Changes in backscattered ultrasonic envelope statistics as a function of thrombus age: an in vitro study.

It is necessary to determine the age of thrombi in planning clinical treatment for thrombolysis. Ultrasound imaging can potentially be used to evaluate thrombus age in real time. The backscattered signals from thrombi may contain useful information regarding their age. On the basis of the randomness of ultrasound backscattering, this study explored changes in backscattered US statistics as a function of thrombus age. Porcine blood samples were used for the in vitro induction of fresh thrombi (day 0) with hematocrits ranging from 0%-40% and aged thrombi (days 0-8) with a hematocrit of 40%. Each thrombus was imaged using a pulse-echo ultrasound scanner equipped with a 7.5-MHz linear array transducer to acquire raw backscattered signals for B-mode and Nakagami imaging, by which the backscattered statistics were visualized. Hematoxylin and eosin staining and scanning electron microscopy were used to observe the histology of fresh and aged thrombi. The results indicated that a decrease in the number of red blood cells in the thrombus caused by the aging effect was observed in the in vitro model, indicating that the proposed model could simulate the structural changes in the thrombus during aging. Compared with fresh thrombi with various hematocrits, the aged thrombi exhibited a trend toward more substantial decreases in the Nakagami parameter with increasing thrombus age (the Nakagami parameter decreased from 1.1 to 0.6 as thrombus age increased from day 0 to day 8), indicating that thrombus aging causes the backscattered statistics to follow a pre-Rayleigh distribution to a high degree. This finding may be applied to the determination of thrombus age using conventional ultrasound imaging in the future.

[1]  Saurabh Datta,et al.  Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model. , 2008, Thrombosis research.

[2]  K.K. Shung,et al.  In vivo measurements of ultrasonic backscattering in blood , 2001, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[3]  V. Fuster,et al.  In vivo noninvasive detection and age definition of arterial thrombus by MRI. , 2002, Journal of the American College of Cardiology.

[4]  T. Wakefield Treatment options for venous thrombosis. , 2000, Journal of vascular surgery.

[5]  D. Keber,et al.  Factors influencing the lysis of ex vivo human thrombi , 1996 .

[6]  Shyh-Hau Wang,et al.  The Effect of Kinetic Properties on Statistical Variations of Ultrasound Signals Backscattered from Flowing Blood , 2007, Ultrasound in medicine & biology.

[7]  P. Tsui,et al.  The effect of transducer characteristics on the estimation of Nakagami paramater as a function of scatterer concentration. , 2004, Ultrasound in medicine & biology.

[8]  Chiao-Yin Wang,et al.  Dependency of Ultrasonic Nakagami Images on the Mechanical Properties of Scattering Medium , 2013 .

[9]  B. Goldberg,et al.  Classification of ultrasonic B-mode images of breast masses using Nakagami distribution , 2001, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[10]  J. Tijssen,et al.  Presence of Older Thrombus Is an Independent Predictor of Long-Term Mortality in Patients With ST-Elevation Myocardial Infarction Treated With Thrombus Aspiration During Primary Percutaneous Coronary Intervention , 2008, Circulation.

[11]  K. Shung,et al.  An approach for measuring ultrasonic backscattering from biological tissues with focused transducers , 1997, IEEE Transactions on Biomedical Engineering.

[12]  K. Ouriel,et al.  Invasive approaches to treatment of venous thromboembolism. , 2004, Circulation.

[13]  J. Hoak,et al.  Management of deep vein thrombosis and pulmonary embolism. A statement for healthcare professionals. Council on Thrombosis (in consultation with the Council on Cardiovascular Radiology), American Heart Association. , 1996, Circulation.

[14]  M. Neri,et al.  Histological age determination of venous thrombosis: a neglected forensic task in fatal pulmonary thrombo-embolism. , 2009, Forensic science international.

[15]  King-Jen Chang,et al.  Relationship between Ultrasound Backscattered Statistics and the Concentration of Fatty Droplets in Livers: An Animal Study , 2013, PloS one.

[16]  F. Foster,et al.  Non-Gaussian statistics and temporal variations of the ultrasound signal backscattered by blood at frequencies between 10 and 58 MHz. , 2004, Journal of the Acoustical Society of America.

[17]  Chien-Cheng Chang,et al.  Imaging local scatterer concentrations by the Nakagami statistical model. , 2007, Ultrasound in medicine & biology.

[18]  Po-Hsiang Tsui,et al.  Artifact Reduction of Ultrasound Nakagami Imaging by Combining Multifocus Image Reconstruction and the Noise-Assisted Correlation Algorithm , 2015, Ultrasonic imaging.

[19]  J. Alison Noble,et al.  Nakagami imaging with small windows , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[20]  Srivalleesha Mallidi,et al.  Combined ultrasound and photoacoustic imaging to detect and stage deep vein thrombosis: phantom and ex vivo studies. , 2008, Journal of biomedical optics.

[21]  Chih-Chung Huang,et al.  Assessing the viscoelastic properties of thrombus using a solid-sphere-based instantaneous force approach. , 2011, Ultrasound in medicine & biology.

[22]  Po-Hsiang Tsui,et al.  Ultrasound imaging of the larynx and vocal folds: recent applications and developments , 2012, Current opinion in otolaryngology & head and neck surgery.

[23]  E. Madsen,et al.  Non-Gaussian versus non-Rayleigh statistical properties of ultrasound echo signals , 1994, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[24]  M. Srinivasan,et al.  Statistics of envelope of high-frequency ultrasonic backscatter from human skin in vivo , 2002, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[25]  Xiaofeng Yang,et al.  Noninvasive evaluation of vaginal fibrosis following radiotherapy for gynecologic malignancies: a feasibility study with ultrasound B-mode and Nakagami parameter imaging. , 2013, Medical physics.

[26]  K. Parker,et al.  Deviations from Rayleigh Statistics in Ultrasonic Speckle , 1988, Ultrasonic imaging.

[27]  R. Kistner,et al.  Surgery in acute and chronic venous disease. , 1979, Surgery.

[28]  Chien-Cheng Chang,et al.  Using ultrasound Nakagami imaging to assess liver fibrosis in rats. , 2012, Ultrasonics.

[29]  Chien-Cheng Chang,et al.  Microvascular Flow Estimation by Contrast-Assisted Ultrasound B-Scan and Statistical Parametric Images , 2009, IEEE Transactions on Information Technology in Biomedicine.

[30]  H. Riess,et al.  Thrombectomy, lysis, or heparin treatment: concurrent therapies of deep vein thrombosis: therapy and experimental studies. , 1989, Seminars in thrombosis and hemostasis.

[31]  R. Colman,et al.  Hemostasis and Thrombosis: Basic Principles and Clinical Practice , 1988 .

[32]  P. Wells,et al.  Diagnosis and treatment of deep-vein thrombosis , 2006, Canadian Medical Association Journal.

[33]  P. Shankar A general statistical model for ultrasonic backscattering from tissues , 2000 .

[34]  J M Rubin,et al.  Triplex ultrasound: elasticity imaging to age deep venous thrombosis. , 2002, Ultrasound in medicine & biology.

[35]  R. Taillefer,et al.  Radiolabeled peptides in the detection of deep venous thrombosis. , 2001, Seminars in nuclear medicine.

[36]  R. F. Wagner,et al.  Describing small-scale structure in random media using pulse-echo ultrasound. , 1990, The Journal of the Acoustical Society of America.

[37]  T. Wilson,et al.  Intervening attenuation affects first-order statistical properties of ultrasound echo signals , 1999, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[38]  Chih-Chung Huang,et al.  Noise-Assisted Correlation Algorithm for Suppressing Noise-Induced Artifacts in Ultrasonic Nakagami Images , 2012, IEEE Transactions on Information Technology in Biomedicine.

[39]  R. W. Rosser,et al.  Rheology of fibrin clots. I. Dynamic viscoelastic properties and fluid permeation. , 1974, Biophysical chemistry.

[40]  C. Molina Imaging the clot: does clot appearance predict the efficacy of thrombolysis? , 2005, Stroke.

[41]  D. Keber,et al.  In-vitro synergism between t-PA and scu-PA depends on clot retraction , 1995 .

[42]  Mingxi Wan,et al.  Feasibility of using Nakagami distribution in evaluating the formation of ultrasound-induced thermal lesions. , 2012, The Journal of the Acoustical Society of America.

[43]  K. Shung,et al.  High-frequency backscatter and attenuation measurements of porcine erythrocyte suspensions between 30-90 MHz. , 2002, Ultrasound in medicine & biology.

[44]  H. Ermert,et al.  Ultrasound elastography for the age determination of venous thrombi , 2005, Thrombosis and Haemostasis.

[45]  Mingxi Wan,et al.  Flow quantification with nakagami parametric imaging for suppressing contrast microbubbles attenuation. , 2013, Ultrasound in medicine & biology.

[46]  W. Lam,et al.  Factor XIII activity mediates red blood cell retention in venous thrombi. , 2014, Journal of Clinical Investigation.

[47]  Benjamin M. W. Tsui,et al.  Principles of Medical Imaging , 1992 .

[48]  Shyh-Hau Wang,et al.  Assessment of Blood Coagulation Under Various Flow Conditions With Ultrasound Backscattering , 2007, IEEE Transactions on Biomedical Engineering.

[49]  A. Çilli,et al.  Doppler ultrasonography versus venography in the detection of deep vein thrombosis in patients with pulmonary embolism , 2006, Journal of Thrombosis and Thrombolysis.

[50]  Shyh-Hau Wang,et al.  The Effect of Kinetic Properties on Statistical Variations of Ultrasound Signals Backscattered from Flowing Blood , 2009 .

[51]  T. Kondo,et al.  Time-dependent organic changes of intravenous thrombi in stasis-induced deep vein thrombosis model and its application to thrombus age determination. , 2010, Forensic science international.

[52]  F. Dunn,et al.  Ultrasonic Scattering in Biological Tissues , 1992 .

[53]  S. Warach,et al.  Diagnostic and prognostic value of early MR Imaging vessel signs in hyperacute stroke patients imaged <3 hours and treated with recombinant tissue plasminogen activator. , 2005, AJNR. American journal of neuroradiology.

[54]  C. R. Hill,et al.  Acoustic properties of normal and cancerous human liver-I. Dependence on pathological condition. , 1981, Ultrasound in medicine & biology.

[55]  Po-Hsiang Tsui Minimum Requirement of Artificial Noise Level for Using Noise-Assisted Correlation Algorithm to Suppress Artifacts in Ultrasonic Nakagami Images , 2012, Ultrasonic imaging.

[56]  H. Azhari Basics of Biomedical Ultrasound for Engineers , 2010 .

[57]  Yi-Hsun Lin,et al.  Quantitative assessments of burn degree by high-frequency ultrasonic backscattering and statistical model , 2011, Physics in medicine and biology.

[58]  W. A. Verhoef,et al.  Texture of B-Mode Echograms: 3-D Simulations and Experiments of the Effects of Diffraction and Scatterer Density , 1985 .

[59]  J. Arenillas,et al.  Differential Pattern of Tissue Plasminogen Activator–Induced Proximal Middle Cerebral Artery Recanalization Among Stroke Subtypes , 2004, Stroke.