Research paper: Association - CranialVenousDrainage/MS

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Postby Sotiris » Sat Nov 06, 2010 4:56 am

Malden wrote:Same study, but now with a full research paper, not only the abstract:
http://jnnp.bmj.com/content/early/2010/10/27/jnnp.2010.223479.full.pdf
(Published online October 27, 2010 in advance of the print journal.)
Locked thread comments was based only on abstract.
[...]
Not exactly: http://www.thisisms.com/ftopic-14402-20.html
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Postby jimmylegs » Sat Nov 06, 2010 5:19 am

sarcasm is not a useful contribution to the discussion, remember we're together in this, not fighting each other, please and thank you.
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Postby malden » Sat Nov 06, 2010 8:20 am

Sotiris wrote:
Malden wrote:Same study, but now with a full research paper, not only the abstract:
http://jnnp.bmj.com/content/early/2010/10/27/jnnp.2010.223479.full.pdf
(Published online October 27, 2010 in advance of the print journal.)
Locked thread comments was based only on abstract.
[...]
Not exactly: http://www.thisisms.com/ftopic-14402-20.html

Yes, you'r right Sotiris, sry, but in a wood of Ug-Jug contests and 500-2000 liberated MS-ers I was anable to find a tree (study link you provided). Unfortunately, that thread about study was already ended miserably, so I started a new thread. Subject is too serious to burry it without considering. Best regards, M.
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Postby Jugular » Sat Nov 06, 2010 9:21 am

Nunzio wrote:I also perfomed a study to disprove Dr. Zamboni theory that MRV is unreliable to diagnose CCSVI because of high false positive and false negative results.

Image
As you can see my right jugular vein (on the left side of the picture) is much smaller then the normal jugular vein on the other side so it is obvious that I have CCSVI based on the above MRV.

A limitation of my study is the limited number of MS patients
( one, me) and no healthy control subjects, which limits the ability to draw
definite conclusions.( so what?) The sample size number was based on the
suggested almost absolute difference in presence of venous
abnormalities between MS patients and healthy controls.
Nevertheless, the present sample size would allow one to find
a difference of 100% or more with a power of about 0.8. In addition,
our results based on MRV have not been confirmed or
refuted by another imaging modality such as Doppler sonography.(Dr. Zamboni standard method to detect CCSVI)
However, my study represents the second largest casecontrol
dataset of MRV in the evaluation cranial venous outflow in MS
patients and no healthy controls so far. Given the fact that the initial
results suggesting that MS is associated with a pathological
venous outflow anatomy , (also confirmed by thousands of catether contrast venography done up to date), presented sensitivity, specificity, positive
and negative predictive values of 100%, my study population
is large enough to confirm these data.

Please let me know if I should publish my study.
Thanks for your attention.


I know this post was done slightly tongue-in-cheek, but it raises a valid point that was succinctly stated by Cheer in the other thread.

Cheer wrote:The pictures included were lovely, with gorgeous, open veins and nothing like the pics I've been seeing of MS patients from Dake and Haacke's MRVs. And not like Jeff's mangled jugulars and squirrelly collaterals at all....


So we have Munzio's, Jeff's, Johnson's and my MRV's each showing much more severe stenoses associated with our positive diagnosis of MS. 4 for 4. I wish others who have had MRV's would chime in because this is strange.

Here is a link to the forbidden thread where you can view comparative MRV's.

http://www.thisisms.com/ftopict-14402.html
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Postby Lyon » Sat Nov 06, 2010 9:50 am

..
Last edited by Lyon on Thu Jun 23, 2011 6:33 pm, edited 1 time in total.
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Postby Jugular » Sat Nov 06, 2010 10:52 am

Lyon wrote:
Jugular wrote: So we have Munzio's, Jeff's, Johnson's and my MRV's each showing much more severe stenoses associated with our positive diagnosis of MS. 4 for 4. I wish others who have had MRV's would chime in because this is strange.
I don't want to start a pissing match but I'm evidently not understanding something.

In this environment where it remains to be proven that the general public doesn't also experience venous stenosis and considering that we only immerse our attention in images of people with MS and venous stenosis it somehow doesn't seem surprising that four people with MS show stenosis on MRV.

You specifically mention
Jugular wrote:each showing much more severe stenoses associated with our positive diagnosis of MS
is that denoting the worst cases of MS in you four correlates with the most severe stenosis on MRV or am I missing the point altogether?


The study suggests that half the MS patients did not demonstrate a stenosis. This is why I am asking for others to comment on their MRV results. Presumably, if the study is valid, half the MS patients going in for MRV's should come out with negative findings.

The other point to this is none of the images displayed in the study appear to show significant stenoses at all - in the MS patients or in the controls. This is the anomaly of which I speak. Look for yourself and see if you disagree. I wasn't trying to link stenosis severity with disease severity.

Haacke better step up to the plate and comment on this because his data set should be much larger on MS patients. I am sure he must have also looked at healthy controls.

I don't think the proper response to this study, however, is to retreat further into the veins by saying it's not a venogram or to jump back into the DU box.
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Postby scorpion » Sat Nov 06, 2010 2:25 pm

If I remember Cheer's husband had very severe stenosis yet had fairly mild MS sympotms. Does anyone find it ironic that pics are posted on this forum and the stenosis is "obvious" yet none of us were trained using Zamboni's STRICT standards? Maybe there is not stenosis in the veins that are posted as "gimmees" but instead they are "normal" for that particular person. Of course since the definition of normal veins have not been established it makes my question rather pointless.
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Postby malden » Sat Nov 06, 2010 3:29 pm

RESULTS MRV:
An anomalous venous system was found in 10 MS patients
compared with eight healthy controls (table 2). An intracranial
and/or extracranial venous stenosis was observed in 10 MS
patients and eight healthy controls; two MS patients showed
a combination of an intracranial and extracranial venous
stenosis. One MS patient and one healthy control had a bilateral
intracranial venous stenosis
; four MS patients and three healthy
controls showed a bilateral extracranial venous stenosis. Two
MS patients showed a combination of a stenosis of the internal
and external jugular vein.

And this is how they acquire data/images:
MRV: 3D (Inhance) phase-contrast angiography (FOV
32326 cm2, slice thickness 1.4 mm, TR 11.6 ms, TE 4.9 ms,
flip angle (FA) 88, 19 projection images, flow encoding 15 cm/
s). Multiphase 3D contrast-enhanced MR angiography
(matrix 3203224, FOV 32324 cm2, slice thickness 3.0 mm,
TR 4.3 ms, TE 1.4 ms, FA 30 degrees, five dynamic
acquisitions). After acquisition, images of all five dynamic
acquisitions were subtracted from the base image for each
location. The Inhance 3D MRA was sagitally acquired
covering the head and neck, and reformatted into 18
maximum intensity projections around the CC axis
. The
FOV of the phase-contrast angiography included the whole
brain and at least the distal half of the neck, and the FOV
multiphase 3D contrast-enhanced MR angiography ranged
from the aortic arch to the confluens sinuum. Therefore, the
crucial area of the skull base and the upper neck (most of the
described cases of venous stenosis were located in this area)
was depicted by both angiographic methods.

And this is how they analyse images:
As a first step, image annotations and identifiers were removed
and replaced by new unique identification numbers. The structural
MR images (PD/T2-weighted, FLAIR and T1-weighted
images) and angiographic images were stored separately.

All angiographic images were scored by two interventional
neuroradiologists (RVDB, JCB) in consensus
. Both readers only
had access to the angiographic series but not to the structural
MR images, and were blinded to the demographic (except date
of birth) and clinical information of all study subjects.

The following intracranial and extracranial venous structures
were analysed separately for possible abnormalities (aplasia,
hypoplasia, stenosis and occlusion). Extracranial: external
jugular veins, internal jugular veins. Intracranial: superior
sagittal sinus, inferior sagittal sinus, straight sinus, transverse
sinus, sigmoid sinus, great cerebral vein (of Galen), internal
cerebral veins.
A stenosis was defined as a narrowing of the
vessel of at least 50%, and an occlusion was defined as no
patency of the vein without any flow on both the phasecontrast
and contrast-enhanced MRV.

In addition, the entire intracranial and extracranial venous
system was scored for alternative venous drainage with or
without associated stenosis of certain venous structures. Indicator
of alternative drainage pattern also considered venous
structures/pathways which were not scored for abnormalities in
the first step such as superficial cerebral veins, cortical veins,
basal vein (of Rosenthal), vein of Trolard, choroidal veins,
thalamostriate (terminal) veins, superior and inferior petrosal
sinus, cavernous sinus, occipital sinus, epidural veins, occipital
plexus, vertebral plexus and deep cervical veins. Physiologically
asymmetrical venous drainage patterns in particular of the
transverse and sigmoid sinus were not considered as pathological.

The final conclusive classification of the venous systems in
terms of findings suggestive of an anomalous intracranial venous
drainage according to our imaging protocol and rating systems
was based on the following definition:
> No evidence of anomalous venous anatomy: normal/physiological
venous drainage without evidence of venous stenosis
and/or alternative venous drainage;
> Anomalous venous anatomy: presence of an extra- and/or
intracranial venous stenosis in combination with or without
alternative (compensatory collateral) venous drainage;
– possibly anomalous venous anatomy: presence of an extraand/
or intracranial venous stenosis without alternative
venous drainage pattern;
– probably anomalous venous anatomy: presence of an extraand/
or intracranial venous stenosis in combination with
alternative (compensatory collateral) venous drainage.


Thats give a better picture about how complex analysis are made and that pictures/examples in the study material are just informative 2D pictures. There is a whole bunch of MRI pictures analysed in 3D for resulting conclusions - not shown here.
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Postby malden » Sun Nov 07, 2010 9:27 am

From a study discussion:
We have to be aware that all available standard imaging
approaches for the evaluation of the cranial venous system
represent rather a snapshot. The venous blood flow is influenced
by many different physiological factors and their interaction such
as respiratory changes, swallowing, central venous pressure,
position of the patient (supine, sitting, upright), muscle
contraction, etc. Regarding the analysis of the intracranial and
cervical venous systems, it is almost impossible to take all of these
factors into account, regardless of the imaging modality used.


Munzio's, Jeff's, Johnson's and Jugular's MRV's each are showing just a snapshot. No hemodynamic at all. Pictures don't represent veins - they represent dye flow inside the some of the veins. And that's not the same - at all.

In contrary, diagrams on
Figure 8 "Examples of quantitative venous blood flow analysis in the straight sinus (top row) and internal cerebral veins (middle and bottom row) of healthy controls (HCs) and multiple sclerosis (MS) patients who were classified as having a normal (left columns), possibly anomalous (middle columns) and probably anomalous (right columns) venous outflow anatomy. No venous backflow/reflux could be observed in any MS patient or HC."
are dynamic, they measure blood flow in ml/s versus time in msec.

That's much better approach then a ECD and TCCS methods, which are strongly operator-dependent, and intracranial venous blood flow is difficult to measure. In contrast, magnetic resonance venography (MRV) is a non-invasive, sensitive, operator-independent technique for the evaluation of venous anatomy and pathological changes, and is widely used in the clinical setting.
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Postby Jugular » Sun Nov 07, 2010 10:32 am

Malden wrote:Munzio's, Jeff's, Johnson's and Jugular's MRV's each are showing just a snapshot. No hemodynamic at all. Pictures don't represent veins - they represent dye flow inside the some of the veins. And that's not the same - at all.

In contrary, diagrams on
Figure 8 "Examples of quantitative venous blood flow analysis in the straight sinus (top row) and internal cerebral veins (middle and bottom row) of healthy controls (HCs) and multiple sclerosis (MS) patients who were classified as having a normal (left columns), possibly anomalous (middle columns) and probably anomalous (right columns) venous outflow anatomy. No venous backflow/reflux could be observed in any MS patient or HC."
are dynamic, they measure blood flow in ml/s versus time in msec.

That's much better approach then a ECD and TCCS methods, which are strongly operator-dependent, and intracranial venous blood flow is difficult to measure. In contrast, magnetic resonance venography (MRV) is a non-invasive, sensitive, operator-independent technique for the evaluation of venous anatomy and pathological changes, and is widely used in the clinical setting.


The MRV images are pretty standard front view images showing the veins as the contrast dye goes through them. While you only see one image depicted there is actually a slideshow to view as you can spin around the view point and look at the same stenoses from front and the side. There are more than one image taken and in the ones presented in the report a few are laced together. The stenoses don't play a game of now you see them now you don't

The point I makes about the images used to illustrate the study's findings is thar they all depict a mild stenosis or minor malformation. If these images are typical, and one required a moderate to severe stenosis to qualify, then none of the patients in the study would fit the bill. Certainly, though a venogram looking at all the involved veins might find different, it would be questionable whether these patients would bother with repair.

So I don't know what gives with this study. I really hope Haacke comments about it because he probably has seen hundreds upon hundreds of MRV's fed to him several imaging centers. If this study is true, half of those images would show no stenoses. He would also be able to comment upon what is typical and whether he's looked at 'normal' patients.

Until then I am going to throw it out there that the type of moderate to severe stenoses and malformation seen in our cases are not normal and are far more likely to be found in MS patients.

Has for the blood flow part you are absolutely right - the images are only part of the 'picture'. In my case (I am not sure about the rest) Haacke's report came with detailed blood flow analysis, complete with charts and tables. The difference between his approach and the Dutch study is that the Dutch study measured flow at one point in the cerebral veins, whereas Haacke measures at two locations, the upper and lower neck.

Perhaps the Dutch researchers believe that flow analysis is more relevant upstream than downstream. I would say that the differences are more patent downstream. The other point is that the Haacke analysis shows if the left and right flow is asynchronous and whether the flow from the jugulars is diverted. To me, having these main exhaust pipes to the brain open and flowing well is what's behind the improvements seen in patients undergoing venoplasty.

Edit: I am pasting a link to a Haacke report from the False Creek site, so you can see for yourself the differences in methodology in flow analysis (as well as another image of a patent stenosis or malformation)

http://www.falsecreekhealthcare.com/sha ... n-2010.pdf
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Postby Jugular » Sun Nov 07, 2010 11:10 am

scorpion wrote:If I remember Cheer's husband had very severe stenosis yet had fairly mild MS sympotms. Does anyone find it ironic that pics are posted on this forum and the stenosis is "obvious" yet none of us were trained using Zamboni's STRICT standards? Maybe there is not stenosis in the veins that are posted as "gimmees" but instead they are "normal" for that particular person. Of course since the definition of normal veins have not been established it makes my question rather pointless.


This is the advantage of an MRV v. DU. As Maiden says, the images are operator independent. A disadvantage is that the images can only be taken when the patient is lying down and in a fixed position. With DU, readings can be taken while the patient is in a variety of positions. For instance it can determine whether the IJV's open and close normall when the patient is upright and lying down. The other advantage is that it is much cheaper and more easily tolerated than being bolted on a board and stuck in a noisy tube for a few hours.
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Postby malden » Sun Nov 07, 2010 1:22 pm

Jugular wrote:The MRV images are pretty standard front view images showing the veins as the contrast dye goes through them. While you only see one image depicted there is actually a slideshow to view as you can spin around the view point and look at the same stenoses from front and the side. There are more than one image taken and in the ones presented in the report a few are laced together. The stenoses don't play a game of now you see them now you don't.

Yes, I totaly agree with you. Lets look at, for example, those two pictures:

Image
Image
(If author has complains about posting this pics, I'will remove them emmediately).

The locations marked as: "Tin Whistle Stenosis" and "?" on the first picture looks normal (without stenosis) on the second picture. Vessel is the same, location is the same, but point of view is about 45 deg. rotated (PL-AR first pic, L-R second pic.)

Is this a real stenosis? Or just a flat twisted vein hose in two different views?
As you said: "The stenoses don't play a game of now you see them now you don't."

Best regards, M.
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Postby Jugular » Sun Nov 07, 2010 3:54 pm

Malden wrote:
Jugular wrote:The MRV images are pretty standard front view images showing the veins as the contrast dye goes through them. While you only see one image depicted there is actually a slideshow to view as you can spin around the view point and look at the same stenoses from front and the side. There are more than one image taken and in the ones presented in the report a few are laced together. The stenoses don't play a game of now you see them now you don't.

Yes, I totaly agree with you. Lets look at, for example, those two pictures:
The locations marked as: "Tin Whistle Stenosis" and "?" on the first picture looks normal (without stenosis) on the second picture. Vessel is the same, location is the same, but point of view is about 45 deg. rotated (PL-AR first pic, L-R second pic.)

Is this a real stenosis? Or just a flat twisted vein hose in two different views?
As you said: "The stenoses don't play a game of now you see them now you don't."

Best regards, Malden.
I'm not sure that we can completely do away with experts in reading MRV images and I am not sure that Johnson would want us to be debating about his veins, but I think he will allow that those are arrows that he drew on his own MRV image.

The specialist reading the images will look at them all not just the frontal view. They also will know more about what is a collateral or not. I was able to see the stenosis in my images before getting Haacke's report, but the report showed so much more and was illustrated with arrows just like the sample report I linked.

I remember the moment of revelation going through my own images. I clicked on a file called "neck MRV". It didn't show anything that I could see until I realized it was a side view and the start of a series of images. It was only after I clicked on "play" did I see my jugulars spinning into view. I could see the severe stenosis in the right that stayed being a stenosis no matter the angle.

I think that Johnson will know more about his own images and any reports that he received, but (with apologies to Johnson) they do look much more messed up than the Dutch ones.

I was more interested in your comments on the different protocols used for blood flow analysis in the Dutch study and the sample we have from Haacke.

Edit to add: one thing that didn't know what I was looking at until I received the Haacke report is that it also has a top-down cross-sectional views of the jugulars at various levels (slices). These are also used in conjunction with the other images to detect a stenosis. They can run, but they can't hide.
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Postby malden » Mon Nov 08, 2010 8:41 am

Jugular wrote:...
I was more interested in your comments on the different protocols used for blood flow analysis in the Dutch study and the sample we have from Haacke.
...

They both use same machine, GE 3.0 Tesla MRI system:
False Creek Healthcare Centre wrote:The 3.0T MRI, used in the newest and most advanced clinical applications, produces images faster and with unprecedented detail.

•State of the art technology
•Double the magnetic field of the 1.5 Tesla MRI
•3T adds certainty to the diagnosis
•Detects diseases that can not be seen with 1.5T
•The highest resolution scanner available for clinical use in the world today
•Key to minimally invasive therapies
•Radiation free

and the phase-contrast flow quantification with the same velocity encoding: 50 cm/s.
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Left Transverse Sinus

Postby drbart » Mon Nov 08, 2010 9:39 am

Nunzio wrote:As you can see my right jugular vein (on the left side of the picture) is much smaller then the normal jugular vein on the other side so it is obvious that I have CCSVI based on the above MRV.


Woa woa woa.. completely aside from the point of your post, I think this MRV is really interesting.

The Haacke contrast-enhanced images don't extend to the back of the head, but yours does ... and what looks like a pinch in your left transverse sinus looks really really interesting.

Can you export a 360-degree movie of this, perhaps with a tilt so we can see the transverse sinus veins more clearly?
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