Investigating the effect of Cerebral Venous Vasculature on Venous Pressure in Multiple Sclerosis
Background
A study undertaken in 2020, demonstrated that transverse sinus venous outflow stenoses caused a reduction in the venous compliance of multiple sclerosis (MS) patients. The findings indicated similarities between MS and idiopathic intracranial hypertension [1]. This year, a study was published by members of this team that used computational fluid dynamics (CFD), to investigate venous sinus pressure and idiopathic intracranial hypertension [2]. The application of this engineering software (CFD) allowed for new insights into the venous system and helped establish the relationship between cerebral blood flow and pressure in the cerebral venous system.
A recent review article completed by this group (currently in review) was conducted to critically summarise the literature available concerning the venous system in multiple sclerosis, primarily concerning specific data on the venous pressure and blood flow in this system. The findings included that the internal jugular vein (IJV) flow was not significantly different between MS patients and controls [3], but there was a variance between stenotic and non-stenotic MS patients [4]. There was limited data on venous pressure and intracranial flow, which indicated a lack of knowledge in this area requiring further investigation.
Current Work
The findings of the review article have led to the development of a new study, whereby CFD is to be used to investigate the venous pressure in MS patients. The MRI scans of 21 patients that have previously been captured will be used to investigate if the transverse sinus stenoses can cause a significant increase in venous pressure. The contrast in the MRI scans allows for a model of the patient’s venous vasculature to be created. This is then used in the CFD model to simulate blood flow through the veins, enabling the venous pressure and blood flow features to be determined. The use of CFD will also allow for other potential causes of venous pressure increase to be investigated, should they become evident in this study. This provides information that would only otherwise be accessible through invasive surgical procedures.
Proposed Research
The research currently being undertaken is limited to MRI scans which have been previously completed with the protocols required for the CFD program. The funding provided by CCSVI Australia Inc would be used to perform MRI scans on a wider demographic of MS patients, as currently it is primarily comprised of female relapsing-remitting MS patients. This would fund MRI scans of up to 20 male control subjects and 20 people with secondary progressive MS (pw-SPMS). Novel MRI protocols would also be included to enable information to be captured which will increase the accuracy of the CFD models. This would be developed through industry collaborations with Siemens. The study hypothesises that male pw-SPMS will yield elevated venous pressures compared to male HC. A study by members of this group (currently in review) discovered evidence of venous vasculature variations between these male and female MS patient sub-groups. A CFD study would confirm how this impacts the venous pressures. These findings would enable potential treatments to be proposed which could reduce the venous pressure and improve MS patient outcomes.
In addition, the funding would allow for 5 year follow up MRI scans to be performed on the subjects of the current study. Based on previous studies, it is likely that approximately 85% of patients would return for a follow up MRI. This would enable a longitudinal study to be completed, which will allow further insight into the cause and effect of the transverse sinus stenosis development and venous pressure changes over time and potential effects of disease modifying therapies. This study hypothesises that stenosis in venous vasculature causes an elevated pressure, contributing to the development of MS. The ability to use CFD in a longitudinal study will enable us to quantify the hemodynamic changes in the cerebral venous system and measure the effect it has on disease course and activity, in particular, if it correlates with the progression of the disease.
Research Team
Alexander Bateman is a first-year mechanical engineering PhD student at the University of New South Wales, in which the current research outlined in this expression of interest is being completed as part of his PhD work.
Jeannette Lechner-Scott is a senior staff specialist in the Department of Neurology and Conjoint Professor at the University of Newcastle. She has a multidisciplinary Multiple Sclerosis Clinic at the John Hunter Hospital (JHH) servicing over 1200 pwMS and has extensive experience in basic research as well as clinical trials.
Saadallah Ramadan is the Director of Magnetic Resonance Research and National Imaging Facility Node Director at the HMRI Imaging Centre and Associate Professor at the University of Newcastle. He is an expert in MRI protocols and techniques relating to MS and his research has included using MRI as a tool to detect markers associated with fatigue and depression in MS.
Grant Bateman is a senior staff specialist in the Department of Medical Imaging and Conjoint Associate Professor at the University of Newcastle. He is a Neuroradiologist and an expert in measurements of venous flow on MRI.
Tracie Barber is a mechanical engineering Professor at the University of New South Wales, specialising in vascular fluid dynamics. She is an expert in modelling vascular blood flow and leads a research group (Vision Fluid Dynamics) with various projects in the area of vascular fluid dynamics.
References
[1] G. A. Bateman, J. Lechner-Scott, A. R. Bateman, J. Attia, and R. A. Lea, “The Incidence of Transverse Sinus Stenosis in Multiple Sclerosis: Further Evidence of Pulse Wave Encephalopathy,” Multiple Sclerosis and Related Disorders, p. 102524, 2020.
[2] A. R. Bateman, G. A. Bateman, and T. Barber, “The relationship between cerebral blood flow and venous sinus pressure: can hyperemia induce idiopathic intracranial hypertension?,” Fluids and Barriers of the CNS, vol. 18, no. 1, pp. 1-10, 2021.
[3] M. Blinkenberg et al., “Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis,” Acta neurologica scandinavica, vol. 126, no. 6, pp. 421-427, 2012.
[4] W. Feng et al., “Characteristics of flow through the internal jugular veins at cervical C2/C3 and C5/C6 levels for multiple sclerosis patients using MR phase contrast imaging,” Neurological research, vol. 34, no. 8, pp. 802-809, 2012.
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