Evaluating a Cellular Microstructure Model Within Apoptotic Cell Death via Diffusion Magnetic Resonance and Long Diffusion Times

The growing trend for personalized cancer treatment needs a complementary system to detect treatment response more rapidly and robustly. Inducing apoptosis is still a common treatment target as the immune system can clear the apoptotic cancer cells. Many studies have demonstrated the potential of diffusion-based MRI techniques for detecting apoptotic changes in tumors by correlating the changes of cellularity. Here we used diffusion data with long diffusion times to elucidate water exchange rates in acute myeloid leukemia cells (AML) which were acquired using stimulated echo acquisition mode (STEAM) in diffusion imaging. The two-pool exchange model was fitted where the key parameters of interest were the intracellular fraction, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:mrow><mml:msub><mml:mi>M</mml:mi> <mml:mi>I</mml:mi></mml:msub> </mml:mrow> <mml:annotation>$$ {M}_{\mathrm{I}} $$</mml:annotation></mml:semantics> </mml:math> , intracellular exchange rate, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:mrow><mml:msub><mml:mi>K</mml:mi> <mml:mi>IE</mml:mi></mml:msub> </mml:mrow> <mml:annotation>$$ {K}_{\mathrm{IE}} $$</mml:annotation></mml:semantics> </mml:math> , and cell radius, r. Apoptosis was induced with cisplatin and significant differences were found for each of the following three parameters: <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:mrow><mml:msub><mml:mi>M</mml:mi> <mml:mi>I</mml:mi></mml:msub> </mml:mrow> <mml:annotation>$$ {M}_{\mathrm{I}} $$</mml:annotation></mml:semantics> </mml:math> decreased by ~53%, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:mrow><mml:msub><mml:mi>K</mml:mi> <mml:mi>IE</mml:mi></mml:msub> </mml:mrow> <mml:annotation>$$ {K}_{\mathrm{IE}} $$</mml:annotation></mml:semantics> </mml:math> increased by ~61%, and r decreased by ~15%. These results highlight the potential of longer diffusion times to monitor cancer treatments that induce apoptosis.