brain Stimulation (DBS), but these are known to lack robustness when anatomic differences between atlases and subjects are large. To improve the localization robustness, we propose a novel two-stage deep learning (DL) framework, where the first stage identifies and crops the thalamus regions from the whole brain MRI and the second stage performs per-voxel regression on the cropped volume to localize the targets at the finest resolution scale. To address the issue of data scarcity, we train the models with the pseudo labels which are created based on the available labeled data using multi-atlas registration. To assess the performance of the proposed framework, we validate two sampling-based uncertainty estimation techniques namely Monte Carlo Dropout (MCDO) and Test-Time Augmentation (TTA) on the second-stage localization network. Moreover, we propose a novel uncertainty estimation metric called maximum activation dispersion (MAD) to estimate the image-wise uncertainty for localization tasks. Our results show that the proposed method achieved more robust localization performance than the traditional multi-atlas method and TTA could further improve the robustness. Moreover, the epistemic and hybrid uncertainty estimated by MAD could be used to detect the unreliable localizations and the magnitude of the uncertainty estimated by MAD could reflect the degree of unreliability for the rejected predictions.

Yiyuan Zhao, Jianing Wang, Rui Li et al.

Cochlear implants (CIs) are a standard treatment for patients who experience severe to profound hearing loss. Recent studies have shown that hearing outcome is correlated with intra-cochlear anatomy and electrode placement. Our group has developed image-guided CI programming (IGCIP) techniques that use image analysis methods to both segment the inner ear structures in pre- or post-implantation CT images and localize the CI electrodes in post-implantation CT images. This permits to assist audiologists with CI programming by suggesting which among the contacts should be deactivated to reduce electrode interaction that is known to affect outcomes. Clinical studies have shown that IGCIP can improve hearing outcomes for CI recipients. However, the sensitivity of IGCIP with respect to the accuracy of the two major steps: electrode localization and intra-cochlear anatomy segmentation, is unknown. In this article, we create a ground truth dataset with conventional CT and micro-CT images of 35 temporal bone specimens to both rigorously characterize the accuracy of these two steps and assess how inaccuracies in these steps affect the overall results. Our study results show that when clinical pre- and post-implantation CTs are available, IGCIP produces results that are comparable to those obtained with the corresponding ground truth in 86.7% of the subjects tested. When only post-implantation CTs are available, this number is 83.3%. These results suggest that our current method is robust to errors in segmentation and localization but also that it can be improved upon. Keywords: cochlear implant, ground truth, segmentation, validation

Camilo Bermudez, William Rodriguez, Yuankai Huo et al.

Deep brain stimulation (DBS) has the potential to improve the quality of life of people with a variety of neurological diseases. A key challenge in DBS is in the placement of a stimulation electrode in the anatomical location that maximizes efficacy and minimizes side effects. Pre-operative localization of the optimal stimulation zone can reduce surgical times and morbidity. Current methods of producing efficacy probability maps follow an anatomical guidance on magnetic resonance imaging (MRI) to identify the areas with the highest efficacy in a population. In this work, we propose to revisit this problem as a classification problem, where each voxel in the MRI is a sample informed by the surrounding anatomy. We use a patch-based convolutional neural network to classify a stimulation coordinate as having a positive reduction in symptoms during surgery. We use a cohort of 187 patients with a total of 2,869 stimulation coordinates, upon which 3D patches were extracted and associated with an efficacy score. We compare our results with a registration-based method of surgical planning. We show an improvement in the classification of intraoperative stimulation coordinates as a positive response in reduction of symptoms with AUC of 0.670 compared to a baseline registration-based approach, which achieves an AUC of 0.627 (p < 0.01). Although additional validation is needed, the proposed classification framework and deep learning method appear well-suited for improving pre-surgical planning and personalize treatment strategies.

Dongqing Zhang, Jianing Wang, Jack H. Noble et al.

Cochlear implants (CIs) are neural prosthetics which are used to treat patients with hearing loss. CIs use an array of electrodes which are surgically inserted into the cochlea to stimulate the auditory nerve endings. After surgery, CIs need to be programmed. Studies have shown that the spatial relationship between the intra-cochlear anatomy and electrodes derived from medical images can guide CI programming and lead to significant improvement in hearing outcomes. However, clinical head CT images are usually obtained from scanners of different brands with different protocols. The field of view thus varies greatly and visual inspection is needed to document their content prior to applying algorithms for electrode localization and intra-cochlear anatomy segmentation. In this work, to determine the presence/absence of inner ears and to accurately localize them in head CTs, we use a volume-to-volume convolutional neural network which can be trained end-to-end to map a raw CT volume to probability maps which indicate inner ear positions. We incorporate a false positive suppression strategy in training and apply a shape-based constraint. We achieve a labeling accuracy of 98.59% and a localization error of 2.45mm. The localization error is significantly smaller than a random forest-based approach that has been proposed recently to perform the same task.