Angiographic Structural Differentiation between Native Arteriogenesis and Therapeutic Synangiosis in Intracranial Arterial Steno-Occlusive Disease

Abstract

Background and Purpose Encephaloduroarteriosynangiosis has been shown to generate collateral vessels from the extracranial to the intracranial circulation in patients with moyamoya disease and intracranial arterial steno-occlusive disease. The mechanisms involved are not well understood. We hypothesize that angiogenesis is the leading mechanism forming collaterals after encephaloduroarteriosynangiosis as there are no preexisting connections, which should exhibit higher architectural complexity compared to native collaterals. Materials and Methods Pre- and postoperative digital subtraction angiograms were analyzed in patients enrolled in a prospective trial of encephaloduroarteriosynangiosis surgery. Branching angioscore, tortuosity index, and local connected fractal dimension were compared between innate and postoperative collaterals. Results 101 angiograms (50 preoperative, 51 postoperative) were analyzed from 44 patients (22 intracranial atherosclerosis and 22 moyamoya disease). There was a significantly higher median branching angioscore (13 vs. 4, p < 0.001) and lower median tortuosity index (1.08 vs. 1.76, p < 0.001) in the encephaloduroarteriosynangiosis collaterals compared to innate collaterals. Higher mean local fractal dimension peaks (1.28 SD 0.1 vs. 1.16 SD 0.11, p < 0.001) were observed in the encephaloduroarteriosynangiosis collaterals compared to innate collaterals for both intracranial atherosclerosis (p < 0.001) and moyamoya disease (p < 0.001) groups. The observed increase in high connectivity was greater in the intracranial atherosclerosis group compared to moyamoya disease cases (p = 0.01). Conclusions The higher median branching angioscore and local connected fractal dimension, along with lower median tortuosity index of encephaloduroarteriosynangiosis collaterals are consistent with the greater complexity observed in the process of sprouting and splitting associated with angiogenesis.

Hypoxia induces de novo formation of cerebral collaterals and lessens the severity of ischemic stroke

“…Interestingly, a presumed hypoxia-driven type of NCF occurs in patients with pMCAO caused by steno-occlusive moyamoya disease or following indirect surgical revascularization to relieve chronic ischemia in the MCA territory. 54 – 58 Also of note, Marushima et al. 59 reported that indirect bypass surgery using implantation of the temporalis muscle with myoblasts expressing VEGFA improved outcome after pMCAO in mice.…”

“…Interestingly, a presumed hypoxia-driven type of NCF occurs in patients with pMCAO caused by steno-occlusive moyamoya disease or following indirect surgical revascularization to relieve chronic ischemia in the MCA territory. [54][55][56][57][58] Also of note, Marushima et al 59 reported that indirect bypass surgery using implantation of the temporalis muscle with myoblasts expressing VEGFA improved outcome after pMCAO in mice. Our finding that systemic hypoxia and pMCAO induce NCF is consistent with preliminary reports in adult mouse heart for systemic hypoxia 21,22 and following coronary artery ligation, 20 with the latter recently being confirmed in neonatal mice.…”

Dynamics of Forest Fragmentation and Connectivity Using Particle and Fractal Analysis

“…The LCFD value equals 1.0 when the object is a one-dimensional straight line. LCFD equals 2.0 when the object is two-dimensional and completely covered 51 . Pixels in the 8 × 8 environment of the seed pixel are considered to be connected.…”

The Potential Mechanism Behind Native and Therapeutic Collaterals in Moyamoya

“…Arteriogenesis involves the recruitment and enlargement of pre-existing vessels, and sprouting and splitting are not parts of this process. A previous study showed that when a collateral develops into a vessel distal to a stenosis, higher flow and increased shear stress are associated with the enlargement of the collateral vessel ( 11 ). We found no significant difference in the CD34 bri CD133 + CD45 dim KDR + cell count among the three spontaneous collateral circulation groups, although the heterozygous c.14429G>A (p.R4810K) of RNF213 was significantly correlated with spontaneous collateral circulation.…”

“…The uncertainty of post-surgical synangiosis is the main consideration that limits the use of this method. According to earlier reports, collateral vessel formation in encephaloduroarteriosynangiosis (EDAS), a commonly used indirect revascularization surgery, may be primarily driven by angiogenesis ( 10 , 11 ). Angiogenesis is induced by hypoxia and involves the formation of new collateral vessels by sprouting or splitting from the pre-existing vascular structures ( 12 , 13 ).…”