Figure 4
In vivo molecular MRI with an albumin-binding probe during the development of aortic aneurysms (week-by-week study). (A1) 3D visualizations showing the suprarenal abdominal aorta (AA) with the renal arteries (rA) of a male ApoE−/− mouse after 2 weeks of Angiotensin II infusion. The green line indicates the orientation of subsequently acquired transverse MRI sequences and the corresponding histological sections. (A2) Time-of-flight angiography of the AA showing the vessel lumen. (A3) Delayed-enhancement imaging after administration of the albumin-binding probe gadofosveset shows intermediate signal enhancement after 2 weeks of AngII infusion, indicated by the red arrows and corresponding to albumin accumulation in the arterial wall and the thrombus area. Fusion A2/A3 shows a fusion of images A2 and A3 for better visualization of in vivo results. Blue signal indicates lower enhancement, whereas green signal shows intermediate enhancement and red signal indicates increased enhancement. A4–A7 are images of ex vivo histology. A4 and its corresponding magnification A5 show an albumin-specific staining with confluent immunopositive fluorescent areas of albumin, confirming the extraluminal accumulation of albumin. A6 corresponds to a Hematoxylin and Eosin (H&E) staining of the aortic tissue and A7 shows an Elastica van Gieson (EvG) staining of elastic fibers. In summary, we see, that there is pathological vascular permeability in the abdominal aortic aneurysm after 2 weeks of Angiotensin II infusion with intermediate signal enhancement from the albumin-binding probe, corresponding to confluent extraluminal accumulation of Albumin. (B1) 3D visualizations showing the suprarenal abdominal aorta (AA) with the renal arteries (rA) of a male ApoE−/− mouse after 4 weeks of Angiotensin II infusion. The green line indicates the orientation of subsequently acquired transverse MRI sequences and the corresponding histological sections. (B2) Time-of-flight angiography of the AA showing the vessel lumen. (B3) Delayed-enhancement imaging after administration of the albumin-binding probe gadofosveset shows a strong signal enhancement after 4 weeks of AngII infusion, indicated by the red arrows and corresponding to albumin accumulation in the arterial wall and the thrombus area. Fusion B2/B3 shows a fusion of images B2 and B3 for better visualization of in vivo results. Blue signal indicates lower enhancement, whereas green signal shows intermediate enhancement and red signal indicates increased enhancement. B4-B7 are images of ex vivo histology. B4 and its corresponding magnification B5 show an albumin-specific staining with large immunopositive fluorescent areas of albumin, confirming an increasing extraluminal accumulation of albumin. B6 corresponds to a Hematoxylin and Eosin (H&E) staining of the aortic tissue and B7 shows an Elastica van Gieson (EvG) staining of elastic fibers. In summary, we see, that there is a further increase in vascular permeability in the abdominal aortic aneurysm after 4 weeks of Angiotensin II infusion with strong enhancement from the albumin-binding probe, corresponding to extensive extraluminal accumulation of Albumin. Abbreviations: H&E: Hematoxylin and Eosin staining; EvG: Elastica van Gieson staining of elastic fibers; TOF-MRA: time-of-flight magnetic resonance angiography; gadofosveset: albumin-binding probe; AA: suprarenal abdominal aorta; RA: right renal artery; gadofosveset: albumin-binding probe; +: vascular lumen in arterial TOF; *: thrombus area.
