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Early origin of the middle cerebral artery M2 segment is a normal variant. When such a vessel is occluded proximally, the parenchyma distal to the vessel may become ischemic. Targeted extracranial to intracranial bypass to such a specific branch may preserve perfusion to the end organ. We describe the use of intra-aneurysmal injection of indocyanine green to identify a target middle cerebral artery branch (MCA) for bypass, immediately followed by proximal parent vessel sacrifice via endovascular embolization.A 45-year-old woman presented to an outside hospital with headaches. Magnetic resonance imaging revealed a giant aneurysm of the right MCA. The aneurysm gave rise to an M2 branch that supplied the right anterior frontal operculum, as well as the anterolateral portion of the superior temporal gyri. Balloon test occlusion was nondiagnostic because of the territory involved, and the risk of sizable infarction after vessel sacrifice was thought to be high. Craniotomy and targeted extracranial to intracranial bypass to an M4 opercular branch was performed with intra-aneurysmal injection of indocyanine green. In our combined endovascular/open cerebrovascular suite, an opercular MCA branch that fluoresced during the first-pass arterial circulation of indocyanine green was identified, and a superficial temporal artery to MCA bypass was performed. Angiographic verification of bypass patency was confirmed, followed by embolic occlusion of the giant aneurysm with preservation of flow to the parenchyma at risk through the bypass.Targeted bypass to distal branches is feasible with intra-arterial and intra-aneurysmal injection of indocyanine green, allowing confident preservation of blood supply to areas distal to the sacrificed vessel.