Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Well, good morning, everyone. We're so happy to have you here with us. To start off, we'll be discussing PET imaging, so molecular neuroimaging, specifically on the diagnosis of early Alzheimer's disease. So as most of you are aware, we've shifted in practice from a clinical or a phenotypical diagnosis to a biological biomarker-based diagnosis of Alzheimer's disease and related neurocognitive disorders. We start with the accumulation of amyloid beta, specifically amyloid beta 42, which serves as a core one biomarker, meaning the earlier stage that we can detect in vivo. Meanwhile, tau neurofibil tangles occur later on in the pathophysiologic cascade. They drive neurodegeneration, and tau tends to spread in a predictive, stepwise pattern, which means that as a core to biomarkers, it allows us for assessment of biological disease severity and disease staging. And so this curve that you see on the right is the famous Jack curve. What it highlights is the various Alzheimer's disease biomarkers, be it fluids, so CSF or plasma, or imaging, and their correlation with clinical disease stages. And what you can note here is that many of these biomarkers become abnormal far earlier than clinical symptom onset. So typically for amyloid PET, it can be abnormal even 2 to 3 decades before clinical symptoms begin. Now in clinical practice, what we have available is amyloid tau and also FDG PET, and all three have value in the clinical workup of Alzheimer's disease. Typically, amyloid PET is also the main scan we use to triage patients for anti-amyloid therapy. Tau is a Attained in order to assess biological disease severity and predict treatment response. And finally, MDGPET is really important in the differential diagnosis of neurodegenerative disease, particularly in the many patients with co-pathologies in the setting of mixed dementia. So, let's move on to our first case. This is an 80 year old female with memory loss. This is an amyloid PET scan. What you see here are 3 millimeter cuts from the vertex to the skull base. And just remember for amyloid PET imaging, we use the cerebellum as a reference region. So in this case, you can see that in contrast to the cerebellum, in the stentorial compartment, we have diffuse accumulation of the radio tracer throughout the neocortex, and so visually this case does indeed look positive. We move on to quantification and you can see that this case has a quantification score in the 70s and then the corresponding SUVR values as well, including both global and regional SUVRs. So this brings us to our first polling question, and the question is which of the following features of AMOI PET imaging findings supports a diagnosis of Alzheimer's disease in this patient? And please choose the best answer. Alright, fantastic. So over 70% of you did select the correct answer visual reinterpretation of amyloid uptake supported by quantification. So just remember the FDA labels for the 3 amyloid PET radio pharmaceuticals on the market in the US were updated last June to add quantification. As an adjunct to visual read, you know, furthermore, quantification metrics, specifically the synthroid score, were used as a secondary outcome measure in the phase 3 clinical trials of both like a nebub and Donnaebub. So they have been definitively integrated into clinical practice. So with that, when we think about the amyloid quantification, I think most of us really do focus on the scentyloid scales for several reasons, including, as I mentioned, it was one of the secondary outcome measures for the phase 3 clinical trials of both drugs on the market. The centralloid scale was created almost a decade ago in the research setting in order to standardize comparisons of scans from different institutions obtained with different protocols and different scanners and with different radio tracers. It's essentially an unbounded scale with two anchor points, a scentoid of zero, which is. Indicative of a scentyloid level or amyloid level in normal healthy controls and a scentilloid of 100, which is indicative of the amyloid level in a typical patient with mild to moderate Alzheimer's disease pathology. So you see here in the graphics some key cutoff points. So some numbers to keep in mind are sentyloid score less than 10, which essentially rules out Alzheimer's disease. Indicates also that beta amyloid plaques are completely absent as well as a score greater than 30, which typically indicates established beta amyloid pathology. Keep in mind that the mean centloid value of the patients that were enrolled in clinical trials for the two therapeutics on the market were in the range of 75 to 95. And of course any discrepancy between the. Visual read and the centi values should then be reported in your reports with a rationale for the final report decision. Thank you. We're going to move on to another case. This is a 72-year-old male presenting with a progressive aphasic dementia. The patient is a neurosurgeon no longer able to see patients based on their exam, has a mild to moderate dementia syndrome. They had an amyloid PET first performed, and the amyloid PET is a florbetape, and it shows regions of cortical amyloid deposition, resulting in blurring of the gray-white junction. This is greatest in the frontal lobes, asymmetric on the left, greater than right, and the enyloid value is 42. So another polling question, is this amyloid PET positive? Uh Correct, so this amyloid PET is positive. There are multiple regions, though patchy regions of blurring of that gray-white junction indicative of cortical amyloid deposition, and the enyloid value of 42 supports the positive visual read. Next, the patient had an FDG PET performed, and this again is to help determine the etiology of the patient's syndrome. So there was a question based on the presentation, whether this was Alzheimer's disease or frontotemporal frontal temporal lobar degeneration. The FDG PEET shows left greater than right temporal and parietal hypometabolism. This is suggestive of underlying Alzheimer's disease and in a pattern of leukopenic primary progressive aphasia. There's also relatively extensive hypometabolism in other regions including the frontal lobes as well as occipital lobes, and based on the patient's clinical presentation, as well as the FDG PEET and a relatively low amyloid level for their degree of clinical impairment, the patient went on to have a tau PET to help discern if it was Alzheimer's disease leading to their dementia. And here the taupet shows extensive neocortical tau deposition involving the temporal parietal as well as frontal lobes. So this is a moderate to advanced tau burden. So in this case, the integration of multiple modes of PET imaging, as well as the clinical features were important in their differential diagnosis. So this patient has a diagnosis of Alzheimer's disease with a logopenic primary progressive aphasia subtype. And the amyloid tau and FDG PET again were all helpful in that the amyloid PET says there is AD pathology here, but again the the amyloid loads was relatively lower than expected and the tau PET here confirmed that Alzheimer's disease was the driver of their clinical syndrome. The taupet also informs prognosis, as was mentioned, as a patient with this high of a tau load is expected to benefit less from amyloid targeting therapies than someone with a low tau load at initiation of therapy. OK, thank you, Patrice. You know these are complicated patients, and I'm, I'm thinking a lot of people in our audience may only read the brain MRI, and it's so important. I think to understand that in the context of the amyloid PET, the tau PET, the FDG, and other testing, I can't tell you, um, how many times I get a call to overread someone else's brain MRI findings because they ignored the PET results. So just like when we're in reading an oncology study, right, if you're doing a head and neck case, you don't ignore the FTG PET. I think it's really important that all the radiologists understand that these PET scans, even if they're not interpreting them. And then the other thing is these patients that we're showing you, these are our actual cases, and they're, they're not squeaky clean like they were in clinical trials. So every case it seems like has some complicating thing to think about. So this is a patient of ours that was a slowly progressive cognitive decline and you know, like Doctor Cogswell's case, it's a primarily a word finding problem and substituting random words, um, losing skills, not cooking or driving. Um, and some remote cancer histories and so, um, um, so the diagnosis this person also had was a, a variant of primary progressive aphasia. They had in our, in this case CSF for their amyloid testing, so you can test for the amyloid with a PET scan. Um, in the past it was more frequently done with lumbar puncture, but now that PET's reimbursed, we're all seeing a lot more amyloid PET as well. And then they also tell us the APOE status. So all of you are familiar with APOE as a risk for C.