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Daria Pawlik – Institutionen för kliniska vetenskaper, Malmö
Title: Positron emission tomography (PET) imaging in diagnosis and staging of neurodegenerative disorders.
Main supervisor: Ruben Smith MD, PhD
Reviewers: Daniel Lindqvist MD, PhD and Alexis Moscoso PhD
Abstract
Background
Alzheimer’s disease (AD) is the most common neurodegenerative disorder (ND). The prevalence of NDs is estimated to triple by 2050, but the costs of dementia already exceed that of cancer, heart disease and stroke combined. AD is characterised by accumulation of β-amyloid and tau in the brain, which causes neurodegeneration and cognitive decline. Over the past years, tau specific tracers have been developed for use with positron emission tomography (PET) brain imaging. The tau tracer 18F-flortaucipir has been shown to mirror post mortem brain tau-burden in AD and can be used to track disease progression. 18F-flortaucipir has been the most common tracer, but new ligands such as 18F-MK-6240 and 18F-RO948 have recently been developed.
Aims
- Establish methods to reliably quantify and track disease pathology in vivo with the aim of establishing imaging tools to assess treatment effects in future treatment trials, taking off-target binding regions into account.
- Better understand how in vivo PET signal corresponds to post mortem tau pathology and which methods (quantitative vs. visual) provide the most sensitive mode for detection.
Preliminary results
In vivo 18F-flortaucipir SUVR and postmortem tau pathology density is highly correlated, which suggests that 18F-flortaucipir PET reflects the amount of in vivo tau pathology. There are regions of the brain where off-target accumulation of tau-PET tracers is observed without evidence of corresponding tau pathology. Choroid plexus off-target binding interferes with the estimation of true hippocampal retention. Using an in-house developed mask to correct for this off-target signal, we improved the diagnostic accuracy of 18F-flortaucipir in the hippocampus.
18F-RO948can separate PSP from controls and α-synucleinopathies patients at a group level. The optimal prediction models include NfL and MRI measures for separating controls from PSP and 18F-RO948, NfL and MRI measures for separating PSP from α-synucleinopathies.
Significance
Due to the overlap in symptoms and clinical presentation across different NDs, setting correct diagnosis is challenging. Development and validation of new biomarkers is therefore crucial for diagnostic purposes. Relevant biomarkers are vital for identifying individuals suitable for clinical trials as well as they allow for adequate follow-up and evaluation of the new drugs.
Published studies
- Project I: Pawlik D, Leuzy A, Strandberg O, Smith R. Compensating for choroid plexus based off-target signal in the hippocampus using 18F-flortaucipir PET. Neuroimage. 2020 Jul 22;221:117193. doi: 10.1016/j.neuroimage.2020.117193.
- Project II: Freiburghaus T§, Pawlik D§, Oliveira Hauer K, Ossenkoppele R, Strandberg O, Leuzy A, Rittmo J, Tremblay C, Serrano GE, Pontecorvo MJ, Beach TG, Smith R, Hansson O. Association of in vivo retention of [18F] Flortaucipir PET with tau neuropathology in corresponding brain regions. Acta Neuropathol. 2024 Sep 19;148(1):44. doi: 10.1007/s00401-024-02801-2. §Shared first authors.
- Project III: Oliveira Hauer K, Pawlik D, Leuzy A, Janelidze S, Hall S, Hansson O, Smith R. Performance of [18F]RO948 PET, MRI and CSF neurofilament light in the differential diagnosis of progressive supranuclear palsy. doi: https://doi.org/10.1016/j.parkreldis.2022.11.018.10.1016/j.parkreldis.2….
Om evenemanget
Plats:
BMC:E11082 Insikten, Sölvegatan 19, 223 62 Lund
Kontakt:
daria [dot] pawlik [at] med [dot] lu [dot] se