Evolution of Flow-Diverter Endothelialization and Thrombus Organization in Giant Fusiform Aneurysms after Flow Diversion: A Histopathologic Study

Abstract

Background and purpose: Treatment of giant fusiform aneurysms with flow diverters has been associated with a relatively high rate of complications. Our goal was to study the evolution of flow-diverter endothelialization and thrombus organization at different time points after flow-diverter treatment in giant fusiform aneurysms to better understand reasons for flow-diverter thrombosis and delayed aneurysm ruptures.

Materials and methods: Two giant anterior and 2 posterior circulation aneurysms, all of which had partially thrombosed before treatment, were studied. An unruptured, untreated posterior circulation aneurysm was used as a control. Each specimen was removed at 7 days or at 6, 9, or 13 months after flow-diverter treatment. The 3 patients who survived longer than 7 days were followed up by angiography and MR imaging. Formaldehyde-fixed paraffin-embedded sections were stained by using H&E, Van Gieson elastic, CD34, h-Caldesmon, and Picrosirius stains and studied by light microscopy.

Results: According to angiography, aneurysms were found to be obliterated partially at 6 and 9 months and completely at 13 months. MR imaging revealed that mass effect remained unchanged in each case. Sections of the flow diverter within the normal parent artery were covered by an endothelialized fibrous layer as early as 6 months, but there was no tissue coverage or endothelialization seen even at 13 months inside the aneurysm itself. Each treated aneurysm had a thin wall with complete lack of smooth muscle cells. No signs of thrombus organization were found at any of the time points studied.

Conclusions: Endothelialization of the flow diverter in giant fusiform aneurysms may not occur and thrombus organization may not be initiated inside these aneurysms for as long as 1 year, which explains delayed flow-diverter thrombosis and the possibility of delayed ruptures.

Fig 1.

Unruptured, nonthrombosed giant fusiform aneurysm involving the vertebrobasilar junction. A, Volume-rendering 3D reconstruction of a CTA, demonstrating fusiform aneurysm of the vertebrobasilar junction. B, Histologic section of the fusiform aneurysm showing fresh clot inside the aneurysm (star), intact elastic lamina (arrow), and thick aneurysm wall (double arrow) (H&E staining). C, Section of the aneurysm wall showing a thick layer of smooth muscle cells (arrow) (h-Caldesmon staining). D, Section of the aneurysm wall showing a thick subintimal layer of connective tissue (Picrosirius staining) (arrows) and no connective tissue invasion into the thrombus inside the aneurysm, indicating a lack of thrombus organization.

Fig 2.

Giant, partially thrombosed, fusiform aneurysm of the left MCA treated with a construct of 2 Pipeline embolization devices; the specimen was removed 6 months after PED implantation. A, T2-weighted MR image before treatment, showing large mass of mixed signal intensity, associated with significant mass effect and white matter edema, consistent with a giant aneurysm. B, DSA of the same aneurysm. The arrow points to the proximal, normal portion of the M1 section. and the double arrow points to the fusiform aneurysm expending into the M2 sections. C, Follow-up DSA 6 months later showing “angiographic reconstruction” of the distal M1 section (arrow), significant enlargement of the dilated proximal section of the cranial M2 branch (bent arrow), and lack of filling (occlusion) of this branch distal to the dilation. The PED construct can be seen between the 2 dotted arrows. D, Follow-up T2-weighted MR image from 6 months after treatment showing unchanged mass effect, edema, and mixed signal intensity. E, Longitudinal cut of the proximal landing zone. The luminal surface of the PED is covered by a smooth tissue layer. F, Microscopic section of the layer removed from the luminal surface of the PED showing neointimal growth consisting of smooth muscle cells (h-Caldesmon staining). G, The same layer is covered by a single cell layer of endothelium (arrow) (CD34 staining). H, Macroscopic cross-section of the specimen at the level of the fusiform aneurysm. The implanted PED construct (arrow) is uncovered and surrounded by fresh clot (bent arrow).

Fig 3.

Giant, partially thrombosed fusiform aneurysm of the right ICA treated by a construct of 2 PEDs. The specimen was removed 13 months after treatment. A, DSA before treatment showing the circulating portion of the partially thrombosed GFA involving the supraclinoid ICA on the right. B, DSA 1 year after treatment showing angiographic reconstruction of the entire length of the fusiform aneurysm. C. Thin fibrin layer removed from the luminal surface of the PED construct by H&E staining. The arrows in C and D point to the impressions of the flow-diverter struts on the outer surface of the fibrin layer. D, h-Caldesmon staining fails to show smooth muscle cells inside this layer. E, CD34 fails to show endothelial coverage on the luminal surface (arrows) of the layer. F, Histologic section showing a thick aneurysm wall with low cell attenuation (star) and fresh thrombus underneath the wall (double star) by H&E staining. G, h-Caldesmon staining fails to show any smooth muscle cells within the wall (star) or invasion into the clot (double star). H, Picrosirius staining reveals subintimal connective tissue within the thick aneurysm wall (star) but no invasion into the thrombus (double star).