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1. (WO2015161101) FIBER OPTIC DISTAL SENSOR CONTROLLED MICRO-MANIPULATION SYSTEMS AND METHODS
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FIBER OPTIC DISTAL SENSOR CONTROLLED MICROMANIPULATION SYTEMS AND METHODS

STATEMENT OF GOVERNMENT SUPPORT

[0001] This invention was made with U.S. Government support under Grant No. R01

EY021540, awarded by the National Institutes of Health National Eye Institute. The Government has certain rights in this invention.

TECHNICAL FIELD

[0002] The field of the currently claimed embodiments of this invention relates to motion-compensated micro-manipulation systems and methods of using the same, and more particularly systems and methods using optical coherence tomography with a motion-compensated micromanipulation systems, including surgical blades.

BACKGROUND

[0003] Optical coherence tomography (OCT) has been viewed as an "optical analogy" of ultrasound sonogram (US) imaging since its invention in early 1990's. Compared to the conventional image-guided interventions (IGI) using modalities such as magnetic resonance imaging (MRI), X-ray computed tomography (CT) and ultrasound (US), OCT has much higher spatial resolution and therefore possesses great potential for applications in a wide range of micro surgeries, such as vitreo-retinal surgery, neurological surgery, otolaryngologic surgery and cochlear implantation. It has recently been demonstrated that OCT can be highly effective in freehand or robotically assisted retinal imaging or cochlear implantation, for example. A single-mode fiber can be lensed with state-of-the-art micro-optics to form a light beam with a spot size around 11 μιη to 18 μιη in retinal imaging, gastrointestinal endoscopy, coronary artery imaging, and needle-based Doppler OCT. Thus, OCT fiber optic sensing and imaging are becoming powerful tools for non-destructive cross-sectional imaging of biological tissues.

[0004] Retinal surgery is one example of microsurgery. In current practice, retinal surgery is performed under an operating microscope with free-hand instrumentation. Human limitations include an inability to clearly view surgical targets, physiological hand tremor, and lack of tactile feedback in tool-to-tissue interactions. In addition, tool limitations, such as lack of proximity sensing or smart functions, are important factors that contribute to surgical risk and reduce the likelihood of achieving surgical goals. Current instruments do not provide physiological or even basic interpretive information. Surgical outcomes (both success and failure) are limited, in part, by technical hurdles that cannot be overcome by conventional instrumentation.

[0005] Surgical blades are one type of hand-held surgical instrument. A hand-held instrument has the following advantages. First, it is small and lightweight, making it easy to access tight spaces. Second, surgeons are intimately familiar with hand-held instruments which can leverage the surgeons' experience and skills with little training. Third, a small hand-held instrument offers greater safety because the surgeon can more easily override or remove the instrument in cases of malfunction.

[0006] A hand-held instrument, however, poses additional challenges over mechanically-rigid instruments. An operator of the hand-held instrument may be require control a tool tip of the instrument within very small tolerances, including sub-millimeter scale. For example, in some applications, surgical blades may need to be controlled at the sub-millimeter or micron scale. A surgeon may be required to perform a cut with a surgical blade that achieves a high level of accuracy with regard to the depth of the cut or it may be desirable to perform a cut that has a substantially even depth across a length of the cut. However, hand tremor, or physiological motion (e.g., the breathing and/or heartbeat, as well as volitional movement of the surgeon and/or patient) can make accurate and/controlled cuts or other micro-manipulations difficult to achieve and may cause damage to surrounding delicate tissues or cause localized hemorrhage or other injury and pose a high risk to the safety of the patient during performance of the procedure. The resulting involuntary changes in relative distance between the blade or other tool tip and the surgical tissue surface, although usually on the order of a few hundreds of micrometer at less than 5Hz, may cause serious error due to the scale of microsurgery. Currently, no hand held

surgical blade system can satisfy all of the above challenges during performance of a cutting operation. There remains a need for improved micro-manipulation systems and methods for surgical or microsurgical applications.

SUMMARY

[0007] A motion-compensated cutting system according to an embodiment includes a tool body having a size and configuration to be used for hand-held operation. The system also includes an actuator that is connected to the tool body and that has a shaft that is movable relative to the tool body. The system further includes a cutting implement attached to the shaft such that a distal end of the cutting implement is movable relative to the tool body in an axial direction. The system includes an optical coherence tomography system and a control unit. The optical coherence tomography system includes an optical fiber with a distal end fixed relative to the distal end of the cutting implement. The control unit is in communication with the optical coherence tomography system and the actuator, and is able to determine a position of the distal end of the cutting implement relative to a reference surface based on a signal received from the optical coherence tomography system. The control unit is also able to control the actuator to move the cutting implement to compensate for relative motion between the tool body and the reference surface at least during a cutting operation. The control unit is further able to maintain a predetermined depth of the distal end of the cutting implement with respect to the reference surface during the cutting operation.

[0008] According to an embodiment, a motion-compensated micro-manipulation system is provided. The micro-manipulation system includes a tool body with a size and configuration to be used for manual manipulation. The system also includes an actuator that is connected to the tool body and that has a shaft that is movable relative to the tool body. The system further includes a tool element attached to the shaft such that a distal end of the tool element is movable relative to the tool body in an axial direction. A position sensor is attached to the tool body and is able to detect a position of the shaft. Additionally, the system includes an optical coherence tomography system and a control unit. The optical coherence tomography system includes an optical fiber with a distal end fixed relative to the distal end of the tool element. The control unit is in communication with the optical coherence tomography system and the actuator, and is also in communication with the position sensor. The control unit is able to move the shaft, at a predetermined stage of a micro-manipulation procedure, to a reset position using input from the position sensor. Additionally or alternatively, the control unit is able to communicate a warning signal when the shaft is in a predetermined position. The control unit is further able to determine a position of the distal end of the tool element relative to a reference surface based on a signal received from the optical coherence tomography system, and to control the actuator to move the tool element to compensate for relative motion between the tool body and the reference surface.

[0009] According to an embodiment, a method of performing a motion-compensated cutting operation is provided. The method includes providing a cutting tool including a tool body and a cutting implement coupled to the tool body. The cutting implement has a distal end able to cut tissue of a patient. The method also includes providing an optical coherence tomography system, at least a portion of which is coupled to the cutting tool. The optical coherence tomography system includes an optical fiber with a distal end fixed relative to the distal end of the cutting implement. The method further includes performing the cutting operation, and controlling a position of the cutting implement along a longitudinal axis of the cutting implement over a duration of the cutting operation based on an input from the optical coherence tomography system to perform a cut of a desired depth.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Further objectives and advantages will become apparent from a consideration of the description, drawings, and examples.

[0011] FIG. 1 shows a motion-compensated surgical blade system according to an embodiment of the current invention.

[0012] FIG. 2 shows a view into the interior of the motion-compensated blade system of Fig. 1 according to an embodiment of the current invention.

[0013] FIG. 3 shows an example of a motion-compensated surgical blade system according to an embodiment of the current invention.

[0014] FIG. 4 shows a schematic view of a motion-compensated surgical blade system according to an embodiment of the current invention.

[0015] FIG. 5 shows an OCT image of an incision made by a motion-compensated surgical blade system according to an embodiment of the current invention.

[0016] FIG. 6 shows an OCT cross-section image of the incision shown in FIG. 5.

[0017] FIG. 7 shows a non-motion-compensated result and motion-compensated results of the cutting depth at different incision angles as an example according to an embodiment of the current invention.

[0018] FIG. 8 shows a non-motion-compensated result and motion-compensated results of a Fourier analysis at different incision angles for an example according to an embodiment of the current invention.

[0019] FIG. 9 shows an example of a control process of a motion-compensated surgical blade system according to an embodiment of the current invention.

[0020] FIG. 10 shows a motion-compensated surgical blade system according to an embodiment of the current invention.

[0021] FIG. 11 shows another view of the motion-compensated surgical blade system shown in Fig. 10.

[0022] FIG. 12 shows a result of signals from two OCT sensors according to an embodiment of the current invention.

[0023] FIG. 13 shows an example of a motion-compensated surgical blade system being used by an operator according to an embodiment of the current invention.

DETAILED DESCRIPTION

[0024] Some embodiments of the current invention are discussed in detail below. In describing embodiments, specific terminology is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology and examples selected. A person skilled in the relevant art will recognize that other equivalent components can be employed and other

methods developed without departing from the broad concepts of the current invention. All references cited anywhere in this specification, including the Background and Detailed

Description sections, are incorporated by reference as if each had been individually incorporated. All references cited in this specification are incorporated herein by reference.

[0025] The term "light" as used herein is intended to have a broad meaning that can include both visible and non- isible regions of the electromagnetic spectrum. For example, visible, near infrared, infrared and ultraviolet light are all considered as being within the broad definition of the term "light."

[0026] The term "real-time" is intended to mean that the OCT images can be provided to the user during use of the OCT system. In other words, any noticeable time delay between detection and image display to a user is sufficiently short for the particular application at hand. In some cases, the time delay can be so short as to be unnoticeable by a user.

[0027] The embodiments of the current invention that are described herein are not intended to be limited to the examples and terminology described. The following applications may contain features and examples that are contemplated as aspects of embodiments of the current invention: U.S. Patent Application No. 13/811,077, filed January 18, 2013, which is a U.S. National Stage entry of PCT Application No. PCT/US2011/044693, filed July 20, 2011, which claims priority to U.S. Provisional Application No. 61/365,998, filed July 20, 2010; U.S. Patent Application No. 14/114,885, filed October 30, 2013, which is a U.S. National Stage entry of PCT Application No. PCT/US2012/036643, filed May 4, 2012, which claims priority to U.S. Provisional Application No. 61/482,300, filed May 4, 2011; U.S. Patent Application No. 13/957,145, filed August 1, 2013, which claims priority to U.S. Provisional Application No. 61/678,397, filed August 1, 2012; PCT Application No. PCT/US2013/059736, filed September 13, 2013, which is a continuation of U.S. Patent Application No. 13/618,810, filed September 14, 2012; and U.S. Patent Application No. 14/163,491, filed January 24, 2014. These references are hereby incorporated by reference in their entirety.

[0028] Some embodiments of the current invention provide a motion-compensated micromanipulation system. According to some embodiments, the micro-manipulation system may be a cutting system, used as a surgical blade, for example, that enables high-precision cutting control. However, embodiments discussed herein include micro-manipulation systems in general,

including embodiments of a cutting system. It is understood that embodiments of the current invention are not limited to those discussed herein, and may include other types of micromanipulation systems including, for example, injectors, forceps, probes, and other surgical or micro-surgical instruments. The micro-manipulation system may include a tool body and an actuator connected to the tool body. The tool body can have a size, shape, and configuration to be used for manual manipulation. For example, the tool body can be handheld and may include a grip. The actuator can include a shaft or some other component that is movable relative to the tool body. In some embodiments, the actuator includes a PZT motor the moves the shaft in an axial direction. A tool element can be attached to the shaft such that a distal end of the tool element also is movable relative to the tool body. For example, when attached to the shaft, the tool element may be movable in an axial direction of the tool element. The system may further include an optical coherence tomography (OCT) system. The OCT system can include an optical fiber with a distal end that is fixed relative to the distal end of the tool element. The OCT system may also include an optical sensor that can receive a signal from the optical fiber.

[0029] The system may further include a control unit that is in communication with the OCT system and the actuator such that the control unit can send and/or receive signals between it and the OCT system and the actuator. The control unit may be able to determine a position of the distal end of the tool element relative to a reference surface based on a signal received from the OCT system. Further, the control unit may be able to control the actuator to move the tool element to compensate for relative motion between the tool body and the reference surface.

[0030] The reference surface may be a part of the subject of the micro-manipulation being performed. For example, in micro-surgical applications, the reference surface may be a tissue surface, including external and internal tissue surfaces, or subsurface structures in the tissue. However, the reference surface is not limited to tissue. According to some embodiments, micromanipulation may be performed on subjects other than living organisms, in which case the reference surface can be any surface whose position is relevant to the micro-manipulation being performed.

[0031] The operation of some motion-compensation devices can be limited by the range of motion of the drive system used to perform the motion compensation. For example, a movable component of a drive system may start at an initial position, but the sum of movements performed during motion compensation may result in the movable component moving, on

average, in one direction until the movable component reaches the limit of its range of motion. After reaching that limit in that direction, the movable component will not be able to move further in that direction, and thus motion compensation will be negatively impacted. However, according to some embodiments of the present invention, improvements are made to decrease the chance and/or negative consequences from the limited range of motion of a motion-compensation device.

[0032] For example, in some embodiments, a position sensor can be incorporated into or attached to the tool body to detect a position of the shaft. Signals from the position sensor can be received by the control unit, thus allowing the position of the shaft to be known to the control unit. Based on a signal received by the control unit from the position sensor or from a user-operable input, the control unit may cause the shaft to be moved to a reset position under certain circumstances. The reset position may be substantially at the center of a range of motion of the shaft, or some other position that provides sufficient freedom of motion of the shaft during motion compensation. For example, the control unit may move the shaft to the reset position at a predetermined stage of a micro-manipulation procedure being performed. The micromanipulation system may also include a manually operable control in communication with the control unit so that an operator of the micro-manipulation system can use the control to signal the predetermined stage to the control unit. For example, the micro-manipulation system may include a button, switch, dial, or other input by which the operator of the system may reset the position of the shaft. The operator may choose to reset the position of the shaft between micromanipulation operations where motion compensation has been in use. In this way, the shaft may start from the reset position for subsequent micro -manipulation operations. Accordingly, it is possible to avoid the situation where a micro-manipulation is started with the shaft already at or near the limit of its range of motion, and thus the odds of the shaft reaching the limit of its range of motion may be decreased.

[0033] In some embodiments, the position sensor may be an optical coherence tomography-based encoder. However, the position sensor is not limited to an OCT-based encoder, and may be another type of optical or electromagnetic encoder, or other some other type of position sensor known by those skilled in the art. In the case of an OCT-based encoder, the OCT-based encoder may use some common components with the OCT system to which the optical fiber is attached, or the OCT-based encoder may be separate from that OCT system.

[0034] According to some embodiments, the predetermined stage for resetting the shaft may be based on exceeding a predetermined distance between the distal end of the tool element and the reference surface. For example, after performing a micro-manipulation procedure, the operator of the system may withdraw the tool body of the system away from the subject of the micromanipulation and thus away from the reference surface. This withdrawing of the tool body from the reference surface may be used to trigger an automatic resetting of the shaft position without necessarily requiring a manual activation of a user operable input to perform the reset. In some embodiments, the resetting of the shaft may be delayed by some amount of time after the predetermined distance is exceeded.

[0035] The control unit may communicate a warning signal when the shaft is in a

predetermined position based on a position of the shaft as determined by the position sensor. For example, the predetermined position may be at or near a limit of a range of motion of the shaft. The micro-manipulation system can further include a warning device that receives the warning signal from the control unit based on a signal from the position sensor. In some embodiments, the warning device may communicate a visual or auditory warning to an operator of the micromanipulation system. Thus, an operator of the micro-manipulation system can be warned when the shaft is at or near the limits of its range of motion and can then take appropriate action to prevent or mitigate undesirable consequences of the shaft reaching the limits of its range of motion. For example, the operator may choose to at least temporarily cease the procedure being performed, to reset the position of the shaft, or to adjust a position of the tool body.

[0036] According to embodiments of the present invention, the control unit may control the actuator to achieve a predetermined distance between the distal end of the tool element and the reference surface. The reference surface need not be distal to the distal end of the tool element. For example, if the distal end of the tool element is distal to the reference surface with respect to the tool body, then the predetermined distance may indicate a depth of the tool element in the reference surface.

[0037] In some embodiments, the tool element may be detachable from the shaft, and may also be disposable. The optical fiber may also be detachable from a remainder of the OCT system, and may also be disposable. The optical fiber can be pre-attached to the tool element so that the distal end of the optical fiber is fixed relative to the distal end of the tool element. The other end of the optical fiber may then be attachable to a remainder of the OCT system. In some

embodiments, the tool element can be a cutting implement, such as a blade, pick, or saw.

However, the tool element is not limited to a cutting implement, and may also include, for example, a needle (e.g., for performing injection), forceps, a probe, or other tools, including tools used in micro-surgery or other micro-manipulation applications.

[0038] According to some embodiments, a motion-compensated cutting system is provided. It is to be understood that features of the above embodiments may also be included in embodiments of the cutting system described herein, even where those features are not explicitly mentioned in the following descriptions of the cutting system embodiments. Correspondingly, features of embodiments of the cutting system described below may also be used in the above discussed embodiments of the micro-manipulation system, even where those features where not explicitly described in the above embodiments.

[0039] The cutting system may include a tool body having a size and configuration that allows for manual cutting with the cutting system. An actuator with a movable shaft can be connected to the tool body. A cutting implement attached to the shaft such that a distal end of the cutting implement is movable relative to the tool body in an axial direction of the cutting implement. An OCT system may be included with the cutting system, and at least a portion of the OCT system may be attached to the tool body and/or the cutting implement. An optical fiber of the OCT system has a distal end that is fixed relative to the distal end of the cutting implement. For example, the optical fiber may be attached to the cutting implement such that at least a portion of the optical fiber extends parallel to a portion of the cutting implement. In some embodiments, the OCT system uses common-path OCT. One or both of the cutting implement and the optical fiber may be detachable from a remainder of the motion-compensated cutting system.

[0040] A control unit in communication with the OCT system and the actuator can determine a position of the distal end of the cutting implement relative to a reference surface based on a signal received from the OCT system. The control unit can control the actuator to move the cutting implement to compensate for relative motion between the tool body and the reference surface at least during a cutting operation. Such relative motion could be caused by, for example, a hand tremor of the operator, or voluntary or involuntary motion of the reference surface or the operator.

[0041] According to some embodiments, the control unit can maintain a predetermined depth of the distal end of the cutting implement with respect to the reference surface during the cutting operation. For example, with the aid of the cutting system according to embodiments of the invention, the operator may perform a cut with a substantially constant depth. However, the control unit may also be able to control the depth of the cut such that the depth of the cut varies across the length of the cut. The variation in the depth of the cut may be preprogrammed or determined by the system during or prior to the cutting operation being performed. For example, the depth of the cut may be varied to cut or avoid cutting a structure, which may be detected by the OCT system.

[0042] During a cutting or other micro-manipulation operation, the subject of the operation may deform or move in response to the micro-manipulation tool being used. Accordingly, the control unit may also detect deformation of the subject of the cutting operation based on a signal from the OCT system. The deformation may result from movement of the subject, insertion of the cutting implement into the subject, or movement of the cutting implement along a length of a cut as a cutting operation is performed. Based on the detected deformation, the control unit can control the actuator to compensate for the deformation. In this way, the cutting operation can be performed according to desired criteria despite the deformation of the tissue.

[0043] According to some embodiments, the cutting system may have a position sensor attached to the tool body and arranged to detect a position of the shaft. The position of the shaft may be the position of a portion of the shaft relative to the position sensor, which can indicate the extent to which the shaft is extended from a motor or other portion of the actuator. Thus, the position sensor may be used to determine not only a current position of the shaft, but also how much room is left for the shaft to move in one or more directions. In some embodiments, the position sensor may be an encoder, including, for example, an optical coherence tomography-based encoder. However, other types of position sensors known in the art may also be used.

[0044] Using input from the position sensor, the control unit may control to actuator to move the shaft in certain ways. For example, the control unit can move the shaft to a reset position after a single cut is completed. In some embodiments, the control unit may communicate a warning signal when the shaft is at or near a limit of a range of motion of the shaft.

[0045] In some embodiments, the motion-compensated cutting system can include a measuring unit to measure a length of a cut performed by the cutting system. The measuring unit can be used in combination with the control unit and the actuator to control the position of the cutting implement as a function of the length of the cut. For example, the depth of the cut can be varied based on the length of the cut, or the cutting implement can be at least partially withdrawn after the cut reaches a certain length. In some embodiments, the measuring unit measures the length of the cut using speckle de-correlation. For example, speckle de-correlation can be used to determine a speed at which the optical fiber traverses the reference surface. This speed of the cutting operation can then be used to determine a distance by using a duration of the cutting operation.

[0046] Some embodiments of the current invention provide a method of performing a motion-compensated cutting operation. The method may include providing a cutting tool that has a tool body and a cutting implement attached to the tool body. A distal end of the cutting implement may be used to cut a surface, including tissue of a patient. The method also includes providing an optical coherence tomography (OCT) system having an optical fiber with a distal end fixed relative to the distal end of the cutting implement. The method further includes performing the cutting operation, and controlling a position of the cutting implement along a longitudinal axis of the cutting implement over a duration of the cutting operation. This controlling of the position is based on an input from the OCT system to perform a cut of a desired depth. The depth may be constant or variable over a length of the cut. In some embodiments, the method also includes controlling the position of the cutting implement to move the cutting implement in a repetitive back-and-forth motion along the longitudinal axis of the cutting implement. This type of control can be used to saw or puncture tissue.

[0047] In some embodiments, the control unit controls the actuator based on a closed-loop proportional-integral-derivative (PID) control algorithm. The control unit and the actuator may reduce or eliminate a change in the distance between the distal end of the optical fiber and the reference surface that would result from one or both of a motion of the reference surface and a motion of a hand of an operator of the tool body. The motion of the reference surface and the motion of the operator's hand may be voluntary or involuntary motion. The motion of the operator's hand may be, for example, a hand tremor of the operator. At the start of and during a micro-manipulation operation, the positioning of a tool element or cutting implement may be even harder to maintain for an operator without motion compensation. Accordingly, the control unit and the actuator may reduce or eliminate the change in the distance during the operation being performed. In some embodiments, the OCT system can monitor the position of the reference surface in real time.

[0048] Some of the embodiments of the current invention use a single fiber probe as a common-path optical coherence tomography (CP-OCT) distance sensor and a high-speed piezoelectric micro linear motor for one-dimensional actuation. The distance between the distal end of the tool element or cutting implement and the target surface may be determined from the OCT signal by, for example, an automatic edge-searching algorithm. The micro linear motor may be controlled by a computer, for example, according to feedback from the CP-OCT distance sensor.

[0049] In micro-surgery, a desired depth or position of the tool element within tissue may be known, and the tissue into which the tool element is inserted may include a variety of tissue layers and the tissue may be deformable. For example, the tissue may deform by a thickness of one or more layers changing when the tool element is inserted into or pressed against the material. The tissue may also deform by movement of the subject or the specific tissue itself. Accordingly, the optical detection system may detect deformation of the tissue resulting from at least one of movement of the tissue and movement of the tool element into or against the tissue. The control unit can control the actuator to compensate for the deformation of the tissue.

[0050] In some embodiments, the optical detection system uses common-path optical coherence tomography (CP-OCT). The optical fiber may include a bare single-mode fiber with a protective sheath. At least a portion of the single-mode fiber with the protective sheath may be parallel to a longitudinal axis of the tool element. In some embodiments, the tool element and/or the optical fiber may be detachable from a remainder of the motion-compensated micromanipulation system. Accordingly, the tool element and the optical fiber may be disposable. The type of optical coherence tomography (OCT) on which the OCT system is based may be, for example, one of swept source or time encoded frequency domain OCT, spatial domain or Fourier transform OCT, and frequency domain OCT. The OCT system may perform an imaging of the tissue or other reference surface via OCT during one or more of before, during, and after performance of the micro-manipulation. The imaging during and after the micro-manipulation may include determining a result of the micro-manipulation, such as, for example, a depth or length of a cut achieved by a cutting operation.

[0051] The actuator of the micro-manipulation system according to some embodiments may include a lead zirconium titanate (PZT) motor and a rod to which the tool element is directly or indirectly fixed. The PZT motor can thus drive the rod to move the tool element. A user-operable mechanism or input may also be included for selectively turning on and off at least one of the actuator and the OCT system. "Turning on and off may include, for example, controlling when the actuator is able to change the position of the tool element.

[0052] Some embodiments of the current invention can be integrated into standard freehand micro-surgical instruments and can enable surgeons to make precise micro-manipulations, such as cuts or incisions, safely and effectively.

[0053] The systems and methods described above may apply to micro-manipulations involving biological material, such as human tissue, but the systems and methods are not limited thereto. For example, the micro-manipulations may be for any object or system for which motion-compensated manipulation can be useful.

[0054] Figs. 1 -3 show examples of a tool body and cutting implement of a motion-compensated cutting system according to an embodiment of the current invention. The motion-compensated cutting system 100 has a tool body 102 that has a size and shape allowing handheld use and manual control by an operator of the system. A cutting implement 104 is attached to an actuator made up of a shaft 108 and a motor 106. In some embodiments, the cutting implement 104 may be detachable from the shaft 108. Although Figs. 1-3 shows an example of a cutting system, a motion-compensated system having a different tool element in place of the cutting implement 104 could be used with the tool body 102 shown in Figs. 1 -3. In these other embodiments, the control unit (not shown) may be programmed to achieve desired performance characteristics depending on the type of tool element in use and the specific micro-manipulation being performed.

[0055] Fig. 4 shows a schematic of a motion-compensated micro-manipulation system according to an embodiment of the present invention. According to various embodiments, the micro-manipulation system 200 shown can be for the cutting system 100 shown in Figs. 1-3, or some other micro-manipulation system. The micro-manipulation system 200 includes a tool element 204 attached to the shaft 108, which is actuated by the motor 106. An optical coherence tomography (OCT) system 110 is shown that includes an optical fiber 112 and an OCT source 114 (e.g., a laser). As one example, a laser having a 1.3 μιη wavelength from AXSUN

Technologies, Inc. has been used as the OCT source 114 in an embodiment. The optical fiber 112 has a distal end 113 that is a fixed distance from a distal end 205 of the tool element 204. A sheath 116 surrounds at least a portion of the optical fiber 112. Light from the OCT source 114 may be fed through a circulator CIRi (from port 1 to port 2) on the way to the distal end 113 of the optical fiber 112. A signal then returns from the sample 126 that is the subject being imaged or detected by the OCT system 110. The return signal may be fed through the circulator CIR2 (from port 2 to port 3) on its way to a detector 130. The detector 130 may be, for example, an unbalanced detector. The OCT system 110 may also include a polarized controller PC and couplers 122, 124, as shown in Fig. 4. A signal from the detector 130 may then be transmitted to a controller 128. The controller 128 can send signals to the motor 106 via a wired or wireless connection. Based on the signal received from the OCT system 110, the controller may determine a distance ΔΖ between the distal end 113 of the optical fiber 112 and the reference surface S. Correspondingly, because the distal end 113 of the optical fiber 112 is fixed relative to the distal end 205 of the tool element 204, the controller 128 may also determine a depth of or distance between the distal end 205 of the tool element 204 with respect to the subject 128. In this way, the controller 128 may determine a depth of a cut or incision made by a cutting implement, for example.

[0056] As shown in Fig. 4, the micro-manipulation system 200 may also include a position sensor 118. In some embodiments, the position sensor 118 can be an OCT-based encoder, or some other mechanical or electromagnetic encoder or other position sensor. The position sensor 118 can detect a position of the shaft 108. A signal from the position sensor 118 may then be transmitted to the controller 128 so that a position of the shaft 108 is Icnown to the controller 128.

[0057] A micro-manipulation system according to embodiments of the invention can perform GPU signal processing and CPU data streaming in real time in order to perform real time control of the micro-manipulation system based on input from the OCT system.

[0058] In some of the embodiments described above and shown in the figures, the optical fiber 112 is attached to the cutting implement 104 or tool element 204. However, embodiments of the invention are not limited to such a configuration. For example, the optical fiber 112 may be mounted onto some portion of the tool body 102 or arranged in some other manner so as to be a fixed distance from the distal end 205 of the tool element 204.

[0059] According to some embodiments, the controller 128 may include, for example, a data processor, software, or a combination of hardware and software. The controller 128 can be a dedicated "hard-wired" device, or it can be a programmable device. For example, it can be, but is not limited to, a personal computer, a work station or any other suitable electronic device for the particular application. In some embodiments, it may be integrated into a unit or it could be attachable, remote, and/or distributed.

[0060] In some embodiments, the controller 128 is further configured to determine an amount, speed and/or direction of movement of the tool element 204 to be moved by the shaft 108 and motor 106 to counter motions of the distal end 205 of the tool element 204 relative to a reference surface S of the tissue or other object of the micro-manipulation.

[0061] In some embodiments, the OCT system 110 can have a light source comprising a superluminescent light emitting diode. In some embodiments, a spectrometer can be used as an optical detector of the OCT system 110. In other embodiments, the light source can be a wavelength swept laser and the optical detector can be a photodetector. The broad concepts of the current invention are not limited to these particular examples.

[0062] Fig. 4 shows a laser as the OCT source 114 for the OCT system 110, according to one embodiment of the present invention. The laser may be optically coupled to the optical fiber 112. As discussing above, an OCT signal can sent back through the optical fiber 112 from the tissue or other sample 126, and circulated through the circulator CIRi to the unbalanced detector 120, passing a polarized controller PC and a coupler 124. For example, the couplers 122, 124 can be 2x2 couplers, as shown in Fig. 1. The optical fiber 112 may provide a common transmit and receive optical path such that the OCT system is a common-path optical coherence tomography system (CP-OCT).

[0063] In addition, as shown in Fig. 4, a second optical fiber 138 can be coupled to the OCT source 114 for use with the position sensor 118, where the position sensor 118 is OCT-based. The signal from the position sensor 118 can be sent through a circulator CIR2 on the signal's way from the OCT source 114 to the position sensor 118, and as the signal travels from the position sensor 1 18 to the unbalanced detector 130.

[0064] The following provides some examples according to some embodiments of the current invention. The general concepts of the current invention are not limited to these particular examples that are provided to explain concepts of the current invention.

EXAMPLES

[0065] The following examples relate to a micro-surgical blade integrated with a common-path swept-source optical coherence tomography (CP-SSOCT) based system for high-precision cutting control. In these examples, the blade was connected to a linear motion motor to provide an accurately and precisely controlled up and down cutting motion with accuracy on the order of 10 μιη during freehand use. In this study, the cutting motion was controlled by a CP-SSOCT sensor driven PZT motor with a step resolution of <5 μη , which concurrently reduces the hand tremor transmitted to the tip of the instrument by the surgeon. The present embodiment uses a closed-loop proportional-integral-derivative (PID) control algorithm based on graphics processing unit (GPU) processing and an analysis rate of up to 500 Hz. A motion-compensated high-precision surgical blade using a fiber optic distal sensor to monitor, in real time, the relative position between the blade tip and the tissue surface was demonstrated. The linear motion motor controlled the blade tip position based on the OCT sensor input to rapidly compensate for unwanted tissue and hand motions providing precise control of the blade cutting depth and motion. The sensor-servo loop in the present example was capable of 500 Hz monitoring and blade position adjustments. Future embodiments may be capable of more rapid processing and instrument response.

[0066] The design of the system used in this example is shown in Figs. 1-3. The examples in Figs. 1-3 have a 12-degree beveled tip. However, the blade tip is not limited in size or shape. Additionally, the embodiment of this example used a piezoelectric motor (LEGS-L01 S-l 1, PiezoMotor) and a commercial small gauge syringe needle (in the present prototype, 25-gauge or smaller or other microblade). A lure-lock hypodermic needle set-up was designed for easy replacement with the front holder and motor shaft. The piezoelectric motor used in this prototype had a maximum speed of 20 mm/s, maximum stroke of 55 mm, maximum force of 6.5 N, and a resolution of less than 1 nm. The front holder had enough inner space to allow the inner needle to move back and forth 12 mm. The tool's overall length was 108 mm excluding the surgical needle and weighed about 0 g, including the motor weight of 20 g.

[0067] The basic performance of the fiber optic sensor driven handheld microsurgical blade of this example was evaluated. Figs. 5 and 6 show OCT images of a clean micro-incision site as performed by the smart blade. Specifically, Fig. 5 shows an OCT image of an incision 132 made

by a motion-compensated cutting system according to an embodiment of the current invention. The field of view of the image is about 2 mm x 2 mm. Fig. 6 shows a cross-sectional OCT image of an incision 132 made by the motion-compensated cutting system according to an embodiment, with a scale bar of 300 μιη.

[0068] Figs. 7 and 8 compare freehand and compensated blade positions while cutting, and also their frequency analyses up to 15 Hz over a 10 second period, at different incision angles. The incision mode of the smart blade was assessed and its performance was analyzed by measuring the tool tip position using a dual fiber-optic OCT distance sensing scheme. The graph in Fig. 7 shows experimental data of the cutting depth according to a non-motion-compensated cutting operation and various motion-compensated operations of the cutting depth at different incision angles as an example according to an embodiment of the current invention. The angle is the angle at which the cutting implement is positioned with respect to the surface being cut. The graph in Fig. 8 shows results from a non-motion-compensated result and various motion-compensated results. The position of the cutting implement is shown using a Fourier analysis for operations performed at different incision angles and for the freehand example.

[0069] Fig. 9 shows an example of a control process used in a motion-compensated cutting system according to an embodiment of the current invention. The PID control algorithm was employed to adaptively move the rod of the PZT motor that is connected to the cutting implement used for cutting tissue. The difference between a target position of the distal end of the cutting implement and the detected OCT peak is called error, e(t). The PZT motor controls the motion of cutting implement to compensate the error so as to consistently maintain the desired depth of the cutting implement. The control output of the PZT motor can be described by the following equation:

u(t) = Kpe(t) + Ki H e(s)ds + Kd de(t)/dt (1)

where Kp, Ki and Kd are the proportional gain, integral gain and derivative gain, respectively. The above parameters are adjusted based on experience and RSME. These parameters are different from the values obtained for active tracking in air space since the tissue damping effects have an impact on the performance of the PID controller. A block diagram of PID control for distance maintaining is illustrated in Fig. 4. The output is converted into the control voltage and compensation frequency of the PZT motor.

[0070] A distance between the tissue and optical fiber tip can be maintained by a real-time feedback PZT motor with a resolution of ~5 μηι (or less than 5 μηι), which also dramatically reduces hand tremor, using a closed-loop PID active control algorithm.

[0071] Figs. 10 and 11 show close-up views of an example of a motion-compensated micromanipulation system according to an embodiment of the current invention. In Fig. 10, the tool body includes two separate pieces 102, 103, with a space between 102 and 103 that shows the arrangement of the position sensor 118 and shaft 108. The optical fiber 112 is fed through a portion of the tool body 102 so that the distal end 113 of the optical fiber 112 emerges near the tool element 204. Fig. 1 1 shows the micro-manipulation system with the portion 102 of the tool body removed to expose the base of the tool element 204 and how it is connected to the shaft 108.

[0072] Fig. 12 shows a result of signals from an OCT-based position sensor and an OCT sensor connected to the optical fiber 112 that is fixed relative to the distal end of the tool implement 204 according to an embodiment. An offset can be seen between the signal 134 from the optical fiber 112 and the sensor 136 from the position sensor that detects the location of the shaft 108.

[0073] Fig. 13 shows an example of an operator using a handheld, motion-compensated cutting system according to an embodiment of the invention.

[0074] To detect the interface between tissue and air, an effective peak detection algorithm is critical to determining the peak position of the OCT A-line signal coming from the interface. The interferometric CP-SSOCT sensor signal at position Δζ after Fourier transform can be described as follows:

7(2ηΔζ) = (p/2e)Sqrt(PrPs)Rs L(2nAz)exp(i2k0n5z) (2)

where n is the tissue refractive index, p is the detector responsivity, and e is the electronic charge. Pr and Ps are the reference and sample power, respectively. Rs is the sample reflection coefficient; L(2nAz) is the normalized-amplitude mutual coherence function; the last term is phase related to central wave number kO, n and fractional imaging depth. The above equation shows that the OCT signal has a peak value at the air-tissue interface since Rs is at a maximum at this location. Simple maximum value peak detection works very well for dry phantoms or less scattering biological tissue. However, it introduces high root mean square error (RMSE) of 30~50μιη for wet or otherwise strong scattering biological tissue. To reduce the false alarm rate of peak detection caused by the random speckle noise in turbid media, the mass center of local peaks was calculated to suppress the impact of strong speckle signals scattering back from the deeper layers of the tissue. Here it was assumed that peak OCT signal is the interface between the tissue and air. This mass center algorithm significantly improves the performance for accurate peak detection with a root mean square (RMS) of 2-3 μιη for still strongly scattering biological tissue with a performance enhancement at least 10 times that of the simple peak maximum value detection algorithm.

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[0107] The embodiments illustrated and discussed in this specification are intended only to teach those skilled in the art how to make and use the invention. In describing embodiments of the invention, specific terminology is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology so selected. The above-described embodiments of the invention may be modified or varied, without departing from the invention, as appreciated by those skilled in the art in light of the above teachings. It is therefore understood that, within the scope of the claims and their equivalents, the invention may be practiced otherwise than as specifically described.