B Siow

Noninvasive Quantification of Solid Tumor Microstructure Using VERDICT MRI

There is a need for biomarkers that are useful for noninvasive imaging of tumor pathophysiology and drug efficacy. Through its use of endogenous water, diffusion-weighted MRI (DW-MRI) can be used to probe local tissue architecture and structure. However, most DW-MRI studies of cancer tissues have relied on simplistic mathematical models, such as apparent diffusion coefficient (ADC) or intravoxel incoherent motion (IVIM) models, which produce equivocal results on the relation of the model parameter estimate with the underlying tissue microstructure. Here, we present a novel technique called VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors) to quantify and map histologic features of tumors in vivo. VERDICT couples DW-MRI to a mathematical model of tumor tissue to access features such as cell size, vascular volume fraction, intra- and extracellular volume fractions, and pseudo-diffusivity associated with blood flow. To illustrate VERDICT, we used two tumor xenograft models of colorectal cancer with different cellular and vascular phenotypes. Our experiments visualized known differences in the tissue microstructure of each model and the significant decrease in cell volume resulting from administration of the cytotoxic drug gemcitabine, reflecting the apoptotic volume decrease. In contrast, the standard ADC and IVIM models failed to detect either of these differences. Our results illustrate the superior features of VERDICT for cancer imaging, establishing it as a noninvasive method to monitor and stratify treatment responses.

A viable isolated tissue system: A tool for detailed MR measurements and controlled perturbation in physiologically stable tissue

In vivo magnetic resonance imaging (MRI) assessment of neuronal tissue is prone to artifacts such as movement, pulsatile flow, and tissue susceptibility. Furthermore, stable in vivo scans of over 3 h are difficult to achieve, experimental design is therefore limited. Using isolated tissue maintained in a viable physiological state can mitigate many of these in vivo issues. This work describes the fabrication and validation of an MRI compatible viable isolated tissue maintenance chamber. Parameters measured from maintained rat optic nerves did not change significantly over 10 h: (i) mean axon radius [electron microscopy — 0 h: 0.75 ± 0.46; 5 h: 0.74 ± 0.35; 10 h: 0.76 ± 0.35 μm (P >> 0.05, t‐test], (ii) action potentials [grease‐gap electrophysiology − 4.89 ± 0.16 mv, (P >> 0.05, Pearson test], and (iii) diffusion tensor imaging parameters [fractional anisotropy: 0.86 ± 0.02 (P >> 0.05, Pearson test), mean diffusivity: 1.48E‐06 ± 9.74E‐08 cm2/s, (P >> 0.05, Pearson test)]. In addition, a thorough diffusion‐weighted MR protocol demonstrated the comparable stability of viable isolated and chemically fixed rat optic nerve. This MRI compatible viable isolated tissue system allows researchers to probe neuronal physiology in a controlled environment by limiting in vivo artifacts and allowing extended MRI acquisitions. Magn Reson Med, 2013.