Journal Article

An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse

Gomes, Ana L., Kinchesh, Paul, Bird, Luke, Kersemans, Veerle, Gilchrist, Stuart, Allen, Philip D., Falzone, Nadia, Thompson, James, Newman, Robert G., Corroyer-Dulmont, Aurelien, Azad, Abul, Sansom, Owen J., Muschel, Ruth J., Hill, Mark A., Tullis, Iain D. C., Vallis, Katherine A., Vojnovic, Borivoj, Fokas, Emmanouil, D’Costa, Zenobia, Beech, John S., Smart, Sean C.

2017

Overview

Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse. A multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI. Each step of the radiotherapy planning procedure was validated initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal adrenal glands with a size-matched collimated beam was performed. Additionally, the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of pancreatic ductal adenocarcinoma were used to demonstrate the applicability of our methods for the accurate delivery of radiation to CT-invisible abdominal tumours. The BANG gel phantoms demonstrated a targeting efficiency error of 0.56 ± 0.18 mm. The in vivo stability tests of body motion during MR-IGRT and the associated cradle transfer showed that the residual body movements are within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal glands with a size-matched collimated beam was confirmed by γH2AX staining. Regression in tumour volume was observed almost immediately post MR-IGRT in the neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally, MR-IGRT in the KPC model facilitated precise contouring and comparison of different treatment plans and radiotherapy dose distributions not only to the intra-abdominal tumour but also to the organs at risk. This is, to our knowledge, the first study to demonstrate preclinical MR-IGRT in intra-abdominal organs. The proposed MR-IGRT method presents a state-of-the-art solution to enabling robust, accurate and efficient targeting of extracranial organs in the mouse and can operate with a sufficiently high throughput to allow fractionated treatments to be given.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abdomen - diagnostic imaging / Abdomen - radiation effects / Abdominal cancer / Abdominal Neoplasms - diagnostic imaging / Abdominal Neoplasms - radiotherapy / Adenocarcinoma / Adrenal glands / Adrenal Glands - diagnostic imaging / Adrenal Glands - radiation effects / Animals / Beams (radiation) / Biology and Life Sciences / Care and treatment / Cell Line, Tumor / Charities / Cognitive science / Computed tomography / Contour matching / Contouring / Dosimetry / Glands / Health aspects / Health risk assessment / Health risks / House mouse / Humans / Image contrast / Immobilization / In vitro methods and tests / In vivo methods and tests / Magnetic resonance imaging / Magnetic Resonance Imaging - instrumentation / Magnetic Resonance Imaging - methods / Medical research / Medicine and Health Sciences / Mice, Inbred BALB C / Mice, Inbred CBA / Mice, Inbred NOD / Mice, Nude / Mice, Transgenic / Motion / Motion stability / Multimodal Imaging - instrumentation / Neoplasm Transplantation / Neuroblastoma / Neuroscience / Organs / Pancreas / Pancreatic cancer / Phantoms, Imaging / Radiation / Radiation dosage / Radiation therapy / Radiometry - instrumentation / Radiotherapy / Radiotherapy Dosage / Radiotherapy Planning, Computer-Assisted - instrumentation / Radiotherapy Planning, Computer-Assisted - methods / Radiotherapy, Image-Guided - instrumentation / Radiotherapy, Image-Guided - methods / Regression models / Research and Analysis Methods / Robustness (mathematics) / Soft tissues / Stability tests / Tomography, X-Ray Computed - instrumentation / Tomography, X-Ray Computed - methods / Tumor Burden / Tumors / Xenografts / Xenotransplantation