Vascular Profile Characterization of Liver Tumors by Magnetic Resonance Imaging Using Hemodynamic Response Imaging in Mice

Abstract

Recently, we have demonstrated the feasibility of using hemodynamic response imaging (HRI), a functional magnetic resonance imaging (MRI) method combined with hypercapnia and hyperoxia, for monitoring vascular changes during liver pathologies without the need of contrast material. In this study, we evaluated HRI ability to assess changes in liver tumor vasculature during tumor establishment, progression, and antiangiogenic therapy. Colorectal adenocarcinoma cells were injected intrasplenically to model colorectal liver metastasis (CRLM) and the Mdr2 knockout mice were used to model primary hepatic tumors. Hepatic perfusion parameters were evaluated using the HRI protocol and were compared with contrast-enhanced (CE) MRI. The hypovascularity and the increased arterial blood supply in well-defined CRLM were demonstrated by HRI. In CRLM-bearing mice, the entire liver perfusion was attenuated as the HRI maps were significantly reduced by 35%. This study demonstrates that the HRI method showed enhanced sensitivity for small CRLM (1-2 mm) detection compared with CE-MRI (82% versus 38%, respectively). In addition, HRI could demonstrate the vasculature alteration during CRLM progression (arborized vessels), which was further confirmed by histology. Moreover, HRI revealed the vascular changes induced by rapamycin treatment. Finally, HRI facilitates primary hepatic tumor characterization with good correlation to the pathologic differentiation. The HRI method is highly sensitive to subtle hemodynamic changes induced by CRLM and, hence, can function as an imaging tool for understanding the hemodynamic changes occurring during CRLM establishment, progression, and antiangiogenic treatment. In addition, this method facilitated the differentiation between different types of hepatic lesions based on their vascular profile noninvasively.

Improved efficacy of a novel anti-angiogenic drug combination (TL-118) against colorectal-cancer liver metastases; MRI monitoring in mice

“…CT-26-murine colorectal adenocarcinoma cells (10 4 cells in 300  μ l per mouse) were intrasplenically injected to 7–8 week-old, anaesthetised male CB6F1 mice (Harlan, Ein-Kerem, Israel) as previously described (Edrei et al , 2011). In this model, 1–5 hepatic nodules per mouse were detected by MRI, 13–17 days after cell inoculation.…”

Inhaled carbon dioxide causes dose-dependent paradoxical bradypnea in animals anesthetized with pentobarbital, but not with isoflurane or ketamine

“…(NH: normoxic hypercapnia; HH: hyperoxic hypercapnia). studies assessing the effects of inspired CO 2 on BOLD-fMRI in the adult (Barash et al, 2008;Edrei et al, 2011) and fetal (Ginosar et al, 2011) circulation, inspired CO 2 elicits a profound hemodynamic effect within 30-60 s, reaching equilibrium by 3 min.…”

“…Animals in the observational data set were 7-8 week old CB6F1/Ola Hsd mice (n = 99) who were all undergoing BOLD-fMRI with a hypercapnic challenge test, as reported in previous studies (Barash et al, 2008;Edrei et al, 2011). These animals were all anes- Fig.…”

“…1 Consequently, in ongoing studies of mice anesthetized with pentobarbital for blood oxygen level dependent functional mag- 1 Lumb, 2010. http://dx.doi.org/10.1016/j.resp.2015.06.003 1569-9048/© 2015 Elsevier B.V. All rights reserved. netic resonance imaging (BOLD-fMRI) (Barash et al, 2008;Edrei et al, 2011), we were surprised to observe paradoxical bradypnea immediately following the administration of small doses of inhaled carbon dioxide. In this brief report, we present the observed effect of both normoxic hypercapnia and hyperoxic hypercapnia on the respiratory rate of a large sample of mice.…”

Photothermal ablation of pancreatic cancer cells with hybrid iron-oxide core gold-shell nanoparticles

“…[25][26][27] microwave coagulation therapy, 28 and cryoablation therapy. 29 These thermal ablation approaches have a common limitation, nonspecific heating of targeted tissues, and potential injury to surrounding healthy tissues Photothermal ablation approaches alternatively may permit improved tumor-specific heating with nanomaterials serving to photosensitize the targeted tissues.…”