Preboske, Greg

Autosomal‐dominant, Dutch‐type cerebral amyloid angiopathy (D‐CAA) offers a unique opportunity to develop biomarkers for pre‐symptomatic cerebral amyloid angiopathy (CAA). We hypothesized that neuroimaging measures of white matter injury would be present and progressive in D‐CAA prior to hemorrhagic lesions or symptomatic hemorrhage. In a longitudinal cohort of D‐CAA carriers and non‐carriers, we observed divergence of white matter injury measures between D‐CAA carriers and non‐carriers prior to the appearance of cerebral microbleeds and >14 years before the average age of first symptomatic hemorrhage. These results indicate that white matter disruption measures may be valuable cross‐sectional and longitudinal biomarkers of D‐CAA progression. ANN NEUROL 2022;92:358–363

AbstractBackgroundThe use of hippocampal volumetry as a biomarker for Alzheimer’s disease (AD) requires that tracers from different laboratories comply with the same segmentation method. Here we present a platform for training and qualifying new tracers to perform the manual segmentation of the hippocampus on magnetic resonance images (MRI) following the European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (EADC‐ADNI) Harmonized Protocol (HarP). Our objective was to demonstrate that the training process embedded in the platform leads to increased compliance and qualification with the HarP.MethodThirteen new tracers' segmentations were compared with benchmark images with respect to: (a) absolute segmentation volume; (b) spatial overlap of contour with the reference using the Jaccard similarity index; and (c) spatial distance of contour with the reference. Point by point visual feedback was provided through three training phases on 10 MRI. Tracers were then tested on 10 different MRIs in the qualification phase.ResultsStatistical testing of training over three phases showed a significant increase of Jaccard (i.e. mean Jaccard overlap P < .001) between phases on average for all raters, demonstrating that training positively increased compliance with the HarP. Based on these results we defined qualification thresholds which all tracers were able to meet.ConclusionsThis platform is an adequate infrastructure allowing standardized training and evaluation of tracers' compliance with the HarP. This is a necessary step allowing the use of hippocampal volumetry as a biomarker for AD in clinical and research centers.