Robot-ultrasound probe for transrectal and transperineal prostate biopsy

Abstract

Rather than retrofitting an ultrasound probe, the present invention is directed to a novel cohesive ultrasound-robotic probe that enables a novel needle insertion path. The tissue-ultrasound probe contact frequently deforms the prostate gland inducing MRI fusion errors. To minimize deformations, the probe of the present invention uses a side-fire probe and robotic rotation about its axis to scan the prostate in 3D. An additional robotic angulation of the needle allows targeting any gland location. Only 2 degrees-of-freedom are required for prostate biopsy. However, the probe and robot must allow clearance to angle the needle, thus a special probe and Remote-Center-of-Motion (RCM) robot kinematics were developed.

Description

ROBOT-ULTRASOUND PROBE FOR TRANSRECTAL AND TRANSPERINEAL PROSTATE BIOPSY CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U. S. Provisional Application No. 63 / 724.029, filed November 22, 2024. The content of the aforementioned application is herein incorporated by reference, in its entirety..FIELD OF THE INVENTION

[0002] The present invention relates generally to medical devices. More particularly, the present invention relates to a robot-ultrasound probe for transrectal and transperineal prostate biopsy.BACKGROUND OF THE INVENTION

[0003] There has been a resurgence of prostate cancer (PCa) incidence in the United States (US) with a steady 3% yearly increase since 2015, and with 299,010 new cases and 35,250 deaths in 2023. PCa is the most commonly diagnosed type of cancer and the second leading cause of cancer related death among US men. Efforts to address the rise in PCa diagnosis without over detection and overtreatment include more targeted biopsy techniques for clinically significant PCa (csPCa) using magnetic resonance imaging (MRI) and precision targeted biopsy.

[0004] The best estimate of PCa aggressiveness is the Gleason score obtained from core needle biopsy. The most common biopsy method is freehand transrectal ultrasound (TRUS) guided biopsy. Since ultrasound suffers from poor sensitivity and specificity for PCa localization and detection, systematic biopsy (SB) intends to obtain tissue that provides a representative sample of the overall gland. However, freehand biopsy is highly inconsistentand subjective, leaving large regions of the prostate unsampled and missing csPCa. Targeted biopsy (TB) emerged in response to the shortcomings of the SB. Multiparametric or biparametric MRI that shows cancer suspicious regions is registered (fused) with real-time transrectal ultrasound (TRUS) to guide the biopsy with improved detection of csPCa.

[0005] Still, TB cores often miss csPCa that are detected by the SB cores possibly due to the manual targeting errors and fusion errors between MRI and TRUS. In addition, csPCa may evade MRI detection. As such. SB cores are typically sampled in addition to TB cores in the same TB+SB procedure.

[0006] Guided by TRUS imaging, the needle path may be transrectal (TR) or transperineal (TP) with the latter potentially reducing infectious complications. Studies could not yet show a difference in the infectious or noninfectious complications between these approaches, nor in terms of csPCa detection rates. Both biopsy approaches remain clinically viable and safe, but the TP approach has gained popularity especially in Europe

[0007] Ultrasound probes are commonly operated manually. The probe is known to deform the prostate gland due to uneven pressures exerted by the probe. Deformations cause image artifacts that complicate fusion with MRI resulting in co-registration and targeting errors. In addition, manual probe handling results in significant inter- and intra-urologist variability.

[0008] Currently available fusion biopsy devices include the Artemis (Eigen), BioJet (DK Technologies), BiopSee (MedCom), RVS (Hitachi / FujiFilm), UroNav (Philips), bkFusion (BK Medical), Navigo (UC Care), FocalBx (Focal Healthcare), and UroStation (Koelis). Large inter- and intra-urologist PCa detection rates (CDR) variability (12%-57%) exists, suggesting that urologist’s training and skills remain critical even with existing technological advances. Robotic ultrasound provides hands-free probe operation to a skill-independentprocedure potentially reducing variability among urologists. Only one commercial biopsy robot exists, Mona Lisa (BioBot Surgical, Singapore), and predominantly requires anesthesia in an operating room setting.

[0009] It would therefore be advantageous to provide a robot-ultrasound probe configured for transrectal and transperineal prostate biopsy.SUMMARY OF THE INVENTION

[0010] The foregoing needs are met, to a great extent, by the present invention, wherein one aspect is a device including a probe. The probe includes a linear side-fire array configured for ultrasound. A shape of the probe is configured to allow for transrectal and transperineal biopsy paths. A needle-guide adapter of the device is configured for transrectal or transperineal biopsy paths by shifting a pivot point of the needle-guide adapter. The device also includes a robot configured for control of the probe.

[0011] In accordance with an aspect of the present invention, the device includes a metallic rib configured to augment the structural integrity and stiffness of the probe The device includes a metallic mount that attaches magnetically to the robot. The robot can take the form of remote center of motion mechanism (RCM). The RCM can take the form of a cable- driven compact RCM.

[0012] In accordance with another aspect of the present invention, a device includes a remote center of motion mechanism (RCM). The RCM is configured to rotate an instrument about a principal axis of the instrument, wherein the principal axis of the instrument is a longitudinal axis of the instrument. The instrument can take the form of a slender instrument.

[0013] In accordance with an aspect of the present invention, the device can include imaging to provide a rotary scan with side-fire to minimize gland deflections. A right angle (cable) transmission can be used to orient the motor along principal axis of device, to save space. The shaft of the probe can be split to make room for a needle. Structural elements can be included within the ultrasound probe. For instance, half of the probe shaft can be filled to bring it back to a round shape. Magnetic support for an ultrasound probe can be provided. A microphone can be included in the device. A passive adjustable slide support in the direction of the probe, with lock can also be included.

[0014] In accordance with an aspect of the present invention, a system includes a probe. The probe comprises a side-fire, linear array configured for ultrasound. A shape of the probe is configured to allow for transrectal and transperineal biopsy paths. The system includes a needle-guide adapter. The needle-guide adapter is configured for transrectal or transperineal biopsy paths by shifting a pivot point of the needle-guide adapter. The system includes a robot configured for control of the probe. The robot includes a remote center of motion mechanism (RCM). The RCM is configured to rotate an instrument about a principal axis of the instrument. The principal axis of the instrument is a longitudinal axis of the instrument.

[0015] In accordance with an aspect of the present invention, a metallic rib is configured to augment the structural integrity and stiffness of the probe. The system includes a metallic mount that attaches magnetically to the robot. The needle-guide adapter couples to the probe. The probe includes a shape configured to accommodate for a path of a needle, as a path of the needle is defined by the needle-guide adapter. The needle-guide adapter defines an oblique path with respect to the probe for a needle passing through the needle-guide adapter. The needle-guide adapter defines a transrectal path for a needle passing through the needle-guideadapter. The needle-guide adapter defines a transperineal path for a needle passing through the needle-guide adapterBRIEF DESCRIPTION OF THE DRAWINGS

[0016] The accompanying drawings provide visual representations, which will be used to more fully describe tire representative embodiments disclosed herein and can be used by those skilled in the art to better understand them and their inherent advantages. In these drawings, like reference numerals identify corresponding elements and:

[0017] FIG. 1 A illustrates a schematic diagram of prostate deformation with atypical endfire probe. FIG. IB illustrates a three-dimensional (3D) rendering of a prostate based on individually deformed two-dimensional (2D) images.

[0018] FIGS 2A and 2B illustrate schematic views of a side-fire linear array and oblique needle path of a probe of the present invention. FIG 2A illustrates a transrectal needle path and FIG. 2B illustrates a transperineal needle path.

[0019] FIGS. 3A and 3B illustrate perspective views of a probe, according to an embodiment of the present invention. FIG. 3A illustrates a perspective view of a geometry of the probe that clears space to angle a needle for biopsy. FIG. 3B illustrates a perspective view of a metallic rib structure included within the probe for structural stiffness.

[0020] FIGS. 4 A and 4B illustrate perspective views of a probe and a remote center of motion (RCM) mechanism used to rotate the probe, according to an embodiment of the present invention

[0021] FIGS. 5 A illustrates a perspective view of a needle-guide actuation mechanism (R2), according to an embodiment of the present invention. FIG. 5B illustrates a perspective view of a needle-guide driver mechanism.

[0022] FIG. 6A illustrates a perspective view of a transrectal biopsy configuration of a device according to an embodiment of the present invention. FIG. 6B illustrates a perspective view of a transperineal biopsy configuration of a device according to an embodiment of the present invention.

[0023] FIGS. 7A-7E illustrates views of a setup for biopsy with patient in left-lateral decubitus position.

[0024] FIG. 8 illustrates perspective views of a setup for biopsy with patient in left-lateral decubitus position, using a device according to an embodiment of the present invention.

[0025] FIGS. 9 A And 9B illustrates a perspective view’ of a device according to an embodiment of the present invention and a control box, respectively.

[0026] FIGS. I0A-I0C illustrate perspective and image views of a 3D scan and needle targeting tests. FIG. 10A illustrates a perspective view of a setup. FIG. 10B illustrates an image view of a scanned grid of strings. FIG. 10C illustrates a perspective view of a needle point at target on the grid crossings.

[0027] FIGS. II A- 11C illustrate perspective and image views of a needle targeting in a prostate mockup with a TP adapter.

[0028] FIGS. 12A-12C illustrate views of needle guides for transrectal biopsy, as illustrated in FIG. I2A. and transperineal biopsy, as illustrated in FIG. 12B. FIG. 12C illustrates a device of the present invention in a Trophon HDL machine.

[0029] FIGS. 13A-13C illustrate image views of a device of the present invention, and views of the resultant ultrasound images from the device of the present invention.DETAILED DESCRIPTION

[0030] The presently disclosed subject matter now will be described more fully hereinafter with reference to the accompanying Drawings, in which some, but not all embodiments of the inventions are shown. Like numbers refer to like elements throughout. The presentlydisclosed subject matter may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Indeed, many modifications and other embodiments of the presently disclosed subject matter set forth herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains having the benefit of the teachings presented in the foregoing descriptions and the associated Drawings. Therefore, it is to be understood that the presently disclosed subject matter is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims.

[0031] Over the past decade the incidence of prostate cancer (PCa) has been on a steady increase. Efforts to improve PCa outcome include targeted biopsy with magnetic resonance imaging (MRI) and precision sampling. Several biopsy devices are currently available to guide biopsy with MRI-ultrasound fusion. These devices commonly use generic handheld ultrasound probes retrofitted for fusion biopsy. Robotic probe manipulation has the potential to reduce training, skill, and outcome variability among urologists.

[0032] Rather than retrofitting an ultrasound probe, the present invention is directed to a novel cohesive ultrasound-robotic probe that enables a novel needle insertion path. The tissue-ultrasound probe contact frequently deforms the prostate gland inducing MRI fusion errors. To minimize deformations, the probe of the present invention uses a side-fire probe and robotic rotation about its axis to scan the prostate in 3D. An additional robotic angulation of the needle allows targeting any gland location Only 2 degrees -of-freedom are required for prostate biopsy However, the probe and robot must allow clearance to angle the needle, thus a special probe and Remote-Center-of-Motion (RCM) robot kinematics were developed.

[0033] Pre-clinical tests showed targeting errors below 0.5mm and have validated the sterilization process. Transrectal prostate biopsy was successfully performed in two patients. Therefore, the probe of the present invention is a novel device for prostate biopsy (robotic, simple, compact, precise) with a successful pilot clinical evaluation. A precision, skill independent biopsy device can impact the management of PCa.

[0034] The present invention is an entirely new device that aims to improve the technology used for prostate biopsy with a novel multifunctional, robotic, simple and compact, skill independent, precise, and cost-effective solution for medical centers as well as clinics in a low resource setting, FIG. 1 A illustrates a schematic diagram of prostate deformation with a typical end-fire probe, FIG. IB illustrates a three-dimensional (3D) rendering of a prostate based on individually deformed two-dimensional (2D) images.

[0035] As illustrated in FIG. 1 A, transrectal (TR) prostate biopsy is typically performed with an end-fire TRUS probe and the needle path parallel to the prostate. To image, the probe must maintain acoustic coupling in contact with the prostate (air gaps prevent imaging). In a human hand, the contact pressure is variable, resulting in variable prostate deformations that are captured in each image. When the probe is moved about the prostate for a 3D scan, these local deformations are captured in all images, and so the 3D rendering shows a global deformation. As illustrated in FIG. IB, the prostate appears deformed on the entire sweep trajectory of the scan as shown in the unrealistic valley shape on the posterior face of the gland. A realistic deformation with the point of the probe would have a crater shape, not a valley. The scan artifact skews the gland shape, volume, and the location of TB from the fused MRI. A biopsy plan made on skewed images is geometrically inaccurate.

[0036] Elastic registration methods attempt to correct deformation errors, but the models used are not patient specific. Meta-analyses comparing rigid vs. elastic registration identified no significant difference between them at detecting csPCa, thus questioning their utility. Moreover, elastic registration is often only performed an initial co-registration, but not at biopsy sampling when additional deformations appear. Prostate deformations impact fusion, TB. and SB targeting accuracy. Because correcting prostate deformations is a problem, preventing and minimizing deformations becomes essential for accurate biopsy.

[0037] FIGS. 2A and 2B illustrate schematic views of a side-fire linear array and oblique needle path of a probe of the present invention. FIG. 2A illustrates a TR needle path and FIG, 2B illustrates a transperineal (TP) needle path. Both TR and TP needle paths can be achieved with the same probe. The ultrasound probe 10 of the present invention uses a linear side-fire array 12, and a path of the needle 14 is oblique, not parallel, to the probe 10. To scan in 3D, the probe 10 is rotated about its axis (Ri) to acquire multiple TRUS slices throughout the gland. Biopsy points selected in the image are then targeted by rotating the probe 10 about Ri and angulating the needle 14 about R2. The rotation of the probe 10 about Ri does not change the compression of the prostate, and so the shape of the gland is preserved throughout image scanning and needle targeting. These improvements should contribute to precise fusion and image-based biopsy targeting.

[0038] The same kinematic principle applies to the TR and TP needle paths. FIG. 2A illustrates the TR path, where the pivot point 16 of the needle 14 is close to the probe 10. For the TP path, the pivot point 16 is shifted close to the perineal site, as illustrated in FIG. 2B Both of the TR and TP paths can be achieved with the same probe. As such, the same Ri, R2 rotations allow TR or TP biopsy. The configuration can be changed simply by using different needle-guide adapters, described further herein with respect to FIGS. 12A and 12B.

[0039] However, in either approach, the specially designed probe of the present invention is needed to avoid the interference of the angled needle with the body of the probe 10 (with a regular probe the dotted part of the needle in FIGS. 2A and 2B interferes with the body of the probe).

[0040] FIGS. 3A and 3B illustrate perspective views of a probe, according to an embodiment of the present invention. FIG. 3 A illustrates a perspective view of a geometry of the probe 10 that clears space to angle a needle for biopsy. FIG. 3B illustrates a perspective view of a metallic rib structure 18 included within the probe for structural stiffness. The probe 10 clears space to angle the needle with an offset shaft and body of the probe 10, as illustrated in FIG.3 A. A metallic rib 18 is included within the probe to augment the structural integrity and stiffness of the probe over the narrower “half’ part of the shaft, as illustrated in FIG. 3A. In operation, needle adapters are placed over the half-shaft and attach to the mounts. Moreover, common ultrasound probes are difficult to mount precisely and repeatedly in a robotic / fusion device because their bodies are designed for manual operation and have uneven geometry Instead, the probe 10 of the present invention includes a metallic mount 20 that attaches magnetically to the robot and two positioning pins for quick and precise attachment, all attached to the internal metallic rib 18, as illustrated in FIG. 3B. The magnetic and pin attachment works over a sterile bag.[00411 Furthermore, common rotation mechanisms are physically’ located on the axis of rotation. If used to rotate the probe, the mechanism would have to be located further away from the tail of the probe, enlarging size and reducing the stiffness of the device (i.e. probe mount about the tail in the Artemis, Eigen biopsy device).

[0042] FIGS. 4A and 4B illustrate perspective views of a probe and a remote center of motion (RCM) mechanism used to rotate the probe, according to an embodiment of the present invention. Instead, to clear the space for the needle in a compact size, the probe 10 ofthe present invention uses a robotic control mechanism 22 having Remote Center of Motion (RCM) mechanism, illustrated in FIGS. 4A and 4B. The cable-driven compact RCM mechanism is paired with a new harmonic drive actuation. FIG. 4A also shows the magnetic mount base 20 of the probe.

[0043] Rotary mechanisms are commonly centered on the rotation axis. To clear space for the needle, the rotary mechanism would need to be placed distally, further away on the probe tail. To reduce size and improve stiffness, the present invention uses a cable-driven compact RCM mechanism with a new hamionic drive actuator. In FIG. 4B, seven superimposed positions of the mechanism (-90° to 90° in 30° steps) show how the probe is rotated about its axis by the RCM.

[0044] FIGS. 5 A illustrates a perspective view’ of a needle-guide actuation mechanism (R2), according to an embodiment of the present invention. FIG. 5B illustrates a perspective view of a needle-guide driver mechanism. The angulation of the needle (R2) is implemented with a 4-bar 1 degree-of-freedom (DoF) mechanism comprising the needle-guide, a connecting link, and an arm connected to a driver, as illustrated in FIG. 5 A. To minimize size at this close to patient location, the motor is oriented along the probe axis and used a cable transmission over pulleys and a spool driven by the motor (see driver detail illustrated in FIG. 5B). The driver also includes a ball-type lock for simple connection / release of the needle-guide arm (sterile components). The same driver is used in both the TR and TP applications. In another embodiment, the needle guide driver uses a womi mechanism, with the worm-gear spinning the needle and the worm actuated by the motor.

[0045] FIG. 6A illustrates a perspective view7of a transrectal biopsy configuration of a device according to an embodiment of die present in\ ention. FIG. 6B illustrates a perspective view of a transperineal biopsy configuration of a device according to an embodiment of the present invention. As shown schematically in FIGS. 6A and 6B. choosing the TR or TP applicationcan be simply achieved by shifting the pivot point of the needle-guide. To use the same driver, the entire needle-guided mechanism consisting of the 4-bar linkage and dnver mechanism is shifted. For the TR approach, the driver is fixed in place, as illustrated in FIG.6A. For the TP approach, the needle-guide mechanism is slightly raised and adjusted along the probe axis to account for patient variability’ in the location of the perineum, as illustrated m FIG. 6B. The needle-guide pivot is connected to the driver with a link. Adjusting the location of the driver also adjusts the pivot, and both are locked in place with the lever lock (see 4 arrows). Both needle adapters include a semicircular body that fills the opposite side of the probe shaft, to be round about the rectal sphincter, described further with respect to FIGS.12A and 12B.

[0046] In image-guided interventions, image-to-robot registrations are normally performed for every7case. An advantage of coupling an ultrasound probe with a robot (or position tracker in fact) is that the registration of their spaces is invariant and set by a one-time calibration procedure. A simple calibration rig with holes that guide a string (036mm) was made for calibration is illustrated in FIG. 6C. The rig attaches to the probe. In a water tank the strings appear as dots in ultrasound. Their image and known positions are used to measure the scale and position of the linear array relative to the probe and therefore robot.

[0047] If the holes and string have the same diameter, the string is difficult to pass through, and so the holes should be made larger. But then the string is no longer centered on the hole making it inaccurate as a marker. FIG. 6D shows how larger holes were offset by design in the opposite direction of winding the string, so that the string is at the correct location when set tangent to the left or right of the holes by tightening it.

[0048] With the present invention, a 3D scan is performed by sweeping the prostate gland side-to-side with parasagittal 2D ultrasound from the side-fire array. Image-position pairs arerecorded while rotating the probe about its axis (Ri) and recording images and their respective angles from the axis encoder. Pixel-size calibrated images may then be represented in place in 3D based on the angles and kinematic robot parameters, and then rendered volunietrically. A point selected in the image is already in robot coordinates, ready to target. At biopsy, there is no longer a need to register the robot to ultrasound.

[0049] Ultrasound images from the side-fire probe are oriented radially on the axis of the rotary scan. Therefore, image pixels distal from the axis are less dense in 3D. The speed of the rotary scan is calculated based on the desired 3D resolution p[mm] at a radius R[mm] measured from the probe axis, as:Fi=180 / ) / ((^'?)) [° / s|where f is the framerate of the image acquisition |frames / s] and is set and typically limited by the ultrasound machine. The pixel-size calibrated images are represented in place in 3D based on the angles where they were acquired, kinematic robot parameters, and then rendered volumetrically. As such, a point selected in ultrasound is already in robot coordinates, ready to target,

[0050] FIGS. 7A-7E illustrate views of a setup for biopsy with patient in left-lateral decubitus position. The present invention uses image navigation methods and software. The fusion uses a novel anatomic landmark approach, the Prostate Coordinate System (PCS). The landmarks are the apex and base of the prostate. FIG. 7 shows the apex (A) and base (B) in a central sagittal view of the gland A and B selection follows several refinement steps: 1) Select A and B points in original ultrasound slices; 2) Refine their locations in reconstructed axial slices and orient the Anterior-Posterior direction; 3) Refine the A and B location m a coronal view; 4) and then in sagittal, rhe origin of the PCS is located at the center of the ABsegment and the direction of the PCS follows the standard LPS (Left, Posterior, Superior) anatomic system of the DICOM standard.

[0051] The PCS enables segmentation in axial, sagittal, and coronal views thus circumventing the common difficulty of segmenting the ends of the prostate in just one view. A wireframe prostate model that is similar to Earth’s longitude and latitude coordinates is used, with the North and South poles at the apex (A) and base (B), as shown in FIGS. 7A-7E. The model includes 26 (2+3*8) control points that are automatically placed and refined by a physician m all 3 views.

[0052] Ahead of the biopsy procedure, the PCS and segmentation are completed on the MR1 of the patient, together with defining the TB targets. At biopsy, the PCS is set in 3D ultrasound. MRI-ultrasound fusion is done by simply superimposing the PCS from MRI to that of ultrasound. This also fuses the segmentation and TB targets. The alignment may be manually adjusted. For the systematic biopsy (SB) cores, both TRUS-Robot and the present invention use a unique optimization method that personalizes the plan for the patient based on a "capsule model”.

[0053] FIG. 8 illustrates perspective views of a setup for biopsy with patient m left-lateral decubitus position, using a device according to an embodiment of the present invention. The robot and probe of the present invention are supported by an adjustable passive arm, as illustrated in FIG. 8. Fine axial adjustment of the probe can be made from a slider and lock mechanism. Its translational axis is aligned with that of the probe, allowing the probe to be manually inserted or retracted without losing the scan-time registration, for the initial setup or should a patient move during the procedure.

[0054] The schematic in FIG. 8 shows a man in the usual left lateral decubitus position for TR biopsy. The probe is placed manually, positioned to show a central sagittal image of the prostate, and then the Support Arm is locked in place. All subsequent operation of the probeis robotic. To scan in 3D, 2D image slices are acquired with an Ri rotary scan together with their frame positions from the robot's Ri axis encoder to render the 3D volume image. A biopsy plan is made including MR1 fusion and personalized biopsy planning. For each biopsy site, the robot automatically rotates the probe (Ri) and angulates the needle-guide (R2) to align the needle-guide on target. A urologist inserts the needle and takes the biopsy through the needle-guide and under live ultrasound feedback. A microphone included within the base of RCM listens for the biopsy needle firing sound and automatically saves the ultrasound of the fired needle.

[0055] A IP biopsy follows similarly with the exception that in the onset stage one or two skin incision are made, the TP adapter is manually advanced until the point of the needle¬ guide is placed at the incision with the pivot near the skin, and the driver is locked in place with the lever. The patient may be in the lithotomy position common for TP; however, the invention size and simplicity may facilitate a left-lateral decubitus positioning approach.

[0056] The results presented herein are the result of substantial research over several years The initial invention of a cohesive robot-ultrasound probe was derived from an MRl-guided robot. A first invention prototype was then built, preclmically tested, and showed outstanding performance.

[0057] FIGS. 9 A and 9B illustrates a perspective view of a device according to an embodiment of the present invention and a control box, respectively. FIG. 9A shows the prototype and lists the components described in previous sections. Parts were manufactured with Computer Numerically Controlled (CNC) machines and 3D printing (FormLabs Inc., Somerville, MA). The probe was built with an ultrasound linear array EUP-U533 (Hitachi Medical Systems). The robot has a small size and weighs only 1.3Kg together with the probe.

[0058] Dedicated robot control electronics were built using EPOS controllers (Maxon Motor Ltd.) to communicate to a PC over USB. The two motors of the axes are electronicallycommutated (EC) motors (Maxon 329041). In addition to their power / size performance, their 3-channel encoders offer fail-safe operation (unlike quadrature encoders) and so redundant encoders were not used.

[0059] The robot control box is shown in FIG. 9B. Safety features include a specialized watchdog, emergency stop buttons, and visual alerts. The software runs on a Windows 11 PC, was developed in C-H- (Visual Studio, Microsoft Corp.) with open-source Visualization Toolkit (VTK), Insight Toolkit (ITK), Grassroots Digital Imaging and Communications in Medicine (DICOM) (GDCM), and EPOS libraries. The software includes robot control, ultrasound scanning, 3D image rendering, biopsy planning, and ultrasound-guided needle targeting components. The user interface shows a virtual clinical environment that includes the robot following in real-time the actual robot together with volumetric and real-time ultrasound (see movie supplement).

[0060] FIGS. 10A-I0C illustrate perspective and image views of a 3D scan and needle targeting tests. FIG 10A illustrates a perspective view of a setup. FIG. 10B illustrates an image view of a scanned grid of strings. FIG. IOC illustrates a perspective view of a needle point at target on the grid crossings. The speed of the scan is calculated automatically by the software using Eq. 1. The speed is based on the scan resolution requested at 50mm away from the probe axis. A rectangular grid of strings 0.36 mm in diameter, equally spaced 10 mm apart submersed in a water tank was 3D scanned with the robot. Image calibration was performed using CAD kinematic parameters and image scale / frame parameters w ere adjusted experimentally on the grid of strings. A re-slice of the rendered volume through the grid plane. As illustrated in FIG. 10B. This show's accurate grid spacing, measured at 10.024mm. Then, the 25 crossings of the grid were targeted robotically (green dots), as illustrated in FIG.10C. The robot automatically aligned the need-guide on each target. The needle was inserted manually through the guide. No trajectory corrections were made, manually or with the robot.The experiment was repeated 10 times at different string depths. In all experiments, the needle touched all stnng crossings. Errors were estimated visually to be less than 0.5 mm.

[0061] FIGS. 11 A- l 1C illustrate perspective and image views of a needle targeting in a prostate mockup with a TP adapter. FIG. 11 A illustrates a test setup. FIG I IB illustrates a 3D virtual environment. FIG. 11 C illustrates an image view- of needle targeting tests in a prostate mockup. Numerous needle targeting experiments were earned out with the invention on prostate mockups (Model 066, CIRS, VA). The mockup was 3D scanned, the PCS w as assigned, the prostate was segmented, and a biopsy plan was defined to target the three ultrasound visible lesions of the mockup. Sequentially, the robot onented the needle-guide on each target and an 18Ga needle was inserted manually, as illustrated in FIG. 11 A. Targeting error was measured as the shortest distance between the biopsy needle direction and the target point, that w as also confirmed to be centered on the visible lesions, as illustrated in FIG. 11C. The maximum error measured over 10 experiments was 0.89 mm, including needle deflections. At TR and TP simulated biopsies over 27 and 30 targets, average errors were 0.30mm (SD 0.19mm) and 0.41mm (SD 0.22mm), and maximum errors were 0.67 and 0.92mm, respectively.

[0062] In operation, the robot and supporting arm are covered wuth a sterile bag (EZ-28, Preferred Medical Products, LLC). Tire probe attaches to the robot over the bag with the magnetic mount. Then, a needle-guide adapter attaches to the probe. According to the Food and Drug Administration (FDA) guidance the ultrasound probe must be processed with high- level disinfection (HLD) prior to each case. Hydrogen Peroxide HLD common for ultrasound probes, with Trophon2 (Nanosonics Inc.) equipment are used. The needle-guide adapters are sterile single use components.

[0063] The needle-guide adapters for TR and TP biopsy, as illustrated in FIGS. I2A and 12B are processed with autoclave sterilization (Hot Steam, Pre-Vacuum cycle, temperature 132°C, exposure time 4 min, dry time 15 mm). Ihe materials used are:• FormLabs resin Surgical Guide: Class I biocompatible (ISO 10993-1:2018, EN ISO 10993-5:2009 Not Cytotoxic, ISO 10993-10:2010 / (R)2014 Non Irritation, ISO 10993- 10:2010 / (R)2014 Not a sensitizer)• FormLabs resin Tough 1500: Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity evaluation - no observed cytotoxicity (NAMSA ISO 10993- 5).• Stainless steel 304 / 316 tubes with certificate of ASTM A908, Fed. Spec. GG-N-196 compliance.• FormLabs provided autoclave sterilization data for both resins, and the IRB Cleaning, Disinfection and Sterilization (CDS) Oversight Committee agreed with their determination and approved processing.

[0064] FIGS 12A-12C illustrate views of needle guides for transrectal biopsy, as illustrated in FIG. 12A, and transperineal biopsy, as illustrated in FIG, 12B. FIG. 12C illustrates a device of the present invention in a Trophon HDL machine. High-level disinfection of the probe, as illustrated in FIG. 12C, however, involved substantial additional testing. The probe is made of the same FormLabs Surgical Guide resin used in the adapters. While the manufacturer tested and certified this resin for autoclave sterilization, they did not for hydrogen-peroxide HLD. these extensive tests were conducted independently, an involved and lengthy process. In short:• Made material specimens according to ISO 527-2 (Plastics - Determination of tensile properties)* Shipped specimens to Nanosonics Inc (Sydney, Australia). NanoSonics processed lire specimens (Hydrogen Peroxide 35% w / w; Temperature of the Disinfection Chamber 60°C: Nebulising Function Time 30s ON / 30s OFF; 30s drive stop; Hydrogen Peroxide Deliver}' Rate 1.8 g / cycle) for 410 and 1053 cycles.* Nanosonics mailed samples backs, and dimensional and mechanical property testing was conducted on a Criterion Electromechanical Test Systems, Model C43-504 (MTS Systems)* Sent new specimens to Australia and Nanosonics performed HLD efficacy testing of Trophon2, ISO 527-2. The efficacy was validated against the Mycobacterium terras microorganism (ATCC15755).

[0065] The tests results showed that:* A material discoloration was observed after 410 cycles.* No appreciable deformations or cracking were observed after all 1053 cycles.* Loss of mechanical properties of the test material in 410 hydrogen peroxide cycles are equivalent to those of 5 autoclave cycles.* However, between 410-1053 cycles the material becomes brittle.

[0066] The worst-case Trophon disinfection process (lowest dosage, minimum concentration of disinfectant) reduced the inoculated Mycobacterium terrae ATCC 15755 bio-burden on the test item (specimen ISO 527-2) by > 6.0 loglO cfu. The specimen ISO 527-2 has passed the simulated use test for Mycobacterium terrae ATCC 15755.

[0067] Overall, Hydrogen peroxide HLD is effective on the Surgical Guide material and is less impactful on mechanical properties than autoclaving. However, it is recommended that the number of sterilization cycles should not exceed 410, which was sufficient for aprototype. Based on these results, the CDS approved processing the probe in the Trophon HLD machine.

[0068] FIGS. 13A-13C illustrate image views of a device of the present invention, and views of the resultant ultrasound images from the device of the present invention. Two transrectal biopsy cases have been recently performed. FIG. 13A illustrates a probe of the present invention during a case with the patient m the left-lateral decubitus position. FIGS. 13B and 13C illustrate ultrasound images with the needle inserted on the novel oblique path that the probe of the present invention enabled. As shown, due to the large array image quality was outstanding, and due to kinematics of the present invention that always keeps the needle within the imaging plane, the entire needle was clearly visible. Side-fire images with an angled needle like these have not been seen before. With end-fire probes images are lower quality7, and the needle is not frequently visible. Prostate volumes were 45.7 and 55.1cm3, the total duration of the cases were 20.07 & 15.68 min of which 0.47 & 0.57 min for the 3D scan, 4.35 & 6.13 min for biopsy planning, and 8.9 & 5.85 min for the actual biopsies, and all 18 and 15 biopsy samples were collected successfully with the robot, for the first and second patient under local anesthesia, respectively. No complications occurred in either case. No prostate deformations nor interference of the probe components with the patients were observed.[00691 The device includes several novel features including higher quality ultrasound, steady¬ probe pressure over the gland to reduce prostate deformations, fully robotic handling with a minimal number of DoF. and potential application to TR and TP biopsies.

[0070] Several robots were made in academia for prostate biopsy. In most situations, these are in pre-clinical validation stages. The probe of the invention approach uses only 2DoF which is the minimum possible. Systems with end-fire probes require at least 4DoF, such asthe TRUS-Robot and Artemis system (Eigen). Reducing DoF offers simplicity and, possibly, increased precision.

[0071] Kinematically, the use of an RCM mechanism to rotate a slender instrument about its axis is novel. RCM mechanisms were developed for laparoscopy and are commonly used to orient the instrument laterally about a fulcrum point on their axes, such as the laparoscopy port. The proposed use could extrapolate to other devices, such as catheter manipulation.

[0072] Several prostate biopsy systems are commercially available (Table 1). Mona Lisa is the only commercial robot for prostate biopsy. Its fundamental deficiency is that it angles the needle relative to the imaging planes. As such, the needle is typically invisible in ultrasound during insertion. Only after firing the biopsy does the needle appear, as a dot, raising concerns in both targeting and safety. In contrast, the present invention maintains the needle within the image plane and provides a unique combination of high-quality images and clear needle visibility in real-time ultrasound and illustrated in FIGS I3B and 13C. Its DoF is also higher. Clinically, Mona Lisa biopsy is performed under general anesthesia at the OR, which is not in-keeping with latest TP biopsy with local anesthesia in clinic. The planned TP approach is with local anesthesia in clinic.

[0073] The next closest biopsy device to the present invention is Artemis because it uses a mechanical arm (not motorized, therefore not a robot). Tire arm is encoded and offers essential support for the probe. Like the present invention, Artemis can maintain uniform pressure over the gland at the time of the 3D scan to reduce prostate deformation. At biopsy, however, maintaining the pressure is more difficult, requiring skill, as with the other manual devices.

[0074] Typical ultrasound machines are 2D. 3D ultrasound is acquired with special probes that use a multitude of arrays or move one array within the probe to scan (i.e. Trinity, Koelis). Image quality is typically lower because more components and less imaging crystals can fitTable 1: ProBot and current commercial prostate biopsy devices features tableTRUS Probe Minimizeprostatedef ormat ions SB Plan dlth N Peeea;FusionName Country Type methodt Supporki TracngdliHanng [dl Neeeiibl i vsenltd Urasoun: uwithin the limited space of the probe. Instead, with the present invention, the scan motion is external, the probe has more room for a bigger array, improving image quality. Future clinical trials will have to investigate if improved imaging correlates with biopsy outcomes. Moreover, robotic motion can do a finer scan than manually. At Biopsy5

[0075] The oblique needle path of variable angle with a side-fire probe is novel. Most suchGienercprobes commonly use a needle path that is parallel to the probe (TP biopsy with needletiiOpmze [d kill S adapter, i.e. Perineologic, Cumberland, MD). But in this case, the TRUS probe needs to be iddtnepenen lii I Cnnc tilted to aim the biopsy target, thus deforming the gland. Side-fire probes with angled needle¬ (t) ORno guide exist but their angle is fixed (i.e. BK). To target, these probes also tilt and deform the 10 gland. The present invention’ s-controlled needle angle targets without tilting the probe. To date only TR biopsy has been clinically tested. Future research will expand to TP biopsy.

[0076] The present invention includes the development of a new side-fire ultrasound probe and simple robot that enables hands-free operation on a novel controlled angle path for TR and TP biopsies. The most important feature is that the only motion of the probe is a rotation 15 about its axis, which preserves gland deformations that are otherwise difficult to control andimpact targeting accuracy. 3D image scanning and needle alignment for biopsy can be performed with only 2 DoF, the minimum number, never used before. Also, kinematic wise, the use of an RCM to spin about the slender axis of an instrument is novel.

[0077] Using a side-fire ultrasound provides the highest image quality and clearly shows the entire needle during insertion. This is expected to contribute to the precision of biopsy targeting. Hands-free robotic probe operation gives additional potential to improve targeting accuracy and reduce the skill required and variability of outcomes among physicians.

[0078] A first-in-man clinical trial has been successfully completed with the present invention for TR biopsy. Safety and feasibility trails that include TP will follow. Clinical efficacy trials are warranted to establish if the technical features reported herein translate into improved clinical outcomes.

[0079] The device can include imaging to provide a rotary’ scan with side-fire to minimize gland deflections. A right angle (cable) transmission can be used to orient the motor along principal axis of device, to save space. The shaft of the probe can be split to make room for needle. Structural elements can be included within the ultrasound probe. For instance, half of the probe shaft can be filled to bring it back to a round shape. Magnetic support of an ultrasound probe can be provided. A microphone can be included in the device. A passive adjustable slide support m the direction of the probe, with lock can also be included.

[0080] It should be noted that aspects of the device, its control, and calculations can be executed with a program(s) fixed on one or more non-transitory computer readable medium. The non-transitory computer readable medium can be loaded onto a computing device, microprocessor, servo, server, actuator, device processor, smartphone, tablet, phablet, the Robotic Control Box, or any other suitable device known to or conceivable by one of skill in the art.

[0081] It should also be noted that herein the steps of the method described can be carried out using a computer, non-transitory computer readable medium, or alternately a computing device, microprocessor, or other computer type device independent of or incorporated with an imaging or signal collection device. The computing device for executing the present invention can be a completely unique computer designed especially for the implementation of this method. Indeed, any suitable method of analysis known to or conceivable by one of skill in the art could be used. It should also be noted that while specific equations are detailed herein, variations on these equations can also be derived, and this application includes any such equation known to or conceivable by one of skill in the art.

[0082] A non-transitory computer readable medium is understood to mean any article of manufacture that can be read by a computer. Such non-transitory computer readable media includes, but is not limited to, magnetic media, such as a floppy disk, flexible disk, hard disk, reel-to-reel tape, cartridge tape, cassette tape or cards, optical media such as CD-ROM, writable compact disc, magneto-optical media in disc, tape or card form, and paper media, such as punched cards and paper tape.

[0083] It should be noted that the software associated with the present invention is programmed onto a non-transitory computer readable medium that can be read and executed by any of the computing devices mentioned in this application. The non-transitory computer readable medium can take any suitable form known to one of skill in the art. The non-transitory computer readable medium is understood to be any article of manufacture readable by a computer. Such non-transitory computer readable media includes, but is not limited to, magnetic media, such as floppy disk, flexible disk, hard disk, reel-to-reel tape, cartridge tape, cassette tapes or cards, optical media such as CD-ROM, DVD, Blu-ray, writable compact discs, magneto-optical media in disc, tape, or card form, and paper media such as punch cardsor paper tape. Alternately, the program for executing the method and algorithms of the present invention can reside on a remote server or other networked device. Any databases associated with the present invention can be housed on a central computing device, server(s), in cloud storage, or any other suitable means known to or conceivable by one of skill in the art. All of the information associated with the application is transmitted either wired or wirelessly over a network, via the internet cellular telephone network, RFID, or any other suitable data transmission means known to or conceivable by one of skill in the art.

[0084] The many features and advantages of the invention are apparent from the detailed specification, and thus, it is intended by the appended claims to cover all such features and advantages of the invention which fall within the true spirit and scope of the invention.Further, since numerous modifications and variations will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation illustrated and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.

Claims

What is claimed is:

1. A device comprising:a probe, wherein the probe comprises a side-fire, linear array configured for ultrasound, and wherein a shape of the probe is configured to allow for transrectal and transperineal biopsy paths;a needle-guide adapter wherein the needle-guide adapter is configured for transrectal or transperineal biopsy paths by shifting a pivot point of the needle-guide adapter; and a robot configured for control of the probe.

2. The device of claim 1 further comprising a metallic rib configured to augment the structural integrity and stiffness of the probe.

3. The device of claim 1 further comprising a metallic mount that attaches magnetically to the robot4. The device of claim 1 wherein the needle-guide adapter couples to the probe.

5. The device of claim 4 wherein the probe comprises a shape configured to accommodate for a path of a needle, as a path of the needle is defined by the needleguide adapter.

6. The device of claim 1 wherein the needle-guide adapter defines an oblique path with respect to the probe for a needle passing through the needle-guide adapter.

7. The device of claim 1 wherein the needle-guide adapter defines a transrectal path for a needle passing through the needle-guide adapter.

8. The device of claim 1 wherein the needle-guide adapter defines a transperineal path for a needle passing through the needle-guide adapter9. The device of claim 1 wherein the robot comprises a remote center of motion mechanism (RCM).

10. The device of claim 4 wherein the RCM comprises a cable-driven compact RCM.

11. A device comprising:a remote center of motion mechanism (RCM);wherein the RCM is configured to rotate an instrument about a principal axis of the instrument, wherein the principal axis of the instrument is a longitudinal axis of the instrument.

12. The device of claim 6 wherein the instrument comprises a slender instrument.

13. A system comprising:a probe, wherein the probe comprises a side-fire, linear array configured for ultrasound, and wherein a shape of the probe is configured to allow for transrectal and transperineal biopsy paths;a needle-guide adapter wherein the needle-guide adapter is configured for transrectal or transperineal biopsy paths by shifting a pivot point of the needle-guide adapter; anda robot configured for control of the probe, wherein the robot comprises a remote center of motion mechanism (RCM);wherein the RCM is configured to rotate an instrument about a principal axis of the instiument, wherein the principal axis of the instrument is a longitudinal axis of the instrument.

14. The system of claim 13 further comprising a metallic rib configured to augment the structural integrity and stiffness of the probe.

15. The system of claim 13 further comprising a metallic mount that attaches magnetically to the robot.

16. The system of claim 13 wherein the needle-guide adapter couples to the probe.

17. The system of claim 16 wherein the probe comprises a shape configured to accommodate for a path of a needle, as a path of the needle is defined by the needle-guide adapter.

18. The system of claim 13 wherein the needle-guide adapter defines an oblique path with respect to the probe for a needle passing through the needle-guide adapter.

19. The system of claim 13 wherein the needle-guide adapter defines atransrectal path for a needle passing through the needle-guide adapter.

20. The system of claim 13 wherein the needle-guide adapter defines a transperineal path for a needle passing through the needle-guide adapter.

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