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Research Study: Histological and Blood Flow Evaluations of AVM and Cerebral Artery Vasculature to Create a Simple Computational Fluid Dynamic Model of Arteriovenous Malformations
Primary Investigator: Nina Moore, MD, MSE, Dept. of Neurosurgery at the Cleveland Clinic Foundation
Background: Carrying a 3% risk of hemorrhage per year, cerebral arterial venous malformations (AVMs) pose a difficult question to physicians who need to decide whether to treat the AVM or monitor conservatively as was recently suggested in the ARUBA trial. With a paucity of prospective studies that stratify the risk of AVM rupture based on specific anatomic features, physicians have to piece together outcome studies that may not fir their patient’s AVM. It would be clinically useful to have the ability to accurately predict whether a patient’s particular AVM anatomy would predispose them to rupture and the timeframe in which to expect rupture.
Computational fluid dynamics (CFD) is a promising technique for modeling the human vascular system and examining vascular disease processes. Models of the cardiac anatomy and cerebral aneurysms with CFD are adding insight into the hemodynamic changes the vessels undergo. CFD models can illuminate risk factors with particular shape, sizes, and flow patterns seen in aneurysms and vascular malformations as different stresses affect the vessels. This knowledge can significantly expand when CFD is coupled with structural analysis of blood vessel walls providing a more comprehensive way to evaluate cerebrovascular disease. To date, this technique has not been applied to modeling of cerebral AVMs.
Research Objective: Utilizing the field’s current understanding of computational fluid dynamics applied to cerebral aneurysm and blood vessels, the object of this research is to develop a simple model of an AVM using properties defined by histologic analysis of cerebral blood vessel wall structure as well as resected arteriovenous malformation vessels. Additionally, the work will seek to obtain intraoperative and angiographic comparisons of velocity within the arteriovenous malformations to correctly simulate arteriovenous malformation flow physiology. Specifically, Dr. Moore hypothesizes that they can create a simple AVM model within a computational fluid dynamics program that incorporates accurate anatomical wall structure properties and accurate flow parameters. This model could then be later evaluated to predict the parameters of distension and failure of the vascular malformation wall. The long term goal of this project is to develop a personalized medical approach to a patient’s unique AVM. The hope is that the information learned from these simulations would serve as the groundwork for the development of a tool that allows for testing of different treatment strategies—embolization, surgery, radiosurgery or conservative therapy, eventually allowing the surgeon to even test details of their approach for treatment of an AVM.
Outcomes: With funding from The Aneurysm and AVM Foundation, Dr. Moore and her team will work in three phases. The first phase will be cerebrovascular wall histological studies, followed by phase two consisting of the study of blood flow rate in live AVMs, and finally phase three which will be the creation of the computational fluid dynamics model. Utilizing the date from this study, Dr. Moore hopes to progress towards building a mathematical model that accurately predicts the natural history of rupture in AVMs giving surgeons and patients a roadmap to better treatment strategies.
Source: Nina Moore, MD, MSE the Cleveland Clinic Foundation. This research summary has been adapted and edited from Dr. Moore's research proposal.
Research Study: Ceruloplasmin concentration and ferroxidase activity in CSF and risk of brain injury after aSAH
Primary Investigator: Joao Gomes, MD (PI), Assistant Professor of Medicine (Neurology), Neurointensivist and Director of the neuro-ICU at Cleveland Clinic; Leah P. Shriver, PhD (Co-I), Assistant Professor at the University of Akron in the Department of Chemistry; and Christopher J. Ziegler, PhD (Co-I, Professor at the University of Akron in the Department of Chemistry
Background: There is accumulating evidence that iron-mediated brain injury and oxidative damage contribute to poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Because of its ferroxidase action, the protein ceruloplasmin (Cp) regulates iron levels in the central nervous system and prevents free radical injury.
Paradoxically, reactive oxygen species can bring about modifications in the structure of Cp that result in decreased ferroxidase activity, potentiating a vicious cycle of oxidative stress.
Research Objective: The objective of Drs. Ziegler, Shriver, and Gomes’ research is to examine the relationship between Cp concentration and its ferroxidase activity in cerebrospinal fluid and the development of delayed cerebral ischemia and neuronal cell injury following aSAH. Furthermore, they want to determine if CNS Cp undergoes oxidation and structural modifications following aSAH that result in decreased enzymatic activity.
This represents a novel pathway for aSAH pathogenesis and a promising potential therapeutic target that thus far remains unexplored.
Outcomes: With funding from The Aneurysm and AVM Foundation, Drs. Ziegler, Shriver and Gomes hope to showcase that Cp has a protective effect following aSAH and that its concentration and ferroxidase activity in CSF are inversely associated with the development of DCI. Furthermore, we hypothesize that the oxidative milieu present in the CSF of high grade aSAH patients will lead to modifications in the protein structure of the Cp molecule that will in turn result in decreased enzymatic activity and higher risk of DCI.
Source: Joao Gomes, MD the Cleveland Clinic. This research summary has been adapted and edited from Dr. Gomes’ research proposal.
