Optimization of a Digital Clutter Filter for Microvascular Volume Quantification using Power Doppler Ultrasound Ryan Fox MBP 3970Z Six Week Project Supervisor: Dr. James C. Lacefield Department of Medical Biophysics Western University April 3, 2012 Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Microvascular Volume Quantification • Study and diagnosis of angiogenesis-related disease – Cancer, psoriasis, atherosclerosis, etc. • Development and monitoring of treatments in-vivo • Typical hemodynamic parameter imaging modalities – Magnetic resonance imaging (MRI) – Positron emission tomography (PET) – X-ray computed tomography (CT) Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Microvascular Volume Quantification • A rapidly advancing, attractive alternative: Power Doppler Ultrasound • Longitudinal studies – No repeated injections of contrast media – Avoids exposure to ionizing radiation • Portable, available, and relatively low-cost Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Conventional Ultrasound Imaging • Brightness mode (B-mode) • Piezoelectric element sends single pulse (high-f sound wave) • Information encoded in echo amplitude Source: http://www.medison.ru/uzi/eho327.htm Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Doppler Ultrasound • L pulses / sample volume • Superposition of echoes: – – – – – Slow flowing blood Fast flowing blood Stationary tissue Slow flowing tissue Flash artifacts ft ft + fd v Source: http://www.medison.ru/uzi/eho327.htm Motivation & Objectives Methods Results & Discussion Power Doppler Signal and Spectrum Conclusions & Future Work Time-Domain Signal • Parseval’s Theorem: Frequency Spectrum • Check: P > Pthreshold? Y Inside Vessel N Outside Vessel Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Ideal High-Pass Filter • fp – passband edge frequency [Hz] Input Filter Output f > f p? Y Unaffected fp = 2.5kHz N Suppressed Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Realizable High-Pass Filter 0 PR = -4.8dB -10 SR = -41.4dB Magnitude (dB) -20 -30 -40 -50 -60 0 0.5 1 1.5 2 2.5 3 Frequency (kHz) 3.5 4 fs = 2.0kHz fp = 2.5kHz TB = fp – fs = 0.5kHz 4.5 Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Wall Filter Cut-Off Velocity (VC) VC too low VC too high 1 mm • false-positive artifacts 1 mm • false-negative artifacts • maintained vessel continuity • loss of vessel continuity S.Z. Pinter and J.C. Lacefield, Ultrasound Med. Biol., 35:1217-1228, 2009. Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Wall Filter Selection Curve (WFSC) 1.2 CPD 1 0.8 0.6 0.4 0.2 0 0 1 2 3 4 5 Wall Filter Cut-Off Velocity (mm/s) GE Logiq 5® Ultrasound System, www.nationalultrasound.com Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Problem Summary • For each data point on WFSC calculate • Search for local maxima in normalized first difference – Interval of Vc in between local maxima = “characteristic interval” • Multi-step decision algorithm to select operating point within interval (right edge or centre) • Coarse sampling of WFSC due to reliance on user controls – First difference is sensitive to distance between samples – More finely sampled -> characteristic intervals in challenging vessels Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Project Objectives • Simulate a realistic, tunable, and physiological-based power Doppler ultrasound backscattered signal • Investigate the relative importance of PR, SR, TB, and transient response on wall filter performance • Determine the effectiveness of various filter designs in the capacity as clutter filters • Gain insight into methods to reduce the impact of the transient response • Determine the optimal filter design and compare its performance to the original filter used in Dr. Lacefield’s laboratory Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Null Hypothesis • The blood flow power estimation error cannot be significantly reduced by means of selecting an optimal filter design Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Approach Doppler Signal Simulation Filter Design Performance Comparison Relative Importance of Filter Characteristics Optimal Filter Selection Evaluate Performance Relative to Benchmark Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Benchmark Power Doppler Images Commercial Scanner (proprietary filter design) Dr. Lacefield’s Lab (3rd order Chebychev I) Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Methods • MATLAB R2011b (The MathWorks Inc., Natick, MA) ~ 20,000 lines of novel code • Doppler signal simulation – Physiologically-relevant frequency spectrum mask generated from 256 * 13 samples (L = 13) – Inverse Fourier transform to obtain complex power Doppler time-domain signal • Process Doppler signal with controlled parameter filters & compare output power to ideal filter • Signal power – Zero time lag autocorrelation (R0) Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Power Doppler Signal Simulation Clutter Spectrum Frequency Spectrum 0.8 3.5 0.6 3 0.4 2.5 Magnitude Magnitude 1 0.2 0 -5 -4 -3 -2 -1 0 1 Frequency [kHz] 2 3 4 Complex, Gaussian distributed white noise 5 + 0.8 x 0.4 Magnitude Magnitude 0.5 0 -5 3 0.6 1 -3 -2 -1 0 1 Frequency [kHz] 2 3 4 5 + Noise Floor Spectrum 0 -5 -3 -2 -1 0 1 Frequency [kHz] 2 3 4 5 0.025 -4 -3 -2 -1 0 1 Frequency [kHz] 2 3 4 0.02 5 Magnitude -4 -4 Time Domain Signal = 2 0.2 0 -5 1.5 1 4 Blood Flow Spectrum 2 0.015 0.01 0.5 Magnitude 0.005 0 0 0 -5 -4 -3 -2 -1 0 1 Frequency [kHz] 2 3 4 5 500 1000 1500 2000 2500 Sample Number 3000 3500 Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Power Doppler Signal Simulation • Clutter-to-Flow Ratio (CFR) – CFR = 0dB for high ft (> 20MHz) - research – CFR = 20dB for low ft - clinical Case 2 2.5 2.5 2.5 2 2 2 1.5 1 1.5 1 0.5 0 -5 -4 -3 -2 -1 0 1 2 3 4 5 Frequency [kHz] 1.5 1 0.5 0 -5 -4 -3 -2 -1 0 1 2 3 4 5 Frequency [kHz] Case 4 0 -5 -4 -3 -2 -1 0 1 2 3 4 5 Frequency [kHz] Case 5 Case 6 3 3 2.5 2.5 2.5 2 2 2 1.5 1 0.5 0 -5 -4 -3 -2 -1 0 1 2 3 4 5 Frequency [kHz] 1.5 1 0.5 0 -5 -4 -3 -2 -1 0 1 2 3 4 5 Frequency [kHz] Magnitude 3 Magnitude Magnitude Magnitude 3 0.5 CFR = 20dB Case 3 3 Magnitude CFR = 0dB Magnitude Case 1 3 1.5 1 0.5 0 -5 -4 -3 -2 -1 0 1 2 3 4 5 Frequency [kHz] Motivation & Objectives Methods Results & Discussion Conclusions & Future Work 1.5 Digital Filter Design Classes Amplitude 1 • Finite Impulse Response (FIR) 0.5 0 -4 Ex: y(n) = 3x(n) – 2x(n-1) + x(n-2) x(n) -3 -2 -1 0 1 Sample Number h(n) 2 3 4 Y(n) • Infinite Impulse Response (IIR) Ex: y(n) = y(n-1) + x(n) – x(n-1) • Regression Ex: y(n) = x(n) – 2n + n2 Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Comparison of FIR and IIR Filter Designs • FIR: Equiripple • IIR: Butterworth, Chebychev I, Chebychev II, Elliptic Butterworth Equiripple 0 -10 0 -20 -10 -20 -30 -40 Magnitude (dB) -60 Magnitude (dB) Magnitude (dB) 0 -40 -20 -80 -100 -120 -160 -60 -30 -40 -50 -140 -50 0 Elliptic -60 -180 0.5 1 1.5 2 2.5 3 Frequency (kHz) 3.5 4 4.5 0 0.5 1 1.5 2 2.5 3 Frequency (kHz) 3.5 4 0 4.5 0.5 1 1.5 2 2.5 3 Frequency (kHz) 3.5 4 4.5 0 0 -10 -50 Magnitude (dB) Chebychev I Magnitude (dB) -20 -100 -150 -30 -200 -50 -250 -60 0 0.5 1 1.5 2 2.5 3 Frequency (kHz) 3.5 4 4.5 Chebychev II -40 -70 0 0.5 1 1.5 2 2.5 3 Frequency (kHz) 3.5 4 4.5 Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Comparison of FIR and IIR Filter Designs Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Transient Response x(n) h(n) Y(n) = Ytransient(n) +Ysteady-state(n) Y(n) 0.3 0.2 Amplitude • Duration & energy dependent on filter design & order 0.1 0 -0.1 -0.2 0 20 40 60 Sample Number 80 100 Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Impact of Filter Parameters on Output Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Impact of Filter Parameters on Output Case 2 (CFR = 0dB) Case 5 (CFR = 20dB) Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Selecting the Optimal Filter Design • From the FIR and IIR filter design comparison results: Filter Design Equiripple Butterworth Chebychev I Chebychev II Elliptic Passband Ripple 1.5 1.5 3.5 3.5 5 Stopband Ripple Transition Band Width 1 2 3.5 3.5 5 1 2 3.5 3.5 5 Transient Response 5 4 2 3 1 • From the impact of filter parameters on output power error results: Passband Ripple Stopband Ripple Transition Band Width Transient Response Weighting Factor (WF) Cases 1-3 Cases 4-6 3.38 3.38 1.00 1.00 -0.069 -0.069 0.050 -2.01 Assumed: Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Selecting the Optimal Filter Design • Scalar multiplication of the performance results with the weighting factors gives: Equiripple Butterworth Chebychev I Chebychev II Elliptic Final Tallies Cases 1-3 Cases 4-6 5.75 -4.06 6.74 -1.12 15.0 11.1 14.9 9.05 21.5 19.5 • Elliptic filter is the best candidate to act as a clutter filter out of all FIR and IIR filters considered • Consistent for both high and low frequency power Doppler Motivation & Objectives Methods Results & Discussion Conclusions & Future Work IIR Initialization Schemes • Zero – x(n) = 0 for n<0 Y(n) = 3x(n) + 2x(n-1) + … • Step – x(n) = x(0) for n<0 • Projection – Predicts and subtracts transient response • Mirroring of the Input Signal – x(-n) = - x(n) for n = 0,1,…,L • Mirroring & Step, Mirroring & Projection Motivation & Objectives Methods Results & Discussion Conclusions & Future Work IIR Initialization Schemes • No significant improvement over zero initialization • Use projection initialization Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Chebychev I vs. Elliptic vs. Regression CFR = 0dB (research) CFR = 20dB (clinical) Regression filter design is always best Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Frequency Spectrum Comparison Case 3 Simulated Doppler Signal Case 3 Simulated Doppler Signal 33 Simulated Doppler Signal Case 33 Simulated Simulated Doppler Doppler Signal Signal Case 2.52.5 33 33 2 2.5 2 2.5 1.51.5 22 1.51.5 22 11 1.5 1.5 11 1.5 1.5 0.510.5 1 0.5 10.5 1 00 Chebychev I (N=3) ChebychevII (N=3) (N=3) Chebychev 2.52.5 33 2 2.5 2 2.5 00 0.5 0.5 Chebychev I (N=3) Chebychev I (N=3) 500 500 1000 1000 1500 1500 2000 2000 2500 2500 3000 3000 500 500 1000 1000 1500 1500 2000 2000 2500 2500 3000 3000 00 0.5 0.5 00 500 500 1000 1000 1500 1500 2000 2000 2500 2500 3000 3000 500 500 1000 1000 1500 1500 2000 2000 2500 2500 3000 3000 Regression (D=2) Regression (D=2) Regression (D=2) 33 Regression (D=2) Regression (D=2) 2.532.5 3 Elliptic (N=3) 2.5 22 2.5 2 1.51.5 2 2 1.51.5 2 1.5 11 1.5 1.5 11 1.5 1 0.50.5 1 1 0.50.5 1 0.5 00 0.5 0.5 00 0.5 1000 1500 2000 Elliptic (N=3), mirror & step init Elliptic (N=3), mirror & step init 3 2.5 3 2.5 2.5 22 2.5 500 Elliptic (N=3), mirror && step initinit Elliptic (N=3), mirror step 33 2500 3000 500 1000 1500 2000 2500 3000 Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Statistical Analysis • Student’s T-test – Two-sample, unequal variances, unpaired, single tail – Microsoft Excel CFR = 0dB (research) CFR = 20dB (clinical) DF t critical T observed P(T<=t) DF t critical T observed P(T<=t) 3 2.353 5.335 0.006 Reject the null hypothesis. With 95% confidence: 3 2.353 3.778 0.016 Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Qualitative Comparison to Benchmark Commercial Scanner (proprietary filter design) Dr. Lacefield’s Lab (3rd order Chebychev I) Proposed Filtering Chain (2nd degree Regression then 3rd order Elliptic) Commercial scanner post-filter image enhancement? Motivation & Objectives Methods Results & Discussion Conclusions & Future Work WFSC Comparisons Dr. Lacefield’s Lab (3rd order Chebychev I) Proposed Filtering Chain (Cascade of 2nd degree Regression with 3rd order Elliptic) Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Conclusions • Novel power Doppler ultrasound signal simulation • Regression is the optimal stand-alone filter design for both research and clinical ultrasound frequencies • With 95% confidence, the regression filter performance was superior to the Chebychev I filter currently used in Dr. Lacefield’s lab • Novel approach to processing power Doppler signal – Cascade regression filter with elliptic – Can be used with automated tuning algorithm for Vc • Qualitatively improved images over all Vc Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Future Work • Use proposed filtering method in coordination with automated wall filter cut-off selection algorithm in Dr. Lacefield’s lab • Future fully automated, online implementation • Possible for non-specialist or time-sensitive operators to produce diagnostic quality Doppler images • Apply WFSC principles to other user controls Motivation & Objectives Methods Results & Discussion Conclusions & Future Work References Goertz, David E., Joanne L. Yu, Robert S. Kerbel, Peter N. Burns, and F. Stuart Foster. "High-frequency Doppler Ultrasound Monitors the Effects of Antivascular Therapy on Tumor Blood Flow." Cancer Research 62.22 (2002): 6371. Print. Miller, Janet C., Homer H. Pien, Dushyant Sahani, Gregory Sorensen, and James H. Thrall. "Imaging Angeogenesis: Applications and Potential for Drug Development." Journal of the National Cancer Institute 97.3 (2005): 172. Print. Hoskins, Peter, Kevin Martin, and Abigain Thrush. Diagnostic Ultrasound: Physics and Equipment. 2nd ed. New York: Cambridge UP, 2010. Print. Bjaerum, Steinar, Hans Torp, and Kjell Kristoffersen. "Clutter Filter Design for Ultrasound Color Flow Imaging." IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 49.2 (2002): 204. Print. Pinter, Stephen Z., and James C. Lacefield. "Objective Selection of High-Frequency Power Doppler Wall Filter Cutoff Velocity for Regions of Interest Containing Multiple Small Vessels." IEEE Transactions on Medical Imaging 29.5 (2010): 1124. Print. Proakis, John G., and Dimitris G. Manolakis. Digital Signal Processing: Principles, Algorithms, and Applications. 4th ed. Upper Saddle River, NJ: Prentice Hall, 2006. Print. Winkler, P., K. Helmke, and M. Mahl. "Major Pitfalls in Doppler Investigations." Pediatric Radiology 20.5 (1990): 304. Print. Motivation & Objectives Methods Results & Discussion Conclusions & Future Work Acknowledgements • Thank you for your mentorship and guidance Supervisor: Dr. James C. Lacefield Ph.D. Candidate: Mai Elfarnawany • Raw power Doppler data obtained via Vevo 770 Ultrasound System owned and operated by Robart’s Research Institute