2aBAb2 – Feasibility of using ultrasound with microbubbles to purify cell lines for immunotherapy application

Thomas Matula – matula@uw.edu
Univ. of Washington
1013 NE 40th St.
Seattle, WA 98105

Oleg A. Sapozhnikov
Ctr. for Industrial and Medical Ultrasound
Appl. Phys. Lab
Univ. of Washington
Seattle, Washington
Phys. Faculty

Lev Ostrovsky
Dept. of Appl. Mathematics
University of Colorado
Inst. of Appl. Phys.
Russian Acad. of Sci.
Boulder, CO

Andrew Brayman
John Kucewicz
Brian MacConaghy
Dino De Raad
Univ. of Washington
Seattle, WA

Popular version of paper 2aBAb2
Presented Tuesday morning, Nov 6, 2018
176th ASA Meeting, Victoria, BC, Canada

Cells are isolated and sorted for a variety of diagnostic (e.g., blood tests) and therapeutic (e.g., stem cells, immunotherapy) applications, as well as for general research. The workhorses in most research and commercial labs are fluorescently-activated cell sorters (FACS) [1] and magnetically-labeled cell sorters (MACS) [2]. These tools use biochemical labeling to identify and/or sort cells which express specific surface markers (usually proteins). FACS uses fluorophores that target specific cell markers. The detection of a specific fluorescence wavelength tells the system to sort those cells. FACS is powerful and can sort based on several different cellular markers. However, FACS is also very expensive and complicated such that they are mostly found only in large core facilities.

MACS uses magnetic beads that attach to cell markers. Permanent magnets can then be used to separate magnetically-tagged cells from untagged cells. MACS is much less expensive than FACS, and can be found in most labs. However, MACS also suffers from weaknesses, such as low throughput, and can only sort based on a single marker.

We describe a new method that merges biochemical labeling with ultrasound-based separation. Instead of lasers and fluorophore tags (i.e., FACS), or magnets and magnetic particle tags (i.e., MACS), our technique uses ultrasound and microbubble tags (Fig. 1). Like FACS and MACS, we attach a biochemical label (an antibody) to attach a microbubble to the cell’s surface protein. We then employ an ultrasound pulse that generates an acoustic radiation force, pushing the microbubbles; the attached cells are dragged along with the microbubbles, effectively separating them from untagged cells. This is accomplished because cells only very lightly interact with ultrasound, whereas microbubbles interact very significantly with the sound waves. We theorized that the force acts on the microbubble while the cell acts as a fluid that adds a viscous drag to the system (see [3]).


Figure 1. Cell separation technologies

We can break down our studies into two categories, cell rotation and cell sorting. In both cases we constructed an apparatus to view cells under a microscope. Figure 2 shows a cell rotating as the attached microbubbles align with the sound field (the movie can be found by clicking here). We developed a theory to describe this rotation, and the theory fits the data well, allowing us to ‘measure’ the acoustic radiation force on the conjugate microbubble-cell system (Fig. 3).

Figure 2. A leukemia cell has two attached microbubbles. An ultrasound pulse from above causes the cell to rotate.

Figure 3. We assume that the microbubbles act as point forces. The projection of these forces perpendicular to the radiation force direction leads to a torque on the cell, which is balanced by the viscous torque. This leads to an equation of motion that can be put in terms of angular displacement. Thus, the parameters are detailed in [3]. The results are plotted along with the data, showing a nice match between the theory and data. For our conditions, the acoustic radiation force was found to be F=1.7×10-12N. [IMAGE MISSING]

When placed in a flow stream with other cells, the tagged cells can be easily pushed with ultrasound. Figure 4a shows how a single leukemia cell is pushed downward while normal erythrocytes (red blood cells) continue flowing in the stream (the movie can be found by clicking here). This shows that one can effectively separate tagged cells. However, in a commercial setting, one wants to sort with a much higher concentration of cells. Figure 4b illustrates that this can be accomplished with our simple setup (the movie can be found by clicking here).

To summarize, we show preliminary data that supports the notion of developing an ultrasound-based cell sorter that has the potential for high throughput sorting at a fraction of the cost of FACS.


Figure 4. (a) A single leukemia cell is pushed downward by an acoustic force while red blood cells continue to flow horizontally. It should be possible to detect rare cells using this technique. (b) For high-throughput commercial sorting, a much larger concentration of cells must be evaluated. Here, a large concentration of red blood cells, along with a few leukemia cells are analyzed. The ultrasound pushes the tagged leukemia cells downward. We used blue for horizontal flow (red blood cells) and red for ultrasound-based forcing downward.

[1] M. H. Julius, T. Masuda, and L. A. Herzenberg, “Demonstration That Antigen-Binding Cells Are Precursors of Antibody-Producing Cells after Purification with a Fluorescence-Activated Cell Sorter,” P Natl Acad Sci USA 69, 1934-1938 (1972).

[2] S. Miltenyi, W. Muller, W. Weichel, and A. Radbruch, “High-Gradient Magnetic Cell-Separation with Macs,” Cytometry 11, 231-238 (1990).

[3] T.J. Matula, et al, “Ultrasound-based cell sorting with microbubbles: A feasibility study,” J. Acoust. Soc. Am. 144, 41-52 (2018).

1aBA5 – AI and the future of pneumonia diagnosis

Xinliang Zheng – lzheng@intven.com
Sourabh Kulhare – skulhare@intven.com
Courosh Mehanian — cmehanian@intven.com
Ben Wilson — bwilson@intven.com
Intellectual Ventures Laboratory
14360 SE Eastgate Way
Bellevue, WA 98007, U.S.A.

Zhijie Chen – chenzhijie@mindray.com
Mindray Building, Keji 12th Road South,High-tech Industrial Park,
Nanshan, Shenzhen 518057, P.R. China

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.

4pBA1 – Kidney stone pushing and trapping using focused ultrasound beams of different structure

Oleg Sapozhnikov – olegs@apl.washington.edu
Mike Bailey – bailey@apl.washigton.edu
Adam Maxwell – amax38@uw.edu

Physics Faculty
Moscow State Univerity

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.

sapozhnikov1 Kidney stone

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.


  1. 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.
  2. 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.
  3. 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.

3aBA1 – Ultrasound-Mediated Drug Targeting to Tumors: Revision of Paradigms Through Intravital Imaging

Natalya Rapoport – natasha.rapoport@utah.edu
Department of Bioengineering
University of Utah
36 S. Wasatch Dr., Room 3100
Salt Lake City, Utah 84112

Popular version of paper 3aBA1, “Ultrasound-mediated drug targeting to tumors: Revision of paradigms through intravital imaging”
Presented Wednesday morning, May 25, 2016, 8:15 AM in Salon H
171st ASA Meeting, Salt Lake City

More than a century ago, Nobel Prize laureate Paul Ehrlich formulated the idea of a “magic bullet”. This is a virtual drug that hits its target while bypassing healthy tissues. No field of medicine could benefit more from the development of a “magic bullet” than cancer chemotherapy, which is complicated by severe side effects. For decades, the prospects of developing “magic bullets” remained elusive. During the last decade, progress in nanomedicine has enabled tumor-targeted delivery of anticancer drugs via their encapsulation in tiny carriers called nanoparticles. Nanoparticle tumor targeting is based on the “Achilles’ heels” of cancerous tumors – their poorly organized and leaky microvasculature. Due to their size, nanoparticles are not capable to penetrate through a tight healthy tissue vasculature. In contrast, nanoparticles penetrate through a leaky tumor microvasculature thus providing for localized accumulation in tumor tissue.  After tumor accumulation of drug-loaded nanoparticles, a drug should be released from the carrier to allow penetration into a site of action (usually located in a cell cytoplasm or nucleus). A local release of an encapsulated drug may be triggered by tumor-directed ultrasound; application of ultrasound has additional benefits: ultrasound enhances nanoparticle penetration through blood vessel walls (extravasation) as well as drug uptake (internalization) by tumor cells.

For decades, ultrasound has been used only as an imaging modality; the development of microbubbles as ultrasound contrast agents in early 2000s has revolutionized imaging. Recently, microbubbles have attracted attention as drug carriers and enhancers of drug and gene delivery. Microbubbles could have been ideal carriers for the ultrasound-mediated delivery of anticancer drugs.  Unfortunately, their micron-scale size does not allow effective extravasation from the tumor microvasculature into tumor tissue. In Dr. Rapoport’s lab, this problem has been solved by the development of nanoscale microbubble precursors, namely drug-loaded nanodroplets that converted into microbubbles under the action of ultrasound[1-6]. Nanodroplets comprised a liquid core formed by a perfluorocarbon compound and a two-layered drug-containing polymeric shell (Figure 1). An aqueous dispersion of nanodroplets is called nanoemulsion.

Rapoport 1 - Ultrasound-Mediated Drug Targeting

Figure 1. Schematic representation of a drug-loaded nanodroplet

A suggested mechanism of therapeutic action of drug-loaded perfluorocarbon nanoemulsions is discussed below [3, 5, 6]. A nanoscale size of droplets (ca. 250 nm) provides for their extravasation into a tumor tissue while bypassing normal tissues, which is a basis of tumor targeting. Upon nanodroplet tumor accumulation, tumor-directed ultrasound triggers nanodroplet conversion into microbubbles, which in turn triggers release of a nanodroplet-encapsulated drug. This is because in the process of the droplet-to-bubble conversion, particle volume increases about a hundred-fold, with a related decrease of a shell thickness. Microbubbles oscillate in the ultrasound field, resulting in a drug “ripping” off a thin microbubble shell (Figure 2). In addition, oscillating microbubbles enhance internalization of released drug by tumor cells.

Rapoport 2 - Ultrasound-Mediated Drug Targeting

Figure 2. Schematic representation of the mechanism of drug release from perfluorocarbon nanodroplets triggered by ultrasound-induced droplet-to-bubble conversion; PFC – perfluorocarbon

This tumor treatment modality has been tested in mice bearing breast, ovarian, or pancreatic cancerous tumors and has been proved very effective. Dramatic tumor regression and sometimes complete resolution was observed when optimal nanodroplet composition and ultrasound parameters were applied.

3A.Rapoport 3A 3B.Rapoport 3B 3C.Rapoport 3C

(Figure 3. A – Photographs of a mouse bearing a subcutaneously grown breast cancer tumor xenograft treated by four systemic injections of the nanodroplet-encapsulated anticancer drug paclitaxel (PTX) at a dose of 40 mg/kg as PTX. B – Photographs of a mouse bearing two ovarian carcinoma tumors (a) – immediately before and (b) – three weeks after the end of treatment; mouse was treated by four systemic injections of the nanodroplet-encapsulated PTX at a dose of 20 mg/kg as PTX; only the right tumor was sonicated. C – Photographs (a, c) and fluorescence images (b, d) of a mouse bearing fluorescent pancreatic tumor taken before (a, b) and three weeks after the one-time treatment with PTX-loaded nanodroplets at a dose of 40 mg/kg as PTX (c,d). The tumor was completely resolved and never recurred)[3, 4, 6].

In the current presentation, the proposed mechanism of a therapeutic action of drug-loaded, ultrasound-activated perfluorocarbon nanoemulsions has been tested using intravital laser fluorescence microscopy performed in collaboration with Dr. Brian O’Neill (then with Houston Methodist Research Institute, Houston, Texas) [2]. Fluorescently labeled nanocarrier particles (or a fluorescently labeled drug) were systemically injected though the tail vein to anesthetized live mice bearing subcutaneously grown pancreatic tumors. Nanocarrier and drug arrival and extravasation in the region of interest (i.e. normal or tumor tissue) were quantitatively monitored. Various drug nanocarriers in the following size hierarchy were tested: individual polymeric molecules; tiny micelles formed by a self-assembly of these molecules; nanodroplets formed from micelles. The results obtained confirmed the mechanism discussed above.

  • As expected, dramatic differences in the extravasation rates of nanoparticles were observed.
  • The extravsation of individual polymer molecules was extremely fast even in the normal (thigh muscle) tissue; In contrast, the extravasation of nanodroplets into the normal tissue was very slow. (Figure 4. A – Bright field image of the adipose and thigh muscle tissue. B,C – extravasation of individual molecules (B – 0 min; C – 10 min after injection); vasculature lost fluorescence while tissue fluorescence increased. D,E – extravasation of nanodroplets; blood vessel fluorescence was retained for an hour of observation (D – 30 min; E – 60 min after injection).
  • Nanodroplet extravasation into the tumor tissue was substantially faster than that into the normal tissue thus providing for effective nanodroplet tumor targeting.
  • Tumor-directed ultrasound significantly enhanced extravasation and tumor accumulation of both, micelles and nanodroplets (Figure 5). Also, pay attention to a very irregular tumor microvasculature, to be compared with that of a normal tissue shown in Figure 4.
  • The ultrasound effect on nanodroplets was 3-fold stronger than that on micelles thus making nanodroplets a better drug carriers for ultrasound-mediated drug delivery.
  • On a negative side, some premature drug release into the circulation that preceded tumor accumulation was observed. This proposes directions for a further improvement of nanoemulsion formulations.

Rapoport 5 - Ultrasound-Mediated Drug Targeting

Figure 5. Effect of ultrasound on the extravasation of Fluorescence of blood vessels dropped while that of the tumor tissue increased after ultrasound

2aBAa7 – Ultrasonic “Soft Touch” for Breast Cancer Diagnosis

Mahdi Bayat – bayat.mahdi@mayo.edu
Alireza Nabavizadeh- nabavizadehrafsanjani.alireza@mayo.edu
Viksit Kumar- kumar.viksit@mayo.edu
Adriana Gregory- gregory.adriana@mayo.edu
Azra Aliza- alizad.azra@mayo.edu
Mostafa Fatemi- Fatemi.mostafa@mayo.edu
Mayo Clinic College of Medicine
200 First St SW
Rochester, MN 55905

Michael Insana- mfi@illinois.edu
University of Illinois at Urbana-Champaign
Department of Bioengineering
1270 DCL, MC-278
1304 Springfield Avenue
Urbana, IL 61801

Popular version of paper 2aBAa7, “Differentiation of breast lesions based on viscoelasticity response at sub-Hertz frequencies”
Presented Tuesday Morning, May 24, 2016, 9:30 AM, Snowbird/Brighton room
171st ASA Meeting, Salt Lake City

Breast cancer remains the first cause of death among American women under the age of 60. Although modern imaging technologies, such as enhanced mammography (tomosynthesis), MRI and ultrasound, can visualize a suspicious mass in breast, it often remains unclear whether the detected mass is cancerous or non-cancerous until a biopsy is performed.

Despite high sensitivity for detecting lesions, no imaging modality alone has yet been able to determine the type of all abnormalities with high confidence. For this reason most patients with suspicious masses, even those with very small likelihood of a cancer, opt in to undergo a costly and painful biopsy.

It is long believed that cancerous tumors grow in the form of stiff masses that, if found to be superficial enough, can be identified by palpation. The feeling of hardness under palpation is directly related to the tissue’s tendency to deform upon compression.  Elastography, which has emerged as a branch of ultrasound, aims at capturing tissue stiffness by relating the amount of tissue deformation under a compression to its stiffness. While this technique has shown promising results in identifying some types of breast lesions, the diversity of breast cancer types leaves doubt whether stiffness alone is the best discriminator for diagnostic purposes.

Studies have shown that tissues subjected to a sudden external force do not deform instantly, rather they deform gradually over a period of time. Tissue deformation rate reveals another important aspect of its mechanical property known as viscoelasticity. This is the main material feature that, for example, makes a piece of memory foam to feel differently from a block of rubber under the touch. Similar material feature can be used to explore mechanical properties of different types of tissue. In breast masses, studies have shown that biological pathways leading to different breast masses are quite different. While in benign lesions an increase in a protein-based component can potentially increase its viscosity, hence a slower deformation rate compared to normal tissue, the opposite trend occurs in malignant tumors.

In this study, we report on using an ultrasound technique that enables capturing the deformation rate in breast tissue. We studied 43 breast masses in 42 patients and observed that a factor based on the deformation rate was significantly different in benign and malignant lesions (Fig. 1).

The results of this study promise a new imaging biomarker for diagnosis of the breast masses. If such technique proves to be of high accuracy in a large pool of patients, then this technology can be integrated into breast examination procedures to improve the accuracy of diagnosis, reduce unnecessary biopsies, and help detecting cancerous tumors early on

Figure 1 breast cancer

Figure1- Distribution of relative deformation rates for malignant and benign breast lesions. A significantly different relative deformation rates can be observed in the two groups, thus allowing differentiation of such lesions.