Artikel
Collagen labelling for visualisation of structural instability in intracranial aneurysms – a pilot study
Kollagenmarkierung zur Darstellung der strukturellen Stabilität von intrakraniellen Aneurysmen – eine Pilotstudie
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Veröffentlicht: | 26. Juni 2020 |
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Objective: The estimation of the individual rupture risk of intracranial aneurysms (IA) remains challenging. Structural integrity of IA is predominantly determined by collagen type I, which is the main molecular constituent in IA. A hallmark of IA pathogenesis is ongoing collagen remodelling in the IA wall and synthesis of immature/structural deficient collagen; the latter cannot be visualized with existing imaging modalities to date. Here, we report our pilot data on a novel Positron Emission Tomography contrast agent to investigate radiolabelling of immature/novel collagen in human IA as a marker for instability.
Methods: Unruptured and ruptured IA samples derived from patients undergoing surgical repair, were used for radio- and immunolabelling. A peptide called collagelin was synthesised, conjugated to NODAGA as a chelator and radiolabelled with 68Gallium (68Ga-NODAGA-Collagelin). Longitudinal cryosections of the IA including the dome and the transition zone (between dome and neck) were performed. 12µm cryosections were incubated with 68Ga-NODAGA-Collagelin for 90 minutes and visualised by autoradiography. 9µm cryosections were used for immunolabelling of collagen alpha 1 chain type I and visualised by confocal laser microscopy. Qualitative assessment was performed by 2 independent investigators. IA regions with unstructured collagen fibres were defined as immature, structured collagen as mature. t-Test was performed as statistics.
Results: Within a pilot study radio- and immunolabelling were performed in 6 IA samples (3 unruptured, 3 ruptured) from 6 female patients. Immunolabelling demonstrated regions of mature collagen, which were predominantly localized in the transition zone of the IA and predominantly in unruptured compared to ruptured IA. Regions of immature collagen were predominantly found in IA domes and especially in ruptured IA (Figure 1 [Fig. 1]). Radiolabelling demonstrated increased uptake in IA regions with immature collagen and less uptake in the regions with mature collagen (Figure 1 [Fig. 1]). Radioactivity per area was higher in ruptured compared to unruptured IA (178.7±45.0 kBq/cm2 vs. 145.7±38.2 kBq/cm2, p=0.03).
Conclusion: Our novel collagen radiotracer seems to specifically label IA regions with immature/structurally deficient collagen, which we found especially in ruptured IA. These findings will be underlined in a larger patient sample.