Patent Publication Number: US-2018042518-A1

Title: Position sensor for a medical probe

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims priority to Provisional Application No. 62/374,559, filed Aug. 12, 2016, which is herein incorporated by reference in its entirety. 
    
    
     TECHNICAL FIELD 
     The present invention relates to medical devices and methods for delivering a therapy to the body. More specifically, the invention relates to devices and methods for detecting a position of the device within the body. 
     BACKGROUND 
     Cardiac arrhythmia and/or other cardiac pathology contributing to abnormal heart function may originate in cardiac cellular tissue. One technique that may be utilized to treat the arrhythmia and/or cardiac pathology may include ablation of tissue substrates contributing to the arrhythmia and/or cardiac pathology. Ablation by heat, chemicals or other means of creating a lesion in the tissue substrate may isolate diseased tissue from normal heart circuits. In some instances, electrophysiology therapy may involve locating tissue contributing to the arrhythmia and/or cardiac pathology using a mapping and/or diagnosing catheter and then using an ablation electrode to destroy and/or isolate the diseased tissue. 
     Prior to performing an ablation procedure, a physician and/or clinician may utilize specialized mapping and/or diagnostic catheters to precisely locate tissue contributing and/or causing an arrhythmia or other cardiac pathology. It is often desirable to precisely locate the targeted tissue prior to performing an ablation procedure in order to effectively alleviate and/or eliminate the arrhythmia and/or cardiac pathology. Further, precise targeting of the tissue may prevent or reduce the likelihood that healthy tissue (located proximate the targeted tissue) is damaged. 
     Several methods and/or techniques may be employed to precisely locate targeted tissue where an ablation or other therapeutic procedure may be performed. An example method may include utilizing an ablation, mapping and/or diagnostic catheter to determine how close the catheter is to targeted tissue. Further, the ablation, mapping and/or diagnostic catheter may include one or more sensing electrodes located on a distal portion of the catheter. The electrodes may sense, measure and/or provide a processor with information relating to electrical characteristics of the cardiac tissue and surrounding media. Using the sensed and/or measured information, the processor may be able to correlate the spatial location of the distal portion of the catheter to the cardiac tissue. For example, electrodes may sense the impedance, resistance, voltage potential, etc. of the cardiac tissue and/or surrounding media and determine how far a distal portion of a diagnostic and/or ablation catheter is to cardiac tissue. 
     To locate the catheter and electrodes within the body, the catheter may include a position sensor configured to provide an indication of a location within a multidimensional magnetic field. 
     SUMMARY 
     A position sensor assembly comprising a base member, a first magnetic field sensor and a second magnetic field sensor. The base member has a substantially linear longitudinal axis, a proximal portion oriented in a first plane along the longitudinal axis, a distal portion oriented in a second plane along the longitudinal axis, the second plane being substantially orthogonal to the first plane, and an intermediate portion extending between the proximal and distal portions in a twisted configuration to operate as a transition between the proximal and distal portions. The base member includes a first base member element defining the proximal portion, and a second base member element defining the distal portion, and further wherein the first and second base member elements are mechanically and electrically coupled together at a joint. The first magnetic field sensor is disposed on the proximal portion of base member, the first magnetic field sensor including a first magnetic field sensing element, the first magnetic field sensor being oriented on the proximal portion of the base member so that the first magnetic field sensing element has a sensitivity to a component of the multi-dimensional magnetic field along a first axis. The second magnetic field sensor is disposed on the distal portion of base member, the second magnetic field sensor including a second magnetic field sensing element, the second magnetic field sensor oriented on the distal portion of the base member so that the second magnetic field sensing element has a sensitivity to a component of the multi-dimensional magnetic field along a second axis. 
     In another embodiment, a medical probe comprising a flexible catheter body having a distal end, an active element coupled to the distal end of the flexible catheter body, and a position sensor assembly carried by the catheter body proximate the active element. The position sensor assembly comprises a base member, a first magnetic field sensor and a second magnetic field sensor. The base member has a substantially linear longitudinal axis, a proximal portion oriented in a first plane along the longitudinal axis, a distal portion oriented in a second plane along the longitudinal axis, the second plane being substantially orthogonal to the first plane, and an intermediate portion extending between the proximal and distal portions in a twisted configuration to operate as a transition between the proximal and distal portions. The base member includes a first base member element defining the proximal portion, and a second base member element defining the distal portion, and further wherein the first and second base member elements are mechanically and electrically coupled together at a joint. The first magnetic field sensor is disposed on the proximal portion of base member, the first magnetic field sensor including a first magnetic field sensing element, the first magnetic field sensor being oriented on the proximal portion of the base member so that the first magnetic field sensing element has a sensitivity to a component of the multi-dimensional magnetic field along a first axis. The second magnetic field sensor is disposed on the distal portion of base member, the second magnetic field sensor including a second magnetic field sensing element, the second magnetic field sensor oriented on the distal portion of the base member so that the second magnetic field sensing element has a sensitivity to a component of the multi-dimensional magnetic field along a second axis. 
     In another embodiment, a medical system comprising a medical probe, a magnetic field generator and a processor. The medical probe comprises a flexible catheter body having a distal end, an active element coupled to the distal end of the flexible catheter body, and a position sensor assembly carried by the catheter body proximate the active element. The position sensor assembly comprises a base member, a first magnetic field sensor and a second magnetic field sensor. The base member has a substantially linear longitudinal axis, a proximal portion oriented in a first plane along the longitudinal axis, a distal portion oriented in a second plane along the longitudinal axis, the second plane being substantially orthogonal to the first plane, and an intermediate portion extending between the proximal and distal portions in a twisted configuration to operate as a transition between the proximal and distal portions. The base member includes a first base member element defining the proximal portion, and a second base member element defining the distal portion, and further wherein the first and second base member elements are mechanically and electrically coupled together at a joint. The first magnetic field sensor is disposed on the proximal portion of base member, the first magnetic field sensor including a first magnetic field sensing element, the first magnetic field sensor being oriented on the proximal portion of the base member so that the first magnetic field sensing element has a sensitivity to a component of the multi-dimensional magnetic field along a first axis. The second magnetic field sensor is disposed on the distal portion of base member, the second magnetic field sensor including a second magnetic field sensing element, the second magnetic field sensor oriented on the distal portion of the base member so that the second magnetic field sensing element has a sensitivity to a component of the multi-dimensional magnetic field along a second axis. The magnetic field generator is configured to generate a multi-dimensional magnetic field in a volume including the medical probe and a patient. The processor is operable to receive outputs from the magnetic field sensors to determine a position of the position sensor assembly within the volume. 
     While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows an exemplary position sensing system for determining the location of a position sensor within a multidimensional magnetic field. 
         FIGS. 2-6  show various embodiments of a position sensor assembly configured for providing an indication of a location within a multidimensional magnetic field. 
     
    
    
     While the invention is amenable to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the invention to the particular embodiments described. On the contrary, the invention is intended to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims. 
     DETAILED DESCRIPTION 
       FIG. 1  is a schematic view of a medical system  10  for accessing a targeted tissue region in the body of a patient for diagnostic and/or therapeutic purposes.  FIG. 1  generally shows the system  10  deployed in a region of the heart. For example, system  10  may be deployed in any chamber of the heart, such as the left atrium, left ventricle, right atrium, or right ventricle, another region of the cardiovascular system, or other anatomical region. The system  10  further is configured to be used in conjunction with a magnetic position tracking system (not shown) that includes a magnetic field generator for producing a multidimensional magnetic field in a predetermined working volume in which the body of the patient is located. The field generator is positioned at known spatial coordinates with respect to the body of the patient. Except as otherwise specifically discussed herein, the magnetic position tracking system may be of any design or configuration, now known or later developed, suitable for use with a medical system such as the system  10 . 
     In the illustrated embodiment, the system  10  includes a mapping catheter or probe  14 . Each probe  14  may be separately introduced into the selected heart region  12  through a vein or artery (e.g., the femoral vein or artery) using a suitable percutaneous access technique. Alternatively, the system  10  may include one or more probes that have both mapping and therapeutic capabilities (e.g., a radiofrequency (RF) ablation catheter having one or more sensing electrodes for acquiring electrical signals from the patient&#39;s heart). 
     In the illustrated embodiment, the mapping probe  14  may include flexible catheter body  18 , the distal end of which carries a three-dimensional multiple electrode structure  20 . In the illustrated embodiment, the electrode structure  20  takes the form of a basket formed from a plurality of splines together defining an open interior space  22 , although other electrode structures could be used. The electrode structure  20  carries a plurality of mapping electrodes  24  each having an electrode location on a respective spline of the electrode structure  20  (for ease of illustration, the electrodes  24  are depicted only on a single spline in  FIG. 1 ; it will be appreciated, however, that each spline may include one or more of the electrodes  24 ). Each mapping electrode  24  may be configured to sense electrical characteristics (e.g. voltage and/or impedance) in an adjacent anatomical region. 
     The electrodes  24  may be electrically coupled to the processor  32 . A signal wire (not shown) may be electrically coupled to each electrode  24  on structure  20 . The signal wires may extend through body  18  of probe  14  and electrically couple each electrode  24  to an input of the processor  32 . Electrodes  24  may sense electrical characteristics correlated to an anatomical region adjacent to their physical location within the heart. The sensed cardiac electrical characteristic (e.g., voltage, impedance, etc.) may be processed by the processor  32  to assist a user, for example a physician, by generating processed output—e.g. an anatomical map (e.g., 3D map of heart chamber)—to identify one or more sites within the heart appropriate for a diagnostic and/or treatment procedure, such as an ablation procedure. 
     The processor  32  may include dedicated circuitry (e.g., discrete logic elements and one or more microcontrollers; application-specific integrated circuits (ASICs); or specially configured programmable devices, such as, for example, programmable logic devices (PLDs) or field programmable gate arrays (FPGAs)) for receiving and/or processing the acquired physiological activity. In some examples, processor  32  may include a general purpose microprocessor and/or a specialized microprocessor (e.g., a digital signal processor, or DSP, which may be optimized for processing activation signals) that executes instructions to receive, analyze and display information associated with the received physiological activity. In such examples, the processor  32  can include program instructions, which when executed, perform part of the signal processing. Program instructions can include, for example, firmware, microcode or application code that is executed by microprocessors or microcontrollers. The above-mentioned implementations are merely exemplary, and the reader will appreciate that processor  32  can take any suitable form for receiving electrical signals and processing the received electrical signals. The processor  32  further includes code for determining a location of the position sensor within the multidimensional magnetic field. 
     The mapping probe  14  including a position sensor (not shown in  FIG. 1 ) carried by the catheter body  18  near the electrode structure  20 . The position sensor is disposed at a location on the mapping probe that allows positioning of the position sensor within the anatomical structure (e.g., the heart) of interest. 
     The position sensor is communicatively coupled to the processor  32  by a wired or wireless communications path such that the processor  32  sends and receives various signals to and from the position sensor. As is known in the art, a position tracking system (not shown) including a magnetic field generator is configured to generate one or more magnetic fields that are sensed by the position sensor on the probe  14 . The processor  32  is configured to process the output signals from the position sensor to resolve the location of the position sensor, and consequently, the distal portion of the probe  14 , within the volume defined by the multi-dimensional magnetic field. 
     The processor  32  may output data to a suitable device, for example display device  40 , which may display relevant information for a user. For example, the display device  40  may provide to the user a three-dimensional electroanatomical map of the cardiac chamber in which the mapping probe  14  is deployed. In some examples, device  40  is a display (e.g. a CRT, LED), or other type of display, or a printer. In addition, the processor  32  may generate position-identifying output for display on device  40  that aids the user in guiding an ablation electrode or other therapeutic device into contact with tissue at the site identified for ablation. 
       FIG. 2  is a schematic view of a position sensor assembly  100  that can be incorporated into the mapping probe  14  of the system  10 , or in other embodiments, an alternative probe (e.g., an ablation catheter) for position tracking purposes. As shown in  FIG. 2  the position sensor assembly  100  includes a base member  104  defining a substantially linear longitudinal axis  108 . As further shown, the base member  104  includes a proximal portion  112 , a distal portion  116 , and an intermediate portion  120  between the proximal and distal portions. As shown, the proximal portion  112  is oriented in a first plane along the longitudinal axis  108 , and the distal portion  116  is oriented in a second plane along the longitudinal axis  108 , with the second plane being substantially orthogonal to the first plane. 
     As further shown, the intermediate portion  120  extends between the proximal and distal portions  112 ,  116  in a twisted configuration to operate as a transition between the proximal and distal portions  112 ,  116 . In various embodiments, the intermediate portion  120  has a reduced stiffness with respect to the proximal and/or distal portions  112 ,  116 , for example by reducing a thickness and/or a width of the transition zone base member. Alternatively, the intermediate portion  120  may be formed from a material having a lower stiffness than that of the proximal and/or distal portions  112 ,  116 . In some embodiments, the axis of rotation about which the intermediate portion is twisted substantially corresponds to the longitudinal axis  108 . 
     The position sensor assembly  100  further includes a first magnetic field sensor  124  having a first magnetic field sensing element  128 , and a second magnetic field sensor  132  having a second magnetic field sensing element  136 . As will be understood by those skilled in the art, the first and second magnetic field sensing elements  128 ,  136  are each configured to have a sensitivity to a component of a multi-dimensional magnetic field generated by an external field generator (as described previously) along a predetermined direction or axis. 
     In the illustrated embodiment, the first magnetic field sensor  124  is disposed on the proximal portion  112  of base member  104 , and consequently, in the first plane. Additionally, the second magnetic field sensor  132  is disposed on the distal portion  116  of base member  104 , and consequently, in the second plane, which as described and shown, is oriented generally orthogonal to the first plane. 
     In various embodiments, the position sensor assembly  100  may also include a third magnetic field sensor (not shown) having a third magnetic field sensing element substantially similar to the first and second magnetic field sensing elements. In such embodiments, the third magnetic field sensor may be disposed on the proximal portion  112  of the base member  104 , but oriented thereon such that its axis of sensitivity is orthogonal to that of the first magnetic field sensing element  128 . Alternatively, the third magnetic field sensor may be disposed on the distal portion  116  of the base member  104 , but oriented thereon such that its axis of sensitivity is orthogonal to that of the second magnetic field sensing element  136 . 
     In some embodiments, one or both of the first magnetic field sensor  124  and the second magnetic field sensor  132  may be a dual-axis sensor having two magnetic field sensing elements disposed on or within a single die, each magnetic field sensing element being oriented so that the axes of sensitivity of the respective magnetic field sensing elements are mutually orthogonal to one another. For example, in one embodiment, the first magnetic field sensor  124  may include both the first magnetic field sensing element  128  as well as the third magnetic field sensing element (not shown). Alternatively, in one embodiment, the second magnetic field sensor  132  may include both the second magnetic field sensing element  136  as well as the third magnetic field sensing element. Thus, the respective individual magnetic field sensing elements need not necessarily all be located on a separate die. 
     In the various embodiments, the position sensor assembly  100  is configured to sense the generated external magnetic fields and provide tracking signals indicating the location and orientation of the position sensor assembly  100  in up to six degrees of freedom (i.e., x, y, and z measurements, and pitch, yaw, and roll angles) when the first, second and third magnetic field sensors are present and oriented along mutually orthogonal axes. 
     In the various embodiments, the magnetic field sensors of the position sensor assembly  100  can include any magnetic field sensing technologies now known (e.g., anisotropic magneto-resistive (AMR) sensing elements, giant magneto-resistive (GMR) sensing elements, tunneling magneto-resistive (TMR) sensing elements, colossal magneto-resistive (CMR) sensing elements, extraordinary magneto-resistive (EMR) sensing elements, spin Hall sensing elements, and the like), or later developed. 
     As further shown, the position sensor assembly  100  includes a encapsulating element  140  (i.e., a housing) surrounding the base member  104  and the magnetic field field sensors disposed thereon. In embodiments, the encapsulating element  140  can be an epoxy material. Additionally, the position sensor assembly  100  includes conductors  150  for coupling the magnetic field sensors to electrical connection components (not shown) at or near the proximal portion  112  of the base member  104 . 
     In various embodiments, position sensor assembly  100 , particularly the base member  104  and the conductors  150  and associated electrical interconnects, may be constructed according to known, or later-developed, printed circuit board construction technologies. For example, the conductors  150  may be constructed as electrical traces formed on the body  104 . Similarly, the body  104  may also be formed of any materials used for flexible printed circuit substrates. In other embodiments, the conductors  150  may be conductor wires that are separately bonded to the body  104  and the respective magnetic field sensors, either before or after forming the twist in the intermediate portion  120 . As will be appreciated, the magnetic field sensors may discrete dies that are mounted to the base member  104  and electrically coupled to the conductors  150  according to known techniques. 
     In embodiments, the conductors  150  are disposed, at least within the intermediate portion  120 , as near as possible to the longitudinal axis  108 , which also constitutes the axis of rotation about which the intermediate portion  120  is twisted. In doing so, rotational and torsional stresses and strains on the conductors  150  disposed along the intermediate portion  120  of the base member  104  can be minimized. 
       FIG. 3  is schematic view of a portion of a position sensor assembly  300  in an intermediate manufacturing state to illustrate the design according to one embodiment. Specifically, the position sensor assembly  300  includes a base member  304  defining a substantially linear longitudinal axis  308 . As further shown, the base member  304  includes a proximal portion  312 , a distal portion  316 , and an intermediate portion  320  between the proximal and distal portions. The position sensor assembly  300  further includes a first magnetic field sensor  324  disposed on the proximal portion  312  of the base member  304 , a second magnetic field sensor  332  disposed on the distal portion  316  of the base member  304 , and a third magnetic field sensor  340  disposed on the proximal portion  312  at a different location than the first magnetic field sensor  324 . As will be appreciated by the preceding discussion, in various embodiments, the third magnetic field sensor  340  may be instead located on the distal portion  316 . Alternatively, in other embodiments, the first or second magnetic field sensor  324 ,  332  may be a dual-axis sensor having sensitivity in two mutually orthogonal axes, thus obviating the need for the third magnetic field sensor  340 . As further shown, the position sensor assembly  300  includes a plurality of conductors  350  that operatively couple the respective magnetic field sensors to other electrical components (not shown). 
     In the particular embodiment illustrated, the intermediate portion  320  has an “hourglass” shape, such that it has concavely-curved outer edges resulting in a width at the middle of the intermediate portion  320  that is smaller than the width of either of the proximal or distal portions  312 ,  316 . The illustrated shape of the intermediate portion  320  provides that portion with a lower torsional stiffness than either of the proximal or distal portions  312 ,  316 , thus facilitating twisting the intermediate portion  320  so that the proximal and distal portions  312 ,  316  can be oriented in different, mutually orthogonal planes. In embodiments, the conductors  350  (e.g., electrical traces) connected to the second magnetic field sensor  332  can be disposed on or proximate the longitudinal axis  308  along the intermediate portion  320  so as to minimize torsional stress and strain on those conductors. 
       FIG. 4  is schematic view of a portion of a position sensor assembly  400  in an intermediate manufacturing state to illustrate the design according to one embodiment. Specifically, the position sensor assembly  400  includes a base member  404  defining a substantially linear longitudinal axis  408 . As further shown, the base member  404  includes a proximal portion  412 , a distal portion  416 , and an intermediate portion  420  between the proximal and distal portions. The position sensor assembly  400  further includes a first magnetic field sensor  424  disposed on the proximal portion  412  of the base member  404 , a second magnetic field sensor  432  disposed on the distal portion  416  of the base member  404 , and a third magnetic field sensor  440  disposed on the proximal portion  412  at a different location than the first magnetic field sensor  424 . As will be appreciated by the preceding discussion, in various embodiments, the third magnetic field sensor  440  may be instead located on the distal portion  416 . Alternatively, in other embodiments, the first or second magnetic field sensor  424 ,  432  may be a dual-axis sensor having sensitivity in two mutually orthogonal axes, thus obviating the need for the third magnetic field sensor  440 . As further shown, the position sensor assembly  400  includes a plurality of conductors  450  that operatively couple the respective magnetic field sensors to other electrical components (not shown). 
     In the particular embodiment illustrated, the intermediate portion  420  has a “serpentine” configuration when in the flat, untwisted state as depicted in  FIG. 4 . The illustrated shape of the intermediate portion  420  provides that portion with a lower torsional stiffness than either of the proximal or distal portions  412 ,  416 , thus facilitating twisting the intermediate portion  420  so that the proximal and distal portions  412 ,  416  can be oriented in different, mutually orthogonal planes. In embodiments, the conductors  450  (e.g., electrical traces) connected to the second magnetic field sensor  432  can be disposed on or proximate the longitudinal axis  408  adjacent the intermediate portion  420 , and then follow the serpentine path of the substrate material of the intermediate portion  420  so as to minimize torsional stress and strain on those conductors when the intermediate portion is twisted into its final configuration. 
       FIG. 5  illustrates top and side schematic views of a portion of a position sensor assembly  500  according to one embodiment. Specifically, the position sensor assembly  500  includes a base member  504  defining a substantially linear longitudinal axis  508 . As further shown, the base member  504  includes a proximal portion  512 , a distal portion  516 , and an intermediate portion  520  between the proximal and distal portions. The position sensor assembly  500  further includes a first magnetic field sensor  524  disposed on the proximal portion  512  of the base member  504 , a second magnetic field sensor  532  disposed on the distal portion  516  of the base member  504 , and a third magnetic field sensor  540  disposed on the proximal portion  512  at a different location than the first magnetic field sensor  524 . As will be appreciated by the preceding discussion, in various embodiments, the third magnetic field sensor  540  may be instead located on the distal portion  516 . Alternatively, in other embodiments, the first or second magnetic field sensor  524 ,  532  may be a dual-axis sensor having sensitivity in two mutually orthogonal axes, thus obviating the need for the third magnetic field sensor  540 . As further shown, the position sensor assembly  500  includes a plurality of conductors  550  that operatively couple the respective magnetic field sensors to other electrical components (not shown). 
     The base member  504  differs from those described in the previous embodiments in that it is a two-piece construction and includes a proximal base member element  560  and a distal base member element  564  mechanically and electrically coupled together at a joint  568 , which can include one or more bond pads  570 ,  574  or other conventional structures for joining PCB components. In the illustrated embodiment the twisted intermediate portion  520  is located on the distal base member element  564 . In other embodiments, the intermediate portion  520  may be located on the proximal base member element  560 . The two-piece construction of the base member  504  can advantageously minimize stresses induced in the base member  504  substrate as well as in the electrical conductors  550  formed on the base member  504 . In various embodiments, the intermediate portion  520  can have an hourglass or serpentine configuration as previously described. 
       FIG. 6  is schematic view of a position sensor assembly  600  according to another embodiment. The position sensor assembly  600  is in many respect similar or identical to the position sensor assembly  200  described above, and includes a base member  604  defining a longitudinal axis  608 , a proximal portion  612 , a distal portion  616  and a twisted intermediate portion  620  therebetween. The position sensor assembly  600  further includes a plurality of magnetic field sensors  624 ,  632  and  640  disposed on the base member  604  in the manner described above in connection with other embodiments, an encapsulating element  644  (e.g., an epoxy coating), and a plurality of conductors  650  electrically coupled to the respective magnetic field sensors  624 ,  632  and  640 . 
     The position sensor assembly  600  differs from the previously described embodiments in that the conductors  650  constitute lead wires that are structurally separated from (i.e., not formed on) the base member  604 . In particular, the conductors  650  connected to the magnetic field sensor  632  located on the distal portion  616  of the base member  604  are carried by the encapsulating element  644  at least across the intermediate portion  620 , to bond pads  660 ,  664  located at the distal tip of the base member  604  and electrically coupled to the magnetic field sensor  632  via short electrical traces (not shown) formed on the distal portion  616 . In this configuration, the conductors  650  extending across the intermediate portion  620  are not exposed to the torsional stresses imposed on the intermediate portion  620  during the manufacturing step of forming the twist in the intermediate portion  620 . 
     Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the present invention. For example, while the embodiments described above refer to particular features, the scope of this invention also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the present invention is intended to embrace all such alternatives, modifications, and variations as fall within the scope of the claims, together with all equivalents thereof.