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

PURPOSE: 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. METHODS: 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: 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. CONCLUSION: 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.