Page 29 - TPIS2022

Lecture title:
Rapid assessment of Gd concentration for Dynamic Contrast-Enhanced MRI

ABSTRACT:

Dynamic contrast-enhanced (DCE) MRI has been used to measure important tumor
microenvironmental parameters that can be used for diagnosis of cancer as well as
for prediction and monitoring of treatment response. However, accurate estimation of the
kinetic parameters from DCE-MRI data still remains a challenging task, particularly due
to difficulties in measurement of the arterial input function (AIF). The accuracy in AIF
estimation directly affects the estimation of contrast kinetic parameters. In DCE-MRI, the
concentration of Gadolinium-based contrast agents (GBCA) is indirectly measured via the
change in the proton relaxation rate induced by the presence of GBCA, which can also be
influenced by other tissue properties contributing to the local magnetic field variation and the
MR measurement conditions such as radiofrequency field inhomogeneity and slice profile.
Recently, we developed a photo-induced triplet harvesting technique to quantify GBCA
using Carbostyril 124 (cs124)-sensitized diethylenetriamine pentaacetic acid (DTPA) via
induced triplet energy transfer to Tb-DTPA using a simple fluorescence plate reader that is
widely available in research labs. It has been shown that the relaxivity r1 of Gd-DTPA-cs124
is quite close to that of Gd-DTPA. Also demonstrated was that a sequential blood sampling
following injection of Gd-DTPA-cs124 can be used to measure the plasma clearance of
Gd-DTPA-cs124 in mice which matched closely with that of Gd-DTPA. We also showed
that cs124 remains effective when conjugated to larger ligands such as Gd-DTPA-DPPE,
which resulted in about 26x amplification in r1 and a 67 nM limit of detection comparable to
ICP-MS. These preliminary studies suggest (i) the feasibility of directly measuring plasma
concentration of GBCA and (ii) the expandability of the cs124 conjugation-based approach
to other ligands such as a macrocyclic ligand dodecane tetraacetic acid (DOTA).
In this talk, we will discuss about uncertainty of GBCA concentration measurement using
a state-of-the-art DCE-MRI method, and recent development of fluorescence-labeled GBCAs
to reduce such uncertainty for reliable estimation of pharmacokinetic model parameters.

5 International TPCF Preclinical Imaging Symposium (2022) 29
th