Distinct effects of nuclear volume fraction and cell diameter on high b‐value diffusion MRI contrast in tumors

Abstract

While many recent studies have demonstrated improved detection and characterization of malignant lesions using high b-value diffusion imaging techniques, little is known about the underlying physical characteristics of tumor cells that modulate the restricted water signal at high b on clinical scanners. Monte Carlo simulations of diffusion in a synthetic tumor cell environment were used to study the specific effects of tumor cell diameter and nuclear volume fraction (ν) on high b diffusion contrast. Results indicate that clinical pulsed-gradient spin-echo diffusion-weighted signals measured at high b (∼4000 s/mm(2)), long diffusion time (Δ ∼40-60 ms), and long echo time (TE ∼60-140 ms) are generally insensitive to tumor cell diameter, but increase exponentially with ν. Moreover, these results are predicted by a simple analytic expression for the intracellular restricted water signal with elevated T2 for the intranuclear versus cytosolic compartment. Nuclear volume fraction is an important characteristic of cancer cells that modulates the apparent restriction of water at high b on clinical scanners. This model offers a possible explanation for the apparent unreliable correlation between tumor cell density (cellularity) and traditional ADC.