Endovascular Embolization by Transcatheter Delivery of Particles: Past, Present, and Future

Abstract

Minimally invasive techniques to occlude flow within blood vessels, initially pioneered in the 1970s with autologous materials and subsequently advanced with increasingly sophisticated engineered biomaterials, are routinely performed for a variety of medical conditions. Contemporary interventional radiologists have at their disposal a wide armamentarium of occlusive agents to treat a range of disease processes through a small incision in the skin. In this review, we provide a historical perspective on endovascular embolization tools, summarize the current state-of-the-art, and highlight burgeoning technologies that promise to advance the field in the near future.

Keywords: biomaterials; biomedical devices; cardiovascular devices; drug delivery systems; microfluidics; microspheres.

Figure 1

A large benign solitary fibrous tumor of the right pleura (A) was pre-operatively embolized with Gelfoam; (B) surgical resection photograph; (C) angiography of the right phrenic artery demonstrated exuberant vascularity within the mass; (D) histology demonstrates fragments of Gelfoam (acellular pink material) within blood vessels in the mass which is entirely infarcted.

Figure 2

A frontal lobe glioblastoma multiforme was pre-operatively embolized using polyvinyl alcohol (PVA) microspheres. A microcatheter (A,B) was advanced to a branch of the middle meningeal artery that supplied the tumor (C). (D) Post-surgical histology demonstrated PVA (acellular light blue mucoid material) within the tumoral blood vessels in the tumor comprised of pleomorphic large tumor cells; of note, the black material represents the “liquid embolic” agent Onyx (Medtronic-Covidien, Irvine, CA, USA).

Figure 3

A falcine meningioma was pre-operatively embolized using PVA microspheres. A microcatheter (A,B) was advanced to a branch of the middle meningeal artery supplying the tumor (C). Post-surgical histology shows PVA microspheres within the tumoral tissue (D).

Figure 4

Scanning electron microscopy (insert) and size distribution of poly (lactic-co-glycolic acid) (PGLA) microparticles fabricated through conventional emulsion methods demonstrate a broad range of sizes even after filtering the particles through sieves. Reproduced with permission from [15].

Figure 5

A leiomyosarcoma metastasis to the liver was embolized with 100–300 μm, doxorubicin-eluting microspheres to reduce tumor size and vascularity prior to surgical resection. Selective catheterization (A) of the tumor was performed, with proper positioning confirmed by cone-beam CT (B). Post-procedure CT (C) demonstrates no residual vascularity within the lesion. Following liver resection, microspheres were identified within the blood vessels in the tumor bed without any evidence of viable metastatic tumor (D).

Figure 6

A breast cancer metastasis to the liver was embolized with 100–300 μm, doxorubicin-eluting microspheres to reduce tumor size and vascularity prior to surgical resection. Selective catheterization (A) of the tumor was performed, with delivery of the microspheres within the blood vessels of the tumor (B). Post-procedure CT (D) demonstrates complete response of the tumor as indicated by fibrosis alone without any evidence of residual tumor compared to the pre-procedure CT (C).

Figure 7

(A) Optical image of a microfluidic chip featuring two parallel droplet formulators. (B) Optical image of an in-line droplet generating nozzle for particle formulation and emulsification. (C) Optical image of a monodisperse population of 10 μm diameter microspheres. Reproduced with permission from [23]. Copyright (2005) American Chemical Society.

Figure 8

Microfluidics systems create monodisperse populations of microspheres. (A,B), scanning electron microscopy shows microspheres produced by microfluidics that are spherical and uniform in size. (C), size distribution chart shows a near “delta” function of particle size, consistent with a monodisperse population. Reproduced with permission from [15].