FIE L D O F T H E INV E NT IO N:

The invention relates to a device for use in diagnosis and treatment of cardiac rhythm disorders. It is aimed to use this device to map the specialized conductive tissue and cardiac muscle tissue by novel 3-dimensional (3D) endocardial biological magnetic field signal mapping with traditional electropotential measurement based 3D electroanatomical mapping system. By the current methods, the cardiac specialized conductive tissue cannot be mapped 3-dimentionally by separating it from the myopotentials on muscle tissue. The 3D mapping of thi s structure wi 11 be abl e to offer new treatment opti ons whi I e maki ng the di agnosti c mappi ng easier to treat the cardiac arrhythmias.

BAC K G ROU ND O F T H E INV E NT ION:

In the field of cardiology, the rhythm problems originated by heart's specialized conductive tissue and muscle tissue are traditionally treated by the measurement of electrical membrane potentials of myocardium and their temporal-spatial differences which is measured by the electrophysiology catheter, placed inside the heart under X -ray fluoroscopy.

Thanks to the technical progress, the actual 3D electroanatomical mapping methods have been developed, which are provided by a 3D visual platform of electropotential measurements from the inner surface of the heart. Recent developments on these methods are intended to increase the electropotential measuring electrodes (poles) on the mapping catheter. By this approach, mapping will be created in less time and at a higher resolution. However, 3D map of heart ^' s specialized conductive tissue cannot be distinguished from muscle tissue by those methods based on electro- potential measurement. On a 3D visual platform, it is not possible to observe route of the wave propagation (the spread of activation or depolarization wave) on the specialized conductive tissue during the heartbeat cycle and how is happens. However, with catheters placed in the appropriate anatomical sites, local single- point electropotential signals can be obtained on the heart's conduction system. Therefore, it is not possible to visualize the body of entire conductive tissue pathways at the same time. As a result, the treatment of rhythm disturbances where the conductive tissue is the source or mediator of arrhythmia, is performed indirectly by looking at the excitation time and location of muscle tissue, not with the direct application of ablation on the specialized conductive tissue.

In the traditional systems for detecting the cardiac signals, possible electroanatomic sites for treatment, are controlled by identification by mapping catheter with contact of each anatomical region individually. Therefore, this process requires a good level of experience of positions and anatomy of heart under fluoroscopy. In addition, similar signals can also be detected from different anatomical areas. Interpretation of appropriate anatomy, and appropriate temporal and morphological changes of the spontaneous or stimulated electropotential signals depends on experience of electrophysiologist. Then, operator applies various ablation treatments to eliminate the conduction feature of tissue in the targeted anatomical areas to treat rhythm disturbance. None of the current 3D electroanatomical mapping systems using known methods can display specialized conduction system of heart and its dynamic functions as a whole (functional and anatomical map of the entire conduction system simultaneously). By current methods, only local signals with catheter contact on certain anatomical points can be perceived and therapeutic ablations are applied if these signals are considered to be compatible with this anatomical structure. Although by current 3D systems, the conduction system cannot be mapped directly, signal points detected in appropriate areas of the usual anatomy can be marked with its coordinates on 3D mapping. This marking ability in complex arrhythmias enhances anatomical familiarity for electrophysiologists, and it also provides superiority to conventional electrophysiological measurements.

In the current 3D mapping, the electropotentials that occur in conductive system and muscle tissue do not have a separable feature, apart from time difference of stimulation. Therefore, the only way to distinguish conductive system from muscle tissue in traditional methods is to place the mapping catheter on conductive tissue and to try finding its confined exact location in which the signal formation is earlier than muscle tissue. But it is not practically possible to find conductive tissue and side branches one by one, and to contact all of them at the same time. Moreover by the approach, the entire conductive system cannot be mapped in 3D. If the device described in this invention, it would be able to distinguish these two tissues from each other by using differences of them, such as frequency band, excitation time, amplitude, activation direction and location information of the biological magnetic field signals originating from conductive system and muscle tissue.

In new mapping system, tissue contact for Hybrid signal collector catheter (Fig. 1) to collect the biological magnetic field signals inside heart is not necessary. Although the catheter does not touch the area of interest the system with sensors located on 3-axis can localize the biological magnetic field signals (these signals are generated by direct electrical current created by depolarization wave in conductive system) originated from the conductive system perceived at the same time from one or more points, using reverse problem-solving technique.

The initiator or driver of many cardiac arrhythmias are originated from the specialized cardiac conductive system. On a visual platform with 3D anatomical reality, a device that displays the specialized cardiac conductive system separating it from myocardial tissue, may help us to develop new treatment approaches, by overcoming limitations of available methods and, it may also offer curative methods in complex arrhythmias, such as atrial fibrillation, which is not understood at the moment precisely and therefore it cannot be cured completely.

In the new system, while electrophysiologist evaluates the conductive system, he/she will be able to directly observe the progression of activation wave on conductive system, instead of using indirect measurement and maneuvers. This observation can also be performed when arrhythmia begins, and it can be understood whether source of arrhythmia is within conductive system or myocardial tissue, or it would be able to determine if conductive tissue is a critical part of the arrhythmia. The new device will able to eliminate use of indirect stimulation or measurement methods in most of cases.

Non-fluoroscopic 3D electroanatomical mapping methods measure membrane potential differences on myocyte membranes in terms of volts. In these methods, and also in conventional electrophysiological methods, by which electropotentials can be measured on the inner surface of the myocardium (to epicardium occasionally by entering the pericardial space), instant-point mapping of conductive system is performed by contacting with electrophysiology catheters the region where the conductive system is estimated. In traditional 3D mapping, intended points can be positioned on a platform of 3D electropotential maps. These measured myopotentials are useful for predicting viability of cells when myocardium is in relaxed state (substrate mapping) and, in understanding main pathway of possible arrhythmia, by following the direction of the activation in muscles (activation mapping). However, in current 3D mapping methods, the activation map shows electrical spread at muscle level, not at the level of conductive system. For this reason, the activation pathway of arrhythmia can be seen as a wide myocardial area, not along a line. Therefore, the cardiac electrophysiologist must test these signals with conventional tissue contact and stimulation methods, by approaching to the related target area with mapping catheter. In a traditional 3D method, if a critical treatment target is identified, ablation of a large area, rather than a point for treatment, is necessary. Therefore, it is possible to damage normal conductive system with these large ablations, and it can also result in unnecessary ablati on or therapy fai I ure caused by not abl e to reach the origi nal source.

In some of conventional 3D systems, magnetic sensors are used (CA RTO, E nsite etc.). However, these sensors are not used to measure biological magnetic field signals; they are used to determine the coordinates of mapping or ablation catheters in the 3D environment. In addition, current techniques to measure the biological magnetic signals of heart have been tested with sensors placed outside the body until now. The most important problem of these systems is that they are away from the biological signal source, especially cardiac specialized conductive system. A second major disadvantage is that heart is a moving structure and these sensors are fixed outside the body and do not move with heart. This situation leads to a significant motion artifact and reduction of resolution in the map. In the new system presented here, Hybrid signal collector catheter that provides high- resolution magnetic field imaging, moves with the heart inside heart chambers and it can be positioned at points ranging from centimeter (cm) to millimeter (mm) in distance to the biological magnetic signal source. This significantly increases resolution of the map of the magnetic field signal.

The cardiac arrhythmias may develop in structurally normal-looking hearts or they may develop in sick hearts after remodeling, which occurs in the course of acquired coronary heart disease or valvular heart disease. Despite the cardiac arrhythmias ultimately affect heart muscle, main source of them is the specialized conductive system. By current methods, it is difficult to restrict the signal source to a precise point on conductive system. For this reason, ablation is frequently performed on large myocardial areas involved in arrhythmia.

Due to these limitations in the current practice, there is a need to add a detailed 3D map of the specialized conductive system on conventional 3D electroanatomical map, to know how the activation wave is dynamically transmitted on this specialized conductive system and then, to track the spread of action potential on the muscle tissue.

The creation of cardiac conductive pathway network map in 3D environment by pulsed biological magnetic field signals in heart (beginning from a point and spreading) and its integration with current 3D electroanatomical mapping, will allow electrophysiologist to apply the treatment on a detailed, actual cardiac anatomy in arrhythmia therapy.

In addition, the new system, which maps signals of biological magnetic fields inside the heart, has some advantages to overcome known limitations of conventional 3D systems. The first of these limitations in conventional method is that mapping catheter can only map inside heart chamber of interest, where catheter is located, because the current electroanatomical mapping requires electrode contact to the tissue. In the new method, absolute contact of Hybrid catheter for acquisition of magnetic field signals is not required. Therefore, Hybrid catheter can also capture and map the magnetic field activity in adjacent heart chamber without approaching it. In addition, in the new system, complex arrhythmias using multiple accessory pathways, arrhythmia sources are not localized by the conventional 3D method, arrhythmia caused by Purkinje fibers can also be treated without loss of time and need of a complex procedure.

The new mapping system will also improve the success rate of treatment in some arrhythmias that cannot be tolerated by the patient, because it will provide a faster 3D map than the conventional method and it will provide a more rapid approach to the source by revealing the source of the problem more accurately and clearly.

B RIE F DE SC RIPT ION OF T H E DRAWING S:

F ig. 1 : Hybrid signal collector catheter specifications (simultaneously senses the electropotential and magnetic field signals)

F 1-A: Hybrid catheter view from side perspective (in use configuration)

F 1 - B : T op vi ew of H ybri d catheter ( i n use conf igurati on)

F 1-C : Open Hybrid catheter with no configuration (pre- use of catheter)

F 1 - D : L ayers of the i nternal structure of H y bri d catheter shaft

F ig. 2: Algorithm for matching with the source of biological magnetic field signals detected at activation time intervals, that are defined by the heart's specific electroanatomic and magnetic signal reference points in the heart prior to mapping

F2-A, Surface E C G recordings: Lead DI and DII (12 leads are used in the system), P wave (atrial activity on the surface E CG), QRS complex (ventricular activation on the surface E CG), T wave (ventricular repolarization), PRI (PR interval)

F2-B, Intracardiac electropotential recordings: H RA (high right atrium), HIS prox-dist. (HIS bundle signals), CS (coronary sinus signals), RVA (right ventricular apex signals), H (HIS activity signals), V (ventricular electropotential), A (atrial electropotential), PA (PA interval), A H (AH interval), HV (HV interval)

F2-C, Algorithm for matching with the source of biological magnetic field signals detected at activation time intervals (AIs) defined by the heart's specific electroanatomic and magnetic signal reference points (R Ps) inside the heart prior to mapping and the forward and backward signal analyses (FSA and BSA) for system signal identification

F ig. 3: Methods for collecting and storing of position/location information of the sensor and biological magnetic field sources in defined time intervals of the heart cycle in mapping

DE SC RIPTION OF R E F E R E NC E S ON T H E DRAWINGS:

F ig. 1 :

1 : The proximal portion of Hybrid catheter (apparatus with mechanisms for maneuvering at the distal end)

2: The hybrid catheter body (main shaft) 3: The distal ring of Hybrid catheter (end portion that can be maneuvered from the proximal portion of the catheter)

4: The hybrid catheter connection point (the port for data transferring of the distal catheter sensors to the system and for signal sending from the system to the transmitter at distal portion of the catheter for coordinate information production)

5: Distal end connecting cable of mechanism for adjusting the diameter of the distal ring of Hybrid catheter

6: The connection line for data exchange with the system of the sensors and signal transmitters located at distal of Hybrid catheter

7: Distal end connecting cable of the mechanism for bending motion (flexion-deflection) of distal part of Hybrid catheter

8: The layer supporting the main shaft of Hybrid catheter and isolating the inner environment from external signals

M 1-3: Built-in magnetometer sensors in the hybrid catheter (M1, at the tip/distal of the catheter; M2, in the body of the catheter ring portion and M3, in the shaft of the catheter). These sensors are placed in 3 dimensional environments at perpendicular coordinates to each other on the catheter.

H 1-20: E lectrode poles placed in the distal ring of Hybrid catheter for electropotential measurement (each pair of electrodes measures voltage of the contact area between them)

F ig. 2:

SA: Sinoatrial node

AV : Atrioventricular node

H IS: His bundle region

J R : J unctional region

PJ : Purkinje activity

BA: Basal signal activity

AC S: Atrial conductive system activity

C SA : C onductive system activity

Reference points (R P 1-6):

R P - 1 ) T he end poi nt of T wave on the pati ent's surface E C G

R P-2) The first magnetic field signal detected by the system on basal activity in the atrium (it originates from the beginning of SA node activity)

R P-3) T he begi nni ng of the P wave on the surface E C G or starti ng poi nt of the A wave on the catheter settled in the H RA inside the heart (it is caused by the depolarization of the atrium muscle). R P-4) Intracardiac HIS activation beginning point (it is marked when the hybrid catheter is located on the HIS bundle).

R P-5) This point is the beginning of the earliest QRS complex on the surface ECG or the earliest V wave in intracardiac recordings (it is caused by ventricular depolarization)

R P-6) This point is determined by the earliest T wave beginning on the superficial E CG (It originates from ventricular repolarization).

FSA: Forward signal analysis

BSA : Backward signal analysis

Activation Intervals (AI 1-12): When the patient is in the sinus rhythm, these time intervals are defined for the system according to the reference points (RP 1-6) before the mapping (at these time intervals, the system identifies all magnetic field signals by the forward and backward signal analyzes and, it matches them with their sources).

A 1-1) This interval includes a sampling interval of 20 milliseconds (ms) after the end of T wave indicating the end of the previous beat. It is the defined time interval after the point marked as R P-1 in the system (it provides a sampling time of up to 2% of the cardiac cycle). Since there is no any mappable activation (depolarization) in this interval on heart ^' s conductive system, the system determines the baseline signal (BA) activity here. FSA-1 analysis is carried through this time interval. The system uses all signal activity detected here to exclude from the map in the filtering process.

AI-2) In this time interval, only sinoatrial node activity (SA) is present. The evaluation of this interval is performed by signal scanning in two directions (forward and backward direction). First 5 ms (0.5% of the cycle) after R P-2, which is analyzed by FSA-2, is used to detect the magnetic field signal generated by the SA. In this interval, the system also performs a second control scanning. The system performs backward analysis from R P-3 to RP-1 by BSA-1 analysis. In this signal scanning, the first detected magnetic wave belongs to the atrial conductive system (AC S) and the second detected wave belongs to the SA node activity.

AI-3) This time interval includes the interval from the RP-3 to the SA activity during backward scan of signals. The system performs BSA -2 within this interval. In this interval prior to RP-3, the SA and the conductive system activities may overlap. For this reason, sequences of these signals are important to assign them to the system. The system by BSA-2 identifies signal of the conductive tissue within 10 ms prior to RP-3 and in the time interval immediately before it also defines the SA activity.

A I -4) This time interval is the scan of 40 ms after RP-3. The system performs FSA-3 at this interval. Herein, the atrial muscle tissue (A) and atrial conductive system (AC S) are actived simultaneously. The system basically separates the ACS signals from the atrial muscle tissue signals with frequency difference.

AI-5) This time interval includes 20 ms before the AV node activity. This time interval is also analyzed by 2- directional signal analysis. These are FSA-3 and BSA-3. First, in this time interval, forward FSA-3 is performed from RP-3 to RP-4. R P-4 is HIS activation. The first new magnetic field frequency after the AI-4 corresponds to the AV activity. This point (the beginning of the AV node activation) determines the end of the AI-5. In BSA-3 control analysis, during backward signal scan from RP-4 to RP-3 within 100 ms prior to HIS activity, the first different frequency belongs to AV node (the hybrid catheter is located on the HIS). Scanning of the 20 ms prior to the AV node activity sequence will give the time interval of A 1-5.

AI-6) This time interval includes the AV node activity. It covers a time interval of about 75 ms. This interval is also confirmed by a two-directional signal scan. In this interval, FSA-3 and BSA-3 signal analyses are performed. This interval is defined as the time of 75 ms after the end of AI-5 during the FSA-3 scan. During this scan, first organized frequency group belongs to the AV node. In the backward control analysis (BSA-3) during scan of the time interval of 100 ms prior to RP-4, first detected signal originates from the junctional region activity (J R, fast and/or slow AV pathway conduction, and if it exists, isolated junctional activity occurs here). Before this signal group, second detected organized signal group belongs to the A V node activity.

AI-7) This time interval is the conductive tissue activity from the RP-4 up to the time of the AV node activity during backward signal scanning. It probably can reflect slow and fast AV pathways and the junctional activity. This time interval is defined by analyzing with FSA-3 and BSA-3.

A I -8) This time interval is evaluated in two-di recti on with signal analysis of FSA-4 and BSA- 4. It includes the time period of 50 ms (5% of the heart cycle) after RP-4 during forward scan (FSA-4) from RP-4 to RP-5. It includes the magnetic field activity up to the Purkinje activity (PJ ) during the FSA-4 analysis. In this interval, the infra-HIS conductive system is activated (the right and left bundle branch and their branches). In addition, the ongoing depolarization of the left atrium muscle can be detected in this interval. The backward scan analysis (BSA-4) is performed from RP-5 to RP-4. The time interval from the end of Purkinje activity until the beginning of HIS activity is analyzed. The infra-HIS conduction system map is created with biological magnetic signals in this time interval.

AI-9) RP-5 is the earliest beginning point of the QRS complex on the patient's 12 lead surface E CG and the earliest V wave on intracardiac recordings. The time interval of 20 ms before RP-5 defines this interval. BSA-5 is performed in this interval and the system primarily defines PJ activity here.

AI-10) This time interval is the scan of 100 ms after RP-5 (10% of the heart cycle). The signal scanning is performed by FSA-5. In this analysis, the PJ activity in the conduction system and the signals of the ventricular muscle depolarization are recorded. Afterwards, using the signal frequency band difference between the muscle and the electrical conduction system in heart, only signals in frequency band of conducting system are used in mapping.

AI-11) By scanning 50 ms back from R P-6, especially epicardial ventricular muscle tissue signal activity is obtained. This time interval is analyzed by BSA-6 and it has only ventricular muscle signal activity. Therefore, ventricular signal activity frequency obtained from this time interval is used to separate PJ conduction from ventricular muscle.

AI-12) This interval is a scan of 100 ms after RP-6. It is analyzed by F SA-6. It primarily reflects the magnetic field signals generated during ventricular repolarization. Signals in this time interval are not stored for use in the conduction system mapping. If desired, it can also be evaluated separately for evaluation of the repolarization. F ig. 3: Appropriate storage of collected data at time intervals according to the position of the hybrid catheter (sensor) and biological magnetic field signal source during mapping:

F3-A, C ollection of the dynamic biological magnetic field signal data while the magnetometer sensors are at a fixed position inside the heart:

The device records the instantaneous data, which is measured for every thousandths of cardiac cycle (for example, for every 1 ms in a heart cycle of 1000 ms), into separately defined timeslots throughout heart cycle focusing on activation wave magnetic signal frequency. Here, signals are recorded when hybrid catheter is at a fixed point. The information about instant location of the conduction system depolarization wave signal, whose frequency is defined by the system before mapping, is separately calculated for the 3 magnetosensors in hybrid catheter using the reverse problem solving technique for each timeslot. At each new heartbeat (during new heart cycle), system creates a new 3D conduction system map when the sensor is located at the same point. The arithmetic mean points of the conduction system pathway coordinates which are determined for every timeslot in each heartbeat are positioned by their time and 3D coordinate information on the conduction system network.

F3-B, C ollection and storing of the same timeslot data of the heart cycle, when sensor is located at different points inside the mapped heart chamber:

In this case, the device collects a location information for same timeslot of heart cycle while hybrid catheter is in different positions and compares this information with location data obtained from different sensors. Thus, signal location data defined for a specific timeslot in each heart cycle is verified for different sensor locations (F3-B).

At a specific time during each new heart cycle (for example 140th ms), signals collected by the sensor are re-analyzed by the system for different distances of the sensor to the signal source. Thus, after a few heartbeats, the activation wave can be localized more precisely on the conduction system pathways in 140th ms. In this way, at a given timeslot, it is demonstrated whether a magnetic field signal reaches to the sensors from a single source or from multiple conduction pathways simultaneously. If magnetic field signals simultaneously reach to sensors from more than one point through the network of conduction pathways, the system records multiple signal source information for that timeslot. This data is checked again for each new heartbeat and sensor position. Thus, the instant location data of signal source is refined by subtracting unlikely computed signal locations and the resolution of the 3D conduction system map is improved.

F3-1, The device defines the timeslots in thousandths of the cycle along a heart cycle (for example, a timeslot includes 1 ms in a heart cycle of 1000 ms). Here, when hybrid catheter is at a fixed or in different positions, the collected magnetic signal locations are re-recorded in each heartbeat for a defi ned ti mesl ot ( i nto same ti mesl ot for every heart beat) .

F3-2, When the sensor is moved to different coordinates inside the heart chamber, system records the arithmetic mean of magnetic field signal location data received over a defined timeslot in each cardiac cycle (for example 140th ms).

F3-3, When the sensor is located at a given coordinate, system records the activation wave magnetic field signals with their coordinates for all of the defined timeslot in the heart cycle (such as 10th, 30th, 50th or 140th ms) separately. This location data is calculated for each new heart cycle and stored in a defined timeslot with the arithmetic average. F3-4, The network of conduction system is entirely visualized with signals of biological magnetic fields, calculated by the coordinates of signals originating simultaneously from one or more conduction pathway. At consecutive timeslots of heart cycle, signal locations are combined on a 3D position data plot. In this way, system creates a 3D signal location data plot against timeslots. By this graph, functional and anatomical map of the specialized cardiac conductive tissue is created in a 3D environment in accordance with actual anatomy. The electrophysiologist can perform therapeutic applications on this 3D visual structure. After the ablation therapy, when re-mapping is performed again, inability to map the conductive tissue in the intended area indicates that conduction has been successfully eliminated.

DE TAIL E D DE SC RIPT ION OF T H E INV E NT ION:

The heart has a network of electrical conduction system similar to nerve cells. On specialized conductive tissue, changes on the cellular membrane potential produce pulsed electrical direct currents (DC). These currents then spread to the myocardial cells. E lectrical direct current in these tissues leads to the formation of magnetic fields in conductive tissue cells and muscle cells. The magnetic fields created by cardiac muscle cells and specialized conduction system can be dissociated from each other in several ways. The differences in these two tissues help us to distinguish their signals.

By the new imaging system described here, to use in the diagnosis and treatment of cardiac rhythm disorders, biological magnetic field signal data are collected from the inner surface of heart and integrated with 3D conventional electropotential data. Subsequently, an anatomical and functional visual map of the conduction system in 3D environment is created after data processing by computer.

The new system has the capability of a hybrid working with state-of-art electroanatomical mapping systems. The device includes a special hybrid catheter that collects the electropotentials and endocardial biological magnetic field signals from the inner surface of heart. In addition, connection cables that transmit these signals to the computer system and hybrid surface equipment with magnetic and electropotential sensors, which receives the coordinate information of magnetic sensors on hybrid catheter and transmits it to the mapping system are also required. An analyzer that includes software that operates algorithms for identifying the frequency (wavelength), amplitude, location and phase (stimulation sequence) of magnetic field waves on specialized conductive tissue and muscle tissue and executes methods for separating of these signals from each other and also uses the signal collecting and data storage algorithms to create the 3D map of the conduction system. A computer where the 3D map will be created; a monitor that reflects the generated 3D map; and a hardware required for the system in which all equipment works together are also required in new system.

The new 3D mapping system/device that maps endocardial biological magnetic field signals will able to work as a hybrid with current 3D electroanatomical systems. The features of the new mappi ng system are as f ol I ows:

I Hybrid signal collector catheter: A special catheter that simultaneously measures the heart's biological magnetic field signals and electropotential data from the inside of heart and it also sends them to the system along with location information of the sensor. Signal acquisition and analysis of signal sources, and introduction to mapping system: Software that calculates time intervals defined in heart cycle according to certain electroanatomic and biological magnetic field signal references and it analyzes the sources of the signals at these intervals, it also processes and classifies the signals along this way.

M ethods for signal processing and the reverse problem solving: Positioning the signal source on the mathematical model of conduction system

Signal analysis: Software that processes and classifies (separation of the signals) the endocardial biological magnetic field signals collected from specialized conductive tissue and muscle tissue, using their time, frequency and amplitude values

Data storage: The software that stores the collected biological magnetic field signals to defined timeslots in heart cycle and to defined location in 3D model, and performs the comparison of data collected with different methods for the same time and location.

Integration of electropotential and magnetic field signal 3D map

H ardware: The device that has the capability of a hybrid working with state-of-art electroanatomical mapping systems, includes a special hybrid catheter that simultaneously collects electropotentials and endocardial biological magnetic field signals from inner surface of heart; the connection cables that transmit collected signals to the computer system; the hybrid surface equipment with magnetic and electropotential sensors which receives the coordinate information of magnetic sensors on the hybrid catheter and transmits it to the mapping system; the analyzer that includes software that operates the algorithms for identifying the frequency (wavelength), amplitude, location and phase (stimulation sequence) of the magnetic field waves on the specialized conductive tissue and muscle tissue and the methods for separating of these signals from each other and also use the signal collecting and data storage algorithms to create the 3D map of the conduction system and; the computer where the 3D map will be created and monitor that reflects the generated 3D map and the hardware required for the system in which al I equi pment works together.

1) Hybrid signal collector catheter:

The hybrid catheter can simultaneously collect the heart's biological magnetic field signals and electropotential data from inside the heart (Fig. 1). The catheter sends these signals to the system along with the location information of the sensor.

Its appearance is similar to a classical ring cardiac electrophysiology catheter. The apparatus (1), located at proximal of the hybrid catheter, allows the electrophysiologist to move the distal tip of the catheter, which reaches into the heart through the vessel from outside the patient (rotation, flexion and change of the diameter of the distal ring, catheter back and forth movement).

The hybrid catheter trunk (shaft) length (2) is enough to be extended it into the heart from the inguinal region (femoral vein and artery) of patient. The catheter has data cables (6) to provide connectivity to the mapping system, and contains a special layer (8) that supports the catheter shaft and isolates the internal environment from external signals. In the catheter, there are mechanical wires to reduce the diameter of the distal ring of the catheter (5) and to provide the bending movement (7).

The distal portion of the hybrid catheter (3) is in ring configuration during mapping. The catheter contains three chip size (mm size) atomic magnetometers (M1 -3) that receive biological magnetic field signals. These sensors are designed to detect ultra-low, direct current magnetic fields and they are capable of operating in both room and body heat. They provide high resolution magnetic field imaging. These sensors are positioned on the hybrid catheter at x, y, and z coordinates, on perpendicular angles to each other in the 3D environment. On the outer surface of this catheter there are 20 electrodes (pole) (H1-20) with equal spacing to receive electropotential signals (conventional electrodes).

There is also a signal transmitter in hybrid catheter that generates ultra- low magnetic field signal with a specific frequency (a special signal band is used other than the biological magnetic signal frequency), which dynamically provides the 3D coordinates of the catheter and magnetometers to the external mapping system. These artificial signals are continuously detected with external magnetic surface sensors. The magnetic field sensitivity of the sensor for the detection of biological magnetic field signals is compatible with magnetic fields between the pico-Tesla and micro-Tesla. The detected signal frequency is at the kHz level. These sensors are sensitive and specific for the collection of time (phase) and frequency domain and amplitude data of the measured signal, when hybrid catheter is positioned in blood circulation within heart chambers.

2) T he methods for detecting the frequency (wavelength), amplitude, location and phase (stimulation sequence) of the magnetic field signals on specialized cardiac conductive tissue and muscle tissue; and algorithms for separating signals from each other:

The hybrid catheter simultaneously transmits electropotential and magnetic field signals to the mapping system. In this way, the map of the magnetic field based conduction system network is simultaneously created together with conventional electropotential 3D map.

Before the system starts mapping, reference electroanatomic and magnetic field points (RP 1-6) are marked by hybrid; and activation time intervals (A I 1-12) in heart cycle are determined according to these references. The system performs forward and backward signal analysis at intervals of heart cycle to determine the source of collected signals (Fig. 2). In this way, the device identifies entire magnetic field signals from the conduction system. These identifications can be reconfirmed at each cardiac cycle, as defined in algorithms with electropotential and magnetic field waves that are provided simultaneously by hybrid catheter. The electrophysiologist scans multiple heart cycles for signal collection from different points with hybrid catheter before mapping; and ensures that matchings of the magnetic field signal with their electropotentials are more reliable. After describing biological magnetic field signal frequencies and their location information to the new mapping device, 3D mapping of conduction system is initiated.

2.1) Stages for applying algorithms used by new mapping system for mapping of the conduction system:

First, heart rate and cycle length in ms are determined by the device. Then heart cycle is divided into equal timeslots thousandths of the cardiac cycle; for example, heart cycle in a person with a heart rate of 60 beats per minute takes 1000 ms, and in this way, every equal time interval includes 1 ms in a heart cycle of 1000 ms). Even if heart cycle length and signal formation time change with heart rate, the defined timeslot of signals will be approximately same or equal to the previous beat. During data storage by this method, previous cardiac cycle data matches the next one correctly.

Activation intervals (A 1 1-12) that are defined according to the reference points (RP 1- 6) shown in Fig. 2, are scanned by the device for magnetic field signals. Then, before mapping, system matches all signals in a cardiac cycle to the source, using defined reference points (magnetic field signal associated with electrical direct current that occurs during depolarization). For these matchings, analyzes of FSA 1-6 and BSA 1-6 are used. Mapped signals are always recorded in the same timeslot of cardiac cycles. Mapped data is compared with the data in same timeslot in the previous cycle, and the arithmetic average is stored in that timeslot.

First, hybrid catheter is in the H RA region. System scans A 1-1. In this time interval, there is stable basal activity of heart. Signals detected here are defined as basal activity and they are used for filtering frequency band of activation. Then AI-2 is scanned. Magnetic fields in this interval are verified by performing a 2-direction signal scan. Activation wave signals and their locations, originating from the SA node are defined. By A 1-3 and 4 scan, atrial specialized conductive tissue (ACS) is separated from atrial muscle signals (A).

The electrical conduction slows down further at the AV node. The transmission of this region is approximately 0.02-0.05 mm/ms. The hybrid catheter is on HIS region. System performs signal scans of AI-5, AI-6 and AI-7 time intervals in turn. With these scans, AV node, HIS bundle and junctional region are scanned and analyzed for biological magnetic signals.

Hybrid catheter is moved through the right ventricle (RV) and finally placed in the right ventricular apex. Meanwhile, 5 activation time interval scans from AI-8 to AI-12 are completed. With these scans, infra-HIS region, right and left bundle branch and Purkinje system are mapped. Because these scans are performed from right heart chambers, Purkinje fibers from right ventricle and right bundle branch will be mapped better than that of the left ventricular side. If a better map of conduction system on left heart chambers is desired, those chambers can also be entered separately; and signals can be perceived more closely.

Mapping of the specialized connective tissue is carried out by following the signal of activation wave, which is flowing on it (Identification of frequencies for the conduction system are determined by specific signal frequency band that occurs during depolarization). For this reason, the system determines activation intervals of the heart cycle according to reference points and follows only the specific activation wave frequency for conductive tissue at these time intervals. The system searches, collects, and localizes the magnetic field signals of the instantaneous depolarization wave on conduction system. Repolarization and resting phases of heart are not used for the cardiac specialized conductive tissue mapping. These time intervals can be used if desired for substrate mapping of muscle tissue (tissue viability).

2.2) Mapping of the conduction system after identification of heart's biological magnetic field signal frequencies:

The system scans the heart cycle for electropotential and magnetic field waves according to the algorithm in Fig. 2, when sinus rhythm is present. The identification process of signal differences is performed to be used during tachycardia by the system. At this stage, basal artifact signals (BA), muscle and other tissue signals aside from specialized conductive tissue are determined; and they are used to filter during the tachycardia mapping. Signals originating from muscle tissue are not used for the activation map of conductive tissue. At defined time intervals, t signals, especially when the conduction system is active, PR interval for atrium (PRI, PR interval, the system maps the conduction system from the atrium to the Purkinje system), and pre-systolic interval (20 ms before the Q wave on surface E CG, and before V wave on intracardiac measurements) for ventricles, are recorded while hybrid catheter is moved through the mapped heart chamber. This signal screening allows mapping of both atrial pathways and the HIS-Purkinje system. The conduction system map can be generated even for each heart cycle. When hybrid catheter is brought closer to the intended field, the conduction system map will be clearer, especially by signal coordinate combining process, which coordinates obtained for each heartbeat are averaged with the previous one. Coordinates of traditional 3D electroanatomical map are equalized to the actual CS anatomy by overlapping of the CS catheter; and the magnetic field map by the HIS electroanatomical reference point. These two maps are then superimposed on top of each other in 3D environment.

After activation intervals (AI 1-12) and sources of magnetic field signals are identified, the system uses specific frequency of magnetic field sources as a marker/indicator for these structures (SA, AV, HIS, conduction pathways, Purkinje tissue). To assess atrial structures and AV conduction, the signal scanning is performed at time intervals from AI-2 to A 1-8, and for ventricular assessment at A 1-9 and 10. Other AIs are used to filter the magnetic fields originating from outside the conduction system during the map, and their analysis is not required in every cardiac cycle. The hybrid catheter is firstly moved through the right atrium and then in the right ventricle and, if necessary, in the left ventricle. Left atrium can be mapped from inside the right atrium. If ablation is to be performed within the left atrium, interatrial septum is appropriately passed and left atrium can be mapped in more detail. The system reconstructs the conduction system 3D map in each new heartbeat and in each different position of Hybrid catheter; and so that, the signal location information is compared with that of same timeslots in previous cycles. As a result of these comparisons, the precise course of conduction system pathways in 3D environment is formed. The conduction system shape is plotted with graph of the activation wave signal coordinate, against the timeslot of heart cycle in 3D environment.

2.3) M apping of the conduction system during the tachycardia

After the new mapping device identifies frequency and location information of the patient's conductive tissue magnetic field signals, tachycardia is induced to be initiated by traditional methods. Since the stimulation sequence of the heart will change during tachycardia, the signal scanning cannot be performed in AIs defined according to RPs. The device no longer accepts as new cardiac cycle within the time between RR waves; and scans all signals, in new defined timeslots (thousandths of RR) without time interval for tachycardia mapping. Previously, location information, depolarization wave frequency and amplitude values that were defined as signals for the conductive tissue, are searched between new scanned signals during tachycardia (these signals are determined by the magnetic field signal frequency generated during phase 0 of the cardiac action potential). Signals of the conductive tissue are selected and others are eliminated. The new course of the depolarization wave transmitted on the atrium and ventricular specialized conduction pathways is mapped in 3D, during tachycardia. If there is a signal that cannot be recognized by the system during tachycardia, the electrophysiologist can manually assign this signal to the system by comparing it with the electropotential sequence.

During tachycardia, it can be observed on which regions, the activation wave is transmitted through the muscular tissue; and on which points only through the communication tissue. If desired, the new system can only scan the frequency of conductive tissue and can only extract the 3D map of the conduction system propagation pattern. This mapping style may provide information of the conduction system has an active role in the development of tachycardia or not. If the conduction system is actively involved in tachycardia, it provides information about critical point will be effective in the ablation treatment or not.

While sinoatrial node (SA), atriums, AV node, HIS and right-left bundle branches are well mapped; the map resolution reduces at the distal end points (Purkinje fibers), where the conduction system is tapered and distributed into the ventricles. If the pathology is detected in these distal areas, the hybrid mapping catheter is brought closer to the relevant area and the pathologic focus is better localized.

In the new system, the device determines where the activation wave is instantly on the conduction system in each timeslot along the cardiac cycle. In traditional 3D methods, since the activation wave is recorded when it is on muscle tissue, the activation line can be mapped as a region rather than as a point of the line. The reason is that electrical transmission spreads over wide regions on muscle tissue, while it spreads on a line over the conduction system. In traditional 3D mapping, the mapping catheter is contacted with muscle tissue in the mapped heart chamber. This means that the resolution of the map will increase in a manner directly proportional to the number of contacts. With the new method, direct contact is not necessary as magnetic field signals are mapped. The entire conductive tissue map can be extracted without catheter contact from a single position, but in order to elaborate the map of the intended region, it will be necessary to collect data from points closer to that area. However, it is unlikely to reveal completely the conductive tissue pathways on the basis of traditional 3D electropotential measurement.

3) Information collection and data storage algorithms for formation of 3D visual platform of conductive tissue pathways:

During mapping, the signal location information is collected and stored at appropriate timeslots, according to changing dynamic positions of sensor and biological magnetic field sources (Fig. 3).

3.1) Data collection when the sensor is positioned at a fixed point, inside the heart chambers:

When the patient's heart rhythm is sinus, the activation wave spreads from SA node to AV node and then to HIS-Purkinje system via the specialized conductive tissue pathways (F3- A). During this transmission, the device records by focusing on the specific frequency of activation wave in defined timeslots of heart cycle. Here, when Hybrid catheter is at a fixed point, signals are recorded separately for each timeslot. The activation wave acts at a rate of about 1-4 mm/ms, with different properties on atrial and ventricular segments of the conduction system. The location of magnetic field source with specific frequency of conductive tissue in each timeslot is calculated for the 3 magnetosensors on the hybrid catheter, with reverse problem solving technique. During each new heart cycle, the system creates a new map, and after a given repetition, arithmetic mean points of determined signal coordinates are located on a conduction system network. 3.2) T he data collection for the same timeslot of the heart cycle while the sensor is positioned at different points inside the heart chamber:

In this case, the device collects signal location information for the same timeslot at different positions of hybrid catheter; and compares this information with data obtained from sensors that are simultaneously present at different positions. Thus, the instantaneous signal location data defined for a given timeslot in each heart cycle is verified (F3-B).

For example, the signals that are received for 140th ms are recalculated in each new heart cycle, while the sensor is located at different distances to the signal source. Thus after a few heartbeats, at 140th ms, the activation wave can be localized more precisely where it is on the conduction system for a moment. Thus, at a given timeslot it is revealed whether the magnetic field signals reach to the sensor from a single source or multiple pathways of the conduction system.

The activation wave (depolarization) location information on the conductive tissue will be on a specific point or transmission line (pathway) rather than a broad area, unlike the activation wave of the muscle tissue. While the activation wave on the conductive tissue moves to a certain direction and on the pathway; it spreads over an area on muscle tissue. For this reason, instead of activation map with sharply defined distinct lines, the areas of muscle tissue presenting with broad activation sites on the current 3D mapping can be visualized. By the new mapping method presented here, this deficiency is also eliminated.

4) M ethods for integrating the data of the conduction system with the electropotential mapping by computer software:

The system firstly measures between two R -waves (V-wave on the intracardiac records, the R-wave of the QRS on the surface E CG) in ms and determines the cardiac cycle. This time is divided by 1000 (0.1 % of cycle). The cardiac cycle in a person with a heart rate of 60 beats per minute takes 1000 ms; and every equal timeslot includes 1 ms in a heart cycle of 1000 ms. The system begins the signal scanning at the RP-1 point of heart cycle and ends it at the same point of the next cycle. The electrophysiologist marks some critical reference points (magnetic signals and electropotentials) on this raw hybrid data scan for the system (P, A wave, PA interval, A H and HV interval, QRS and V waves, and T wave, RPs). Fig. 2 shows which regions of the heart are electrically activated; and which regions are at rest in these time intervals (A I 1-12). E lectropotential and magnetic field data are recorded simultaneously. The system analyzes the time intervals on the algorithm (Fig. 2) and the magnetic fields of each active structure are identified separately.

For each defined timeslot in the heart cycle, depolarized, repolarized and deactivated intervals are determined. After this scan, the specific frequency of activation (depolarization) wave for the conduction system is determined. The frequencies of other tissues are also defined for the filtering process. Magnetic field frequencies, activation amplitudes and anatomical location information of SA node, intra/interatrial conduction system (ACS), AV node, HIS-Purkinje system are saved by the system. This pre-mapping information is then used in the real scanning and mapping.

The location of conduction system components and their magnetic fields and frequencies are constant. For this reason, since all parameters of the conduction system except the direction of activation wave (it can be in two directions, antegrade and retrograde) would remain same during the tachycardia, the system recreates the 3D map of conduction system with a different activation wave direction, using the same information previously obtained by the conductive tissue in the sinus rhythm. In order to be able to do the mapping right the electroanatomical map that are used in the conventional 3D mapping method is required to combine with the new biological magnetic field map. In overlapping of the coordinates on two maps, the coordinates of actual HIS and CS electroanatomical references need to be matched on both maps.

By using a mathematical model template defined for conduction system pathways, the new system generates high resolution 3D map of the conduction system during both sinus rhythm and tachycardia, by processing of position data of the Hybrid mapping catheter and signals obtained from the conduction system in defined timeslots of heart cycle. The difference in two maps created during sinus rhythm and tachycardia is not the actual anatomical structure of conduction system, it is the information about the beginning point of activation wave spreads to other points on this network. The new generated 3D map is positioned on the electroanatomical map that is obtained by the conventional 3D method; and it is determined if the conduction system is the main arrhythmia source or it has a critical anatomical point for arrhythmia. In this way, only one- point ablation for arrhythmia treatment may be sufficient rather than an area.

5) M ethods for signal processing and reverse problem solving

After all signal-source matchings are finished, points where the conduction system is active are placed on the 3D coordinate system for all timeslot of cardiac cycle. The system uses reverse problem solving technique to detect the source of biological magnetic field. The system simultaneously records all of magnetic field signals incoming from 3 magnetosensors located on the coordinates of Hybrid catheter. Magnetosensors ^" 3D positions are continuously monitored by the mapping system. All selected signals are analyzed by computer with reverse problem solving method and they are localized to one or more 3D points.

Separation of conductive tissue magnetic field signals from muscle tissue signals can be provided with difference in time domain, strength of magnetic field and frequency domain of them. Using these differences, the system places signals on the 3D model, calculating the source-sensor distance.

The activation wave of conduction system is transmitted on specialized conductive tissue pathways, from the SA node until Purkinje fibers. In this transition course, the signal source travels sometimes on one line at a single point, and sometimes simultaneously on more than one anatomical point on the network of conductive structures. In order to localize the magnetic field waves originating from multiple sources, the new mapping system re-analyzes the data received from multiple sensors at the same timeslot with varying sensor distances and multiple source information. When the mapping system evaluates the magnetic field signal detected by the sensor, it selects the specific frequency band of conduction system, defined prior to the tachycardia mapping (in pre- mapping evaluation). Then the system compares data collected for each timeslot of heart cycle. For example, when hybrid catheter is in a stable position at 140th ms of cardiac cycle, location of signal source obtained with reverse problem solving is compared with the location data that is calculated while the hybrid catheter is at different positions in the same chamber. If there is a deviation in the calculated signal source location information, with more than acceptable error, new mapping system determines that detected signals by different sensors in the same frequency band and the same timeslot are originated from locations more than one point on the conduction system. The system recalculates source distances by changing the number and location of the source variables in the reverse problem solving technique. The number of active magnetic field signal source and location information that can be verified for all sensor locations are marked on the 3D map as signal source points where the conduction system is active at 140th ms (3D location graph against time). The hybrid catheter is moved to different locations at each heartbeat and calculated coordinates for the map are clarified.

Tachycardia is induced after anatomical mapping of the conduction system is completed. During tachycardia, all signals are re- scanned by Hybrid catheter during a heart cycle. The activation pattern of the conduction system is reconstructed during tachycardia. This pattern is placed on the conventional 3D electroanatomic map. Critical points/pathways of the conduction system that involve the tachycardia are shown on this map. If a point on the conduction system is an active part of the tachycardia main pathway or the initiator of the tachycardia, the determined point is ablated.

6) T he addition of the generated mathematical model of conduction system on the traditional mathematical model of heart:

Traditional 3D mapping, in terms of providing a platform presenting the 3D coordinate of the mapped cardiac surface on which diagnostic marking can also be performed, offers additional benefits with increasing operation success. However, both conventional electrophysiology and current traditional 3D electroanatomical mapping can only provide us information about a point of the conduction system. They cannot provide an integrated view of the entire conduction system at the same time and the visualization of the activation wave over it. For this reason, there is a need to place a conductive tissue map on traditional muscle tissue mapping in 3D environment.

Many mathematical models for the actual anatomy of the heart are designed. In traditional 3D mapping, electropotentials are positioned on the map based on this model. The distance information and the change intervals in the calculations are based on this modeling. However, these models are designed to place the electropotents of muscle tissue on the map.

The specialized conductive tissue pathways, unlike the muscles in the heart, are located on a narrow line. For this reason, the actual anatomical patterns of conduction system pathways in all of cardiac chambers and the possible changes of distance must be determined. Because, reverse problem solving method basically uses this anatomical modeling in the detection of magnetic field sources. Using this model, the system places the signals detected at different points on the conduction system on the 3D map with high accuracy. In this model, the coordinates at which all possible signals can be located for each position of the magnetometers inside the heart are predetermined. If the conductive tissue map reveals a new path other than the predicted conduction system pathways, it is referred to as " the accessory path".

Unlike the traditional mapping method, the new mapping method can simultaneously detect magnetic field signals beyond the heart chamber in which the mapping catheter is located. The catheter can detect the signals at good quality from other heart chambers where magnetic field signals can reach the sensor simultaneously. The map of the heart chamber in which the sensor is located will have a higher resolution than other chambers, but this additional feature will guide the electrophysiology to direct the source of the arrhythmia.

7) Software:

The computer software includes the methods to operate the algorithms that are necessary to distinguish the magnetic field signals from each other and from other signals inside and outside of the heart. It also contains the order in which the data will be identified and the interpretation will be performed. The mapping system uses the data obtained by taking a record for each timeslot during the mapping (by millisecond-level recording rate). In pre-mapping evaluation before tachycardia mapping by the new mapping system, the electropotentials of the heart's conductive tissues (SA, HIS) are matched to their magnetic field signals. The device then completes the missing fields of the conduction system in each new heartbeat, in accordance with the algorithms defined for it (AV node, intraatrial conductive tissues, right and left bundle branches and Purkinje system). Then the magnetic fields generated by each point of the conduction system and their location information inside the heart are used again by the system when the arrhythmia is induced. Thus, the involvement of the conductive tissue and muscle tissue for the formation of arrhythmia is determined, and the critical points for arrhythmia treatment are presented on 3D map. The software uses a partial artificial intelligence algorithm for comparison of the data and establishment of locations, and to el i mi nate the i mpossi bl e I ocati on opti ons.

8) H ardware:

In the new device, a special Hybrid signal collection catheter is used instead of the mapping catheter used in the conventional 3D mapping method for signal acquisition. Ablation treatment can be achieved with conventional ablation catheters that can be identified in the new system.

The device that has the capability of a hybrid working with state-of-the-art electroanatomical mapping systems, includes a special hybrid catheter that simultaneously collect the electropotentials and endocardial biological magnetic field signals from the inner surface of the heart; the connection cables that transmit the collected signals to the computer system; the hybrid surface equipment with magnetic and electropotential sensors which receives the coordinate information of magnetic sensors on Hybrid catheter from outside of the patient and transmits it to the mapping system; the analyzer that includes software that operates the algorithms for identifying the frequency (wavelength), amplitude, location and phase (stimulation sequence) of the magnetic field waves on the specialized conductive tissue and muscle tissue and the methods for separating of these signals from each other and also use the signal collecting and data storage algorithms to create the 3D map of the conduction system and; the computer where the 3D map will be created and monitor that reflects the generated 3D map and the hardware required for the system in which all equipment works together.

The analyzer on which the data is processed and analyzed, and the computer on which the 3D map is created are the main elements of the device. A more memory space and faster processor support in computer is required for the analysis of the acquired data, since a faster and more frequent scan is performed in mapping the conduction system according to the conventional 3D method.

Industrial implementation of the invention:

A new device will be developed to increase the success rates of diagnosis and treatment of cardiac rhythm disorders.