modelling of CCSVI physics

[Cece]

Fourth Chilean Workshop on Numerical Analysis of Partial Differential Equations
January 14 - 18, 2013

http://www.ci2ma.udec.cl/wonapde2013/mi ... r-TORO.pdf

Lucas Mueller and Eleuturio Toro are presenting on the mathematical modelling of CCSVI.

MODELLING OF CHRONIC CEREBRO SPINAL VENOUS
INSUFFICIENCY (CCSVI)

Abstract. Recently, Zamboni (2009) and collaborators have empirically discovered that a signiffcant number of Multiple Sclerosis (MS) patients suffer from malformations in the veins that drain blood from the brain and the spinal cord. Such condition has become known as Chronic Cerebro Spinal Venous Insuciency, or CCSVI for short. Zamboni and collaborators go further, see Singh and Zamboni (2009). They have put forward the hypothesis that anomalous venous haemodynamics could ultimately be the triggering mechanism of axon demyelination and MS.

In this presentation we describe our current work that aims at the construction of a closed-loop mathematical model of the human circulatory system to study the haemodynamical implications observed by Zamboni. Based on MRI data we have been able to construct a complex vascular network treated in multi-scale fashion as a combination of 0D (ODEs) and 1D hyperbolic systems. Here we address some of the mathematical and numerical challenges posed by the problem of interest. See Mueller et al. (2012). Preliminary results will be shown.

Computational physics is not something I've studied, to say the least. But this looks interesting.

[Cece]

some more information
http://www.ing.unitn.it/~toroe/Document ... roject.pdf

Computer simulation of blood flow in the intra/extra cranial venous
system in humans with multiple sclerosis and the CCSVI condition

Summary and aims of the research programme

This research programme is motivated by the recently proposed association between multiple sclerosis (MS) and a vascular anomaly termed chronic cerebro-spinal venous insufficiency (CCSVI) by Zamboni and collaborators. The CCSVI condition is characterized by the presence of obstructions of various kinds in the extracranial veins. Such obstructions prevent a normal drainage of blood from the brain to the heart. CCSVI is present in a relevant number of MS patients and such occurrence is of great clinical interest. However such association does not yet explain the gestation of MS, although it has been hypothesized a potential link between the altered fluid dynamics, transport and deposition of iron, disruption of the brain- blood barrier and penetration of autoaggressive immune cells into the CNS, with the known consequences of demyelization of the nerve’s sheath.

This research programme is limited to a theoretical study of the bio-fluid dynamical aspects of the CCSVI condition by means of a mathematical model. The aim is to further investigate the physical phenomena observed empirically by Zamboni and collaborators by means of colour Doppler sonography measurements. The research programme has several distinct parts, including (1) the determination of the computational domain, (2) the construction of a mathematical model for the fluid dynamical problem and (3) the development of computational methods that would allow a computer simulation of the phenomena of interest. There would follow a (4) comparison between theoretical simulation and empirical measurements, (5) use of the theoretical model to study of Zamboni's protocol for testing the CCSVI condition and (6) the formulation of recommendations. If successful, the theoretical tool developed could subsequently be used as the basis for further research, for example to assist potential surgery and to perhaps even associate the anomalous fluid dynamics to the anomalous behaviour of the brain blood barrier, an accepted component of multiple sclerosis.

http://www.ing.unitn.it/~toroe/Research ... oject.html

REMISSION: a long-term research project on REsearch into Mathematical modelling of multIple SclerosiS and its vascular connectION
Professor Eleuterio Toro

[ttucker3]

Cece

Thanks for posting this. The application of Computational Fluid Dynamics to venous flow in CCSVI is exactly what I had advocated in my papers and presentations a year ago. I expect this approach should be able to calculate the dynamic pressure distributions in the venules and hopefully relate the over-pressures to BBB disruption. I note they are using US for trials validation of computational results. I suspect they may have, ultimately, to use Flow Quantification MRI for the trial measurement accuracy they may need for computational model validation. However, to me it looks like a great initiative.

Thanks again for posting this because except for the occasional browse through TIMS, other things in my life have dictated I put down my watching brief on the science as it occurs.

Trev. Tucker

[Cece]

The aim is to further investigate the physical phenomena observed empirically by Zamboni and collaborators by means of colour Doppler sonography measurements.

Based on MRI data we have been able to construct a complex vascular network treated in multi-scale fashion as a combination of 0D (ODEs) and 1D hyperbolic systems.

The doppler sonography measurements is mentioned but then MRI data is mentioned too. Based on MRI data, we have been able to construct a complex vascular network treated in multi-scale fashion as a combination of 0D and 1D hyperbolic systems -- could that mean they are using flow quantification MRI data?

I expect this approach should be able to calculate the dynamic pressure distributions in the venules and hopefully relate the over-pressures to BBB disruption.

I am curious if their equations and findings will be in agreement with some of the ideas you presented a year ago. The incoming pressure wave combining additively with the refluxing pressure to create points of focal hypertension.

[Bluejeans]

I understand only enough of this to wonder why CSF is not being included in a study of the fluid dynamics of the brain. CSF and it's flow (or lack of) affects pressure in the brain and venous system.

[dania]

I understand only enough of this to wonder why CSF is not being included in a study of the fluid dynamics of the brain. CSF and it's flow (or lack of) affects pressure in the brain and venous system.

I am with Bluejeans here. From my experience and others that angioplasty did not have lasting effects, possibly It starts with impaired CSF flow which will cause blood flow problems. Check this out.
http://uprightdoctor.wordpress.com

[ttucker3]

I also agree that ultimately CSF pressure distributions will have to be included is CFD analysis. With compliant vein walls the pressure distributions in the veins are going to be transmitted into the CSF and the boundary conditions for CFD analysis, including both blood and CSF pressures, will ultimately be the non-compliant hard shell of the skull. I have a vision of an outline for the solution direction, but I don't have the patient trials data and I don't have the CFD analysis software. But I am fully familiar with doing computations of models of equal or even greater complexity.
Trev. Tucker

[Billmeik]

An animal model has been slow in arriving, comp sic models sound good.

[Cece]

http://www.fondazionehilarescere.org/pdf/VHISS-CSF.pdf

Our findings, demonstrating that CCSVI has a significant impact on brain pathophysiology, and particularly on the balance of intracranial fluids, could provide stimulation for the development, in the future, of mathematical models currently lacking (probably because the description of CCSVI is so recent). A model is needed in which increased resistance of venous outflow is partially corrected by the development of collateral circulations (2, 19). Speculatively the imbalance in CSF filtration-reabsorption processes might be related to increased transmural pressure in the condition of CCSVI (1,5,23,24).

Dr. Zamboni himself sees the need for the mathematical modelling of CCSVI.

[Cece]

http://www.ing.unitn.it/~toroe/

My research includes the construction of computational methods for solving differential equations, with particular emphasis on hyperbolic balance laws. Scientists world-wide have applied these methods to many areas, such as astrophysics, shock-wave physics, relativity, meteorology, combustion, propulsion, aerodynamics, environmental sciences, industrial and biomedical problems.

For the last 20 years I have been working on the construction of non-linear numerical methods of arbitrary order of accuracy in space and time, the ADER methods. Very high order methods have a huge efficiency gain that increases the power of mathematical modelling and simulation in science and engineering. The ADER numerical techniques have so far been found to be relevant in astrophysics, aero-acoustics, seismology, tsunami wave propagation and biomedical applications.

I am currently focused on the study of the physics of neurodegenerative diseases and their potential link to venous haemodynamics. Of particular interest is the theoretical elucidation of the link between Multiple Sclerosis and vascular anomalies, such as Chronic Cerebro-Spinal Venous Insufficiency (CCSVI), empirically discovered by Zamboni (2009). We are making progress on this very timely theme of practical relevance to so many people around the world. Advances are possible thanks to the contribution of PhD students, post-doctoral fellows, colleagues in Trento and collaboration with academics and medical doctors in Europe, USA and elsewhere.

Professor Toro is moderating a workshop today in Italy: http://www.ing.unitn.it/~toroe/Document ... 2012_B.pdf

14:00-14:15. Professor Eleuterio Toro. Welcome address and introduction
14:15-15:15. Dr. MD Franz Schelling. Invited Speaker. Predictable outcomes of interventions for CCSVI in Multiple Sclerosis?
15:15-16:00. Lucas Mueller. Introduction by Professor Eleuterio Toro. Construction of a mathematical model for the study of haemodynamical aspects of CCSVI
16:00-16:15. Break
16:15-16:45. Dr. Alfonso Caiazzo and Gino Montecinos. Computational haemodynamics in stenotic internal jugular veins.
16:45-17:15. Miss Laura Facchini. Introduction by Professor Alberto Bellin. The impact of pressure disorder on solute exchange across micro-vessel walls.
17:15-17:30. Discussion.
Everyone welcome!
Contact: Professor E F Toro.

[Bluejeans]

Would upright positioning add value to the computer modeling?

[ttucker3]

Thank you Prof. Toro and U Trento. Brilliant set of initiatives. May your vision on the application of CFD to venous haemodynamics match that of Prof Zamboni in his vision of relating MS to venous haemodynamics. I shouldn't be surprised if, from these initiatives, the origins of MS (and some similar diseases) are identified with sufficient scientific substance to be broadly accepted. If so, all those involved will deserve to be on the short list for the Nobel Prize for Medicine - perhaps win it outright at some point in time.
Trev. Tucker

[Cece]

If the abstract mentions Navier-Stokes, then I know we're talking physics, even if I don't understand all of the abstract.
Dr. Tucker, your work is listed in the references.

COMPUTATIONAL HAEMODYNAMICS IN STENOTIC INTERNAL JUGULAR VEINS

Alfonso Caiazzo, PhD1, Gino Montecinos, MS1, Lucas Mueller Omar, MS1, Eleuterio
Toro Francisco, PhD1, Ewart Haacke Mark, PhD2

1 Universita di Trento, via Mesiano 77, Trento, TN, Trento, Italy
2 Wayne State University, 3990 John R Road, Detroit, MI 48201, USA.

Figure 1 shows a set of preliminary results for a stenotic LIJV. In particular, in the original configuration (Fig.1, left) the pressure difference between LIJVs inlet and outlet is around 1 mmHg, while, in the case of a stenosis, we observe that a significant increase in IJV pressure drop (above 1.5 mmHg) is achieved with a reduction of the CSA of more than 50% (Fig. 1, center and right). Further results will be presented during the conference.

This work represents a first step towards a computer-aided understanding of CCSVI haemodynamics in a patient-specific context. Future developments will focus on the implementation of Fluid-Structure Interaction models to account for veins compliance, and on the incorporation of this framework into a multi-scale global model of the cardiovascular system.

The full abstract and the graphs are here: http://isnvd2013.euromedicpoland.com/us ... tracts.pdf

[Cece]

Prof. Toro is presenting again next week in Italy at an international symposium.
http://isnvd.org/pdf/simposio.pdf

MODELLI E RICERCA TRASLAZIONALE SULLA
CIRCOLAZIONE CEREBRALE
Moderatori: Mauro Gambaccini, Simon Shepherd

14.00 Introduzione.
Paolo Zamboni, Ferrara, Italy

14.15 Venous hypertension and cerebrospinal fluid dynamics.
Clive Beggs, Bradford, UK

14.45 A model for calculating brain blood outflow in collateral vessels
Francesco Sisini, Ferrara, Italy

15.15 Simulating cerebral venous haemodynamics with a global multi scale mathematical model
Eleuterio Toro, Trento, Italy

15.45 Clinical application of the lumped model for the study of jugular-vertebral blood flow dynamic
Angelo Taibi, Ferrara, Italy

Both Prof. Taibi and Prof Sisini are also presenting models. Not that I know what a 'lumped model' is but I'm excited about it. If these models provide the logical underpinnings for why CCSVI is a disease state and not a normal variant, then the next logical step is treatment.

[Cece]

http://www2.mate.polimi.it/ocs/viewabst ... =297&cf=31

A global solver for blood flow in arteries and veins, including cerebrospinal fluid and brain dynamics: towards a global, close-loop extended human circulation model.

Lucas Omar Mueller
Laboratory of Applied Mathematics, University of Trento

*Eleuterio Francisco Toro
Laboratory of Applied Mathematics, University of Trento

Full text: Not available
Last modified: January 14, 2013

Abstract
A global solver for blood flow in arteries and veins, including cerebrospinal fluid and brain dynamics: towards a global, close-loop extended human circulation model.

LO Mueller* & E F Toro

* Presenting author

Blood flow modelling of the venous system has been given less attention than its arterial counterpart, even though many cardiovascular pathologies offer a broad range of applications for mathematical models of the venous system. Examples include arterio-venous malformations, Deep Venous Thrombosis (DVT), Cerebral Venous Thrombosis (CVT) and the recently identified condition called Chronic Cerebrospinal Venous Insufficiency1, or CCSVI.

Given the interconnected nature of the venous system we have been compelled to work towards the construction of a closed-loop multi-scale model of the entire cardiovascular system. The heart, the pulmonary circulation and the peripheral circulation are modelled via lumped parameter models (0D). On the other hand, major arteries and veins are modelled via one-dimensional (1D) formulations. Our current model includes 240 major vessels. There are few examples in the literature of closed-loop multi-scale models of the cardiovascular system. To the best of our knowledge the one presented here is the first model that includes a 1D description of the venous system.

The high compliance of the venous system and the influence of external tissues and body forces requires the implementation and further development of robust and accurate numerical schemes2. For the same reason, to reproduce venous flow waveforms measured experimentally, the incorporation of cerebrospinal fluid (CSF) and brain tissue dynamics into the model is mandatory. Thus we have embedded a lumped parameter model for CSF and brain dynamics3 to our cardiovascular model. This allows full coupling of the interaction between the cerebral vasculature, ventricles and brain parenchyma.

One of the motivating applications for the development of our model was the CCSVI condition. Therefore, a distinct aspect of our global solver is the detailed description of the veins of the head and neck. MRI data was used to segment major vessels of interest. The segmented vessels were then processed to extract centerline information and cross-sectional areas. For the smaller veins the geometric description was completed using information retrieved from the open literature. Flow data for major arteries and veins of the head and neck, as well as CSF flow between the intracranial subarachnoid space and the spine, were extracted from Phase Contrast MRI data for healthy controls3. The ability of the model to reproduce physiological flow patterns has been thoroughly validated using the gathered flow quantification data. Realistic computations compared to experimental measurements will be shown.