Gamma Knife radiosurgery of saccular aneurysms in a rabbit model

Mark Meadowcroft, Timothy K. Cooper, Sebastian Rupprecht, Thaddeus C. Wright, Elizabeth E. Neely, Michele Ferenci, Weimin Kang, Qing Yang, Robert Harbaugh, James Connor, James McInerney

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE Intracranial aneurysms are vascular abnormalities associated with neurological morbidity and mortality due to risk of rupture. In addition, many aneurysm treatments have associated risk profiles that can preclude the prophylactic treatment of asymptomatic lesions. Gamma Knife radiosurgery (GKRS) is a standard treatment for trigeminal neuralgia, tumors, and arteriovenous malformations. Aneurysms associated with arteriovenous malformations have been noted to resolve after treatment of the malformation. The aim of this study was to determine the efficacy of GKRS treatment in a saccular aneurysm animal model. METHODS Aneurysms were surgically produced using an elastase-induced aneurysm model in the right common carotid artery of 10 New Zealand white rabbits. Following initial observation for 4 years, each rabbit aneurysm was treated with a conformal GKRS isodose of 25 Gy to the 50% margin. Longitudinal MRI studies obtained over 2 years and terminal measures obtained at multiple time points were used to track aneurysm size and shape index modifications. RESULTS Aneurysms did not rupture or involute during the observation period. Whole aneurysm and blood volume averages decreased with a linear trend, at rates of 1.7% and 1.6% per month, respectively, over 24 months. Aneurysm wall percent volume increased linearly at a rate of 0.3% per month, indicating a relative thickening of the aneurysm wall during occlusion. Nonsphericity of the average volume, aspect ratio, and isoperimetric ratio of whole aneurysm volume all remained constant. Histopathological samples demonstrated progressive reduction in aneurysm size and wall thickening, with subintimal fibrosis. Consistent shape indices demonstrate stable aneurysm patency and maintenance of minimal rupture risk following treatment. CONCLUSIONS The data indicate that GKRS targeted to saccular aneurysms is associated with histopathological changes and linear reduction of aneurysm size over time. The results suggest that GKRS may be a viable, minimally invasive treatment option for intracranial aneurysm obliteration.

Original languageEnglish (US)
Pages (from-to)1530-1540
Number of pages11
JournalJournal of neurosurgery
Volume129
Issue number6
DOIs
StatePublished - Jan 1 2018

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Radiosurgery
Aneurysm
Rabbits
Rupture
Arteriovenous Malformations
Intracranial Aneurysm
Therapeutics
Observation
Trigeminal Neuralgia
Pancreatic Elastase
Common Carotid Artery
Blood Volume

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

Meadowcroft, M., Cooper, T. K., Rupprecht, S., Wright, T. C., Neely, E. E., Ferenci, M., ... McInerney, J. (2018). Gamma Knife radiosurgery of saccular aneurysms in a rabbit model. Journal of neurosurgery, 129(6), 1530-1540. https://doi.org/10.3171/2017.6.JNS17722
Meadowcroft, Mark ; Cooper, Timothy K. ; Rupprecht, Sebastian ; Wright, Thaddeus C. ; Neely, Elizabeth E. ; Ferenci, Michele ; Kang, Weimin ; Yang, Qing ; Harbaugh, Robert ; Connor, James ; McInerney, James. / Gamma Knife radiosurgery of saccular aneurysms in a rabbit model. In: Journal of neurosurgery. 2018 ; Vol. 129, No. 6. pp. 1530-1540.
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abstract = "OBJECTIVE Intracranial aneurysms are vascular abnormalities associated with neurological morbidity and mortality due to risk of rupture. In addition, many aneurysm treatments have associated risk profiles that can preclude the prophylactic treatment of asymptomatic lesions. Gamma Knife radiosurgery (GKRS) is a standard treatment for trigeminal neuralgia, tumors, and arteriovenous malformations. Aneurysms associated with arteriovenous malformations have been noted to resolve after treatment of the malformation. The aim of this study was to determine the efficacy of GKRS treatment in a saccular aneurysm animal model. METHODS Aneurysms were surgically produced using an elastase-induced aneurysm model in the right common carotid artery of 10 New Zealand white rabbits. Following initial observation for 4 years, each rabbit aneurysm was treated with a conformal GKRS isodose of 25 Gy to the 50{\%} margin. Longitudinal MRI studies obtained over 2 years and terminal measures obtained at multiple time points were used to track aneurysm size and shape index modifications. RESULTS Aneurysms did not rupture or involute during the observation period. Whole aneurysm and blood volume averages decreased with a linear trend, at rates of 1.7{\%} and 1.6{\%} per month, respectively, over 24 months. Aneurysm wall percent volume increased linearly at a rate of 0.3{\%} per month, indicating a relative thickening of the aneurysm wall during occlusion. Nonsphericity of the average volume, aspect ratio, and isoperimetric ratio of whole aneurysm volume all remained constant. Histopathological samples demonstrated progressive reduction in aneurysm size and wall thickening, with subintimal fibrosis. Consistent shape indices demonstrate stable aneurysm patency and maintenance of minimal rupture risk following treatment. CONCLUSIONS The data indicate that GKRS targeted to saccular aneurysms is associated with histopathological changes and linear reduction of aneurysm size over time. The results suggest that GKRS may be a viable, minimally invasive treatment option for intracranial aneurysm obliteration.",
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Gamma Knife radiosurgery of saccular aneurysms in a rabbit model. / Meadowcroft, Mark; Cooper, Timothy K.; Rupprecht, Sebastian; Wright, Thaddeus C.; Neely, Elizabeth E.; Ferenci, Michele; Kang, Weimin; Yang, Qing; Harbaugh, Robert; Connor, James; McInerney, James.

In: Journal of neurosurgery, Vol. 129, No. 6, 01.01.2018, p. 1530-1540.

Research output: Contribution to journalArticle

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T1 - Gamma Knife radiosurgery of saccular aneurysms in a rabbit model

AU - Meadowcroft, Mark

AU - Cooper, Timothy K.

AU - Rupprecht, Sebastian

AU - Wright, Thaddeus C.

AU - Neely, Elizabeth E.

AU - Ferenci, Michele

AU - Kang, Weimin

AU - Yang, Qing

AU - Harbaugh, Robert

AU - Connor, James

AU - McInerney, James

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N2 - OBJECTIVE Intracranial aneurysms are vascular abnormalities associated with neurological morbidity and mortality due to risk of rupture. In addition, many aneurysm treatments have associated risk profiles that can preclude the prophylactic treatment of asymptomatic lesions. Gamma Knife radiosurgery (GKRS) is a standard treatment for trigeminal neuralgia, tumors, and arteriovenous malformations. Aneurysms associated with arteriovenous malformations have been noted to resolve after treatment of the malformation. The aim of this study was to determine the efficacy of GKRS treatment in a saccular aneurysm animal model. METHODS Aneurysms were surgically produced using an elastase-induced aneurysm model in the right common carotid artery of 10 New Zealand white rabbits. Following initial observation for 4 years, each rabbit aneurysm was treated with a conformal GKRS isodose of 25 Gy to the 50% margin. Longitudinal MRI studies obtained over 2 years and terminal measures obtained at multiple time points were used to track aneurysm size and shape index modifications. RESULTS Aneurysms did not rupture or involute during the observation period. Whole aneurysm and blood volume averages decreased with a linear trend, at rates of 1.7% and 1.6% per month, respectively, over 24 months. Aneurysm wall percent volume increased linearly at a rate of 0.3% per month, indicating a relative thickening of the aneurysm wall during occlusion. Nonsphericity of the average volume, aspect ratio, and isoperimetric ratio of whole aneurysm volume all remained constant. Histopathological samples demonstrated progressive reduction in aneurysm size and wall thickening, with subintimal fibrosis. Consistent shape indices demonstrate stable aneurysm patency and maintenance of minimal rupture risk following treatment. CONCLUSIONS The data indicate that GKRS targeted to saccular aneurysms is associated with histopathological changes and linear reduction of aneurysm size over time. The results suggest that GKRS may be a viable, minimally invasive treatment option for intracranial aneurysm obliteration.

AB - OBJECTIVE Intracranial aneurysms are vascular abnormalities associated with neurological morbidity and mortality due to risk of rupture. In addition, many aneurysm treatments have associated risk profiles that can preclude the prophylactic treatment of asymptomatic lesions. Gamma Knife radiosurgery (GKRS) is a standard treatment for trigeminal neuralgia, tumors, and arteriovenous malformations. Aneurysms associated with arteriovenous malformations have been noted to resolve after treatment of the malformation. The aim of this study was to determine the efficacy of GKRS treatment in a saccular aneurysm animal model. METHODS Aneurysms were surgically produced using an elastase-induced aneurysm model in the right common carotid artery of 10 New Zealand white rabbits. Following initial observation for 4 years, each rabbit aneurysm was treated with a conformal GKRS isodose of 25 Gy to the 50% margin. Longitudinal MRI studies obtained over 2 years and terminal measures obtained at multiple time points were used to track aneurysm size and shape index modifications. RESULTS Aneurysms did not rupture or involute during the observation period. Whole aneurysm and blood volume averages decreased with a linear trend, at rates of 1.7% and 1.6% per month, respectively, over 24 months. Aneurysm wall percent volume increased linearly at a rate of 0.3% per month, indicating a relative thickening of the aneurysm wall during occlusion. Nonsphericity of the average volume, aspect ratio, and isoperimetric ratio of whole aneurysm volume all remained constant. Histopathological samples demonstrated progressive reduction in aneurysm size and wall thickening, with subintimal fibrosis. Consistent shape indices demonstrate stable aneurysm patency and maintenance of minimal rupture risk following treatment. CONCLUSIONS The data indicate that GKRS targeted to saccular aneurysms is associated with histopathological changes and linear reduction of aneurysm size over time. The results suggest that GKRS may be a viable, minimally invasive treatment option for intracranial aneurysm obliteration.

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Meadowcroft M, Cooper TK, Rupprecht S, Wright TC, Neely EE, Ferenci M et al. Gamma Knife radiosurgery of saccular aneurysms in a rabbit model. Journal of neurosurgery. 2018 Jan 1;129(6):1530-1540. https://doi.org/10.3171/2017.6.JNS17722