Dynamic NIR Fluorescence Imaging and Machine Learning Framework for Stratifying High vs. Low Notch-Dll4 Expressing Host Microenvironment in Triple-Negative Breast Cancer. Cancers (Basel) 2023 Feb 25;15(5)
Date
03/12/2023Pubmed ID
36900252Pubmed Central ID
PMC10000786DOI
10.3390/cancers15051460Scopus ID
2-s2.0-85149856201 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Delta like canonical notch ligand 4 (Dll4) expression levels in tumors are known to affect the efficacy of cancer therapies. This study aimed to develop a model to predict Dll4 expression levels in tumors using dynamic enhanced near-infrared (NIR) imaging with indocyanine green (ICG). Two rat-based consomic xenograft (CXM) strains of breast cancer with different Dll4 expression levels and eight congenic xenograft strains were studied. Principal component analysis (PCA) was used to visualize and segment tumors, and modified PCA techniques identified and analyzed tumor and normal regions of interest (ROIs). The average NIR intensity for each ROI was calculated from pixel brightness at each time interval, yielding easily interpretable features including the slope of initial ICG uptake, time to peak perfusion, and rate of ICG intensity change after reaching half-maximum intensity. Machine learning algorithms were applied to select discriminative features for classification, and model performance was evaluated with a confusion matrix, receiver operating characteristic curve, and area under the curve. The selected machine learning methods accurately identified host Dll4 expression alterations with sensitivity and specificity above 90%. This may enable stratification of patients for Dll4 targeted therapies. NIR imaging with ICG can noninvasively assess Dll4 expression levels in tumors and aid in effective decision making for cancer therapy.
Author List
Shafiee S, Jagtap J, Zayats M, Epperlein J, Banerjee A, Geurts A, Flister M, Zhuk S, Joshi AAuthors
Anjishnu Banerjee PhD Associate Professor in the Data Science Institute department at Medical College of WisconsinAron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin
Amit Joshi PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin
Shayan Shafiee Postdoctoral Researcher in the Biomedical Engineering department at Medical College of Wisconsin
