Diagnostic Approaches 

 

Overview

CCSVI is diagnosed by using high resolution imaging technologies to view (or “image”) the primary veins that drain blood from the brain and spinal cord (CNS). The goal of this imaging is to detect either one or both of the following key indicators of CCSVI:

1. Stenoses and other malformations of the primary veins draining the CNS. Stenoses that impede blood flow through the vein by more than 50% are potential contributors of CCSVI
2. Abnormal venous hemodynamics (for example, reflux, or increased mean transit times)

Emerging state of the art imaging technologies allow well trained technicians and interpreters to view the body’s veins, arteries, and tissues with a degree of detail never before possible. However, despite availability of new technologies, imaging centers in the United States have focused primarily on arterial imaging and often have limited or no experience imaging the venous system. Accurate CCSVI diagnosis is further complicated by the fact that diagnostic protocols for CCSVI imaging are not fully documented and thus are not being consistently applied across centers. This lack of training and standards allows for more disagreement and potential error in diagnosis than is ideal. Nevertheless, experienced CCSVI diagnosticians with access to the correct equipment can reach broad agreement about several critical components of CCSVI.

Factors Contributing to Accurate Diagnosis

1.  Types of Stenoses

Some types of stenosis are relatively easy to “see” and thus more reliably diagnosed. For example, the veins of some MS patients are so obviously atypical that there is little room for disagreement among observers. Here, veins are missing entirely, or obviously malformed (agenesis, hypoplasia, atresia, twisting). There is no subtlety: the vascular problem is apparent to physicians or researchers possessing even modest levels of experience. Non-invasive CCSVI diagnostic tools like Duplex Ultrasonography, Magnetic Resonance Venography (MRVs) and CT Venograms can all reveal these larger venous problems. (Note that these technologies can reveal more subtle problems as well.)

Alternatively, stenoses caused by abnormally functioning valves, abnormally located septums or membranes, or web-like formations of tissues inhibiting blood flow, are often more difficult to diagnose via common non-invasive procedures.

2. Training and Technology

A specific type of high resolution ultrasound called duplex ultrasonography (often called “color-coded" Doppler sonography) has been clinically tested and proven effective for diagnosing abnormal vascular conditions, particularly blood flow rates and reflux¹. The use of Duplex Ultrasonography for diagnosing CCSVI was pioneered by Dr. Zamboni and his colleagues at the University of Ferrara, Italy. However, duplex ultrasonography requires specialized equipment and, most importantly, extensive training and experience. At present, there are very few imaging centers in the U.S. possessing both the correct equipment and the extensive training in CCSVI diagnosis for obtaining accurate results. Nonetheless, in the hands of properly training physicians and technicians, duplex ultrasonography produces excellent diagnostic results. 

While all magnetic resonance and ultrasound technologies used to diagnose CCSVI are non-invasive, catheter venography, obtained during a minimally invasive endovascular procedure, is often considered the “gold standard” for CCSVI diagnosis.

Catheter venography (also called “selective venography”) allows physicians to highlight suspect areas of a vein with a locally injected contrast dye, and then take highly detailed x-rays of only the suspect areas. Examples of images produced by catheter venography are available here. Note again that catheter venography requires an endovascular procedure, which introduces basic medical risks not associated with noninvasive diagnostic procedures like MRV, CT Venography, or Doppler ultrasound.

Diagnostic Technologies

Below, the principal technologies for diagnosing CCSVI are presented, along with basic pros and cons for each approach.

• CT Venography- A CT scan combines a series of x-rays taken from a variety of angles to produce a detailed, cross-sectional view of the human body. Through the use of contrast agents, which are injected into the veins of the patient being imaged, CT scans can produce very precise images of the vascular system, including the veins associated with the CNS. Because CT scans use x-ray technology, they do expose the patient to radiation.
  Images produced through CT venography effectively reveal large-scale venous issues, such as atresia/agenesis, twisting, as well as evidence of collateral veins or clusters that are commonly associated with CCSVI.
  
  However, CT venograms have several limitations. First, CT venography cannot always accurately image abnormal valves, septums, or membranous tissues. Also, CT Venography does not reveal abnormal hemodymics, which are central to CCSVI, including mean transit times or reflux.


• MRV- Magnetic Resonance Venography is a technique that uses MRI (Magnetic Resonance Imaging) technology to generate images of the CNS venous anatomy. MRIs use magnetic fields and radio waves to produce detailed images of body tissues.
  
  MRVs can quickly produce detailed time-resolved 3D MR images of the entire head, neck, and aortic arch areas by collecting the data before and after injection of contrast agents. These images can reveal many forms of stenosis and venous abnormalities, including agenesis, hypoplasia, atresia, twisting, and presence of collateral veins clusters and shunts. Visually, MRV can create more detailed 3D images of the venous system than other commonly available technologies. Further, specialized MRV techniques, particularly Time of Flight (TOF) compensation, can reveal blood flow rate and patterns, potentially revealing abnormal mean transit times and reflux. (More details about blood flow quantification are provided in the MRFQ section below.)
  
  However, MRV does have two important limitations. First, MRV’s do not yet reliably detail all abnormal valves, septums, or other membranous obstructions. Second, MRV must be taken in a supine position, and thus cannot image types of stenosis or abnormal blood flow patterns that may only effect a patient who is in the upright position (whereas duplex ultrasonography, for example, can image blood flow patterns of patients in any position, supine or upright).
  
  While MRV imaging and data acquisition methods are straight forward, and MR machines are common, most MRI technicians are not familiar with performing MRVs. Because accurate results from MRV scans are dependent on operator and interpreter proficiency, few MRI centers currently provide reliable CCSVI diagnostic scanning. Nonetheless, in the hands of experienced practitioners who follow approved CCSVI diagnostic protocols, MRV images can be a vital tool in diagnosing a wide range of venous obstructions and abnormalities. For detailed information on using MRV to diagnose CCSVI, please see Dr. E. Mark Haacke’s* site: www.ms-mri.com.


• MRFQ – Magnetic Resonance Flow Quantification is a method for using MRI technology to collect blood flow rate and direction information. Because abnormal hemodynamics is highly correlated with venous obstructions, obtaining blood flow information is a critical component of CCSVI diagnosis. With MR Flow Quantification performed on an axis perpendicular to the neck, blood flow characteristics of most of the arteries and veins in the neck can be quantitatively assessed, providing highly detailed information of cardiovascular input to and output from the brain. Results can capture both increased mean transit times and reflux. These results can be compared to results obtained from advanced ultrasound (e.g. duplex ultrasonography). However, as with other MRV technologies, MR Flow Quantification is limited to patients in the supine position; flow quantification of patients in a sitting position cannot currently be made via MR-based techniques.


• MRI/SWI- Susceptibility Weighted Imaging (SWI) is a specialized type of MRI using “susceptibility” (the magnetic variance of a given material when exposed to a magnetic field) in conjunction with traditional MRI techniques to generate images that are extremely sensitive to venous blood flow and, particularly, iron deposits. Iron deposits are highly associated both with CCSVI and the presence of MS plaques. 
  
  SWI can reveal changes in iron content over time, and how iron build-up appears in different structures in different parts of the brain. SWI may prove to be a valuable tool in detecting CCSVI, and in corroborating CCSVI-related damage in the CNS. As a best practice, some researchers insist on MRI/SWI both before and after any type of CCSVI treatment, or even when adding or changing a DMT, in order to document iron buildup in the CNS both before and after the proposed change.


• Duplex Ultrasonography - This noninvasive test bounces high-frequency sound waves off red blood cells to measure blood flow and blood pressure. In order to properly diagnose CCSVI, a specialized type of ultrasound probe, called  a “transcranial probe,” is required. For CCSVI diagnosis, both ‘extracranial’ and ‘transcranial’ ultrasonography is recommended, as this approach covers both the veins in the head, neck, and upper chest.
  
  An experienced duplex ultrasonographer can accurately assess whether or not blood is refluxing back into the central nervous system, or flowing at abnormal rates. However, even with the proper Ultrasound equipment, accurate data acquisition and interpretation is highly operator dependent. For example, a recent study¹ documenting the reliability of diagnosing CCSVI with Doppler Ultrasound found that technicians with specialized training in CCSVI diagnosis became extremely accurate (about 95% correct diagnosis), while technicians who had not had specialized CCSVI training were significantly less accurate.
  
  Currently, however, few operators in the United States are properly trained, and results obtained via technicians and/or physicians who haven’t undergone specific CCSVI diagnostic training with duplex ultrasonography may be limited or inaccurate.


• Catheter Venogram- In this diagnostic endovascular procedure, a long, thin, flexible plastic tube (called a catheter) is inserted into the body, usually through a vein in the groin. The catheter is then threaded through the vascular system via a guidewire to the area(s) needing inspection. Once correctly placed, a dye is injected through the catheter, and a rapid series of x-rays is taken, offering a detailed look at the suspect blood vessels. Some practitioners also use an intervascular ultrasound device attached to the catheter to provide ultrasound imaging from inside the blood vessel. Blood flow can also be assessed during catheter venography, typically via a manometer attached to the catheter. 
  
  Note that the same catheter-based endovascular procedure used during catheter venography is also used during CCSVI treatment. In fact, catheter venography typically accompanies CCSVI treatment, and is performed immediately prior to treatment in order to confirm stenoses that have been previously imaged through noninvasive diagnostics methods (like MRVs or duplex ultrasonography).
  
  Because catheter venography produces pictures of stenosis and venous abnormalities of specific vein segments, it is sometimes referred to as the “gold standard” for diagnosing or confirming CCSVI. However, it is not perfect. First, the presence of the catheter itself, particularly as it moves through valves and/or septums, can alter venous hemodynamics, potentially skewing flow quantification results. Second, catheter venography is the only diagnostic procedure that requires an endovascular procedure, and thus introduces patient risks not associated with noninvasive diagnostic methods. Lastly, as with other CCSVI diagnostic technologies, physicians or researchers must be well trained in interpreting the results.

Summary

At present, a variety of technologies are used for diagnosing CCSVI. The most successful are duplex ultrasonography, catheter venography, and MRV.  Each has unique advantages and disadvantages, and in most cases the combined results of multiple approaches provide the best diagnosis (e.g. MRV, MRI/SWI together with duplex ultrasonography for noninvasive diagnosis, with confirmation via catheter venography).
Importantly, CCSVI diagnosis is an emerging practice requiring either specialized devices, specialized training, or both. As a result, anyone interested in being diagnosed should consider doing so only through facilities with the correct equipment, and, most importantly, by practitioners with documented training  and proven expertise in CCSVI diagnosis. Otherwise, results may be of limited value, or may even lead to inaccurate diagnosis.

*About Dr. E. Mark Haacke: While there is currently no universally accepted standard for MR Imaging of CCSVI, E. Mark Haacke, PhD, Director of MR Research Facility at Wayne State University in Detroit, and McMaster University in Hamilton, Ontario, and Director of the Neurovascular Imaging Center of Excellence (NICE), is helping lead the way.  Dr. Haacke's research includes MR Angiography, MR Venography, and Susceptibility Weighted Imaging (SWI) to study vascular disease, vascular conditions, and CCSVI.  Dr. Haacke has been at the forefront of developing imaging techniques and protocols for CCSVI scanning, interpretation, and archiving. Moreover, Dr. Haacke is a world leader in developing Susceptibility Weighted Imaging (SWI) MRI protocols for identifying and quantifying iron deposition in the central nervous system.  MRI/SWI makes use of existing MRI equipment, with modified scanning and software analysis protocols.

For more information, please visit Dr. Haacke’s CCSVI website at: http://www.ms-mri.com/

Additional Imaging research by Dr. Haacke and his team is described at the National Center for Excellence in MRI:http://www.nice-mri.com/

Dr. Haake’s recommended MRV/SWI scanning protocol can be found at: http://www.ms-mri.com/potential.php

To donate to Dr. Haacke’s MRI/SWI fund, click here.

References

1. Hojnacki D, Zamboni P, Lopez-Soriano A, Galleotti R, Menegatt E, Weinstock-Guttman B, Schirda C, Magnano C, Malagoni AM, Kennedy C, Bartolomei I, Salvi F, Zivadinov R. Use of neck magnetic resonance venography, Doppler sonography and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: a pilot study in multiple sclerosis patients and healthy controls. International Angiology.  April, 2010; 29(2):127-139