Dynamic contrast‐enhanced MR microscopy identifies regions of therapeutic response in a preclinical model of colorectal adenocarcinoma. Issue 5 (21st April 2015)

• Record Type: Journal Article
• Authors: Subashi, Ergys; Qi, Yi; Johnson, G. Allan
• Is Part Of: Medical physics. Volume 42:Issue 5(2015)
• Page Start: 2482
• Page End: 2488
• Publication Date: 2015-04-21
• Subjects: biomedical MRI -- cancer -- image resolution -- image sampling -- medical image processing -- patient treatment -- prosthetics -- tumours; Clinical applications -- Spatial resolution -- Contrast -- Cancer; Involving electronic [emr] or nuclear [nmr] magnetic resonance, e.g. magnetic resonance imaging -- Prostheses implantable into the body -- Biological material, e.g. blood, urine; Haemocytometers -- Digital computing or data processing equipment or methods, specially adapted for specific applications -- Image data processing or generation, in general; MRI -- functional imaging -- biological target volume; Cancer -- Therapeutics -- Time measurement -- Image analysis -- Medical magnetic resonance imaging -- Spatial analysis -- Tissues -- Spatial dimensions; Medical physics -- Periodicals; Medical physics; Geneeskunde; Natuurkunde; Toepassingen; Biophysics; Periodicals; Periodicals; Electronic journals; 610.153
• DOI: 10.1118/1.4917525
• Languages: English
• ISSNs: 0094-2405

Abstract

Abstract : Purpose: A typical dynamic contrast‐enhanced (DCE)‐MRI study often compares the derived pharmacokinetic parameters on manually selected tumor regions or over the entire tumor volume. These measurements include domains where the interpretation of the biomarkers may be unclear (such as in necrotic areas). Here, the authors describe a technique for increasing the sensitivity and specificity of DCE‐MRI by identifying tumor regions with a variable response to therapy. Methods: Two cohorts ( n = 8/group) of nu / nu mice with LS‐174T implanted in the mammary fat pad were imaged at five time points over four weeks. The treatment/control group received bevacizumab/saline at a dose of 5 mg/kg or 5 ml/kg twice weekly; imaging experiments were performed weekly. MR images were acquired at an isotropic resolution of 156 μ m 3 (2.4 nl) and with a sampling rate of 9.9 s. The histogram of the time‐to‐peak (TTP) was used to identify two (fast‐ and slow‐enhancing) regions based on a threshold of TTP = 1000 s. The regions were correlated with histology, and the effect of therapy was locally examined. Results: Tumors in the treatment group had a significantly longer doubling time. The regions defined by thresholding the TTP histogram identified two distinct domains correlating significantly with tumor permeability and microvessel density. In the fast‐enhancing region, the mean permeability constant ( K trans ) was significantly lower in the treatment group at day 9; in the slow‐enhancing region, K trans was not different between the control and treatment groups. At day 9, the relative volume of the fast‐enhancing region was significantly lower in the treatment group, while that of the slow‐enhancing region was significantly higher. Conclusions: Two regions with distinct kinetic parameters were identified based on the histogram of TTP. The effect of bevacizumab, as measured by a decrease in K trans, was confined to one of these regions. High spatiotemporal resolution MR studies may contribute unique insights into the response of the tumor microenvironment to therapy.