Due to Europe's ageing society, there has been a dramatic increase in the occurrence of osteoporosis (OP) and related diseases. Sufferers have an impaired quality of life, and there is a considerable cost to society associated with the consequent loss of productivity and injuries. The current understanding of this disease needs to be revolutionized, but study has been hampered by a lack of means to properly characterize bone structure, remodeling dynamics and vascular activity. This project, 4D nanoSCOPE, will develop tools and techniques to permit time-resolved imaging and characterization of bone in three spatial dimensions (both in vitro and in vivo), thereby permitting monitoring of bone remodeling and revolutionizing the understanding of bone morphology and its function.
To advance the field, in vivo high-resolution studies of living bone are essential, but existing techniques are not capable of this. By combining state-of-the art image processing software with innovative 'precision learning' software methods to compensate for artefacts (due e.g. to the subject breathing or twitching), and innovative X-ray microscope hardware which together will greatly speed up image acquisition (aim is a factor of 100), the project will enable in vivo X-ray microscopy studies of small animals (mice) for the first time. The time series of three-dimensional X-ray images will be complemented by correlative microscopy and spectroscopy techniques (with new software) to thoroughly characterize (serial) bone sections ex vivo.
The resulting three-dimensional datasets combining structure, chemical composition, transport velocities and local strength will be used by the PIs and international collaborators to study the dynamics of bone microstructure. This will be the first time that this has been possible in living creatures, enabling an assessment of the effects on bone of age, hormones, inflammation and treatment.
One focus of our research is data acquisition (e.g. data from imaging MRI or CT, basic research, clinical trial data, digital applications Apps) and the distribution of data for analysis using AI methods to improve early diagnosis, differential diagnosis and prediction of the course of the disease of rheumatic diseases such as rheumatoid arthritis or psoriatic arthritis.
Research projects
Molecular Assessment of Signatures ChAracterizing the Remission of Arthritis
(Third Party Funds Single)
Funding source: Bundesministerium für Bildung und Forschung (BMBF)
MASCARA zielt auf eine detaillierte, molekulare Charakterisierung der Remission bei Arthritis ab. Das Projekt basiert auf der kombinierten klinischen und technischen Erfahrung von Rheumatologen, Radiologen, Medizinphysikern, Nuklearmedizinern, Gastroenterologen, grundlagenwissenschaftlichen Biologen und Informatikern und verbindet fünf akademische Fachzentren in Deutschland. Das Projekt adressiert 1) den Umstand der zunehmenden Zahl von Arthritis Patienten in Remission, 2) die Herausforderungen, eine effektive Unterdrückung der Entzündung von einer Heilung zu unterscheiden und 3) das begrenzte Wissen über die Gewebeveränderungen in den Gelenken von Patienten mit Arthritis. MASCARA wird auf der Grundlage vorläufiger Daten vier wichtige mechanistische Bereiche (immunstoffwechselbedingte Veränderungen, mesenchymale Gewebereaktionen, residente Immunzellen und Schutzfunktion des Darms) untersuchen, die gemeinsam den molekularen Zustand der Remission bestimmen. Das Projekt zielt auf die Sammlung von Synovialbiopsien und die anschließende Gewebeanalyse bei Patienten mit aktiver Arthritis und Patienten in Remission ab. Die Gewebeanalysen umfassen (Einzelzell)-mRNA-Sequenzierung, Massenzytometrie sowie die Messung von Immunmetaboliten und werden durch molekulare Bildgebungsverfahren wie CEST-MRT und FAPI-PET ergänzt. Sämtliche Daten, die in dem Vorhaben generiert werden, werden in einem bereits bestehenden Datenbanksystem mit den Daten der anderen Partner zusammengeführt und gespeichert. Das Zusammenführen der Daten soll – mit Hilfe von maschinellem Lernen – krankheitsspezifische und mit der Krankheitsaktivität verbundene Mustermatrizen identifizieren.
Advancing osteoporosis medicine by observing bone microstructure and remodelling using a four-dimensional nanoscope
(Third Party Funds Single)
Funding source: European Research Council (ERC)
URL: https://cordis.europa.eu/project/id/810316
Due to Europe's ageing society, there has been a dramatic increase in the occurrence of osteoporosis (OP) and related diseases. Sufferers have an impaired quality of life, and there is a considerable cost to society associated with the consequent loss of productivity and injuries. The current understanding of this disease needs to be revolutionized, but study has been hampered by a lack of means to properly characterize bone structure, remodeling dynamics and vascular activity. This project, 4D nanoSCOPE, will develop tools and techniques to permit time-resolved imaging and characterization of bone in three spatial dimensions (both in vitro and in vivo), thereby permitting monitoring of bone remodeling and revolutionizing the understanding of bone morphology and its function.
To advance the field, in vivo high-resolution studies of living bone are essential, but existing techniques are not capable of this. By combining state-of-the art image processing software with innovative 'precision learning' software methods to compensate for artefacts (due e.g. to the subject breathing or twitching), and innovative X-ray microscope hardware which together will greatly speed up image acquisition (aim is a factor of 100), the project will enable in vivo X-ray microscopy studies of small animals (mice) for the first time. The time series of three-dimensional X-ray images will be complemented by correlative microscopy and spectroscopy techniques (with new software) to thoroughly characterize (serial) bone sections ex vivo.
The resulting three-dimensional datasets combining structure, chemical composition, transport velocities and local strength will be used by the PIs and international collaborators to study the dynamics of bone microstructure. This will be the first time that this has been possible in living creatures, enabling an assessment of the effects on bone of age, hormones, inflammation and treatment.
2021
2020
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