Deep learning for automatic organ and tumor segmentation in nanomedicine pharmacokinetics.

Journal: Theranostics
Published Date:

Abstract

: Multimodal imaging provides important pharmacokinetic and dosimetry information during nanomedicine development and optimization. However, accurate quantitation is time-consuming, resource intensive, and requires anatomical expertise. : We present NanoMASK: a 3D U-Net adapted deep learning tool capable of rapid, automatic organ segmentation of multimodal imaging data that can output key clinical dosimetry metrics without manual intervention. This model was trained on 355 manually-contoured PET/CT data volumes of mice injected with a variety of nanomaterials and imaged over 48 hours. : NanoMASK produced 3-dimensional contours of the heart, lungs, liver, spleen, kidneys, and tumor with high volumetric accuracy (pan-organ average %DSC of 92.5). Pharmacokinetic metrics including %ID/cc, %ID, and SUV achieved correlation coefficients exceeding R = 0.987 and relative mean errors below 0.2%. NanoMASK was applied to novel datasets of lipid nanoparticles and antibody-drug conjugates with a minimal drop in accuracy, illustrating its generalizability to different classes of nanomedicines. Furthermore, 20 additional auto-segmentation models were developed using training data subsets based on image modality, experimental imaging timepoint, and tumor status. These were used to explore the fundamental biases and dependencies of auto-segmentation models built on a 3D U-Net architecture, revealing significant differential impacts on organ segmentation accuracy. : NanoMASK is an easy-to-use, adaptable tool for improving accuracy and throughput in imaging-based pharmacokinetic studies of nanomedicine. It has been made publicly available to all readers for automatic segmentation and pharmacokinetic analysis across a diverse array of nanoparticles, expediting agent development.

Authors

  • Alex Dhaliwal
    Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, M5G 1L7, Ontario, Canada.
  • Jun Ma
    State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China.
  • Mark Zheng
    Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, M5G 1L7, Ontario, Canada.
  • Qing Lyu
  • Maneesha A Rajora
    Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, M5G 1L7, Ontario, Canada.
  • Shihao Ma
    Department of Computer Science, University of Toronto, Toronto, ON, Canada.
  • Laura Oliva
    Techna Institute, University Health Network, 190 Elizabeth Street, Toronto, M5G 2C4, Ontario, Canada.
  • Anthony Ku
    Department of Radiology, Stanford University, 1201 Welch Road, Stanford, 94305-5484, California, United States of America.
  • Michael Valic
    Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, M5G 1L7, Ontario, Canada.
  • Bo Wang
    Department of Clinical Laboratory Medicine Center, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China.
  • Gang Zheng
    Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.