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Spot the Signal: Global Radiology Training for ARIA Detection in Alzheimer’s Care

 

Nicola Hanson (DCE): Hi, everyone. Good afternoon or good evening, depending on where you're joining us from. And welcome to this webinar. This is entitled Spot the Signal: Global Radiology Training for ARIA Detection in Alzheimer’s Care. This is a CME activity provided by Decera Clinical Education, formerly known as Clinical Care Options. And we are supported in this activity by an educational grant from Lilly.

 

[00:12:36]

 

Faculty and Disclosures

 

The faculty we have with us today, I'd like to introduce Dr. Tammie Benzinger, who is Hugh Monroe Wilson Professor of Radiology and Professor of Neurological Surgery at the Mallinckrodt Institute of Radiology at Washington University in St. Louis, Missouri. And we also have Dr. Karl-Olof Lovblad, who is full professor and the Head of Division of Diagnostic and Interventional Neuroradiology at the Geneva University Hospitals in Switzerland. Thank you both very much for being with us here today.

 

[00:13:08]

 

Learning Objectives

 

Let me just go over the learning objectives very quickly for today's session. They are to:

 

• interpret ARIA-related imaging findings using validated grading scales in simulated case scenarios in alignment with current expert recommendations;
• To implement evidence-based MRI protocols for ARIA monitoring in patients receiving ATTs;
• Demonstrate proficiency in documenting ARIA findings using standardized reporting templates; and
• Collaborate with referring clinicians to effectively share actionable imaging insights for ARIA management.

 

[00:13:42]

 

Poll 1

 

We're going to start off with just a couple polls about you and your practice. So poll number one, how many patient MRIs do you assess related to amyloid-targeting therapy initiation or monitoring in a typical month? Please choose:

 

1. 1-2;
2. 3-5;
3. 6-10;
4. 11-15;
5. More than 15; or
6. Not applicable.

 

[00:14:14]

 

Poll 2

 

All right, moving on to poll number two. How confident are you in your ability to assess these patient MRIs related to amyloid-targeting therapy initiation or monitoring? Are you:

 

1. Not at all confident;
2. Not confident;
3. Neutral;
4. Confident;
5. Very confident;
6. Not applicable in your practice.

 

All right, and with that, I will give you into the hands of Dr. Benzinger. Please take it away.

 

[00:14:46]

 

Background and US Guidelines

 

Dr. Tammie Benzinger (Washington University in St Louis): Well, thank you so much. It's really a pleasure to be here with all of you today. I'm excited to walk over some background, and then I'm going to share with you some of the cases that we've seen during ARIA monitoring, and then really excited to be here with Dr. Lovblad to talk about the experience in Europe and how things are changing there as well.

 

Dr. Karl-Olof Lovblad (Geneva University Hospitals): Yes, I am really also excited to participate about this.

 

[00:15:15]

 

What Are Amyloid-Related Imaging Abnormalities (ARIA)?

 

Dr. Benzinger: So, you know, first and foremost, you know, what is ARIA? So this is amyloid-related imaging abnormalities, and I think that the most important word in this is imaging but these are findings that we see on brain MRIs. Usually these are ordered in asymptomatic patients who are undergoing these new treatments for Alzheimer's disease.

 

These are amyloid-targeting therapies. They're monoclonal antibody infusions, and there can be, quite commonly, a side effect of vasogenic edema, which can show up on FLAIR, or sulcal effusions also on FLAIR, as well as microhemorrhages and superficial sclerosis, which is what we call ARIA-H for hemorrhage. And I think, you know, many of us in the audience here are radiologists and are very familiar with these features because it looks very much like what we're used to calling cerebral amyloid angiopathy, or CAA, but when patients are on therapies, it's really important to identify these findings on the imaging as soon as possible because it changes the management for the patient.

 

Predictors of this are the same things that are predictors for CAA, honestly, so the APOE4 genotype, as well as evidence of prior hemorrhages, so the baseline microhemorrhages and baseline sclerosis give us a sense that somebody may have preexisting vascular amyloid, and that would be potentially dangerous for them to go on to these therapies.

 

When people do get symptoms, they're pretty nonspecific. It's things like headache, confusion, visual changes, dizziness, sometimes nausea or gait difficulty. It's very rarely serious, so less than 2% of patients progress to the serious level, which would be seizures, encephalopathy, hospitalization, neurologic deficits, but it's really important for us as radiologists to make this finding on the imaging as early as possible so that the patient's symptoms can be assessed and the therapies can be paused in order for it not to progress.

 

I'm going to say it again. It's important for the radiologist to call it on the images, not assume that somebody else is going to make that decision.

 

[00:18:01]

 

Question 1

 

Okay, so question number one. Approximately what percentage of patients treated with amyloid-targeting therapies do you expect will have a finding of ARIA on the MRI? So is this something you're going to see:

 

1. 2% of the time;
2. 5%;
3. 10%;
4. 20%;
5. 30%.

 

You should have a polling question popping up, and if you click through that, it's going to take us through. All right, and I can see, you know, we have kind of a wide spread of choices.

 

[00:18:54]

 

ALZ-NET Real-world ARIA Rates

 

So in the real world, this is about 20% of cases will have asymptomatic ARIA, and this is important to know because if you read five of these scans in a week, you should be seeing one case of ARIA that week.

 

So it's not a rare thing. It's a very, very common finding to see on the MRIs, and that's, I think, a surprise to a lot of us. We think about, oh, you know, there may or may not, we may or may not ever see this. You should be seeing it quite commonly.

 

[00:19:40]

 

MRI Monitoring Schedule for ATTs

 

Okay, this is actually showing you schedules. So in the United States, we have two different therapies available, donanemab and lecanemab, and they have slightly different dosing regimens, and then the key for us is they also have a bunch of different MRIs that are scheduled.

 

Now, these MRIs are performed, they're basically usually just scheduled out at the time the person signs up to start their infusions. If we see a positive finding on the MRI, then we recommend additional scans for follow-up one or two months after that positive MRI until the ARIA-E, until the edema has completely resolved and the hemorrhages have to be stabilized. But you can see, this is a lot of scans, and it's a pretty busy addition to most practices.

 

[00:20:40]

 

American Society for Neuroradiology

 

There are some really important guidelines. There's a lot of technical information on this slide. You don't need to try to remember this, but the most important thing to know is that you have to perform the scans consistently, and there are guidelines you can go to make sure that you're doing the scan correctly.

 

If you go to the AFNR website, for example, it'll give you linkouts, and you can actually download the protocols for Siemens, GE, and Philips scanners, for example, so you don't have to build this from scratch yourself.

 

[00:21:17]

 

Management of ARIA with ATTs

 

Now, this is another complicated slide. The key here is, you can see it starts at the top, ARIA-E or H detected.

 

So that's the MRI finding. So if we see it on the MRI, the next step that happens is the correlation for symptoms. So whenever I see a positive case for ARIA, if it's new or if it's getting worse, I have to call that referring physician's office so that they can get in touch with the patient and assess if they're having symptoms or not.

 

You can see, if they're having symptoms, they go down one side of this tree. If they're asymptomatic, then it's going to depend upon how severe the findings are on the MRI, and there's a standardized grading scale, and we'll go through this during the webinar because the radiologist needs to apply the correct grading scale to the images. And mild, moderate, and severe here is not just, oh, it looks pretty bad to me. There's an actual standardized scale that's being used across all of these therapies.

 

And you can see, depending upon the grading scale on the images and the symptoms of the patient, there are different management decisions that have to be made.

 

[00:22:41]

 

Baseline and Monitoring MRIs

 

So what is this grading scale and how does it work?

 

[00:22:46]

 

Case 1: Eligibility (Baseline)

 

So we'll take you through it in terms of going through cases. So the first patient case I'm going to talk to you about is an 83-year-old woman. She was complaining of memory loss. She lived alone in a freestanding house, cooks, does her own shopping and laundry, and she had two different standardized tests that were performed. We had a Mini-Mental Status Exam, or MMSE, and her score was 27 out of 30, so that's a pretty good score. And then she also had a clinical dementia rating, or CDR, which was 0.5, which is the lowest score you can have that's abnormal. So very, very early in terms of those test scores.

 

The reason it has the information about living alone and independently is that's actually a component of the CDR, is what sorts of activities is this person able to do in their daily life. And the goal of therapy for a lot of these families is maintaining independence. So she's somebody who's currently living independently.

 

The other features that are important are, are they taking anticoagulants or antiplatelets, because we know we're going to be worried about hemorrhages later on, as well as the ApoE genotype. So ApoE, as I mentioned before, ApoE4 gives you a higher risk of ARIA, and in some places, including in the Veterans Administration system in the United States, if you're a double carrier of ApoE4, you're not eligible for these therapies because of the increased risk of the vascular amyloid.

 

These are images from a PET scan that was done at a hospital and shared with us. And if you see, this is an example of a positive amyloid PET scan. We can see there's very little uptake in the cerebellar Cortechs, but then a lot of uptake in the white matter and in the gray matter. And so this would be a positive amyloid PET scan.

 

[00:25:06]

 

Case 1: Baseline MRI

 

This is her brain MRI. And I know in our institution, we do a baseline MRI at 3 Tesla, and we include a volumetric analysis.

 

And in this case, you can see that her brain MRI is basically very normal with the exception of the temporal lobes and hippocampi, which are small.

 

[00:25:33]

 

Case 1: Baseline MRI

 

We also have her baseline MRI images, and she does not have any microhemorrhages. We perform both the SWI and the GRE/T2* at our institution.

 

Clinical trials were performed with the T2*. The SWI has, in most cases, more sensitivity for small microhemorrhages. And so we've chosen to do both of those because the neurologists in our practice want to know about the maximum number of findings that there are. But the inclusion of the T2* helps them calibrate what we're seeing to what we know about from clinical trials.

 

On the FLAIR images, you can see that we have essentially a very close to normal FLAIR examination. So maybe some mild white matter hyperintensities, but not severe and no signs of a prior infarct or other abnormality.

 

So important things that we want to report on the baseline MRI are no microhemorrhages, no cirrhosis, no infarcts, no other structural abnormalities.

 

[00:26:48]

 

Question 2

 

So we'll go on to question number two. So would you report this patient is eligible for therapy?

 

And I'm going to click again just so you guys can see the images while we talk through this. So your choices are:

 

1. No, his patient is not eligible for therapy because the MRI is normal;
2. No, they're not eligible for therapy because they have superficial sclerosis;
3. No, they would not be eligible because they have brain edema;
4. No, they would not be eligible because they have something that looks like CAA-related inflammation;
5. Yes, the MRI findings would make them eligible for therapy.

 

Now I'll give you guys a chance to put in your answers.

 

Okay. And here are the responses. So Dr. Lovblad, would you like to talk about the answers that we're seeing here?

 

Dr. Lovblad: Yes, indeed. So from what we see from the answers is that most people answered actually yes. Overall, there was 21%. No, I mean, it was the biggest percentage, 21 out of 45 participants answered yes. So they would report that this patient is eligible with therapy. Whereas 11 answered no, this is a normal MRI without atrophy, indicating AD.

 

No, due to superficial sclerosis was four participants answered that. No, due to edema was given by two participants and seven participants answered no, due to cerebral amyloid angiopathy-related inflammation. So the answer that got most results was no, was the last one.

 

Dr. Benzinger: Right, yeah, the last one. Yeah, I think that first question is a little bit tricky because I think we're so used to thinking about Alzheimer's, MRIs as having a lot of atrophy. So we see a scan like this, we think, oh, no, they can't have Alzheimer's disease. This looks too normal. But in fact, these therapies are targeting such an early stage of disease that it really should just have minor changes. Yeah, it's so surprising.

 

Dr. Lovblad: Yeah, that's right, and this is a new paradigm for us radiologists, like you say, to see Alzheimer's looking a little bit different from what we're used to because it's very early on.

 

Dr. Benzinger: Okay, let us, we're going to go through now.

 

[00:29:58]

 

Case 1

 

So this patient has started some therapy and these are images that we're getting coming up to an infusion. The top row is the current exam, the bottom row is her prior exam.

 

I know these images are small, but this is kind of to mimic a little bit what happens when you're in the reading room and you have a lot of cases and you're going quickly. You might miss some subtle findings. So I'm just going to sit here for a moment before I click on the magical red arrow.

 

Okay, so now you've got the arrow sign, which doesn't come with cases in real life, right?

 

[00:30:38]

 

Question 3

 

So we have a question and I'm going to let you see the image again. So, would you report, would you report on ARIA-E for this patient? And your choices are:

 

1. No, this is a normal MRI;
2. Yes, mild ARIA-E;
3. Yes, moderate; or
4. Yes, severe.

 

Okay, so Dr. Lovblad, do you want to walk them through this one as well?

 

Dr. Lovblad: Yes, I will. So what we can agree on, if you look, if you compare with the prior examination, which is in the lower row, is that of course, no, the MRI is normal. We agree that, especially with the help of the arrows, we see that there is ARIA both frontally and in the occipital region.

 

So, I mean, it is not normal and everybody agreed on that. But when we look at the staging of the ARIAs, we see that 69% of the participants graded this as mild ARIA, whereas 31% graded it as moderate. Where also everybody agrees is that it's not severe.

 

So, I mean, everybody agrees that the MRI is abnormal, it's not normal, and they also agree that it's not severe. Then there is some discussion about is it mild or moderate?

 

Dr. Benzinger: Yeah, and this is the tricky thing with them because, you know, it looks overall, we might say, oh, it looks mild. But in fact, if you have two separate regions of the brain, in this case, frontal and occipital, automatically it becomes moderate according to the grading classification.

 

[00:33:02]

 

Case 1

 

All right, and now we have another image for this one.

 

So, and again, we have the nice arrow sign on it. So on susceptibility-weighted imaging, we're looking in the same places that had ARIA-E. And we can see there are three microhemorrhages in the right frontal lobe and one microhemorrhage in the right occipital lobe.

 

[00:33:32]

 

Question 4

 

And so would we report this as ARIA-H? And I'm going to let you guys do your poll, and you can look at the image. And the questions are:

 

1. No, it's normal;
2. Yes, it's mild;
3. Yes, it's moderate for microhemorrhage; or
4. Yes, it's mild; or
5. Moderate for siderosis.

 

And this is quite a common finding, is that we will see the hemorrhages in the same regions as the edema. And sometimes it's easier to spot the edema, and sometimes it's easier to spot the hemorrhages, actually.

 

Dr. Lovblad: So if we now look at the answers we get, we get one answer that says the MRI is normal, surprisingly. Okay, that can happen, but yeah. Then everybody agrees that it is not moderate siderosis, but most people do agree that this patient has ARIA-H. Most people classified it as a moderate microhemorrhage, it's 70%. Mild was staged by nine participants, and mild microhemorrhage and mild siderosis was staged by three participants.

 

[00:35:18]

 

Case 1

 

Dr. Benzinger: So this will probably help our audience quite a bit. So we'll introduce to you, now that you've seen a case and you've seen how confusing it can be to apply the scale, again, the scale is not necessarily what you might think. So in this case, there were only four new microhemorrhages, so it's still just mild, even though it might have looked bad since they're in two different parts of the brain. And then the reverse is true, is that on FLAIR, it was moderate, even though they were small regions, because it was two different regions.

 

So for ARIA-E, the grading is mild, is if it's a single region, less than five cm. Moderate, if it's two or more regions, or if you have any regions, they can't be more than 10 cm. And then to be severe, it actually is pretty bad. It has to be 10 cm to get to severe ARIA-E.

 

And then the microhemorrhages, it's basically just the count, and it doesn't matter if they're clustered or in multiple different regions, it's just the number. So once you get to five microhemorrhages, you go to moderate, and when you get to 10, you go to severe.

 

Siderosis, which is a sign that someone has had a small subarachnoid hemorrhage, this has a much tighter grading scale. So one is mild, two is moderate, and if you have three or more, you're automatically into the severe category.

 

[00:37:08]

 

So in this case, we have a really nice example of moderate ARIA-E, mild ARIA-H, with the findings both occurring in the same regions as each other.

 

[00:37:24]

 

Question 5

 

Question five. So what's recommended for management when this happens? So patient has, we're going to say if they're on donanemab, and they have this finding. Now, in this case, it probably depends on what your role is in the hospital system, because I would say if you're a radiologist, your main thing is going to be to call somebody else and tell them these findings so they can do it. But if you're the clinician on this case, what would you do? Would you:

 

1. Continue treatment, suspending if there are symptoms;
2. Continuing treatment with more monitoring;
3. Reducing doses;
4. Suspending treatment; or
5. Discontinuing treatment permanently.

 

All right, and I'll let Dr. Lovblad walk you through this and the slides.

 

Dr. Lovblad: Yes, so here the answers are much more spread out between all the answers. So what would you recommend as clinical management? Most people think one should suspend treatment, may resume treatment if resolved on follow-up MRI. That was in 33% of cases, whereas only 2% would discontinue treatment permanently. However, 26% believe one may continue treatment as usual with increased frequency or MRI monitoring. 24% say to reduce dose for next infusion, perform follow-up MRI before the following infusion. And 14% believe one may continue treatment as usual with clinical monitoring and suspend if symptoms develop.

 

Dr. Benzinger: Yes, so we have kind of a wide range of choices here. The key here is, you know, it's a combination. There's a scoring for severity on the MRI, and there's a scoring for the clinical symptoms.

 

[00:39:56]

 

Case 1: Clinical Management of ARIA With ATTs

 

So, you know, we decided this was mild ARIA-H, so we're in the first column on the chart, and it really is going to depend upon whether this patient is having symptoms, whether they need to suspend the dosing or not. Definitely, though, what we'll recommend from the radiology standpoint is they do need to get a follow-up MRI to make sure that these findings, we expect that the ARIA-E will resolve over time. We expect that those hemorrhages should stabilize and not see new ones. And if we're still seeing new hemorrhages, we need to keep checking with MRI.

 

[00:40:40]

 

Case 1: Summary

 

Okay, so just some take-home messages from this. So this patient did have one ApoE4 allele, so we know that they're going to be at higher risk for ARIA than the general population.

 

This is a great example of how, you know, these scoring systems are not necessarily intuitive for the radiologist. What we think of as mild or moderate or severe, we really have to follow the standardized grading system. And this case really emphasizes why. It's because that drives the clinical management as well. So if we, as radiologists, don't grade it correctly, then the actions that the neurologists take could have a mistake that happens. It does help for radiology to talk about recommending that they get that follow-up scan, because I have seen patients that they'll pause the therapy and they'll stop getting scans, but they are still at risk for progression even when the therapy pauses. So it's important for us to remember to recommend that scan.

 

In this case, the patient did not have symptoms, but the clinical team decided to hold the infusion anyway because it was in two separate areas and both of those had hemorrhages with it. So there is leeway on the clinical side to be more cautious than what the labels say.

 

Dr. Lovblad: Yes, indeed. Therapy has to be adapted on a case-by-case basis. That's very important.

 

[00:42:22]

 

Case 2: Eligibility (Baseline)

 

Dr. Benzinger: Yeah. Okay. So now I've got everyone scared because those are subtle findings in a hard grading system. Let's try another case. Hopefully this one will be a little more straightforward.

 

So we're going to start again with eligibility. This is a 74-year-old male. He complains of gradual onset memory loss, lives at home with a spouse, does home repairs, just installed a new thermostat, drives his car independently. His Mini-Mental Status was 23 out of 30, so a little bit lower, but still in the reasonable range for therapy. His CDR is 0.5. So again, that very low score, which would be ideal candidates for therapy. He does not take any anticoagulants, but he is taking aspirin, 81 mg a day. He is also an ApoE3/4 carrier, so he has one ApoE4 allele. And he did have an amyloid PET scan with 4-beta-pure, and this is another example of a positive amyloid PET scan with uptake in the Cortechs in general and sparing in the cerebellum.

 

So, you know, key clinical factors here is that he is living very independently right now. His symptoms are mild. He's biomarker-positive for amyloid. These are amyloid drugs, so you need to have biomarker positivity of some type. He has a little bit elevated risk for ARIA because of that one ApoE4 allele. And then antiplatelets. So in the U.S., taking aspirin is allowed when you go on these therapies.

 

[00:44:12]

 

Case 2: Baseline MRI

 

Let's take a look at his brain MRI. So, again, another case where the brain MRI is looking almost normal.

 

You can see that his brain volumetrics are normal. The hippocampal volumes are actually better than normal. He's not having hippocampal atrophy. Someone astute in the audience may notice that he's had a burr hole in the past, so we would definitely want to try to figure out why he had a craniotomy and what was going on with that.

 

[00:44:49]

 

And then here's example images from his MRI. Again, FLAIR, susceptibility, and a GRE/T2*. So these were all really good-looking images.

 

[00:45:04]

 

Case 2: Monitoring

 

So he did start the therapy, and now I'm doing the same thing that I did to you last time where I'm showing you a lot of images, and the findings that you're looking for are a little bit small, but hopefully you've had a chance before I blow it up. Ready, guys?

 

[00:45:28]

 

Okay. Now you can see the findings. So I'm going to go back one again just so you can see how hard it can be to see those findings.

 

[00:45:42]

 

So we're looking at the middle row, and unless you're comparing it to the prior study or comparing it side to side, left, right, you could easily overlook these findings.

 

[00:46:00]

 

Case 2: ARIA MRI Classification Criteria (PI)

 

Okay, so here is our ARIA classification, and it looks like we're not going to have a question pop up for this one. So to the audience, we have a single region, but it's over 9 cm in size on FLAIR, and if you look carefully, you'll see the effacement of the sulci and even some small sulcal effusions.

 

Those same ARIA regions that have the sulcal effusions, you can see have that drop loss of signal on susceptibility, so a little bit of cirrhosis starting.

 

[00:46:46]

 

So the FLAIR is only moderate because it's less than 10 cm, but we had three different cirrhosis findings, so that puts us over to the severe on the cirrhosis.

 

[00:47:04]

 

Case 2: ARIA-E Effusion on Head CT

 

Okay, and then I wanted to show you this.

 

You get a head CT. I'll admit you do not need to get a head CT when you see these findings. So this was a case that went out to one of our general radiologists who didn't have the education and background to understand ARIA, and in fact, they saw the cirrhosis and they saw the sulcal effusions, and they said, oh, this patient could have a subarachnoid hemorrhage. Let's get a head CT.

 

So you don't need to get a head CT when you see this finding. You need to recognize that this is actually a classic presentation for ARIA, and what you need to do is call the referring provider so that they can check for symptoms, and you need to apply the grading scale so that they can have the right management.

 

But if you look carefully, you can see on that head CT, if you look really carefully, you'll see that that same sulcal effusion is showing up as just a little bit of gray area in the sulcus on the head CT as well.

 

Dr. Lovblad: Yes, that's right. But this is also an important point that sometimes CT, if the blood is not entirely fresh, which might be the case here, you may not see it as well on a CT as on the combined MR sequences, and this is very important.

 

Dr. Benzinger: Yes, yes, really important to know. And in fact, so if the patient shows up in the emergency room with a headache or other symptoms of ARIA, a lot of ERs are not set up to perform MRI, but if you just got the head CT, you would miss the finding. So it's important to understand that the exam they need is the MRI.

 

[00:49:00]

 

Case 2: Lessons Learned

 

Yes. Okay, so lessons learned is this is what ARIA looks like, and you may not always have the right history when the patient comes to you, but you need to be thinking about it now in all of our older patients because Alzheimer's disease is very common. And then the second lesson is you don't need a head CT or a CTA.

 

In our system, we have built out nice templates for reporting these examinations that come up automatically for us so that if you could just click three for siderosis, it'll say severe ARIA-H. You don't have to memorize it. But if you modify the template or load the wrong template, then you'll come to the wrong conclusion.

 

So just a lesson that we've learned with that case as well.

 

[00:50:00]

 

AI-Assisted Tools

 

All right. Our next section is talking about AI-assisted tools.

 

[00:50:06]

 

AI-Assisted Neuroimaging for ARIA Detection

 

So these are available in a lot of places. There are a couple of them in the United States, one from Icometrix and one from Cortechs that have FDA clearance. These can help people with identifying subtle features.

 

So they are looking at they're requiring two different exams, and they can find the changes from the baseline or from the prior examination. And a lot of groups are using this and are finding it to be really helpful at picking up the subtle findings. Caveat being you can also potentially have more false positives with it or introduce additional QC questions that you're going to have to follow up with.

 

So they can't replace the radiologists, but it can certainly be a tool for many radiology groups.

 

[00:51:00]

 

AI-Assisted Neuroimaging for ARIA Detection

 

So, yes, it can help with standardization and inter-reader variability. They did have training data sets from clinical trials, but, again, the caveats could be some false positives. And essentially, when these are in use, it's recommended that you still need this independent review by a radiologist as well as a final interpretation by a radiologist.

 

[00:51:34]

 

Workflows and Severity Scoring

 

Okay, so getting into the workflows and the severity scoring.

 

[00:51:40]

 

Case 3: Monitoring

 

So this is another case, a new patient, also on therapy.

 

I'll give you a second to look at three different visits for this patient. So as with the other cases, we have a FLAIR, an SWI, and a GRE/T2*. I'm giving you a second because since we're in an ARIA webinar, you're probably thinking there must be ARIA somewhere, but it's pretty subtle.

 

[00:52:14]

 

So if we start with the one, the image on the bottom. So what happened here is in the left frontal lobe, there's some really subtle darkness or loss of signal, which, if you go back, is new compared to the baseline.

 

[00:52:39]

 

And if you look carefully, it actually was associated with a very subtle effusion and edema on that middle visit.

 

So on the middle visit, he had ARIA-E on the monitoring, but we missed it. And on the follow-up visit, he develops the siderosis at the same location, and that's when we see it, and that's when we go back and we can detect the subtle finding on the prior one.

 

[00:53:12]

 

Case 3: ARIA MRI Classification Criteria (PI)

 

So in this case, he had mild ARIA-E on the prior visit and now mild ARIA-H as well.

 

[00:53:40]

 

Case 3: Lessons Learned

 

Okay, so this is the kind of thing that will happen in your clinical practice, is that you may have cases where you see something in retrospect, and then it is important to go back to the clinical team and talk to them about these findings, because it does put this patient at risk for developing additional episodes in the future. It also is really important to always, because sometimes the changes are subtle over time, make sure, even if you have five or six time points that you're looking at, look not just at your most recent prior, but pull up the third time point, which was the baseline. I think about this the same way I think about a low-grade glioma, for example, where it's changing just a little bit each visit, and sometimes you don't even notice how much it's changed unless you've pulled up that baseline image again for the comparison.

 

And also, you know, the prior radiologist called it normal. That doesn't mean it was normal. You better make sure that you look at it carefully yourself.

 

As we said earlier in the presentation, you should be seeing a positive case about one in every five scans that you read. So if you're not seeing it, you're probably missing it, and it can be subtle.

 

[00:55:10]

 

Case 4: Monitoring

 

Okay. So here we go again. Let you guys take a look. Another case for monitoring. It does have tiny purple arrows.

 

[00:55:36]

 

Okay. So we'll zoom in. And again, it's this nice example of the edema and the effusions on FLAIR having the similar findings on SWI for the siderosis. So, again, the two findings kind of come together in the same brain regions.

 

[00:56:02]

 

Case 4: ARIA MRI Classification Criteria (PI)

 

So it's going to be moderate because we had two different regions, but they're less than 10 cm each. And then it's going to be two regions of siderosis, so moderate for that as well. So, of course, our actions would be to call them, let them know we have this finding, give them the grading, put that in our report, recommend that they get a follow-up MRI to show that it's resolving, and then they'll go and correlate for symptoms and decide whether or not to alter the therapy and think under all the algorithms. So once you're in this moderate range, you would be pausing therapy.

 

[00:56:47]

 

Case 4: Lessons Learned

 

And in this one, yeah, the lessons learned were initially we missed the siderosis. So you have to go back and look carefully whenever you have edema because there probably could be microhemorrhage or siderosis hiding on the same scan.

 

[00:57:06]

 

Case 5: Monitoring

 

All right. Here's another example. We promised we would give you lots of examples. Give you guys a second.

 

[00:57:20]

 

Now I'll blow it up. So probably everybody's seeing the vasodic edema in the right frontal lobe.

 

Now the trick is there's also a little bit of signal loss happening on this susceptibility scan, and it helps a lot to have the comparison to the baseline to know that these are not just veins in that area, but this was a change as well.

 

[00:57:52]

 

Case 5: ARIA MRI Classification Criteria (PI)

 

So mild ARIA-E, moderate ARIA-H, phone call, correlation for symptoms, recommend a follow-up scan.

 

[00:58:07]

 

Case 5: ARIA is not easily identified on a head CT and CTA are NOT indicated

 

And again, another example where we have a head CT for correspondence.

 

You can't see it really. You know, I struggled. I thought for sure maybe we would see some of the edema over on the head CT, but you really can't find it.

 

So getting a head CT instead is not a good idea. I'll stick with MRI.

 

[00:58:37]

 

Case 5: Lessons Learned

 

All right. And this was another one where a couple of the findings were missed by the original radiologist. They saw the edema but didn't know that that meant it was ARIA.

 

[00:58:56]

 

Case 6

 

Okay. Here is another case. So this is a patient coming into the emergency department after a motor vehicle collision. They're from out of town. We don't have their medical records. They're visiting their family. And here is the head CT that we have here.

 

So multifocal vasogenic edema, some focal hyperdensities concerning for hemorrhage as well.

 

[00:59:32]

 

Case 6: What is the differential diagnosis?

 

We get brain MRI. It does not have diffusion restriction. So we do always include diffusion in these protocols because the symptoms of stroke and the edema findings, a lot of findings can overlap with stroke. So that's why we include diffusion. Diffusion should be negative.

 

Here we see this large area of vasogenic edema, the right temporal lobe, right occipital lobe, and multiple micro hemorrhages. So now we need to have a differential diagnosis. We're seeing this patient in the ER. We're thinking, oh, I know we're in the ARIA seminar. Maybe he's getting therapy. Maybe he had trauma.

 

[01:00:21]

 

But in this case, it's actually cerebral amyloid angiopathy. And so I threw this case in just to remind you that if you see something that looks like ARIA, but they're not on therapy, you can definitely be thinking about CAA as an alternative diagnosis. And that's actually what this patient has.

 

And it's just a reminder of this kind of shared mechanism that we think about between CAA and ARIA being the vascular amyloid depositions that are responsible for a lot of the features that we're seeing.

 

[01:01:02]

 

Case 7: Monitoring

 

Okay, I think we have one more case. All right, so same setup, three different visits, baseline monitoring, and follow-up.

 

I gave you guys a minute to try to think about the findings.

 

[01:01:23]

 

I'll blow it up for you. So once again, we have the vasogenic edema and socal effusions, and then findings on our susceptibility-weighted imaging scan, and very subtle on the GRE/T2* as well.

 

So this is somebody who's on therapy.

 

[01:01:52]

 

Case 7: ARIA MRI Classification Criteria (PI)

 

So same idea, mild ARIA-E, moderate ARIA-H because of two siderosis.

 

[01:02:06]

 

Case 7: Monitoring

 

Now, there was another feature that shows up then on another MRI, and that is this left centrum semi valley.

 

We can see there's a lesion that has FLAIR hyperintensity but suppresses centrally. That is not the place where he was having ARIA.

 

[01:02:34]

 

And in fact, if we go back to one of his other visits, what we can see is that when he developed that FLAIR hyperintensity, it had diffusion restriction. So ARIA and infarct have a lot of overlapping features.

 

When we look at something like FLAIR, they can look alike, but ARIA does not have diffusion restriction, and ARIA, the edema, when it goes away, it resolves. So in this case, he had both findings.

 

[01:03:16]

 

So let me just go back for you guys to try to help you see it.

 

[01:03:28]

 

Okay. I just went back so we could talk about it a little bit more. So if you look at the middle row, when he has that right occipital FLAIR hyperintensity, and that's where he gets the siderosis, that goes away on the follow-up visit.

 

But then you see that finding in the left periventricular white matter, that's where he had the infarct on a different visit. And it's just a warning that you have to watch for both of these things, and an infarct is not ARIA, but it needs to get worked up just as you would any other incidental stroke.

 

[01:04:16]

 

And then the last thing I wanted to show you on this case is if we go back to his baseline at the very beginning, he actually has one area of superficial siderosis back there, and this is the same place where he develops ARIA later on.

 

So it's really important when you read that baseline MRI to comment on whether or not you see the superficial siderosis. And when you're monitoring the patients, places where they've had some sort of prior siderosis are a really good place to look for subtle findings of new ARIA as well.

 

[01:05:04]

 

Case 7: Lessons Learned

 

Okay. So some findings here. So this is just showing you the baseline siderosis and then the new ARIA-E and ARIA-H. So baseline siderosis is very predictive of future ARIA.

 

[01:05:22]

 

Second important lesson is that ARIA-E resolves on FLAIR, but an infarct does not. So always be thinking about other pathologies that these patients can have. These are real-life patients.

 

Very common for Alzheimer's disease and vascular dementia to coexist, and most of the patients in my practice, and I'm sure in yours as well, have a lot of comorbidities, a lot of medical problems.

 

All right. So that's it with the challenging cases, and I'm going to hand the program over to Dr. Loveblad.

 

[01:06:00]

 

European Protocols

 

Dr. Lovblad: Thank you very much, and I will try to follow up this wonderful presentation about ARIA imaging and really good illustrated cases you showed us by discussing a little bit what we're starting to do in Europe, because treatment was initiated in the United States somewhat earlier.

 

[01:06:24]

 

EMA Authorizations of Antiamyloid Therapies

 

So the EMA has authorized some anti-amyloid therapies now. The first ones to have been authorized in Europe have been lecanemab in May 2025 and donanemab in October 2025.

 

As of today in Switzerland, donanemab was authorized this week only, and we're still waiting for further drugs. And so we're really at the start here. So, I mean, we're also very happy to gain all the experience that you have already acquired through these kinds of presentations.

 

As for the indications, they are basically the same as in the United States. It's going to be patients who have MCI or mild dementia due to Alzheimer's disease with confirmed amyloid pathology. What's a little bit different from the United States is that, at least for now, it is only going to take into account ApoE4 non-carriers or heterozygotes.

 

This is a way of a little bit narrowing down the number of patients, at least for the start. And the monitoring schedule is basically also the same as the United States. And much of the work we have done also in the various societies has been based on the American recommendation.

 

[01:08:08]

 

Management of ARIA With ATTs

 

So, again, if we see the slide that we already saw before, it is important to perform, first of all, a baseline scan and then to do follow-ups that are going to be done technically in pretty much the same way. And that's quite important. It should ideally be done on the same scanner at the same field strength.

 

That might not always be possible because sometimes patients are going to go to other clinics or hospitals than the place where they actually were initially treated. But as much standardization as possible should be done because, as we saw during the presentation before, it's very important very often to be able to look back at the previous image files. And if they are slightly different, it might be somewhat difficult even for people who are trained.

 

So, you're going to be looking for ARIA-E edema or ARIA-H. And in order to do that, as we saw, you will do FLAIR for edema and some type of SWI T2* images for hemorrhage. And you're going to deal with the patients differently according to if they're symptomatic or asymptomatic in order to classify them and to see if you can either resume treatment or if you have to simply stop treatment or even continue with clinical monitoring and monthly MRI, as we discussed before.

 

[01:09:56]

 

Swiss Society for Neuroradiology

 

So, if we look at our recommendations from the Swiss Society that are pretty close to or almost identical to the ones that are proposed by the American Society of Neuroradiology, in order to detect the microhemorrhages, one has to do gradient echo and SWI images like we saw before. Having them both is really helpful. You will do also diffusion-weighted imaging in order to see if there is a suspicion of stroke or not or anything else.

 

Diffusion imaging is extremely helpful in detecting other pathologies that might also be causing symptoms when the patients come in urgently. And then, of course, FLAIR imaging in order to look for the presence of hyperintensities that are going to be either in the white matter or also infarcts that might be older and not necessarily detected by diffusion-weighted imaging. The communication is going to be, in the first-line, standard reporting for the baseline and then, of course, on the follow-ups, it's going to be slightly different if we have asymptomatic patients or symptomatic patients.

 

Because in asymptomatic patients, we will not do IV contrast like we did not do at baseline, but if they are symptomatic, IV contrast we find may be useful and then we re-perform the combination of the four basic sequences or five, including SWI, which is diffusion, gradient echo, SWI, T2 and 3D imaging. So, we get a basic set of four to five sequences and in case of symptoms, like I said, one may add IV contrast and some additional sequences. And, of course, in these two settings, ARIA must be reported according to the grading that we saw before and if we have the asymptomatic patients, we will have a closed-loop communication.

 

Of course, like we also discussed or as we said before, even though we want everything to be standard and repeated in a very strict way, all patients, as is the case for any disease, will have to be handled in a case-by-case way. Meaning that some adaptations may be necessary if, for example, in one patient, like we saw before, maybe the clinicians feel a little bit more cautious and want to stop therapy for a short period in order to resume a little bit later on. So, a certain flexibility is still to be had, even though when it comes to building up the protocols, the same sequences have to be used.

 

And, as was said during the presentation before, the American Society of Neuroradiology has done a great job in that paper where there's those lists of protocols and sequences for the various manufacturers. And I, again, encourage everybody to look at that. And as you can see, the protocols are rather simple.

 

One reason is also because we're expecting to have quite a big additional workload, so we cannot come up also with huge protocols for these patients. And that's why, at least in Switzerland, we decided to keep it rather short, as also was the case in the United States, if I'm not wrong.

 

[01:13:56]

 

Updated Guidelines and Resources for Dementia Imaging

 

And you will find those guidelines and resources for dementia imaging on various websites.

 

Here you have the QR codes for the Alzheimer's Association, Society for Nuclear Medicine and Molecular Imaging, have some recommendations. Of course, there are the excellent recommendations of the ASNR from 2022 and the more recent ones from 2025, as those from the American College of Radiology from 2024. And there is the European consensus for the diagnosis of MCI and early AD by the European Society of Neuroradiology and the European Association of Nuclear Medicine from 2023.

 

And also, there is a site for the treatment-related clearance Alzheimer's and dementia from 2025. And finally, the recommendations of our society, the Swiss Society for Neuroradiology, that were published this month. And based on this, it is possible for most people to gain a lot of at least basic knowledge about the way that imaging should be done and in what setting.

 

And I recommend everybody should look into those various papers in order to complement what we have seen and heard here today.

 

[01:15:26]

 

Acknowledgements

 

And of course, what's very important to know is that all this cannot be done without the help of patients, research participants and also faculty, staff and students in the various institutions that you see here and also all over the world. Because this has been a long journey. I mean, we have been waiting for treatments for Alzheimer's disease almost since I was in medical school. They always said it's in the pipeline. I remember back then and now it's here. So, it's a revolution actually. And what's also important is that radiology has a very important role. That was maybe a little bit unexpected a few years ago when all we did were PET CTs to see advanced Alzheimer's.

 

But now we see that we have to do many examinations in order to perform monitoring of the disease. And I think this is a big challenge for the whole radiological community to be able to absorb this and to help patients and referring clinicians.

 

[01:16:42]

 

What Do You Remember?

 

Nicola Hanson: All right. Well, I will take back over here. Thank you.

 

Thank you very much to both of you. And first, before we do the posttest, let me address a few questions about materials that have been coming in. So, you can download these slides right now if you go to the Resources button at the bottom of the Zoom.

 

You can download this slide set and that will include the QR codes to all the guidelines that were just shown a couple slides ago. There will be an on-demand video of this recording. This will be on the Decera website probably a week or 10 days from now. And then sometime following that, we are also going to create a text module based on this training. So, a detailed slide-by-slide explanation. So, please look out for that in the future.

 

So, now the posttest. So, what do you remember? These would be the same questions that you answered earlier in the presentation. So, let's see if you remember the answer.

 

[01:17:38]

 

Question 1

 

Number one. Approximately what percentage of patients treated with amyloid-targeting therapies do you expect to have asymptomatic ARIA detected by routine MRI monitoring? Is it:

 

1. 2%;
2. 5%;
3. 10%;
4. 20%; or
5. 30%.

 

Please answer. All right. And I see we've got the majority of you have answered correctly this time.

 

[01:18:20]

 

The answer is 20%. There you can go. You see the two pivotal trials of these therapies found about 25% and 18%, respectively.

 

[01:18:34]

 

Question 2

 

Next question. And I'll show you the image that goes along with this in just a second. Would you report that this patient is eligible for treatment with amyloid-targeting therapy?

 

[01:18:44]

 

Here you can see the scans. So, would you report eligible for treatment with amyloid-targeting therapy?

 

1. No, this a normal MRI without atrophy indicating Alzheimer's disease;
2. No, not eligible because of superficial sclerosis;
3. No, not eligible because of edema;
4. No, not eligible due to cerebral amyloid angiopathy-related inflammation; or
5. Yes, this patient is eligible for treatment.

 

Please vote.

 

All right. Here comes the answer. And very good. Almost everybody remembered this patient with these scans is eligible.

 

Next.

 

[01:19:35]

 

Oh, here. And you showed the answer that this MRI does show atrophy characteristic of early Alzheimer's disease and does not show any findings that would exclude them from this treatment.

 

[01:19:46]

 

Question 3

 

Question number three. Would you report ARIA-E for this patient shown in these scans?

 

1. No, this is a normal MRI;
2. Yes, mild ARIA-E;
3. Yes, moderate; or
4. Yes, severe.

 

Please vote.

 

All right. And again, the majority of you got this correct.

 

[01:20:29]

 

This is a moderate ARIA-E. It is moderate, if you see the guidelines below, because it is a single site between 5-10 cm in this case.

 

[01:20:44]

 

Question 4

 

Question number four. For this patient, would you report ARIA-H?

 

1. No, this is a normal MRI;
2. Yes, this is a mild microhemorrhage;
3. Yes, this is a moderate microhemorrhage;
4. Yes, this is a mild cirrhosis; or
5. Yes, this is a moderate cirrhosis.

 

Please vote. All right. Again, about half of you remembered that this one.

 

[01:21:34]

 

This one is a mild microhemorrhage, shown by the guidelines, because it is four or fewer new incident microhemorrhages.

 

[01:21:44]

 

Question 5

 

And then our last posttest question. No image for this one, but what would you recommend as clinical management for a patient treated with donanemab if moderate-grade ARIA-E and mild-grade ARIA-H microhemorrhage were found on routine monitoring? So these would be asymptomatic.

 

1. May continue treatment as usual with clinical monitoring and suspend treatment if symptoms develop;
2. May continue treatment as usual but with increased frequency of MRI monitoring;
3. Reduce dose for the next infusion and perform follow-up MRI before the following infusion;
4. Suspend treatment, but you may resume treatment if this is resolved on follow-up MRI; or
5. Discontinue treatment permanently.

 

Please vote.

 

[01:22:52]

 

All right. And in this case, the answer is D, as we covered.

 

You should suspend treatment and may resume treatment when these are resolved on a follow-up MRI for ARIA of this grade.

 

Thank You!

 

Question and Answer Session

 

So we come then to the question-and-answer session. And I see that there have already been a few questions that have come into the chat box.

 

So please submit your questions if you have any more that you'd like our faculty to answer live. And I'd like to start with either of you. Do either of you have any experience with the Icometrix or Cortechs products or any AI assistant?

 

Dr. Benzinger: We do not use that at our institution. I did show you the examples. We do the volumetric analysis at baseline, but we don't have access to the ARIA monitoring software right now.

 

Dr. Lovblad: We have other software provided by the manufacturer that either count microbleeds or that also do baseline volumetrics, but we don't use those products also.

 

Nicola Hanson: Okay. And then if we could just reiterate so that everybody can – the questions that already came in. There are a couple of questions about distinction between GRE and SWR. Could you go into a little more detail about that?

 

Dr. Benzinger: Yeah. And I just want to say I'm very pleased and relieved at how well everyone did on the posttest because these were really subtle cases, and I was starting to get worried that maybe we were going to lose all of you in the subtlety of it. So hopefully we've now given you at least a glimpse of what are the subtle findings that you need to try to look for.

 

And you can see how we all get a little bit confused when it comes to, like, the grading scale and how to use it. This is why I really recommend you build yourself some solid reporting templates so that, as a radiologist, all you have to do is make the finding, and then if you click in your reporting template the number of microhemorrhages, it can come back and give you the grading scale. So just one less thing you have to keep in your mind.

 

This question next of the SWI versus the T2*, it comes up in every single conversation with radiologists about this. Then the other thing related to this that I didn't hear in this call, but I'll go ahead and say it out loud, is the field strength, 1.5 versus 3 Tesla. And, you know, to people who aren't in our specialty, it can be pretty simple to just say, oh, 3 Tesla SWI is always the best.

 

But those of us in neuroradiology actually know pretty well, if I take my oldest 3 Tesla scanner and my newest 1.5T scanner, I can usually get better images of the brain out of that new 1.5T because of improvements in gradients and coils and software, you know, just the pulse sequences that we have. So it's not always clear that one is better or not. The most important thing, in my experience, has been consistency, that you're performing the protocols the same way.

 

If you have the luxury of being able to have a patient stay at a single scanner the whole time, you're going to have the best result. But most of us don't practice in that kind of a setting. You know, within my hospital system, we have 60 MRI scanners, and our patients live geographically spread out over a 300-mile radius.

 

So, you know, I just can't manage to have them always go to the same scanner and get the same one. And so that's why I like to start out with 3T, with SWI, and GRE, because I feel like that way I'm going to have a glimpse of where are the hemorrhages, and what do they look like from the beginning, sort of what's my grounding in reality.

 

And then people will say, well, why do you still get both of them in follow-up? Well, part of that reason is because of motion. So the SWI sequence is very sensitive and able to identify small findings, but only if the patient holds still. And a patient with dementia who's on top of that having symptoms of ARIA, they're not the most able to tolerate getting the MRI exam.

 

And I have many cases I could show you where the SWI just fails entirely. But because it's fast and simple to acquire, that GRE/T2* can save the day and really help me make the findings. So that's why in our practice we choose to do both of them.

 

And by using the ASNR protocols, I've eliminated a bunch of other things from my exam. So really all I get on the monitoring is I get the FLAIR, I get the GRE and the SWI, and I get a diffusion, and that's it. I don't get T2, I don't get T1, I don't do ASL, I don't do an MRI, you know, all of these other things.

 

So my monitoring exam visit is about 10 minutes start to finish. And when I'm reading the case, those are the only images I have to look at. And I need to look at them carefully because the findings are very subtle sometimes, but it's not lost in a sea of 3,000 other images.

 

So that's the philosophy that we've used in our practice.

 

Nicola Hanson: And you raise very, very important points about in the real world, what can the patients tolerate and what are those practical considerations?

 

Dr. Lovblad: Now that's very important because that's also why we try to say you should at the most do four or five sequences. Because it's a question of time and of the patients being able to tolerate it. Because like you said, these patients, they will maybe not be able to be in the scanner for 30 minutes or so.

 

So keeping it as short as possible. And basically, like you say, if everything goes wrong, you need the FLAIR and the GRE, right? And the rest, well, you can live without. But time is of prime importance in these patients, really.

 

Nicola Hanson: All right. Well, we don't have any more audience questions. So Dr. Benzinger, Dr. Lovblad, before we close, were there any other last points that you wanted to make or maybe just closing thoughts for our learners?

 

Dr. Benzinger: Well, it's just it is really exciting to finally be at this time when patients are getting treatment. And as Dr. Lovblad said earlier, just amazing that radiology is so central to this patient care. So it's really an honor and a privilege to be able to participate this way in this patient journey.

 

Dr. Lovblad: Yes, I think it's completely exciting and it's going to be a revolution, of course, first for the patients, but also for us. And it means that we're going to have this new flow of patients that we have to handle also. And that's why I agree with you, it's not always possible to manage them on the same scanners. But here in Switzerland, what we did a little bit differently, you saw we triage a little bit by not doing as wide a population as is done in the US. And that is in order to concentrate, at least at the beginning, the patients around memory clinics.

 

And therefore, they will be close to the scanners that are related to those memory clinics. And it's not that we want to reduce availability to the population, but we want to try to make the whole start more manageable. Because we also see that there might be problems with scanner availability and things like that. Because these patients are going to need up to six, seven, eight MRIs. And we have to find those time slots.

 

But I think we will. Because we, at least in Switzerland, as in the US, we do have lots of scanners. But it's going to be a challenge. We might have to extend scanning hours or whatever, partly to accommodate these new patients.

 

Dr. Benzinger: Yeah. And this is where these build your protocols early, build the dedicated studies on the scanner, these short, focused exams. So for us, 100 patients on therapy was 1,000 new brain MRIs that we performed. And when we were at 300 patients on therapy, it was 3,000 new brain MRIs that were performed. And it just keeps scaling that way. Because everyone that goes on therapy needs six MRIs. And for every one patient that goes on therapy, there are going to be three or four more that get the baseline MRI, but then screen fail for some other eligibility. So it's a big practice implementation.

 

Dr. Lovblad: Yeah, the numbers are incredible, also taking into account the increasing age of the population, and also improved detection methods, screening methods.

 

Dr. Benzinger: Yeah. Yeah. Well, Nicole, thank you so much for having us. This has been a great conversation.

 

Nicola Hanson: Well, thank you. Thank you so much. Thank you so much for your time.

 

Dr. Lovblad: Thanks a lot. And I hope that everybody enjoyed it as much as we did. Really, it was a great time. And it was prepared really well by Dr. Benzinger and also the team who set up this webinar.

 

Thank you to everybody. And also thank you to the audience for attending.

 

Nicola Hanson: Yes. Thank you. Well, thank you. Thank you, everybody. And that will close us. Have a good rest of your day.

 

Dr. Lovblad: Yes, goodbye. Have a nice day.