Improved Left Ventricular Mass Quantification with Partial Voxel Interpolation – In-Vivo and Necropsy Validation of a Novel Cardiac MRI Segmentation Algorithm

Background—CMR typically quantifies LV mass (LVM) via manual planimetry (MP), but this approach is time consuming and does not account for partial voxel components - myocardium admixed with blood in a single voxel. Automated segmentation (AS) can account for partial voxels, but this has not been used for LVM quantification. This study used automated CMR segmentation to test the influence of partial voxels on quantification of LVM. Methods and Results—LVM was quantified by AS and MP in 126 consecutive patients and 10 laboratory animals undergoing CMR. AS yielded both partial voxel (ASPV) and full voxel (ASFV) measurements. Methods were independently compared to LVM quantified on echocardiography (echo) and an ex-vivo standard of LVM at necropsy. AS quantified LVM in all patients, yielding a 12-fold decrease in processing time vs. MP (0:21±0:04 vs. 4:18±1:02 min; pFV mass (136±35gm) was slightly lower than MP (139±35; Δ=3±9gm, pPV yielded higher LVM (159±38gm) than MP (Δ=20±10gm) and ASFV (Δ=23±6gm, both pPV and ASFV correlated with larger voxel size (partial r=0.37, pPV yielded better agreement with echo (Δ=20±25gm) than did ASFV (Δ=43±24gm) or MP (Δ=40±22gm, both pPV and ex-vivo results were similar (Δ=1±3gm, p=0.3), whereas ASFV (6±3g, P\u3c0.001) and MP (4±5 g, P=0.02) yielded small but significant differences with LVM at necropsy

Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria

SummaryThe PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRα1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRα1:EPCR complexes with analysis of 885 CIDRα1 sequences, showing that the EPCR-binding surfaces of CIDRα1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRα1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding