Pyruvate and lactate dynamics from 2D EPSI in canine patient with tumor. The figure also shows the spectrum with GLM fitting at the tumor site in the EPSI frame acquired 27 s from time of injection.

Early detection of response to treatment in cancer by Hyperpolarized Metabolic MR

Abubakr Eldirdiri

Research focus
Since the introduction of Dynamic Nuclear Polarization (DNP) techniques that allowed for hyperpolarized agent to be used in-vivo and resulted in increasing the Magnetic Resonance sensitivity for more than 10,000 folds, Magnetic Resonance Spectroscopy (MRS) of hyperpolarized 13C molecules has emerged as powerful imaging modality to probe cancer response to treatment. Early detection of cancer response to treatment can have great benefit on patients, because it allows selecting the prober treatment fast and effectively.

Conventionally, tumor response to treatment is often assessed by monitoring shrinkages in tumor size as indicated by CT or MR images. However, these measurements do not give an early response in most cases.

On the other hand, MRS of hypeplarized 13C substrates, which falls under the functional imaging category, facilitates tracking metabolic fluxes and enzymatic pathways of endogenous carbon substrates and thus the characterization of normal and cancer tissues. 13C pyruvate, for instance, has been used to investigate metabolic processes associated with the Warburg effect which is typically increased in active cancer tissues. In addition, MRS of 13 C bicarbonate provides a method to measure the pH of the tumor’s extracellular environment which typically acidic and might mediate in tumor migration and invasion. Moreover, the oxidation and reduction of hyperpolarized substrates like 13C ascorbate and 13C dehydroascorbate were proposed to determine the tumor redox state and 13C fumarate has been proposed to assess the degree of necrosis induced by treatment.

The purpose of the project is to develop fast imaging methods to overcome the limitation imposed from the relatively short life of polarization of the hyperpolarized 13C substrates (typically in the order of tens of seconds). In addition, the relevance of the parameters obtained from these substrates with tumor progression or response to treatment will be validated.

Scientific output
Find Bakri's publications at DTU's online research database ORBIT.

Funding
The project is funded by Independent Research Fund Denmark, Medical Sciences (DFF-1331-00259B) and DTU Elektro. The project is part of the HYPERMAG Center of Excellence funded by the Danish National Research Foundation (DNRF124). 

Supervisors
Professor Jan Ardenkjær-Larsen, Associate Professor Lars G. Hanson and Professor Andreas Kjær from Copenhagen University Hospital.

Project period
January 2014 - December 2016

Caption top photo: Pyruvate and lactate dynamics from 2D EPSI in canine patient with tumor. The figure also shows the spectrum with GLM fitting at the tumor site in the EPSI frame acquired 27 s from time of injection.

PhD thesis

Bakri succesfully defended his PhD thesis on 30 June 2017.

 

You can download his thesis here.

http://www.hypermag.dtu.dk/Research/PhD-projects/Abubakr-Eldirdiri
27 SEPTEMBER 2020