PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers
This thesis explores technical factors influencing brain PET quantification, developing brain PET harmonization framework, assessing Centiloid robustness as a clinical biomarker, and evaluating the associations between fluid biomarkers and amyloid and tau PET imaging in the early stage of preclinica...
| Autor: | |
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| Tipo de documento: | Tesis doctoral |
| Estado: | Published version |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/690636 |
| Acceso en línea: | http://hdl.handle.net/10803/690636 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Preclinical Alzheimer’s Disease Fluid biomarkers PET Harmonization Enfermedad de Alzheimer Preclínica Biomarcadores en Fluidos Harmonización Malaltia d'Alzheimer Preclínica Biomarcadors en Fluids Harmonització 616.8 |
| _version_ | 1878741980109864960 |
|---|---|
| author | Shekari, Mahnaz |
| author_browse | Shekari, Mahnaz |
| author_facet | Shekari, Mahnaz |
| author_role | author |
| collection | TDR. Tesis Doctorales en Red |
| description | This thesis explores technical factors influencing brain PET quantification, developing brain PET harmonization framework, assessing Centiloid robustness as a clinical biomarker, and evaluating the associations between fluid biomarkers and amyloid and tau PET imaging in the early stage of preclinical AD. Findings support prospective and retrospective harmonization using the developed framework, soon to be EARL accreditation's new harmonization criteria for brain PET imaging. Centiloid metric showed to be a robust metric, that can be used as a reliable biomarker. Additionally, promising results from CSF and blood biomarker studies, notably new blood biomarkers (blood ptau231 and ptau217), revealed their predictive abilities of for amyloid progression and moderate correlations with tau PET signals. This underscores their potential as valuable tools for cohort enrichment and recruitment of clinical trials. The thesis's outcomes contribute to the EARL accreditation program's first brain PET harmonization guideline, EMA approval for Centiloid use in clinical routine studies, and improving the understanding of new blood biomarkers and their application in preclinical AD. |
| eu_rights_str_mv | openAccess |
| format | doctoralThesis |
| id | ES_ee4e1b8eae7f0c15760a7b8da6f90e4e |
| institution | CBUC, CESCA |
| instname_str | CBUC, CESCA |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:www.tdx.cat:10803/690636 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | Universitat Pompeu Fabra |
| publisherStr | Universitat Pompeu Fabra |
| reponame_str | TDR. Tesis Doctorales en Red |
| spelling | PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers Shekari, Mahnaz Preclinical Alzheimer’s Disease Fluid biomarkers PET Harmonization Enfermedad de Alzheimer Preclínica Biomarcadores en Fluidos Harmonización Malaltia d'Alzheimer Preclínica Biomarcadors en Fluids Harmonització 616.8 This thesis explores technical factors influencing brain PET quantification, developing brain PET harmonization framework, assessing Centiloid robustness as a clinical biomarker, and evaluating the associations between fluid biomarkers and amyloid and tau PET imaging in the early stage of preclinical AD. Findings support prospective and retrospective harmonization using the developed framework, soon to be EARL accreditation's new harmonization criteria for brain PET imaging. Centiloid metric showed to be a robust metric, that can be used as a reliable biomarker. Additionally, promising results from CSF and blood biomarker studies, notably new blood biomarkers (blood ptau231 and ptau217), revealed their predictive abilities of for amyloid progression and moderate correlations with tau PET signals. This underscores their potential as valuable tools for cohort enrichment and recruitment of clinical trials. The thesis's outcomes contribute to the EARL accreditation program's first brain PET harmonization guideline, EMA approval for Centiloid use in clinical routine studies, and improving the understanding of new blood biomarkers and their application in preclinical AD. Esta tesis explora los factores técnicos que influyen en la cuantificación de la PET cerebral, desarrollando un marco de armonización para la PET cerebral, evaluando la robustez del Centiloide como biomarcador clínico y analizando las asociaciones entre biomarcadores en fluidos e imágenes de PET de amiloide y tau en las etapas tempranas de la enfermedad de Alzheimer preclínica. Los hallazgos respaldan la armonización prospectiva y retrospectiva mediante el marco desarrollado, que pronto será el nuevo criterio de armonización para el PET cerebral según la acreditación EARL. La escala Centiloide ha demostrado ser una métrica sólida y confiable como biomarcador. Además, resultados prometedores de estudios con biomarcadores de líquido cefalorraquídeo y sangre, especialmente con los nuevos biomarcadores sanguíneos (ptau231 y ptau217), han revelado sus habilidades predictivas para la progresión de la amiloidosis y correlaciones moderadas con señales de PET de tau. Este hecho enfatiza su potencial como herramientas valiosas para la selección y reclutamiento de cohortes en ensayos clínicos. Los resultados de la tesis contribuyen a la primera guía de armonización de PET cerebral del programa de acreditación EARL, la aprobación de la EMA para el uso de Centiloides en estudios clínicos de rutina, y al avance en la comprensión de nuevos biomarcadores sanguíneos y su aplicación en la enfermedad de Alzheimer preclínica. Programa de Doctorat en Biomedicina Universitat Pompeu Fabra http://hdl.handle.net/10803/690636 |
| spellingShingle | PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers Shekari, Mahnaz Preclinical Alzheimer’s Disease Fluid biomarkers PET Harmonization Enfermedad de Alzheimer Preclínica Biomarcadores en Fluidos Harmonización Malaltia d'Alzheimer Preclínica Biomarcadors en Fluids Harmonització 616.8 |
| status_str | publishedVersion |
| title | PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers |
| title_full | PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers |
| title_fullStr | PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers |
| title_full_unstemmed | PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers |
| title_short | PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers |
| title_sort | PET in preclinical AD: image harmonization, characterization of the centiloid metric of Aβ load and associations with tau fluid biomarkers |
| topic | Preclinical Alzheimer’s Disease Fluid biomarkers PET Harmonization Enfermedad de Alzheimer Preclínica Biomarcadores en Fluidos Harmonización Malaltia d'Alzheimer Preclínica Biomarcadors en Fluids Harmonització 616.8 |
| topic_facet | Preclinical Alzheimer’s Disease Fluid biomarkers PET Harmonization Enfermedad de Alzheimer Preclínica Biomarcadores en Fluidos Harmonización Malaltia d'Alzheimer Preclínica Biomarcadors en Fluids Harmonització 616.8 |
| url | http://hdl.handle.net/10803/690636 |