Columbia University, 1210 Amsterdam Ave, New York, New York, 10027-7003, United States
Popular version of 2aBAa1 – Neuronavigated focused ultrasound for clinical bbb opening in alzheimer’s and brain cancer patients
Presented at the 184 ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0018295
Ultrasound is widely known as an imaging modality in obstetrics and cardiology as well as several other applications but less known regarding its therapeutic effects despite its recent approvals in the clinic for ablation of prostate cancer and essential tremors. In the studies presented, we demonstrate that focused ultrasound (FUS) can be used in conjunction with microbubbles to open the blood-brain barrier (BBB) through the intact scalp of Alzheimer’s and pediatric tumor patients. The BBB is the main defense of the brain against toxic molecules but also prevents drugs from treating brain disease. In the case of Alzheimer’s, we demonstrate for the first time that the BBB opening resulting from FUS in the prefrontal cortex acts as an antibody in the brain. BBB opening results into a beneficial immune response in the brain that significantly reduces the beta amyloid in the region where ultrasound opened the blood-brain barrier. This was shown in 5 patients with Alzheimer’s.
In the case of the pediatric tumor patients, we aimed into the stem, which is a critical region between the spinal cord and the brain. The tumors in the pediatric patients are gliomas that grow in the stem where critical nerve fibers run through and they are therefore inoperable. We showed for the first time that BBB opening can be repeatedly induced with FUS in conjunction with microbubbles safely and efficiently in patients with pediatric glioma tumors in the stem. In this case, we used FUS in conjunction with a drug that, when crossing the blood-brain barrier, increases its efficiency. The patients reported smoother limb movement after treatment with the drug potentially acting more potently on the tumor.
It was concluded that ultrasound can safely open the blood-brain barrier in both patients as young as 6 years old to as old as 83 years old completely noninvasively and more importantly reduce the disease pathology and/or symptoms. The system is thus versatile, does not require a dedicated MR system or to be performed in the MR scanner unlike other systems and the entire procedure can last less than 30 min from start to finish. Ultrasound can thus be used alone or in conjunction with a drug in order to change the current dire landscape of treatment of brain disease. Finally, we show how Alzheimer’s beta amyloid and tau are excreted from the brain and can be detected with a simple blood test.
Christopher Kube – kube@psu.edu
Twitter: @_chriskube
Penn State University, 212 Earth and Engineering Sciences Bldg, University Park, PA, 16802, United States
Tao Sun, University of Virginia
Samuel Clark, Advanced Photon Source, Twitter: @advancedphoton
Find the authors on LinkedIn:
www.linkedin.com/in/chriskube
www.linkedin.com/in/suntao
Popular version of 3pID2-Acoustics for in-process melt pool monitoring during metal additive manufacturing, presented at the 183rd ASA Meeting.
3D printed or additively manufactured (AM) metal parts are disrupting the status quo in a variety of industries including defense, transportation, energy, and space exploration. Engineers now design and produce customizable parts unimaginable only a decade ago. New geometrical or part shape freedom inherent to AM has already led to part performance often beyond traditionally manufactured counterparts. In the years to come, another revolutionary performance jump is expected by enabling the AM process to control the grain layout and structural features on the microscopic scale. Grains are the building blocks of metal parts that dictate many of the performance metrics associated with the descriptors of bigger, faster, and stronger.
The second performance revolution of AM metal parts requires uncovering new knowledge in the complicated physics present during the AM process. 3D printed metals are born from an energy source such as a laser or electron beam to selectively melt feedstock material at microscopic locations dictated by the computerized part drawing. Melted locations temporarily form liquid metal melt pools that solidify after the energy source moves to another location. Resulting grain structure and pore/defect formation strongly depends on how the melt pool cools and solidifies.
Over the past five years, high-energy X-rays only available at particle accelerators are used for direct real-time visualization of AM melt pool dynamics and solidification. Figure 1 shows an example X-ray frame, which captured a laser-generated melt pool moving in a single direction with a speed of 800 mm/ms.
This situation mimics the laser and melt pool movement found during 3D printing metal parts. Being able to directly observe melt pool behavior has led to new and improved understanding of the underlying physics. Unfortunately, experiments at such X-ray sources is difficult to ascertain because of extremely high demand across the sciences. Additionally, the measurement technique relegated to high-energy X-ray sources is not transferrable to metal 3D printers that exist in normal industrial settings. For these reasons, ultrasonics are being explored as a melt pool monitoring technology that can be deployed within real 3D printers.
Ultrasound is commonly used for imaging and detecting features inside of solid materials. For example, ultrasound is applied in medical settings during pregnancy or for diagnostics. Application of ultrasound for melt pool monitoring is made possible because of the tendency of ultrasound to scatter from the melt pool’s solid/liquid boundary. The development of the technique is being supported alongside X-ray imaging at the Advanced Photon Source at Argonne National Laboratory. X-ray imaging is providing the extremely important ground truth melt pool behavior allowing for easy interpretation of the ultrasonic response. In Figure 1, the ultrasonic response from the exact same melt pool given in the X-ray video is being shown for two different sensors. As the melt pool enters the field of view of the ultrasonic sensors (see online video), features in the ultrasound response confirms their sensitivity to the melt pool.
In this research, high-energy X-rays are being used to develop the ultrasonic technique and technology. In the coming year, the knowledge developed will be leveraged such that ultrasound can be applied on its own for melt pool monitoring in real metal 3D printers. Currently, no existing technology can capture the highly dynamic melt pool behavior through the depth of the part or substrate.
Practical benefits and value of melt pool monitoring within 3D printers are significant. Ultrasound can provide a quick check to determine the optimal laser power and speed combinations toward accelerated determination of process parameters. Currently, determination of the optimal process parameters requires destructive postmortem microscopy techniques that are extremely costly, time-consuming (sometimes more than a year), and wasteful. Ultrasound has the potential to reduce these factors by an order of magnitude. Furthermore, metal 3D printing processes are highly variable over many months, across different machines, and even when using feedstock powder from different suppliers. Ultrasonic melt pool monitoring can provide period checks to assure variability is minimized.
University of Washington 1013 NE 40th St. Seattle WA 98105
Popular version of 2aPAb – Designing an array for acoustic manipulation of kidney stones Presented Tuesday morning, May 24, 2022 182nd ASA Meeting Click here to read the abstract
Ultrasound technology is becoming an important treatment tool. For instance, sound waves can apply a radiation pressure that can displace an object. Multi-element arrays are complex ultrasound sources that consist of several small transducers that can be driven in sync or a specific order to output pressure waves with different shapes. Pressure wave shapes that have a doughnut shape or a long tube are useful as they can trap an object in the center and as we control the location of the doughnut the object follows. This technology can be used to trap small kidney stones or stone fragments and move them from the kidney collection areas toward the kidney exit without surgery. We have demonstrated the ability to move kidney stone models in the bladders transcutaneously in live pigs under anesthesia. We are currently designing a new multi-element array that will enable us to adapt this technology to move stones in the complex structure of the kidney over larger distances. This technology will reduce the surgery associated with kidney stone treatments by removing small stones or fragments before they become larger, which will lead to surgery, and eliminating emergency room visits by relieving blockages from these stones or fragments.
Controlled steering of kidney stones toward the kidney exit with an ultrasound array.
Popular version of paper 1aBA5 Presented Monday morning, November 5, 2018 176th ASA Meeting, Minneapolis, MN
A key gap for underserved communities around the world is the lack of clinical laboratories and specialists to analyze samples. But thanks to advances in machine learning, a new generation of ‘smart’ point-of-care diagnostics are filling this gap and, in some cases, even surpassing the effectiveness of specialists at a lower cost.
Take the case of pneumonia. Left untreated, pneumonia can be fatal. The leading cause of death among children under the age of five, pneumonia claims the lives of approximately 2,500 a day – nearly all of them in low-income nations.
To understand why, consider the differences in how the disease is diagnosed in different parts of the world. When a doctor in the U.S. suspects a patient has pneumonia, the patient is usually referred to a highly-trained radiologist, who takes a chest X-ray using an expensive machine to confirm the diagnosis.
Because X-ray machines and radiologists are in short supply across much of sub-Saharan Africa and Asia and the tests themselves are expensive, X-ray diagnosis is simply not an option for the bottom billion. In those settings, if a child shows pneumonia symptoms, a cough and a fever, she is usually treated with antibiotics as a precautionary measure and sent on her way. If, in fact, the child does not have pneumonia, this means she receives unnecessary antibiotics, leaving her untreated for her real illness and putting her health at risk. The widespread overuse of antibiotics also contributes to the buildup in resistance of the so-called “superbug” – a global threat.
In this context, an interdisciplinary team of algorithm developers, software engineers and global health experts at Intellectual Ventures’ Global Good—a Bill and Melinda Gates-backed technology fund that invents for humanitarian impact—considered the possibility of developing a low-cost tool capable of automating pneumonia diagnosis.
The team turned to ultrasound – an affordable, safe, and widely-available technology that can be used to diagnose pneumonia with a comparable level of accuracy to X-ray.
It wouldn’t be easy. To succeed, the device would need to be cost-effective, portable, easy-to-use and able to do the job quickly, accurately and automatically in challenging environments.
Global Good started by building an algorithm to recognize four key features associated with lung conditions in an ultrasound image – pleural line, B-line, consolidation and pleural effusion. This called for convolutional neural networks (CNNs)—a machine learning method well-suited for image classification tasks. The team trained the algorithm by showing it ultrasound images collected from over 70 pediatric and adult patients. The features were annotated on the images by expert sonographers to ensure accuracy.
Figure 1: Pleural line (upper arrow) and a-lines (lower arrow), indication of normal lung
Figure 2: Consolidation (upper arrow) and merged B-line (lower arrow), indication of abnormal lung fluid and potentially pneumonia
Early tests show that the algorithm can successfully recognize abnormal lung features in ultrasound images and those features can be used to diagnose pneumonia as reliably as X-ray imaging—a highly encouraging outcome.
The algorithm will eventually be installed on an ultrasound device and used by minimally-trained healthcare workers to make high-quality diagnosis accessible to children worldwide at the point of care. Global Good hopes that the device will eventually bring benefits to patients in wealthy markets as well, in the form of a lower-cost, higher quality and faster alternative to X-ray.
Physics Faculty Moscow State Univerity Moscow RUSSIAN FEDERATION
Center for Industrial and Medical Ultrasound Applied Physics Laboratory University of Washington Seattle, WashingtonUNITED STATES
Popular version of paper 4pBA1, “Kidney stone pushing and trapping using focused ultrasound beams of different structure.” Presented Thursday afternoon, December 1, 2016 at 1:00pmHAST. 172nd ASA Meeting, Honolulu
Urinary stones (such as kidney or bladder stones) are an important health care problem. One in 11 Americans now has urinary stone disease (USD), and the prevalence is increasing. According to a 2012 report from the National Institute of Diabetes and Kidney and Digestive Diseases (Urological Diseases in America), the direct medical cost of USD in the United States is $10 billion annually, making it the most expensive urologic condition.
Our lab is working to develop more effective and more efficient ways to treat stones. Existing treatments such as shock wave lithotripsy or ureteroscopy are minimally invasive, but can leave behind stone fragments that remain in the kidney and potentially regrow into larger stones over time. We have successfully developed and demonstrated the use of ultrasound to noninvasively move stones in the kidney of human subjects. This technology, called ultrasonic propulsion (UP), uses ultrasound to apply a directional force to the stone, propelling it in a direction away from the sonic source, or transducer. Some stones need to be moved towards the ureteropelvic junction (the exit from the kidney that allows stones to pass through the ureter to the bladder) to aid their passage. In other cases, this technology may be useful to relieve an obstruction caused by a stone that may just need a nudge or a rotation to pass, or at least to allow urine to flow and decompress the kidney.
While UP is able to help stones pass, it is limited in how the stones can be manipulated by an ultrasound transducer in contact with the skin from outside the body. Some applications require the stone to be moved sideways or towards the transducer rather than away from it.
To achieve more versatile manipulation of stones, we are developing a new strategy to effectively trap a stone in an ultrasound beam. Acoustic trapping has been explored by several other researchers, particularly for trapping and manipulating cells, bubbles, droplets, and particles much smaller than length of the sound wave. Different configurations have been used to trap particles in standing waves and focused fields. By trapping the stone in an ultrasound beam, we can then move the transducer or electronically steer the beam to move the stone with it.
Figure 1. The cross section at the focus for the ultrasound pressure of a vortex beam. The pressure magnitude (left) has a donut-shape distribution, whereas the phase (right) has a spiral-shape structure. A stone can be trapped at the center of the ring.
In this work, we accomplished trapping through the use of vortex beams. Typical focused beams create a single region of high ultrasound pressure, producing radiation force away from the transducer. Vortex beams, on the other hand, are focused beams that create a tube-shaped intensity pattern with a spiraling wave front (Fig. 1). The ultrasound pressure in the middle is very low, while the pressure around the center is high. The result is that there is a component of the ultrasound radiation force pushing the stone towards the center and trapping it in the middle of the beam. In addition to trapping, such a beam can apply a torque to the stone and can rotate it.
To test this idea, we simulated the radiation force on spheres of different materials (including stones) to determine how each would respond in a vortex beam. An example is shown in Fig 2. A lateral-axial cross section of the beam is displayed, with a spherical stone off-center in the tube-shaped beam. The red arrow shows that the force on the sphere is away from the center because the stone is outside of the vortex. Once the center of the stone crosses the peak, the force is directed inward. Usually, there is also some force away from the transducer still, but the object can be trapped against a surface.
Figure 2. The simulated tubular field such as occurs in a vortex beam and its force on a stone. In this simulation the transducer is on the left and the ultrasound propagates to the right. The arrow indicates the force which depends on the position of the stone.
We also built transducers and electrically excited them to generate the vortex in experiments. At first, we used the vortex to trap, rotate, and drag an object on the water surface (Fig. 3). By changing the charge of the vortex beam (the rate of spiraling generated by the transducer), we controlled the diameter of the vortex beam, as well as the direction and speed at which the objects rotated. We also tested manipulation of objects placed deep in a water tank. Glass or plastic beads and kidney stones placed on a platform of tissue-mimicking material. By physically shifting the transducer, we were able to move these objects a specified distance and direction along the platform (Fig 4). These results are best seen in videos at apl.uw.edu/pushingstones.
Figure 3. A small object trapped in the center of a vortex beam on the water surface. The ring-shaped impression due to radiation force on the surface can be seen. The phase difference between each sector element of the transducer affects the diameter of the beam and the spin rate. The 2 mm plastic object floating on the surface is made to rotate by the vortex beam.
Figure 4. A focused vortex beam transducer in water (shown on the top) traps one of the styrofoam beads (shown in the bottom) and translates it in lateral direction.
We have since worked on developing vortex beams with a 256-element focused array transducer. Our complex array can electronically move the beam and drag the stone without physically moving the transducer. In a highly focused transducer, such as our array, sound can even be focused beyond the stone to generate an axial high pressure spot to help trap a stone axially or even pull the stone toward the transducer.
There are several ways in which this technology might be useful for kidney stones. In some cases, it might be employed in gathering small particles together and moving them collectively, holding a larger stone in place for fragmentation techniques such as lithotripsy, sweeping a stone when the anatomy inhibits direct radiation force away from the transducer, or, as addressed here dragging or pulling a stone. In the future, we expect to continue developing phased array technology to more controllably manipulate stones. We are also working to develop and validate new beam profiles, and electronic controls to remotely gather the stone and move it to a new location. We expect that this sort of tractor beam could also have applications in manufacturing, such as ever shrinking electronics, and even in space.
This work was supported by RBBR 14-02- 00426, NIH NIDDK DK43881 and DK104854, and NSBRI through NASA NCC 9-58.
References
O.A. Sapozhnikov and M.R. Bailey. Radiation force of an arbitrary acoustic beam on an elastic sphere in a fluid. – J. Acoust. Soc. Am., 2013, v. 133, no. 2, pp. 661-676.
A.V. Nikolaeva, S.A. Tsysar, and O.A. Sapozhnikov. Measuring the radiation force of megahertz ultrasound acting on a solid spherical scatterer. – Acoustical Physics, 2016, v. 62, no. 1, pp. 38-45.
J.D. Harper, B.W. Cunitz, B. Dunmire, F.C. Lee, M.D. Sorensen, R.S. Hsi, J. Thiel, H. Wessells, J.E. Lingeman, and M.R. Bailey. First in human clinical trial of ultrasonic propulsion of kidney stones. – J. Urology, 2016, v. 195, no. 4 (Part 1), pp. 956–964.
