Durable thrombosis in a rat model of arteriovenous malformation treated with radiosurgery and vascular targeting

Reddy, Rajesh; Duong, T. T. Hong; Fairhall, Jacob; Smee, Robert; Stoodley, Marcus A.

doi:10.3171/2013.9.jns122056

Cited by 18 publications

(14 citation statements)

References 62 publications

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“…36,39,40 Months or years later, delayed radiation effects are seen as a proliferation of injured endothelium, intravascular thrombosis, stromal collagen accumulation, and hyaline degeneration. 17,41 The thrombus formation is promoted by intimal injury, increased platelet aggregation, and turbulent blood flow that play an important role in the obliteration cascade of the small pathologic vessels of the AVM nidus. 35,41,42 Also, the subendothelial and the periadventitial proliferation and the contraction of the myofibroblasts, particularly the A phenotype, play an important role in shrinkage and eventual luminal closure of the thrombosed AVM after SRS.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Appearance of MRI Perinidal T2 Hyperintensity Signal and Eventual Nidus Obliteration Following Photon Radiosurgery of Brain AVMs: Combined Results of LINAC and Gamma Knife Centers

Abdelaziz

Shereen

Inoue

et al. 2019

J Neurol Surg A Cent Eur Neurosurg

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Background A wide variety of radiologic changes occur within and adjacent to the nidus of arteriovenous malformations (AVMs) after stereotactic radiosurgery (SRS). Our objective was to study the magnetic resonance imaging(MRI)-defined changes following photon radiosurgery of AVMs and specifically to correlate the appearance of a perinidal T2 hyperintensity signal with the eventual angiographic obliteration of an AVM nidus in response to SRS treatment. Material and Methods This retrospective study was conducted on 62 patients with brain AVMs who received photon SRS treatments between 2004 and 2017, using either a technique based on a linear accelerator at the Alexandria LINAC Radiosurgery Center in Egypt (21 patients/AVMs) or a technique based on a gamma unit at the Koto Memorial Gamma Knife Center in Japan (41 patients/AVMs). All patients included in the study had serial clinical and radiologic follow-ups for ≥ 2 years after SRS treatments. Results In the combined study series of 62 patients/AVMs treated with photon SRS, the follow-up MRIs revealed that 50 AVMs (80.6%) showed nonvisualized nidus and 12 AVMs (19.4%) showed decreased nidus size. Radiation-induced changes, defined as appearance of perinidal T2 hyperintensities in post-SRS MRIs, occurred in 34 patients (54.8%). Of the 35 patients with available follow-up angiographic studies, 30 AVMs (85.7%) demonstrated complete nidus obliteration at a mean of 36 months (range: 8–66 months) after SRS. Of the 30 AVMs with both MRI evidence of a nonvisualized nidus and angiographic verification of complete nidus obliteration, 20 AVMs (66.7%) were associated with prior MRI evidence of the appearance of a perinidal T2 hyperintensity signal at an average of 12 months (range: 6–45 months) after SRS. Of the five AVMs with both MRI evidence of decreased nidus size and angiographic verification of partial nidus obliteration, four AVMs (80%) showed perinidal T2 hyperintensity signal on post-SRS follow-up MRIs. Lower Spetzler-Martin grade (p = 0.013), smaller AVM volume (p = 0.017), and appearance of post-SRS perinidal T2 hyperintensity signal (p = 0.007) were the statistically significant independent predictors of AVM obliteration. The appearance of perinidal T2 hyperintensity signal in the post-SRS MRIs had a sensitivity of 66.7%, a specificity of 20%, and an overall accuracy of 60% in predicting the eventual obliteration of the AVM nidus. Conclusions The present study may help improve our current understanding of the mechanisms behind the radiation-induced tissue changes following AVM SRS. Because the SRS-induced hemodynamic changes within the AVM nidus initiate the cascade of the subsequent formation of perinidal vasogenic brain edema, the appearance of perinidal high T2 signal in the follow-up MRIs after SRS would be a valuable indicator of the AVM response to SRS. The development of perinidal hyperintensity was the strongest predictive factor of AVM obliteration (p = 0.007), with relatively high sensitivity (66.7%) and accuracy (60%) and fairly low specificity (20%), as a prognostic sign of eventual complete angiographic obliteration of the AVM nidus following SRS.

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Section: Discussionmentioning

confidence: 99%

Correlation of Appearance of MRI Perinidal T2 Hyperintensity Signal and Eventual Nidus Obliteration Following Photon Radiosurgery of Brain AVMs: Combined Results of LINAC and Gamma Knife Centers

Abdelaziz

Shereen

Inoue

et al. 2019

J Neurol Surg A Cent Eur Neurosurg

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“…16,35,50 Identification of genetic mutations associated with cerebral AVM formation has facilitated the development of animal models that have provided new insights into the etiology of these lesions. 9,34,39,50 Although inheritable mutations are most frequently discussed, environmental factors are also believed to play an important role in single allele mutations. 23 Osler-Weber-Rendu syndrome, or HHT, is the most common syndrome associated with AVMs.…”

Section: Molecular and Cellular Biology Associated With Syndromic Avmsmentioning

confidence: 99%

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment

Rangel-Castilla¹,

Russin²,

Martinez-del-Campo³

et al. 2014

FOC

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Object Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management. Methods A PubMed search was performed using the key words “genetic,” “molecular,” “brain,” “cerebral,” “arteriovenous,” “malformation,” “rupture,” “management,” “embolization,” and “radiosurgery.” Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed. Results Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed. Conclusions Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

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“…25,33,38 A highly discriminating target, which dominantly expresses on AVM endothelium, is required for the success of this technique. We have investigated the molecular characteristics of the endothelial surface of AVM vessels 20,39,40 and, although differences were found in comparison with normal blood vessels, no target with adequate discriminating power has been found to date.…”

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confidence: 99%

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations

Zhao

Johnson

Chen

et al. 2016

JNS

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Brain arteriovenous malformations (AVMs) are congenital abnormalities that consist of direct connections between arteries and veins, allowing highpressure arterial blood to flow into fragile cerebral veins, resulting in a high risk of hemorrhagic stroke. 16,37 The aim of AVM treatment is to prevent hemorrhage. 29 Treatment is effective only with complete AVM removal or obliteration. 14 Current treatments-namely surgery, endovascular occlusion, or stereotactic radiosurgery-are all associated with significant limitations.1,42 The surgical risk is generally unacceptable for lesions that are large, located in critical brain structures, or involve deep perforating arterabbreviatioNs AVM = arteriovenous malformation; FWD = forward; PI = propidium iodide; PS = phosphatidylserine; pSIVA = polarity-sensitive indicator of viability and apoptosis; SRS = stereotactic radiosurgery. obJective Stereotactic radiosurgery (SRS) is an established intervention for brain arteriovenous malformations (AVMs). The processes of AVM vessel occlusion after SRS are poorly understood. To improve SRS efficacy, it is important to understand the cellular response of blood vessels to radiation. The molecular changes on the surface of AVM endothelial cells after irradiation may also be used for vascular targeting. This study investigates radiation-induced externalization of phosphatidylserine (PS) on endothelial cells using live-cell imaging. methods An immortalized cell line generated from mouse brain endothelium, bEnd.3 cells, was cultured and irradiated at different radiation doses using a linear accelerator. PS externalization in the cells was subsequently visualized using polarity-sensitive indicator of viability and apoptosis (pSIVA)-IANBD, a polarity-sensitive probe. Live-cell imaging was used to monitor PS externalization in real time. The effects of radiation on the cell cycle of bEnd.3 cells were also examined by flow cytometry. results Ionizing radiation effects are dose dependent. Reduction in the cell proliferation rate was observed after exposure to 5 Gy radiation, whereas higher radiation doses (15 Gy and 25 Gy) totally inhibited proliferation. In comparison with cells treated with sham radiation, the irradiated cells showed distinct pseudopodial elongation with little or no spreading of the cell body. The percentages of pSIVA-positive cells were significantly higher (p = 0.04) 24 hours after treatment in the cultures that received 25- and 15-Gy doses of radiation. This effect was sustained until the end of the experiment (3 days). Radiation at 5 Gy did not induce significant PS externalization compared with the sham-radiation controls at any time points (p > 0.15). Flow cytometric analysis data indicate that irradiation induced growth arrest of bEnd.3 cells, with cells accumulating in the G2 phase of the cell cycle. coNclusioNs Ionizing radiation causes remarkable cellular changes in endothelial cells. Significant PS externalization is induced by radiation at doses of 15 Gy or higher, concomitant with a block in the cell cycle. Ra...

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Durable thrombosis in a rat model of arteriovenous malformation treated with radiosurgery and vascular targeting

Cited by 18 publications

References 62 publications

Correlation of Appearance of MRI Perinidal T2 Hyperintensity Signal and Eventual Nidus Obliteration Following Photon Radiosurgery of Brain AVMs: Combined Results of LINAC and Gamma Knife Centers

Correlation of Appearance of MRI Perinidal T2 Hyperintensity Signal and Eventual Nidus Obliteration Following Photon Radiosurgery of Brain AVMs: Combined Results of LINAC and Gamma Knife Centers

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations

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