Pulsed Focused Ultrasound (pFUS) exposures and devices for tissue permeabilization without contrast agents

PROJECT SUMMARYAccording to recent reports from across the world, the need to continuously evaluate lung edema in critically illCOVID-19 patients is essential.

Chest x-ray has reduced sensitivity early in the disease; the contagiousness ofthe virus and the risk of transporting unstable patients with hypoxemia make chest CT a limited option for thepatient with suspected or established COVID-19.

Lung ultrasound (LUS) is non-ionizing and safe, and hasrecently emerged as a useful triage and monitoring tool for lung edema quantification in COVID-19 patients.

InLUS, imaging artifacts termed A-lines (periodic horizontal lines parallel to the lung surface indicating a normalaeration pattern) and B-lines (comet-like hyperechoic regions indicating an alveolar or interstitial abnormality)are evaluated.

B-lines stem from acoustic reverberations within regions of alveolar edema, and their number andthickness are known to be correlated with edema severity.

However, visualization and quantification of B-linesrequires substantial training, and even then, are highly operator and machine dependent. This is in part due toa still incomplete understanding of the exact physical mechanism of B-line formation.

In this emergencycompetitive revision to the current award on ultrasound cavitation-aided drug delivery to solid tumors we proposeto build on our expertise in dissecting the origins of US imaging artifacts and ultrasound instrumentationcapabilities to 1) identify the origins of B-line artifact in LUS and specific associated RF signal features, and 2)based on the attained understanding, develop a single-element, wearable, automated, non-imaging lungultrasound sensor (LUSS) for continuous monitoring of lung pathology while minimizing provider time, risk ofvirus exposure, and radiation.

Individual adhesive LUSS elements will be attached to patients in specificanatomic locations similarly to ECG leads, and ultrasound signals will be collected and processed withautomated algorithms to provide lung edema score that can be used in clinical decision making.

We havedesigned a proof of principle study scaled to the shortest timeline possible to get the device into the clinic quickly,with the following specific aims.

In SA1 we will perform standard LUS exams in non-COVID patients withcardiogenic pulmonary edema while collecting raw RF signal data to understand the manifestation of B-lines inraw RF signals and develop automated signal processing algorithm.

In SA2 we will design and fabricate single-element LUSS prototype and validate the automated signal processing algorithm against LUS imaging in lung-mimicking sponge-based phantom.

By the end of the 9-month project the prototype device will be ready for usein not only COVID19 patients, but other ED patients for whom continuous evaluation of lung condition is essential(bacterial pneumonia, cardiogenic edema, dialysis).

Our commercialization approach here is to broadly licensethis simple technology so that large ultrasound manufacturers with broad sales and distribution capabilities canget the technology to the users.