To date, the combination of histological sectioning, staining, and microscopic assessment of the 2D sections is still the golden standard for structural and compositional analysis of biological tissues. X-ray microfocus computed tomography (microCT) is an emerging 3D imaging technique with high potential for 3D structural analysis of biological tissues with a complex and heterogeneous 3D structure, such as the trabecular bone. However, its use has been mostly limited to mineralized tissues because of the inherently low X-ray absorption of soft tissues. To achieve sufficient X-ray attenuation, chemical compounds containing high atomic number elements that bind to soft tissues have been recently adopted as contrast agents (CAs) for contrast-enhanced microCT (CE-CT); this novel technique is very promising for quantitative “virtual” 3D anatomical pathology of both mineralized and soft biological tissues. In this paper, we provided a review of the advances in CE-CT since the very first reports on the technology to date. Perfusion CAs for in vivo imaging have not been discussed, as the focus of this review was on CAs that bind to the tissue of interest and that are, thus, used for ex vivo imaging of biological tissues. As CE-CT has mostly been applied for the characterization of musculoskeletal tissues, we have put specific emphasis on these tissues. Advantages and limitations of multiple CAs for different musculoskeletal tissues have been highlighted, and their reproducibility has been discussed. Additionally, the advantages of the “full” 3D CE-CT information have been pinpointed, and its importance for more detailed structural, spatial, and functional characterization of the tissues of interest has been shown. Finally, the remaining challenges that are still hampering a broader adoption of CE-CT have been highlighted, and suggestions have been made to move the field of CE-CT imaging one step further towards a standard accepted tool for quantitative virtual 3D anatomical pathology.

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A novel synthetic strategy toward N-acyl sulfamates was developed. Interestingly, fluorosulfates, a new emerging class of electrophiles, were used to construct the sulfamate core. This precludes handling of chlorosulfonyl isocyanate and sulfamoyl chloride. In combination with amides, a wide and diverse set of N-acyl sulfamates was synthesized, including functionalized bioactive compounds. Furthermore, initial results showed that this method is also amenable to access N-thioacyl sulfamates.

Biological tissues comprise a spatially complex structure, composition and organization at the microscale, named the microstructure. Given the close structure-function relationships in tissues, structural characterization is essential to fully understand the functioning of healthy and pathological tissues, as well as the impact of possible treatments. Here, we present a nondestructive imaging approach to perform quantitative 3D histo(patho)logy of biological tissues, termed Cryogenic Contrast-Enhanced MicroCT (cryo-CECT). By combining sample staining, using an X-ray contrast-enhancing staining agent, with freezing the sample at the optimal freezing rate, cryo-CECT enables 3D visualization and structural analysis of individual tissue constituents, such as muscle and collagen fibers. We applied cryo-CECT on murine hearts subjected to pressure overload following transverse aortic constriction surgery. Cryo-CECT allowed to analyze, in an unprecedented manner, the orientation and diameter of the individual muscle fibers in the entire heart, as well as the 3D localization of fibrotic regions within the myocardial layers. We foresee further applications of cryo-CECT in the optimization of tissue/food preservation and donor banking, showing that cryo-CECT also has clinical and industrial potential.

A carbonylative route towards the synthesis of benzimidazo[2,1b]quinazolin-12-ones was developed. The key step in this strategy consists of an intramolecular carbonylative lactam formation, starting from N-(2-bromophenyl)-1H-benzimidazol-2amines. These precursor molecules were synthesized by two different methods to introduce a variety of substituents on the aromatic ring systems. Interestingly, only near-stoichiometric amounts of carbon monoxide were required in the ring-closing aminocarbonylation reaction, rendering the developed strategy also suitable for late-stage 13 C-isotopic labelling.