Piyusha S Gade1, Riikka Tulamo2, Kee-Won Lee1, Fernando Mut3, Eliisa Ollikainen4,5, Chih-Yuan Chuang4, Bong Jae Chung6, Mika Niemelä5, Behnam Rezai Jahromi5, Khaled Aziz7, Alexander Yu7, Fady T Charbel8, Sepideh Amin-Hanjani8, Juhana Frösen9, Juan R Cebral3, Anne M Robertson1,4. 1. From the Department of Bioengineering (P.S.G., K.L., A.M.R.), University of Pittsburgh, PA. 2. Department of Vascular Surgery (R.T.), Helsinki University Hospital, University of Helsinki, Finland. 3. Department of Bioengineering, George Mason University, Fairfax, VA (F.M., J.R.C.). 4. Department of Mechanical Engineering and Materials Science (E.O., C.-Y.C., A.M.R.), University of Pittsburgh, PA. 5. Department of Neurosurgery (E.O., M.N., B.R.J.), Helsinki University Hospital, University of Helsinki, Finland. 6. Department of Mathematical Sciences, Montclair State University, NJ (B.J.C.). 7. Department of Neurosurgery, Allegheny General Hospital, Pittsburgh, PA (K.A., A.Y.). 8. Department of Neurosurgery, University of Illinois at Chicago (F.T.C., S.A.-H.). 9. Department of Neurosurgery, Kuopio University Hospital, Finland (J.F.).
Abstract
OBJECTIVE: Although the clinical and biological importance of calcification is well recognized for the extracerebral vasculature, its role in cerebral vascular disease, particularly, intracranial aneurysms (IAs), remains poorly understood. Extracerebrally, 2 distinct mechanisms drive calcification, a nonatherosclerotic, rapid mineralization in the media and a slower, inflammation driven, atherosclerotic mechanism in the intima. This study aims to determine the prevalence, distribution, and type (atherosclerotic, nonatherosclerotic) of calcification in IAs and assess differences in occurrence between ruptured and unruptured IAs. Approach and Results: Sixty-five 65 IA specimens (48 unruptured, 17 ruptured) were resected perioperatively. Calcification and lipid pools were analyzed nondestructively in intact samples using high resolution (0.35 μm) microcomputed tomography. Calcification is highly prevalent (78%) appearing as micro (<500 µm), meso (500 µm-1 mm), and macro (>1 mm) calcifications. Calcification manifests in IAs as both nonatherosclerotic (calcification distinct from lipid pools) and atherosclerotic (calcification in the presence of lipid pools) with 3 wall types: Type I-only calcification, no lipid pools (20/51, 39%), Type II-calcification and lipid pools, not colocalized (19/51, 37%), Type III-calcification colocalized with lipid pools (12/51, 24%). Ruptured IAs either had no calcifications or had nonatherosclerotic micro- or meso-calcifications (Type I or II), without macro-calcifications. CONCLUSIONS: Calcification in IAs is substantially more prevalent than previously reported and presents as both nonatherosclerotic and atherosclerotic types. Notably, ruptured aneurysms had only nonatherosclerotic calcification, had significantly lower calcification fraction, and did not contain macrocalcifications. Improved understanding of the role of calcification in IA pathology should lead to new therapeutic targets.
OBJECTIVE: Although the clinical and biological importance of calcification is well recognized for the extracerebral vasculature, its role in cerebral vascular disease, particularly, intracranial aneurysms (IAs), remains poorly understood. Extracerebrally, 2 distinct mechanisms drive calcification, a nonatherosclerotic, rapid mineralization in the media and a slower, inflammation driven, atherosclerotic mechanism in the intima. This study aims to determine the prevalence, distribution, and type (atherosclerotic, nonatherosclerotic) of calcification in IAs and assess differences in occurrence between ruptured and unruptured IAs. Approach and Results: Sixty-five 65 IA specimens (48 unruptured, 17 ruptured) were resected perioperatively. Calcification and lipid pools were analyzed nondestructively in intact samples using high resolution (0.35 μm) microcomputed tomography. Calcification is highly prevalent (78%) appearing as micro (<500 µm), meso (500 µm-1 mm), and macro (>1 mm) calcifications. Calcification manifests in IAs as both nonatherosclerotic (calcification distinct from lipid pools) and atherosclerotic (calcification in the presence of lipid pools) with 3 wall types: Type I-only calcification, no lipid pools (20/51, 39%), Type II-calcification and lipid pools, not colocalized (19/51, 37%), Type III-calcification colocalized with lipid pools (12/51, 24%). Ruptured IAs either had no calcifications or had nonatherosclerotic micro- or meso-calcifications (Type I or II), without macro-calcifications. CONCLUSIONS: Calcification in IAs is substantially more prevalent than previously reported and presents as both nonatherosclerotic and atherosclerotic types. Notably, ruptured aneurysms had only nonatherosclerotic calcification, had significantly lower calcification fraction, and did not contain macrocalcifications. Improved understanding of the role of calcification in IA pathology should lead to new therapeutic targets.
Authors: Anne M Robertson; Xinjie Duan; Khaled M Aziz; Michael R Hill; Simon C Watkins; Juan R Cebral Journal: Ann Biomed Eng Date: 2015-01-30 Impact factor: 3.934
Authors: Annelotte Vos; Wim Van Hecke; Wim G M Spliet; Roel Goldschmeding; Ivana Isgum; Remko Kockelkoren; Ronald L A W Bleys; Willem P T M Mali; Pim A de Jong; Aryan Vink Journal: Stroke Date: 2015-10-29 Impact factor: 7.914
Authors: Juan R Cebral; Marcelo A Castro; Sunil Appanaboyina; Christopher M Putman; Daniel Millan; Alejandro F Frangi Journal: IEEE Trans Med Imaging Date: 2005-04 Impact factor: 10.048
Authors: Juan R Cebral; Fernando Mut; Piyusha Gade; Fangzhou Cheng; Yasutaka Tobe; Juhana Frosen; Anne M Robertson Journal: Int J Numer Method Biomed Eng Date: 2018-08-21 Impact factor: 2.747
Authors: Redi Rahmani; Jacob F Baranoski; Felipe C Albuquerque; Michael T Lawton; Tomoki Hashimoto Journal: Exp Neurol Date: 2022-03-25 Impact factor: 5.620
Authors: Jason M Acosta; Anne F Cayron; Nicolas Dupuy; Graziano Pelli; Bernard Foglia; Julien Haemmerli; Eric Allémann; Philippe Bijlenga; Brenda R Kwak; Sandrine Morel Journal: Front Cardiovasc Med Date: 2021-12-08
Authors: Ashrita Raghuram; Alberto Varon; Jorge A Roa; Daizo Ishii; Yongjun Lu; Madhavan L Raghavan; Chaorong Wu; Vincent A Magnotta; David M Hasan; Timothy R Koscik; Edgar A Samaniego Journal: Sci Rep Date: 2021-09-15 Impact factor: 4.379