Imaging pH: Development of MRI Probes for In-Vivo pH Mapping

Imaging pH:  Development of MRI Probes for In-Vivo pH Mapping



The purpose of this project funded by the Ontario Institute of ‘Cancer Research is to understand how intracellular pH is altered in mouse models of brain cancer.  High grade brain tumours represent a major treatment challenge with median survival times ranging from 12 – 18 months.  As the brain tumour increase in volume patents experience a range of symptoms ranging from epileptic seizures to cognitive dysfunction.  Improved diagnosis, prognosis, and treatment monitoring could lead to a significant improvement in patient quality of life including cognitive function.  We are investigating whether pharmacologic manipulation of intracellular pH (acidification) in brain tumours is indicative of tumour treatment response, and can be used directly as method of tumour control by inducing apoptosis.  This study will use novel measurements of tumour pH made by chemical exchange saturation transfer (CEST).  Data will be aquired in mouse models on the 9.4T MRI and in healthy people and people with brain tumours on the 7T MRI.

Patients will be characterized using clinical assessments.  The objective of the mouse study is to determine the combination of approved drugs that induces the greatest tumour acidification.  The purpose of the human study is to assess the feasibility of pharmacologic pH-weighted CEST MRI and to qanitify the magnitude of pharmacological induced pH response.

This project aligns with the strategic priorities of BrainsCAN.  It involves the development and use of pH-weighted pharmacologic MRI in a pre-clincial model of brain cancer and in patients with brain cancer (glioma), which results in impairments of cognitive function.  It involves collaboration of basic-scientists and clinicians to achieve this goal.  The reduced rate will allow acquisition of data  on a greater variety of drugs to modulate intracellular pH in clinical models and in patients.