Hepatic Radiofrequency Ablation: Monitoring of Ablation-Induced Macrophage Recruitment in the Periablational Rim Using SPION-Enhanced Macrophage-Specific Magnetic Resonance Imaging.
Journal
Investigative radiology
ISSN: 1536-0210
Titre abrégé: Invest Radiol
Pays: United States
ID NLM: 0045377
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
pubmed:
1
4
2021
medline:
16
10
2021
entrez:
31
3
2021
Statut:
ppublish
Résumé
Macrophages accumulating in the periablational rim play a pivotal role in initiating and sustaining the perifocal inflammatory reaction, which has been shown to be at least 1 of the mechanisms responsible for the systemic pro-oncogenic effects of focal hepatic radiofrequency ablation (RFA). Herein, we tested the hypothesis to use superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI) for noninvasive quantification of iron-loaded macrophages in the periablational rim of VX2 tumor-bearing rabbits. Twelve VX2 tumor-bearing rabbits underwent MRI immediately after and up to 3 weeks after focal hepatic RFA. For noninvasive quantification of macrophage accumulation in the periablational rim, animals were scanned before and 24 hours after SPION injection. T2*-weighted images were analyzed and correlated with histopathological and immunohistochemical findings. Furthermore, correlations with quantitative measurements (ICP-MS [inductively coupled plasma-mass spectrometry] and LA-ICP-MS [laser ablation-ICP-MS]) were performed. SPION-enhanced T2*-weighted MRI scans displayed a progressive increase in the areas of signal intensity (SI) loss within the periablational rim peaking 3 weeks after RFA. Accordingly, quantitative analysis of SI changes demonstrated a significant decline in the relative SI ratio reflecting a growing accumulation of iron-loaded macrophages in the rim. Histological analyses confirmed a progressive accumulation of iron-loaded macrophages in the periablational rim. The ICP-MS and LA-ICP-MS confirmed a progressive increase of iron concentration in the periablational rim. SPION-enhanced MRI enables noninvasive monitoring and quantification of ablation-induced macrophage recruitment in the periablational rim. Given the close interplay between ablation-induced perifocal inflammation and potential unwanted tumorigenic effects of RFA, SPION-enhanced MRI may serve as a valuable tool to guide and modulate adjuvant therapies after hepatic RFA.
Identifiants
pubmed: 33787536
doi: 10.1097/RLI.0000000000000777
pii: 00004424-202109000-00007
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
591-598Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
Conflicts of interest and sources of funding: The authors have declared that conflict of interest exists. This study was funded by the German-Israeli Foundation of Scientific Research and Development (research grant agreement number: G-1319-201.2/2015). This study was also funded by the Deutsche Forschungsgemeinschaft (German Research Foundation)—SFB 1340/1 2018 and MA 5943/3-1/4-1/9-1.
Références
European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol . 2018;69:182–236.
Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol . 2016;27:1386–1422.
Rozenblum N, Zeira E, Scaiewicz V, et al. Oncogenesis: an "off-target" effect of radiofrequency ablation. Radiology . 2015;276:426–432.
Rozenblum N, Zeira E, Bulvik B, et al. Radiofrequency ablation: inflammatory changes in the periablative zone can induce global organ effects, including liver regeneration. Radiology . 2015;276:416–425.
Ahmed M, Kumar G, Moussa M, et al. Hepatic radiofrequency ablation-induced stimulation of distant tumor growth is suppressed by c-Met inhibition. Radiology . 2016;279:103–117.
Shan Z, Ju C. Hepatic macrophages in liver injury. Front Immunol . 2020;11:322.
Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol . 2017;66:1300–1312.
Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol . 2014;60:1090–1096.
Guillot A, Tacke F. Liver macrophages: old dogmas and new insights. Hepatol Commun . 2019;3:730–743.
Dal-Secco D, Wang J, Zeng Z, et al. A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury. J Exp Med . 2015;212:447–456.
Ahmed M, Kumar G, Navarro G, et al. Systemic siRNA nanoparticle-based drugs combined with radiofrequency ablation for cancer therapy. Plos One . 2015;10:e0128910.
Ahmed M, Kumar G, Gourevitch S, et al. Radiofrequency ablation (RFA)–induced systemic tumor growth can be reduced by suppression of resultant heat shock proteins. Int J Hyperthermia . 2018;34:934–942.
Erinjeri JP, Thomas CT, Samoilia A, et al. Image-guided thermal ablation of tumors increases the plasma level of interleukin-6 and interleukin-10. J Vasc Interv Radiol . 2013;24:1105–1112.
Hauger O, Grenier N, Deminere C, et al. USPIO-enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial results in humans. Eur Radiol . 2007;17:2898–2907.
Bierry G, Jehl F, Boehm N, et al. Macrophage imaging by USPIO-enhanced MR for the differentiation of infectious osteomyelitis and aseptic vertebral inflammation. Eur Radiol . 2009;19:1604–1611.
Lancelot E, Raynaud JS, Desché P. Current and future MR contrast agents: seeking a better chemical stability and relaxivity for optimal safety and efficacy. Invest Radiol . 2020;55:578–588.
Wang YX, Hussain SM, Krestin GP. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol . 2001;11:2319–2331.
Smits LP, Coolen BF, Panno MD, et al. Noninvasive differentiation between hepatic steatosis and steatohepatitis with MR imaging enhanced with USPIOs in patients with nonalcoholic fatty liver disease: a proof-of-concept study. Radiology . 2016;278:782–791.
Iv M, Samghabadi P, Holdsworth S, et al. Quantification of macrophages in high-grade gliomas by using ferumoxytol-enhanced MRI: a pilot study. Radiology . 2019;290:198–206.
Smits LP, Tiessens F, Zheng KH, et al. Evaluation of ultrasmall superparamagnetic iron-oxide (USPIO) enhanced MRI with ferumoxytol to quantify arterial wall inflammation. Atherosclerosis . 2017;263:211–218.
Mori K, Fukuda K, Asaoka H, et al. Radiofrequency ablation of the liver: determination of ablative margin at MR imaging with impaired clearance of ferucarbotran—feasibility study. Radiology . 2009;251:557–565.
Nagai M, Yamaguchi M, Mori K, et al. Magnetic resonance-based visualization of thermal ablative margins around hepatic tumors by means of systemic ferucarbotran administration before radiofrequency ablation: animal study to reveal the connection between excess iron deposition and T2*-weighted hypointensity in ablative margins. Invest Radiol . 2015;50:376–383.
Koda M, Tokunaga S, Miyoshi K, et al. Ablative margin states by magnetic resonance imaging with ferucarbotran in radiofrequency ablation for hepatocellular carcinoma can predict local tumor progression. J Gastroenterol . 2013;48:1283–1292.
Goldberg SN, Gazelle GS, Compton CC, et al. Radio-frequency tissue ablation of VX2 tumor nodules in the rabbit lung. Acad Radiol . 1996;3:929–935.
Bierry G, Jehl F, Boehm N, et al. Macrophage activity in infected areas of an experimental vertebral osteomyelitis model: USPIO-enhanced MR imaging—feasibility study. Radiology . 2008;248:114–123.
Bierry G, Lefevre S, Dietemann JL, et al. In vivo macrophage imaging using MR targeted contrast agent for longitudinal evaluation of septic arthritis. J Vis Exp . 2013;:e50296.
Kooi ME, Cappendijk VC, Cleutjens KB, et al. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation . 2003;107:2453–2458.
Reimann C, Brangsch J, Kaufmann JO, et al. Dual-probe molecular MRI for the in vivo characterization of atherosclerosis in a mouse model: simultaneous assessment of plaque inflammation and extracellular-matrix remodeling. Sci Rep . 2019;9:13827.
Botnar RM, Brangsch J, Reimann C, et al. In vivo molecular characterization of abdominal aortic aneurysms using fibrin-specific magnetic resonance imaging. J Am Heart Assoc . 2018;7:e007909.
Brangsch J, Reimann C, Kaufmann JO, et al. Concurrent molecular magnetic resonance imaging of inflammatory activity and extracellular matrix degradation for the prediction of aneurysm rupture. Circ Cardiovasc Imaging . 2019;12:e008707.
Adams LC, Brangsch J, Reimann C, et al. Simultaneous molecular MRI of extracellular matrix collagen and inflammatory activity to predict abdominal aortic aneurysm rupture. Sci Rep . 2020;10:15206.
Karlmark KR, Weiskirchen R, Zimmermann HW, et al. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology . 2009;50:261–274.
Jaeschke H, Williams CD, Ramachandran A, et al. Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int . 2012;32:8–20.
Fadok VA, Bratton DL, Konowal A, et al. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest . 1998;101:890–898.
McDonald PP, Fadok VA, Bratton D, et al. Transcriptional and translational regulation of inflammatory mediator production by endogenous TGF-beta in macrophages that have ingested apoptotic cells. J Immunol . 1999;163:6164–6172.
Huynh ML, Fadok VA, Henson PM. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest . 2002;109:41–50.
Chapiro J, Geschwind JF. Science to practice: the changing face of local tumor therapies-do we have to think systemically when treating cancer locally? Radiology . 2015;276:315–317.
Shi LR, Wang JJ, Ding NH, et al. Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy. Nat Commun . 2019;10:5421.
Kumar G, Goldberg S, Wang Y, et al. 3:48 PM, Abstract No. 148. Adjuvant liposomal clodronate reduces periablational inflammatory cell recruitment and “off-target” stimulation of distant tumor growth after hepatic radiofrequency ablation (RFA). J Vasc Intervent Radiol . 2015;26:S71.
Lefevre S, Ruimy D, Jehl F, et al. Septic arthritis: monitoring with USPIO-enhanced macrophage MR imaging. Radiology . 2011;258:722–728.
Bulvik BE, Rozenblum N, Gourevich S, et al. Irreversible electroporation versus radiofrequency ablation: a comparison of local and systemic effects in a small-animal model. Radiology . 2016;280:413–424.
Velez E, Goldberg SN, Kumar G, et al. Hepatic thermal ablation: effect of device and heating parameters on local tissue reactions and distant tumor growth. Radiology . 2016;281:782–792.
Chouly C, Pouliquen D, Lucet I, et al. Development of superparamagnetic nanoparticles for MRI: effect of particle size, charge and surface nature on biodistribution. J Microencapsul . 1996;13:245–255.