A universal biventricular coordinate system incorporating valve annuli: Validation in congenital heart disease.

Universal coordinate systems have been proposed to facilitate anatomic registration between three-dimensional images, data and models of the ventricles of the heart. However, current universal ventricular coordinate systems do not account for the outflow tracts and valve annuli where the anatomy is complex. Here we propose an extension to the 'Cobiveco' biventricular coordinate system that also accounts for the intervalvular bridges of the base and provides a tool for anatomically consistent registration between widely varying biventricular shapes. CobivecoX uses a novel algorithm to separate intervalvular bridges and assign new coordinates, including an inflow-outflow coordinate, to describe local positions in these regions uniquely and consistently. Anatomic consistency of registration was validated using curated three-dimensional biventricular shape models derived from cardiac MRI measurements in normal hearts and hearts from patients with congenital heart diseases. This new method allows the advantages of universal cardiac coordinates to be used for three-dimensional ventricular imaging data and models that include the left and right ventricular outflow tracts and valve annuli.

Animal Model Dependent Response to Pentagalloyl Glucose in Murine Abdominal Aortic Injury.

Abdominal aortic aneurysms (AAAs) are a local dilation of the aorta and are associated with significant mortality due to rupture and treatment complications. There is a need for less invasive treatments to prevent aneurysm growth and rupture. In this study, we used two experimental murine models to evaluate the potential of pentagalloyl glucose (PGG), which is a polyphenolic tannin that binds to and crosslinks elastin and collagen, to preserve aortic compliance. Animals underwent surgical aortic injury and received 0.3% PGG or saline treatment on the adventitial surface of the infrarenal aorta. Seventeen mice underwent topical elastase injury, and 14 mice underwent topical calcium chloride injury. We collected high-frequency ultrasound images before surgery and at 3-4 timepoints after. There was no difference in the in vivo effective maximum diameter due to PGG treatment for either model. However, the CaCl2 model had significantly higher Green-Lagrange circumferential cyclic strain in PGG-treated animals (p < 0.05). While ex vivo pressure-inflation testing showed no difference between groups in either model, histology revealed reduced calcium deposits in the PGG treatment group with the CaCl2 model. These findings highlight the continued need for improved understanding of PGG's effects on the extracellular matrix and suggest that PGG may reduce arterial calcium accumulation.

A Wireless Implantable Passive Intra-Abdominal Pressure Sensing Scheme via Ultrasonic Imaging of a Microfluidic Device.

In this article, we demonstrate a wireless and passive physiological pressure sensing scheme that utilizes ultrasound imaging of an implantable microfluidic based pressure sensitive transducer. The transducer consists of a sub-mm scale pressure sensitive membrane that covers a reservoir filled with water and is connected to a hydrophobic micro-channel. Applied pressure onto the transducer deflects the membrane and pushes the water from the reservoir into the channel; the water's travelling distance in the channel is a function of the applied pressure, which is quantitatively measured by using a 40 MHz ultrasound imaging system. The sensor presents a linear sensitivity of 42 kPa/mm and a spatial resolution of 1.2 kPa/30 µm in the physiological range of abdominal compartment syndrome. Reliability assessments of the transducer confirm its ability to remain functional after more than 600 cycles of pressure up to 55 kPa over the course of 2 days. Ex vivo experimental results verify the practical capability of the technology to effectively measure pressures under a 15 mm thick porcine skin. It is anticipated that this technology can be applied to a broad range of implantable pressure measurement, by simply tuning the thickness of the thin polydimethylsiloxane membrane and the geometry of the reservoir.

Anti-tumor efficacy of theliatinib in esophageal cancer patient-derived xenografts models with epidermal growth factor receptor (EGFR) overexpression and gene amplification.

Targeted therapy is not yet approved for esophageal cancer (EC). In this study, we first evaluated EGFR gene and protein expression in 70 Chinese EC patient tumor samples collected during surgery. We then established 23 patient-derived EC xenograft (PDECX) models and assessed the efficacy of theliatinib, a potent and highly selective EGFR inhibitor currently in Phase I clinical study, in 9 PDECX models exhibiting various EGFR expression levels. Immunohistochemical analysis showed that 50 patient tumor samples (71.4%) had high EGFR expression. Quantitative PCR showed that eight tumors (11.6%) had EGFR gene copy number gain, and fluorescence in situ hybridization (FISH) revealed that four tumors had EGFR gene amplification. These results suggest that EGFR protein may be overexpressed in many EC tumors without gene amplification. Also detected were rare hot-spot mutations in EGFR and PIK3CA, whereas no mutations were found in K-Ras or B-Raf. Theliatinib exhibited strong antitumor activity in PDECX models with high EGFR expression, including remarkable tumor regression in two PDECX models with both EGFR gene amplification and protein overexpression. However, the efficacy of theliatinib was diminished in models with PI3KCA mutations or FGFR1 overexpression in addition to high EGFR expression. This study demonstrates that theliatinib could potentially benefit EC patients with high EGFR protein expression without mutations or aberrant activities of associated factors, such as PI3KCA or FGFR1.