Characterizing tumor response to chemotherapy at various length scales using temporal diffusion spectroscopy

Area of Science:

• Oncology
• Biophysics
• Medical Imaging

Background:

• Apparent diffusion coefficient (ADC) measurements via MRI are explored as tumor treatment response biomarkers.
• Conventional methods (PGSE) have limitations in detecting early intracellular changes due to long diffusion times and sensitivity to necrosis.
• Diffusion temporal spectroscopy (OGSE) probes short length scales, potentially revealing intracellular microstructural alterations independent of cell density.

Purpose of the Study:

• To investigate if diffusion temporal spectroscopy can detect intracellular microstructural changes following anti-cancer treatment.
• To compare diffusion MRI at short and long diffusion times in response to barasertib treatment in SW620 xenografts.

Main Methods:

• SW620 xenografts were treated with barasertib (AZD1152), an Aurora B kinase inhibitor.
• Diffusion MRI using pulsed-gradient spin echo (PGSE) and oscillating gradient spin echo (OGSE) sequences was performed.
• Apparent diffusion coefficient (ADC) values were analyzed at varying diffusion times (gradient frequencies).

Main Results:

• ADC values increased at long diffusion times (PGSE and low-frequency OGSE) after treatment.
• ADC values significantly decreased at short diffusion times (high-frequency OGSE) in treated tumors.
• Observed opposite ADC changes at short and long diffusion times indicate distinct microstructural variations at different length scales.

Conclusions:

• Diffusion temporal spectroscopy provides a more comprehensive assessment of tumor microstructure at multiple length scales.
• Short diffusion time MRI can detect intracellular microstructural changes (e.g., polyploidy) following treatment.
• This technique offers potential pharmacodynamic biomarkers for early tumor response, distinguishing subcellular and supracellular changes.