Andrew Wiens– Andrew.wiens@gatech.edu Andrew Carek Omar T. Inan Georgia Institute of Technology Electrical and Computer Engineering
Popular version of poster 3aBA12 “Sternal vibrations reflect hemodynamic changes during immersion: underwater ballistocardiography.” Presented Wednesday, May 19, 2015, 11:30 am, Kings 2 169th ASA Meeting, Pittsburgh
In 2014, one out of every four internet users in the United States wore a wearable device such as a smart watch or fitness monitor. As more people incorporate wearable devices into their daily lives, better techniques are needed to enable real, accurate health measurements.
Currently, wearable devices can make simple measurements of various metrics such as heart rate, general activity level, and sleep cycles. Heart rate is usually measured from small changes in the intensity of the light reflected from light-emitting diodes, or LEDs, that are placed on the surface of the skin. In medical parlance, this technique is known as photoplethysmography. Activity level and sleep cycles, on the other hand, are usually measured from relatively large motions of the human body using small sensors called accelerometers.
Recently, researchers have improved a technique called ballistocardiography, or BCG, that uses one or more mechanical sensors, such as an accelerometer worn on the body, to measure very small vibrations originating from the beating heart. Using this technique, changes in the heart’s time intervals and the volume of pumped blood, or cardiac output, have been measured. These are capabilities that other types of noninvasive wearable sensors currently cannot provide from a single point on the body, such as the wrist or chest wall. This method could become crucial for blood pressure measurement via pulse-transit time, a promising noninvasive, cuffless method that measures blood pressure using the time interval from when blood is ejected from the heart to when it arrives at the end of a main artery.
Figure. 1. The underwater BCG recorded at rest.
The goal of the preliminary study reported here was to demonstrate similar measurements recorded during immersion in an aquatic environment. Three volunteers wore a waterproof accelerometer on the chest while immersed in water up to the neck. An example of these vibrations recorded at rest appear in Figure 1. The subjects performed a physiologic exercise called a Valsalva maneuver to temporarily modulate the cardiovascular system. Two water temperatures and three body postures were tested as well to discover differences in the signal morphology that could arise under different conditions.
Measurements of the vibrations that occurred during single heart beats appear in Figure 2. Investigation of the recorded signals shows that the amplitude of the signal increased during immersion compared to standing in air. In addition, the median frequency of the vibrations also decreased substantially.
Figure. 2. Single heart beats of the underwater BCG from three subjects in three different environments and body postures.
One remaining question is, why did these changes occur? It is known that a significant volume of blood shifts toward the thorax, or chest, during immersion, leading to changes in the mechanical loading of the heart. It is possible that this phenomenon wholly or partially explains the changes in the vibrations observed during immersion. Finally, how can we make accurate physiologic measurements from the underwater wearable BCG? These are open questions, and further investigation is needed.
Diane Dalecki, Ph.D. Eric S. Comeau, M.S. Denise C. Hocking, Ph.D. Rochester Center for Biomedical Ultrasound University of Rochester Rochester, NY 14627
Popular version of paper 3aBA5, “Applications of acoustic radiation force for microvascular tissue engineering” Presented Wednesday morning May 20, 9:25 AM, in room Kings 2 169th ASA Meeting, Pittsburgh
Tissue engineering is the field of science dedicated to fabricating artificial tissues and organs that can be made available for patients in need of organ transplantation or tissue reconstructive surgery. Tissue engineers have successfully fabricated relatively thin tissues, such as skin substitutes, that can receive nutrients and oxygen by simple diffusion. However, recreating larger and/or more complex tissues and organs will require developing methods to fabricate functional microvascular networks to bring nutrients to all areas of the tissue for survival.
In the laboratories of Diane Dalecki, Ph.D. and Denise C. Hocking, Ph.D., research is underway to develop new ultrasound technologies to control and enhance the fabrication of artificial tissues1. Ultrasound fields are sound fields at frequencies higher than humans can hear (i.e., > 20 kHz). Dalecki and Hocking have developed a technology that uses a particular type of ultrasound field, called an ultrasound standing wave field, as a tool to non-invasively engineer complex spatial patterns of cells2 and fabricate microvessel networks3,4 within artificial tissue constructs.
When a solution of collagen and cells is exposed to an ultrasound standing wave field, the forces associated with the field lead to the alignment of the cells into planar bands (Figure 1). The distance between the bands of cells is controlled by the ultrasound frequency, and the density of cells within each band is controlled by the intensity of the sound field. The collagen polymerizes into a solid gel during the ultrasound exposure, thereby maintaining the spatial organization of the cells after the ultrasound is turned off. More complex patterning can be achieved by use of more than one ultrasound transducer.
Figure 1. Acoustic-patterning of microparticles (dark bands) using an ultrasound standing wave field. Distance between planar bands is 750 µm. Scale bar = 100 μm
An exciting application of this technology involves the fabrication of microvascular networks within artificial tissue constructs. Specifically, acoustic-patterning of endothelial cells into planar bands within collagen hydrogels leads to the rapid development of microvessel networks throughout the entire volume of the hydrogel. Interestingly, the structure of the resultant microvessel network can be controlled by choice of the ultrasound exposure parameters. As shown in Figure 2, ultrasound standing wave fields can be employed to fabricate microvessel networks with different physiologically relevant morphologies, including capillary-like networks (left panel), aligned non-branching vessels (center panel) or aligned vessels with hierarchically branching microvessels. Ultrasound fields provide an ideal technology for microvascular engineering; the technology is rapid, noninvasive, can be broadly applied to many types of cells and hydrogels, and can be adapted to commercial fabrication processes.
Figure 2. Ultrasound-fabricated microvessel networks within collagen hydrogels. The ultrasound pressure amplitude used for initial patterning determines the final microvessel morphology, which can resemble torturous capillary-like networks (left panel), aligned non-branching vessels (center panel) or aligned vessels with hierarchically branching microvessels. Scale bars = 100 μm.
[1] Dalecki D, Hocking DC. Ultrasound technologies for biomaterials fabrication and imaging. Annals of Biomedical Engineering 43:747-761; 2015.
[2] Garvin KA, Hocking DC, Dalecki D. Controlling the spatial organization of cells and extracellular matrix proteins in engineered tissues using ultrasound standing wave fields. Ultrasound Med. Biol. 36:1919-1932; 2010.
[3] Garvin KA, Dalecki D, Hocking DC. Vascularization of three-dimensional collagen hydrogels using ultrasound standing wave fields. Ultrasound Med. Biol. 37:1853-1864; 2011.
[4] Garvin KA, Dalecki D, Youssefhussien M, Helguera M, Hocking DC. Spatial patterning of endothelial cells and vascular network formation using ultrasound standing wave fields. J. Acoust. Soc. Am. 134:1483-1490; 2013.
Australian researchers are the first to demonstrate milk fat separation at large-scales using an ultrasonic separation technique, with potential industrial dairy applications
WASHINGTON, D.C., May 20, 2015 — Recently, scientists from Swinburne University of Technology in Australia and the Commonwealth Scientific and Industrial Research Organization (CSIRO), have jointly demonstrated cream separation from natural whole milk at liter-scales for the first time using ultrasonic standing waves–a novel, fast and nondestructive separation technique typically used only in small-scale settings.
At the 169th Meeting of the Acoustical Society of America (ASA), being held May 18-22 2015 in Pittsburgh, Pennsylvania, the researchers will report the key design and effective operating parameters for milk fat separation in batch and continuous systems.
The project, co-funded by the Geoffrey-Gardiner Dairy Foundation and the Australian Research Council, has established a proven ultrasound technique to separate fat globules from milk with high volume throughputs up to 30 liters per hour, opening doors for processing dairy and biomedical particulates on an industrial scale.
“We have successfully established operating conditions and design limitations for the separation of fat from natural whole milk in an ultrasonic liter-scale system,” said Thomas Leong, an ultrasound engineer and a postdoctoral researcher from the Faculty of Science, Engineering and Technology at the Swinburne University of Technology. “By tuning system parameters according to acoustic fundamentals, the technique can be used to specifically select milk fat globules of different sizes in the collected fractions, achieving fractionation outcomes desired for a particular dairy product.”
The Ultrasonic Separation Technique According to Leong, when a sound wave is reflected upon itself, the reflected wave can superimpose over the original waves to form an acoustic standing wave. Such waves are characterised by regions of minimum local pressure, where destructive interference occurs at pressure nodes, and regions of high local pressure, where constructive superimposition occurs at pressure antinodes.
When an acoustic standing wave field is sustained in a liquid containing particles, the wave will interact with particles and produce what is known as the primary acoustic radiation force. This force acts on the particles, causing them to move towards either the node or antinode of the standing wave, depending on their density. Positioned thus, the individual particles will then rapidly aggregate into larger entities at the nodes or antinodes.
To date, ultrasonic separation has been mostly applied to small-scale settings, such as microfluidic devices for biomedical applications. Few demonstrations are on volume-scale relevant to industrial application, due to the attenuation of acoustic radiation forces over large distances.
Acoustic Separation of Milk Fat Globules at Liter Scales To remedy this, Leong and his colleagues have designed a system consisting of two fully-submersible plate transducers placed on either end of a length-tunable, rectangular reaction vessel that can hold up to two liters of milk.
For single-plate operation, one of the plates produces one or two-megahertz ultrasound waves, while the other plate acts as a reflector. For dual-plate operation, both plates were switched on simultaneously, providing greater power to the system and increasing the acoustic radiation forces sustained.
To establish the optimal operation conditions, the researchers tested various design parameters such as power input level, process time, transducer-reflector distance and single or dual transducer set-ups etc.
They found that ultrasound separation makes the top streams of the milk contain a greater concentration of large fat globules (cream), and the bottom streams more small fat globules (skimmed milk), compared to conventional methods.
“These streams can be further fractionated to obtain smaller and larger sized fat globules, which can be used to produce novel dairy products with enhanced properties,” Leong said, as dairy studies suggested that cheeses made from milk with higher portion of small fat globules have superior taste and texture, while milk or cream with more large fat globules can lead to tastier butter.
Leong said the ultrasonic separation process only takes about 10 to 20 minutes on a liter scale – much faster than traditional methods of natural fat sedimentation and buoyancy processing, commonly used today for the manufacture of Parmesan cheeses in Northern Italy, which can take more than six hours.
The researchers’ next step is to work with small cheese makers to demonstrate the efficacy of the technique in cheese production.
WORLDWIDE PRESS ROOM In the coming weeks, ASA’s Worldwide Press Room will be updated with additional tips on dozens of newsworthy stories and with lay language papers, which are 300 to 500 word summaries of presentations written by scientists for a general audience and accompanied by photos, audio and video. You can visit the site during the meeting at https://acoustics.org/world-wide-press-room/.
PRESS REGISTRATION We will grant free registration to credentialed journalists and professional freelance journalists. If you are a reporter and would like to attend, contact AIP Media Services at media@aip.org. For urgent requests, staff at media@aip.org can also help with setting up interviews and obtaining images, sound clips, or background information.
ABOUT THE ACOUSTICAL SOCIETY OF AMERICA The Acoustical Society of America (ASA) is the premier international scientific society in acoustics devoted to the science and technology of sound. Its 7,000 members worldwide represent a broad spectrum of the study of acoustics. ASA publications include The Journal of the Acoustical Society of America (the world’s leading journal on acoustics), JASA Express Letters, Proceedings of Meetings on Acoustics, Acoustics Today magazine, books, and standards on acoustics. The society also holds two major scientific meetings each year. See https://acousticalsociety.org/.
Oleg A. Sapozhnikov1,2, Sergey A. Tsysar1, Wayne Kreider2, Guangyan Li3, Vera A. Khokhlova1,2, and Michael R. Bailey2,4 1. Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia 2. Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40th Street, Seattle WA 98105, USA 3. Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr. MS 5055 Indianapolis, IN 462025120 4. Department of Urology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356510, Seattle, WA 98195, USA
In focused ultrasound surgery (FUS), an ultrasound source radiates pressure waves into the patient’s body to achieve a desired therapeutic effect. FUS has already gained regulatory approval in the U.S. for treating uterine fibroids and pain palliation for bone metastases; other applications – including prostate cancer, liver cancer, and neurosurgery – remain active topics for clinical trials and research. Because applications of FUS often involve high intensity levels, insufficient knowledge of the acoustic field in the patient could lead to damage of healthy tissue away from the targeted treatment site. In this sense, high-intensity ultrasound treatments could cause collateral effects much like radiotherapy treatments that use ionizing radiation. In radiotherapy, treatment planning is critical for delivery of an effective and safe treatment: Typically, CT or MRI is used to form a virtual patient and the treatment is planned by computer-aided design. Simulations are used to plan the geometric, radiological, and dosimetric aspects of the therapy using radiation transport simulations. Analogous to a radiation beam, ultrasound therapy uses an acoustic beam as a 3D “scalpel” to treat tumors or other tissues. Accordingly, there is motivation to establish standard procedures for FUS treatment planning that parallel those in radiotherapy [1, 2]. However, such efforts toward treatment planning first require very precise knowledge of the source transducer in order to accurately predict the acoustic beam structure inside the patient.
Fig. 1 Acoustic holography to characterize an ultrasound source, with schematic illustration of the corresponding ultrasound field. A measured hologram in a plane can be used to reconstruct the entire wave field anywhere in 3D space.
Toward this end, it is instructive to recognize that ultrasound comprises pressure waves and thus possesses several basic features of wave physics that can be used in practice. One such feature is the potential to reproduce a 3D wave field from a 2D distribution of the wave amplitude and phase. This principle was made famous in optics by Dennis Gabor (Nobel Prize, 1971), who invented holography [3]. A similar approach is possible in acoustics [4 – 8] and is illustrated in Fig. 1 for a therapeutic ultrasound source. To measure an acoustic hologram, a hydrophone (i.e., a microphone used underwater) can be scanned across a plane in front of the transducer. Because these measurements in 2D capture the whole field, this measured hologram can be used to reconstruct the surface vibrations of the source transducer. In turn, once the vibrations of the source are known, the corresponding acoustic field can be computed in water or tissue or any other medium with known properties.
Besides ultrasound surgery, holography techniques can be applied to characterize ultrasound transducers used for other therapeutic and diagnostic ultrasound-based applications. In this work we have used it for the first time to characterize a shock wave lithotripter source. Shock wave lithotripters radiate high intensity pulses that are focused on a kidney stone. High pressure, short rise time, and path-dependent nonlinearity make characterization in water and extrapolation to tissue difficult.
The electromagnetic lithotripter characterized in this effort is a commercial model (Dornier Compact S, Dornier MedTech GmbH, Wessling, Germany) with a 6.5 mm focal width. A broadband hydrophone (a fiber optic probe hydrophone, model FOPH 2000, RP Acoustics; Leutenbach, Germany) was used to sequentially measure the field over a set of points in a plane in front of the source. Following the previously developed transient holography approach, the recorded pressure field was numerically back-propagated to the source surface (Fig. 2). The method provides an accurate boundary condition from which the field in tissue can be simulated.
Fig. 2 Characterization of an electro-magnetic shock wave lithotripter. Top: A photo of the lithotripter head. Bottom: Holographically reconstructed peak-to-peak pressure along the transducer face.
In addition, we use acoustic holography to characterize imaging probes, which generate short, transient pulses of ultrasound (Fig. 3). Accurate 3D field representations have been confirmed [9].
Fig. 3 Characterization of a diagnostic imaging probe. Left: A photo of the HDI C5-2 probe, which was excited at a frequency of 2.3 MHz. Middle: Holographically reconstructed pattern of vibration velocities along the probe surface. Right: Corresponding phase distribution.
We believe that our research efforts on acoustic holography will make it possible in the near future for manufacturers to sell each medical ultrasound transducer with a “source hologram” as a part of its calibration. This practice will enable calculation of the 3D ultrasound and temperature fields produced by each source in situ, from which the “dose” delivered to a patient can be inferred with better accuracy than is currently achievable.
LITERATURE 1. White PJ, Andre B, McDannold N, Clement GT. A pre-treatment planning strategy for high-intensity focused ultrasound (HIFU) treatments. Proceedings 2008 IEEE International Ultrasonics Symposium, 2056-2058 (2008). 2. Pulkkinen A, Hynynen K. Computational aspects in high intensity ultrasonic surgery planning. Comput. Med. Imaging Graph. 34(1), 69-78 (2010). 3. Gabor D. A new microscopic principle. Nature 161, 777-778 (1948). 4. Maynard JD, Williams EG, and Lee Y. Nearfield acoustic holography: I. Theory of generalized holography and the development of NAH. J. Acoust. Soc. Am. 78, 1395-1413 (1985). 5. Schafer ME, Lewin PA. Transducer characterization using the angular spectrum method. J. Acoust. Soc. Am. 85(5), 2202-2214 (1989). 6. Sapozhnikov O, Pishchalnikov Y, Morozov A. Reconstruction of the normal velocity distribution on the surface of an ultrasonic transducer from the acoustic pressure measured on a reference surface. Acoustical Physics 49(3), 354–360 (2003). 7. Sapozhnikov OA, Ponomarev AE, Smagin MA. Transient acoustic holography for reconstructing the particle velocity of the surface of an acoustic transducer. Acoustical Physics 52(3), 324–330 (2006). 8. Kreider W, Yuldashev PV, Sapozhnikov OA, Farr N, Partanen A, Bailey MR, Khokhlova VA. Characterization of a multi-element clinical HIFU system using acoustic holography and nonlinear modeling. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 60(8), 1683-1698 (2013). 9. Kreider W, Maxwell AD, Yuldashev PV, Cunitz BW, Dunmire B, Sapozhnikov OA, Khokhlova VA. Holography and numerical projection methods for characterizing the three-dimensional acoustic fields of arrays in continuous-wave and transient regimes. J. Acoust. Soc. Am. 134(5), Pt 2, 4153 (2013).
Tatiana Khokhlova – tdk7@uw.edu George Schade – schade@uw.edu Yak-Nam Wang – ynwang@uw.edu Joo Ha Hwang – jooha@uw.edu University of Washington 1013 NE 40th St Seattle, WA 98105
John Chevillet – jchevill@systemsbiology.org Institute for Systems Biology 401 Terry Ave N Seattle, WA 98109
Maria Giraldez – mgiralde@med.umich.edu Muneesh Tewari – mtewari@med.umich.edu University of Michigan 109 Zina Pitcher Place 4029 Ann Arbor, MI 48109
Popular version of paper 4pBA1 High intensity focused ultrasound-induced bubbles stimulate the release of nucleic acid cancer biomarkers Presented Thursday afternoon, October 30, 2014, at 1:30 pm 168th ASA Meeting, Indianapolis
The clinical evaluation of solid tumors typically includes needle biopsies, which can provide diagnostic (benign vs. cancer) and molecular information (targetable mutations, drug resistance, etc). This procedure has several diagnostic limitations, most notably, the potential to miss the mutations only millimeters away. In response to these limitations, the concept of “liquid biopsy” has emerged in recent years: the detection of nucleic acid cancer biomarkers, such as tumor-derived microRNAs (miRNAs) and circulating tumor DNA (ctDNA). These biomarkers have shown high diagnostic value and could guide the selection of appropriate targeted therapies. However, the abundance of these biomarker classes in the circulation is often too low to be detectable even with the most sensitive techniques because of their low levels of release from the tumor.
Figure caption: Experimental setup and the basic concept of “ultrasound-aided liquid biopsy”. Pulsed high intensity focused ultrasound (HIFU) waves create, grow and collapse bubbles in tissue, which leads to puncturing of cell membranes and capillary walls. Cancer-derived microRNAs are thus released from the cells into the circulation and can be detected in a blood sample.
How can we make tumor cells release these biomarkers into the blood? The most straightforward way would be to puncture the cell membrane so that its content is released. One technology that allows for just that is high intensity focused ultrasound (HIFU). HIFU uses powerful, controlled ultrasound waves that are focused inside human body to ablate the targeted tissue at the focus without affecting the surrounding organs. Alternatively, if HIFU waves are sent in short, infrequent but powerful bursts, they cause mechanical disruption of tissue at the focus without any thermal effects. The disruption is achieved by small gas bubbles in tissue that appear, grow and collapse in response to the ultrasound wave– a phenomenon known as cavitation. Depending on the pulsing protocol employed, the outcome can range from small holes in cell membranes and capillaries to complete liquefaction of a small region of tumor. Using this technology, we seek to release biomarkers from tumor cells into the circulation in the effort to detect them using a blood test and avoiding biopsy.
To test this approach, we applied pulsed HIFU exposures to prostate cancer tumors implanted under the skin of laboratory rats, as illustrated in the image above. For image guidance and targeting we used conventional ultrasound imaging. Blood samples were collected immediately before and at periodic intervals after HIFU treatment and were tested for the presence of microRNAs that are associated with rat prostate cancer. The levels of these miRNAs were elevated up to 12-fold within minutes after the ultrasound procedure, and then declined over the course of several hours. The effects on tissue were evaluated in the resected tumors, and we found only micron-sized areas of hemorrhage scattered through otherwise intact tissue, suggesting damage to small capillaries. These data provided the proof of principle for the approach that we termed “ultrasound-aided liquid biopsy”. We are now working on identifying other classes of clinically valuable biomarkers, most notably tumor-derived DNA, that could be amplified using this methodology.
Timothy J Hall, Helen Feltovich, Lindsey C. Carlson, Quinton W. Guerrero, Ivan M. Rosado-Mendez University of Wisconsin, Madison, WI (tjhall@wisc.edu) Click here to read the abstract
The cervix, which is the opening into the uterus, is a remarkable organ. It is the only structure in the entire body that has diametrically opposed functions. The normal cervix stays stiff and closed throughout most of pregnancy while the baby develops and then completely softens and opens at just the right time so the full-grown baby can be born normally, through the vagina. This process of softening and opening involves remodeling, or breaking down, of the cervix’s collagen structure together with an increase in water, or hydration, of the cervix. When the process happens too soon, babies can be born prematurely, which can cause serious lifelong disability and even death. When it happens too late, mothers may need a cesarean delivery. [1,2]
Amazingly, even after 100 years of research, nobody understands how this happens. Specifically, it is unclear how the cervix knows when to soften, or what molecular signals initiate and control this process. As a result, obstetrical providers today evaluate cervical softness in exactly the same way as they did in the 1800s: they feel the cervix with their fingers and classify it as ‘soft’, ‘medium’ or ‘firm’. And, unsurprisingly, despite significant research effort, the preterm birth rate remains unacceptably high and more than 95% of preterm births are intractable to any available therapies.
The cervix is like a cylinder with a canal in the middle that goes up into the uterus. This is where the sperm travels to fertilize the egg, which then nests in the uterus. Cervical collagen is roughly arranged in 3 layers. There is a thin layer on the inner part that where collagen is mostly aligned along the cervical canal, and similarly a thin layer that runs along the outside of the cervix. Between these layers, in the middle of the cervix is a thicker layer of collagen that is circumferential, aligned like a belt around the canal. Researchers theorize that the inner and outer layers stabilize the cervix from tearing off as it shortens and dilates for childbirth, while the middle circumferential layer is most important for the strength and stiffness of the cervix to prevent it from opening prematurely, but nobody is certain. This information is critical to understanding the process of normal, and abnormal, cervical remodeling, and that is why recently there is growing interest in developing technology that can non-invasively and thoroughly assess the collagen in the cervix and measure its softness and hydration status. The most promising approaches use regular clinical ultrasound systems that have special processing strategies to evaluate these tissue properties.
One approach to assessing tissue softness uses ultrasound pressure to induce a shear wave, which moves outward like rings in water after a stone is dropped. The speed of the shear wave provides a measurement of tissue stiffness because these waves travel slower in softer tissue. This method is used clinically in simple tissues without layers of collagen, such as the liver for staging fibrosis. Cervical tissue is very complex because of the collagen layers, but, after many years of research, we finally have adapted this method for the cervix. The first thing we did was compare shear wave speeds in hysterectomy specimens (surgically removed uterus and cervix) between two groups of women. The first group was given a medicine that softens the cervix in preparation for induction of labor, a process called “ripening”. The second group was not treated. We found that the shear wave speeds were slower in the women who had the medicine, indicating that our method could detect the cervices that had been softened with the medicine.[3] We also found that the cervix was even more complex than we’d thought, that shear wave speeds are different in different parts of the cervix. Fortunately, we learned we could easily control for that by measuring the same place on every woman’s cervix. We confirmed that our measurements were accurate by performing second harmonic generation microscopy on the cervix samples in which we measured shear wave speeds. This is a sophisticated way of looking at the tiny collagen structure of a tissue. It told us that indeed, when the collagen structure was more organized, the shear wave speeds were faster, indicating stiffer tissue, and when the collagen started breaking down, the shear wave speeds were slower, indicating softer tissue.
The next step was to see if our methods worked outside of the laboratory. So we studied pregnant women who were undergoing cervical ripening in preparation for induction of labor. We took measurements from each woman before they got the ripening medicine, and then afterwards. We found that the shear wave speeds were slower after the cervix had been ripened, indicating the tissue had softened.[4] This told us that we could obtain useful information about the cervix in pregnant women.
We also evaluated attenuation, which is loss of ultrasound signal as the wave propagates, because attenuation should increase as tissue hydration increases. This is a very complicated measurement, but we found that if we carefully control the angle of the ultrasound beams relative to the underlying cervical structure, attenuation estimates are sensitive to the difference between ripened and unripened tissue in hysterectomy specimens. This suggests the potential for an additional parameter to quantify and monitor the status of the cervix during pregnancy, and we are currently analyzing attenuation in the pregnant women before and after they received the ripening medicine.
This technology is exciting because it could change clinical practice. On a very basic level, obstetrical providers would be able to talk in objective terms about a woman’s cervix instead of the subject “soft, medium, or firm” designation they currently use, which would improve provider communication and thus patient care. More importantly, it could provide a means to thoroughly study normal and abnormal cervical remodeling, and associate structural changes in the cervix with molecular changes, which is the only way to discover new interventions for preterm birth.
References 1. Feltovich H, Hall TJ, and Berghella V. Beyond cervical length: Emerging technologies for assessing the pregnant cervix. Am J Obst & Gyn, 207(5): 345-354, 2012. 2. Feltovich, H and Hall TJ. Quantitative Imaging of the Cervix: Setting the Bar. Ultrasound Obstet Gynecol. 42(2): 121-128, 2013. 3. Carlson LC, Feltovich H, Palmeri ML, Dahl JJ, Del Rio AM, Hall TJ, Estimation of shear wave speed in the human uterine cervix. Ultrasound Obstet Gynecol. 43( 4): 452–458, 2014. 4. Carlson LC, Romero ST, Palmeri ML, Munoz del Rio A, Esplin SM, Rotemberg VM, Hall TJ, Feltovich H. Changes in shear wave speed pre and post induction of labor: A feasibility study. Ultrasound Obstet Gynecol.published online ahead of print Sep.2014.
