HAI Book 2025 - Flipbook - Page 128
Geremia, Danielle
13
Evaluation of a label-free X-ray based method for estimating amyloid
load in the human brain
Danielle Geremia1, Sabri Amer1, Eshan Dahal1, Aldo Badano1
1
Division of Imaging, Diagnostics, and Software Reliability, Office of Science and Engineering Laboratories, Center
for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, US
Introduction: Amyloid accumulation in the brain hallmarks several neurodegenerative diseases, including
Alzheimer9s disease (AD). Despite this, quantifying amyloid plaque levels remains limited to methods requiring
tracers or amyloid-specific labeling. Spectral small-angle X-Ray scattering (sSAXS) is a label-free technique for
estimating amyloid load using X-rays. Here we report on the sSAXS setup and evaluate its amyloid load estimation
performance in postmortem human brains.
Methods: Paraffin-embedded brain slabs approximately 11 mm thick from AD and amyotrophic lateral sclerosis
(ALS) patients were studied with our sSAXS setup (Figures 1a and 1b). A polychromatic pencil beam (2.5 mm
diameter) collimated using two pinholes (P1 and P2) was generated using an 80-kVp tube voltage and 2-mA
current. A 2D spectroscopic detector (PCD) recorded scattered photons for 300 s per ROI. For histology, 10-µm
brain slices were stained with an 6E10 antibody to detect amyloid plaques. We correlated histological and sSAXS
amyloid load estimations to evaluate the performance of our method.
Results: X-ray scattering signals from grey matter regions (GM1 and GM2) in the AD brain were consistently high,
regardless of how background scattering from the brain was subtracted, to recover signal from amyloid plaques
(Figure 1c). This is consistent with histology images showing a high number of amyloid plaques in the grey matter
of the AD brain in comparison to the ALS brain (Figure 2a). A strong correlation was found between area under the
peak (AUP) values, representing X-ray based amyloid load and the amyloid load estimated from histology (ground
truth), as shown in Figures 2b and 2c.
Conclusion: We showed the first results demonstrating label-free estimation of amyloid load using X-rays in a 1
cm thick human brain with AD. Additional ROIs and samples are being studied to provide more data points for
evaluating the correlation with histology.
HAI2025 - 128
