Study on CCSVI in MS at University of Wisconsin School of Medicine and Public Health
In June 2010, the National MS Society (USA) and the MS Society of Canada committed over $2.4 million to support seven new research projects on the role of CCSVI (chronic cerebrospinal venous insufficiency) in MS (http://www.nationalmssociety.org/ccsvi), an abnormality of blood drainage from the brain and spinal cord in MS originally reported by Dr. Paolo Zamboni. The new projects take a comprehensive look at the structure and function of veins draining the brain and spinal cord in people representing a spectrum of MS types, severities and durations, and compare them to structure and function of veins in people with other diseases and healthy volunteers. The studies incorporate high standards of experimental blinding and controls designed to provide unbiased results.
Title: “Study of CCSVI in MS using quantitative time-resolved 3D MRV”
Aaron Field MD, PhD
University of Wisconsin School of Medicine and Public Health
Term/Amount: 7/1/10-6/30/14 (extended at grantee's request); $586,436
- A series of recent publications have suggested that some people with MS have obstructions in the veins that drain blood in the brain and spinal cord that may contribute to nervous system damage in MS.
- Dr. Field’s team is using alternative imaging methods, in addition to the ultrasound method used in Dr. Zamboni’s original reports, to conduct a controlled study of the CCSVI hypothesis in people with MS.
- If this technique obtains similar results as the ultrasound method originally used, it would represent a powerful confirmation of the CCSVI hypothesis.
About the Investigator: Dr. Field is currently Associate Professor with Tenure in the Department of Radiology at UW-Madison with an affiliate appointment in Biomedical Engineering. He is Director of the Clinical Neuroradiology Fellowship Program and Co-Director of the Clinical Neurosciences Clerkship for UW medical students. Dr. Field completed the MD/PhD Program in Bioengineering at the University of Illinois College of Medicine at Chicago. Dr. Field's postgraduate training included a medical internship at Northwestern University/Evanston Hospital, residency in diagnostic radiology at Rush-Presbyterian-St. Luke's Medical Center in Chicago, and a fellowship in neuroradiology at Wake Forest University, Winston-Salem, NC. A primary goal of his research is non-invasive tracking of myelin repair following stem cell transplantation.
Dr. Field has put together a team that includes the director of the university’s MS clinic, experts in MRI physics and ultrasound, a neuroradiologist with extensive experience in vascular imaging, and a statistician with ample experience in clinical research.
Project Details: Recent preliminary studies have suggested that a phenomenon called Chronic Cerebrospinal Venous Insufficiency (CCSVI), a reported abnormality in blood drainage from the brain and spinal cord, may contribute to nervous system damage in MS. This hypothesis has been put forth by Dr. Paolo Zamboni from the University of Ferrara in Italy. This pilot study warrants a subsequent larger and better controlled study to definitively evaluate the possible impact of CCSVI on the disease process in MS.
Dr. Field’s team is using alternative imaging methods, in addition to the ultrasound method used in Dr. Zamboni’s original reports, to conduct a controlled study of the CCSVI hypothesis in people with MS. This study uses an MRI scanner to generate highly detailed images of the head and neck veins in 112 people with early and later MS, 56 controls without MS, and 56 people with other neurological conditions. The team is also measuring the rate at which blood flows in the veins. Dr. Field’s collaborates have years of experience in bioengineering, radiology, and medical physics.
If this technique obtains similar results as the ultrasound method originally used, it would represent a powerful confirmation of the CCSVI hypothesis and help lead the way toward trials of appropriate treatment targeting abnormal veins.
Dr. Field's team requested and was granted an extension to continue progress in this study, since his study was delayed by one year awaiting approval by the Institutional Review Board. As of July his team had enrolled and scanned 121 people.
Researchers continue with their progress in the seven Society-funded CCSVI studies in MS. Read about the most recent progress
Official approval of this study protocol was issued on June 28, 2011. The team continues to actively recruit study subjects from a database of approximately 100 MS patients who had contacted them since the study was first announced, as well as from the patient population seen regularly in their MS clinic. Thus far, 17 people with MS and 12 healthy controls have undergone both MRI/MRV and ultrasound imaging. No results are yet available as the study is blinded.
Since the previous progress report, Dr. Field was awarded a $27,000 grant from his institution to further investigate the novel MRI components of this study in healthy controls, particularly with regard to reliability and reproducibility. Specifically, they investigated (1) the use of a novel method to adjust venous flow measurements for variations related to breathing and heartbeat, (2) the use of a novel MRI method for measuring the iron content in brain tissue, and (3) the use of a relatively new, FDA-approved MRI contrast agent (a drug administered intravenously to enhance the visibility of blood vessels on MRI) that can enhance the visibility of head/neck veins and enable the measurement of blood flow through brain tissue. Ten healthy subjects underwent these components of the team’s CCSVI protocol twice, on separate days. Progress made in these studies includes:
- The team’s novel approach to measuring venous flow with MRI is able to detect clear differences in venous flow between inspiration and expiration, and demonstrates evidence of expiration-related reflux (backwards flow) in the jugular veins of healthy subjects.
- The team’s system of rating the degree of venous narrowing on MR images of the azygous and jugular veins yields comparable results when performed by different individuals.
- Their novel MRI method for measuring iron content in brain tissue provides reproducible results that are comparable to previously described methods of iron measurement, with fewer technical pitfalls.
- A single dose of a relatively new MRI contrast agent is sufficient to enhance the visibility of head/neck veins and generate reproducible maps of blood flow through the brain. (It would normally require two separate doses of a conventional contrast agent to accomplish both of these objectives.)
These investigations have yielded two abstracts presented or to be presented at national/international imaging meetings:
“Comprehensive assessment of cerebral venous return with MRA: preliminary results.” Wieben O, Johnson K, Schrauben E, Reeder S, Field A. 23rd annual meeting of the “MRA Club” (International Magnetic Resonance Angiography Workshop), Calgary, Alberta, Canada, September 25-28, 2011.
“The importance of the sonographer in the investigation of chronic cerebrospinal venous insufficiency.” Kohn S, Kliewer K, Field AS. American Institute of Ultrasound in Medicine (AIUM) Annual Convention, Phoenix, AZ, March 29-April 1, 2012.
In addition, three abstracts have been submitted for consideration for the American Society of Neuroradiology (ASNR) 50th Annual Meeting, New York, NY, April 21-26, 2012, and two have been submitted for the International Society of Magnetic Resonance in Medicine (ISMRM) 20th Annual Meeting & Exhibition, Melbourne, Victoria, Australia, May 5-11, 2012.
Quotes -- Dr. Aaron Field
- “A relatively new theory on the nature of MS was recently proposed suggesting that MS is caused by chronically insufficient drainage of blood from the brain… If true, this would prompt a drastic change in our approach to MS treatment.”
“Currently, all the evidence for this theory has come from just one research group; it is now critical for other investigators, working independently, to confirm or refute this evidence. If our approach… obtains similar results, it would represent a powerful confirmation of this new theory and lead the way toward a larger-scale trial of appropriate treatment targeting the abnormal veins.”