Exploring the origins of frequent tau-PET signal in vermal and adjacent regions DOI Creative Commons

A. Kling,

Julia Kusche‐Palenga,

Carla Palleis

et al.

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Purpose Off-target binding remains a significant challenge in tau-PET neuroimaging. While off-targets including monoamine oxidase enzymes and neuromelanin-containing cells have been identified, recent studies indicated relevant of novel tau tracers to melanin-containing structures. To date, little is known about the effect melanocytes meninges on tracer signals brain PET data. Thus, we aimed identify target structure causal for frequently observed [ 18 F]PI-2620 signal vermis adjacent cerebellar regions. Methods 274 participants underwent dynamic tau-PET: 3/4R-tauopathies (n = 85), 4R-tauopathies 147), tau-negative disease controls 24), healthy 18). Standardized uptake value ratio (SUVR) kinetic parameters distribution volume (DVR), clearance (k2) relative perfusion (R1), were compared among cohorts sexes using Automated Anatomical Labelling (AAL) atlas. Age p-Tau levels cerebrospinal fluid (CSF) assessed their relationship with vermal signal. Furthermore, combined autoradiographic histochemical experiments post-mortem tissue deceased patients 9). Results Male revealed higher mean DVR (0.95 ± 0.13; vs. females 0.88 0.10, p < 0.0001). Sex-related differences most pronounced 3/4R-tauopathy cohort (p Mean SUVR Ver/Cbl , k2 correlation analyses did not differ groups. Histological assessments co-localization leptomeningeal pigmented strong autoradiography spots within fissures. Tau-related signals, age or correlate significantly signals. Iron deposits cause vermis. Conclusion Leptomeningeal are primary anterior vermis, whereas iron do contribute significantly.

Language: Английский

Assessment and staging of A/T/N with a single dynamic [18F]PI-2620 recording DOI Creative Commons
Johannes Gnörich,

Julia Kusche‐Palenga,

A. Kling

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Patients with Alzheimer’s disease (AD) and clinically overlapping neurodegenerative diseases are classified molecularly using the A/T/N classification system. Apart from fluid biomarkers structural MRI, three-dimensional system incorporates characteristic features β-amyloid-PET (A), tau-PET (T), FDG-PET (N). We evaluated if dynamic of [ 18 F]PI-2620 allow assessment in individual patients a single imaging session. Cortical tissue clearance (K2a) was validated as surrogate β-amyloid status against cerebrospinal (CSF) Aβ 42/40 ratio, demonstrating remarkable positive (91.5%) negative (95.1%) predictive values at an AUC 0.99 (P<0.0001). K2a outperformed cortical tau burden for 47 participants clinical diagnosis probable AD (3/4-repeat(R)-tauopathy) 82 β-amyloid-negative primary 4R-tauopathies. Perfusion-like images (R1) were marker neuronal injury, exhibiting strong quantitative visual correlations early-phase β-amyloid-PET, well volumetric MRI CSF total levels. Composite indices facilitated personalized staging along temporal trajectories. Our results suggest that has potential to facilitate region stage dependent PET-based during PET Graphical

Language: Английский

Citations

0
Exploring the origins of frequent tau-PET signal in vermal and adjacent regions DOI Creative Commons

A. Kling,

Julia Kusche‐Palenga,

Carla Palleis

et al.

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Purpose Off-target binding remains a significant challenge in tau-PET neuroimaging. While off-targets including monoamine oxidase enzymes and neuromelanin-containing cells have been identified, recent studies indicated relevant of novel tau tracers to melanin-containing structures. To date, little is known about the effect melanocytes meninges on tracer signals brain PET data. Thus, we aimed identify target structure causal for frequently observed [ 18 F]PI-2620 signal vermis adjacent cerebellar regions. Methods 274 participants underwent dynamic tau-PET: 3/4R-tauopathies (n = 85), 4R-tauopathies 147), tau-negative disease controls 24), healthy 18). Standardized uptake value ratio (SUVR) kinetic parameters distribution volume (DVR), clearance (k2) relative perfusion (R1), were compared among cohorts sexes using Automated Anatomical Labelling (AAL) atlas. Age p-Tau levels cerebrospinal fluid (CSF) assessed their relationship with vermal signal. Furthermore, combined autoradiographic histochemical experiments post-mortem tissue deceased patients 9). Results Male revealed higher mean DVR (0.95 ± 0.13; vs. females 0.88 0.10, p < 0.0001). Sex-related differences most pronounced 3/4R-tauopathy cohort (p Mean SUVR Ver/Cbl , k2 correlation analyses did not differ groups. Histological assessments co-localization leptomeningeal pigmented strong autoradiography spots within fissures. Tau-related signals, age or correlate significantly signals. Iron deposits cause vermis. Conclusion Leptomeningeal are primary anterior vermis, whereas iron do contribute significantly.

Language: Английский

Citations

0