Ergys Subashi1, Yi Qi2, G Allan Johnson2. 1. Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 and Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710. 2. Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.
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 μm(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.
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 μm(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.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Radka Stoyanova; Kris Huang; Kiri Sandler; Hyungjoon Cho; Sean Carlin; Pat B Zanzonico; Jason A Koutcher; Ellen Ackerstaff Journal: Transl Oncol Date: 2012-12-01 Impact factor: 4.243
Authors: Milica Medved; Greg Karczmar; Cheng Yang; James Dignam; Thomas F Gajewski; Hedy Kindler; Everett Vokes; Peter MacEneany; Myrosia T Mitchell; Walter M Stadler Journal: J Magn Reson Imaging Date: 2004-07 Impact factor: 4.813
Authors: M J van Amerongen; A M Vos; W van der Woude; I D Nagtegaal; J H W de Wilt; J J Fütterer; J J Hermans Journal: PLoS One Date: 2021-01-26 Impact factor: 3.240
Authors: Kooresh I Shoghi; Cristian T Badea; Stephanie J Blocker; Thomas L Chenevert; Richard Laforest; Michael T Lewis; Gary D Luker; H Charles Manning; Daniel S Marcus; Yvonne M Mowery; Stephen Pickup; Ann Richmond; Brian D Ross; Anna E Vilgelm; Thomas E Yankeelov; Rong Zhou Journal: Tomography Date: 2020-09