"4D Flow" cardiac magnetic resonance allows for measurement of the haemodynamic velocity fields in the cardiac chambers. 4D Flow created particle tracing simulations in left ventricles of a control group (n=14), obese group with preserved ejection fraction (n=8), and with dilated cardiomyopathy (DCM, n=15). Transit time of blood was quantified with a residence time distribution (RTD) based on intraventricular particle lifespans. Examination of the 4D Flow velocity fields determined flow patterns responsible for the difference in (RTD) outcomes. Controls had faster transit times than the obese group (p=0.495) and the DCM group (p<0.01), with no difference between the non-control groups (p=0.22). A vortex that develops around the E-Wave was responsible for redirecting flow in the control group from its initial heading toward the apex around toward the left ventricular outflow tract, which has been reported in literature. In the non-control groups, the redirection phenomenon was disrupted. The volume of the redirected blood was quantified with a novel marker of diastolic function, the redirection index (RI), the ratio of the redirected blood to the stroke volume. There was improved performance between control and non-control groups (p<0.01 for control vs both non-controls), and virtually identical diastolic flow performance between the non-controls (p=0.998). Particle pathlines are strongly influenced by redirection, and this phenomenon largely explains the difference in RTD outcomes between heathy controls and pathology.

Previous studies suggest cardiac imaging in cancer patients for detection of cancer-therapy-related cardiac dysfunction (CTRCD) is discordant with international guidelines, with clinical implications unknown. Cancer patients were recruited prior to either anthracyclines or trastuzumab administration and underwent concurrent imaging strategy of Multigated Acquisition Scan (MUGA)-based cardiac imaging with timing determined by treating oncologist, and echocardiographic-based cardiac imaging with timing advised by European Society of Medical Oncology (ESMO) guidelines. Outcomes included: (a) adherence to imaging timepoints; (b) limits-of-agreement (LoA) between MUGA and echocardiographic LVEF measurements; (c) detection of CTRCD; and (d) global longitudinal strain accuracy in predicting cardiac dysfunction. 35 patients were recruited (15 breast cancer, 19 hematological malignancy and 1 gastric cancer patient). 14 patients were treated with trastuzumab and 21 with anthracyclines. Adherence to guideline-advised timing was 37.1% for MUGA-guided approach, and 83.8% for echocardiographic-guided approach (p<0.001 for difference). 2D-LVEF and MUGA-LVEF correlated poorly (r=0.51, 95%CI [-0.09 to 0.37], p=0.22), with poor agreement (bias=0.2%, LoA=37.0%, 95%CI [-18.45 to +18.7%]). Significant correlation was seen between 3D-LVEF and MUGA-LVEF (r=0.33, 95%CI [0.1 to 0.53], p=0.005) with poor agreement (bias=1.8%, LoA=29.9%, 95% CI [-13.1 to 16.8%]). Only 1 case (2.9%) of CTRCD was diagnosed by MUGA, compared to 6 (17.1%) by 3D-LVEF. Four patients (11%) had >10% decrement in 3D-LVEF not detected by MUGA. GLS at 2 months displayed significant ability to predict CTRCD as defined by 3D-LVEF (AUC 0.75,95%CI [0.55 – 0.94]). Cardiac imaging in patients at risk of CTRCD diverges from recommended guidelines and the frequently-chosen modality of MUGA correlates poorly with echocardiographic measurements.

This laboratory has been using a derivatized bead assay to study cell surface properties in many experimental systems. Here we test its efficacy in the yeast/concanavalin A (Con A) binding model to determine if immobilized Con A is inhibited by the same saccharides that inhibit free Con A binding. This system offers an excellent test case for the efficacy and validity of the derivatized bead assay. Con A binds to yeast because yeast are rich in cell surface mannose residues, a Con A preferential binding sugar. Here we examine the effects of 30 different sugars (0.05 M) on the binding of yeast to agarose beads derivatized with Con A, in a total of 3998 trials, with an average of over 133 replicates for each sugar. The most inhibitory sugars included D(+) melezitose, D(+) trehalose and maltotriose, the same sugars that effectively inhibit binding of free Con A. The results suggest that the bead assay is an effective approach to study the binding properties of cells, and most important, it is so rapid that hundreds of trials can be done in the time it would take to do one trial using conventional assays (supported by NIH NIGMS SCORE, RISE, MARC, the ITQ program, and the Joseph Drown Foundation).