Validation of MR-free PET Pipeline in Alzheimer Disease with & without Major Depression
Poster No:
206
Submission Type:
Abstract Submission
Authors:
Kaitlyn Dombrowski1, Shaney Flores1, Jacqueline Rizzo1, Chen Chen1, Matthew Blake1, David Brown1, Jalen Scott1, Charles Chen2, Randall Batmeman1, John Morris1, Yiqi Zhu1, Tammie Benzinger1, Ganesh Babulal1
Institutions:
1Washington University in St. Louis, St. Louis, MO, 2Massachusetts General Hospital, Charlestown, MA
First Author:
Co-Author(s):
Introduction:
Amyloid-β (Aβ) position emission tomography (PET) enables in-vivo measurements of Aβ aggregation in Alzheimer disease (AD) and typically requires an additional structural magnetic resonance imaging (MRI) scan. However, participants might not be eligible for an MRI for safety reasons or may produce an unusable MRI due to imaging artifacts. These exclusions hinders longitudinal follow-up studies and limits the generalizability of study outcomes. MR-free PET quantification offers a way to include participants in a study even when no accompanying structural MRI is available. We extended the MR-free PET pipeline (Landau et al, 2023) by validating a MR-free Centiloid (CL) equation for 11C-Pittsburgh Compound B (PiB) in a general population cohort and in a cohort of individuals with and without Major Depressive Disorder (MDD) (Babulal et al., 2020; Javaherian et al., 2019).
Methods:
Clinical and imaging data for 167 participants were analyzed from the Study to Evaluate Amyloid in Blood and Imaging Related to Dementia (SEABIRD) (n=64) and the DRIVES Project (n=103) at the Washington University School of Medicine. For the DRIVES study, enrolled participants were evaluated for MDD based on a diagnosis from their Primary Care Physician (PCP) or their baseline Patient Health Questionnaire-9 (PHQ-9) if a PCP diagnosis was absent. All participants completed PiB PET and 3T structural head MR imaging. PET data were processed using both the MR-free PET pipeline and the MR-dependent FreeSurfer-based PET Unified Pipeline. For the MR-dependent method, regional Centiloids (CLs) were calculated for the participant's native-space FreeSurfer segmentations using our published equations (Chen et al., 2023; Su et al., 2018, 2019). To calculate CLs for the MR-free method, we performed a Level-2 CL calibration (Klunk et al., 2015) of the MR-free pipeline and derived a CL equation for PiB. MR-free regional CLs were then calculated using the template-space ADNI200 FreeSurfer segmentations for the MR-free pipeline (Landau et al, 2023). Pearson's correlations assessed agreement between the MR-free and MR-dependent CLs for SEABIRD and for the DRIVES depressed and non-depressed cohorts.
Results:
Within the SEABIRD cohort, the lowest correlations between regional CLs for the MR-free and MR-dependent methods were observed in frontal pole (r=0.66, p<0.001), a region known to have high levels of atrophy, and pallidum (r=0.73, p<0.001), a relatively small region. All other cortical and subcortical regions had Pearson's correlations above 0.8 and were statistically significant (all regions p<0.001; see Figure 1). For the DRIVES cohort, 62 individuals were categorized as as depressed, while 41 individuals were qualified as non-depressed. Among those with MDD, the lowest correlations between regional CLs for the MR-free and MR-dependent methods were observed in several regions: frontal pole (r=0.37, p<0.001), entorhinal cortex (r=0.54, p<0.001), parahippocampal cortex (r=0.55, p<0.001), and hippocampus (r=0.66, p<0.001; see Figure 2). Comparatively, the lowest correlations between regional CLs in the non-MDD individuals were observed in lingual gyrus (r=0.64, p<0.001), choroid plexus (r=0.78, p<0.001) and hippocampus (r=0.77, p<0.001). Individuals with MDD showed greater variability in their regional CL values compared to their non-depressed counterparts.
·Figure 1. Relationship between MR-free and MR-dependent individuals in SEABIRD study.
·Figure 2. Relationship between MR-free and MR-dependent individuals in DRIVES study.
Conclusions:
The MR-free PET pipeline produced comparable results to an MR-dependent method for PiB in a general population cohort and a cohort that included clinically-diagnosed depressed and non-depressed individuals. However, agreement between MR-free and MR-dependent methods were more variable within the MDD cohort. This variability in regional CLs for MDD could be the result of levels of atrophy that could typically render an MRI unreliable for ROI delineation. Further research is needed to examine the variability difference between those with and without MDD using MR-free methods.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
PET Modeling and Analysis
Novel Imaging Acquisition Methods:
PET 2
Keywords:
ADULTS
Aging
Degenerative Disease
DISORDERS
MRI
Neurological
Positron Emission Tomography (PET)
Psychiatric Disorders
Spatial Warping
Other - Alzheimer's Disease
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
Chen, C. D., McCullough, A., Gordon, B., Joseph-Mathurin, N., Flores, S., McKay, N. S., Hobbs, D. A., Hornbeck, R., Fagan, A. M., Cruchaga, C., Goate, A. M., Perrin, R. J., Wang, G., Li, Y., Shi, X., Xiong, C., Pontecorvo, M. J., Klein, G., Su, Y., … for the DIAN-TU Study Team. (2023). Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease. European Journal of Nuclear Medicine and Molecular Imaging, 50(9), 2669–2682. https://doi.org/10.1007/s00259-023-06209-0
Javaherian, K., Newman, B. M., Weng, H., Hassenstab, J., Xiong, C., Coble, D., Fagan, A. M., Benzinger, T., & Morris, J. C. (2019). Examining the Complicated Relationship Between Depressive Symptoms and Cognitive Impairment in Preclinical Alzheimer Disease. Alzheimer Disease & Associated Disorders, 33(1), 15–20. https://doi.org/10.1097/WAD.0000000000000284
Klunk, W. E., Koeppe, R. A., Price, J. C., Benzinger, T. L., Devous, M. D., Jagust, W. J., Johnson, K. A., Mathis, C. A., Minhas, D., Pontecorvo, M. J., Rowe, C. C., Skovronsky, D. M., & Mintun, M. A. (2015). The Centiloid Project: Standardizing quantitative amyloid plaque estimation by PET. Alzheimer’s & Dementia, 11(1), 1. https://doi.org/10.1016/j.jalz.2014.07.003
Su, Y., Flores, S., Hornbeck, R. C., Speidel, B., Vlassenko, A. G., Gordon, B. A., Koeppe, R. A., Klunk, W. E., Xiong, C., Morris, J. C., & Benzinger, T. L. S. (2018). Utilizing the Centiloid scale in cross-sectional and longitudinal PiB PET studies. NeuroImage: Clinical, 19, 406–416. https://doi.org/10.1016/j.nicl.2018.04.022
Su, Y., Flores, S., Wang, G., Hornbeck, R. C., Speidel, B., Joseph‐Mathurin, N., Vlassenko, A. G., Gordon, B. A., Koeppe, R. A., Klunk, W. E., Jack, C. R., Farlow, M. R., Salloway, S., Snider, B. J., Berman, S. B., Roberson, E. D., Brosch, J., Jimenez‐Velazques, I., Van Dyck, C. H., … Benzinger, T. L. S. (2019). Comparison of Pittsburgh compound B and florbetapir in cross‐sectional and longitudinal studies. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 11(1), 180–190. https://doi.org/10.1016