Background: There are controversies concerning the natural history of arteriovenous malformations (AVMs) in literature and it is not clear which AVMs should be treated and which should be just observed. Objective criteria beyond growth in serial MRIs or angiographies are needed. The use of black blood MRI is currently under investigation for evaluating the rupture risk of cerebral aneurysms, however its use for assessment of AVMs has yet to be evaluated. We therefore conducted a feasibility study on the application of black blood MRI (bbMRI) in AVMs to assess rupture risk. Methods: Retrospective study of 10 patients with intracranial AVMs and 4 patients with arteriovenous fistulas who received a black blood MRI before treatment. Results: AVM niduses (9/10) show contrast enhancement irrespective of rupture or size. All arteriovenous fistulas (4 / 4) were contrast enhancing irrespective of rupture. Conclusion: High flow malformations are in a permanent stage of inflammation which does not seem to allow conclusions on their rupture risk at the current stage. BbMRI is a feasible method of identifying inflammation in AVMs and arteriovenous fistulas. However, future prospective studies are needed to evaluate whether bbMRI contrast enhancement correlates with rupture risk. Keywords: Arteriovenous malformation, Arteriovenous fistula, Black blood MRI, Inflammation Background enhancement in the aneurysm wall reflects inflammatory The natural history of arteriovenous malformations processes and inflammation in the AVM vessel wall has (AVMs) represents a controversial topic. While the been shown histologically , we studied the possibility ARUBA study shows a low rupture risk, epidemiologic of bbMRI on high flow AVMs in order to evaluate studies suggest a high risk of bleeding throughout a differences in inflammatory processes which could patient´s life [1, 2]. Little is known about the patho- signify instability. One study with 4 patients using physiological processes in an AVM and even less about ferumoxytol-enhanced MRI showed the feasibility of any factors which could predict a risk of bleeding. The MRIs in visualizing inflammation in AVMs . A study black blood MRI (bbMRI) appeared on the diagnostic on cavernomatous malformations conducted by our horizon and offers a promising outlook in predicting group showed no significant contrast enhancement of rupture risk in intracranial aneurysms [3, 4]. As contrast the walls of brain cavernomas (low flow malformations, results submitted for publication). The main question was whether inflammatory reactions in the walls of high * Correspondence: firstname.lastname@example.org Department of Neurosurgery, Heinrich Heine University, Duesseldorf, flow malformations can be visualized by bbMRI and Germany Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Petridis et al. Chinese Neurosurgical Journal (2018) 4:13 Page 2 of 5 Table 1 Characteristics of the study population Gender Age S-M Localization Hemorrhage Size Treatment Contrast enhancement in black blood MRI Male 51 y 1 temporal non bleeding 25 mm Surgery Contrast at fistulas Female 19 y 1 temporal bleeding 15 mm Surgery Contrast atnidus Male 19 y 2 frontal bleeding 14 mm Surgery Contrast at nidus Male 53 y 2 frontal bleeding 15 mm Surgery Contrast at nidus Male 77 y 2 cerebellar bleeding 17 mm Embolisation Contrast at nidus Male 46 y 2 frontal non bleeding 9 mm Radiation No contrast Female 49 y 2 parietal non bleeding 36 mm Observation Contrast at nidus Female 53 y 2 temporal non bleeding 33 mm Surgery Contrast at nidus Female 61 y 4 Temporo-parietal non bleeding 46 mm Observation Contrast at fistulas Male 57 y 5 fronto-parietal non bleeding 67 mm Observation Contrast at nidus whether the contrast enhancement can predict any sta- the MRIs of 10 patients with AVMs treated in our de- tus of instability of an AVM. partment. In addition, N = 4 patients with arteriovenous fistulas received a bbMRI. The patients presented in our Methods outpatient facilities or in case of AVM bleeding in the From January 2017 until July 2017 patients with AVMs emergency room. The analysis of bbMRIs was per- treated in our department received a bbMRI sequence in formed by a neuroradiologists and the result of contrast addition to the regular MRI. We retrospectively analyzed enhancement in the AVM was rated as positive or Fig. 1 Case with incidental AVM. a Digital subtraction angiography showing the frontal AVM in sagittal (left) and b. coronal (right) views. c. BbMRI shows no contrast enhancement in the AVM Petridis et al. Chinese Neurosurgical Journal (2018) 4:13 Page 3 of 5 negative. Three cases are illustrated. AVM size was de- fined as the longest diameter in mm. Cranial MRI was performed on a 3T MR scanner (Magnetom Skyra, Siemens, Erlangen) with a 20 channel head coil. The protocol included a 3 D T1 space sequence with fat saturation (SPAIR) and blood suppression (field of view 179*230, repetition time 693 ms, echo time 18 ms, matrix 256 x 256, spatial resolution 0.9 x .09 x 0.9 mm) before and after administration of gadolinium (0,2 ml/kg/ BW, maximum 20 ml; ProHance, Bracco Imaging, Germany). Total scan time was 8 min. Results N = 10 patients with AVMs of which 4 were female re- ceived a bbMRI. The mean age of patients with bleeding AVMs (N = 4) was 42 y (19-77 y) and 52.8 y (46-61 y) for the non-bleeding cases. Five patients were operated on; 3 AVMs are still under observation, one was embolized and one irradiated. In 9 / 10 cases the AVM vessel walls showed contrast enhancement. Four patients presented with intracranial bleeding all of which showed strong con- trast enhancement in their AVM niduses. Only one AVM with no haemorrhage and a Spetzler-Martin Grade 2 had no contrast enhancement. There was no difference in con- trast enhancement between bleeding and non-bleeding Fig. 2 Incidental AVM a Digital subtraction angiography showing the AVMs. Additionally, the contrast enhancement was local- AVM b BbMRI with contrast shows a moderate contrast ized to the whole nidus, whereas in the 4 studied arterio- enhancement of the nidus venous fistula patients the contrast enhancement was exclusively in the walls of the abnormal vein. All 4 patients with arteriovenous fistulas had contrast enhancement (2 therapy she did not have any new seizures and because with haemorrhage and 2 without). Further analysis of the she rejected surgery we decided to observe the patient. patients with fistulous malformation was not possible due to the low sample size. Discussion Table 1 summarizes some of the characteristics of the The present study evaluates feasibility of bbMRI for AVMs in the 10 studied patients. assessment of AVMs. It has been shown that inflamma- tory processes play a crucial role in AVM growth with Illustrative Cases increased expression of inflammatory cytokines and We show the typical bbMRI contrast enrichment in the proteases in these lesions [7, 8]. Recruitment of leuko- AVMs in the following 3 cases. cytes and leukocyte-derived metalloproteinases lead to The first case illustrates a 46 y.o. male patient who structural degradation of the AVM walls which could presented in our outpatient clinic with the diagnosis of lead to rupture . On the other hand, macrophages an incidental AVM of 9 mm and a deep venous drainage. and other inflammatory cells are detected in the vascular The bbMRI shows no contrast enhancement. Neverthe- walls of AVMs which did not rupture [7, 8, 10]. There- less, the patient was treated by radiation therapy (Fig. 1). fore, it cannot be concluded that the inflammation is a The second case is that of a 53 y.o. female patient who sign of AVM instability and a risk factor for rupture un- presented with an epileptic seizure. The AVM (Fig. 2) like in intracranial aneurysms [3, 4]. After demonstrating was known for over 10 years but after the seizure and an that bbMRI contrast enhancement is present in AVMs increase in size we decided to remove the AVM. Before as well as in arteriovenous fistulas we looked for differ- surgery the bbMRI was performed and showed an intra- ences between ruptured and non-ruptured AVMs as well nidal contrast enhancement of the vascular walls (Fig.2). as size and inflammation. Although there is a strong up- The third case is of 61 y.o. female with an epileptic take of contrast enhancement in the AVM nidus and in seizure. The diagnostic MRI revealed a 46 mm the abnormal vein of arteriovenous fistulas in the pa- temporo-parietal AVM. The bbMRI shows contrast en- tients, indicating a high probability of ongoing inflam- hancement of the nidus (Fig. 3). Under antiepileptic mation there was no difference between ruptured and Petridis et al. Chinese Neurosurgical Journal (2018) 4:13 Page 4 of 5 Fig. 3 Non-hemorrhaged temporoparietal AVM. a MR-Angiography (left) and b reconstruction (right) of the AVM. c In the bbMRI (w/o contrast, left and d with contrast, right) there is a strong contrast enhancement of the AVM nidus unruptured malformations in size. It can be concluded looking for differences between stable AVMs and that there are dynamic inflammatory processes in AVMs those prone to rupture are needed. Objective criteria and arteriovenous fistula walls but it seems that it is not of inflammatory activity could be of use in determin- more prevalent in AVMs prone to rupture. The observa- ing which AVMs should be treated and which are to tions of inflammation in AVM walls which could indi- be observed. cate a rupture risk have to be seen critically because unlike aneurysms, AVMs appear to be in a permanent Conclusions stage of inflammation as seen in our study in which 6 The study is the first one using black blood MRI in /10 AVMs with no bleeding displayed strong contrast AVMs. What we could show is an indication of a high enhancement in bbMRI. The same phenomenon can be inflammatory acticvity in the AVM wall speaking for a observed in the four cases of arteriovenous fistulas possible instability. Never the less and because of the which were all contrast enhancing: there was no differ- small case number, it has to be evaluated in a prospect- ence between the haemorrhaged (2 out of 4) and the ive study if the inflammatory activity seen in the black non-haemorrhaged cases but sample sizes are of course blood MRI is associated with a higher bleeding rate. low. Histological specimens of AVMs together with black Never the less the number of patients studied does blood MRIs should be evaluated in further studies. not allow drawing of conclusions other than that bbMRI is feasible in indicating inflammation in AVMs Abbreviations and that AVMs are highly active in terms of inflam- AVM: Arteriovenous Malformations; bbMRI: Black Blood Magnetic Resonance matory processes. Based on this first observation with Imaging; ARUBA: A Randomised Trial of Unruptured Brain Arteriovenous bbMRI further prospective and controlled studies Malformations. Petridis et al. Chinese Neurosurgical Journal (2018) 4:13 Page 5 of 5 Acknowledgement 5. Zhang R, Han Z, Degos V, Shen F, Choi EJ, Sun Z, et al. Persistent infiltration We hereby take opportunity to thank the Department of Neurosurgery and and pro-inflammatory differentiation of monocytes cause unresolved the Institute of neuroradiology of the Heinrich Heine University, Duesseldorf, inflammation in brain arteriovenous malformation. Angiogenesis. 2016;19(4): Germany for their constant supports throughout the period of this study. 451–61. 6. Zanaty M, Chalouhi N, Starke RM, Jabbour P, Hasan D. Molecular Imaging in Neurovascular Diseases: The Use of Ferumoxytol to Assess Cerebral Funding Aneurysms and Arteriovenous Malformations. Top Magn Reson Imaging. This study did not receive any grant funding. 2016;25(2):57–61. 7. Chen Y, Fan Y, Poon KY, Achrol AS, Lawton MT, Zhu Y, et al. MMP-9 Availability of data and supporting materials expression is associated with leukocytic but not endothelial markers in brain Data sharing not applicable to this article arteriovenous malformations. Front Biosci. 2006;11:3121–8. 8. Chen Y, Pawlikowska L, Yao JS, Shen F, Zhai W, Achrol AS, et al. Interleukin-6 Authors’ contributions involvement in brain arteriovenous malformations. Ann Neurol. 2006;59:72–80. HJS and BT participated in the design of the study. AKP and MDA 9. Mun-Bryce S, Rosenberg GA. Matrix metalloproteinases in cerebrovascular Participated in the patient selection, design of the study, surgical follow-up disease. J Cereb Blood Flow Metab. 1998;18:1163–72. and co-ordination of manuscript drafting.YA, MS, LL - Patient follow up, draft- 10. Chen Y, Zhu W, Bollen AW, Lawton MT, Barbaro NM, Dowd CF, et al. ing and correction of the manuscript. JFC, MAK, RM– Valuable input in deci- Evidence of inflammatory cell involvement in brain arteriovenous sion making, treatment option and interpretation of the MRI and BB-MRI. All malformations. Neurosurgery. 2008;62(6):1340–9. authors read and approved the final manuscript. Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For retrospective studies like the present one there is no ethical approval needed according to the Physicians Chamber (Ärtzekammer Nordrhein). All patients of the study were informed oraly about possible presentation of their data, however no identification of the patient is possible in the presented data. There are no individual images of the patients contained in this manuscript. Competing interests All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Maxine Dibué-Adjei is an employee of LivaNova PLC, maufacturer of vagus nerve stimulators. Consent for Publication Not applicable. This is not a case report. As long as the patient can not be identified in the images presented no informed consent is needed. However, the patient was oraly informed and consented to publish his case. Author details Department of Neurosurgery, Heinrich Heine University, Duesseldorf, Germany. LivaNova Deutschland GmbH (a LivaNova PLC-owned subsidiary), Lindberghstr 25, D-80939 Munich, Germany. Diagnostic and Interventional Neuroradiology,Heinrich Heine University, Duesseldorf, Germany. Department of Neurosurgery, Niederrhein Hospital, Duisburg, Germany. Received: 5 December 2017 Accepted: 9 May 2018 References 1. Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicenter, non-blinded, randomized trial. Lancet. 2014;383:614–21. 2. Petridis AK, Fischer I, Cornelius JF, Kamp MA, Ringel F, Tortora A, et al. Demographic distribution of hospital admissions for brain arteriovenous malformations in Germany–estimation of the natural course with the big- data approach. Acta Neurochir (Wien). 2016;158(4):791–6. 3. Hu P, Yang Q, Wang D, Guan S, Zhang H. Wall enhancement on high- resolution magnetic resonance imaging may predict an unsteady state of an intracranial saccular aneurysm. Neuroradiol. 2016;58:979–85. 4. Park JK, Lee CS, Sim KB, Huh JS, Park JC. Imaging of the walls of saccular cerebral aneurysms with double inversion recovery black.blood sequence. J Magn Res Imag. 2009;30:1179–83.
Chinese Neurosurgical Journal – Springer Journals
Published: May 25, 2018
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