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1. (WO2018078445) JIGS FOR USE IN MEDICAL IMAGING AND METHODS FOR USING THEREOF
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

JIGS FOR USE IN MEDICAL IMAGING AND METHODS FOR USING THEREOF

CROSS REFERENCE TO RELATED APPLICATION

[0001] This is an international (PCT) application relating to and claiming the benefit of commonly-owned copending U.S. Provisional Patent Application No. 62/415,146, filed October 31, 2016, entitled "METHODS AND SYSTEMS FOR USING MULTI VIEW POSE ESTIMATION," the contents of which are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

[0002] The embodiments of the present invention relate to interventional devices and methods of use thereof.

BACKGROUND

[0003] Minimally invasive procedures such as endoscopic procedures, video-assisted thoracic surgery, or similar medical procedures can be used as diagnostic tools for suspicious lesions or as treatment means for cancerous tumors.

SUMMARY OF INVENTION

[0004] In an embodiment, a device for use during a medical imaging process includes a support structure and a plurality of radiopaque markers attached to the support structure, the support structure configured to be positioned in proximity to at least a portion of a body of a patient during the medical imaging process, the plurality of radiopaque markers being positioned in a pattern such that an image capturing a given portion of the pattern is unique from an image capturing any other given portion of the pattern.

[0005] In an embodiment, the radiopaque markers include at least one of (a) a radiopaque metal or (b) a radiopaque plastic. In an embodiment, the radiopaque markers have a uniform shape. In an embodiment, the shape is selected from the group consisting sphere-shaped, rod-shaped, and cube-shaped. In an embodiment, the pattern includes one of (a) concentric circles or (b) a pattern of points arrayed along lines. In an embodiment, the pattern is generated using linear feedback shift registers. In an embodiment, the pattern is generated using XOR cross connection of two one-dimensional linear feedback shift register gold-codes with different principal polynomials of the same order and NxM register stages.

[0006] In an embodiment, the support structure is substantially planar. In an embodiment, the support structure is three-dimensional. In an embodiment, the support structure is configured to be positioned above a patient's bed. In an embodiment, the support structure is configured to be positioned below a patient's bed. In an embodiment, the support structure is configured to be positioned between a patient's bed and a mattress positioned thereon. In an embodiment, the support structure is configured to be attached to a patient's chest. In an embodiment, the support structure is at least the size of a human chest.

[0007] In an embodiment, a method includes providing a jig including a support structure and a plurality of radiopaque markers attached to the support structure, the support structure configured to be positioned in proximity to at least a portion of a body of a patient during a medical imaging process, the plurality of radiopaque markers being positioned in a pattern such that an image capturing a given portion of the pattern is unique from an image capturing any other given portion of the pattern; obtaining a first image from a first imaging modality; extracting at least one element from the first image from the first imaging modality, wherein the at least one element comprises an airway, a blood vessel, a body cavity, or any combination thereof; obtaining, from a second imaging modality, at least (i) a first image of the jig in a first pose of second imaging modality and (ii) a second image of the jig in a second pose of second imaging modality, wherein the jig is positioned in proximity to a body of a patient; generating at least two augmented bronchograms, wherein a first augmented bronchogram corresponds to the first image of the second imaging modality in the first pose, and wherein a second augmented bronchogram corresponds to the second image of the second imaging modality in the second pose, determining mutual geometric constraints between: (i) the first pose of the of second imaging modality, and (ii) the second pose of the of second imaging modality, estimating the first pose of the of second imaging modality and the second pose of the of second imaging modality ,wherein the estimation is performed using: (i) the first augmented bronchogram, (ii) the second augmented bronchogram, and (iii) the at least one element, and wherein the estimated first pose of the of second imaging modality and the estimated second pose of the of second imaging modality meets the determined mutual geometric constraints, generating a third image; wherein the third image is an augmented image derived from the second imaging modality which highlights an area of interest, wherein the area of interest is determined from projecting data from the estimated first pose and the estimated second pose.

[0008] In an embodiment, the mutual geometric constraints are generated by: a. estimating a difference between (i) the first pose and (ii) the second pose by comparing the first image of the jig and the second image of the jig, wherein the estimating is performed using a device comprising a protractor, an accelerometer, a gyroscope, or any combination thereof, and wherein the device is attached to the second imaging modality; b. extracting a plurality of image features to estimate a relative pose change, wherein the plurality of image features comprise anatomical elements, non-anatomical elements, or any combination thereof, wherein the image

features comprise: patches attached to a patient, radiopaque markers positioned in a field of view of the second imaging modality, or any combination thereof, and wherein the image features are visible on the first image of the radiopaque instrument and the second image of the radiopaque instrument; c. estimating a difference between (i) the first pose and (ii) the second pose by using at least one camera, wherein the camera comprises: a video camera, an infrared camera, a depth camera, or any combination thereof, wherein the camera is at a fixed location, wherein the camera is configured to track at least one feature, wherein the at least one feature comprises: a marker attached the patient, a marker attached to the second imaging modality, or any combination thereof, and tracking the at least one feature; d. or any combination thereof.

[0009] In an embodiment, the method also includes tracking the jig for: identifying a trajectory, and using the trajectory as a further geometric constraint.

BRIEF DESCRIPTION OF THE FIGURES

[0010] The present invention will be further explained with reference to the attached drawings, wherein like structures are referred to by like numerals throughout the several views. The drawings shown are not necessarily to scale, with emphasis instead generally being placed upon illustrating the principles of the present invention. Further, some features may be exaggerated to show details of particular components.

[0011] Figure 1 shows a block diagram of a multi-view pose estimation method used in some embodiments of the method of the present invention.

[0012] Figures 2, 3, and 4 show exemplary embodiments of intraoperative images used in the exemplary method of Figure 1. Figures 2 and 3 illustrate fluoroscopic images obtained from one specific pose. Figure 4 illustrates a fluoroscopic image obtained in a different pose, as compared to Figures 2 and 3, as a result of C-arm rotation. The bronchoscope (240, 340, 440), the instrument (210, 310, 410), ribs (220, 320, 420), and the body boundary (230, 330, 430) are visible. The multi view pose estimation method of Figure 1 uses the visible elements in Figures 2, 3, and 4 as inputs.

[0013] Figure 5 shows a schematic drawing of the structure of bronchial airways as utilized in the exemplary method of Figure 1. The airway centerlines are indicated by reference numeral 530. A catheter is inserted into the airways structure and imaged by a fluoroscopic device with an image plane 540. The catheter projection on the image is illustrated by the curve 550 and the radiopaque markers attached to it are projected onto points G and F.

[0014] Figure 6 is an image of a bronchoscopic device tip attached to a bronchoscope, in which the bronchoscope can be used in the exemplary method of Figure 1.

[0015] Figure 7 is an illustration according to an embodiment of the method of the present invention, where the illustration is of a fluoroscopic image of a tracked scope (701) used in a bronchoscopic procedure with an operational tool (702) that extends from it. The operational tool (702) may contain radio opaque markers or a unique pattern attached thereto.

[0016] Figure 8 is an illustration of an exemplary embodiment, showing a two-dimensional ("2D") jig with a linear pattern of radiopaque markers. The rectangular area denoted by reference numeral 810 indicates a portion of the jig that may be captured in the field of view of a fluoroscopic image. The portion of the pattern captured in the area 810 is locally unique and distinct from any other portion of the pattern.

[0017] Figure 9 is an illustration of an exemplary embodiment, showing a 2D jig with a circular pattern of radiopaque markers. The rectangular area denoted by reference numeral 910 illustrates a portion of the jig that may be captured in the field of view of a fluoroscopic image.

The portion of the pattern captured in the area 910 is locally unique and distinct from any other portion of the pattern.

[0018] Figure 10 is an illustration of an exemplary embodiment, showing a three-dimensional ("3D") jig with a linear pattern of radiopaque markers. The radiopaque markers are placed in two different planes separated by a distance H.

[0019] The figures constitute a part of this specification and include illustrative embodiments of the present invention and illustrate various objects and features thereof. Further, the figures are not necessarily to scale, some features may be exaggerated to show details of particular components. In addition, any measurements, specifications and the like shown in the figures are intended to be illustrative, and not restrictive. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a representative basis for teaching one skilled in the art to variously employ the present invention.

DETAILED DESCRIPTION

[0020] Among those benefits and improvements that have been disclosed, other objects and advantages of this invention will become apparent from the following description taken in conjunction with the accompanying figures. Detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely illustrative of the invention that may be embodied in various forms. In addition, each of the examples given in connection with the various embodiments of the invention which are intended to be illustrative, and not restrictive.

[0021] Throughout the specification and claims, the following terms take the meanings explicitly associated herein, unless the context clearly dictates otherwise. The phrases "in one embodiment" and "in some embodiments" as used herein do not necessarily refer to the same

embodiments, though it may. Furthermore, the phrases "in another embodiment" and "in some other embodiments" as used herein do not necessarily refer to a different embodiment, although it may. Thus, as described below, various embodiments of the invention may be readily combined, without departing from the scope or spirit of the invention.

[0022] As used herein, the term "based on" is not exclusive and allows for being based on additional factors not described, unless the context clearly dictates otherwise. In addition, throughout the specification, the meaning of "a," "an," and "the" include plural references. The meaning of "in" includes "in" and "on."

[0023] As used herein, a "plurality" refers to more than one in number, e.g., but not limited to, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc. For example, a plurality of images can be 2 images, 3 images, 4 images, 5 images, 6 images, 7 images, 8 images, 9 images, 10 images, etc.

[0024] As used herein, an "anatomical element" refers to a landmark, which can be, e.g.: an area of interest, an incision point, a bifurcation, a blood vessel, a bronchial airway, a rib or an organ.

[0025] As used herein, "geometrical constraints" or "geometric constraints" or "mutual constraints" or "mutual geometric constraints" refer to a geometrical relationship between physical organs (e.g., at least two physical organs) in a subject's body which construct a similar geometric relationship within the subject between ribs, the boundary of the body, etc. Such geometrical relationships, as being observed through different imaging modalities, either remain unchanged or their relative movement can be neglected or quantified.

[0026] As used herein, a "pose" refers to a set of six parameters that determine a relative position and orientation of the intraoperative imaging device source as a substitute to the optical camera device. As a non-limiting example, a pose can be obtained as a combination of relative

movements between the device, patient bed, and the patient. Another non-limiting example of such movement is the rotation of the intraoperative imaging device combined with its movement around the static patient bed with static patient on the bed.

[0027] As used herein, a "position" refers to the location (that can be measured in any coordinate system such as x, y, and z Cartesian coordinates) of any object, including an imaging device itself within a 3D space.

[0028] As used herein, an "orientation" refers the angles of the intraoperative imaging device. As non-limiting examples, the intraoperative imaging device can be oriented facing upwards, downwards, or laterally.

[0029] As used herein, a "pose estimation method" refers to a method to estimate the parameters of a camera associated with a second imaging modality within the 3D space of the first imaging modality. A non-limiting example of such a method is to obtain the parameters of the intraoperative fluoroscopic camera within the 3D space of a preoperative computed tomography (CT) image. A mathematical model uses such estimated pose to project at least one 3D point inside of a preoperative CT image to a corresponding 2D point inside the intraoperative X-ray image.

[0030] As used herein, a "multi view pose estimation method" refers a method to estimate to poses of at least two different poses of the intraoperative imaging device. Where the imaging device acquires image from the same scene/subject.

[0031] As used herein, "relative angular difference" refers to the angular difference of the between two poses of the imaging device caused by their relative angular movement.

[0032] As used herein, "relative pose difference" refers to both location and relative angular difference between two poses of the imaging device caused by the relative spatial movement between the subject and the imaging device.

[0033] As used herein, "epipolar distance" refers to a measurement of the distance between a point and the epipolar line of the same point in another view. As used herein, an "epipolar line" refers to a calculation from an x, y vector or two-column matrix of a point or points in a view.

[0034] As used herein, a "similarity measure" refers to a real-valued function that quantifies the similarity between two objects.

[0035] In some embodiments, the present invention provides a method, comprising:

obtaining a first image from a first imaging modality,

extracting at least one element from the first image from the first imaging modality,

wherein the at least one element comprises an airway, a blood vessel, a body cavity, or any combination thereof;

obtaining, from a second imaging modality, at least (i) a first image of a radiopaque instrument in a first pose and (ii) a second image of the radiopaque instrument in a second pose,

wherein the radiopaque instrument is in a body cavity of a patient; generating at least two augmented bronchograms,

wherein a first augmented bronchogram corresponds to the first image of the radiopaque instrument in the first pose, and

wherein a second augmented bronchogram corresponds to the second image of the radiopaque instrument in the second pose,

determining mutual geometric constraints between:

(i) the first pose of the radiopaque instrument, and

(ii) the second pose of the radiopaque instrument,

estimating the first pose of the radiopaque instrument and the second pose of the radiopaque instrument by comparing the first pose of the radiopaque instrument and the second pose of the radiopaque instrument to the first image of the first imaging modality , wherein the comparing is performed using:

(i) the first augmented bronchogram,

(ii) the second augmented bronchogram, and

(iii) the at least one element, and

wherein the estimated first pose of the radiopaque instrument and the estimated second pose of the radiopaque instrument meets the determined mutual geometric constraints, generating a third image; wherein the third image is an augmented image derived from the second imaging modality which highlights an area of interest,

wherein the area of interest is determined from data from the first imaging modality.

[0036] In some embodiments, the at least one element from the first image from the first imaging modality further comprises a rib, a vertebra, a diaphragm, or any combination thereof. In some embodiments, the mutual geometric constraints are generated by:

a. estimating a difference between (i) the first pose and (ii) the second pose by comparing the first image of the radiopaque instrument and the second image of the radiopaque instrument,

wherein the estimating is performed using a device comprising a protractor, an accelerometer, a gyroscope, or any combination thereof, and wherein the device is attached to the second imaging modality;

b. extracting a plurality of image features to estimate a relative pose change,

wherein the plurality of image features comprise anatomical elements, non- anatomical elements, or any combination thereof,

wherein the image features comprise: patches attached to a patient, radiopaque markers positioned in a field of view of the second imaging modality, or any combination thereof,

wherein the image features are visible on the first image of the radiopaque instrument and the second image of the radiopaque instrument;

c. estimating a difference between (i) the first pose and (ii) the second pose by using a at least one camera,

wherein the camera comprises: a video camera, an infrared camera, a depth camera, or any combination thereof,

wherein the camera is at a fixed location,

wherein the camera is configured to track at least one feature,

wherein the at least one feature comprises: a marker attached the patient, a marker attached to the second imaging modality, or any combination thereof, and

tracking the at least one feature;

d. or any combination thereof.

[0037] In some embodiments, the method further comprises: tracking the radiopaque instrument for: identifying a trajectory, and using the trajectory as a further geometric constraint, wherein the radiopaque instrument comprises an endoscope, an endo-bronchial tool, or a robotic arm.

[0038] In some embodiments, the present invention is a method, comprising:

generating a map of at least one body cavity of the patient,

wherein the map is generated using a first image from a first imaging modality, obtaining, from a second imaging modality, an image of a radiopaque instrument comprising at least two attached markers,

wherein the at least two attached markers are separated by a known distance, identifying a pose of the radiopaque instrument from the second imaging modality relative to a map of at least one body cavity of a patient,

identifying a first location of the first marker attached to the radiopaque instrument on the second image from the second imaging modality,

identifying a second location of the second marker attached to the radiopaque instrument on the second image from the second imaging modality, and

measuring a distance between the first location of the first marker and the second location of the second marker,

projecting the known distance between the first marker and the second marker, comparing the measured distance with the projected known distance between the first marker and the second marker to identify a specific location of the radiopaque instrument inside the at least one body cavity of the patient.

[0039] In some embodiments, the radiopaque instrument comprises an endoscope, an endobronchial tool, or a robotic arm.

[0040] In some embodiments, the method further comprises: identifying a depth of the radiopaque instrument by use of a trajectory of the radiopaque instrument.

[0041] In some embodiments, the first image from the first imaging modality is a pre-operative image. In some embodiments, the at least one image of the radiopaque instrument from the second imaging modality is an intra-operative image.

[0042] In some embodiments, the present invention is a method, comprising:

obtaining a first image from a first imaging modality,

extracting at least one element from the first image from the first imaging modality, wherein the at least one element comprises an airway, a blood vessel, a body cavity or any combination thereof;

obtaining, from a second imaging modality, at least (i) a one image of a radiopaque instrument and (ii) another image of the radiopaque instrument in two different poses of second imaging modality

wherein the first image of the radiopaque instrument is captured at a first pose of second imaging modality,

wherein the second image of the radiopaque instrument is captured at a second pose of second imaging modality, and

wherein the radiopaque instrument is in a body cavity of a patient; generating at least two augmented bronchograms correspondent to each of two poses of the imaging device, wherein a first augmented bronchogram derived from the first image of the radiopaque instrument and the second augmented bronchogram derived from the second image of the radiopaque instrument,

determining mutual geometric constraints between:

(i) the first pose of the second imaging modality, and

(ii) the second pose of the second imaging modality,

estimating the two poses of the second imaging modality relatively to the first image of the first imaging modality, using the correspondent augmented bronchogram images and at least one element extracted from the first image of the first imaging modality;

wherein the two estimated poses satisfy the mutual geometric constrains.

generating a third image; wherein the third image is an augmented image derived from the second imaging modality highlighting the area of interest, based on data sourced from the first imaging modality.

[0043] In some embodiments, anatomical elements such as: a rib, a vertebra, a diaphragm, or any combination thereof, are extracted from the first imaging modality and from the second imaging modality.

[0044] In some embodiments, the mutual geometric constraints are generated by:

a. estimating a difference between (i) the first pose and (ii) the second pose by

comparing the first image of the radiopaque instrument and the second image of the radiopaque instrument,

wherein the estimating is performed using a device comprising a protractor, an accelerometer, a gyroscope, or any combination thereof, and wherein the device is attached to the second imaging modality;

b. extracting a plurality of image features to estimate a relative pose change,

wherein the plurality of image features comprise anatomical elements, non-anatomical elements, or any combination thereof,

wherein the image features comprise: patches attached to a patient, radiopaque markers positioned in a field of view of the second imaging modality, or any combination thereof,

wherein the image features are visible on the first image of the radiopaque instrument and the second image of the radiopaque instrument;

c. estimate a difference between (i) the first pose and (ii) the second pose by using a at least one camera,

wherein the camera comprises: a video camera, an infrared camera, a depth camera, or any combination thereof,

wherein the camera is at a fixed location,

wherein the camera is configured to track at least one feature,

wherein the at least one feature comprises: a marker attached the patient, a marker attached to the second imaging modality, or any combination thereof, and

tracking the at least one feature;

d. or any combination thereof.

[0045] In some embodiments, the method further comprises tracking the radiopaque instrument to identify a trajectory and using such trajectory as additional geometric constrains, wherein the radiopaque instrument comprises an endoscope, an endo-bronchial tool, or a robotic arm.

[0046] In some embodiments, the present invention is a method to identify the true instrument location inside the patient, comprising:

using a map of at least one body cavity of a patient generated from a first image of a first imaging modality,

obtaining, from a second imaging modality, an image of the radiopaque instrument with at least two markers attached to it and having the defined distance between them , that may be perceived from the image as located in at least two different body cavities inside the patient,

obtaining the pose of the second imaging modality relative to the map

identifying a first location of the first marker attached to the radiopaque instrument on the second image from the second imaging modality,

identifying a second location of the second marker attached to the radiopaque instrument on the second image from the second imaging modality, and

measuring a distance between the first location of the first marker and the second location of the second marker.

projecting the known distance between markers on each of the perceived location of the radiopaque instrument using the pose of the second imaging modality

comparing the measured distance to each of projected distances between the two markers to identify the true instrument location inside the body.

[0047] In some embodiments, the radiopaque instrument comprises an endoscope, an endobronchial tool, or a robotic arm.

[0048] In some embodiments, the method further comprises: identifying a depth of the radiopaque instrument by use of a trajectory of the radiopaque instrument.

[0049] In some embodiments, the first image from the first imaging modality is a pre-operative image. In some embodiments, the at least one image of the radiopaque instrument from the second imaging modality is an intra-operative image.

[0050] Multi view pose estimation

[0051] The application PCT/IB2015/000438 includes a description of a method to estimate the pose information (e.g., position, orientation) of a fluoroscope device relative to a patient during an endoscopic procedure, and is herein incorporated by reference in its entirety.

[0052] The exemplary embodiments include a method which includes data extracted from a set of intra-operative images, where each of the images is acquired in at least one (e.g., 1, 2, 3, 4, etc.) unknown pose obtained from an imaging device. These images are used as input for the pose estimation method. As an exemplary embodiment, Figures 3, 4, 5, are examples of a set of 3 Fluoroscopic images. The images in Figures 4 and 5 were acquired in the same unknown pose while the image in Figure 3 was acquired in a different unknown pose. This set, for example, may or may not contain additional known positional data related to the imaging device. For example, a set may contain positional data, such as C-arm location and orientation, which can be provided by a Fluoroscope or acquired through a measurement device attached to the Fluoroscope, such as protractor, accelerometer, gyroscope, etc.

[0053] In some embodiments, anatomical elements are extracted from additional intraoperative images and these anatomical elements imply geometrical constraints which can be introduced into the pose estimation method. As a result, the number of elements extracted from a single intraoperative image can be reduced prior to using the pose estimation method.

[0054] In some embodiments, the multi view pose estimation method further includes overlaying information sourced from a pre-operative modality over any image from the set of

intraoperative images. In some embodiments, a method for overlaying information includes: selecting, by a user, an area of interest on a preoperative image; generating a volume of interest on the preoperative image; acquiring an intraoperative image or video; calculating the pose of the intraoperative imaging modality; performing coarse registration between intraoperative images and preoperative images; generating a set of features or patterns from a volume of interest of the preoperative image; implementing fine registration to find the best fit between each of the features or patterns; enhancing a signal matching pattern to highlight anatomy found in the area of interest; and overlaying the signal sourcing from the reference image on the display/image. In some embodiments, a description of overlaying information sourced from a pre-operative modality over intraoperative images can be found in International Patent Application No. PCT/IB2015/000438, which is incorporated herein by reference in its entirety.

[0055] In some embodiments, the plurality of second imaging modalities allow for changing a Fluoroscope pose relatively to the patient (e.g., but not limited to, a rotation or linear movement of the Fluoroscope arm, patient bed rotation and movement, patient relative movement on the bed, or any combination of the above) to obtain the plurality of images, where the plurality of images are obtained from abovementioned relative poses of the fluoroscopic source as any combination of rotational and linear movement between the patient and Fluoroscopic device.

[0056] While a number of embodiments of the present invention have been described, it is understood that these embodiments are illustrative only, and not restrictive, and that many modifications may become apparent to those of ordinary skill in the art. Further still, the various steps may be carried out in any desired order (and any desired steps may be added and/or any desired steps may be eliminated).

[0057] Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non limiting fashion.

[0058] Example: Minimally Invasive Pulmonary Procedure

[0059] A non- limiting exemplary embodiment of the present invention can be applied to a minimally invasive pulmonary procedure, where endo-bronchial tools are inserted into bronchial airways of a patient through a working channel of the Bronchoscope (see Figure 6). Prior to commencing a diagnostic procedure, the physician performs a Setup process, where the physician places a catheter into several (e.g., 2, 3, 4, etc.) bronchial airways around an area of interest. The Fluoroscopic images are acquired for every location of the endo-bronchial catheter, as shown in Figures 2, 3, and 4.

[0060] After estimating the pose in the area of interest, pathways for inserting the bronchoscope can be identified on a pre -procedure imaging modality, and can be marked by highlighting or overlaying information from a pre-operative image over the intraoperative Fluoroscopic image. After navigating the endo-bronchial catheter to the area of interest, the physician can rotate, change the zoom level, or shift the Fluoroscopic device for, e.g., verifying that the catheter is located in the area of interest. Typically, such pose changes of the Fluoroscopic device, as illustrated by Figure 4, would invalidate the previously estimated pose and require that the physician repeats the Setup process. However, since the catheter is already located inside the potential area of interest, repeating the Setup process need not be performed.

[0061] Figure 4 shows an exemplary embodiment of the present invention, showing the pose of the Fluoroscope angle being estimated using anatomical elements, which were extracted from Figures 2 and 3 (in which, e.g., Figures 2 and 3 show images obtained from the initial Setup process and the additional anatomical elements extracted from image, such as catheter location, ribs anatomy and body boundary). The pose can be changed by, for example, (1) moving the Fluoroscope (e.g., rotating the head around the c-arm), (2) moving the Fluoroscope forward are backwards, or alternatively through the subject position change or either through the combination of both etc. In addition, the mutual geometric constraints between Figure 2 and Figure 4, such as positional data related to the imaging device, can be used in the estimation process.

[0062] Figure 1 is a block diagram of an exemplary method, and shows the following:

[0063] I. The component 120 extracts 3D anatomical elements, such as Bronchial airways, ribs, diaphragm, from the preoperative image, such as, but not limited to, CT, magnetic resonance imaging (MRI), Positron emission tomography-computed tomography (PET-CT), using an automatic or semi-automatic segmentation process, or any combination thereof. Examples of automatic or semi-automatic segmentation processes are described in "Three-dimensional Human Airway Segmentation Methods for Clinical Virtual Bronchoscopy", Atilla P. Kiraly, William E. Higgins, Geoffrey McLennan, Eric A. Hoffman, Joseph M. Reinhardt, which is hereby incorporated by reference in its entirety.

[0064] II. The component 130 extracts 2D anatomical elements (which are further shown in Figure 4, such as Bronchial airways 410, ribs 420, body boundary 430 and diaphragm) from a set of intraoperative images, such as, but not limited to, Fluoroscopic images, ultrasound images, etc.

[0065] III. The component 140 calculates the mutual constraints between each subset of the images in the set of intraoperative images, such as relative angular difference, relative pose difference, epipolar distance, etc.

[0066] In another embodiment, the method includes estimating the mutual constraints between each subset of the images in the set of intraoperative images. Non- limiting examples of such methods are: (1) the use of a measurement device attached to the intraoperative imaging device to estimate a relative pose change between at least two poses of a pair of fluoroscopic images. (2) The extraction of image features, such as anatomical elements or non-anatomical elements including, but not limited to, patches (e.g., ECG patches) attached to a patient or radiopaque markers positioned inside the field of view of the intraoperative imaging device, that are visible on both images, and using these features to estimate the relative pose change. (3) The use of a set of cameras, such as video camera, infrared camera, depth camera, or any combination of those, attached to the specified location in the procedure room, that tracks features, such as patches attached to the patient or markers, markers attached to imaging device, etc. By tracking such features the component can estimate the imaging device relative pose change.

[0067] IV. The component 150 matches the 3D element generated from preoperative image to their corresponding 2D elements generated from intraoperative image. For example, matching a given 2D Bronchial airway extracted from Fluoroscopic image to the set of 3D airways extracted from the CT image.

[0068] V. The component 170 estimates the poses for the each of the images in the set of intra-operative images in the desired coordinate system, such as preoperative image coordinate system, operation environment related, coordinated system formed by other imaging or navigation device, etc.

[0069] The inputs to this component are as follows:

• 3D anatomical elements extracted from the patient preoperative image.

• 2D anatomical elements extracted from the set of intra-operative images. As stated herein, the images in the set can be sourced from the same or different imaging device poses.

• Mutual constraints between each subset of the images in the set of intraoperative images [0070] The component 170 evaluates the pose for each image from the set of intra¬

operative images such that:

• The 2D extracted elements match the correspondent and projected 3D anatomical

elements.

• The mutual constraint conditions 140 apply for the estimated poses.

[0071] To match the projected 3D elements, sourcing a preoperative image to the

correspondent 2D elements from an inter-operative image, a similarity measure, such as a

distance metric, is needed. Such a distance metric provides a measure to assess the distances

between the projected 3D elements and their correspondent 2D elements. For example, a

Euclidian distance between 2 polylines (e.g., connected sequence of line segments created as a

single object) can be used as a similarity measure between 3D projected Bronchial airway

sourcing pre-operative image to 2D airway extracted from the intra-operative image.

[0072] Additionally, in an embodiment of the method of the present invention, the

method includes estimating a set of poses that correspond to a set of intraoperative images by

identifying such poses which optimize a similarity measure, provided that the mutual constraints

between the subset of images from intraoperative image set are satisfied. The optimization of the

similarity measure can be referred to as a Least Squares problem and can be solved in several

methods, e.g., (1) using the well-known bundle adjustment algorithm which implements an

iterative minimization method for pose estimation, and which is herein incorporated by reference

in its entirety: B. Triggs; P. McLauchlan; R. Hartley; A. Fitzgibbon ( 1999) "Bundle Adjustment

— A Modern Synthesis". ICCV '99: Proceedings of the International Workshop on Vision

Algorithms. Springer- Verlag. pp. 298-372, and (2) using a grid search method to scan the parameter space in search for optimal poses that optimize the similarity measure.

[0073] Markers

[0074] Radio-opaque markers can be placed in predefined locations on the medical instrument in order to recover 3D information about the instrument position. Several pathways of 3D structures of intra-body cavities, such as bronchial airways or blood vessels, can be projected into similar 2D curves on the intraoperative image. The 3D information obtained with the markers may be used to differentiate between such pathways.

[0075] In an exemplary embodiment of the present invention, as illustrated by Figure 5, an instrument is imaged by an intraoperative device and projected to the imaging plane 505. It is unknown whether the instrument is placed inside pathway 520 or 525 since both pathways are projected into the same curve on the image plane 505. In order to differentiate between pathway 520 and 525, it is possible to use at least 2 radiopaque markers attached to the catheter having predefined distance "m" between the markers. In Figure 5, the markers observed on the preoperative image are named "G" and "F".

[0076] The differentiation process between 520 and 525 can be performed as follows:

[0077] (1) Project point F from intraoperative image on the potential candidates of correspondent airways 520, 525 to obtain A and B points.

[0078] (2) Project point G from intraoperative image on the potential candidates of correspondent airways 520, 525 to obtain points C and D.

[0079] (3) Measure the distance between pairs of projected markers |AC| and |BD|.

[0080] (4) Compare the distances |AC| on 520 and |BD| on 525 to the distance m predefined by tool manufacturer. Choose appropriate airway according to a distance similarity. [0081] Tracked Scope

[0082] As non-limiting examples, methods to register a patient CT scan with a

Fluoroscopic device are disclosed herein. This method uses anatomical elements detected both in the Fluoroscopic image and in the CT scan as an input to a pose estimation algorithm that produces a Fluoroscopic device Pose (e.g., orientation and position) with respect to the CT scan. The following extends this method by adding 3D space trajectories, corresponding to an endobronchial device position, to the inputs of the registration method. These trajectories can be acquired by several means, such as: attaching positional sensors along a scope or by using a robotic endoscopic arm. Such an endo -bronchial device will be referred from now on as Tracked Scope. The Tracked scope is used to guide operational tools that extends from it to the target area (see Figure 7). The diagnostic tools may be a catheter, forceps, needle, etc. The following describes how to use positional measurements acquired by the Tracked scope to improve the accuracy and robustness of the registration method shown herein.

[0083] In one embodiment, the registration between Tracked Scope trajectories and coordinate system of Fluoroscopic device is achieved through positioning of the Tracked Scope in various locations in space and applying a standard pose estimation algorithm. See the following paper for a reference to a pose estimation algorithm: F. Moreno-Noguer, V. Lepetit and P. Fua in the paper "EPnP: Efficient Perspective -n-Point Camera Pose Estimation", which is hereby incorporated by reference in its entirety.

[0084] The pose estimation method disclosed herein is performed through estimating a

Pose in such way that selected elements in the CT scan are projected on their corresponding elements in the fluoroscopic image. In one embodiment of the current invention, adding the Tracked Scope trajectories as an input to the pose estimation method extends this method. These trajectories can be transformed into the Fluoroscopic device coordinate system using the methods herein. Once transformed to the Fluoroscopic device coordinate system, the trajectories serve as additional constraints to the pose estimation method, since the estimated pose is constrained by the condition that the trajectories must fit the bronchial airways segmented from the registered CT scan.

[0085] The Fluoroscopic device estimated Pose may be used to project anatomical elements from the pre-operative CT to the Fluoroscopic live video in order to guide an operational tool to a specified target inside the lung. Such anatomical elements may be, but are not limited to,: a target lesion, a pathway to the lesion, etc. The projected pathway to the target lesion provides the physician with only two-dimensional information, resulting in a depth ambiguity, that is to say several airways segmented on CT may correspond to the same projection on the 2D Fluoroscopic image. It is important to correctly identify the bronchial airway on CT in which the operational tool is placed. One method used to reduce such ambiguity, described herein, is performed by using radiopaque markers placed on the tool providing depth information. In another embodiment of the current invention, the Tracked scope may be used to reduce such ambiguity since it provides the 3D position inside the bronchial airways. Having such approach applied to the branching bronchial tree, it allows eliminating the potential ambiguity options until the Tracked Scope tip 701 on Figure 7. Assuming the operational tool 702 on Figure 7 does not have the 3D trajectory, although the abovementioned ambiguity may still happen for this portion 702 of the tool, such event is much less probable to occur. Therefore this embodiment of current invention improves the ability of the method described herein to correctly identify the current tool's position.

[0086] A Jig and Methods of Using

[0087] An exemplary method to calculate mutual constraints between images by using radiopaque markers positioned in the fluoroscopic device field of view is described above. This section will describe methods to position, detect, and/or identify these markers in fluoroscopic images.

[0088] In some embodiments, radiopaque markers are attached to a rigid jig in predetermined, fixed positions. In some embodiments, the radiopaque markers include a radiopaque metal. In some embodiments, the radiopaque markers include a radiopaque plastic. In some embodiments, the radiopaque markers include another radiopaque material. In some embodiments, the radiopaque markers have uniform shapes. In some embodiments, the shapes are spheres. In some embodiments, the shapes are rods. In some embodiments, the shapes are cubes. In some embodiments, the shapes are another uniform shape not mentioned herein. In some embodiments, the radiopaque markers are positioned on the jig. In some embodiments, the radiopaque markers are configured to be detected in a fluoroscopic image using an image processing algorithm. In some embodiments, the image processing algorithm is a blob detection algorithm.

[0089] In some embodiments, the blob detection algorithm is a template matching algorithm. In some embodiments, a template of a blob is moved over the search image and blobs are detected where the template matches a part of the image. In some embodiments, a template matching algorithm includes the following steps: 1. Overlay the template on the initial image position (0,0). 2. Calculate the sum of squared differences (SSD) or the sum of absolute differences (SAD) for the overlaid area and store it in a correlation matrix. 3. Move on to the next image position and repeat step 2 until the final image position is reached. In some embodiments, bright spots in the correlation image correspond to probable blob locations. In some embodiments, by defining a threshold, an exact number of blobs and exact locations can be used as result. In some embodiments, when the template covers pixels outside the image, those values could be calculated by mirroring or extrapolation. In some embodiments, the template positions could be restricted to positions with template coverage within the image. In some embodiments, small templates can be used to detect primitive blobs while large templates can detect specifically shaped blobs. In some embodiments, to get a more flexible blob detection, multiple templates could be designed.

[0090] In some embodiments, the blob detection algorithm is a watershed detection algorithm. In some embodiments, the watershed method assumes an image to be grey value mountains and simulates the process of rain falling onto the mountains, running down the mountain range and accumulating in basins. In some embodiments, this process is repeated until all basins are filled and only the watersheds between different basins remain. In some embodiments, these watersheds correspond to bright blobs, whereas dark blobs can also be obtained by taking the gradient amplitude image. In some embodiments, this flooding process is performed on the gradient image, i.e. the basins should emerge along the edges. Normally, this algorithm will lead to an oversegmentation of the image, especially for noisy image material, e.g. medical CT data. Either the image must be pre-processed or the regions must be merged on the basis of a similarity criterion afterwards.

[0091] In some embodiments, the blob detection algorithm is a spoke filter algorithm. In some embodiments, a spoke filter algorithm includes the following steps: 1. Apply edge filters to extract local edge elements of all (8) orientations. 2. Mark pixels as "interior", which lie within a certain distance of an edge element on a line perpendicular to the edge tangent direction. 3. Mark spoke crossings as being interior pixels marked by edge elements of different

orientations. 4. Mark blobs as being crossings marked by 6, 7 or all 8 directions. In some embodiments, by varying the distance, blobs of various sizes can be detected. In some embodiments, an intensity pyramid is defined as a set of fine to coarse resolution images. In some embodiments, at each level, the spoke filter is applied to detect blobs. In some embodiments, for each image in the intensity pyramid, the edge elements can be calculated and summed for all images. In some embodiments, for the summed gradient image, step 2 to 4 of the spoke filter algorithm can be followed to detect blobs at multiple scales.

[0092] In some embodiments, the blob detection algorithm is an automatic scale selection algorithm. In some embodiments, an automatic scale selection algorithm operates based on the principle that, in the absence of other evidence, assume that a scale level, at which some combination of normalized derivatives assumes a local maximum over scales, reflects the size of the corresponding blob. In some embodiments, scale levels are obtained by Gaussian smoothing. In some embodiments, the Gaussian function meets the requirement that no details are generated when resolution decreases and it provides simpler pictures at coarse scale. In some embodiments, combinations to be used as basic blob detectors in Gaussian scale-space are Laplacian and the Monge-Ampere operator. In some embodiments, the Laplacian operator is defined as the trace of the Hessian matrix, which is the square matrix of second-order partial derivatives of the image function. In some embodiments, by multiplying the trace with a scale parameter, the Laplacian operator can be used to detect scale-space maxima. In some embodiments, the Monge-Ampere operator is defined as the scale-normalized determinant of the Hessian matrix. In some embodiments, the scale parameter is multiplied twice to obtain scale invariance. In some embodiments, maxima over scales have a nice behavior under rescalings of the intensity pattern: if an image is rescaled with a constant factor, than the scale at which the maximum is assumed, will be multiplied with the same factor. In some embodiments, this guarantees that image operations transform with size variations. In some embodiments, in practice, blobs may be detected at coarse scales, and the localization properties may not be the best. Therefore, in some embodiments, a coarse-to-fine approach is needed to compute more accurate localization estimates.

[0093] In some embodiments, the blob detection algorithm is a sub-pixel precise blob detection algorithm. In some embodiments, a sub-pixel precise blob detection algorithm operates according to the following steps: 1. Initialize the expected rectangle orientations of the shorter and larger side. 2. Calculate the Hessian matrix, the eigenvector and the direction of the rectangle's shorter side using Gaussian smoothing with an ID kernel in the expected orientation of the shorter side of the rectangle. 3a. Compute the curvature maximum along the direction of the rectangle's shorter side using the profile along the direction of the larger side. 3b. Analyze the gradients of the used profile to determine bias and remove it. 4a. Compute the curvature maximum along the direction of the rectangle's larger side using the profile along the direction of the shorter side. 4b. Analyze the gradients of the used profile to determine bias and remove it. 5. Reconstruct the rectangle's center point from both profiles. In some embodiments, this method provides a way to construct the boundary of the blob and approximate the boundary by an ellipse. In some embodiments, for blob classification, this method can extract attributes like the blob's boundary length, area, geometric moments and the parameters of the fitted ellipse.

[0094] In some embodiments, the blob detection algorithm is an effective maxima line detection algorithm. In some embodiments, an effective maxima line detection algorithm is a method where connected curves of modulus maxima at different scales - called maxima lines -are effectively selected, to divide blobs from noise. In some embodiments, the selection of

maxima lines is performed by the following steps: 1. Compute the 2D Gaussian scale-space. 2. Compute modulus maxima at every scale. 3. Connect modulus maxima in adjacent scales that are close to each other and have the same sign (plus or minus) to obtain maxima lines. 4. Remove maxima lines that consist of coefficients that increase on average when scale decreases; they associate to noise. 5. Remove maxima lines that do not cross at least 5 integer scales; they associate to white noise. 6. Compute the global maximum for each maxima line and remove maxima lines which deviate at scales larger than the global maximum scale; they associate to blob structures outside the blob boundary. 7. Join maxima lines that cross in scalespace; the blob location is given by the cross point and its characteristic scale by the median of the global maximum scales of all joined maxima lines.

[0095] In some embodiments, the blob detection algorithm is a confidence measurement algorithm. In some embodiments, a confidence measurement algorithm operates as follows: 1. The image is first converted into channel images using a set of windowed cosine kernel functions. 2. For each of the images, a low-pass pyramid is generated 3. Because the filter sums up to 1, a threshold of 0.5 is used to obtain binary confidence values, resulting in a clustering pyramid. 4. The image is pruned by deleting similar clusters that lie on top of each other. 5. The pixels left in the pyramid are used as seeds for region growing resulting in a region image. 6. For all regions, the raw moments of order 0 to 2 are computed to approximate blobs by ellipses. In some embodiments, this results in an image of ellipses with different sizes and orientations, overlapping each other.

[0096] In some embodiments, the jig includes a support structure (e.g., a board, a box, etc.) having radiopaque markers positioned thereon in a pattern. In some embodiments, the jig includes a substantially two-dimensional object (e.g., a board) having radiopaque markers

positioned thereon in a two-dimensional pattern. In some embodiments, the jig includes a three-dimensional object (e.g., a box) having radiopaque markers positioned therein in a three-dimensional space. In some embodiments, the jig is configured to be positioned above a patient's bed. In some embodiments, the jig is configured to be positioned below a patient's bed. In some embodiments, the jig is configured to be positioned between a patient's bed and a mattress positioned thereon. In some embodiments, the jig is configured to be attached to or positioned on a patient's chest. In some embodiments, the jig is at least the size of a human chest. In some embodiments, the jig is larger than a human chest. In some embodiments, the pattern of the radiopaque markers attached to the jig is unique. As used herein, the term "unique" means the pattern of radiopaque markers is non-repeating and that any portion of the pattern of radiopaque markers (e.g., as may be captured in a fluoroscopic image having a field of view encompassing a portion of a patient's body and a portion of the jig) is distinct from any other portion of the pattern of radiopaque markers. In some embodiments, the pattern includes a set of lines as shown in Figure 8, in which the radiopaque markers in each line form a unique pattern. In some embodiments, the pattern includes a set of concentric circles as shown in Figure 9.

[0097] In some embodiments, the unique pattern is generated using linear feedback shift registers ("LFSR"). In some embodiments, a Gold Code LFSR is used. In some embodiments, a Gold Code LFSR connects selected bits from two feedback shift registers to the last produced code part with exclusive or (XOR) gates to the input of the next sequence. In some embodiments, the period of the code sequence depends on the register length N and the feedback pattern. In some embodiments, the maximum period is 2N - 1. In some embodiments, to produce a Gold Code from an LFSR, the XOR connected bits are connected according to two principal

polynomials of the same order N. In some embodiments, five lines of one-dimensional six -bit LFSR code are used. In some embodiments, two-dimensional LFSR code is used. In some embodiments, the unique pattern is generated through the use of XOR cross connection of two one-dimensional LFSR Gold-Codes with different principal polynomials of the same order and N X M register stages.

[0098] Consequently, in some embodiments, a user is able to identify a portion of a human's chest based on the location of the radiopaque markers on the jig. In some embodiments, the jig is configured to be attached to the patient's chest during the procedure, thereby allowing the estimation of the relative pose of the imaging device with respect to the patient even if the patient moves during the procedure.

[0099] In some embodiments, when the radiopaque markers on the jig are imaged in different poses, the user can identify the poses of the markers with the image(s) obtained to generate mutual constraints (e.g., component 140 shown in Figure 1). In some embodiments, this is accomplished by matching each visible marker in the user's field of view with its mate on the jig (which has a known position due to the nature of the pattern of radiopaque markers on the jig). In some embodiments, the correct pairing of visible markers can be achieved through designing the positions of the radiopaque markers on the jig such that that in any field of view, the visible markers are projected as a unique pattern. In some embodiments, by matching the visible unique pattern to the corresponding unique pattern in the jig design, a correct pairing may be achieved since there is only one possible option of correspondence.

[0100] In some embodiments, the jig with patterned radiopaque markers is used to determine the imaging device pose during an intervention procedure. For example, the section "Multi view pose estimation" above describes a method to estimate imaging device poses for

each image in a set of images. In some embodiments, provided that the jig is visible in each image, a user can estimate the jig's position in the coordinate system of the imaging device. In some embodiments, the jig may not be attached to the bed during pre -procedure imaging, such as, but not limited to, CT imaging. In such embodiments, after the jig position is calculated at least once, this jig position may be used to determine the intra-operative imaging device pose during the procedure from a single image or a set of images (taken after the first calculation).

[0101] In some embodiments, the methods described herein can utilize the jig's position to determine the imaging device pose from a single view image. In some embodiments, a point-based pose estimation method (referred to herein as "method A") is performed utilizing only the jig markers extracted from the intra-operative image as fiducial registration points (i.e., points that are used as a fixed basis of comparison). In some embodiments, a point-based pose estimation method is performed using a combination of anatomical elements (referred to herein "method B") with the jig markers serving as additional artificial fiducial registration points for the pose estimation method. In some embodiments, method B is performed according to the following: (1) identifying a plurality of elements of a first image; (2) identifying a plurality of elements of a second image (3) pairing the plurality of elements of the first image to a corresponding plurality of elements of the second image (or vice versa); (4) registering a plurality of elements of the first image to corresponding pairs of the plurality of elements of the second image (or vice versa). In some embodiments, the registering is performed by fine and/or coarse registration. In some embodiments, method B is performed according to the following: (1) identifying a plurality (e.g., but not limited to, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc., elements) of elements (e.g., bronchi, ribs, etc.) from a first image (e.g., a CT image), (2) identifying a plurality of fluoroscopic elements on the first image (e.g., a CT image) and a plurality of fluoroscopic

elements on the second image (e.g., a fluoroscopic image); (3) pairing a subset of the plurality of elements that correspond to elements (e.g., to bronchi, ribs, etc.) on the second image; and (4) registering the elements to the corresponding pairs of the elements on the second image, where the mapping results in a representation of the airway of the first image, or any combination thereof. In some embodiments, an image can be derived from a raw image, e.g., but not limited to, a DDR image, an edited image, a processed image, etc.

[0102] The point-based pose estimation method (method A) has the advantage of being fast and robust since it relies on artificial markers introduced to the scene. Method B includes additional anatomical constraints as compared to the point-based pose estimation method (method A), thereby increasing registration accuracy. The accuracy of the point-based pose estimation method (method A) depends on the complexity of the jig design. Additional markers with a larger 3D spread (for example, a larger distance H in the jig shown in Figure 10) result in increased pose estimation accuracy; therefore, a 3D jig (e.g., as shown in Figure 10) may provide improved accuracy as compared to a 2D jig (e.g., the jigs shown in Figures 8 and 9). To overcome that, additional constraints may be added such as the ones introduced by method B.

[0103] All publications, patents and sequence database entries mentioned herein are hereby incorporated by reference in their entireties as if each individual publication or patent was specifically and individually indicated to be incorporated by reference.

[0104] While a number of embodiments of the present invention have been described, it is understood that these embodiments are illustrative only, and not restrictive, and that many modifications may become apparent to those of ordinary skill in the art. The full scope of the invention should be determined by reference to the claims, along with their full scope of equivalents, and the specification, along with such variations. Further still, the various steps may be carried out in any desired order (and any desired steps may be added and/or any desired steps

may be eliminated).