Compact, Ruggedized Ultrasound for Rapidly Detecting Traumatic Brain Injury
The Department and its partners intend to develop and demonstrate a 3D ultrasound-based technology that detects fast-onset changes in intracranial pressure resulting from concussive forces associated with traumatic brain injuries.
There is an urgent need for a compact, portable and easy to use tool for rapid diagnosis of traumatic brain injury (TBI). TBI accounts for a very many sports injuries, vehicle accident injuries, and combat-related injury. “Closed brain” injury resulting from the concussive effect of sudden air pressure changes is often invisible to the eye, and often detected only after cognitive ability, physical functionality, and/or emotional and personality are noticeably impaired. Secondary damage through endogenous biochemical processes can result in tissue injury and cell death.
These processes may last hours or days before clinical signs and symptoms develop. Therefore, it is vital to detect TBI quickly to prevent long term damage or even death.
CT scans are typically used for detecting head related injuries. However, Ct scanners are large, need special power, are very expensive, and are not usually portable to the point of care. Ultrasound has none of these deficits, and ultrasonographic methods can exploit changes in intracranial dynamics that result from the concussive forces that lead to TBI and provide a novel and more efficient approach to rapidly identifying deep or bilateral traumatic brain injuries compared to CT and other currently available technologies.
Figure 1: Ultrasonographic image of optic nerve sheath. Two “x” marks represent the point at which the diameter of the optical nerve sheath was measured
Because of the unique neuro-anatomy of the eye, increased intracranial pressure forces the inflow of cerebrospinal fluid into the perineural space between the dura and the optic nerve, leading to the sonographic (B-mode ultrasound) appearance of increased diameter of the nerve. Postmortem studies have shown that the optic nerve sheath diameter is sensitive to changes in intracranial pressure, and that the sheath starts to become “normally” distensible 3 mm posterior to the globe. Increased intracranial pressure is associated with an optic nerve sheath diameter that exceeds 4 mm in patients younger than 1 year and 4.5 to 5 mm in older children, and 5mm in adult, measured 3 mm posterior to the papilla in the axial transbulbar view. Figure 1 shows a typical ultrasonographic image of optic nerve sheath. This type of measurement requires sub-millimeter accuracy therefore, high frequency ultrasound (5-8MHz) is needed.
To obtain an image of the optic nerve sheath using current technology the patient is instructed to direct their gaze at the midline so that the optic nerve was aligned opposite to the ultrasonic probe (transducer). If the patient is not cooperative, the probe is manipulated until an adequate image of the optic nerve sheath is obtained. However, this kind of measurement is not conducive for medical technicians working under conditions of high stress typical of sports, accident, and battlefield environments.
Proposed Solution: MEP will develop a system with a 2D ultrasound probe that has the sensitivity and specificity for detecting elevated intracranial pressure resulting from TBI equivalent to the current CT gold standard with dimensions similar to a standard hand-held personal data assistant. The sensor will function across the wide range of harsh operating environments typical of combat. The 2D ultrasound probe will automatically scan the 3D volume, and detect the diameter of the optical nerve sheath with minimum physician operation.
Most available commercial USB B-ultrasound probes can directly connect to a laptop computer, and in at least one case to a smartphone. However, most B-mode ultrasound probes use a mechanically scanning single transducer or a linear array to get single depth profile (2D imaging). This means that only very experienced physicians can successfully image the optical nerve sheath.
Three-dimensional (3D) ultrasound imaging provides important additional clinical benefits including the ability to acquire and display volumetric data and to obtain 2D cross-sectional scans at arbitrary orientations relative to the transducer array, thus providing views of anatomy new to ultrasound imaging. 3D imaging examinations are also much easier and less expensive to administer and analyze. Large area 2D transducer arrays, which are desirable for their high signal-to-noise ratio and image resolution, can acquire 3D volumetric data which, with appropriate software, enables automatic measurement of the diameter of the optical nerve sheath.
Some commercially available 2D ultrasound arrays, such as the Philips xMatrix 50×50 array, use single crystal piezoelectric materials called PureWave transducers. Stanford University and commercial companies like Siemens and GE are developing capacitive micro-machined ultrasound (CMUT) arrays. Duke University has developed a volumetric medical imaging array (VMI) using bulk PZT on flexible printed circuit board, and makes up to 256×256 sparse arrays. The University of Virginia is developing a low cost 2D array technology called “Sonic Window” using bulk PZT on printed circuit board. The array size is about 60×60.
In order to increase sensitivity and S/N ratio, and decrease the cost of a complete ultrasound system, it is important to integrate the probe head with the Si integrated circuit. Using MEMS technology, the transducer can be tuned at resonant frequency, so the probe’s acoustic performance can be greatly improved. An example is the CMUT array integrated with a CMOS chip. Another method is to put piezoelectric film on a piezoelectric micro machined ultrasound (pMUT) transducer. The most widely used piezoelectric film, PZT, has the largest piezoelectric coefficient. The main methods to fabricate PZT films are screen-printing and sol-gel, but these methods require high temperatures and are therefore incompatible with Si CMOS technology.
We are developing a 2D pMUT device using aluminum nitride (AlN) and Polyvinylidenefluoride (PVDF) piezoelectric films. Compared with materials used in conventional ultrasonic transducers, AlN:
- has very high thickness mode propagation velocity and high Curie temperature,
- is competitive with pMUT, and
- can transmit and receive the ultrasound signal from 5MHz to 350MHz.
We will use a plasma source molecular beam epitaxy (PSMBE) system to make AlN film at temperatures below 500°C, compatible with standard CMOS technology.
PVDF has been used in ultrasonic hydrophones for a number of years. However, polymeric materials have rarely been incorporated into medical imaging phased arrays due to lower emitted power levels (relative to PZT transducers), and higher transducer element impedance. PVDF’s advantages as a transducer material lie in its inherent wide bandwidth and the potential to create high-resolution images whilst maintaining low transducer manufacturing costs.
IC integration: Spatial sampling of a 2D transducer aperture requires that the element pitch in both dimensions be less than about one-half the wavelength of ultrasound in tissue. The result is that 2D arrays can have a very large number of elements. For comparison, 1D arrays in current commercial systems commonly have 128 elements. A 128 × 128-element 2D array has 16,384 elements, which gives significant data processing and packaging challenges. Conventional 1D arrays can be connected to an external imaging system by matching to 50-Ω micro-coaxial cables. However, even for a modestly sized 2D array, the necessary cables and matching circuits would result in a bulky and complex system.
Because 2D array elements are smaller in both dimensions they have higher electrical impedance than comparable 1D array elements  and are thus more susceptible to parasitic capacitance. In a 1D array, the effects of parasitic cable capacitance can be avoided by electrically matching the transducer elements with the cables and terminating electronics . However, because of the high equivalent impedance of the 2D array elements, broadband electrical matching is difficult.
A solution to interfacing electronics with 2D transducer arrays is to combine the transducer array with an integrated circuit (IC). A compact connection between an IC and a transducer array results in minimal parasitic capacitance and eliminates cables. Implementing more of the system electronics with an IC can reduce the cost of 3D imaging systems significantly. The extra functionality provided by the IC may also produce new imaging techniques that better utilize large arrays; examples include multiplexing the array over a limited number of cables or electronic channels , electronically reconfiguring the array for different element patterns , and implementing an analog-to-digital converter ,  or beam-former  within the IC to reduce the number of connections with an external system.
Phase I Technical Objectives
The overall objective of the proposal is to develop a low cost ultrasound detection system that can measure the diameter of the optical nerve sheath conveniently and reliably. The specific objectives of this Phase I program are as follows:
- Design and Fabricate a 2D AlN and PVDF pMUT
- Design and Fabricate a CMOS circuit for pMUT integration
- Integrate the pMUT device with the Si CMOS chip
- Construct a laboratory prototype sensor
Phase I Plan of Work
Phase 1 research will be concentrate on device and system development. As the first step, we will fabricate and characterize an AlN and PVDF prototype pMUT device.
Specific Aim 1: Develop a 2D AlN and PVDF pMUT
In this task, we will design the MEMS resonant chamber for pMUT device, and simulate its acoustic performance by COMSOL multi-physics simulation software. We will fabricate MEMS device in our Advanced Microsystems Clean Room Fabrication Laboratory. Then we will grow AlN film on MEMS device to form pMUT. We will also fabricate PVDF pMUT by grow or glue commercial PVDF film on MEMS device. We will optimize the AlN growth condition using PSMBE, and also optimize PVDF attachment method. We will develop through wafer interconnection technology for device integration. We will test the structure, electric and acoustic performance of AlN and PVDF device, and chooses the best one based on acoustic performance and the fabrication cost.
Specific Aim 2: Design and fabricate CMOS circuit for pMUT integration
The CMOS chip will be able to integrate with the pMUT device. Every pixel will have transmit pulser, receiver amplifier, pulse echo switch, and element selection circuits. We will design the CMOS chip by Cadence IC design software, and fabricate the chip from MOSIS Company.
Specific Aim 3: Integrate the pMUT with the CMOS chip to a compact ultrasound probe
We will use flip chip bonding technology to integrate pMUT device with CMOS chip. We will also test the pulse-echo and imaging performance of the assembled ultrasound probe.
Specific Aim 4: Construct a compact laboratory prototype 3D ultrasound system
In this task we will develop a breadboard to brassboard prototype to provide proof of concept evaluation of the design and transducer. This will include consultation with clinicians at the Kresge Eye Institute and the Beaumont Hospital Brain Trauma unit. The CTO has had extensive collaborations with these clinicians and will use their expertise to help evaluate efficacy and feature design in the hand held probe to be developed in Phase II of the program. Figure 2 provides an illustration of the hand held system to be developed. Development of initial prototype application specific integrated circuits for the ultrasound imaging system with 3-dimensional reconstruction will provide for a rapid progression during Phase I of the work.
Figure 2: Illustration of the ultrasound probe
Approximately 80 percent of our research involves the development of biomedical microsystems and BioMEMS. Our group has worked on the AlN film growth, characterization and application for many years, as well as COMSOL multi-physics software simulation, Cadence IC design, MEMS technology, and electric and acoustic characterization of ultrasound device.
We have fabricated 128×128 array elements pMUT ultrasound sensor devices. A side profile of the bond/etch back design is shown in Figure 3. This design shows two wafers bonded together. Both wafers were etched down to 20um before bonding and the top wafer was thinned down to 20um. The sandwich structure of Al/PVDF/Al or Al/AlN/Al is on the top. A top view of the device is shown in Figure 4.
Figure 4: Top view of pMUT sensor array without top layer Al and polyimide layer
The following plot shows the received signal from one pixel in the 128 x 128 array located towards the center of the PVDF pMUT array. The measured frequency is about 3MHz.
Figure 5: Signal from one pixel in the 128×128 array
We also observed the resonant pattern of AlN and PVDF pMUT by the MSV-300 Laser Doppler Vibrometer. It proves that both AlN and PVDF pMUT can be good ultrasound transmitters.
Figure 6: pMUT ultrasound radiation pattern at the fundamental flexural resonant frequency. (a) AlN device; (b) PVDF device
In addition, we designed and fabricated a CMOS chip containing a pre-amplifier, signal store capacitor array and element selection circuit. Figure 7 show a CMOS chip with 4×4 pixel array designed by Cadence software and fabricated with MOSIS AMI 0.5um technology.
Figure 7: CMOS chip with 4×4 pixels
- Le A, Hoehn ME, Smith ME, Spentzas T, Schlappy D, Pershad J. “Bedside Sonographic Measurement of Optic Nerve Sheath Diameter as a Predictor of Increased Intracranial Pressure in Children”; Ann Emerg Med. 2009 Jun;53(6):785-91
- Tayal VS, Neulander M, Norton HJ; Emergency Department Sonographic Measurement of Optic Nerve Sheath Diameter to Detect Findings of Increased Intracranial Pressure in Adult Head Injury Patients; Ann Emerg Med vol. 49, 508 – 514, 2007
- W.D. Richard, D.M. Zar, and R. Solek, “A Low-Cost B-Mode USB Ultrasound Probe,” Ultrasonic Imaging, vol. 30, pp. 21-28, 2008. http://record.wustl.edu/news/page/normal/14109.html
- Ergun, A.S. (Edward L. Ginzton Lab., Stanford Univ., CA, USA); Cheng, C.-H.; Demirci, U.; Khuri-Yakub, B.T. “Fabrication and characterization of 1-dimensional and 2-dimensional Capacitive Micromachined Ultrasonic Transducer (CMUT) arrays for 2-dimensional and volumetric ultrasonic imaging” Oceans 2002 Conference and Exhibition. Conference Proceedings (Cat. No.02CH37362), p 2361-7 vol.4, 2002
- Fisher, R. (GE Global Research, Niskayuna, NY, United States); Wodnicki, R.; Cogan, S.; Thomas, R.; Mills, D.; Woychik, C.; Lewandowski, R.; Thomenius, K. “Packaging and design of reconfigurable arrays for volumetric imaging” Proceedings – IEEE Ultrasonics Symposium, p 407-410, 2007, 2007 IEEE Ultrasonics Symposium Proceedings, IUS
- Yen JT and Smith SW “Real time rectilinear volumetric imaging with receive mode multiplexers”, IEEE Trans. Ultras. Ferro and Freq. Control 30, 216-226, 2004
- Fuller, Michael I. (PocketSonics, Inc., Charlottesville, VA 22901, United States); Ranganathan, Karthik; Zhou, Shiwei; Blalock, Travis N.; Hossack, John A.; Walker, William F. “Experimental system prototype of a portable, low-cost, C-scan ultrasound imaging device” IEEE Transactions on Biomedical Engineering, v 55, n 2, p 519-530, February 2008
- Wygant, Ira O. (E. L. Ginzton Laboratory, Stanford University, Stanford, CA 94305-4088); Jamal, Nafis; Lee, Hyunjoo J.; Nikoozadeh, Amin; Zhuang, Xuefeng; Oralkan, Omer; Ergun, Arif S.; Karaman, Mustafa; Khuri-Yakub, Butrus T. “An integrated circuit with transmit beamforming and parallel receive channels for 3D ultrasound imaging: Testing and characterization” Proceedings – IEEE Ultrasonics Symposium, p 25-28, 2007, 2007 IEEE Ultrasonics Symposium Proceedings, IUS
- Dausch, David E. (Center for Materials and Electronic Technologies, RTI International, Research Triangle Park, NC, United States); Gilchrist, Kristin H.; Castellucci, John B.; Chou, Derrick R.; Von Ramm, Olaf T “Performance of flexure-mode pMUT 2D arrays” Proceedings – IEEE Ultrasonics Symposium, p 1053-1056, 2007, 2007 IEEE Ultrasonics Symposium Proceedings, IUS
- Hedegaard, T. (Dept. of Micro & Nanotechnol., Tech. Univ. of Denmark, Lyngby, Denmark); Pedersen, T.; Thomsen, E.V.; Lou-Moeller, R.; Hansen, K.; Zawada, T. “Screen printed thick film based pMUT arrays” 2008 IEEE International Ultrasonics Symposium, p 2126-9, 2008
- Belgacem, B. (Ceramics Lab., Ecole Polytech. Fed. de Lausanne, Lausanne, Switzerland); Calame, F.; Muralt, P. “Piezoelectric micromachined ultrasonic transducers with thick PZT sol gel films” Journal of Electroceramics, v 19, n 4, p 369-73, Dec. 2007
- Hood, John Paul (Mioroscale Sensors, School of Engineering and Science, University of Paisley, Paisley, PA1 2BE, United Kingdom); Elgoyhen, Jocelyn; Hutson, David; Kirk, Katherine J. “Modelling the Operating frequency of thin film piezoelectric transducers” Proceedings – IEEE Ultrasonics Symposium, p 1705-1708, 2007, 2007 IEEE Ultrasonics Symposium Proceedings, IUS
- Danylyuk, Yuri (Smart Sensor and Integrated Microsystems, Electrical and Computer Engineering Dept., Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, United States); Perooly, Soma; Rahman, Md; Auner, Gregory “Growth of a-plane AlN on r-plane sapphire by plasma source molecular beam epitaxy” Physica Status Solidi C: Conferences, v 2, n 7, p 2228-2231, 2005
- Gessert, J. (Sonora Med. Syst., Inc, Longmont, CO, USA); Moore, G.W.; Schafer, M.E. “Development of a novel hand-held ultrasonic probe test device” 2006 IEEE Ultrasonics Symposium (IEEE Cat. No.06CH37777), p 3 pp., 2006
- Wygant, Ira O. (IEEE); Zhuang, Xuefeng; Yeh, David T.; Oralkan, Omer; Ergun, A. Sanli; Karaman, Mustafa; Khuri-Yakub, Butrus T. “Integration of 2D CMUT arrays with front-end electronics for volumetric ultrasound imaging” IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, v 55, n 2, p 327-341, February 2008