Neuroimaging for Movement Disorders

[00:00:51] Cecilia Peralta: Cecilia Thank you, Michele. Thank you for the invitation having me here today. Great pleasure.

[00:00:56] Michele Matarazzo: We were saying that you have an important role. You are the vice chair of the Neuroimaging Study Group. And to disclose also this, I'm also part of the study group, so I have inside information. I know that the study group is doing a lot of different things.

So can you share with our listeners what are the major things that are happening or have happened recently?

[00:01:13] Cecilia Peralto: We have a fantastic group, and together with Thilo van Eimeren, who is the chair, we are working very hard and together with the other members of the group. I must say the group is very dynamic and is doing fantastic things. I may say we are very good at some things. We are good at bringing people together to engage in collaborative research papers and projects. We are good at writing papers and publishing, and also somehow I think we are good at mentorship. That's something very important for especially young members, because those young members are looking for opportunities to join a group to write a paper, to have some research. So that's a good group for this.

And just to reflect on that, in 2022, we published a paper on pragmatic approach of new imaging techniques for the diagnosis of Parkinson's disease that was recognized as the most impactful paper in the MDCP for the term 2021-2022. That somehow we try with this paper and with a new one I'm going to tell now to cover the full spectrum of imaging in daily practice and in research, because this paper was mainly clinically orientated.

It was to make imaging techniques usable in daily practice for the general clinician, for the general practitioner, for the general neurologist. And now we are working, and we have already submitted a very beautiful and important paper. I hope to see it published soon to Movement Disorders, let's see how it works, on imaging biomarkers to image the phenoconversion from prodromal Parkinson's disease to clinically established Parkinson's disease, which is very important.

It's very timely with the times we are living. We are transitioning somehow the concepts of clinically defining diseases to biological defining diseases and neurodegenerative diseases and Parkinson's disease. Although we may criticize the use of biological term, biologically define it

Disease, but still it is a word that is representative of the times we are living.

And this paper has meant a huge amount of work because we searched the whole literature to search for imaging biomarkers that SPECT, FDG PET, synaptic density PET, and also MRI biomarkers, iron, neuromelanin, and DTI. And we tried to evaluate those imaging markers within a comparative hierarchical research framework, and we tried to evaluate each of them within some domains that were agreed upon the group in a kind of Delphi-like process, regarding predictive power, regarding timely and mechanism, regarding robustness and usability, and regarding usability in research frameworks.

And also, we graded these domains from zero to four, where zero is the lowest probability or lowest availability to detect predictive power, and four is the highest. So has been huge work, and it's a beautiful paper. We came up with a clear hierarchical organization of these biomarkers, which we think would be quite useful for research and also for advancing the field.

Advancing the field in developing disease-modifying therapies, advancing the field in detecting prodromal and phenoconversion to Parkinson's disease. And now we have another project that is to somehow replicate the same thing we did with the motor part, with the cognitive part, and to see how it goes searching all the literature looking for imaging biomarkers to predict phenoconversion to dementia.

We're still in the discussion what populations to include, if only prodromal patients, if to include MCI, if to include only established PD without MCI. Let's see how it works.

[00:05:00] Michele Matarazzo: So it definitely a very active study group and did a lot of things. So I look forward to see the paper published and, you never know, it might be another best article of the year next year, and maybe we'll have to talk again.

Now let's get a little bit outside of the study group and see what is happening in the general and broad scenario of neuroimaging in our field.

What has happened? What would you highlight as the major scientific or clinical interesting things that are happening in the field in the last year or so?

[00:05:29] Cecilia Peralto: Yeah. One of the large unmet needs is developing of synuclein PET tracers.

And there have been some papers published. And yesterday we had a beautiful session at a congress where Hitoshi Shimada, he presented some research and some data there in a tracer, which is 18F-CO505, that has shown in their research a high affinity and binding in midbrain and striatum in PD patients, DLB, and to lesser extent in MSA patients.

However, they also find some binding to amyloid and to tau. So they are trying to refine the molecule and to see whether they can obtain better results. But it's a promising alpha-synuclein marker. That is something very much needed and that connects very well to the times that we are living in the thing of transitioning from prodromal to clinical, and also connects well with a paper that you published.

As you said before, you're also a member of the Neuroimaging Study Group on multi and co-pathology. It's a very relevant concept. It's a concept that has come up also in the last few months. It's a beautiful paper that you published with a subcommittee dedicated to these scientific issues, specificity that really brings light into this important concept and make us understand that Parkinson's disease is more than a single entity.

It's more than alpha-synuclein, that there are other proteins out there and how they can interfere, let's say, in some way, in the way the patients develop symptoms and how they can produce different trajectories in disease progression. And somehow this makes our life a little bit more complicated.

But still, the other positive sign that it brings clarity. It explains many other things that before were unknown or were difficult to understand or to explain in patients. And hopefully all this knowledge brings light into the development of disease-modifying therapies and all these things that we want for our patients.

[00:07:38] Michele Matarazzo: Great. Thank you for this overview of what has happened. Now normally we try to change the guest who we invite every year for this highlight of the year. So probably won't be you next year, but let's say we meet you again in one year and we talk again about the highlights of neuroimaging.

What would be the thing that you would expect to have happened over the next year that you will highlight in 2027?

[00:08:02] Cecilia Peralto: Apart-- I'm not sure, but I would like to see is an advance on how to integrate imaging to research to document biological processes and to find some drugs or some interventions that we may develop that can result or can turn out into slowing disease progression. I think that will be a lovely way to integrate imaging into the current landscape and to see how they can reflect the pathological changes that are ongoing and hopefully to have some interventions, drugs, which are some that are currently being tested. I've seen some abstracts in the congress for instance, with prasinezumab. It is very preliminary, this data. Of course, it has to be confirmed in further trials or further studies, but has been shown that patients receiving prasinezumab and using neuromelanin and volumetry and ion imaging, it has been shown some biological effect compared to patients who received placebo in terms of those who were on the drug with neuromelanin, they showed increased signal compared to placebo patients who presented a decrease in signal.

The same happened with ion and with volumetry. So that's something I would love to see.

[00:09:25] Michele Matarazzo: And indeed, just today it was presented, a clinical trial targeting microglial activation whose primary outcome was neuroinflammatory PET imaging, so TSPO imaging. So we're starting to even see neuroimaging as a primary outcome in our field, which has happened already in other fields of neurology or even neurodegeneration but it's something still new in our world,

right?

[00:09:48] Cecilia Peralto: Yeah. That's absolutely true, and this is an evolving scape, and I think imaging is going to come back somehow because we have not seen much of imaging outside parallel sessions or something like that in our congresses. So we're going to see hopefully kind of comeback of imaging as an endpoint.

[00:10:07] Michele Matarazzo: And do you have any highlight of the congress itself that you want to share?

[00:10:11] Cecilia Peralto: We had two sessions that one was a clinical session on practical aspects on how to use MRI in daily life. That was impressively very well attended for a neuroimaging session. There was people standing in the back, which is something not usual in a imaging session.

We see this in other types, but not in imaging. And yesterday, we had a more scientific session that aimed to reflect on the use of neuroimaging in 2026. What's next? What are the next steps? And that session included the topic of how to use imaging markers to identify phenoconversion, PET synuclein tracers, and the concept of imaging co-pathology.

That's something has been very useful and was very nice. I would love to highlight this. And other things... there are other abstracts. There are several abstracts which are quite important. I may mention one that impressed me or caught my attention. I remember on florbetapir tau PET that showed that PD patients with RBD presented a larger uptake compared to patients without poor cognition and without RBD in the striatum, in the insula.

And that's a good way to reflect how patients with cognitive impairment have increased tau binding compared to those who don't have. So there are some things that I can highlight

[00:11:38] Michele Matarazzo: Perfect. Cecilia, thank you very much for joining me today. A lot of things going on in the field and specifically a lot of work done by the Neuroimaging Study Group helping to move the field forward. Keep up with the good work.

Thank you very much, Cecilia, and thank you all for listening .

[00:11:54] Cecilia Peralto: Thank you so much for your time.