Enhancing r1 Relaxivity in GdDOTA-Monoamide Complexes through Polar Group-Mediated Ordering of Second-Sphere Water Molecules.

This study was designed to test whether the single appended phosphonate group in GdDOTA-1AmP is sufficient for catalyzing the exchange of proton from the single inner-sphere water-exchanging molecule. Unlike the other phosphonate derivatives in this series, GdDOTA-1AmP showed a surprisingly smooth increase in r1 relaxivity from 3.0 to 6.3 mM-1 s-1 at 20 MHz as the pH was lowered from 9 to 2.5. In comparison to the bis-, tris-, and tetrakis-phosphonate analogues, which all show a biphasic dependence of r1 with changes in pH, the unique r1 versus pH characteristics of GdDOTA-1AmP are shown to closely parallel deprotonation of the single appended phosphonate group. Although the tissue biodistribution and clearance rates of GdDOTA-1AmP are more favorable than the other more highly charged phosphonate derivatives, the pH dependency of r1 is substantially reduced at magnetic fields typically used for small animal imaging (7 and 9.4T), so the attractiveness of this new molecule for quantitative imaging of tissue pH is diminished. However, this study provides some new insights into the feasibility of designing pH-responsive MRI contrast agents based upon fundamental acid-base prototropic mechanisms.

Paramagnetic encoding of molecules.

Contactless digital tags are increasingly penetrating into many areas of human activities. Digitalization of our environment requires an ever growing number of objects to be identified and tracked with machine-readable labels. Molecules offer immense potential to serve for this purpose, but our ability to write, read, and communicate molecular code with current technology remains limited. Here we show that magnetic patterns can be synthetically encoded into stable molecular scaffolds with paramagnetic lanthanide ions to write digital code into molecules and their mixtures. Owing to the directional character of magnetic susceptibility tensors, each sequence of lanthanides built into one molecule produces a unique magnetic outcome. Multiplexing of the encoded molecules provides a high number of codes that grows double-exponentially with the number of available paramagnetic ions. The codes are readable by nuclear magnetic resonance in the radiofrequency (RF) spectrum, analogously to the macroscopic technology of RF identification. A prototype molecular system capable of 16-bit (65,535 codes) encoding is presented. Future optimized systems can conceivably provide 64-bit (~10^19 codes) or higher encoding to cover the labelling needs in drug discovery, anti-counterfeiting and other areas.

Stereoselective Synthesis of Ezetimibe via Cross-Metathesis of Homoallylalcohols and α-Methylidene-ß-Lactams.

Ru-catalyzed cross-metathesis (CM) reaction between ß-arylated α-methylidene-ß-lactams and terminal olefins was developed. The CM reaction is effectively catalyzed with Hoveyda-Grubbs second-generation catalyst affording corresponding α-alkylidene-ß-aryl-ß-lactams in good isolated yields (41-83%) with exclusive Z-selectivity. The developed protocol was successfully applied for stereoselective preparation of Ezetimibe, the commercial cholesterol absorption inhibitor.

ADR--Anatomy-Driven Reformation.

Dedicated visualization methods are among the most important tools of modern computer-aided medical applications. Reformation methods such as Multiplanar Reformation or Curved Planar Reformation have evolved as useful tools that facilitate diagnostic and therapeutic work. In this paper, we present a novel approach that can be seen as a generalization of Multiplanar Reformation to curved surfaces. The main concept is to generate reformatted medical volumes driven by the individual anatomical geometry of a specific patient. This process generates flat views of anatomical structures that facilitate many tasks such as diagnosis, navigation and annotation. Our reformation framework is based on a non-linear as-rigid-as-possible volumetric deformation scheme that uses generic triangular surface meshes as input. To manage inevitable distortions during reformation, we introduce importance maps which allow controlling the error distribution and improving the overall visual quality in areas of elevated interest. Our method seamlessly integrates with well-established concepts such as the slice-based inspection of medical datasets and we believe it can improve the overall efficiency of many medical workflows. To demonstrate this, we additionally present an integrated visualization system and discuss several use cases that substantiate its benefits.

Interactive patient-specific vascular modeling with sweep surfaces.

The precise modeling of vascular structures plays a key role in medical imaging applications, such as diagnosis, therapy planning and blood flow simulations. For the simulation of blood flow in particular, high-precision models are required to produce accurate results. It is thus common practice to perform extensive manual data polishing on vascular segmentations prior to simulation. This usually involves a complex tool chain which is highly impractical for clinical on-site application. To close this gap in current blood flow simulation pipelines, we present a novel technique for interactive vascular modeling which is based on implicit sweep surfaces. Our method is able to generate and correct smooth high-quality models based on geometric centerline descriptions on the fly. It supports complex vascular free-form contours and consequently allows for an accurate and fast modeling of pathological structures such as aneurysms or stenoses. We extend the concept of implicit sweep surfaces to achieve increased robustness and applicability as required in the medical field. We finally compare our method to existing techniques and provide case studies that confirm its contribution to current simulation pipelines.