What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

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What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby TheBrain » Tue Aug 07, 2018 9:53 am

CAUTION: If you don't really want to know any more about brain atrophy than you do now, STOP READING. Personally, I'm glad I know my own status, but not everyone will feel that way.

The following information differs from what appears in NeuroQuant's Triage Brain Atrophy Report with any structures that are highlighted in red. A brain structure is highlighted in red when atrophy for the structure is at the 5th percentile or lower, as compared to healthy controls of your same age and gender. So yes, those red areas are pointing out atrophy, but according to the following neuroimaging expert, atrophy occurs at larger volumes. I can't speak specifically about Neuroreader reports with respect to how they indicate atrophy, as I'm only vaguely familiar with Neuroreader. However, the percentiles for atrophy are the same for both technologies, per this neuroimaging expert.

The information is from Evolving Past Alzheimer's Episode #6: Is My Brain Shrinking? The interviewee is Cyrus Raji, MD, PhD, an expert in neuroimaging. He's an advisor for Neuroreader, but from what he has said just in this podcast, it sounds very much like NeuroQuant, at least in terms of how volumes are reported.

First, here's a paragraph from the summary in the show notes:

What do my MRI volumetric numbers mean?
To be considered abnormal and potentially consistent with Alzheimer’s diagnosis – the “magic number” for hippocampal volumes on MRI of the brain (using the Neuroreader or Neuroquant tool) is a number below the 25 percentile (this information is included in the report provided by Neuroreader or Neuroquant). Ventricular volumes, if higher than 75th percentile, may be too big and suggestive of Alzheimer’s or another disorder as well.


Note: I think the above summary should say "below the 26th percentile," given what Dr. Raji actually says in the interview.

If you're interested in the details, go to 30 min, 20 seconds in the podcast (of course, the preceding discussion is also interesting). But I transcribed Dr. Raji's words here. He says that the consensus is that:

for brain volumes, you should really be worried about volume loss and atrophy when a given brain structure like the hippocampus is only 25th percentile of normal or lower. So that means that if it's only 25% as large as we would expect it to be—or lower, like 20% or 15%—then that should be cause for concern of genuine volume loss in that area. And that number seems to be a good compromise between the sensitivity we want in detecting abnormality but also the specificity we want to make sure that it's a genuine abnormality and not some variation of normal. We don't want to make an over-call. So what happens if you're in the 26th percentile? Or 30th percentile? For me, I still raise the possibility that there could be something abnormal about that structure. I'll typically call that borderline-normal.

Typically, most of the brain structures we see are in the median; they're 50th percentile. So if you see that number, you shouldn't be concerned and say, 'oh my goodness, I'm only 50% of the norm' because that's still a very healthy number. And sometimes you see people that are really brilliant, it seems, and they have 99th percentile hippocampal volumes, and they're very large. You can see that as well, and that's not abnormal. It's just abnormal if it's too low.

Then for the ventricular volumes, those fluid-filled spaces that exist in the brains for housing cerebral spinal fluid, we typically call those abnormally enlarged if they're higher than 75th percentile of normal. So when brain structures shrink, that's not good. When ventricular structures get bigger, that's not good either. They're both indicative of the underlying atrophy process. So we use the 75th percentile for the ventricular volumes and the 25th percentile or lower for the other brain structures.


He then goes into asymmetry, which I have in multiple brain structures... I need to listen again to understand the significance of this phenomenon.
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Re: What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby NF52 » Tue Aug 07, 2018 5:45 pm

TheBrain wrote:CAUTION: If you don't really want to know any more about brain atrophy than you do now, STOP READING. Personally, I'm glad I know my own status, but not everyone will feel that way....

Thanks for using your Brain to listen, transcribe (!!) and post this information. I'd say your brain is humming along quite nicely, no matter what peculiarities they've found on imaging.
4/4 and still an optimist!

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Re: What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby TheBrain » Tue Aug 07, 2018 7:15 pm

Thanks you, NF52. I appreciate what you wrote. You are very kind. :)
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Re: What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby Kurt » Thu Aug 23, 2018 4:46 pm

A brain is what I need these days. Finding THE BRAIN must be my lucky day! I would like to consider getting a MRI brain volume calculation. I have some MRI CD's from 2 years ago and have a fresh one scheduled soon. Would you know (1) what would one need to do in order to get a volume calculation (hippocampus and/or other areas) and (2), is there a possibility that I might be able to get the calcs on the older MRI's discs (calculate loss)? I have no knowledge if it takes special MRI equipment / data resolution, etc. The radiologists/neurologist from the original MRI's had never heard of brain volume calculations. My understanding is the calculations are done off-line with various math techniques. I have noticed the companies you note, but have not talked with them. Of course, the calculation cost may be a consideration, but this could be an opportunity since I expect that insurance will likely cover some of the MRI since my neurologist initiated the new test. Thanks for any comments.

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Re: What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby TheBrain » Fri Aug 24, 2018 8:16 am

Hi Kurt,

To get a quantitative MRI, your best bet is to call around and find an imaging center that actually uses either NeuroQuant or Neuroreader. The MRI must be performed in a certain way in order for the volumetrics software to be run against it. So, to the best of my knowledge, your older MRI images can't be used with either product. (And, to the best of my knowledge, the two products are roughly equivalent in terms of the information they provide.)

The good news is that addition of the NeuroQuant or Neuroreader to the MRI doesn't cost that much. I recall it was less than $200, but I'd have to look at my insurance paperwork to confirm that. My insurance covered it.

I got an MRI with NeuroQuant. After the MRI was done, my images were uploaded to CorTech Labs' server and three reports were generated for me: Age-Related Atrophy Report, Triage Brain Atrophy Report, and General Morphometry Report. If you go with NeuroQuant, I'd suggest making sure you get all three reports. The second one provides the volumes of 39 brain structures, compared to healthy controls of the same age and gender. This report includes the hippocampus but so much more. The first one also includes the hippocampus, as well as the volumes of ventricles, and comes up with an hippocampal occupancy score (HOC).

I had to drive 2 1/2 hours (5 hours roundtrip) to find an imaging center that did NeuroQuant. Unfortunately, no radiologist at that center knew how to interpret the NeuroQuant reports. The vast majority of the MRI with NeuroQuant orders for that center came from a doctor who specializes in Chronic Inflammatory Response Syndrome (CIRS). She knows how to interpret the reports. So my doctor handed me my reports and said, "Good luck figuring out what all those numbers mean." (Since then, the imaging center is taking initial steps to train at least some of their radiologists. More patients like me are showing up at their door.)

I won't bore you with all the details, but it was hell trying to find someone who could interpret the reports. The process took months, and I can't recommend the imaging center that did a "second read" on my MRI images; I have concluded that the radiologist at this second center never looked at the Triage Brain Atrophy Report or else didn't know how to interpret it.

If you run into the same problem I did, I can recommend Mary Ackerley, MD. She is a CIRS expert. I had a one-hour consultation with her, and she went through my results with me. The cost was $250. Note: I found out after posting that Dr. Ackerley now charges $290 for a consultation. I did mine using Skype, but it can be a phone call (or in person, I'd assume, if you live near her).

I think a quantitative MRI is invaluable. I believe that all radiologists and neurologists should use this technology. It's much more accurate than having a doctor just look at the images; in fact, they can get it wrong!

I recommend watching this video June 17, 2015 - Dr. James Brewer, UC San Diego - NeuroQuant 2.0 for Neurodegenerative Assessment.

Good luck!
Last edited by TheBrain on Fri Aug 24, 2018 2:51 pm, edited 1 time in total.
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Re: What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby TheBrain » Fri Aug 24, 2018 8:26 am

Let me add that supposedly, any imaging center can create the MRI images in the proper format, even if they don't have NeuroQuant or NeuroReader. Still, you'd have to get your images uploaded to the server of the brain volumetrics company you choose. That would have to be coordinated in some way.

A while back, I was consulting with Dr. Bredesen. He gave me the following instructions for an MRI technician and my MD to do just this. He mentions Neuroreader, but I suspect these instructions also apply to NeuroQuant; that would need to be confirmed. I tried getting my doctor to order an MRI with these instructions, but he didn't feel comfortable doing so because he didn't understand them. (He later ordered the MRI with NeuroQuant after I found an imaging center that used this technology.) But here they are:

MRI protocol should be ordered for Neuroreader analysis.

Axial, sagittal, and coronal T1 weighted 3D MPRAGE (if Siemens Scanner) or SPGR (if GE scanner) isotropic voxels with coronal reformats being perpendicular to the hippocapi. The T1 sequence is the only sequence that gets analyzed by Neuroreader so it's the most important sequence to get right. The most important part of getting this sequence right is the 3D part because if the scan is not acquired at 1 mm slices then the Neuroreader algorithm will lose accuracy.

Axial FLAIR with 3 mm slices, 1 mm isotropic voxels.

T2 weighted image with 3 mm slices, 1 mm isotropic voxels.

Gradient echo (GRE) scan with 3 mm slices.

Axial diffusion weighted sequences including apparent diffusion coefficient (ADC) maps.

The injection of intravenous contrast should NOT be done with this protocol.
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Re: What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby Kurt » Fri Aug 24, 2018 10:04 pm

Terrific info. I was able to locate a company named Diagnostic Imaging Services today that apparently offers NeuroQuant Volumetric MRI’s at some of their sites. Only about 80 miles from my house! Appears they just provide imaging services and try to capture a large segment from other medical organizations. I only got to talk with a front end “sign up” person today and could not get anywhere regarding interpreting the reports. I’ll try again next week and see if I can get a more technical person to address the items you noted and experience levels. Thanks for recommending Dr. Ackerley, she sounds great. I see she is in Arizona, far away from me. But who knows, I got a potential surprise recently regarding CIRS.

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Re: What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby circular » Fri Aug 24, 2018 10:58 pm

I could be wrong, but it was my impression that depending on the MRI specifications, some old ones can be run through the NeuroQ and NeuroR software, so no harm asking.

TheBrain thanks for the excerpt from Dr. Raji. Since my hippocampal volumes are reasonably robust, but my ventricles are climbing up to 75th %ile, perhaps I'm not close to having AD, but something else is causing atrophy. A suggestion has been that mold if not other toxic inputs is disrupting volumes. I can come up with quite a list of areas below or near the 25th %ile, but they're not all highlighted on the NQ report. I look forward to getting more time to dig into this.

Here's a 2009 paper by Raji and others that compares volumes in aging vs AD and identifies overlapping areas of brain shrinkage. Anyone connecting volume loss in specific areas to mold and other CIRS processes should probably compare these with patterns in 'normal aging' to be sure it's a different pattern. Maybe that's been done?

Age, Alzheimer disease, and brain structure

Wow, I didn't know our forum threads are now showing up in Google searches. This one is in the hits for 'Dr. Raji brain'.
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Re: What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby TheBrain » Sat Aug 25, 2018 6:40 am

Kurt wrote:Terrific info. I was able to locate a company named Diagnostic Imaging Services today that apparently offers NeuroQuant Volumetric MRI’s at some of their sites. Only about 80 miles from my house! Appears they just provide imaging services and try to capture a large segment from other medical organizations. I only got to talk with a front end “sign up” person today and could not get anywhere regarding interpreting the reports. I’ll try again next week and see if I can get a more technical person to address the items you noted and experience levels. Thanks for recommending Dr. Ackerley, she sounds great. I see she is in Arizona, far away from me. But who knows, I got a potential surprise recently regarding CIRS.


Kurt, any chance you’re in North Carolina? That’s the same name of the imaging company I used for my initial MRI with NeuroQuant. However, it sounds like it could be a commonly used name for this purpose. If it is the same company, they probably still don’t have anyone trained to interpret NeuroQuant, at least not yet.

Dr. Ackerley does phone and Skype consultations, so you don’t need to go in person.
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Re: What is considered atrophy in a brain structure per MRI volumetrics (NeuroQuant and Neuroreader)?

Postby TheBrain » Sat Aug 25, 2018 7:43 am

circular wrote:I could be wrong, but it was my impression that depending on the MRI specifications, some old ones can be run through the NeuroQ and NeuroR software, so no harm asking.


I have heard/read otherwise, but yes, definitely no harm in asking. I had an MRI at age 30 and recently tried to locate my MRI images. I couldn't. It would be very helpful to know how I was doing then versus now.

TheBrain thanks for the excerpt from Dr. Raji. Since my hippocampal volumes are reasonably robust, but my ventricles are climbing up to 75th %ile, perhaps I'm not close to having AD, but something else is causing atrophy. A suggestion has been that mold if not other toxic inputs is disrupting volumes. I can come up with quite a list of areas below or near the 25th %ile, but they're not all highlighted on the NQ report. I look forward to getting more time to dig into this.


Yes, mold and other toxins can cause generalized brain atrophy. So can sleep apnea, per my neurofeedback therapist who is also a naturopath. I experienced hypoxia during sleep while living at high altitude, which has a similar effect on the brain.

I recently typed up text from Dr. Bredesen's book and other resources from him regarding CIRS and brain atrophy. Check out: CIRS/Type 3 AD and Generalized Brain Atrophy per Dr. Bredesen. For example, here's the first quote I included:

It [Type 3 Alzheimer's] affects many brain areas, not only or even predominantly the hippocampus with MRIs showing that regions throughout the brain have atrophied (shrunk). (p. 106)


I have come to the conclusion that the Triage Brain Atrophy Report is misleading by only highlighting atrophy if a percentile is below 5%. The only caution I can say about Dr. Ackerley is that she failed to mention to me the atrophy in my total cerebral white matter. I recall her getting to that part of my report and hesitating with a long, pregnant pause. I sensed that she was trying to decide what to say, but in the end, she decided to say nothing. Of course, I don't know why (and I now wish I had been more assertive). Maybe she doesn't know why that structure would be atrophied or maybe she didn't want to scare me. I'd rather know the truth, even if she doesn't know the why. Otherwise, it was a great consultation, and I learned a lot. When I consult with her on my next MRI with NeuroQuant, I'll say "please don't hold back." I already sent her via email the information from Dr. Raji about atrophy and borderline-normal percentiles. I didn't get a response but wasn't expecting to.

Here's a 2009 paper by Raji and others that compares volumes in aging vs AD and identifies overlapping areas of brain shrinkage. Anyone connecting volume loss in specific areas to mold and other CIRS processes should probably compare these with patterns in 'normal aging' to be sure it's a different pattern. Maybe that's been done?

Age, Alzheimer disease, and brain structure


Thanks for sharing this paper. My pattern definitely doesn't match normal aging; I blame the probably decades-long mold toxicity and hypoxia during sleep I experienced. Also, remember that the percentiles in two of the three NeuroQuant reports are adjusted for each patient based on the volumes of healthy controls of his or her same age and gender. The 50th percentile is the mean for healthy controls of the same age and gender, and that's a great place to be.

Wow, I didn't know our forum threads are now showing up in Google searches. This one is in the hits for 'Dr. Raji brain'.


Wow! I didn't know that either.
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