The Leaflex™ Catheter System - a viable treatment option alongside valve replacement? Preclinical feasibility of a novel device designed for fracturing aortic valve.

AIMS: To demonstrate the feasibility of the Leaflex™ Catheter System, a novel percutaneous device for fracturing valve calcification using mechanical impact in order to regain leaflet mobility. METHODS AND RESULTS: Radiographic analysis of calcium patterns in 90 ex vivo human aortic valve leaflets demonstrated that 82% of leaflets had a typical "bridge" or "half-bridge" pattern, which formed the basis for the catheter design. The therapeutic effect was quantified in 13 leaflets showing a reduction of 49±16% in leaflet resistance to folding after treatment. A pulsatile flow simulator was then used with 11 ex vivo valves demonstrating an increase in aortic valve area of 35±12%. Using gross pathology and histology on fresh calcified leaflets, we then verified that mechanical impacts do not entail excessive risk of embolisation. In vivo safety and usability were then confirmed in the ovine model. CONCLUSIONS: We demonstrated preclinically that it is feasible to improve valve function using the Leaflex™ technology. Once demonstrated clinically, such an approach may have an important role as preparation for or bridging to TAVI, as destination treatment for patients where TAVI is clinically or economically questionable and, in the future, maybe even as a means to slow disease progression in asymptomatic patients.

Neuronal activity significantly reduces water displacement: DWI of a vital rat spinal cord with no hemodynamic effect.

Changes in the diffusion weighted MRI (DWI) signal were observed to be correlated with neuronal activity during chemically induced brain activity, epileptic seizures, or visual stimulation. These changes suggest a possible reduction in water displacement that accompanies neuronal activity, but were possibly affected by other physiological mechanisms such as blood oxygenation level and blood flow. We developed an imaging experiment of an excised and vital newborn rat spinal cord to examine the effect of neuronal function on the displacement of water molecules as measured by DWI signal. This approach provides a DWI experiment of a vital mammalian CNS tissue in the absence of some of the systemic sources of noise. We detected a significant and reproducible drop with an average value of 19.5 ± 1.6% (mean ± SE) upon activation. The drop repeated itself in three orthogonal directions. ADC values corresponded to an oblate anisotropy. This result was validated by high resolution DWI of a fixed tissue, imaged with an ultra-high field MRI. The results support our working hypothesis that water displacement is affected by neuronal activation. These results further imply that water displacement might serve as a potential marker for brain function, and that, although commonly viewed as wholly electrochemical, neuronal activity includes a significant mechanical dimension that affects water displacement.