Biomedical Commons^™

Radiomic Texture Feature Descriptor To Distinguish Recurrent Brain Tumor From Radiation Necrosis Using Multimodal Mri, M. S. Sadique, A. Temtam, E. Lappinen, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Despite multimodal aggressive treatment with chemo-radiation-therapy, and surgical resection, Glioblastoma Multiforme (GBM) may recur which is known as recurrent brain tumor (rBT), There are several instances where benign and malignant pathologies might appear very similar on radiographic imaging. One such illustration is radiation necrosis (RN) (a moderately benign impact of radiation treatment) which are visually almost indistinguishable from rBT on structural magnetic resonance imaging (MRI). There is hence a need for identification of reliable non-invasive quantitative measurements on routinely acquired brain MRI scans: pre-contrast T1-weighted (T1), post-contrast T1-weighted (T1Gd), T2-weighted (T2), and T2 Fluid Attenuated Inversion Recovery (FLAIR) that can …

Uncertainty Estimation In Classification Of Mgnt Using Radiogenomics For Glioblastoma Patients, W. Farzana, Z. A. Shboul, A. Temtam, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Glioblastoma Multiforme (GBM) is one of the most malignant brain tumors among all high-grade brain cancers. Temozolomide (TMZ) is the first-line chemotherapeutic regimen for glioblastoma patients. The methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) gene is a prognostic biomarker for tumor sensitivity to TMZ chemotherapy. However, the standardized procedure for assessing the methylation status of MGMT is an invasive surgical biopsy, and accuracy is susceptible to resection sample and heterogeneity of the tumor. Recently, radio-genomics which associates radiological image phenotype with genetic or molecular mutations has shown promise in the non-invasive assessment of radiotherapeutic treatment. This study proposes a machine-learning framework …

Qu-Brats: Miccai Brats 2020 Challenge On Quantifying Uncertainty In Brain Tumor Segmentation - Analysis Of Ranking Scores And Benchmarking Results, Raghav Mehta, Angelos Filos, Ujjwal Baid, Chiharu Sako, Richard Mckinley, Michael Rebsamen, Katrin Dätwyler, Raphael Meier, Piotr Radojewski, Gowtham Krishnan Murugesan, Sahil Nalawade, Chandan Ganesh, Ben Wagner, Fang F. Yu, Baowei Fei, Ananth J. Madhuranthakam, Joseph A. Maldjian, Laura Daza, Catalina Gómez, Pablo Arbeláez, Chengliang Dai, Shuo Wang, Hadrien Reynaud, Yuan-Han Mo, Elsa Angelini, Yike Guo, Wenjia Bai, Subhashis Banerjee, Lin-Min Pei, Murat Ak, Sarahi Rosas-González, Ilyess Zemmoura, Clovis Tauber, Minh H. Vu, Tufve Nyholm, Tommy Löfstedt, Laura Mora Ballestar, Veronica Vilaplana, Hugh Mchugh, Gonzalo Maso Talou, Alan Wang, Jay Patel, Ken Chang, Katharina Hoebel, Mishka Gidwani, Nishanth Arun, Sharut Gupta, Mehak Aggarwal, Praveer Singh, Elizabeth R. Gerstner, Jayashree Kalpathy-Cramer, Nicholas Boutry, Alexis Huard, Lasitha Vidyaratne, Md. Monibor Rahman, Khan M. Iftekharuddin, Joseph Chazalon, Elodie Puybareau, Guillaume Tochon, Jun Ma, Mariano Cabezas, Xavier Llado, Arnau Oliver, Liliana Valencia, Sergi Valverde, Mehdi Amian, Mohammadreza Soltaninejad, Andriy Myronenko, Ali Hatamizadeh, Xue Feng, Quan Dou, Nicholas Tustison, Craig Meyer, Nisarg A. Shah, Sanjay Talbar, Marc-André Weber, Abhishek Mahajan, Andras Jakab, Roland Wiest, Hassan M. Fathallah-Shaykh, Arash Nazeri, Mikhail Milchenko1, Daniel Marcus, Aikaterini Kotrotsou, Rivka Colen, John Freymann, Justin Kirby, Christos Davatzikos, Bjoern Menze, Spyridon Bakas, Yarin Gal, Tal Arbel

Electrical & Computer Engineering Faculty Publications

Deep learning (DL) models have provided the state-of-the-art performance in a wide variety of medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder the translation of DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties, could enable clinical review of the most uncertain regions, thereby building trust and paving the way towards clinical translation. Recently, a number of uncertainty estimation methods have been introduced for DL medical image segmentation tasks. …

Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied By Immunogenic Cell Death In Murine Models Of Lymphoma And Colorectal Cancer, Alessandra Rossi, Olga N. Pakhomova, Peter A. Mollica, Maura Casciola, Uma Mangalanathan, Andrei G. Pakhomov, Claudia Muratori

Bioelectrics Publications

Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of …

Il-12 Gene Electrotransfer Triggers A Change In Immune Response Within Mouse Tumors, Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller

Bioelectrics Publications

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell …

Classification Of Intensity-Modulated Proton Therapy Plans, Louise Gabrielle Lima '19, Alice Liu '19

Student Publications & Research

Proton Radiotherapy

Proton radiotherapy is a form of radiation treatment that uses energized protons to break DNA, leading to cell death and killing cancers.

Consistent And Reproducible Cultures Of Large-Scale 3d Mammary Epithelial Structures Using An Accessible Bioprinting Platform, John A. Reid, Peter M. Mollica, Robert D. Bruno, Patrick C. Sachs

Medical Diagnostics & Translational Sciences Faculty Publications

Background: Standard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, limitations persist owing to the lack of control over cellular placement within the hydrogel. This results in experimental inconsistencies and random organoid morphology. Robust, high-throughput experimentation requires greater standardization of 3D epithelial culture techniques.

Methods: Here, we detail the use of a 3D bioprinting platform as an investigative tool to control the 3D formation of organoids through the "self-assembly" of human mammary epithelial cells. Experimental bioprinting procedures …

Moderate Heat Application Enhances The Efficacy Of Nanosecond Pulse Stimulation For The Treatment Of Squamous Cell Carcinoma, Chelsea M. Edelblute, Sigi Guo, Embo Yang, Chunqi Jiang, Karl Schoenbach, Richard Heller

Bioelectrics Publications

Nanosecond pulse stimulation as a tumor ablation therapy has been studied for the treatment of various carcinomas in animal models and has shown a significant survival benefit. In the current study, we found that moderate heating at 43°C for 2 minutes significantly enhanced in vitro nanosecond pulse stimulation-induced cell death of KLN205 murine squamous cell carcinoma cells by 2.43-fold at 600 V and by 2.32-fold at 900 V, as evidenced by propidium iodide uptake. Furthermore, the ablation zone in KLN205 cells placed in a 3-dimensional cell-culture model and pulsed at a voltage of 900 V at 43°C was 3 times …

Upregulation Of Dna Sensors In B16.F10 Melanoma Spheroid Cells After Electrotransfer Of Pdna, Katarina Znidar, Masa Bosnjak, Tanja Jesenko, Loree C. Heller, Maja Cemazar

Bioelectrics Publications

Increased expression of cytosolic DNA sensors, a category of pattern recognition receptor, after control plasmid DNA electrotransfer was observed in our previous studies on B16.F10 murine melanoma cells. This expression was correlated with the upregulation of proinflammatory cytokines and chemokines and was associated with cell death. Here, we expanded our research to include the influence of features of cells in a 3-dimensional environment, which better represents the tumors’ organization in vivo. Our results show that lower number of cells were transfected in spheroids compared to 2-dimensional cultures, that growth was delayed after electroporation alone or after electrotransfer of plasmid …

Design Of Novel Sensors And Instruments For Minimally Invasive Lung Tumour Localization Via Palpation, Anish Srinivasan Naidu

Electronic Thesis and Dissertation Repository

Minimally Invasive Thoracoscopic Surgery (MITS) has become the treatment of choice for lung cancer. However, MITS prevents the surgeons from using manual palpation, thereby often making it challenging to reliably locate the tumours for resection. This thesis presents the design, analysis and validation of novel tactile sensors, a novel miniature force sensor, a robotic instrument, and a wireless hand-held instrument to address this limitation. The low-cost, disposable tactile sensors have been shown to easily detect a 5 mm tumour located 10 mm deep in soft tissue. The force sensor can measure six degrees of freedom forces and torques with temperature …

Altered Cholesterol Metabolism In Human Cancers Unraveled By Label-Free Spectroscopic Imaging, Shuhua Yue

Open Access Dissertations

Despite tremendous scientific achievements, cancer remains the second leading cause of death in the United States. Metabolic reprogramming has been increasingly recognized as a core hallmark of cancer. My dissertation work identified novel diagnostic markers and therapeutic targets for human cancers through the study of cholesterol in cancer cells.

Enabled by label-free Raman spectromicroscopy, we performed the first quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases, but not in normal prostate, benign prostatic hyperplasia, or …

Implementation Of Gy-Eq For Deterministic Effects Limitation In Shield Design, John W. Wilson, Myung-Hee Y. Kim, Giovanni De Angelis, Francis A. Cucinotta, Nobuaki Yoshizawa, Francis F. Badavi

Mathematics & Statistics Faculty Publications

The NCRP has recently defined RBE values and a new quantity (Gy-Eq) for use in estimation of deterministic effects in space shielding and operations. The NCRP's RBE for neutrons is left ambiguous and not fully defined. In the present report we will suggest a complete definition of neutron RBE consistent with the NCRP recommendations and evaluate attenuation properties of deterministic effects (Gy-Eq) in comparison with other dosimetric quantities.