title: Demonstration of Non-Gaussian Restricted Diffusion in Tumor Cells Using Diffusion Time-Dependent Diffusion-Weighted Magnetic Resonance Imaging Contrast.
abstract: The diffusion-weighted magnetic resonance imaging (DWI) technique enables quantification of water mobility for probing microstructural properties of biological tissue and has become an effective tool for collecting information about the underlying pathology of cancerous tissue. Measurements using multiple b-values have indicated biexponential signal attenuation, ascribed to "fast" (high ADC) and "slow" (low ADC) diffusion components. In this empirical study, we investigate the properties of the diffusion time (Δ)-dependent components of the diffusion-weighted (DW) signal in a constant b-value experiment. A xenograft gliobastoma mouse was imaged using Δ = 11 ms, 20 ms, 40 ms, 60 ms, and b = 500-4000 s/mm(2) in intervals of 500 s/mm(2). Data were corrected for EPI distortions, and the Δ-dependence on the DW-signal was measured within three regions of interest [intermediate- and high-density tumor regions and normal-appearing brain (NAB) tissue regions]. In this study, we verify the assumption that the slow decaying component of the DW-signal is non-Gaussian and dependent on Δ, consistent with restricted diffusion of the intracellular space. As the DW-signal is a function of Δ and is specific to restricted diffusion, manipulating Δ at constant b-value (cb) provides a complementary and direct approach for separating the restricted from the hindered diffusion component. We found that Δ-dependence is specific to the tumor tissue signal. Based on an extended biexponential model, we verified the interpretation of the diffusion time-dependent contrast and successfully estimated the intracellular restricted ADC, signal volume fraction, and cell size within each ROI.
authors.affiliation: The Interventional Centre, Oslo University Hospital, Oslo, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Tuva R
authors.initials: TR
authors.lastname: Hope
authors.affiliation: Department of Radiology, University of California San Diego , La Jolla, CA , USA.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: White
authors.affiliation: Department of Radiology, University of California San Diego , La Jolla, CA , USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kuperman
authors.affiliation: Department of Neurosciences, University of California San Diego , La Jolla, CA , USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Department of Radiology, University of California San Diego , La Jolla, CA , USA.
authors.forename: Ghiam
authors.initials: G
authors.lastname: Yamin
authors.affiliation: Department of Radiology, University of California San Diego , La Jolla, CA , USA.
authors.forename: Hauke
authors.initials: H
authors.lastname: Bartch
authors.affiliation: Department of Radiology, University of California San Diego , La Jolla, CA , USA.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Schenker-Ahmed
authors.affiliation: Department of Radiology, University of California San Diego , La Jolla, CA , USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rakow-Penner
authors.affiliation: Department of Radiology, University of California San Diego , La Jolla, CA , USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bussell
authors.affiliation: Department of Neurosciences, University of California San Diego , La Jolla, CA , USA.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Nomura
authors.affiliation: Department of Neurosciences, University of California San Diego , La Jolla, CA , USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
authors.affiliation: The Interventional Centre, Oslo University Hospital, Oslo, Norway; Department of Physics, University of Oslo, Oslo, Norway.
authors.forename: Atle
authors.initials: A
authors.lastname: Bjørnerud
authors.affiliation: Department of Radiology, University of California San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
keywords: DWI; MRI; cancer; diffusion time-dependence; glioblastoma multiforme; restricted diffusion; xenograft tumor model