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arXiv subjects

Saad Nadeem

Publications and source records attributed to Saad Nadeem.

At least 19 recordsLinked to original sources

ImPartial: Multi-channel Whole-Cell Segmentation using Partial Annotations

Accurate cell segmentation in pathology images typically requires dense pixel-wise annotations, which are costly and time-consuming to obtain. This challenge is especially important for emerging biological imaging modalities and multiplexed datasets with variable channel configurations, where expert-labeled data are scarce. In this work, we introduce ImPartial, a deep learning framework designed to achieve state-of-the-art segmentation performance in low-annotation regimes using sparse scribbles and limited supervision. ImPartial augments the segmentation objective via self-supervised multi-channel quantized imputation. This approach leverages the observation that perfect pixel-wise reconstruction or denoising of the image is not needed for accurate segmentation, and thus, introduces a self-supervised classification objective that better aligns with the overall segmentation goal. We demonstrate that ImPartial achieves performance at par with fully supervised models while requiring substantially fewer annotations. Extensive experiments on benchmark multiplexed cellular imaging and single-plex clinical brightfield immunohistochemistry datasets show consistent improvements over strong baselines with only partial annotations. All benchmark datasets and code are available via our Github: https://github.com/nadeemlab/ImPartial.

cs.CV

RT-GAN: Recurrent Temporal GAN for Adding Lightweight Temporal Consistency to Frame-Based Domain Translation Approaches

Fourteen million colonoscopies are performed annually just in the U.S. However, the videos from these colonoscopies are not saved due to storage constraints (each video from a high-definition colonoscope camera can be in tens of gigabytes). Instead, a few relevant individual frames are saved for documentation/reporting purposes and these are the frames on which most current colonoscopy AI models are trained on. While developing new unsupervised domain translation methods for colonoscopy (e.g. to translate between real optical and virtual/CT colonoscopy), it is thus typical to start with approaches that initially work for individual frames without temporal consistency. Once an individual-frame model has been finalized, additional contiguous frames are added with a modified deep learning architecture to train a new model from scratch for temporal consistency. This transition to temporally-consistent deep learning models, however, requires significantly more computational and memory resources for training. In this paper, we present a lightweight solution with a tunable temporal parameter, RT-GAN (Recurrent Temporal GAN), for adding temporal consistency to individual frame-based approaches that reduces training requirements by a factor of 5. We demonstrate the effectiveness of our approach on two challenging use cases in colonoscopy: haustral fold segmentation (indicative of missed surface) and realistic colonoscopy simulator video generation. We also release a first-of-its kind temporal dataset for colonoscopy for the above use cases. The datasets, accompanying code, and pretrained models will be made available on our Computational Endoscopy Platform GitHub (https://github.com/nadeemlab/CEP). The supplementary video is available at https://youtu.be/UMVP-uIXwWk.

cs.CV

Rethinking Histology Slide Digitization Workflows for Low-Resource Settings

Histology slide digitization is becoming essential for telepathology (remote consultation), knowledge sharing (education), and using the state-of-the-art artificial intelligence algorithms (augmented/automated end-to-end clinical workflows). However, the cumulative costs of digital multi-slide high-speed brightfield scanners, cloud/on-premises storage, and personnel (IT and technicians) make the current slide digitization workflows out-of-reach for limited-resource settings, further widening the health equity gap; even single-slide manual scanning commercial solutions are costly due to hardware requirements (high-resolution cameras, high-spec PC/workstation, and support for only high-end microscopes). In this work, we present a new cloud slide digitization workflow for creating scanner-quality whole-slide images (WSIs) from uploaded low-quality videos, acquired from cheap and inexpensive microscopes with built-in cameras. Specifically, we present a pipeline to create stitched WSIs while automatically deblurring out-of-focus regions, upsampling input 10X images to 40X resolution, and reducing brightness/contrast and light-source illumination variations. We demonstrate the WSI creation efficacy from our workflow on World Health Organization-declared neglected tropical disease, Cutaneous Leishmaniasis (prevalent only in the poorest regions of the world and only diagnosed by sub-specialist dermatopathologists, rare in poor countries), as well as other common pathologies on core biopsies of breast, liver, duodenum, stomach and lymph node. The code and pretrained models will be accessible via our GitHub (https://github.com/nadeemlab/DeepLIIF), and the cloud platform will be available at https://deepliif.org for uploading microscope videos and downloading/viewing WSIs with shareable links (no sign-in required) for telepathology and knowledge sharing.

eess.IV

Vis-SPLIT: Interactive Hierarchical Modeling for mRNA Expression Classification

We propose an interactive visual analytics tool, Vis-SPLIT, for partitioning a population of individuals into groups with similar gene signatures. Vis-SPLIT allows users to interactively explore a dataset and exploit visual separations to build a classification model for specific cancers. The visualization components reveal gene expression and correlation to assist specific partitioning decisions, while also providing overviews for the decision model and clustered genetic signatures. We demonstrate the effectiveness of our framework through a case study and evaluate its usability with domain experts. Our results show that Vis-SPLIT can classify patients based on their genetic signatures to effectively gain insights into RNA sequencing data, as compared to an existing classification system.

cs.HC

Stain-invariant self supervised learning for histopathology image analysis

We present a self-supervised algorithm for several classification tasks within hematoxylin and eosin (H&E) stained images of breast cancer. Our method is robust to stain variations inherent to the histology images acquisition process, which has limited the applicability of automated analysis tools. We address this problem by imposing constraints a learnt latent space which leverages stain normalization techniques during training. At every iteration, we select an image as a normalization target and generate a version of every image in the batch normalized to that target. We minimize the distance between the embeddings that correspond to the same image under different staining variations while maximizing the distance between other samples. We show that our method not only improves robustness to stain variations across multi-center data, but also classification performance through extensive experiments on various normalization targets and methods. Our method achieves the state-of-the-art performance on several publicly available breast cancer datasets ranging from tumor classification (CAMELYON17) and subtyping (BRACS) to HER2 status classification and treatment response prediction.

cs.CV

An AI-Ready Multiplex Staining Dataset for Reproducible and Accurate Characterization of Tumor Immune Microenvironment

We introduce a new AI-ready computational pathology dataset containing restained and co-registered digitized images from eight head-and-neck squamous cell carcinoma patients. Specifically, the same tumor sections were stained with the expensive multiplex immunofluorescence (mIF) assay first and then restained with cheaper multiplex immunohistochemistry (mIHC). This is a first public dataset that demonstrates the equivalence of these two staining methods which in turn allows several use cases; due to the equivalence, our cheaper mIHC staining protocol can offset the need for expensive mIF staining/scanning which requires highly-skilled lab technicians. As opposed to subjective and error-prone immune cell annotations from individual pathologists (disagreement > 50%) to drive SOTA deep learning approaches, this dataset provides objective immune and tumor cell annotations via mIF/mIHC restaining for more reproducible and accurate characterization of tumor immune microenvironment (e.g. for immunotherapy). We demonstrate the effectiveness of this dataset in three use cases: (1) IHC quantification of CD3/CD8 tumor-infiltrating lymphocytes via style transfer, (2) virtual translation of cheap mIHC stains to more expensive mIF stains, and (3) virtual tumor/immune cellular phenotyping on standard hematoxylin images. The dataset is available at \url{https://github.com/nadeemlab/DeepLIIF}.

eess.IV

RMSim: Controlled Respiratory Motion Simulation on Static Patient Scans

This work aims to generate realistic anatomical deformations from static patient scans. Specifically, we present a method to generate these deformations/augmentations via deep learning driven respiratory motion simulation that provides the ground truth for validating deformable image registration (DIR) algorithms and driving more accurate deep learning based DIR. We present a novel 3D Seq2Seq deep learning respiratory motion simulator (RMSim) that learns from 4D-CT images and predicts future breathing phases given a static CT image. The predicted respiratory patterns, represented by time-varying displacement vector fields (DVFs) at different breathing phases, are modulated through auxiliary inputs of 1D breathing traces so that a larger amplitude in the trace results in more significant predicted deformation. Stacked 3D-ConvLSTMs are used to capture the spatial-temporal respiration patterns. Training loss includes a smoothness loss in the DVF and mean-squared error between the predicted and ground truth phase images. A spatial transformer deforms the static CT with the predicted DVF to generate the predicted phase image. 10-phase 4D-CTs of 140 internal patients were used to train and test RMSim. The trained RMSim was then used to augment a public DIR challenge dataset for training VoxelMorph to show the effectiveness of RMSim-generated deformation augmentation. We validated our RMSim output with both private and public benchmark datasets (healthy and cancer patients). The proposed approach can be used for validating DIR algorithms as well as for patient-specific augmentations to improve deep learning DIR algorithms. The code, pretrained models, and augmented DIR validation datasets will be released at https://github.com/nadeemlab/SeqX2Y.

cs.CV

Domain Knowledge Driven 3D Dose Prediction Using Moment-Based Loss Function

Dose volume histogram (DVH) metrics are widely accepted evaluation criteria in the clinic. However, incorporating these metrics into deep learning dose prediction models is challenging due to their non-convexity and non-differentiability. We propose a novel moment-based loss function for predicting 3D dose distribution for the challenging conventional lung intensity modulated radiation therapy (IMRT) plans. The moment-based loss function is convex and differentiable and can easily incorporate DVH metrics in any deep learning framework without computational overhead. The moments can also be customized to reflect the clinical priorities in 3D dose prediction. For instance, using high-order moments allows better prediction in high-dose areas for serial structures. We used a large dataset of 360 conventional lung patients with 2Gy $\times$ 30 fractions to train the deep learning (DL) model using clinically treated plans. We trained a UNet-like CNN architecture using computed tomography (CT), planning target volume (PTV) and organ-at-risk contours (OAR) as input to infer corresponding voxel-wise 3D dose distribution. We evaluated three different loss functions: (1) Mean Absolute Error (MAE) Loss, (2) MAE + DVH Loss, and (3) the proposed MAE + Moments Loss. The quality of the predictions was compared using different DVH metrics as well as dose-score and DVH-score, recently introduced by the AAPM knowledge-based planning grand challenge. Model with (MAE + Moment) loss function outperformed the model with MAE loss by significantly improving the DVH-score (11%, p$<$0.01) while having similar computational cost. It also outperformed the model trained with (MAE+DVH) by significantly improving the computational cost (48%) and the DVH-score (8%, p$<$0.01). The code, models, docker container, and Google Colab project are available on our DoseRTX GitHub (https://github.com/nadeemlab/DoseRTX).

cs.CV

CIRDataset: A large-scale Dataset for Clinically-Interpretable lung nodule Radiomics and malignancy prediction

Spiculations/lobulations, sharp/curved spikes on the surface of lung nodules, are good predictors of lung cancer malignancy and hence, are routinely assessed and reported by radiologists as part of the standardized Lung-RADS clinical scoring criteria. Given the 3D geometry of the nodule and 2D slice-by-slice assessment by radiologists, manual spiculation/lobulation annotation is a tedious task and thus no public datasets exist to date for probing the importance of these clinically-reported features in the SOTA malignancy prediction algorithms. As part of this paper, we release a large-scale Clinically-Interpretable Radiomics Dataset, CIRDataset, containing 956 radiologist QA/QC'ed spiculation/lobulation annotations on segmented lung nodules from two public datasets, LIDC-IDRI (N=883) and LUNGx (N=73). We also present an end-to-end deep learning model based on multi-class Voxel2Mesh extension to segment nodules (while preserving spikes), classify spikes (sharp/spiculation and curved/lobulation), and perform malignancy prediction. Previous methods have performed malignancy prediction for LIDC and LUNGx datasets but without robust attribution to any clinically reported/actionable features (due to known hyperparameter sensitivity issues with general attribution schemes). With the release of this comprehensively-annotated CIRDataset and end-to-end deep learning baseline, we hope that malignancy prediction methods can validate their explanations, benchmark against our baseline, and provide clinically-actionable insights. Dataset, code, pretrained models, and docker containers are available at https://github.com/nadeemlab/CIR.

eess.IV

CLTS-GAN: Color-Lighting-Texture-Specular Reflection Augmentation for Colonoscopy

Automated analysis of optical colonoscopy (OC) video frames (to assist endoscopists during OC) is challenging due to variations in color, lighting, texture, and specular reflections. Previous methods either remove some of these variations via preprocessing (making pipelines cumbersome) or add diverse training data with annotations (but expensive and time-consuming). We present CLTS-GAN, a new deep learning model that gives fine control over color, lighting, texture, and specular reflection synthesis for OC video frames. We show that adding these colonoscopy-specific augmentations to the training data can improve state-of-the-art polyp detection/segmentation methods as well as drive next generation of OC simulators for training medical students. The code and pre-trained models for CLTS-GAN are available on Computational Endoscopy Platform GitHub (https://github.com/nadeemlab/CEP).

eess.IV

DeepLIIF: An Online Platform for Quantification of Clinical Pathology Slides

In the clinic, resected tissue samples are stained with Hematoxylin-and-Eosin (H&E) and/or Immunhistochemistry (IHC) stains and presented to the pathologists on glass slides or as digital scans for diagnosis and assessment of disease progression. Cell-level quantification, e.g. in IHC protein expression scoring, can be extremely inefficient and subjective. We present DeepLIIF (https://deepliif.org), a first free online platform for efficient and reproducible IHC scoring. DeepLIIF outperforms current state-of-the-art approaches (relying on manual error-prone annotations) by virtually restaining clinical IHC slides with more informative multiplex immunofluorescence staining. Our DeepLIIF cloud-native platform supports (1) more than 150 proprietary/non-proprietary input formats via the Bio-Formats standard, (2) interactive adjustment, visualization, and downloading of the IHC quantification results and the accompanying restained images, (3) consumption of an exposed workflow API programmatically or through interactive plugins for open source whole slide image viewers such as QuPath/ImageJ, and (4) auto scaling to efficiently scale GPU resources based on user demand.

cs.CV

An exact test for significance of clusters in binary data

Unsupervised clustering of feature matrix data is an indispensible technique for exploratory data analysis and quality control of experimental data. However, clusters are difficult to assess for statistical significance in an objective way. We prove a formula for the distribution of the size of the set of samples, out of a population of fixed size, which display a given signature, conditional on the marginals (frequencies) of each individual feature comprising the signature. The resulting "exact test for coincidence" is widely applicable to objective assessment of clusters in any binary data. We also present a software package implementing the test, a suite of computational verifications of the main theorems, and a supplemental tool for cluster discovery using Formal Concept Analysis.

math.ST

Deformation Driven Seq2Seq Longitudinal Tumor and Organs-at-Risk Prediction for Radiotherapy

Purpose: Radiotherapy presents unique challenges and clinical requirements for longitudinal tumor and organ-at-risk (OAR) prediction during treatment. The challenges include tumor inflammation/edema and radiation-induced changes in organ geometry, whereas the clinical requirements demand flexibility in input/output sequence timepoints to update the predictions on rolling basis and the grounding of all predictions in relationship to the pre-treatment imaging information for response and toxicity assessment in adaptive radiotherapy. Methods: To deal with the aforementioned challenges and to comply with the clinical requirements, we present a novel 3D sequence-to-sequence model based on Convolution Long Short Term Memory (ConvLSTM) that makes use of series of deformation vector fields (DVF) between individual timepoints and reference pre-treatment/planning CTs to predict future anatomical deformations and changes in gross tumor volume as well as critical OARs. High-quality DVF training data is created by employing hyper-parameter optimization on the subset of the training data with DICE coefficient and mutual information metric. We validated our model on two radiotherapy datasets: a publicly available head-and-neck dataset (28 patients with manually contoured pre-, mid-, and post-treatment CTs), and an internal non-small cell lung cancer dataset (63 patients with manually contoured planning CT and 6 weekly CBCTs). Results: The use of DVF representation and skip connections overcomes the blurring issue of ConvLSTM prediction with the traditional image representation. The mean and standard deviation of DICE for predictions of lung GTV at week 4, 5, and 6 were 0.83$\pm$0.09, 0.82$\pm$0.08, and 0.81$\pm$0.10, respectively, and for post-treatment ipsilateral and contralateral parotids, were 0.81$\pm$0.06 and 0.85$\pm$0.02.

cs.CV

Multitask 3D CBCT-to-CT Translation and Organs-at-Risk Segmentation Using Physics-Based Data Augmentation

In current clinical practice, noisy and artifact-ridden weekly cone-beam computed tomography (CBCT) images are only used for patient setup during radiotherapy. Treatment planning is done once at the beginning of the treatment using high-quality planning CT (pCT) images and manual contours for organs-at-risk (OARs) structures. If the quality of the weekly CBCT images can be improved while simultaneously segmenting OAR structures, this can provide critical information for adapting radiotherapy mid-treatment as well as for deriving biomarkers for treatment response. Using a novel physics-based data augmentation strategy, we synthesize a large dataset of perfectly/inherently registered planning CT and synthetic-CBCT pairs for locally advanced lung cancer patient cohort, which are then used in a multitask 3D deep learning framework to simultaneously segment and translate real weekly CBCT images to high-quality planning CT-like images. We compared the synthetic CT and OAR segmentations generated by the model to real planning CT and manual OAR segmentations and showed promising results. The real week 1 (baseline) CBCT images which had an average MAE of 162.77 HU compared to pCT images are translated to synthetic CT images that exhibit a drastically improved average MAE of 29.31 HU and average structural similarity of 92% with the pCT images. The average DICE scores of the 3D organs-at-risk segmentations are: lungs 0.96, heart 0.88, spinal cord 0.83 and esophagus 0.66. This approach could allow clinicians to adjust treatment plans using only the routine low-quality CBCT images, potentially improving patient outcomes. Our code, data, and pre-trained models will be made available via our physics-based data augmentation library, Physics-ArX, at https://github.com/nadeemlab/Physics-ArX.

eess.IV

FoldIt: Haustral Folds Detection and Segmentation in Colonoscopy Videos

Haustral folds are colon wall protrusions implicated for high polyp miss rate during optical colonoscopy procedures. If segmented accurately, haustral folds can allow for better estimation of missed surface and can also serve as valuable landmarks for registering pre-treatment virtual (CT) and optical colonoscopies, to guide navigation towards the anomalies found in pre-treatment scans. We present a novel generative adversarial network, FoldIt, for feature-consistent image translation of optical colonoscopy videos to virtual colonoscopy renderings with haustral fold overlays. A new transitive loss is introduced in order to leverage ground truth information between haustral fold annotations and virtual colonoscopy renderings. We demonstrate the effectiveness of our model on real challenging optical colonoscopy videos as well as on textured virtual colonoscopy videos with clinician-verified haustral fold annotations. All code and scripts to reproduce the experiments of this paper will be made available via our Computational Endoscopy Platform at https://github.com/nadeemlab/CEP.

eess.IV

Augmenting Colonoscopy using Extended and Directional CycleGAN for Lossy Image Translation

Colorectal cancer screening modalities, such as optical colonoscopy (OC) and virtual colonoscopy (VC), are critical for diagnosing and ultimately removing polyps (precursors of colon cancer). The non-invasive VC is normally used to inspect a 3D reconstructed colon (from CT scans) for polyps and if found, the OC procedure is performed to physically traverse the colon via endoscope and remove these polyps. In this paper, we present a deep learning framework, Extended and Directional CycleGAN, for lossy unpaired image-to-image translation between OC and VC to augment OC video sequences with scale-consistent depth information from VC, and augment VC with patient-specific textures, color and specular highlights from OC (e.g, for realistic polyp synthesis). Both OC and VC contain structural information, but it is obscured in OC by additional patient-specific texture and specular highlights, hence making the translation from OC to VC lossy. The existing CycleGAN approaches do not handle lossy transformations. To address this shortcoming, we introduce an extended cycle consistency loss, which compares the geometric structures from OC in the VC domain. This loss removes the need for the CycleGAN to embed OC information in the VC domain. To handle a stronger removal of the textures and lighting, a Directional Discriminator is introduced to differentiate the direction of translation (by creating paired information for the discriminator), as opposed to the standard CycleGAN which is direction-agnostic. Combining the extended cycle consistency loss and the Directional Discriminator, we show state-of-the-art results on scale-consistent depth inference for phantom, textured VC and for real polyp and normal colon video sequences. We also present results for realistic pendunculated and flat polyp synthesis from bumps introduced in 3D VC models. Code/models: https://github.com/nadeemlab/CEP.

eess.IV

Visualizing Missing Surfaces In Colonoscopy Videos using Shared Latent Space Representations

Optical colonoscopy (OC), the most prevalent colon cancer screening tool, has a high miss rate due to a number of factors, including the geometry of the colon (haustral fold and sharp bends occlusions), endoscopist inexperience or fatigue, endoscope field of view, etc. We present a framework to visualize the missed regions per-frame during the colonoscopy, and provides a workable clinical solution. Specifically, we make use of 3D reconstructed virtual colonoscopy (VC) data and the insight that VC and OC share the same underlying geometry but differ in color, texture and specular reflections, embedded in the OC domain. A lossy unpaired image-to-image translation model is introduced with enforced shared latent space for OC and VC. This shared latent space captures the geometric information while deferring the color, texture, and specular information creation to additional Gaussian noise input. This additional noise input can be utilized to generate one-to-many mappings from VC to OC and OC to OC. The code, data and trained models will be released via our Computational Endoscopy Platform at https://github.com/nadeemlab/CEP.

eess.IV

Deep Learning 3D Dose Prediction for Conventional Lung IMRT Using Consistent/Unbiased Automated Plans

Deep learning (DL) 3D dose prediction has recently gained a lot of attention. However, the variability of plan quality in the training dataset, generated manually by planners with wide range of expertise, can dramatically effect the quality of the final predictions. Moreover, any changes in the clinical criteria requires a new set of manually generated plans by planners to build a new prediction model. In this work, we instead use consistent plans generated by our in-house automated planning system (named ``ECHO'') to train the DL model. ECHO (expedited constrained hierarchical optimization) generates consistent/unbiased plans by solving large-scale constrained optimization problems sequentially. If the clinical criteria changes, a new training data set can be easily generated offline using ECHO, with no or limited human intervention, making the DL-based prediction model easily adaptable to the changes in the clinical practice. We used 120 conventional lung patients (100 for training, 20 for testing) with different beam configurations and trained our DL-model using manually-generated as well as automated ECHO plans. We evaluated different inputs: (1) CT+(PTV/OAR)contours, and (2) CT+contours+beam configurations, and different loss functions: (1) MAE (mean absolute error), and (2) MAE+DVH (dose volume histograms). The quality of the predictions was compared using different DVH metrics as well as dose-score and DVH-score, recently introduced by the AAPM knowledge-based planning grand challenge. The best results were obtained using automated ECHO plans and CT+contours+beam as training inputs and MAE+DVH as loss function.

cs.CV