Disease-Modifying Therapy, Quantitative Imaging, and AI for Managing Patients with Alzheimer Disease
Editor’s Note: Moderated by Lawrence Tanenbaum, MD, FACR, Applied Radiology hosted a series of conversations with experts on Alzheimer disease imaging and management at the 2024 Radiological Society of North America Annual Meeting and Scientific Exhibition.
In this discussion, Dr Tanenbaum and Suzie Bash, MD, a Medical Director at RadNet in Los Angeles, cover the intersection of disease-modifying therapies (DMTs), quantitative imaging, and artificial intelligence (AI) in managing Alzheimer disease.
The Role of Quantitative Imaging in Early Detection
It is becoming increasingly apparent that one of the most valuable diagnostic tools in the fight against Alzheimer disease (AD) is quantitative assessment. The reason: Quantitative MRI (QMRI) reduces reader subjectivity and provides an objective measure of whether brain volume is normal for age or there is statistically significant loss of brain volume compared to a large age- and gender-matched normative database. QMRI also permits tracking of brain volumes over time, which is particularly important as brain structures pertinent to Alzheimer disease (such as the hippocampi) will atrophy at an accelerated rate and more rapidly drop off the normative curve compared to healthy cohorts.
Our referrers like this technology because it identifies and labels anatomic structures in the brain and quantitates the volume of those structures. And then it allows you to have longitudinal tracking over time,” says Dr Bash, who has been using quantitative imaging to evaluate neurological conditions for almost 20 years. “It really is very useful in the dementia landscape because it reduces reader subjectivity and tells you what's statistically significant for patient age and gender.”
The emergence of disease modifying therapies (DMTs) like lecanemab and donanemab has dramatically changed the clinical landscape by slowing the progression of AD, thus bringing hope to millions. Dr. Bash underscores that it is critical to identify patients at the earliest stage possible since we know from the sub-study analysis of the lecanemab CLARITY AD trial that patients with early initiation of DMT obtain the greatest benefit. Quantitative assessment assists in identifying patients in the earliest stage of disease (such as in patients with early cognitive decline and a positive Amyloid PET, but with preserved brain volumes). “If you catch them early, like the low Tau group, 76% will have no cognitive decline at 18 months and 60% will actually have cognitive improvement,” she notes.
Consistent Protocols
RadNet’s approach to imaging patients with memory loss and suspected AD employs a “quantitation capable” 3D T1 sequence along with other routine sequences likeT2, FLAIR, GRE, and DWI, she says. Inclusion of a 3D series allows accurate brain-volume tracking over time. Appropriate and standardized imaging parameters are critically important, especially for GRE images where sensitivity to susceptibility scales with TE and field strength. On a 1.5T, you would like the TE to be around 30 ms and on a 3T around 20 ms. The problem is if the TE is too low, you actually will miss the microhemorrhages,” says Dr Bash.
Detecting and Managing ARIA
Amyloid-related imaging abnormalities (ARIA) represent a significant risk associated with DMT. Two types of ARIA can develop: ARIA-H, which consists of micro- hemorrhages or superficial sideroses, and ARIA-E, which consists of vasogenic edema or sulcal effusions. “It is absolutely critical that the neuroradiologist identifies this accurately because the disease modifying therapy has to be paused if the degree of radiographic ARIA is moderate or severe, says Dr Bash. These findings can be unfamiliar and challenging to appreciate; AI-fueled tools offer valuable assistance in detecting, quantifying, and grading ARIA. In one study, 84% of local radiologists actually missed ARIA initially. And that accuracy can go up if you use a quantitative tool. These cases of ARIA can be actually quite subtle, and computers are better at pattern recognition,” she says.
Education Is Vital
Dr Tanenbaum urges the neuroradiology community to embrace the opportunities afforded by patients undergoing amyloid mobilizing immunotherapies as well as the challenges in imaging this unique group of patients. Training in the subtleties of ARIA and understanding the impact on treatment is essential.
“At RadNet, I did a training webinar for ARIA and people could watch that and get comfortable with what the grading system is. I think really it doesn't matter if you're outpatient or private practice or hospital based, it's important to have that training. The ASNR also offers training. You can see cases [that are very useful] because, prior to DMTs [neuroradiologists] really were not familiar with ARIA,” she says.
Effective communication between neuroradiologists and neurologists treating patients is so important, said Dr. Bash. “[Neurologists] need to get back good communication about whether ARIA is present before the next infusion can take place. The onus is really on the neuroradiologist to grade it correctly and then effectively communicate back to our neurology referrers to make sure that they get the image interpretation quickly and accurately so that they can make a decision about whether or not they need to hold therapy,” Dr Bash says.