Invasive Mediastinal Aspergillosis in an 18-Year-Old Immunocompetent Female Leading to Stroke.

We present a case of invasive pulmonary aspergillosis in an immunocompetent young female. An 18-year-old female presented with symptoms of a left-sided middle cerebral artery (MCA) stroke with right arm weakness and aphasia. Computed tomography (CT) brain confirmed the diagnosis of stroke.

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.

The Use of Reframing: Increasing the Importance of Lifestyle Medicine.

Lifestyle behavior modification is an essential component to prevention and treatment of non-communicable diseases worldwide. For the last 40 years, studies have recognized that there is suboptimal training of physicians in lifestyle medicine and its implementation in clinical settings. The lack of nutrition and exercise counseling occurring in the medical office does not reflect the high level of evidence supporting its use.

Exploring published and novel pre-treatment CT and PET radiomics to stratify risk of progression among early-stage non-small cell lung cancer patients treated with stereotactic radiation.

Purpose: Disease progression after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) occurs in 20-40% of patients. Here, we explored published and novel pre-treatment CT and PET radiomics features to identify patients at risk of progression.

Materials/methods: Published CT and PET features were identified and explored along with 15 other CT and PET features in 408 consecutively treated early-stage NSCLC patients having CT and PET < 3 months pre-SBRT (training/set-aside validation subsets: n = 286/122).

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.

Ki67 proliferation index in medullary thyroid carcinoma: a comparative study of multiple counting methods and validation of image analysis and deep learning platforms.

Aims: The International Medullary Thyroid Carcinoma Grading System, introduced in 2022, mandates evaluation of the Ki67 proliferation index to assign a histological grade for medullary thyroid carcinoma. However, manual counting remains a tedious and time-consuming task.

Methods And Results: We aimed to evaluate the performance of three other counting techniques for the Ki67 index, eyeballing by a trained experienced investigator, a machine learning-based deep learning algorithm (DeepLIIF) and an image analysis software with internal thresholding compared to the gold standard manual counting in a large cohort of 260 primarily resected medullary thyroid carcinoma.

Integration of peripheral blood- and tissue-based biomarkers of response to immune checkpoint blockade in urothelial carcinoma.

As predictive biomarkers of response to immune checkpoint inhibitors (ICIs) remain a major unmet clinical need in patients with urothelial carcinoma (UC), we sought to identify tissue-based immune biomarkers of clinical benefit to ICIs using multiplex immunofluorescence and to integrate these findings with previously identified peripheral blood biomarkers of response. Fifty-five pretreatment and 12 paired on-treatment UC specimens were identified from patients treated with nivolumab with or without ipilimumab. Whole tissue sections were stained with a 12-plex mIF panel, including CD8, PD-1/CD279, PD-L1/CD274, CD68, CD3, CD4, FoxP3, TCF1/7, Ki67, LAG-3, MHC-II/HLA-DR, and pancytokeratin+SOX10 to identify over three million cells.

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.

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.

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).

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.

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.

Deep Learning-Inferred Multiplex ImmunoFluorescence for Immunohistochemical Image Quantification.

Reporting biomarkers assessed by routine immunohistochemical (IHC) staining of tissue is broadly used in diagnostic pathology laboratories for patient care. To date, clinical reporting is predominantly qualitative or semi-quantitative. By creating a multitask deep learning framework referred to as DeepLIIF, we present a single-step solution to stain deconvolution/separation, cell segmentation, and quantitative single-cell IHC scoring.

Domain knowledge driven 3D dose prediction using moment-based loss function.

To propose a novel moment-based loss function for predicting 3D dose distribution for the challenging conventional lung intensity modulated radiation therapy plans. The moment-based loss function is convex and differentiable and can easily incorporate clinical dose volume histogram (DVH) domain knowledge in any deep learning (DL) framework without computational overhead.We used a large dataset of 360 (240 for training, 50 for validation and 70 for testing) conventional lung patients with 2 Gy × 30 fractions to train the DL model using clinically treated plans at our institution.

Incorporating Nutrition Counseling into Lifestyle Medicine.

Despite considerable evidence that plant-based diets can significantly improve health, medical professionals seldom discuss this with their patients. This issue might occur due to minimal training received in medical education, lack of time, and low self-efficacy for counseling patients about diet. Nutrition and lifestyle change should be considered a core competency for all physicians and health professionals looking for cost-effective ways to improve patient health outcomes and reduce nutrition-related chronic diseases.

Tumor Immune Microenvironment and Response to Neoadjuvant Chemotherapy in Hormone Receptor/HER2+ Early Stage Breast Cancer.

Background: Pathologic response at the time of surgery after neoadjuvant therapy for HER2 positive early breast cancer impacts both prognosis and subsequent adjuvant therapy. Comprehensive descriptions of the tumor microenvironment (TME) in patients with HER2 positive early breast cancer is not well described. We utilized standard stromal pathologist-assessed tumor infiltrating lymphocyte (TIL) quantification, quantitative multiplex immunofluorescence, and RNA-based gene pathway signatures to assess pretreatment TME characteristics associated pathologic complete response in patients with hormone receptor positive, HER2 positive early breast cancer treated in the neoadjuvant setting.

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.

Tumor MHC Class I Expression Associates with Intralesional IL2 Response in Melanoma.

Cancer immunotherapy can result in lasting tumor regression, but predictive biomarkers of treatment response remain ill-defined. Here, we performed single-cell proteomics, transcriptomics, and genomics on matched untreated and IL2 injected metastases from patients with melanoma. Lesions that completely regressed following intralesional IL2 harbored increased fractions and densities of nonproliferating CD8+ T cells lacking expression of PD-1, LAG-3, and TIM-3 (PD-1-LAG-3-TIM-3-).

Volume Exploration Using Multidimensional Bhattacharyya Flow.

We present a novel approach for volume exploration that is versatile yet effective in isolating semantic structures in both noisy and clean data. Specifically, we describe a hierarchical active contours approach based on Bhattacharyya gradient flow which is easier to control, robust to noise, and can incorporate various types of statistical information to drive an edge-agnostic exploration process. To facilitate a time-bound user-driven volume exploration process that is applicable to a wide variety of data sources, we present an efficient multi-GPU implementation that (1) is approximately 400 times faster than a single thread CPU implementation, (2) allows hierarchical exploration of 2D and 3D images, (3) supports customization through multidimensional attribute spaces, and (4) is applicable to a variety of data sources and semantic structures.

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. We present a framework to visualize the missed regions per-frame during OC, 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.

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 (DVFs) 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.

Multitask 3D CBCT-to-CT translation and organs-at-risk segmentation using physics-based data augmentation.

Purpose: 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 performed 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.

Generalizable cone beam CT esophagus segmentation using physics-based data augmentation.

Automated segmentation of the esophagus is critical in image-guided/adaptive radiotherapy of lung cancer to minimize radiation-induced toxicities such as acute esophagitis. We have developed a semantic physics-based data augmentation method for segmenting the esophagus in both planning CT (pCT) and cone beam CT (CBCT) using 3D convolutional neural networks. One hundred and ninety-one cases with their pCTs and CBCTs from four independent datasets were used to train a modified 3D U-Net architecture and a multi-objective loss function specifically designed for soft-tissue organs such as the esophagus.