4pBA3 – Focusing Sound to Disrupt Microorganisms

Timothy A Bigelow – bigelow@iastate.edu
Iowa State University
2113 Coover Hall
Ames, IA 50014

Popular version of paper 4pBA3
Presented Thursday afternoon, October 30, 2014
168th ASA Meeting, Indianapolis

During the civil war, the risk of lethal infection drove surgeons to perform multiple amputations on wounded soldiers. The loss of life from the infection outweighed the loss of the limb. In modern medicine, the occurrence of amputations is much less due to the development of sterile surgical techniques, but a type of “amputation” is still the only treatment option for many patients battling infection.

In modern medicine, numerous implants have been developed to treat many different ailments ranging from basic hernia, to pacemakers, to neuronal implants to control seizures. These implants play a vital role in the restoration of function or quality of life for these patients. However, if an infection grows on the implant despite sterile surgical techniques, then the only treatment option is to remove and replace the infected implant with a new device. The bacteria responsible for the infection protect themselves by forming a biofilm on the surface of the implant. Bacteria in the biofilm are protected from antibiotics and the administration of antibiotics can even cause the formation of antibiotic resistant strains. Recently, however, we have shown that focused ultrasound can precisely target and destroy these biofilms (Figure 1). Therefore, in the future, we hope to develop a noninvasive therapy to treat infections on medical implants based on ultrasound.

bigelow disrupting biofilms - high-intensity focused ultrasound

Fig 1: The surface of graphite plates after growing Pseudomonas aeruginosa biofilms and exposing to high-intensity focused ultrasound. Green shows live cells while red shows dead cells. In the absence of treatment, a live biofilm is clearly visible. The ultrasound exposures resulted in almost complete biofilm destruction with few if any live cells remaining.

There are two primary types of therapy that can be performed with ultrasound. The first uses the energy in the sound to heat the tissue. The second uses the sound to excite microscopic bubbles in the tissue resulting in a mechanical change to the tissue structure. Our technology is based on the generation and subsequent excitation of the microscopic bubbles. The high-intensity of the sound causes the bubbles to violently collapse shredding cells adjacent to the bubbles. In addition to treating biofilm infections, we have also shown that the excitation of these microscopic bubbles can lyse microalgae for the release of lipids. These lipids can then be utilized in the formation of biofuels. The use of focused ultrasound was shown to be more energy efficient than other comparable methods of lysing the microalgae.

Evaluating kidney stone size in children using the posterior acoustic shadow

Franklin C. Lee1 – franklee@uw.edu
Jonathan D. Harper1 – jdharper@uw.edu
Thomas S. Lendvay1,2 – Thomas.lendvay@seattlechildrens.org
Ziyue Liu3 – ziliu@iupui.edu
Barbrina Dunmire4 – mrbean@uw.edu
Manjiri Dighe5 – dighe@uw.edu
Michael Bailey4 – bailey@apl.washington.edu
Mathew D. Sorensen1,6 – mathews@uw.edu

University of Washington
1 Department of Urology, Box 356510
5 Department of Radiology, Box 357115
1959 NE Pacific St, Seattle, WA 98195

2 Seattle Children’s Hospital
Urology, Developmental Pediatrics
4800 Sand Point WA NE, Seattle, WA 98105

3 Indiana University
Department of Biostatistics
410 W. Tenth St, Suite 3000, Indianapolis, IN 46202

4 University of Washington
Applied Physics Lab – Center for Industrial and Medical Ultrasound2
1013 NE 40th St, Seattle, WA 98105

6 Department of Veteran Affairs Medical Center
Division of Urology
1660 South Columbian Way, Seattle, WA 98108

Stone disease in the children is becoming more commonplace. Over the past 25 years the incidence has increased approximately 6-10% annually and is now 50 per 100,000 adolescents1. The diagnosis of kidney stones in children, as in adults, relies primarily on diagnostic imaging. In adults, the most common imaging study performed in the United States for the initial diagnosis of kidney stones is a computed tomography (CT) scan, due to its superior sensitivity and specificity. This is not preferred for children as CT utilizes ionizing radiation and children have an increased sensitivity to radiation effects. In addition, stone formers often have recurrent stone episodes over their lifetime, which is especially relevant to younger stone formers. The repeated exposures of a CT scan could lead to an increased risks of secondary cancers2. As a result, ultrasound is often performed in children instead because there is no radiation associated with its use1. Ultrasound, however, is less sensitive and specific compared with CT, and is known to overestimate kidney stone size3-5, which is one of the primary determinants of how stones are managed.

We have identified a new technique to improve the accuracy of US stone sizing. Traditionally, a kidney stone will show up as a bright, or hyperechoic, object on US, and radiologists measure the longest linear dimension of the bright area to represent the stone size. We believe that the dark, or hypoechoic, acoustic shadow that appears behind a kidney stone provides additional information for predicting stone size. The resolution of the stone is affected by the distortion of the waves traveling through the intervening tissues; the resolution of the shadow is only affected by the local stone obstruction.

We screened 660 stone diagnoses over an 11 year period (2004 – 2014) at Seattle Children’s Hospital, a tertiary care referral center serving the greater Pacific Northwest. Over the study period, there were 37 patients presenting with an initial diagnosis of a kidney stone, and who had both a US and CT within three months of each other. Two reviewers retrospectively measured both the stone size and the shadow width from the ultrasound image. We compared the results to the stone size measured from the CT scan. A total of 48 stones were included in the study with an average size based on CT imaging of 7.85 mm. The shadow width was present in 88% of the cases, and, on average, was more accurate than measuring the stone itself. Measuring the stone width on ultrasound tended to overestimate the size of the stone by 1.2 ± 2.5 mm (reviewer 1) and 2.0 ± 1.7 mm (reviewer 2), while measuring the shadow width on ultrasound underestimated the size of the stone by -0.6 ± 2.5 mm (reviewer 1) and overestimated the stone size by 0.3 ± 1.2 mm (reviewer 2). In both cases, the shadow was a better predictor of stone size and, for reviewer 2, there was less variability in the data. Stone sizes based on CT are typically considered within 1 mm, with low variability.

Our technique is simple and can be easily adopted by pediatricians, radiologists, and urologists. It improves the accuracy of US and gives physicians more confidence that the reported size is more representative of the true stone size, without having to expose children to the radiation of a CT scan. This also allows the physician to make more accurate decisions about when to perform a surgery for a large stone or continue to observe a small stone that may pass on its own. The findings from this study may also potentially be applicable to stones in adult patients. We believe that with continued advancements in US, we can reduce the number of CT scans for both adults and children. The results in part highlight one of the drawbacks of ultrasound, which is user dependence; two users can have very different results. It is anticipated that future work on automated stone and shadow sizing can reduce this along with standardizing the method in which the shadow measurement is taken.

References
1. Tasian G and Copelovitch L. Evaluation and Management of Kidney Stones in Children. J Urol. 2014: Epub ahead of print
2. Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 2012; 380: 499-505.
3. Ray AA, Ghiculete D, Pace KT, Honey RJD. Limitations to ultrasound in the detection and measurement of urinary tract calculi. Urology 2010; 76(2):295-300.
4. Fowler KAB, Locken JA, Duchesne JH, Williamson MR. US for detecting renal calculi with nonehnanced CT as a reference standard. Radiology 2002; 222(1):109-113.
5. Dunmire B, Lee FC, Hsi RS, Cunitz BW, Paun M, Bailey MR, Sorensen MD, Harper JD. Tools to improve the accuracy of kidney stone sizing with ultrasound. Aug 2014; [Epub ahead of print].

2pBA14 – Waves by Ultrasound help better Breast Cancer Diagnosis

Max Denis – denis.max@mayo.edu     507-266-7449
Mohammad Mehrmohammadi – mehr@wayne.edu
Pengfei Song – song.pengfei@mayo.edu
Duane D. Meixner – meixner.duane@mayo.edu
Robert T. Fazzio – fazzio.robert@mayo.edu
Sandhya Pruthi – pruthi.sandhya@mayo.edu
Shigao Chen – chen.shigao@mayo.edu
Mostafa Fatemi – fatemi.mostafa@mayo.edu
Azra Alizad – alizad.azra@mayo.edu   507-254-5970

Mayo Clinic College of Medicine
200 1st St SW
Rochester, MN 55905

Popular version of paper 2pBA14
Presented Monday morning, October 28, 2014
168th ASA Meeting, Indianapolis

Currently, a large number of patients with suspicious breast masses undergo biopsy, more than half of which turn out to be benign. The huge number false positive cases results in an enormous unnecessary cost plus psychological and physical trauma to patients. To avoid such biopsies, one needs to use a modality that can better differentiate between the benign and malignant lesions.

Palpation, the examination of tissue through the use of touch, remains one of the simplest yet effective methods for detecting breast tumors. However, the sense of touch is not sensitive enough to detect small or very deep lesions. It is well known that breast tumors are often much harder than the normal tissue, and cancerous masses are harder than the benign ones [1]. Therefore, scientists have been trying to develop new imaging tools that are sensitive to tissue stiffness. Elasticity medical imaging is an emerging field that provides information about a tissue’s stiffness property [2].

This paper presents application of a new tool called “Comb Push ultrasound elastography (CUSE)”, developed in our ultrasound laboratory at Mayo Clinic Rochester [3,4,5] for accurate measurement and imaging of breast mass stiffness. This new tool will help improving detection and differentiation of breast masses, which will eventually help physicians in better diagnosis of breast cancer. We attempt to assess a tissue’s stiffness property noninvasively by applying ultrasound to tap on breast mass and determine its stiffness by measuring the speed of the resulting waves. These waves are called shear waves. Thereafter, a two-dimensional shear wave speed map is reconstructed. Having already identified the region of interest from the ultrasound, the shear wave speed map is overlaid onto the ultrasound image. Therefore, the shear wave speed within the breast mass can be measured which allows us to determine the stiffness of the mass.

Denis_WaveBreastCancerUltrasound_ASA_pictures

Figure 1. Examples of CUSE evaluations of (a) benign and (b) cancerous breast masses.

Hence, the CUSE imaging technique may be useful as a noninvasive method as an adjunct to breast ultrasound for differentiating benign and malignant breast masses, and may help in reducing the number of unnecessary biopsies. This ongoing project is being done under an approved protocol by Mayo Institutional Review Board and funded by grants and R01CA148994- R01CA148994-04S1 from National Institute of Health and is led by Dr. Azra Alizad.

 

References:

  1. Sewell CW (1995) Pathology of benign and malignant breast disorders. Radiologic Clinics of North America 33: 1067-1080.
  2. Sarvazyan A, Hall TJ, Urban MW, Fatemi M, Aglyamov SR, et al. (2011) An overview of elastography–an emerging branch of medical imaging. Current medical imaging reviews 7: 255.
  3. Song P, Manduca A, Zhao H, Urban MW, Greenleaf JF, et al. (2014) Fast Shear Compounding Using Robust 2-D Shear Wave Speed Calculation and Multi-directional Filtering. Ultrasound in medicine & biology 40: 1343-1355.
  4. Song P, Urban MW, Manduca A, Zhao H, Greenleaf JF, et al. (2013) Comb-push Ultrasound Shear Elastography (CUSE) with Various Ultrasound Push Beams.
  5. Song P, Zhao H, Manduca A, Urban MW, Greenleaf JF, et al. (2012) Comb-push ultrasound shear elastography (CUSE): a novel method for two-dimensional shear elasticity imaging of soft tissues. Medical Imaging, IEEE Transactions on 31: 1821-1832.