Objectives

The main objective of this Workpackage is the study of microvascular function and histopathology after irradiation.

Task 1:  In vivo functional imaging of microvascular perfusion of irradiated hearts
Task 2:  Morphometry of microvascular density

Work description

• In vivo functional imaging of microvascular perfusion of irradiated hearts after injection of suitable tracers will be performed by using a range of novel imaging methods available in the animal facilities there, including microSPECT/CT, MRI and CT. Aim of these studies is the development of suitable methods to quantify the expected focal and/or overall reduction of blood perfusion in the heart as a result of late microvascular radiation damage. This will be validated by morphometric analysis of regional variation of the various tracers which will permit the localisation and quantification of essential parameters of microvascular patency of the myocardium.
• The morphometric analysis of microvascular density will be performed by TUM and TUD. Criteria of response, in mice as well as in rats, will be the kinetics, severity and focality of reduction of capillary density in the myocardium of hearts in dependence of the dose of local radiation.

WP leader

Dr. Fiona Stewart (NKI) runs the normal tissue radiation biology program, within the Division of Experimental Therapy. This research program uses patient material, animal models and in vitro models to study underlying mechanisms of normal tissue damage after radiotherapy. Dr Stewart has ongoing collaborations with Prof. Dr. Mat Daemen, CARIM, University of Maastricht, to study mechanisms of radiation induced atherosclerosis, and a new collaboration with Prof. Christine Mummery, Hubrecht laboratory, Utrecht, to study molecular mechanisms of radiation induced cardiovascular damage.

Participating consortium partners

Technische Universität München, Germany
University of Technology, Dresden; Germany
Maria Sklodowska - Curie Cancer Institute, Poland
Cardiovascular Research Institute, Maastricht, The Netherlands