Liver fibrosis: scarring of the liver tissue Due to liver damage and healing Progresses through 4 stages, ending in cirrhosis Liver cirrhosis causes more than 1 million deaths per year Fibrotic Liver Ultrasonic Imaging Diagnostic (FLUID) System Student Researchers: Meredith Huszagh, Fahad Iqbal, Sara Keller, Lauren Severance, Patricia Twilley, Alison Williams BEAM Lab, Department of Biomedical Engineering, Vanderbilt University School of Engineering Mentor: Brett Byram PhD, Assistant Professor of Biomedical Engineering [1] Asrani SK. Incorporation of Noninvasive Measures of Liver Fibrosis Into Clinical Practice: Diagnosis and Prognosis. Clin Gastroenterol Hepatol. 2015;13(12): [2] Schuppan D, Afdhal NH. Liver Cirrhosis. Lancet. 2008;371(9615): doi: /S (08) [3] Ziol, Marianne et al. “Noninvasive Assessment of Liver Fibrosis by Measurement of Stiffness in Patients with Chronic Hepatitis C.” Hepatology 41.1 (2005): 48–54. Wiley Online Library. Web. 28 Oct [4] [5] [6] Problem Statement Ultrasound elastography is a promising new technique for the noninvasive diagnosis of liver fibrosis and cirrhosis. At the moment, however, this method is considered suboptimal, particularly in diagnosis of intermediate stages of the disease [1]. Recent progress in magnetic resonance and ultrasonic imaging has shown promise of an effective technique for diagnosis, but these methods are currently too expensive for implementation in most low resource environments. In addition, measurement sensitivity in the early stages of disease is a concern for these techniques [2]. The purpose of our work is to engineer a system consisting of an inexpensive, handheld, ultrasound­-based device and accompanying software for noninvasively assessing liver fibrosis and cirrhosis. Background System Diagram Receive Circuitry 8 th Order Bandpass Chebyshev Filter LT6254 chip and socket Low Noise Amplifier LMH6629 Evaluation Board Arduino Uno sends information via serial communication to MATLAB for data processing and tissue elasticity quantification Device Housing Acrylic box Current Methods The gold standard is a liver biopsy, but this method produces a qualitative result, is expensive, and the process of retrieving a liver biopsy is painful for the patient and increases their risk of bleeding and infection. Non-invasive techniques also exist, but this imaging modalities are extremely complex and expensive and generally are not portable. Needs Assessment In order to more efficiently diagnose liver fibrosis, we propose the development of an ultrasound-based system that: 1.Is non-invasive to reduce patient discomfort 2.Requires minimal training by the provider to eliminate need of designated ultrasound technician 3.Is accessible to patients in low-resource environments 4.Takes advantage of freely available software for data processing 5.Uses a single-element as opposed to a multi-array transducer 6.Quantitatively diagnoses stage of fibrosis progression (through correlation with tissue stiffness) in a way comparable to existing gold standard 7.Characterizes risk of healthy tissue for becoming diseased 8.Provides consistent and reliable measurements despite tissue inhomogeneity 9.Reduces signal noise resulting from patient motion 10.Utilizes a processor which decreases cost and increases portability Design Approach Design Components Results Conclusion Future Directions Acknowledgements References Transmission Signal 4 and 6 MHz square waves generated with Arduino Uno and AD9850 Direct Digital Synthesizer (DDS) Voltage divider circuit RF Power Amplifier with a gain of 4000 and impedance matching Piston GE ultrasound transducer Single element 5 cm focal length Phantom Representing tissue stiffness of 4 and 6 KPa Transmit/Receive switch MAX4516 active switch Default open circuit Figure 2. Pin-out diagram for the MAX4516 active transmit/receive switch utilized in our design. Digital/dp/B0085N592S?ie=UTF8&psc=1&redirect=true&ref_=oh_aui_det ailpage_o00_s00 Figure 1. GE Ultrasound Transducer staging/core-concept/all Acoustic Radiation Force Impulse (ARFI) Elastography Uses a long ultrasound pulse to displace tissue and shorter receiving pulses to measure the displacement in tissue Tissue displacement is proportional to stiffness which can then be used to determine the stage of scarring. Liver fibrosis describes the scarring of liver tissue due to repeated liver damage and healing. Fibrosis can lead to liver cirrhosis, which causes more than 1 million deaths per year. There exists a need to diagnose this condition in a wide variety of environments. To address this problem, we designed a non-invasive and inexpensive method to detect fibrosis. We are utilizing the method of acoustic radiation force impulse (ARFI) elastography to deform tissue and measure this deformation to provide a stiffness measurement. Currently, we have demonstrated a working transmission circuit and future objectives include incorporating a receive circuit and associated T/R switch. We also plan to demonstrate radiation force using phantoms of differing stiffness. Our goal is to meet or exceed the specificity and sensitivity of liver biopsies and ultimately obtain FDA approval and market our device to clinics. Receive Circuitry Impedance matching Filtering and low noise amplification on receive signal Post-processing of receive signal to achieve a stiffness measurement T/R Switch Delineate between high transmitted voltages and low received voltages Demonstrate radiation force using different phantoms Product refinement Package product to make more robust and rugged Reduce size Further reduce cost by replacing parts Figure 3. Signal received by the hydrophone from the transducer when sinusoidal input was sent to the transducer.. Signal Received by Hydrophone Transmitted a 5 MHz sinusoidal waveform produced by the function generator Sent transmit signal through transducer and measured signal with a hydrophone Observed the signal received by the hydrophone as output on an oscilloscope We would like to thank the following people for their support and encouragement during the design process: Dr. Brett Byram and the BEAM Lab, Dr. Matthew Walker III Dr. Rene Harder