A Need for Close Integration

By Sergio Cerutti, Giuseppe Baselli, Anna Maria Bianchi, Enrico Caiani, Davide Contini, Rinaldo Cubeddu, Fabio Dercole, Luca Di Rienzo, Diego Liberati, Luca Mainardi, Paolo Ravazzani, Sergio Rinaldi, Maria Gabriella Signorini, and Alessandro Torricelli

G

enerally, physiological modeling and biomedical signal processing constitute two important paradigms of biomedical engineering (BME): their fundamental concepts are taught starting from undergraduate studies and are more completely dealt with in the last years of graduate curricula, as well as in Ph.D. courses. Traditionally, these two cultural aspects were separated, with the first one more oriented to physiological issues and how to model them and the second one more dedicated to the development of processing tools or algorithms to enhance useful information from clinical data. A practical consequence was that those who did models did not do
Digital Object Identifier 10.1109/MPUL.2011.941522

Date of publication: 2 June 2011
©BRAND X PICTURES, IMAGE SOURCE

2154-2287/11/$26.00©2011 IEEE

MAY/JUNE 2011

IEEE PULSE 41

showing with a wide possibility of applications in biomedical field. Fithe natural tendency to phase opposition of two peripheral disnally. which are finding a growing interest in both diagnostic resistances was further analyzed in a lumped model study of and therapeutic applications. Such clusion of respiration recording entering at both HRV and AP a paradigm is called the multivariate. and as an answer to unknown questions (e. In parallel with a linear analysis of causal interactions.e. Variable-phase locking patterns between eling” section. signals with images. the This article deals with three basic topics.e.e.g. Studies on multiple sclerosis and Alzheimer’s disease [15].e. where it is clear how important information the statistical power of data analysis by the inclusion of genenhancement and synergy are obtained with certainty when erally accepted knowledge while leaving sufficient degrees of integrating multivariate analysis (i.e. The availability of multiple contemporaneous signals contain42 IEEE PULSE ▼ Linear time-invariant multivariable models have been used earlier to investigate central [13] and autonomic [14] nervous systems.. unmeasured inputs) parameters and observations detected at differof both HRV and AP. time-frequency and time-scale approaches. to properly prepare the new professional memtion compared with the information delivered by single signals bers of BME) but also for the development of newly conor by a black box multivariate analysis. MAY/JUNE 2011 .g. adjusting heart rate to have been used ever vices for vital sign monitoring and others do correct AP in turn (see Figure 2)..ing information of different sites within CV regulation circuits signal processing and vice versa. A first examanalysis of the cardiovascular (CV) system. various contributions will approach different respiratory activity and sympathetic outflow were analyzed in application fields in which the fusion of signal processing and decerebrate artificially ventilated cats under sympathetic or vamodeling will be a recurrent keyword. The advantage of this approach relies in augmenting scale approach. which are arranged complexity of the system shown in Figure 1 was investigated as follows.. In the “Advanced Algal activation [10]. more signals from the freedom for fitting individual or condition-related features same physiological system) with a multiorgan approach (i. finding a rich variety of behaviors typical of gorithms for Biomedical Signal Processing” section. as well tion/desynchronization conditions of distributed vasomotor LF as complexity measurements derived from nonlinear dynamics) oscillators were described in a simulation study [11]. Linear time-invariant integration of sensory-motor characteristics ple was provided by a model of HRV-AP loop multivariable models aimed at the building of advanced prostheregulation [6]. The synchronizarecalled (i. as well as an autoregressive structure of This integration process could comprehend the stochastic parts (i. including gain of mechanical action of HR as in sleep). by finding physiological pathways for respiratory sinus arrhythmia. both). which could be more specific to autonomic regulaposes (i. some physiological ing plays a crucial role. which feeds back baroreflex ses and rehabilitation tools. ceived research projects in which the integration between The complexity of CV regulation renders it difficult to biomedical signal and image processing (BSIP) and modelachieve a direct modeling..e. scale. nonetheless. and with multiscale integration too (i. loop. resonance of loops and role in generating HRV (i.e. learning and stress [16] as well as intention [17] also benefit from such techniques... up to the entire organ level of detail). either anatomical or functional or rhythms versus spectral content of stochastic residuals [8]. the vascular tree connected to peripheral districts with active autoregulation [12]. topics a priori information can be easily included in such as brain–computer machine or interfacthe layout of multivariate closed-loop identies. tainly peculiar of our discipline of BME [3]. multimodality. The prosince in investigating require an intelligent fusion of modeling and posed causal interaction layout and parametcentral and autonomic signal processing competences that are cerric structure considered an additional AP-AP nervous systems. Integration of BSIP and Biological Modeling Toward Systems Biology: Modeling Biosignals Model-Based Signal Processing of Cardiovascular Regulation The research line on heart rate variability (HRV) signal. mainly arterial pressure (AP). Just to give simple examples. as shown in Figure 1. Deconvolution [18] has been successfully applied in reconstructing the course of the not directly accessible pituitary secretion from blood concentration [19]. which at the time was invasively monitored [5] while reliable noninvasive pletismographic recordings were being introduced. in recent years. such reflex activity [7]. started in the mid-1980s for the assessment of autonomic control. However. (e. the “Electromagnetic Field Imaging in Biomedical Applitricts and maximum phase distribution of many when a sympacations” section will deal with innovative electromagnetic mapthetic drive is switched off. [2]. advanced complex nonlinear interactions between oscillators at high (HF) methods for biomedical signal and system interpretation will be and low frequencies (LF) on a forcing input.. The nonlinear nature of peripheral pings. with integration between different modalities on AP [8]. level of barocorrelating information derived from different organs. autonomic outflow to the heart by HRV and response to the need for closer integration between signal processing cardiac ejection combined to vasomotor activity by AP) brought and modeling of the relevant biological systems emerged forward the problem of a suitable analysis of the physiological very clearly [1]. and relationships passing from gene to protein scale to cellular role of cardiopulmonary reflexes [9]). In the “Integration of BSIP and Biomedical Modin several directions. This is not only true for training purinteractions. and wearable deresponses on the heart. neuroengineering. A key point was the inent scales and organs and with different modalities [4].. nonlinear dynamical fication.. multilevels. was soon extended to other CV signals.

Logical networks have been developed to infer prognostic factors in oncology [20]. outflow to left ventricle (LV). and HRV interactions superimposed to a sketch of physiological mechanisms and neural structures: supraspinal circuits (mainly brainstem parasympathetic). Time-variant dynamics has been initially modeled via Kalman filtering [22]. such as principal components analysis [21]. s) series represents AP variability. Severe MV regurgitation associated with degenerative MV prolapse is one of the most common valvular pathologies in the industrialized FIGURE 2 Translation of Figure 1 interactions into an identifiable linear parametric closed-loop model. Ws Ms Respiration Vasomotor Modulation Wr Mr r Rs Mechanical Hst Rt t HP Us SAP S Hss Hts Sinus Node Modulation Ut Mt Wt Baroreceptive Mechanisms AP Regulation Clinical Parameter Detection Through Cardiac Modeling The research activity at the Department of Biomedical Engineering in the field of cardiac image processing and modeling has been recently focused on the development and application of image processing techniques for diagnosis and support in mitral valve (MV) surgery repair procedures. Stochastic parts (Mt. low-frequency (LF) vasomotor activity. t) series represents HRV and systolic AP (SAP. Windkessel (WK). The overall structure is multivariate dynamic adjustment (alias ARXAR. From [6]. MAY/JUNE 2011 ▼ IEEE PULSE 43 . and Mr) are autoregressive (AR). peripheral vascular districts. Biophysics simulation of the modeled behavior allows to in silico emulate pathophysiology [26] toward systems biology [27]. Various applications are described in [24] and [25]. Heart period (HP. Ms. besides selecting salient features.CNS Cardiopulmonary Reflex Respiration HF Lungs Heart SN LV Stroke Volume Heart Rate Spinal Circuits AB LF LF Arterial Pressure LF LF Phrenic Nerve HF LF Supraspinal Circuits Baroreceptive Mechanisms HF LF LF Peripheral Vascular Districts LF LF LF Vessels Total Peripheral Conductance WK FIGURE 1 Causal structure (thick arrows) of respiration. Piecewise affine identification [23] of hybrid logical and dynamical processes has been finally developed to reduce the investigated problems as piecewise linear by identifying data from switches among subsequent epochs. Deterministic blocks (Hst. AR eXogenous AR). arterial baroreceptors (AB). sinus node (SN). spinal circuits (mainly sympathetic). and Rt) are moving average. and cardiopulmonary reflexes. AP. Rs. Hss. Hts.

and it is characterized by high morof MV regurgitation. The MV repair. annulus is enlarged and less bidity and mortality. independent of LV dimensions. together with papillary muscle tips posiLesion Evaluation in Fluorodeoxyglucose-PET tion. Preliminary results of cal solution for this pathology. 44 IEEE PULSE ▼ MAY/JUNE 2011 . position in the scanner. advanced image processing and finite element modeling techThe obtained results give new insight for the in vivo perforniques (Figure 3). with a high dependence on object (lesion and backible (FLEX) band or a complete rigid (RIG) ring. As expected. (c) stress distribution computed from finite element model.surgaid. modeling.MA 1 Displacement (mm) (a) Maximum Principal Stresses (MPa) 0. cardiac magnetic resonance] with (S) and conicity (C). www. and count statistics. an algorithm for LV shape assessment from advanced cardiac imaging techniques [realRT3DE data [30] was developed.org for more details). space from RT3DE data sets to evaluate the dynamic pattern of change of several geometric and functional valvular parameters. is currently the primary surgiassociated with more planar annular shape. Annuloplasty resulted sertion of a prosthetic ring on the MV annulus regurgitation in reduced areas in both RIG and FLEX and in a (annuloplasty). valvular pathologies (PRIN 2007. to obtain patient-specific information on an mance of the implanted rings and for the subsequent cardiac reMV (see www. as well as in a ground). control group (NL). and this information. offering new indices for the clinical decision process Mitral annulus was tracked frame by frame [28] in a 3-D and follow-up. resulting in the time three-dimensional (3-D) echocardiogracomputation of 3-D shape indices of sphericity phy (RT3DE). with inSevere MV planar compared with NL.55 X Z 13 Y (b) –. In this scenario. degenerative MV the modeling approach are also promising to use our efforts were aimed at characterizing the in prolapse is one of this patient-specific analysis in a surgical planning vivo behavior of the prosthetic device as well as the most common scenario as a predictive tool [29].01 0 0 (c) C di C l (%) Cardiac Cycle (d) 10 100 FIGURE 3 From RT3DE to finite element model of an MV: (a) RT3DE data set. was used as a boundary condition in the definition of fiThe quantitative information theoretically delivered by positron nite element structural models. in the presence countries.surgaid. and (d) MV annulus displacement throughout the cardiac cycle. studying the effects of this surgery on left venIn the context of a nationally funded project tricular (LV) remodeling. Micombined analysis and integration of the most countries lan.org) and in collaboOur innovative approach is based on the in the industrialized ration with Centro Cardiologico Monzino. (b) extracted MV annulus. This approach was applied in a emission tomography (PET) is consistently smeared by its limited group of patients with severe MV regurgitation receiving a flexresolution.

the correction of count Starting almost 30 years ago with the pioneering work of data. oxyhemoglobin. To preserve Poissonian features. aij/ACFi.000 AWOSEM avoids application of attenuation cornm. brain sonian assumption. and 4) background. A two-dimensional transaxial approach was used after a suitably optimized Fourier rebinning (FORE). The main conclusion of these studies was that resolution recovery was able to improve the estimate of the total activity within a lesion. the most common approach of fNIRS is in the Nuclear Medicine Department. noninvasive functional near-infrared spectroscopy (fNIRS) has been first used to invesexplicit in the iterations to preserve the Poistigate. 3) transition region affected by lesion spill-out. The Department of Bioengineering in cooperation with the So far. The key limitations of CW fNIRS ring in a 3-D modern scanner for resolution recovery [35]. ACFi.. An fNIRS employs ith measure.The theoretical framework provided by maximum likeliTime-Resolved Functional hood [31] and the relevant iterative algorithm of attenuationNear-Infrared Spectroscopy weighted ordered subset expectation maximization (AWOSEM) [32] provides a powerful means to deal with the Poissonian feaBasic Principles and Instrumentation tures of collected data. link activity li in the jth image eleA key point in TR used to assess muscle oxidative metabolism ment (either voxel or basis function [33]) to the fNIRS is the ability in pathophysiology [38]. these two species. the rest of image is frozen at low resolution. and efficients. on data. has explored several aspects tenuation at two wavelengths between a couple of optical in this field. providing a reliable estimate of FIGURE 4 PET/CT pulmonary patient data reconstructed with (a) standard voxel-based AWOSEM and (b) AWOSEM region. the iterations required for quantification did not improve the diagnostic readability compared with the standard clinical images that are smooth and far from convergence to avoid false positives. at a known relative disand validation of a parametric model of space-variant blurtance (typically 2–4 cm). placed on the tissue surface. Absorption and cluding further features such as space-variant activation.and deoxyhemoglobin lyzed concerning their effects on lesion detectability and leallows the separate measurements of the concentration of sion quantification.e. 2) partial volume voxels. The elements of the system oxygenation in neonates and adults and later matrix. mainly centered on the construction. yi. nonetheless. a 3-D blurring model was worked out for a full resolution recovery: radial. In this algorithm. to separate systemic optical radiation in the range 600–1. MAY/JUNE 2011 ▼ IEEE PULSE 45 . Fondazione IRCCS Ca’Granda continuous wave (CW) regime. by the specific attenuation correction factor. and targeted eter describes the tissue content while the object features. but it corrects system cohemodynamic stituents (water. as shown in Figure 4. The difference [34] and their object/algorithm dependence have been anain the absorption spectra of oxy. that is to measure light atOspedale Maggiore Policlinico. Iteration (b) of this procedure with lesion segmentation adjustment proved to recover blurring and partial volume effects. yi. is Jobsis [37]. i. experimentally and clinically. fibers. aij. The flexibility and robustness of the blurring model permitted a thorough analysis of convergence and its object dependence. and axial. Finally. regularizing cally characterize tissues: the first paramfactors through basis functions. changes from deoxyhemoglobin) is relatively low and acIntensive research has been carried out functional changes counts for an optical penetration through in recent years to evaluate the benefits of inrelated to brain several centimeters of tissue. convergence properties second characterizes the tissue structure. lipid. which considered few image elements: 1) voxels 100% within lesion. where light attenuation by tissue conrection. ACFi. with better control over noise amplification (noise breakup) phenomena. scattering coefficient are measured to optiblurring for resolution recovery. through an iterative formula. tangential. estimation. lesion volume and total activity. (a) However. an AWOSEM-region algorithm [36] was proposed. also.

The accuracy of hemodynamic parameters estimametabolic brain activity [44]. from scattering is based on the use of modulated laser sources In our opinion.000 5. for their practical Many biomedical signals are characterized by oscillatory patand effective use with TR or FD setup. broadening. Intensity (ph) 46 IEEE PULSE ▼ MAY/JUNE 2011 Early Gate . Analytical model for homogeneous meAdvanced Algorithms for Biomedical Signal Processing dium or simple structured medium (e. dium such as a biological tissue. In fact. analyzing the first part approach is the study of photon migration in of the TR curve (early gate). which carry relevant information for diagcomputational time and a priori information about the structure nostic and therapeutic purposes as well as for understanding of the head [e. problem of noninvasively probing a diffusive medium. 2) the knowledge of the real bulk optical properties of the tissue. layered medium) can be derived [40]. FD and TR fNIRS provide a richer insight to the and intracerebral activities [42]. the spectral features of these signals evolve with time. Thus. TR should be preferred to FD fNIRS... and resonance imaging (MRI) scan]. or numerical methods with the real tissue structure. and 3) the knowledge of the real tissue structure. Typical examples are the d. brain activity (Figure 5). However. some groups have develoscillatory patterns. such as Time-Frequency and Time-Variant the human head. the main The analysis of these oscillatory patterns is usually performed by spectral analysis using both nonparametric [fast Fourier transform (FFT)-based] and parametric [autoregressive (AR)/moving average (ARMA) model based] approaches. beand on the measurement of signal phase and amplitude cause TR techniques rely on an easier approach to the probchanges caused by propagation. to date. occurring efficients of the probed medium.g. As a result. naturally encoded Continuous Wave fNIRS Data Analysis into the photon’s arrival time. u. to the arrival time of the photons is highlighted. The frequency domain (FD) lem of depth sensitivity. A key point in TR fNIRS is the abiltechnique extracts both mean scattering and absorption coity to separate systemic hemodynamic changes. the anatomical images provided by magnetic the underlying physiology. The different penetration depth related mary of the main findings will be reported. require a large amount of terns (or rhythms). we consider medium. and the capability to track these changes is relevant for the characterization of the dynamics that occur in a wide range of clinical and physiological studies. it is possible to discriminate extraIn principle.e. causing the lack of quantitative assesshas accurately measured the optical properties of the different ment and sensitivity. Apart from some technical b rhythms of the EEG and the LF and HF components of the problems for the implementation and integration of analytical HRV signal.000 2. 1. from functional changes related to calibration of collection efficiencies is performed. 10 The possibility to track spectral changes with time has been made possible by the application of time-frequency and timeLate Gate variant methods.000 These tools require the signal to be stationary in the analysis window. we consider phothe time domain.g.000 3. they are intrinsically 100 nonstationary). These apTR fNIRS can be integrated with other functional techniques proaches can discriminate between absorption and scattering such as electroencephalography (EEG) to merge different types contributions and derive absolute values for the hemodynamic of data to better explain the relation between electrical and parameters. thus.000 4. biomedical signals are characterized by transient waveforms of various natures (i. have a low probabildelay experienced by a short (hundreds of pisignals are ity to reach the brain cortex. photons with a higher probability to go deep oped compact systems for time-resolved (TR) into the tissue and bring information about fNIRS [39]. only a brief sumFIGURE 5 TR fNIRS curve. TR fNIRS can also be integrated tion mainly depends on three aspects: 1) the accuracy of the with fMRI to compensate for the lack of anatomical informatheoretical model describing photon propagation in a turbid metion [45].. This approach is based on tons that travel few hundreds of picoseconds the detection of attenuation. Here. exploiting the depth information. it is possible to use numerical methods such as Methods for Biomedical Signal Processing Monte Carlo or finite elements. [43]. A review of these activities in the analysis of HRV signals can be found in [46]–[48]. Recently. For a highly heterogeneous medium. no one scattering coefficient. The Department of Bioengineering of Politec1 nico di Milano has been very active in this field since the begin0 1. a. These methods. provided that a nontrivial particularly in the scalp.000 ning and contributed with both methodological innovations and Time (ps) novel applications. and Many biomedical into the tissue and. In fact. while analyzing coseconds) laser pulse injected in a diffusive characterized by the tail of the TR curve (late gate). The dual brain activation.limitation of these approaches is the lack of knowledge about the techniques are the coupling between the absorption and in vivo bulk optical properties of the head. A possible way to uncouple absorption structures of the head [41].

the sample-by-sample basis functions are time-windowed sinusoids. thus. estimation is able to track changes in the signal characteristics. being more evident in patients with syncope [51]. different trends were observed. The response is dependent on the amplitude of the stimulus: a faster (and larger) sympathetic response was observed for more pronounced tilt angles [47]. a new PSD can be calcuanalysis functions are complex sinusoids. in fact. can be made recursive. whose parameters are. but preceding the ST displacement on the ECG [53]. the better the time resolution (Dt) and poorer the frequency resolution (Df). Different versions of WD have been proposed in literature to reduce the presence of cross terms in the time-frequency plane. An example of HRV signal analysis during stable angina is presented in Figure 6. Spontaneous Myocardial Ischemia An interesting field of application is the study of relationships between autonomic nervous system (ANS) and myocardial ischemia. using the time-variant model in the bivariate form. unknown. puts into evidence an LF increase within the 2 min preceding the ischemic attack. a compromise is needed in the choice of the proper basis. if with the concept of ting factor can be added in the estimation procethe basis functions are localized in both time and instantaneous power dure to make the updating parameter procedure frequency. MAY/JUNE 2011 ▼ Adaptive Parametric Models The parametric approach to the estimation of PSD assumes that the time series under analysis is the output of a given process. oscillations and nonstationarity characterized the trend of the LF components. In practice. The parametric spectral approach is a procedure that can be summarized in three steps: 1) choice of the correct model for the description of the data. When the A quadratic TFR is made available. which may be either sudden or progressive. In addition. respectively. To overcome this limitation. This is the wellknown Wigner–Ville (WD) distribution. In particular. During pharmacological tests (dipyridamole stress test). are linked by the Heisenberg’s inequality according to the following expression: The most diffused approaches for time-frequency representation (TFR) of a signal can be summarized in three main categories: 1) linear decomposition. and these are enclosed in the Cohen class. In such a way. The time-variant parameters were therefore documented to be an early sign of ischemia of clinical interest. either spontaneous or induced. Usually. a signal is characterized by shorttime. an autonomic mismatch between HR and blood pressure regulation was also observed before syncope [52]. Many clinical tests (such as stress test) induce changes in ANS modulation of the heart beat. and 3) The fundamental mathematical tool for time-frequency analycalculation of the PSD through proper equations (according to sis is based on signal expansion and inner product. A forgetobtain a Fourier transform (FT) of the signal. a multiresolution decomposition can be achieved through the wavelet transform (WT). according to the selected model). LF components. they and a TFR of the signal is obtained. where the decomposition basis is obtained from a mother wavelet (or function) that is stretched or shrunk in time to obtain orthonormal bases characterized by different time-frequency resolutions. we is usually associated lated for each new sample in the data. and a new model can be the signal is expressed as a linear combination estimated each time a new sample of the signal of a set of elementary components. 2) quadratic distributions. however. obtained by AR-based time-varying methods [49]. the model IEEE PULSE 47 . and 3) adaptive parametric models. Applications 1 Df # Dt $ . An alternative quadratic distribution is obtained by calculating the FT of the instantaneous autocorrelation function (ACF) of the signal. the process is completely described by the model parameters. the oldest ones are forgotten with an exponengiven by the short-time FT (STFT) in which the tial decay. the trend of spectral parameter puts into evidence an increase of the LF component in coincidence with the echocardiographic marker of ischemia. An example is spectral density. Provocative Tests Quadratic Distributions A quadratic TFR is usually associated with the concept of instantaneous power spectral density (PSD). 4p The smaller the time duration of the basis functions. a different interplay between ANS and variant or stable angina was documented [50]. When different ischemic events are considered. which preserves both the time and the frequency information of the signal. the coefficients of the decomposition more dependent on the more recent data while constitute the TFR of the signal. obtained by squaring the coefficients of STFT and WT. 2) estimation Linear Decomposition of the Signal of the model parameters based on the recorded data. Two popular examples of quadratic distributions are the spectrogram and scalogram. An early result. HF components superimposed to long-time. and its formulation is based on the input–output relationships according to the so-called black-box approach. Time and frequency properties are not independent. all documenting an important involvement of ANS in either generating or sustaining the attack. The parameter estimation proper orthogonal basis functions. When the tilt was prolonged.Methods is independent of the physiology or the anatomy of the biological process generating the data. The study also documented a sympathetic withdrawal preceding syncope. Thus. Usually. thus.

time-frequency methods are required for correct analysis. during the execution of voluntary movements or even during motor imagery. [58]. As the HRV signal is highly nonstationary during sleep.00000 520 510 500 490 480 470 460 450 440 430 420 410 400 390 380 370 360 350 340 330 320 310 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 ⊥ (t) 00 09 10 27 36 0..PSD B E y (t ) e(t ) ⊥ Updating Algorithm Δa (t ) ⊥ a (t ) y (t ) z–1 a(t –1) a (t φ (t ) = (y (t –1) y (t –2). peak-to-peak analysis and symbolic methods have been proposed as systematic tools EEG Processing It is well known that. 45 . significantly change in the different sleep stages and in the presence of pathological events such as sleep apneas and microarousals. Bifurcation theory has been successfully applied to the analysis of evolutionary processes in biology. and a marked power increasing in the beta range [beta event-related synchronization (ERS)] at the end of the movement. (b) Sequence of the PSDs as output of the recursive algorithm during a stable angina episode. 0.02000 0. 0. 0. and applications in diverse fields. while smoothed pseudo-Wigner-Ville was used for the characterization of ANS during microarousals [56]. 0.06000 0. the typical parameters that quantify the dynamical changes of the HRV signal. studies have yielded theoretical contributions [59]–[61]. such dynamics are quantified through the time-frequency technique. but preceding its execution. Sleep Studies Sleep is a physiological condition that can be altered by many pathological events. In a recent article. [63]. it also affects the peripheral systems and the related signals. namely LF and HF powers. As far as signal analysis is concerned. numerical methods [62].08000 0.y (t –n)) (a) (s2/Hz) 0. because in this way it is possible to put into evidence both power and frequency changes in the rhythms of interest [57]. Even if sleep evaluation is mainly based on the analysis of EEG. (Hz) (b) FIGURE 6 (a) Recursive algorithm for the time-variant estimation of AR model coefficients..04000 0. Thus. namely adaptive parametric models that are particularly suitable for this application. ning of the movement. there is a power decreasing in the alpha range [alpha desynchronization or alpha event-related desynchronization (ERD)] related to the begin48 IEEE PULSE ▼ MAY/JUNE 2011 0. such as the HRV and the respiration signal. Time-variant AR model has been used for automatic sleep classification [54] and for apnea detection [55] from the HRV. Complexity in Biomedical Systems and Nonlinear Parameters Measurements Methods and Modeling Approach The research group at the Department of Electronics and Information at Politecnico has been actively working on the methodologies for the analysis of complex signals and systems. In the area of bifurcation analysis [57]. Each PSD corresponds to a single sample in the signal.

In this context. The most recent trends in the by this signal may not be totally explained by study of epidemics are based on the theory of a linear approach [71]. and Fourier spectrum) with original series. and constructure of the physiological rhythms of the trol of chaotic systems. one of the main issues is the The null hypothesis the test wants to reject is. 2008). methods quantifying fractal and self-similar monofractal obtained within the research group on this issue have been characteristics [1/f a spectrum. eration and control [72]. tems oscillate in unison. either in many epidemiological regimes that are observed make feasible a less time or FD. Their estimation An important class of networks is that in which each node must be associated with a determinism test based on surrogate is an oscillator (e. The results (collected in several papers in the HRV signal characteristics by a nonlinear approach is based leading international journals and in a book [66]) range from on the different methods investigating both geometric and dythe classification of the evolutionary regimes of resourcenamic signal features. The evaluation of adaptive dynamics. through classical linear methods. the study of the spreading of This second statement confirms the value of the analysis some specific disease has pointed out some nontrivial interplay approach through nonlinear methods. in particular in (mean. such as fractal dimension evolutionary attractor [58]. consumer systems and the evolutionary origins of cooperative At first.. namely. the cardiomagnetic fields are recorded with superconductbeen widely studied to identify the complex nature of its coning quantum interference devices (SQUIDs) [76]. the short period and the information carried pact of epidemics. but they have also been described in detail in plenary lectures at the 2006 Inter(DFA)] and regularity and complexity statistics (approximate national Symposium on Nonlinear Theory and its Applications and sample entropy: ApEn. The signal shows apparently erratic the research group has contributed to the methodological debehavior but abrupt changes and patterns are also present in velopment and to the application of the approach known as which a more regular behavior is detectable.. examples of this approach conThe modern signal processing approach to the biomedical time cern CV pathologies and fetal heart rate analysis. Results on HRV sigbetween network topology and infection peculiarities [65].trol mechanisms. variance. This has led to the introduction of large amount of signal analysis techniques aimed Electromagnetic Field Imaging at the extraction of nonlinear parameters from experimental in Biomedical Applications time series. Typidominant role. the system model is often unknown. proportional integral derivative) restrictive sensor the regulating action performed by the ANS in and fuzzy control schemes for reducing the impositioning. The aim is to investigate the for modeling. at the 6th European Conference on plexity) allow to characterize the HRV signal distinguishing Ecological Modeling (ECEM 2007. SQUIDs are MAY/JUNE 2011 ▼ IEEE PULSE 49 .e. neurosciences. Furtherpathologies (e. detrended fluctuation analysis collected in a series of papers [67]–[70]. The full magnetic sensor affect the HRV signal both in short and long two-parameter bifurcation analysis of the classisystems for temporal windows. As in biological field. and Lyapunov exponents. series received a significant improvement by the development of nonlinear dynamical system analysis. Parkinson’s disease and epilepsy). Time-Series Analysis Among other applications. and at the Internapathological from healthy subjects [74]. complex networks: in this context. Corsica. Figure 7(a) reports a tional Meeting on Chaos and Dynamics in Biological Networks 24-h HRV signal recorded from a Holter tape in a normal case (Cargese. methods based on the reconstruction of the HRV and cannibalistic attitudes to the discovery of the first chaotic time series in an embedding space. were computed. A huge numdata are series of casual data sharing some linear properties ber of systems naturally call for this modeling. Bologna). “a stochastic linstudy of synchronization.. Recently. The analysis of HRV sigcal SIR/SEIR models has disclosed and classified magnetocardiography nal. including the study of many generating the signal is neither linear nor stochastic. Magnetocardiographic Field and Diagnostic Imaging the measured signals are the only information we can have Magnetocardiographic field imaging (MFI) is a technique used about the system itself. a dynamical system data confirming that it is a deterministic mechanism instead of that behaves periodically or chaotically when isolated (pera linear correlation that controls the HRV dynamics.. a neuron). compared with a transplanted heart patient [Figure 7(b)]: apower law coefficient in 24 hours is significantly different in the two cases. SampEn as well as Lempel-Ziv com(NOLTA 2006.g. Surrogate haps by producing recurrent spikes or bursts). Trieste). The complex structure of the HRV signal has cally.e. provided two main outcomes: the in real-world data [64] and has paved the way quantification of some important properties of to classical (i. This is precisely the case of the huto record the contact-free magnetic field distribution and estiman life support systems among which the heart plays a mate the underlying source distribution in the heart [75]. The results more. parameter estimation.g. i. the possibility that all the sysear process generates the HRV time series” [73]. In particular. new cardiac system by assessing how the presence Epidemic spreading is one of the areas where technologies of of nonlinear deterministic phenomena could the earlier methods have been exploited. since this fact is of paramount imResults in 24-h HRV series have shown that the structure portance in many applications. nal analysis have shown that its dynamic behavior involves Bifurcation theory has been successfully applied to the nonlinear components that also contribute in the signal genanalysis of evolutionary processes in biology.

Therefore. All setups provide approximately the same number of measurement channels and are positioned in front of the chest of a healthy volunteer [77]. Comparison of Existing Sensor Arrays Using different FOMs. currents. To this end. new technologies of magnetic sensor systems for magnetocardiography make feasible a less restrictive sensor positioning.59 Slope = –1. Consequently. Heart-Transplanted Subject 0 –1 –2 log (sec2/Hz) –3 –4 –5 –6 –7 –8 –5 –4 –3 –2 log (Hz) (b) –1 0 R = 0. recently.2 S/m) and lungs (0. Knowledge of these parameters is of crucial importance in understanding such interactions and is a prerequisite when assessing the impact of EMF exposure on health or when assessing or optimizing therapeutic or diagnostic medical application that employ EMF. since they require liquid helium (low-temperature superconductors) or nitrogen (high-temperature superconductors) cooling. and rate of energy deposition within the human body caused by the exposure to such an EMF.08 –5 –4 –3 –2 log (Hz) (a) –1 0 restricted in their positioning to cryostats. FIGURE 8 The BEM and source models. the general question arises: how to optimally place the sensors obeying a technical minimum distance between them. We model the cardiac sources with 13 dipoles regularly arranged around the LV blood mass. covering the same area. Numerical modeling of that interaction provides a unique way for assessing the resulting spatial distribution of internal EMF. The slope represents the α coefficient in α-power law spectrum. The realistic setup is the Argos200 comprising 65 three axial sensors. we compare three different SQUID sensor setups: one realistic and two idealized ones. The sensors are modeled as a coil with a single winding and a diameter of 1 cm.04 S/m) is created from a T1-weighted MRI for a 72-year-old participant (Figure 8). The measure of the averaged heart cycle (PQRST) data from the patient (195-channel vectorial magnetometer system Argos200. Italy) serves for the estimation of the orientation of the dipoles with a minimum norm approach with L-curve regularization. The idealized setups are an 8 3 8 three-axial (measuring three magnetic field components) magnetometers array and a 14 3 14 monoaxial magnetometers array (in Figure 8. 50 IEEE PULSE ▼ MAY/JUNE 2011 . the search space of the optimization scheme is discretized. FIGURE 7 (a) Log–log spectra calculated in 24-h HRV signal in a normal subject and (b) in a patient after heart transplant.34 Slope = –1. Electromagnetic Field Exposure and Biomedical Applications The Milan Unit of the CNR Institute of Biomedical Engineering (ISIB CNR) is internationally acknowledged for their studies on the effects of human exposure to electromagnetic fields (EMFs) and on computational modeling of the interaction between EMF and the dielectrically inhomogeneous human body. However. a typical goal function used in sensor array optimization is the condition number (CN) of the kernel (leadfield) matrix. 14 3 14 1-D). [78]. Since the generation of the kernel matrix for a given position of magnetic sensors is computationally expensive. a precomputation for a dense enough grid of sensor positions and orientations is needed. [78]. AtB SrL.Normal Subject 8 6 log (sec2/Hz) 4 2 0 –2 –4 –6 R = 0.66 Simulation Setup A three-compartment boundary element model (BEM) of the torso (conductivity 0. More sophisticated figures of merit (FOM) to compare sensor arrays efficiency have been introduced [77].

stimulation. Enrico netic Fields Exposure (EFHRAN) Project. and Maria Gabriella Signorini are with previously served as a central coordinator of three multicenMAY/JUNE 2011 ▼ IEEE PULSE 51 . evaluation of the electric fields and curin BME.5 1. in the form of signals and images properly detected. Along this direction. [85]–[88]. radio frequency identiEMF-NET (FP6) was a large coordination action aimed to infication (RFID) applications in health environterpret the mass of results of scientific research ment. including the time of use of the device close to the body was proposed. cal measure in both animals and humans.0 GHz) frequencies. such as main findings were related to the study of the effects time-frequency and time-variant approaches. identifying tive research as well as the implementation in exposure to WiFi the different influence on the fields because of many clinical procedures extensively makes network do not the use of different electrodes in terms of size use of these concepts in more or less sophistiinterfere with the and shape in tDCS. the functionality of exposure to passive RFID reader during newimportant links between BSIP and physiological implanted born–mother identity reconfirmation promodeling and their important derived synergies cochlear implants. and an innovative relationCV system studies.The main results of the ISIB unit in this area were on: 1) Numerical estimation (using finite integration techniques) of the radio frequencies EMF distribution in human head or 0. detected information between multiple signals. maximum permitted power. electric (FP5) and EMFnEAR (DG Health and Consumer Protection) [transient direct current stimulation (tDCS)] and magnetic that were focused on mobile phone exposure and hearing. (b) distribution of the magnetic field in unit quantitatively demonstrated that the use of mobile a whole-body newborn model generated by an RFID identity phones and the exposure to WiFi network do not interfere reconfirmation system. In this article. TR fNIRS. with the functionality of implanted cochlear implants. Moreover. the integration operation of the See Figure 9 for an illustrative example. This also includes the computational estimation of the coupling of environmental EMF with active and passive medical implants in the human body. In particular. organs. In particuapproaches where. In support of this aim. The main recent findings were related to the The ISIB unit quantitative estimation of the current density Summary and Conclusions quantitatively in terms of pattern and values in the cochlear BSIP constitutes a major field of interest in both demonstrated tissue around the cochlear implant electrode educational aspects and research environments that the use of mobile array. are particularly stressed. [80]. the ISIB primary motor cortex. and electromagnetic sensor [83]. and has Caiani. 2) Optimization of health support systems and procedures tric projects funded by the European Commission: GUARD that make use of EMF. In fact. cedure in neonatal clinics. have a relevant impact on various biomedical applications. a few examples have been described in which the study controlled exposure to GSM and UMTS phones at the of EMFs.57 V/m rates (SARs) at the level of the peripheral hearing organs in 0 humans due to exposure to mobile phones at global system (a) (b) for mobile communication (GSM) and universal mobile telecommunications system (UMTS) frequencies are extremely FIGURE 9 (a) Electric field distribution on the head tissues on a transversal plane passing through the anode during tDCS of the lower than the current exposure limits. by using different modalities. also in this context. and the assessment of the cated medical applications. Currently. as well as in neurosciences ship between the maximum generated magnetic fields and and functional imaging. modalities. the physiological knowledge phones and the rent densities generated by brain stimulators improvement in a wide variety of innovain the cortex and white matter. The advanced methods in the area of information treatment. deep brain stimulation. and across multiple scales (from gene/protein levels up to 3) Study of the potential health effects of exposure of cell and organ levels) seems to be extremely promising. Anna Maria Bianchi. Further. ISIB CNR is serving as a central coordinator of the European Health Risk Assessment Network on ElectromagSergio Cerutti.800 MHz) surements. Giuseppe Baselli. 2009–2012. Luca Mainardi.073 (A/m) trunk by devices and systems for mobile communication. no acute effect was found on the main audiologimodeling and information processing plays a fundamental role. most often carried out through nonlinear dynamical and UMTS (around 2. the main recent findings of these studies were related to the quantitative confirmation that the EMFs and the specific absorption 0 1. the integration between lar. on EMF and health impact. In the latter case. have been investiof exposure of the animal and human hearing system gated in the biomedical field together with the complexity meato mobile phone radiation at GSM (900–1. sensitive levels of exposure of the newborns examples have been provided in the areas of were identified. mainly focusing on cochlear implants and neural stimulators [79]–[82]. such as cochlear implants. especially on mobile phones and wireless fidelity (WiFi). considering Finally. [84]. biological systems to EMFs [79].

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