Andrew F. Laine

Xuzhe Zhang, Yuhao Wu, Elsa Angelini et al.

Robust segmentation is critical for deriving quantitative measures from large-scale, multi-center, and longitudinal medical scans. Manually annotating medical scans, however, is expensive and labor-intensive and may not always be available in every domain. Unsupervised domain adaptation (UDA) is a well-studied technique that alleviates this label-scarcity problem by leveraging available labels from another domain. In this study, we introduce Masked Autoencoding and Pseudo-Labeling Segmentation (MAPSeg), a $\textbf{unified}$ UDA framework with great versatility and superior performance for heterogeneous and volumetric medical image segmentation. To the best of our knowledge, this is the first study that systematically reviews and develops a framework to tackle four different domain shifts in medical image segmentation. More importantly, MAPSeg is the first framework that can be applied to $\textbf{centralized}$, $\textbf{federated}$, and $\textbf{test-time}$ UDA while maintaining comparable performance. We compare MAPSeg with previous state-of-the-art methods on a private infant brain MRI dataset and a public cardiac CT-MRI dataset, and MAPSeg outperforms others by a large margin (10.5 Dice improvement on the private MRI dataset and 5.7 on the public CT-MRI dataset). MAPSeg poses great practical value and can be applied to real-world problems. GitHub: https://github.com/XuzheZ/MAPSeg/.

Aaron Cao, Zongyu Li, Jordan Jomsky et al.

Widely used traditional pipelines for subcortical brain segmentation are often inefficient and slow, particularly when processing large datasets. Furthermore, deep learning models face challenges due to the high resolution of MRI images and the large number of anatomical classes involved. To address these limitations, we developed a 3D patch-based hybrid CNN-Mamba model that leverages Mamba's selective scan algorithm, thereby enhancing segmentation accuracy and efficiency for 3D inputs. This retrospective study utilized 1784 T1-weighted MRI scans from a diverse, multi-site dataset of healthy individuals. The dataset was divided into training, validation, and testing sets with a 1076/345/363 split. The scans were obtained from 1.5T and 3T MRI machines. Our model's performance was validated against several benchmarks, including other CNN-Mamba, CNN-Transformer, and pure CNN networks, using FreeSurfer-generated ground truths. We employed the Dice Similarity Coefficient (DSC), Volume Similarity (VS), and Average Symmetric Surface Distance (ASSD) as evaluation metrics. Statistical significance was determined using the Wilcoxon signed-rank test with a threshold of P < 0.05. The proposed model achieved the highest overall performance across all metrics (DSC 0.88383; VS 0.97076; ASSD 0.33604), significantly outperforming all non-Mamba-based models (P < 0.001). While the model did not show significant improvement in DSC or VS compared to another Mamba-based model (P-values of 0.114 and 0.425), it demonstrated a significant enhancement in ASSD (P < 0.001) with approximately 20% fewer parameters. In conclusion, our proposed hybrid CNN-Mamba architecture offers an efficient and accurate approach for 3D subcortical brain segmentation, demonstrating potential advantages over existing methods. Code is available at: https://github.com/aaroncao06/MedSegMamba.

Vishwanatha M. Rao, Zihan Wan, Soroush Arabshahi et al.

Brain tissue segmentation has demonstrated great utility in quantifying MRI data through Voxel-Based Morphometry and highlighting subtle structural changes associated with various conditions within the brain. However, manual segmentation is highly labor-intensive, and automated approaches have struggled due to properties inherent to MRI acquisition, leaving a great need for an effective segmentation tool. Despite the recent success of deep convolutional neural networks (CNNs) for brain tissue segmentation, many such solutions do not generalize well to new datasets, which is critical for a reliable solution. Transformers have demonstrated success in natural image segmentation and have recently been applied to 3D medical image segmentation tasks due to their ability to capture long-distance relationships in the input where the local receptive fields of CNNs struggle. This study introduces a novel CNN-Transformer hybrid architecture designed for brain tissue segmentation. We validate our model's performance across four multi-site T1w MRI datasets, covering different vendors, field strengths, scan parameters, time points, and neuropsychiatric conditions. In all situations, our model achieved the greatest generality and reliability. Out method is inherently robust and can serve as a valuable tool for brain-related T1w MRI studies. The code for the TABS network is available at: https://github.com/raovish6/TABS.

Aaron Cao, Vishwanatha M. Rao, Kejia Liu et al.

Subcortical segmentation remains challenging despite its important applications in quantitative structural analysis of brain MRI scans. The most accurate method, manual segmentation, is highly labor intensive, so automated tools like FreeSurfer have been adopted to handle this task. However, these traditional pipelines are slow and inefficient for processing large datasets. In this study, we propose TABSurfer, a novel 3D patch-based CNN-Transformer hybrid deep learning model designed for superior subcortical segmentation compared to existing state-of-the-art tools. To evaluate, we first demonstrate TABSurfer's consistent performance across various T1w MRI datasets with significantly shorter processing times compared to FreeSurfer. Then, we validate against manual segmentations, where TABSurfer outperforms FreeSurfer based on the manual ground truth. In each test, we also establish TABSurfer's advantage over a leading deep learning benchmark, FastSurferVINN. Together, these studies highlight TABSurfer's utility as a powerful tool for fully automated subcortical segmentation with high fidelity.

Xinliu Zhong, Ruiying Liu, Emily S. Nichols et al.

Accurate placental segmentation is essential for quantitative analysis of the placenta. However, this task is particularly challenging in T2*-weighted placental imaging due to: (1) weak and inconsistent boundary contrast across individual echoes; (2) the absence of manual ground truth annotations for all echo times; and (3) motion artifacts across echoes caused by fetal and maternal movement. In this work, we propose a contrast-augmented segmentation framework that leverages complementary information across multi-echo T2*-weighted MRI to learn robust, contrast-invariant representations. Our method integrates: (i) masked autoencoding (MAE) for self-supervised pretraining on unlabeled multi-echo slices; (ii) masked pseudo-labeling (MPL) for unsupervised domain adaptation across echo times; and (iii) global-local collaboration to align fine-grained features with global anatomical context. We further introduce a semantic matching loss to encourage representation consistency across echoes of the same subject. Experiments on a clinical multi-echo placental MRI dataset demonstrate that our approach generalizes effectively across echo times and outperforms both single-echo and naive fusion baselines. To our knowledge, this is the first work to systematically exploit multi-echo T2*-weighted MRI for placental segmentation.

Sneha N. Naik, Elsa D. Angelini, Eric A. Hoffman et al.

The ratio of airway tree lumen to lung size (ALR), assessed at full inspiration on high resolution full-lung computed tomography (CT), is a major risk factor for chronic obstructive pulmonary disease (COPD). There is growing interest to infer ALR from cardiac CT images, which are widely available in epidemiological cohorts, to investigate the relationship of ALR to severe COVID-19 and post-acute sequelae of SARS-CoV-2 infection (PASC). Previously, cardiac scans included approximately 2/3 of the total lung volume with 5-6x greater slice thickness than high-resolution (HR) full-lung (FL) CT. In this study, we present a novel attention-based Multi-view Swin Transformer to infer FL ALR values from segmented cardiac CT scans. For the supervised training we exploit paired full-lung and cardiac CTs acquired in the Multi-Ethnic Study of Atherosclerosis (MESA). Our network significantly outperforms a proxy direct ALR inference on segmented cardiac CT scans and achieves accuracy and reproducibility comparable with a scan-rescan reproducibility of the FL ALR ground-truth.

Artur Wysoczanski, Nabil Ettehadi, Soroush Arabshahi et al.

Pulmonary emphysema, the progressive, irreversible loss of lung tissue, is conventionally categorized into three subtypes identifiable on pathology and on lung computed tomography (CT) images. Recent work has led to the unsupervised learning of ten spatially-informed lung texture patterns (sLTPs) on lung CT, representing distinct patterns of emphysematous lung parenchyma based on both textural appearance and spatial location within the lung, and which aggregate into 6 robust and reproducible CT Emphysema Subtypes (CTES). Existing methods for sLTP segmentation, however, are slow and highly sensitive to changes in CT acquisition protocol. In this work, we present a robust 3-D squeeze-and-excitation CNN for supervised classification of sLTPs and CTES on lung CT. Our results demonstrate that this model achieves accurate and reproducible sLTP segmentation on lung CTscans, across two independent cohorts and independently of scanner manufacturer and model.

Xuzhe Zhang, Elsa D. Angelini, Eric A. Hoffman et al.

Robust quantification of pulmonary emphysema on computed tomography (CT) remains challenging for large-scale research studies that involve scans from different scanner types and for translation to clinical scans. Existing studies have explored several directions to tackle this challenge, including density correction, noise filtering, regression, hidden Markov measure field (HMMF) model-based segmentation, and volume-adjusted lung density. Despite some promising results, previous studies either required a tedious workflow or limited opportunities for downstream emphysema subtyping, limiting efficient adaptation on a large-scale study. To alleviate this dilemma, we developed an end-to-end deep learning framework based on an existing HMMF segmentation framework. We first demonstrate that a regular UNet cannot replicate the existing HMMF results because of the lack of scanner priors. We then design a novel domain attention block to fuse image feature with quantitative scanner priors which significantly improves the results.

Elena Alexander, Kam W. Leong, Andrew F. Laine

Circulating Tumor Cells (CTCs) bear great promise as biomarkers in tumor prognosis. However, the process of identification and later enumeration of CTCs require manual labor, which is error-prone and time-consuming. The recent developments in object detection via Deep Learning using Mask-RCNNs and wider availability of pre-trained models have enabled sensitive tasks with limited data of such to be tackled with unprecedented accuracy. In this report, we present a novel 3-stage detection model for automated identification of Circulating Tumor Cells in multi-channel darkfield microscopic images comprised of: RetinaNet based identification of Cytokeratin (CK) stains, Mask-RCNN based cell detection of DAPI cell nuclei and Otsu thresholding to detect CD-45s. The training dataset is composed of 46 high variance data points, with 10 Negative and 36 Positive data points. The test set is composed of 420 negative data points. The final accuracy of the pipeline is 98.81%.

Sang Won Lee, Yueh-Ting Chiu, Philip Brudnicki et al.

Recent advances in the interdisciplinary scientific field of machine perception, computer vision, and biomedical engineering underpin a collection of machine learning algorithms with a remarkable ability to decipher the contents of microscope and nanoscope images. Machine learning algorithms are transforming the interpretation and analysis of microscope and nanoscope imaging data through use in conjunction with biological imaging modalities. These advances are enabling researchers to carry out real-time experiments that were previously thought to be computationally impossible. Here we adapt the theory of survival of the fittest in the field of computer vision and machine perception to introduce a new framework of multi-class instance segmentation deep learning, Darwin's Neural Network (DNN), to carry out morphometric analysis and classification of COVID19 and MERS-CoV collected in vivo and of multiple mammalian cell types in vitro.

Jie Yang, Elsa D. Angelini, Pallavi P. Balte et al.

Pulmonary emphysema overlaps considerably with chronic obstructive pulmonary disease (COPD), and is traditionally subcategorized into three subtypes previously identified on autopsy. Unsupervised learning of emphysema subtypes on computed tomography (CT) opens the way to new definitions of emphysema subtypes and eliminates the need of thorough manual labeling. However, CT-based emphysema subtypes have been limited to texture-based patterns without considering spatial location. In this work, we introduce a standardized spatial mapping of the lung for quantitative study of lung texture location, and propose a novel framework for combining spatial and texture information to discover spatially-informed lung texture patterns (sLTPs) that represent novel emphysema subtypes. Exploiting two cohorts of full-lung CT scans from the MESA COPD and EMCAP studies, we first show that our spatial mapping enables population-wide study of emphysema spatial location. We then evaluate the characteristics of the sLTPs discovered on MESA COPD, and show that they are reproducible, able to encode standard emphysema subtypes, and associated with physiological symptoms.

Haoran Sun, Xueqing Liu, Xinyang Feng et al.

Cerebral blood volume (CBV) is a hemodynamic correlate of oxygen metabolism and reflects brain activity and function. High-resolution CBV maps can be generated using the steady-state gadolinium-enhanced MRI technique. Such a technique requires an intravenous injection of exogenous gadolinium based contrast agent (GBCA) and recent studies suggest that the GBCA can accumulate in the brain after frequent use. We hypothesize that endogenous sources of contrast might exist within the most conventional and commonly acquired structural MRI, potentially obviating the need for exogenous contrast. Here, we test this hypothesis by developing and optimizing a deep learning algorithm, which we call DeepContrast, in mice. We find that DeepContrast performs equally well as exogenous GBCA in mapping CBV of the normal brain tissue and enhancing glioblastoma. Together, these studies validate our hypothesis that a deep learning approach can potentially replace the need for GBCAs in brain MRI.

Nanyan Zhu, Chen Liu, Zakary S. Singer et al.

The ability to extrapolate gene expression dynamics in living single cells requires robust cell segmentation, and one of the challenges is the amorphous or irregularly shaped cell boundaries. To address this issue, we modified the U-Net architecture to segment cells in fluorescence widefield microscopy images and quantitatively evaluated its performance. We also proposed a novel loss function approach that emphasizes the segmentation accuracy on cell boundaries and encourages shape feature preservation. With a 97% sensitivity, 93% specificity, 91% Jaccard similarity, and 95% Dice coefficient, our proposed method called Residual Attention U-Net with edge-enhancement surpassed the state-of-the-art U-Net in segmentation performance as evaluated by the traditional metrics. More remarkably, the same proposed candidate also performed the best in terms of the preservation of valuable shape features, namely area, eccentricity, major axis length, solidity and orientation. These improvements on shape feature preservation can serve as useful assets for downstream cell tracking and quantification of changes in cell statistics or features over time.

Jie Yang, Siqi Liu, Sasa Grbic et al.

Though large-scale datasets are essential for training deep learning systems, it is expensive to scale up the collection of medical imaging datasets. Synthesizing the objects of interests, such as lung nodules, in medical images based on the distribution of annotated datasets can be helpful for improving the supervised learning tasks, especially when the datasets are limited by size and class balance. In this paper, we propose the class-aware adversarial synthesis framework to synthesize lung nodules in CT images. The framework is built with a coarse-to-fine patch in-painter (generator) and two class-aware discriminators. By conditioning on the random latent variables and the target nodule labels, the trained networks are able to generate diverse nodules given the same context. By evaluating on the public LIDC-IDRI dataset, we demonstrate an example application of the proposed framework for improving the accuracy of the lung nodule malignancy estimation as a binary classification problem, which is important in the lung screening scenario. We show that combining the real image patches and the synthetic lung nodules in the training set can improve the mean AUC classification score across different network architectures by 2%.

Xinyang Feng, Jie Yang, Andrew F. Laine et al.

In neuroimaging studies, the human cortex is commonly modeled as a sphere to preserve the topological structure of the cortical surface. Cortical neuroimaging measures hence can be modeled in spherical representation. In this work, we explore analyzing the human cortex using spherical CNNs in an Alzheimer's disease (AD) classification task using cortical morphometric measures derived from structural MRI. Our results show superior performance in classifying AD versus cognitively normal and in predicting MCI progression within two years, using structural MRI information only. This work demonstrates for the first time the potential of the spherical CNNs framework in the discriminative analysis of the human cortex and could be extended to other modalities and other neurological diseases.

Xinyang Feng, Jie Yang, Andrew F. Laine et al.

Automated detection and segmentation of pulmonary nodules on lung computed tomography (CT) scans can facilitate early lung cancer diagnosis. Existing supervised approaches for automated nodule segmentation on CT scans require voxel-based annotations for training, which are labor- and time-consuming to obtain. In this work, we propose a weakly-supervised method that generates accurate voxel-level nodule segmentation trained with image-level labels only. By adapting a convolutional neural network (CNN) trained for image classification, our proposed method learns discriminative regions from the activation maps of convolution units at different scales, and identifies the true nodule location with a novel candidate-screening framework. Experimental results on the public LIDC-IDRI dataset demonstrate that, our weakly-supervised nodule segmentation framework achieves competitive performance compared to a fully-supervised CNN-based segmentation method.

Jie Yang, Elsa D. Angelini, Benjamin M. Smith et al.

Pulmonary emphysema is traditionally subcategorized into three subtypes, which have distinct radiological appearances on computed tomography (CT) and can help with the diagnosis of chronic obstructive pulmonary disease (COPD). Automated texture-based quantification of emphysema subtypes has been successfully implemented via supervised learning of these three emphysema subtypes. In this work, we demonstrate that unsupervised learning on a large heterogeneous database of CT scans can generate texture prototypes that are visually homogeneous and distinct, reproducible across subjects, and capable of predicting accurately the three standard radiological subtypes. These texture prototypes enable automated labeling of lung volumes, and open the way to new interpretations of lung CT scans with finer subtyping of emphysema.