Liver Radioembolization: An Analysis of Parameters that Influence the Catheter-Based Particle-Delivery via CFD

Radioembolization (RE) is a valuable treatment for liver cancer. It consists of administering radioactive microspheres by an intra-arterially placed catheter with the aim of lodging these microspheres, which are driven by the bloodstream, in the tumoral bed. Even though it is a safe treatment, some radiation-induced complications may arise. In trying to detect or solve the possible incidences that cause nontarget irradiation, simulating the particle- hemodynamics in hepatic arteries during RE by computational fluid dynamics (CFD) tools has become a valuable approach. This paper reviews the parameters that influence the outcome of RE and that have been studied via numerical simulations. In this numerical approach, the outcome of RE is regarded as successful if particles reach the artery branches that feed tumor-bearing liver segments. Up to 10 parameters have been reviewed. The variation of each parameter actually alters the hemodynamic pattern in the vicinities of the catheter tip and locally alters the incorporation of the particles into the bloodstream. Therefore, in general, the local influences of these parameters should result in global differences in terms of particle distribution in the hepatic artery branches. However, it has been observed that under some (qualitatively described) appropriate conditions where particles align with blood streamlines, the local influence resulting from a variation of a given parameter vanishes and no global differences are observed. Furthermore, the increasing number of CFD studies on RE suggests that numerical simulations have become an invaluable research tool in the study of RE.

A New Catheter for Tumor Targeting With Radioactive Microspheres in Representative Hepatic Artery Systems. Part I: Impact of Catheter Presence on Local Blood Flow and Microsphere Delivery

Building on previous studies in which the transport and targeting of 90Y microspheres for liver tumor treatment were numerically analyzed based on medical data sets, this two-part paper discusses the influence of an anchored, radially adjustable catheter on local blood flow and microsphere delivery in an idealized hepatic artery system (Part I). In Part II a patient-inspired case study with necessary conditions for optimal targeting of radioactive microspheres (i.e., yttrium 90) onto liver tumors is presented. A new concept of optimal catheter positioning is introduced for selective targeting of two daughter-vessel exits potentially connected to liver tumors. Assuming laminar flow in rigid blood vessels with an anchored catheter in three controlled positions, the transient three-dimensional (3D) transport phenomena were simulated employing user-enhanced engineering software. The catheter position as well as injection speed and delivery function may influence fluid flow and particle transport. Although the local influences of the catheter may not be negligible, unique cross-sectional particle release zones exist, with which selectively the new controlled targeting methodology would allow optimal microsphere delivery. The insight gained from this analysis paves the way for improved design and testing of a smart microcatheter (SMC) system as well as new investigations leading to even more successful treatment with 90Y microspheres or combined internal radiation and chemotherapy.

Abstract 892: The Importance of Mitochondrial Oxidative Stress and Integrity of Mitochondrial DNA in Coronary Arteriogenesis

The prediabetic metabolic syndrome (pdMS) leads to many pathological cardiac and vascular phenotypes including impaired arteriogenesis. Mitochondrial (mt) oxidative stress (mtOxStress) is postulated to contribute to the development of such phenotypes, but whether reduction of mtOxStress, or imposition of a maneuver to mimic its effects, would restore or inhibit coronary arteriogenesis (CA), respectively, has not been determined. We tested the hypothesis that in the pdMS, mtOxStress plays a key role in inhibition of coronary arteriogenesis. Lean (LN, n = 6) and obese (OB, n = 6) Zucker obese fatty rats (model of pdMS) were instrumented with a pneumatic snare around the left anterior descending artery (LAD), and subjected to a protocol of repetitive ischemia (RI: 24, 40 sec occlusions/day for 10 days) to stimulate growth. CA was determined from the ratio of flows (radioactive microspheres) measured during LAD occlusion to collateral-dependent and normal zones (CZ/NZ). Prior to RI, CZ/NZ in all groups was less than 0.2 indicating that the native collateral conductance could supply less than 20% of the normally occurring flow during LAD occlusion. After RI, CZ/NZ was 0.82Â ± 0.09 in LN, which was markedly higher (p < 0.05) than that in the OB (0.21Â ± 0.08) indicating impaired CA in the OB rats. To reduce mtOxStress, OB animals (n = 5) were given mito-Quinone (mt-directed free radical scavenger) in drinking water (750 mg/L); this treatment restored CA (CZ/NZ = 0.79Â ± 0.03) comparable to that in LN. Because one manifestation of mt-OxStress is mt-DNA fragmentation, which results in impaired expression of key mt-proteins and compromised mt-function, we determined if administration of a recombinant protein engineered with a TAT sequence to enable intracellular delivery, a mt-localization sequence, and exonuclease ExoIII (mt-tat-ExoIII) to fragment mtDNA would impair coronary arteriogenesis in LN (n = 5). Mt-tat-ExoIII (iv, 0.2 ug/g, every other day) in LN rats impaired CA in response to RI (CZ/NZ = 0.32Â ± 0.09, p < 0.05 vs. LN controls). We conclude that mitochondrial oxidative stress, and its effects on mtDNA integrity, are pivotal in the abrogation of CA in the pdMS.