Lesions and SWI

cheerleader · Post by **cheerleader** » Wed Sep 16, 2009 2:00 pm

Many disease modifying treatments use the reduction of lesions as shown on MRI as proof a treatment is "working" in MS. This has baffled me, since we know that the number of lesions does not correlate to level of disease progression. Someone like Jeff or Mel can have 20 brain lesions and function quite well. Someone else can have one or two lesions and be wheelchair-bound. Also, at a certain point, lesion progression stops when MS turns progressive. There must be another mechanism of injury, aside from the immune system, at work in the MS brain.

In Bologna, Dr. Mark Haacke addressed another means of measuring brain tissue injury in MS, Susceptibility Weighted MRI. What SWI shows us, is that iron deposited in the brain is a bio marker for MS progression.

What is different in SWI-MRI, according to Dr. Haacke, is that damage and lesions shown due to iron deposition actually CORRESPONDS to disability in MS.

The more iron deposed, the more disability, the more progressive MS is. This is different than the usual measuring of hyperintense lesions on MRI, which have no correlation to disease severity.

The susceptibility information is an adjunct to what is available with conventional spin density, T1-, and T2-weighted imaging methods. SWI offers information about any tissue that has a different susceptibility than its surrounding structures such as deoxygenated blood, hemosiderin, ferritin, and calcium. There are numerous neurologic disorders that can benefit dramatically from a very sensitive method that monitors the amount of iron in the brain, whether in the form of deoxyhemoglobin, ferritin, or hemosiderin. Such diseases and conditions include, but are not limited to, aging, multiple sclerosis (MS), stroke, trauma, vascular malformations, and tumors. There is no doubt that as SWI becomes more broadly accepted, we will see many new applications develop because of the astute observations of clinical researchers and the wide availability of information for the whole spectrum of neurologic diseases seen on a daily basis in the clinical setting.

http://www.ajnr.org/cgi/content/full/30/1/19

Haacke EM, Makki M, Ge Y, Maheshwari M, Sehgal V, Hu J, Selvan M, Wu Z, Latif Z, Xuan Y, Khan O, Garbern J, Grossman RI.
Department of Radiology, Wayne State University, Detroit, Michigan 48201, USA. nmrimaging@aol.com
PURPOSE: To investigate whether the variable forms of putative iron deposition seen with susceptibility weighted imaging (SWI) will lead to a set of multiple sclerosis (MS) lesion characteristics different than that seen in conventional MR imaging. MATERIALS AND METHODS: Twenty-seven clinically definite MS patients underwent brain scans using magnetic resonance imaging including: pre- and postcontrast T1-weighted imaging, T2-weighted imaging, FLAIR, and SWI at 1.5 T, 3 T, and 4 T. MS lesions were identified separately in each imaging sequence. Lesions identified in SWI were reevaluated for their iron content using the SWI filtered phase images. RESULTS: There were a variety of new lesion characteristics identified by SWI, and these were classified into six types. A total of 75 lesions were seen only with conventional imaging, 143 only with SWI, and 204 by both. From the iron quantification measurements, a moderate linear correlation between signal intensity and iron content (phase) was established. CONCLUSION: The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics. SWI showed many lesions missed by conventional methods and six different lesion characteristics. SWI was particularly effective at recognizing the presence of iron in MS lesions and in the basal ganglia and pulvinar thalamus. Copyright (c) 2009 Wiley-Liss, Inc.

http://www.ncbi.nlm.nih.gov/pubmed/19243035
cheer

mrhodes40 · Post by **mrhodes40** » Wed Sep 16, 2009 4:24 pm

Cheer you're right! the iron deposition as a surrogate marker for disability level has been noticed for a while and it supports the idea that iron, thus leaking, NOT inflammation and just lesions, are the important thing.

Conclusions Gray matter T2 hypointensity in MS is associated with brain atrophy and is a stronger predictor of disability and clinical course than are conventional MRI findings. While longitudinal studies are warranted, these results suggest that pathologic iron deposition is a surrogate marker of the destructive disease process

from
http://archneur.ama-assn.org/cgi/conten ... ct/59/1/62

IHateMS · Post by **IHateMS** » Wed Sep 16, 2009 4:59 pm

so with this idea, does that mean a person's iron count (blood) would be high <if the person had high iron deposits>?

cheerleader · Post by **cheerleader** » Wed Sep 16, 2009 5:09 pm

I'm not sure but I don't think this would correlate with blood (serum) iron levels. Everyone's blood has certain iron levels, and that wouldn't change due to microbleeding in the brain. Once the iron is in the brain, it stays there and wouldn't recirculate.

The brain is injured by the blood entering brain tissue because of slowed perfusion and microbleeding cause by reflux...the only way to see it is with SWI-MRI technology.
The pictures Dr. Haacke showed us of MS brains had dark gray areas where the iron was being deposited and absorbed by brain tissue. He compared it to SWI-MRIS of normal brains, where there were no dark gray areas.

Dr. Haacke's presentation was the most conclusive evidence of CCSVI to me- because it showed the method of brain injury, the reason the immune system is activated (to clean up dead cells), the reason for disease progression and the correlation with stenosis.

cheer

Rokkit · Post by **Rokkit** » Wed Sep 16, 2009 6:20 pm

cheerleader wrote:Dr. Haacke's presentation was the most conclusive evidence of CCSVI to me- because it showed the method of brain injury, the reason the immune system is activated (to clean up dead cells), the reason for disease progression and the correlation with stenosis.

Hi Cheer, can you explain more about the correlation with stenosis. Is he seeing the iron concentrated near where the blood comes back into the brain directly from being refluxed by the stenosis? Is that where the micro-bleeds always are? I'm trying to understand if there's evidence of jugular stenosis causing lesions in the thoracic or lumbar spine. Hoping SWI can shed some light.

Rokkit

cheerleader · Post by **cheerleader** » Wed Sep 16, 2009 6:49 pm

Rokkit...check out this Russian study Marie posted, as translated by Dr. Simka- it shows how jugular blockage can cause venous reflux issues that can affect the spine. Not sure if SWI has been used for spinal scans, all I can find is brain-

http://www.thisisms.com/ftopict-7648.html

As far CCSVI causing the iron deposition, yes, the iron is deposited around veins, and veins are inside each lesion...Dr. Haacke said that it makes sense when looking at the MS brains from the CCSVI perspective, how reflux of blood back into the brain stresses the veins and leads to microbleeding. Dawson's Fingers lesions are venocentric, and contained the most iron. He is going research the connection further. He felt that CCSVI was putting the pieces together.

Dr. Haacke also said that this is not new. We've known about iron deposition and vein problems in the MS brain for many years.

Here is a study from 1988

Abstract
Evidence of damage to cerebral vein walls was sought in 70 cases of multiple sclerosis. Seventy control cases were also examined. The multiple sclerosis cases showed venous intramural fibrinoid deposition (7%), recent haemorrhages (17%), old haemorrhages revealed by haemosiderin deposition (30%), thrombosis (6%) and thickened veins (19%). In all, 41% of all multiple sclerosis cases showed some evidence of vein damage. Occasional control cases showed haemosiderin deposition in the brain but, unlike the multiple sclerosis cases, these were diffuse and almost entirely related to coexistent cardiovascular or cerebrovascular disease. Haemosiderin deposition was common in the substantia nigra and other pigmented nuclei in all cases. It is concluded that the cerebral vein wall in multiple sclerosis is subject to chronic inflammatory damage, which promotes haemorrhage and increased permeability, and constitutes a form of vasculitis.

Read the paper...it is enlightening:
http://www.pubmedcentral.nih.gov/articl ... id=1031540

Why no one looked at the jugular veins, the drainage system for the brain, in relation to this venous injury of the brain, still baffles me.
cheer

mrhodes40 · Post by **mrhodes40** » Wed Sep 16, 2009 7:32 pm

this is op-ed

It is concluded that the cerebral vein wall in multiple sclerosis is subject to chronic inflammatory damage, which promotes haemorrhage and increased permeability, and constitutes a form of vasculitis.

This is the thing that bugs me, the conclusion that is drawn from that data.

they are saying that it is a form of vasculitis, vasculitis is an inflammatory disease in which the inflammation of the vessel causes leaking=it is one of the differential diagnoses for MS and is a rheumatic disease.

So in their conclusion they decided that the chicken came first.....even though that was a leap not supported or refuted by the data.

I submit that this leap was made because they already believed that MS was caused by inflammation and this conclusion not only could fit the data, but it also supported the "inflammation came first" point of view that they already held as correct.

Haemosideran was already known as a by product of venous ulcer, they could have instead drawn the conclusion they needed to look at the circulation.

That they did not is proof that our evidence based medicine is not merely evidence based and objective, it is biased.

The presence of papers such as these in my mind constitute a huge back data base for the idea of CCSVI. When people go on and on about "one paper, one man" which is a gross understatement anyway, they are ignoring all of these other kinds of materials.

That is just how I see it in my biased world........

Jamie · Post by **Jamie** » Wed Sep 16, 2009 7:50 pm

It's not necessarily 'biased' more influenced by the paradigm.

Paradigms shift faster and faster though due to technology and communications.

Most researches have grown up with an assumption of autoimmunity even those trying to remain genuinely unbiased are influenced, they aren't robots!

It's all good anyway, maybe its Lew feeling good and Dake learning more and being positive he can make further changes for people now - maybe its the very relaxed state I'm in but I'm feeling so good about all this now, the genie is out of the bottle and things are accelerating.

Hopefully there will be a spirit of 'well this does change things lets work together to find out all the answers'.

What's great is at least SOME influential neuros seem to be interested and no one from the vascular 'side' is claiming to have all the answers or even most of the answers.

BUT this isn't holding up treatment for those who want it and are fortunate to live somewhere they can get it and afford it.

The future is brighter than its ever been!

whyRwehere · Post by **whyRwehere** » Wed Sep 16, 2009 10:59 pm

So, is this SWI available for seeing on a 1.5 Tesla, or is it additional machinery/software? If I send my husband for an MRI, will I be able to tell the radiologist to apply this method? Should I not bother going through with booking the MRI if the technology is not available here?

cheerleader · Post by **cheerleader** » Thu Sep 17, 2009 6:32 am

whyRwehere wrote:So, is this SWI available for seeing on a 1.5 Tesla, or is it additional machinery/software? If I send my husband for an MRI, will I be able to tell the radiologist to apply this method? Should I not bother going through with booking the MRI if the technology is not available here?

Dr. Haacke said there are now 1,000 MRI machines in the world with SWI technology, and he has also made the software available on line:
http://www.MRimaging.com/
Go to the site and look at the images- astounding.
The standard MRI will continue to be the "gold standard" until we change the paradigm. We need to inform doctors and the general public that iron deposition and hypoxia (as measured by BOLD and SWI technology) is the real means of brain tissue injury in MS.

If standard MRI is all that is available, it is still a marker of some sort. Just know that those lesions do not truly tell us the whole story.
cheer

mrhodes40 · Post by **mrhodes40** » Thu Sep 17, 2009 7:11 am

Most researches have grown up with an assumption of autoimmunity even those trying to remain genuinely unbiased are influenced, they aren't robots!

You're right! It didn't come fast enough for me--5 years ago I could walk well, that is part of my 'feelings of betrayal' so to speak. That, and a desire to have someone locally to recheck me

the fact that this newer technology is zooming forward is very positive! How awesome that Dr Haacke has offered the program for free so others can do this, wow!!

cheerleader · Post by **cheerleader** » Thu Sep 17, 2009 8:13 am

Here's the rub:
Pharma companies use the lesions shown on MRI as "proof" that their particular drug is working. Look! We've reduced hyperintensities on MRI! Our amaze-a-bub is curing MS! Stock prices go up, investors are happy, and MS patients continue to decline.

If we look at the TRUE cause of disability- the only measurement in the brain that correlates to disability is IRON DEPOSITION and HYPOXIC INJURY.

This is why my Jeff had 20 lesions and could mountain bike, and someone with one lesion could be in a wheelchair.

If we understand that the macrophages and immune system are activated as janitors to clean up the death in the brain, we understand that the lesions we see on standard MRI mean NOTHING. Just like they are secondary in a stroke patient.

Thank God for Dr. Haacke, and other scientists that are crying out....it is not about the lesions on MRI. We will be told it is, because we can be sold drugs that make these lesions go away...but that has not stopped MS. There is no drug to stop reflux, iron deposition and hypoxic injury in the brain, and this is why it has not been explored before, and will be fought.
cheer

Ana · Post by **Ana** » Thu Sep 17, 2009 8:23 am

I agree. This is probably also the reason why some people have no visuable changes in their normal MRT's over years but get more and more disabled.

chrishasms · Post by **chrishasms** » Thu Sep 17, 2009 8:28 am

skydog · Post by **skydog** » Thu Sep 17, 2009 10:33 am

Cheer said it best in a earlier post. Live life like your recovering from a major heart attack. Live peacefully and pay close attention how you are feeling. No Stress !!! The combination of a extremely healthy life style will keep your immune system strong. Good food for thought and the best foods for the system at large. Lots of nutritious fruits and vegetables. Until we can come up with a safe way of chelating the iron in our brains we best do all we can to keep it out. Lots of great new stuff hear. Keep it coming. Peace, Mark