Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types

Piyusha S. Gade, Riikka Tulamo, Kee Won Lee, Fernando Mut, Eliisa Ollikainen, Chih Yuan Chuang, Bong Jae Chung, Mika Niemelä, Behnam Rezai Jahromi, Khaled Aziz, Alexander Yu, Fady T. Charbel, Sepideh Amin-Hanjani, Juhana Frösen, Juan R. Cebral, Anne M. Robertson

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2157-2167
Number of pages11
JournalArteriosclerosis, thrombosis, and vascular biology
Volume39
Issue number10
DOIs
StatePublished - 1 Oct 2019

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Intracranial Aneurysm
Lipids
Ruptured Aneurysm
X-Ray Microtomography
Vascular Diseases
Pathology
Inflammation

Keywords

  • aneurysm, ruptured
  • calcification
  • intracranial aneurysms
  • lipid
  • prevalence

Cite this

Gade, Piyusha S. ; Tulamo, Riikka ; Lee, Kee Won ; Mut, Fernando ; Ollikainen, Eliisa ; Chuang, Chih Yuan ; Jae Chung, Bong ; Niemelä, Mika ; Rezai Jahromi, Behnam ; Aziz, Khaled ; Yu, Alexander ; Charbel, Fady T. ; Amin-Hanjani, Sepideh ; Frösen, Juhana ; Cebral, Juan R. ; Robertson, Anne M. / Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types. In: Arteriosclerosis, thrombosis, and vascular biology. 2019 ; Vol. 39, No. 10. pp. 2157-2167.
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title = "Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types",
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.",
keywords = "aneurysm, ruptured, calcification, intracranial aneurysms, lipid, prevalence",
author = "Gade, {Piyusha S.} and Riikka Tulamo and Lee, {Kee Won} and Fernando Mut and Eliisa Ollikainen and Chuang, {Chih Yuan} and {Jae Chung}, Bong and Mika Niemel{\"a} and {Rezai Jahromi}, Behnam and Khaled Aziz and Alexander Yu and Charbel, {Fady T.} and Sepideh Amin-Hanjani and Juhana Fr{\"o}sen and Cebral, {Juan R.} and Robertson, {Anne M.}",
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Gade, PS, Tulamo, R, Lee, KW, Mut, F, Ollikainen, E, Chuang, CY, Jae Chung, B, Niemelä, M, Rezai Jahromi, B, Aziz, K, Yu, A, Charbel, FT, Amin-Hanjani, S, Frösen, J, Cebral, JR & Robertson, AM 2019, 'Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types', Arteriosclerosis, thrombosis, and vascular biology, vol. 39, no. 10, pp. 2157-2167. https://doi.org/10.1161/ATVBAHA.119.312922

Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types. / Gade, Piyusha S.; Tulamo, Riikka; Lee, Kee Won; Mut, Fernando; Ollikainen, Eliisa; Chuang, Chih Yuan; Jae Chung, Bong; Niemelä, Mika; Rezai Jahromi, Behnam; Aziz, Khaled; Yu, Alexander; Charbel, Fady T.; Amin-Hanjani, Sepideh; Frösen, Juhana; Cebral, Juan R.; Robertson, Anne M.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 39, No. 10, 01.10.2019, p. 2157-2167.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types

AU - Gade, Piyusha S.

AU - Tulamo, Riikka

AU - Lee, Kee Won

AU - Mut, Fernando

AU - Ollikainen, Eliisa

AU - Chuang, Chih Yuan

AU - Jae Chung, Bong

AU - Niemelä, Mika

AU - Rezai Jahromi, Behnam

AU - Aziz, Khaled

AU - Yu, Alexander

AU - Charbel, Fady T.

AU - Amin-Hanjani, Sepideh

AU - Frösen, Juhana

AU - Cebral, Juan R.

AU - Robertson, Anne M.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - aneurysm, ruptured

KW - calcification

KW - intracranial aneurysms

KW - lipid

KW - prevalence

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U2 - 10.1161/ATVBAHA.119.312922

DO - 10.1161/ATVBAHA.119.312922

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JO - Arteriosclerosis, thrombosis, and vascular biology

JF - Arteriosclerosis, thrombosis, and vascular biology

SN - 1524-4636

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