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MEASUREMENT 2011, 8th International Conference Recent Topics in Non-Invasive Cardiac Electroimaging Prof. György KOZMANN Head, R & D Center of Medical Informatics, Faculty of Information Technology, University of Pannonia, Veszprém, Hungary 27-30 April 2011, Smolenice Castle, Slovakia Co-workers, 2011 Prof. Kozmann György Prof. Nagy Zoltán Prof. Maros István Dr. Starkné Werner Ágnes Butsi Zoltán Dr. Juhász Zoltán Dr. Kósa István Dr. Magos Tibor Dr. Vassányi István Dr. Gaál Balázs Dulai Tibor Tarjányi Zsolt Végső Balázs Cserti Péter Fülöp Kornél Pintér Balázs Takács István Tuboly Gergely Dr. Dombovári Magdolna Nemes Márta Essential motivation • “Cardiac arrhythmias are a major cause of death and disability. Despite the clinical need and the importance of studying arrhythmia mechanisms in humans, a noninvasive imaging modality for cardiac electrophysiology is not yet available for routine application” (Rudy Y. Ann N Y Acad Sci. 2010 Feb;1188:214-21. ) Levels of cardiac electroimaging Body surface level • need for reproducible, high-density measurements • need for biophysically meaningful features • need for improved inverse computations Epicardial level • understanding the cellular level prerequisites of arrhythmia • need for achiving compatibility with experimental findings First generation of data acquisition and data presentation Improvements in measurement technology Electrode-vest under development at the Innomed Inc., Budapest Prerequisites of arrhythmia According to our current understanding the biophysical substrate of leathal arrhythmia is the fragmented propagation and the repolarization heterogeneity Fragmented propagation is due to static and dynamic obstacles Determinants of dynamic obstacles: • determinants of Um membran potentials like APD, AP restitution, CV restitution, cardiac memory, and • the properties of the Cai (intracellular) transport between the sarcoplasmic reticulum and the cytoplasm Body surface characterization of repolarization heterogeneity QRST integrál vs repolarization heterogeneity: ( P, t )dt k z( P, r) (r)dV QRST s Vs m (r, t ) mr (r)dt QRST Geselowitz DB.: The ventricular gradient revisited: relation to the area under the action potential. IEEE Trans Biomed Eng. 1983 Jan;30(1):76-7. Hubley-Kozey CL et al.: Spatial features in body-surface potential maps can identify patients with a history of sustained ventricular tachycardia. Circulation. 1995 Oct 1;92(7):1825-38. 8 Extension of depolarization and repolarization characterization QRS integrál vs activation sequence ( P, t )dt c z( P, r) m QRS QRST integrál vs repolarization heterogeneity dVs Vs ( P, t )dt k z( P, r) (r)dV QRST s Vs m (r, t ) mr (r)dt QRST Relationship of QRS of QRST integrals (in KL-domain) KL(QRST ) T KL(QRS ) b e a1,1 a 2 ,1 T a12,1 a1, 2 a 2, 2 a12, 2 a1,12 a 2,12 a12,12 Kozmann G et al: Beat-to-beat interplay of heart rate, ventricular depolarization, and repolarization. J Electrocardiol. 2010 Jan-Feb;43(1):15-24. 9 Definition of NDI 12 Definition of the index of non-dipolarity (NDI) in terms of Karhunen-Loeve (KL) coefficients NDI c 2 i c 2 i i 4 12 i 1 Dipolar ei „eigenmaps” (KL1-KL3): ant BSPM approximation by the weighted sum of KL coefficients F(t) ≈ S ei ci post + PND PD PND Non-dipolar ei „eigenmaps” (KL4-KL12): ant post ant post ant post QRST integral SD/M ratio in NOR vs ICD groups Bubble Scatterplot 16000 ICD 14000 12000 SD 10000 8000 NOR 6000 4000 2000 0 -50000 0 50000 1E5 1,5E5 2E5 2,5E5 3E5 3,5E5 M(KL_N) Bubble diagram of M and SD values of NOR (small circles) and ICD group (large circles) QRST integral map KL components Experimental evidence #1: Effect of cell-tocell coupling modulation • Single ventricular myocites paced at constant rate (and held at a constant temperature) exhibit beat-to-beat variations in action potential duration (APD) and in intQRST as well. • On the body surface the variability is manifested in beat-to-beat changes of QRST integral map patterns. • The increase of cell-to-cell coupling resistance increase action potential heterogeneity. Consequently, there is a need for beat-to-beat evaluation of repolarization variability. Zaniboni M, Pollard AE, Yang L, Spitzer KW. Beat-to-beat repolarization variability in ventricular myocytes and its suppression by electrical coupling. Am J Physiol Heart Circ Physiol. 278(3):H677-87, 2000. NDI spikes in the QRST integral of ICD patients # of cycles QRS dQRS QRST dQRST I_T (series) 1100 40 i-2 35 i=198 30 900 RR[MS]: 25 800 20 700 15 600 NDI(intQRST) [%]: 1000 i-1 i 10 szívciklusok 500 400 150 200 RR[MS] (L) (a) 250 300 NDI(intQRST) [%] (R) 5 i+1 0 350 i+2 (b) NDI(intQRST) spikes and RR intervals in a sequence of 200 consequtive cardiac cycles of an ICD patient (a). QRS and QRST integral maps and their difference maps around the cycle i=198 (b) 13 Modelling the possible mechanisms of NDI spikes NDI(QRS) Study in progress: By the use of the slovakian numerical heart and thoracic models the QRS and QRST integral responses as well as the NDI responses of wave initiation point modulations and AP alterations are studied. NDI(QRST) normal 0,0646 0,322 lah2ap-40 0,009 0,0132 lph4ap-40 0,076 0,0162 Experimental evidence #2: concordant and discordant T-wave alternans Cellular properties of the cardiac action potential and Cai cycling dynamically may generate wave instability and wavebreak, even in tissue that is initially completelly homogeneous. There is a need for the spatiotemporal analysis of the QRST integrals. Weiss JN et al.: : The dynamics of cardiac fibrillation., Circulation. 2005 Aug 23;112(8):1232-40. Review. Qu Z, Xie Y, Garfinkel A, Weiss JN.:T-wave Alternans and Arrhythmogenesis in Cardiac Diseases., Front Physiol. 2010 Nov 1;1(154):1-15. Alternating intQRST KL components in the heart cycles of an ICD patient ant Spectral analysis: KL9(intQRST) No. of cases: 348 Hamming weights:,0357 ,2411 ,4464 ,2411 ,0357 post Spectral Density + KL9 + 5E8 5E8 4E8 4E8 3E8 3E8 2E8 2E8 1E8 1E8 0 0 0,00 0,05 0,10 0,15 0,20 0,25 0,30 0,35 0,40 0,45 0,50 Frequency Spectral peaks of alternation ant KL12 Spectral analysis: KL12(intQRST) No. of cases: 348 Hamming weights:,0357 ,2411 ,4464 ,2411 ,0357 post + + - - Spectral Density + 1E8 1E8 8E7 8E7 6E7 6E7 4E7 4E7 2E7 2E7 0 0 0,00 0,05 0,10 0,15 0,20 0,25 0,30 0,35 0,40 0,45 0,50 Frequency Green’s theorem, forms of inverse solutions n Hi Epicardial sources: n Hi Bj Hi Hi i = 1, …,N dFHi Body surface sources: Bj j = 1, …,M dFB Equation of cardiac electroimaging Relationship of body surface and epicardial potentials (for homogeneous thorax model) B1 B2 z11 z 21 . z31 . . z n1 Bn z12 z 22 . . zn 2 z13 . . . zn3 . . . zij . . . . . . . . . . . H1 H 2 H 3 z1m z2m z3 m . . . z nm H ,m 1 Hm Usually: m>>n In forward direction the equation is solvable, in inverse direction: ill-posed Conventional and some recent approaches Tikhonov regularizition attempts to control the oscillation of the solution. To this end introduces a single parameter ( γ ) and minimizes the expression: ~ R F B TBO F O 2 FO 2 By this approach the correlation of the real epicardial potential vectors and the estimated vectors is in the range of 0.7-0.8, which provides qualitatively correct potential patterns though the numerical values are often quite different. In some recent solutions: • truncated singular-value decomposition (TSVD) methods, or • least-squares QR (LSQR) method, based on Lanczos bidiagonalization and QR factorization was used. • Results show that the inverse solutions recovered by the LSQR method were more accurate than those recovered by the Tikhonov and TSVD methods. • By combing the LSQR with genetic algorithms (GA), the performance can be improved further. Approaches in progress • In our approach we wish elaborate optimization techniques for making the problem “well-posed”. • In this respect we plan to further develop ideas of (Maros). This approach will open up considerable flexibility that can be utilized to take into account a priori knowledge (if available). • The other aim is to utilize the idea of “important points” for making the problem well-posed. Maros, I., Thielemans, K., PET Image reconstruction by vector norm optimization, in Guang-Zhong Yang (ed.) Proceedings of MIAR 2001, Medical Imaging and Augmented Reality, IEEE Computer Society, 2001, 152-156. Maros I: Computational Techniques of the Simplex Method. Kluwer Academic Publishers, Boston, 2003. Thank you for your attention!