Patent Publication Number: US-2021177504-A1

Title: Tissue proximity indication based on a subset of electrodes

Description:
FIELD OF INVENTION 
     The present invention relates to systems, apparatuses, and methods for improving medical procedures and mapping. 
     BACKGROUND 
     Medical conditions such as cardiac arrhythmia (e.g., atrial fibrillation (AF)) are often diagnosed and treated via intra-body procedures. For example, electrical pulmonary vein isolation (PVI) from the left atrial (LA) body is performed using ablation for treating AF. PVI, and many other minimally invasive catheterizations, cause damage to targeted organ tissue to prevent electrical activity through the organ tissue. 
     Intra-body organs include tissue that can vary within different portion of the intra-body organ and that can also vary within different areas of chambers of the intra-body organ, such as different chambers of the heart. Accordingly, tissue proximity, as determined based on electronic signals provided by one or more electrodes may be based on the specific tissue properties at a given location of an intra-body organ, such as at different areas of a heart. 
     SUMMARY 
     Methods, apparatus, and systems for medical procedures are disclosed herein and include receiving, at a location agnostic system and at a first time, a first plurality of electronic signals each from a respective plurality of electrodes of a catheter. A subset of electronic signals of the first plurality of electronic signals may be received at a location aware system. The location aware system may determine a location of the catheter within an intra-body organ. The location aware system may determine that the catheter is in contact with the tissue at the location, based on the subset of electronic signals and at least one tissue property at the location. A location agnostic system contact profile for the catheter may be generated based on determining, by the location aware system, that the catheter is in contact with the tissue at the location. 
     Methods, apparatus, and systems for medical procedures are disclosed herein and include a system for determining a contact profile, the system including a catheter that includes a plurality of electrodes configured to sense a first plurality of electronic signals. A location aware system may be configured to receive a subset of electronic signals from the first plurality of electronic signals, determine a location of the catheter within an intra-body organ, and determine that the catheter is in contact with the tissue at the location, based on the subset of electronic signals and at least one tissue property at the location. A location agnostic system may be configured to receive the first plurality of electronic signals each from the respective plurality of electrodes of the catheter and generate, at a first time, a location agnostic system contact profile for the catheter based on the determination, by the location aware system, that the catheter is in contact with the tissue at the location. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       A more detailed understanding can be had from the following description, given by way of example in conjunction with the accompanying drawings wherein: 
         FIG. 1  is a diagram of an exemplary system of the present invention; 
         FIG. 2  is a flowchart for generating a location agnostic system profile in accordance with the present invention; 
         FIG. 3  is an illustration of a location aware system and a location agnostic system in accordance with the present invention; 
         FIG. 4  is an illustration of generating a location agnostic system profile in accordance with the present invention; and 
         FIGS. 5A and 5B  show graphs corresponding to a location agnostic system and a location aware system in accordance with the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     Intra-body organs, such as a heart, are often mapped, examined, and/or operated on using catheter based medical procedures. During a catheter based medical procedure, a catheter with multiple electrodes may be inserted into the intra-body organ. The multiple electrodes of the catheter may be used to, for example, map the surfaces of the intra-body organ based on proximity sensing such that a surface at a given location may be mapped if a determination is made that one or more electrodes are proximate to or in contact with the surface. The number of electrodes on the catheter may determine the resolution of the data captured by a catheter. Additionally, the number of electrodes may determine the flexibility in performing electrode-based procedures such as an ablation procedure. A higher number of electrodes may result in a higher resolution such that, for example, a larger data set may be collected based on the higher number of electrodes or a finer ablation procedure may be performed based on a higher number of electrodes. 
     Utilization of a higher number electrodes from one or more electrodes may depend on the ability of a system to determine if the number of electrodes are proximate to (e.g., in contact with) tissue of an intra-body organ. For example, in order to determine if electrodes of a catheter are in contact with tissue of a heart chamber, a system may need to determine if the electrodes of the catheter are in contact with the tissue of the heart chamber. A proximity determination may be made by determining that the impedance sensed at the location of a tissue is above an impedance threshold for that specific location. 
     The impedance threshold in a first area (e.g., a first area of the heart) may be different than the impedance threshold at a second area (e.g., a second area of the heart). The impedance thresholds may vary between different areas of an intra-body organ based on properties of the tissue corresponding to the different areas of the intra-body organ. For example, properties such as tissue thickness, tissue density, tissue type, and the like may affect the impedance thresholds to determine whether an electrode or catheter is proximate (e.g., in contact) with the tissue. Accordingly, an electrode measured impedance value X (e.g., change in impedance or percentage change in impedance) at a first location may correspond to the electrode being proximate to a tissue surface at the first location (e.g., in contact with a tissue surface) whereas the same electrode measured impedance value X at a second location may not correspond to the electrode being proximate to a tissue surface at the second location. 
     Accordingly, a proximity determination may be based on knowledge of the location of a catheter as well as calculation of a property (e.g., impedance) of the intra-body organ as detected by the electrodes. However, location aware systems may be limited in the number of electrode signals that such a location aware system can analyze, thereby limiting the resolution that may be made available by a catheter or group of catheters that exceed the electrode count past the limit of the location aware system. Exemplary embodiments of the present invention enable a location agnostic system to determine proximity using a location agnostic system contact profile (i.e., a tissue contact profile for determining proximity to tissue) that is based on proximity determinations by a location aware system that is providing a subset of signals from a subset of the electrodes. 
     The exemplary embodiments disclosed herein may enable the use of a resource intensive location aware system that may be limited to a certain number of electrode inputs (e.g., 22 inputs as disclosed in examples herein) in combination with a high resolution location agnostic system that is capable of analyzing a greater number of inputs (e.g., 120 inputs as disclosed in examples herein). Accordingly, one advantage of implementing the exemplary embodiments disclosed herein may be to use a cost effective high resolution location agnostic system to obtain a higher resolution of data in combination with an existing lower resolution but location aware system to correlate the high resolution data with location based attributes (e.g., location based tissue impedance thresholds). 
       FIG. 1  is a diagram of an exemplary system  20  in which one or more exemplary features of the present invention can be implemented. System  20  may include components, such as a catheter  40 , that are configured to damage tissue areas of an intra-body organ. The catheter  40  may also be further configured to obtain biometric data. Although catheter  40  is shown to be a single point catheter with multiple electrodes  47 A-N, it will be understood that a catheter of any shape that includes one or more elements (e.g., electrodes) may be used to implement the embodiments disclosed herein. System  20  includes a probe  21 , having shafts that may be navigated by a physician  30  into a body part, such as heart  26 , of a patient  28  lying on a bed  29 . According to exemplary embodiments, multiple probes may be provided, however, for purposes of conciseness, a single probe  21  is described herein but it will be understood that probe  21  may represent multiple probes. As shown in  FIG. 1 , physician  30  may insert shaft  22  through a sheath  23 , while manipulating the distal end of the shaft  22  using a manipulator  32  near the proximal end of the catheter  40  and/or deflection from the sheath  23 . As shown in an inset  25 , catheter  40  may be fitted at the distal end of shaft  22 . Catheter  40  may be inserted through sheath  23  in a collapsed state and may be then expanded within heart  26 . Catheter  40 , as set forth above, may include at least one electrode or a plurality of electrodes  47 A-N, as further disclosed herein. 
     According to exemplary embodiments, catheter  40  may be configured to map and/or ablate tissue areas of a cardiac chamber of heart  26 . Inset  45  shows catheter  40  in an enlarged view, inside a cardiac chamber of heart  26 . As shown, catheter  40  may include at least one electrode (or a plurality of electrodes  47 A-N) coupled onto the body of the catheter  40 . According to other exemplary embodiments, multiple elements may be connected via splines that form the shape of the catheter  40 . One or more other elements (not shown) may be provided and may be any elements configured to ablate or to obtain biometric data and may be electrodes, transducers, or one or more other elements. 
     According to exemplary embodiments disclosed herein, the electrodes, such as electrodes  47 A-N, may be configured to provide energy to tissue areas of an intra-body organ such as heart  26 . The energy may be thermal energy and may cause damage to the tissue area starting from the surface of the tissue area and extending into the thickness of the tissue area. 
     According to exemplary embodiments disclosed herein, biometric data may include one or more of LATs, electrical activity, topology, bipolar mapping, dominant frequency, impedance, or the like. The local activation time may be a point in time of a threshold activity corresponding to a local activation, calculated based on a normalized initial starting point. Electrical activity may be any applicable electrical signals that may be measured based on one or more thresholds and may be sensed and/or augmented based on signal to noise ratios and/or other filters. A topology may correspond to the physical structure of a body part or a portion of a body part and may correspond to changes in the physical structure relative to different parts of the body part or relative to different body parts. A dominant frequency may be a frequency or a range of frequency that is prevalent at a portion of a body part and may be different in different portions of the same body part. For example, the dominant frequency of a pulmonary vein of a heart may be different than the dominant frequency of the right atrium of the same heart. Impedance may be the resistance measurement at a given area of a body part. 
     As shown in  FIG. 1 , the probe  21 , and catheter  40  may be connected to a console  24 . Console  24  may include a processor  41 , such as a general-purpose computer, with suitable front end and interface circuits  38  for transmitting and receiving signals to and from catheter, as well as for controlling the other components of system  20 . In some exemplary embodiments, processor  41  may be further configured to receive biometric data, such as electrical activity, and determine if a given tissue area conducts electricity. According to an exemplary embodiment, the processor may be external to the console  24  and may be located, for example, in the catheter, in an external device, in a mobile device, in a cloud-based device, or may be a standalone processor. 
     As noted above, processor  41  may include a general-purpose computer, which may be programmed in software to carry out the functions described herein. The software may be downloaded to the general-purpose computer in electronic form, over a network, for example, or it may, alternatively or additionally, be provided and/or stored on non-transitory tangible media, such as magnetic, optical, or electronic memory. The example configuration shown in  FIG. 1  may be modified to implement the exemplary embodiments disclosed herein. The disclosed exemplary embodiments may similarly be applied using other system components and settings. Additionally, system  20  may include additional components, such as elements for sensing electrical activity, wired or wireless connectors, processing and display devices, or the like. 
     According to an embodiment, a display connected to a processor (e.g., processor  41 ) may be located at a remote location such as a separate hospital or in separate healthcare provider networks. Additionally, the system  20  may be part of a surgical system that is configured to obtain anatomical and electrical measurements of a patient&#39;s organ, such as a heart, and performing a cardiac ablation procedure. An example of such a surgical system is the Carto® system sold by Biosense Webster. 
     The system  20  may also, and optionally, obtain biometric data such as anatomical measurements of the patient&#39;s heart using ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) or other medical imaging techniques known in the art. The system  20  may obtain electrical measurements using catheters, electrocardiograms (EKGs) or other sensors that measure electrical properties of the heart. The biometric data including anatomical and electrical measurements may then be stored in a memory  42  of the mapping system  20 , as shown in  FIG. 1 . The biometric data may be transmitted to the processor  41  from the memory  42 . Alternatively, or in addition, the biometric data may be transmitted to a server  60 , which may be local or remote, using a network  62 . 
     Network  62  may be any network or system generally known in the art such as an intranet, a local area network (LAN), a wide area network (WAN), a metropolitan area network (MAN), a direct connection or series of connections, a cellular telephone network, or any other network or medium capable of facilitating communication between the mapping system  20  and the server  60 . The network  62  may be wired, wireless or a combination thereof. Wired connections may be implemented using Ethernet, Universal Serial Bus (USB), RJ-11 or any other wired connection generally known in the art. Wireless connections may be implemented using Wi-Fi, WiMAX, and Bluetooth, infrared, cellular networks, satellite or any other wireless connection methodology generally known in the art. Additionally, several networks may work alone or in communication with each other to facilitate communication in the network  62 . 
     In some instances, the server  62  may be implemented as a physical server. In other instances, server  62  may be implemented as a virtual server a public cloud computing provider (e.g., Amazon Web Services (AWS)®). 
     Control console  24  may be connected, by a cable  39 , to body surface electrodes  43 , which may include adhesive skin patches that are affixed to the patient  30 . The processor, in conjunction with a current tracking module, may determine position coordinates of the catheter  40  inside the body part (e.g., heart  26 ) of a patient. The position coordinates may be based on impedances or electromagnetic fields measured between the body surface electrodes  43  and the electrode  48  or other electromagnetic components of the catheter  40 . Additionally or alternatively, location pads may be located on the surface of bed  29  and may be separate from the bed  29 . 
     Processor  41  may comprise real-time noise reduction circuitry typically configured as a field programmable gate array (FPGA), followed by an analog-to-digital (A/D) ECG (electrocardiograph) or EMG (electromyogram) signal conversion integrated circuit. The processor  41  may pass the signal from an A/D ECG or EMG circuit to another processor and/or can be programmed to perform one or more functions disclosed herein. 
     Control console  24  may also include an input/output (I/O) communications interface that enables the control console to transfer signals from, and/or transfer signals to electrodes  47 A-N. 
     During a procedure, processor  41  may facilitate the presentation of a body part rendering  35  to physician  30  on a display  27 , and store data representing the body part rendering  35  in a memory  42 . Memory  42  may comprise any suitable volatile and/or non-volatile memory, such as random-access memory or a hard disk drive. In some exemplary embodiments, medical professional  30  may be able to manipulate a body part rendering  35  using one or more input devices such as a touch pad, a mouse, a keyboard, a gesture recognition apparatus, or the like. For example, an input device may be used to change the position of catheter  40  such that rendering  35  is updated. In alternative exemplary embodiments, display  27  may include a touchscreen that can be configured to accept inputs from medical professional  30 , in addition to presenting a body part rendering  35 . 
     As shown in the process flow chart  200  of  FIG. 2 , at step  210 , a plurality of electronic signals may be received from a respective plurality of electrodes. The plurality of electrodes may be attached to or part of one or more catheters. The one or more catheters may be inserted into an intra-body organ via an incision or via a natural orifice and may be directed to the intra-body organ. The plurality of electrodes may transmit electronic signals (e.g., voltage signals) to a processor (e.g., processor  41  of  FIG. 1 ) via a wired or wireless connection. The processor may calculate impedance values based on the electronic signals provided by the plurality of electrodes and the impedance values may be applied to determine if the catheter or, more specifically, one or more of the plurality of electrodes are proximate (e.g., in contact) with the tissue of the intra-body organ, as further disclosed herein. 
     The plurality of electronic signals sensed by respective plurality of electrodes may be provided to/received by a location agnostic system. A location agnostic system may be any applicable system that is not aware of the location of the plurality of electrodes within the intrabody organ. The location agnostic system may include a processor (e.g., processor  40  of  FIG. 1 ), a memory, and other components configured to at least determine proximity in accordance with the techniques disclosed herein. As an example, as shown in  FIG. 3 , the one or more catheters  310  inserted into an intra-body organ  305  that provide the respective plurality of electronic signals may have one hundred twenty (120) electrodes  320 . The electronic signals  322  sensed by the one hundred twenty electrodes  320  may be provided to a location agnostic system  330  such that the location agnostic system  330  is configured to receive and process all one hundred twenty electronic signals  322  corresponding to the one hundred and twenty electrodes. 
     At step  220  of the process  200  of  FIG. 2 , a subset of the plurality of electronic signals sensed by the plurality of electrodes may be split and may be provided to a location aware system. Accordingly, the plurality of electronic signals may be provided to the location agnostic system, as described at step  210 , and a subset of the plurality of electronic signals may be provided to both the location agnostic system (i.e., as described at step  210 , as part of the plurality of electronic signals) and to the location aware system (i.e., as described in this step  220 ). Continuing the example provided herein, as shown in  FIG. 3 , of the one hundred twenty electronic signals  322  that are provided to the location agnostic system  330 , a subset  325  of twenty-two (22) electronic signals may be split such that they are also provided to a location aware system  340 . 
     As described herein, a location agnostic system  330  may not receive or otherwise generate location information corresponding to the one or more catheters within an intra-body organ. Accordingly, the location agnostic system  330  may not be able to determine if a catheter or, more specifically, one or more electrodes are proximate to (e.g., in contact with) tissue of the intra-body organ. Notably, the location agnostic system  330  may not be able to determine if the catheter is proximate to such tissue without the location of the catheter because such proximity determinations may require location information to determine the correct impedance thresholds such that proximity can be determined based on whether received electronic signals meet the location specific impedance thresholds for tissue at the location. 
     At step  230  of the process  200  of  FIG. 2 , a location of a catheter and, more specifically, of one or more electrodes may be determined by the location aware system. The location of the catheter may be determined based on one or more of electromagnetic transmissions, body surface electrodes, a location pad, a mapping system, or the like. For example, the location aware system may be configured to receive electromagnetic signals between a catheter and a location pad and, based on the electromagnetic signals, may determine the catheter&#39;s location. As another example, the location aware system may compare electromagnetic signals from the catheter to body surface electrode signals to determine the catheter&#39;s location relative to the body surface electrodes. Continuing the example, as shown in  FIG. 3 , the location aware system  340  may determine the location of the one or more catheters  310   
     At step  240  of the process  200  of  FIG. 2 , a determination that the catheter and, more specifically, one or more electrodes, is proximate to (e.g., in contact with) the tissue of the intra-body organ may be made by the location aware system. The determination that the catheter is proximate to the tissue of the intra-body organ may be based on the location of the catheter and an impedance determined based on the electrical signals sensed by the one or more electrodes. Notably, an impedance threshold may be determined based on the location of the catheter, as provided by the location aware system. The impedance threshold may be specific to the tissue at the location of the catheter such that a proximity determination can be made based on the location specific impedance threshold. The location aware system may determine that the catheter is proximate to (e.g., in contact with) the tissue of the intra-body organ based on the applicable location specific impedance threshold and the impedance value sensed by one or more of the electrodes, such that the impedance value exceeds the location specific impedance threshold to indicate proximity (e.g., contact). 
     At step  250  of the process  200  of  FIG. 2 , a location agnostic system profile for the catheter may be generated based on the proximity determination by the location aware system at step  240 . Notably, when the location aware system determines that a catheter is proximate to (e.g., in contact with) tissue, at step  240 , the location agnostic system may also determine impedance values based on electrical signals sensed by the one or more electrodes. The location agnostic system may generate a location agnostic system profile based on such impedance values such that the profile includes the impedance values determined by the location agnostic system while the location aware system generates a proximity determination. 
       FIG. 4  shows an example illustration for generating a location agnostic system profile. As shown in  FIG. 4 , a catheter  405  comprising a plurality of electrodes  405   a - 405   n  may be inserted into a heart chamber  400 . Electronic signals  422  from the plurality of electrodes  405   a - 405   n  may be provided to location agnostic system  410 . Additionally, a subset  425  of the electronic signals from the plurality of electrodes  405   a - 405   n  may be provided to a location aware system  420 . 
     The location aware system  420  may be aware of the location of the catheter  405  and, based on the location of the catheter  405 , may apply an impedance threshold to determine proximity (e.g., contact) with the tissue of the heart chamber  400 . The location aware system  420  may determine that the subset of the electronic signals from the plurality of electrodes  405   a - 405   n  are in contact with the surface of tissue in the heart chamber  400 , at a first time, based on a change in impedance values such that the change in impedance values exceeds the threshold impedance. The location aware system  420  may provide a contact indication  450  to the location agnostic system  430  upon determining contact with the intra-body organ tissue. According to an implementation, the percentage of change in impedance may be applied when determining if an impedance value exceeds the threshold impedance. Upon detection of the contact, the location agnostic system  410  may record the impedance values sensed by the plurality of electrodes  405   a - 405   n  at the first time. Notably, the impedance values determined by the location aware system  420  may differ from the impedance values determined by the location agnostic system  410  at the first time. However, based on the contact determination by the location aware system  420 , the impedance values determined by the location agnostic system  410  for the plurality of electrodes  405   a - 405   n  may be stored as the location agnostic system profile  411  such that subsequent determination of impedance values that meet the location agnostic system profile are marked as contact with the tissue at the location. 
     At a second time, after the first time, the location agnostic system  410  may apply the location agnostic system profile to determine if the plurality of electrodes  405   a - 405   n  are in contact with the surface of tissue of the heart chamber  400 . For example, the location agnostic system profile may be applied to a set of electrical signals received by the location agnostic system  410  at the second time. Electrodes that sense electronic signals that correspond to impedance values greater than those in the location agnostic system profile may be determined to be in contact with the tissue of heart organ  400 . Electronic signals that correspond to impedance values greater than those in the location agnostic system profile may be considered to meet the location agnostic system profile such that they exceed impedance thresholds as provided in the location agnostic system profile. 
     After the determination of the location agnostic system profile, the location aware system  420  may not be needed to determine contact with the tissue surface of the heart chamber  400  at the location. According to an exemplary embodiment of the present invention, the location aware system  420  may be disconnected at the second time such that electrical signals from the one or more electrodes are only provided to the location aware system  410 . Based on the process  200  of  FIG. 2 , a number of location agnostic system profiles may be generated and stored in memory for a number of different locations. 
       FIG. 5B  shows a graph  510  corresponding to voltages detected by the location agnostic system  410  of  FIG. 4  and  FIG. 5A  shows a graph  520  corresponding to voltages detected by the location aware system  420  of  FIG. 4 . Although graphs  510  and  520  show the voltage corresponding to a single electrical signal from a single electrode, it will be understood that multiple electronic signals may be used to determine a location agnostic system profile. 
     As shown in  FIGS. 5A and 5B , the voltage difference determined by the location aware system  420  shown in graph  520  may be 7 volts when the location aware system  420  determines that the corresponding electrode is in contact with the tissue surface of the heart organ  400  of  FIG. 4 , based on a location specific impedance threshold. The corresponding voltage difference determined by the location agnostic system  410  may be 5 volts at the same time. Accordingly, a location agnostic system profile may be determined such that a 5 volt difference determined by the location agnostic system at the location may correspond a contact with the tissue of the heart organ  400 , as determined by the location agnostic system. 
     Notably, a location aware system (e.g.,  420  of  FIG. 4 ) may determine that a subset of electrodes are proximate to (e.g., in contact with) tissue of an intra-body organ at a specific location. The determination may be made based on the subset of electrodes sensing an impedance value (e.g., current and voltage) that exceeds the impedance threshold for that specific location, as determined by the location aware system. A location agnostic system (e.g.,  410  of  FIG. 4 ) may also sense impedance values by the entire set of electrodes (i.e., a greater number of electrode based electrical signals than those provided to the location aware system). Based on the proximity determined by the location aware system, the location agnostic system may generate a location agnostic contact profile such that the impedance values determined by the location agnostic system, when the location aware system indicates proximity, are recorded as the impedance values that indicate contact for the location agnostic system. As noted herein, such one or more impedance values of a location agnostic contact profile may be different for the location agnostic system than those sensed by the location aware system (e.g.,  FIGS. 5A and 5B ), even when the same signals are provided to the two different systems (e.g.,  FIG. 4 ). The differences may be due to any applicable reason such as circuitry, electricity propagation, internal components, conversion mechanisms, or the like. Accordingly, a location agnostic contact profile with at least one impedance threshold may be generated for the location agnostic system and may be used to determine proximity of the one or more catheters, by the location agnostic system, at the specific location. 
     Proximity (e.g., contact) indicated by the location agnostic system based on a location agnostic system profile may be used to map the surfaces of all or a part of an intra-body organ such as a heart chamber. Alternatively, or in addition, proximity indicated by the location agnostic system may be used to initiate ablation by an ablation electrode during a medical procedure. 
     Any of the functions and methods described herein can be implemented in a general-purpose computer, a processor, or a processor core. Suitable processors include, by way of example, a general purpose processor, a special purpose processor, a conventional processor, a digital signal processor (DSP), a plurality of microprocessors, one or more microprocessors in association with a DSP core, a controller, a microcontroller, Application Specific Integrated Circuits (ASICs), Field Programmable Gate Arrays (FPGAs) circuits, any other type of integrated circuit (IC), and/or a state machine. Such processors can be manufactured by configuring a manufacturing process using the results of processed hardware description language (HDL) instructions and other intermediary data including netlists (such instructions capable of being stored on a computer-readable media). The results of such processing can be maskworks that are then used in a semiconductor manufacturing process to manufacture a processor which implements features of the disclosure. 
     Any of the functions and methods described herein can be implemented in a computer program, software, or firmware incorporated in a non-transitory computer-readable storage medium for execution by a general-purpose computer or a processor. Examples of non-transitory computer-readable storage mediums include a read only memory (ROM), a random access memory (RAM), a register, cache memory, semiconductor memory devices, magnetic media such as internal hard disks and removable disks, magneto-optical media, and optical media such as CD-ROM disks, and digital versatile disks (DVDs). 
     It should be understood that many variations are possible based on the disclosure herein. Although features and elements are described above in particular combinations, each feature or element can be used alone without the other features and elements or in various combinations with or without other features and elements.