2018 Projects

The Ultrasound Research Center is pleased to announce the recipients of the 2018 Pilot Grants Supporting Novel Directions in Ultrasound Research.

Shear Wave Elastography and Stiffness of the Median Nerve in the Carpal Tunnel: A Validation Study

Investigative team

Peter C. Amadio, M.D.; Mostafa Fatemi, Ph.D.

Central hypothesis

Carpal tunnel syndrome (CTS) is caused by compression of the median nerve inside the carpal tunnel. Currently, it is hard to predict how patients will respond to treatment and thus, which treatment would benefit them most.

The study team would like to know whether shear wave elastography (SWE) can detect changes in median nerve stiffness, for example, associated with fibrosis after prolonged compression. We propose a cadaver validation study with the hypothesis that SWE can measure differences in median nerve stiffness accurately compared with a gold standard (compression testing).

Potential outcomes and advances

If our hypothesis is supported, SWE may have diagnostic and prognostic clinical value and can be incorporated in a clinical study assessing the relation between ultrasound measurements and clinical outcome after intervention. Also, placing results in a broader perspective, validity for the median nerve would indicate that other peripheral nerves and similarly shaped anatomical structures can be measured using SWE, opening a new research direction for other peripheral neuropathies.

Novel Spinal Echo Catheter for Imaging and Guided Therapy

Investigative team

Neil G. Feinglass, M.D.; Matthew W. Urban, Ph.D.; Charles J. Bruce, M.D.; Christopher B. Robards, M.D.; Magdalena A. Cichon, Ph.D.

Central hypothesis

Spinal imaging of important structures is potentially possible through the development of a novel multi-array miniaturized ultrasound catheter. The investigative team has engineered a unique portable device that can easily be inserted at the bedside or in the operating theater quickly, easily and at low cost, allowing for real-time assessment of spinal structures, spinal cord blood flow at multiple levels and patient pathology.

This pilot study attempts to refine the design and improve the reliability of this prototype in vitro and in vivo (animal testing). This study further begins to develop concepts and design of a catheter-based system that might allow for monitored therapeutic treatment delivery.

In this project, an early prototype is to be engineered from three commercially available intracoronary catheters (Volcano Corporation Eagle Eye Platinum catheter) such that a multi-array ultrasound device with three evenly spaced ultrasound crystal arrays will be built.

Previous work demonstrated limited device reliability, but available operating ultrasound segments did show promise of 2D ultrasound imaging of the spinal cord and spinal vessels. Further testing and development will hopefully demonstrate improved visibility of structures in the CSF containing intrathecal space in a canine model and improved reliability of the arrays.

Potential outcomes and advances

Imaging of the spine and its contents is today limited to advanced complex technologies (magnetic resonance angiography, or MRA, fluoroscopy, CT angiography) that are neither portable nor available to many patients due to many factors, including: lack of resources, patient hemodynamic instability, or during intraoperative or ICU care.

Clinical application for such a catheter device include, but are not limited to, thoracoabdominal aortic aneurysm (TAAA) repair (45,000 U.S. surgeries a year with increasing prevalence due to an aging population), scoliosis repair and spinal fusion (38,000 cases a year in the U.S.). In TAAA and endovascular aortic repair (EVAR), spinal cord ischemia and resultant paraplegia (incidence of 2 to 5 percent) remains a tragically unpredictable, random and challenging event to avoid with current technology.

The proposed device could potentially provide clinicians with real-time information that the spinal segments in jeopardy could be safely bypassed or re-vascularized, possibly preventing this devastating outcome. Furthermore, patients with spinal cord trauma and spinal cord malformations such as arteriovenous malformations, potentially could benefit from intraoperative cord monitoring and be followed with this technology into their ICU stay, allowing for early detection of potential complications.

Pilot Study to Investigate Neuromodulatory Effect of Ultrasound

Investigative team

Su-Youne Chang, Ph.D.; Gregory A. Worrell, M.D., Ph.D.

Central hypothesis

Neurostimulation has been traditionally defined as electrical stimulation delivered through implantable electrodes. These penetrating electrodes provide high spatial resolution to target a specific brain region; however, they are invasive.

To overcome the limitation, noninvasive neuromodulation techniques such as direct-current stimulation and transcranial magnetic stimulation (TMS) have been developed and tested in clinical settings; however, they have limitations in providing high spatial resolution. Therefore, under this proposal, we seek to develop an alternative neuromodulation approach using much less invasive but highly focused stimulation technology using ultrasound.

Ultrasound has long been used in the clinical environment for noninvasive imaging. In addition, growing evidences support that acoustic energy modulates neuronal activities in both the peripheral and central nervous systems. More recently, in clinic, high-intensity ultrasound has been tested and used to ablate a highly focused brain region. These evidences suggest that ultrasound can become a platform for a less invasive and highly focused neuromodulation.

Potential outcomes and advances

In this pilot project, the study team will evaluate neuromodulatory functions of low-intensity ultrasound. If successful, our project is to provide a prototype design for a transducer and optimize ultrasound operation parameters to modulate neuronal activities without damage by heat or mechanical alterations in the brain. Ultrasound neuromodulation technology will advance the field of neural stimulation due to its less invasiveness and high spatial resolution.

Ultrafast High-Frequency Ultrasound Imaging for Chemo Sensitivity Screening in a Chick Embryo Patient-Derived Xenograft Model of Metastatic Lung Cancer

Investigative team

Jin Jen, M.D., Ph.D.; Shigao Chen, Ph.D.

Central hypothesis

Chemotherapeutic agents, such as cisplatin, remain the mainstay of treatment for non-small cell lung cancer (NSCLC). However, a subpopulation of patients will have primary lung tumors and metastases that are intrinsically resistant to chemotherapy and will achieve no survival benefit from receiving this treatment.

As there are no established predictive biomarkers available to personalize therapy selection in NSCLC, we propose the use of our high-throughput patient-derived xenograft (PDX) model using chick embryos in conjunction with ultrafast ultrasound to produce a phenotype-based imaging biomarker for the screening of patient-specific cisplatin resistance.

Potential outcomes and advances

Developing a phenotype-based imaging biomarker combining our PDX platform with ultrafast ultrasound is a strategy for personalized medicine that would allow us to screen for patient-specific cisplatin resistance. Patients that are identified as chemo-resistant might be spared of the side effects of cisplatin therapy and could be placed on second line therapies instead (erlotinib, ramucirumab or nivolumab).

Application of Lung Ultrasound Surface Wave Elastography in Assessment of Extravascular Lung Water

Investigative team

Brandon M. Wiley, M.D.Xiaoming Zhang, Ph.D.James F. Greenleaf, Ph.D.

Central hypothesis

A common cause of decreased lung compliance is the presence of extravascular lung water (EVLW) due to cardiogenic pulmonary edema. Lung ultrasound surface wave elastography (LUSWE) is a novel technique that can measure superficial lung tissue elastic properties. LUSWE has been shown to successfully differentiate the lung elastic properties of patients with interstitial lung disease and healthy controls.

The aim of this study is to determine if LUSWE can accurately detect changes in lung elasticity (compliance) caused by the presence of pulmonary edema in patients presenting with congestive heart failure.

Potential outcomes and advances

LUSWE would provide quantitative analysis of compliance and as a result permit accurate evaluation of longitudinal changes in lung compliance. Thus, one could envision the use of LUSWE to guide diuresis or other therapeutic interventions in the inpatient or outpatient setting.

For example, the practitioner performing the LUSWE on a clinic patient could compare the current LUSWE value with prior values for the patient and appropriately adjust diuretics or vasodilators. In addition, LUSWE is a noninvasive modality without ionizing radiation that is readily portable and can be utilized at the bedside or in the outpatient exam room.

Making Ultrasound Smart for Localization and Diagnosis of Thyroid Nodules

Investigative team

Bradley J. Erickson, M.D., Ph.D.; Matthew R. Callstrom, M.D., Ph.D.

Central hypothesis

The hypothesis of this project is that deep learning techniques applied to 3D ultrasound images of thyroid nodules will be able to identify those nodules that are highly likely to be benign. Thyroid nodules are extremely common lesions and are detectable in 4 to 8 percent of adults by means of palpation, and in 10 to 41 percent by means of ultrasound.

While some lesions are clearly benign, only about 10 percent of biopsied lesions are malignant. Our goal is to significantly reduce the number of benign biopsies while missing no, or very few, malignant lesions.

Potential outcomes and advances

In this project, we will use a 3D ultrasound imaging system along with shear wave elastography to identify thyroid nodules and characterize their stiffness. Cancers are typically stiffer than benign lesions. These data will be used to train a convolutional neural network, which will be validated with actual biopsy results.

Deep learning methods have been shown to effectively identify image features that humans can not readily see. These deep learning methods can also be applied in a robust and repeatable way. If successful, this project will allow confident and widespread identification of clearly benign thyroid nodules, which can reduce morbidity in patients and reduce the overall cost of health care.

The Clinical Value of Ultrasound Strain Magnitude Imaging for Assessment of Placental Attachment Abnormalities

Investigative team

Azra Alizad, M.D.; Rodrigo Ruano, M.D., Ph.D.; Mostafa Fatemi, Ph.D.; Wendaline VanBuren, M.D.

Central hypothesis

Placenta accreta is a clinical condition in which a part or the whole placenta abnormally invades the uterine wall and becomes inseparable from the uterine wall. It is a potentially life-threatening condition with maternal mortality approaching 7 percent. Prenatal suspicion of placenta accreta usually depends on clinical history and imaging using ultrasound and MRI, although no single modality can provide complete assurance for the presence or absence of placenta accreta.

Due to different levels of attachment between the placenta and uterine wall, placental abnormalities such as placenta accreta and placental abruption exhibit sliding motion patterns that are different from those obtained in normally implanted placentae. Strain magnitude imaging is a novel technique that can detect sliding of two adjacent organs. In this method, we use an algorithm that estimates the relative motion of the tissue at the interface of two organs from a sequence of ultrasound images.

Potential outcomes and advances

The purpose of this research is to develop, optimize and evaluate the efficacy of strain magnitude imaging as a noninvasive ultrasound-based method for prediction of placental attachment abnormalities in pregnant women at risk. This method is safe because it uses ultrasound within the FDA guidelines for fetal imaging.

We hypothesize that ultrasound-based strain magnitude imaging of the placental interface can be used as a predictor for placental attachment abnormalities (placenta accreta and placenta abruption) in pregnant women at risk.