Histological validation of neuroimaging modalities


In recent years, there have been considerable efforts to develop biomarkers for neurodegenerative diseases. Imaging markers that directly detect core pathologic features are particularly appealing, as demonstrated by the transformative impact that amyloid-beta (Aβ) PET has had on Alzheimer’s disease (AD) research and drug development. Analogously, the recent advent of PET tracers specific for tau brain aggregates could be a “game changer” by enabling “molecular diagnosis” of individuals with underlying tauopathies. Furthermore, tau tracers have the potential benefit to inform on disease progression and detect subtle effects of modifying-treatments.

Postmortem examination is the gold standard for the diagnosis of neurodegenerative diseases. The use of histological examination as a reference matrix in a voxel-by-voxel approach to validate neuroimaging findings provides a unique tool to understand the nature of in vivo imaging signals. The Grinberg Lab has developed a pipeline using ex-vivo and in-vivo MRI scans to map in-vivo images point-to-point to their histological counterpart at an unprecedented 0.1x0.1x0.1mm resolution. This pipeline overcomes challenges faced by previous attempts to co-register MRI to histology as the innovative brain-tissue processing was specially designed to yield higher quality images with considerably fewer distortions and to support big-data analysis.

Our lab is collaborating with the Rabinovici lab to build an initial database of co-registered MRI/PET scans and high-resolution histology data across a range of tauopathies. In addition to the extensive MAC longitudinal assesment, patients will undergo aditional structural and molecular imaging that includes florbetapir and [18F]-AV-1451 PET, and their brains will be analyzed postmortem to develop datasets co-registered point-to-point generating thousands of readouts per patient. This library will enable in-depth investigation of the value and limitations of [18F]-AV-1451 PET in non-AD tauopathies. The long term goals of this research aims to identify the best antemortem predictors of pathology in patients with tau-related neurodegenerative diseases beyond AD.

Funding Sources

Lilly Research Award Program
AVID Radiopharmecuticals

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