Patent Application
20230380902
The present disclosure relates generally to the field of thermal therapy for cancer treatment and, in particular, to using laser ablation therapy to treat prostate cancer.
Prostate cancer is the most frequently diagnosed non-dermatological cancer in men. Although prostate cancer mortality rates have dropped, one in six men will be diagnosed with prostate cancer in his lifetime. The two most common treatments for clinically localized prostate cancer (e.g., cancer that is localized to the prostate and has not spread) are radical prostatectomy and external beam radiation therapy. In a radical prostatectomy procedure, the prostate gland and some of the surrounding tissue is removed. With external beam radiation therapy, high-energy x-rays or other particles are focused into the prostate cancer site to kill the cancer cells. Another treatment option for prostate cancer is brachytherapy, in which radioactive implants are placed directly in the prostate to kill the cancer cells.
However, radical prostatectomy procedures are often invasive and may have lasting side effects, such as urinary incontinence, erectile dysfunction, and sterility. Likewise, men undergoing external beam radiation therapy or brachytherapy may suffer from similar side effects. Moreover, because external beam radiation therapy and brachytherapy use radiation to treat the prostate cancer, men undergoing these treatments have a small risk of developing a secondary cancer from the radiation therapy.
One embodiment relates to a method for magnetic resonance imaging (MRI)-guided interstitial thermal therapy. The method includes receiving MRI data for tissue of a patient, generating an apparent diffusion coefficient (ADC) map from the MRI data, and identifying a target site for thermal therapy based on the ADC map, wherein the target site is identified based on an area on the ADC map with a lowest ADC value. The method further includes planning the thermal therapy for the target site including identifying localized areas of the target site to be ablated first during delivery of the thermal therapy, activating a laser to deliver the thermal therapy with a laser fiber, and monitoring progress of the thermal therapy using MRI. In some arrangements, the progress of the thermal therapy is monitored using MR thermometry.
Another embodiment relates to a system for MRI-guided interstitial thermal therapy. The system includes a laser, a guide configured to direct the laser fiber to a target site for thermal therapy, and a processing circuit. The processing circuit includes a processor and a memory having instructions stored thereon that, when executed by the processor, cause the processing circuit to receive MRI data for a tissue of a patient, generate an ADC map from the MRI data, and identify the target site for the thermal therapy based on the ADC map, wherein the target site is identified based on an area on the ADC map with a lowest ADC value. The instructions further cause the processing circuit to plan the thermal therapy for the target site including identifying localized areas of the target site to be ablated first during delivery of the thermal therapy, activate the laser to deliver the thermal therapy via a laser fiber, and monitor progress of the thermal therapy using MRI. In some arrangements, the progress of the thermal therapy is monitored using MR thermometry.
Another embodiment relates to a non-transitory computer readable medium including instructions contained thereon. When executed by a processor, the instructions cause a processing circuit to receive MRI data for a tissue of a patient, generate an ADC map from the MRI data, and identify the target site for the thermal therapy based on the ADC map, wherein the target site is identified based on an area on the ADC map with a lowest ADC value. The instructions further cause a processing circuit to plan the thermal therapy for the target site including identifying localized areas of the target site to be ablated first during delivery of the thermal therapy, activate a laser to deliver the thermal therapy via a laser fiber, and monitor progress of the thermal therapy using MRI. In some arrangements, the progress of the thermal therapy is monitored using MR thermometry.
The present disclosure introduces an MRI-guided interstitial thermal therapy that may be used, for example, to treat prostate cancer. With MRI-guided interstitial thermal therapy, a laser fiber is guided to the treatment site and used to ablate target cells. The progress of the thermal therapy is planned and monitored using MRI, as discussed in further detail below. As noted above, current methods for treating prostate cancer are often invasive and/or have lasting side effects, such as a urinary incontinence, erectile dysfunction, and sterility. Additionally, radiation therapies are associated with a small risk of developing a secondary cancer from the radiation. By contrast, MRI-guided interstitial therapy is targeted and minimally-invasive. The therapy may also be monitored in near real-time through MRI. Furthermore, MRI-guided interstitial therapy may be performed as an outpatient procedure. It should be understood, however, that although the present disclosure makes reference to treating prostate cancer, the systems and methods disclosed herein may be used to treat other cancers or medical conditions.
Referring now to
The MRI system 100 includes an MRI scanner 102 with a scanner table 104. A patient is placed on the scanner table 104, and a portion of the patient's anatomy is moved into a scanner bore 106 of the MRI scanner 102. When in use, the MRI scanner 102 uses a magnet (not shown) to generate a magnetic field that excites hydrogen atoms in the patient anatomy being imaged that, in turn, emit radio frequency signals that are measured by a receiving coil (not shown) of the MRI scanner 102. In some embodiments, the MRI may utilize two coils. The MRI scanner 102 is connected to a computing system, such as the computing system 300 or a separate computing system, that processes the MRI data (e.g, the radio frequency signals) to create images of the patient anatomy. Additionally, to improve the contrast of MR images, the patient may be injected with a contrast agent such as gadolinium. As an illustration, with dynamic contrast-enhanced (“DCE”) imaging, the patient is injected with a contrast agent and subjected to perfusion MRI scanning to detect, for example, the flow of blood through the patient's vessels in the target tissue.
Further, the MRI system 100 may be configured to produce differently weighted images with different contrasts. As an illustration, when excited, the patient anatomy returns to an equilibrium state through T1 relaxation (associated with relaxation parallel to the magnetic field) and through T2 relaxation (associated with relaxation perpendicular to the magnetic field). As such, the image may be T1-weighted by changing the repetition time (i.e., the time between two successive excitations of the same tissue) or T2-weighted by changing the echo time (i.e., the time between an excitation pulse and the peak of the signal). As another illustration, in diffusion-weighted imaging (“DWI”), the MRI system 100 is configured to measure the random Brownian motion of water molecules within the target tissue. Apparent diffusion coefficient (“ADC”) values, which measure the magnitude of diffusion of water molecules within tissue, for the areas in the target tissue may then be calculated using the DWI data and be displayed as a parametric map. As yet another illustration, the MRI system 100 may be configured to measure the proton resonant frequency shift that occurs when water molecules in imaged tissue are heated and produce MR thermometry images (e.g., thermal maps) of the tissue. Accordingly, in some embodiments, the MRI system 100 used with MRI-guided interstitial thermal therapy described herein is configured for (a) T1 or T2-weighted axial, sagittal, and coronal imaging, (b) DWI, (c) DCE imaging, and (d) MR thermometry imaging.
Additionally, MRI systems, such as the MRI system 100, may be configured with magnets capable of generating differently sized magnetic fields. Commonly, diagnostic MRI systems are configured with a magnetic capable of generating a magnetic field of 1.5 Tesla or 3.0 Tesla. However, while an MRI system configured with a 3.0 Tesla magnet has a greater magnetic field strength than an MRI system configured with a 1.5 Tesla magnet, many artifacts are more apparent, and may be problematic, at higher field strengths. These artifacts include motion susceptibility and metallic and dielectric signal losses. Additionally, thermal maps are gradient echo-based and therefore less influenced by bowel gas, motion, and other artifact-generating problems at 1.5 Tesla. As such, in some embodiments, the MRI system 100 used with the MRI-guided interstitial thermal therapy is a 1.5 Tesla system (e.g., an MRI system configured with a 1.5 Tesla magnet or an MRI system only used with a 1.5 Tesla magnetic field).
As shown in
Referring now to
The thermal therapy system 200 also includes the laser control system 204 and the laser system 232. The laser control system 204 (e.g., a 15 W laser control system 204 with a 980 nm diode adapted to perform ablation on target tissue) is used to power the laser system 232, which delivers the therapy. For example, the laser control system 204 and the laser system 232 may be, or include components from, the Visualase® system sold by Medtronic, Inc. As shown in
Referring now to
In various embodiments, to position the laser fiber 240 at the target ablation area, the sheath 246 with a trochar fitted inside the lumen of the sheath 246 is threaded through the lumen 218 of the needle guide 216 to the target ablation site. The trochar is then removed and replaced with the cooling catheter 244 with a stiffener inside the catheter 244. The stiffener is removed, and the laser fiber 240 is threaded inside the catheter 244 to the target ablation site.
Referring now to
Alternatively, in other embodiments, the laser fiber 240 is configured to distribute heat while applying thermal therapy such that cooling the laser fiber 240 with saline is unnecessary. In such embodiments, the laser control system 204 may accordingly include just the laser power source 234, and the laser system 232 may consist of the laser fiber 240 with the heat-diffusing laser tip 242 and the sheath 246. As an example, the laser control system 204 and the laser system 232 may be, or include components of, the Tranberg® system sold by Clinical Laserthermia Systems AB. Thus, when the laser system 232 is positioned at the target ablation site, the sheath 246 with the trochar is first threaded to the site, and the trochar is removed and replaced with the non-cooled laser fiber 240.
The computing system 300 includes hardware and software for operation and control of the components of the surgical system 10. As such, in various embodiments, the computing system 300 includes hardware and/or software for operation and control of the MRI system 100 and the thermal therapy system 200. However, it should be understood that while the computing system 300 is shown in
Referring now to
A processor may receive instructions, as well as input data, from a read only memory (“ROM”), a random access memory (“RAM”), or both. Accordingly, the memory 314 (e.g., memory, memory unit, storage device, etc.) comprises one or more devices (e.g., RAM, ROM, Flash-memory, hard disk storage, etc.) structured for storing instructions and/or data for completing or facilitating the various processes described in the present application. The memory 314 may be or include volatile memory or non-volatile memory. Moreover, the memory 314 may include database components, object code components, script components, or any other type of information structure for supporting the various activities described in the present application. Accordingly, in the embodiment of
In various embodiments, the computing system 300 may be implemented as a system that includes a back-end component (e.g., as a data server), includes a middleware component (e.g., an application server), or includes a front-end component (e.g., a client computer having a graphical user interface (“GUI”) or a web browser through which a user may interact with an embodiment of the subject matter described in this specification), or that includes any combination of one or more such back-end, middleware, or front-end components. The components of the computing system 300 may be interconnected by any form or medium of digital data communication (e.g., a communication network). Moreover, the computing system 300 may at least partially be embedded in another device, such as a mobile telephone, a tablet, a personal digital assistant (“PDA”), a mobile audio or video player, a game console, a Global Positioning System (“GPS”) receiver, or a portable storage device (e.g., a universal serial bus (“USB”) flash drive), to name just a few. Devices suitable for storing computer program instructions and data include all forms of non-volatile memory, media, and memory devices, including by way of example semiconductor memory devices (e.g., EPROM, EEPROM, and flash memory devices), magnetic disks (e.g., internal hard disks or removable disks), magneto optical disks, and CD ROM and DVD-ROM disks. Further, the processor 312 and the memory 314 can be supplemented by, or incorporated in, special purpose logic circuitry.
Additionally, the computing system 300 includes at least one input device 304 and at least one output device 306. Input device(s) 304 enable a user to communicate with the computing system 300. For example, as shown in
Output device(s) 306 enable the computing system 300 to provide information to a user. Such information may include images of anatomy generated from an image data set obtained using conventional imaging techniques (e.g., MRI), graphical models (e.g., CAD models of implants, instruments, anatomy, etc.), graphical representations of a tracked object (e.g., anatomy, tools, implants, etc.), constraint data (e.g., axes, articular surfaces, etc.), representations of implant components, digital or video images, registration information, calibration information, patient data, user data, measurement data, software menus, selection buttons, status information, and the like. As such, as shown in
Moreover, in some embodiments, the input device 304 may also serve as the output device 306 and accordingly be configured to gather inputs from and provide feedback to the user. As an example, the input device 304 and the output device 306 may be a touchscreen. Further, in some embodiments, the input device 304 and/or the output device 306 may be a separate computing system, such as a personal computing system that the user uses to interact with the computing system 300. For example, the user may use a personal computing system to request and receive web pages from the computing system 300.
In various embodiments, as discussed in further detail below, the computing system 300 is used to generate MR images (e.g., using the image processing module 314a), plan thermal therapy (e.g., using the planning module 314b), and control the laser control system 204 (e.g., using the laser control module 314c). With respect to generating MRI images, the computing system 300 is configured to receive MRI data (e.g., radio frequency signals) from the MRI system 100 and process the MRI data to create images of the target tissue, both for planning and real-time or near real-time (e.g., with a 5-7 s refresh rate) therapy purposes. Furthermore, the computing system 300 is configured to generate ADC parametric map from DWI data, as discussed above.
With respect to planning thermal therapy, a user may use the computing system 300 to carry out various planning processes for the thermal therapy, as described in further detail below. For example, a practitioner may user the computing system 300 to identify the target site, calculate a trajectory of the laser 232 into the target site, determine localized areas of the target site to be ablated first, and the like.
With respect to controlling the laser control system 204, the computing system 300 may be used, for example, to control the output of the laser power source 234 (e.g., the amount of power provided the timing of the provided power). Additionally, the computing system 300 may be configured to implement a temperature safety system for the laser control system 204. As an example the computing system 300 may enable a user to place safety cursors associated with warning temperatures (e.g., 90° C.) on images of the target therapy site. The computing system 300 then estimates the real-time or near real-time temperature at the cursor points (e.g., using MR thermometry) and automatically deactivates the heat-diffusing laser tip 242 if the estimated temperature exceeds the warning temperature (e.g., exceeds 90° C.). In some embodiments, the computing system 300 may allow the user to place both high-temperature safety cursors (e.g., adjacent to the laser system 232) and low-temperature safety cursors (e.g., adjacent to heat-sensitive critical structures, such as the rectal wall or the external urethral sphincter) on the image of the area targeted for therapy. Alternatively, in some embodiments, one or more of the functions of controlling the computing system 300 may instead be performed by the laser power source 234.
Referring now to
Next, MR images of the patient's prostate tissue are obtained (step 404). As discussed above, in some embodiments, computing system 300 receives T2-weighted axial, sagittal, and coronal imaging data, DWI data, DCE imaging data, and MR thermometry data and generates MR images from the received MRI data. Additionally, the computing system 300 generates ADC maps for the patient's prostate based on the DWI data. The target site for the thermal therapy is then identified using the ADC map (step 406). In particular, prostate cancer tissue may be associated with significantly lower ADC values than surrounding noncancerous tissue. As such, a practitioner uses the ADC map to identify, or the computing system 300 automatically identifies, the area of the prostate with the lowest ADC value. In some embodiments, as the practitioner moves a cursor on a screen providing an image of the area, the ADC value at that location is shown. The ADC value is updated as the cursor is moved, and in this way, the practitioner is able to identify the lowest ADC area. This area is determined to be the target site for beginning the thermal therapy.
Once the target area is identified, a periprostatic nerve block (step 408) is performed utilizing MR guidance (e.g., based on MR images) and a 22 gauge MR-compatible needle. A volume (e.g., 10 cc) of a numbing agent such as Marcaine is bilaterally injected into the periprostatic fat at the junction between the prostate gland and the seminal vesicle. In some embodiments, 0.5% Marcaine is used, while in other embodiments, 0.25% Marcaine is used.
Next, the transrectal guide 202 is positioned for the thermal therapy (step 410). Accordingly, as described above, the needle guide 216 is inserted into the patient's rectum, for example, using a viscous lidocaine delivered transrectally as both a lubricant and an anesthetic (e.g., 11 cc of sterile 2% lidocaine jelly, or 220 mg of lidocaine HCl). In this way, the needle guide 216 is positioned to direct the laser 232 to the target site in the patient's prostate gland. Because the needle guide 216 is also configured to be an MRI fiducial marker, the position of the needle guide 216 may be verified in near real-time (e.g. with a 5-7 s delay per update) using MR images. The needle guide 216 is then fixed in place by sliding the clamp stand 212 to the needle guide 216 along the runner 214 and attaching the needle guide 216 to the clamp stand 212.
The thermal therapy procedure is then planned (step 412). Planning the thermal therapy procedure includes calculating the trajectory for the laser system 232 using the computing system 300. For example, the user may use the mouse 304b to place a cursor on the tip of the needle guide 216 and a cursor on the target site as shown on an MR image displayed on the displays 306a and/or 306b. The computing system 300 may then determine the difference between the starting position of the needle guide 216 and the target site and display (e.g., via the display 306a and/or 306b) coordinates to adjust the needle guide 216 to achieve the desired trajectory. The user may then adjust the needle guide 216 accordingly. In some examples, the position of the needle guide 216 may further be verified by inserting a needle system (e.g., a 150 nm 13-gauge MR-conditional coaxial needle system) through the needle guide 216 and obtaining a confirmation scan of the needle system using MR images. Adjustments may then be made as needed. In various embodiments, the planning process may be carried out using specialized hardware and/or software incorporated as part of the computing system 300, such as the DynaCAD processing system sold by Invivo Corporation.
Further, planning the thermal therapy procedure may include additional steps, such as placing high-temperature safety cursors and/or low-temperature safety cursors on an MR image of the target site using the computing system 300, as discussed above. As an example, the user may use the mouse 304b to place low-temperature safety cursors on tissues that are sensitive to heat, such as the rectal wall or the external urethral sphincter, and place high-temperature safety cursors on tissues that will be adjacent to the laser system 232. In various embodiments, the placement of safety cursors may be carried out using specialized hardware and/or software incorporated as part of the computing system 300, such as the Visualase system sold by Medtronic Inc.
Once the thermal therapy is planned, the laser system 232 is positioned for the thermal therapy (step 414). In some embodiments, first, the sheath 246, with a trochar inside, is inserted into the patient's rectum and guided to the target site through the rectal wall via the lumen 218 of the needle guide 216. Once the placement of the sheath 246 is verified using MRI (e.g., using a two-dimensional fast steady-state acquisition in the axial and sagittal planes), the stiffener is removed and replaced with the cooling catheter 244 with a stiffener inside. When the cooling catheter 244 is in position, the stiffener is removed and replaced with the laser fiber 240. For example, the laser fiber 240 selected for the procedure may have a 1 cm heat-diffusing tip (e.g., for smaller tumors) or a 1.5 cm heat-diffusing tip (e.g., for larger tumors). Alternatively, in other embodiments, the laser system 232 may include just the sheath 246 and the laser fiber 240 (e.g., because the laser fiber 240 does not require cooling). Accordingly, once the placement of the sheath 246 is verified, the laser fiber 240 is threaded directly through the sheath 246 to the target site.
Once the laser system 232 is positioned at the target site, the position of the laser system 232, and specifically the laser fiber 240, is then verified by activating the heat-diffusing laser tip 242 of the laser fiber 240 at a low setting (step 416). For example, the laser tip 242 is activated using a test dose of 4.5 W (i.e., at 30% power on a 15 W system). The heat from the laser tip 242 is visualized using MRI (e.g., quantitative temperature images produced via MR thermometry) to ensure that the laser fiber 240 is in the correct location before thermal therapy is started. However, the temperature remains below 43° C. and therefore will not cause damage if the laser fiber 240 is in the incorrect location. If the laser fiber 240 is in the correct location, the method 400 proceeds. If the laser fiber 240 is not in the correct location, the positions of the needle guide 216, sheath 246, cooling catheter 244, and/or laser fiber 240 are modified, and the planning performed at step 412 may be revised.
If the position of the laser fiber 240 is correct, the heat-diffusing laser tip 242 of the laser fiber 240 is activated at a therapeutic level to deliver the thermal therapy (step 418). For example, the therapeutic level for a 15 W laser fiber 240 operating at 980 nm may be 80-90% of the maximum power, or 12-13.5 W, with an exposure time of 120-150 s. Additionally, rather than applying therapy to the target site as a whole, at step 420 the laser fiber 240 is used to ablate discrete, localized areas within and/or around the target site. Referring now to
The localized areas 502 to be burned may be identified during the planning process at step 412. As an illustration, during the planning process, the practitioner may use the computing system 300 to define the boundaries of the tumor and plan locations for the localized areas 502 to be within and/or on the defined boundaries. Alternatively, the localized areas 502 may be chosen by the practitioner during the procedure. In some embodiments, and as illustrated in
Additionally, during the thermal therapy procedure at step 420, the computing system 300 is used to monitor the progress of the thermal therapy using MRI (e.g., using MR thermometry). In particular, a practitioner may note locations of heat-sensitive structures and monitor these structures during the ablation of the target site, or may observe estimates of irreversible damage. For example, when areas proximate to the rectal wall, external urethral sphincter, and neurovascular bundles need to be ablated, the laser fiber 240 may be used with multiple, low-energy, long-duration treatments to ablate those areas rather than at the standard therapeutic level in order to avoid irreversible damage to those tissues. Alternatively, the saline flow rate through the catheter 244 may be increased while the laser fiber 240 is being used to ablate these areas. The practitioner may manually take these measures to ensure that these heat-sensitive structures are not damaged, or the computing system 300 may automatically take these measures in response, for example, to the practitioner marking these areas with low-temperature safety cursors. Additionally, the computing system 300 may monitor the temperature of the target site (e.g., via quantitative temperature images produced using MR thermometry) to verify that the temperatures associated with the safety cursors have not been exceeded and, if they have, to automatically power down the heat-diffusing laser tip 242 of the laser fiber 240.
Once the practitioner has used the laser fiber 240 to ablate the target site, the target site is assessed to ensure that all of the target tissue (e.g., the prostate cancer tissue) has been ablated (step 422). If necessary, the laser fiber 240 is reused to ablate any remaining areas that are identified as still needing treatment. In some embodiments, the computing system 300 may further be used to plan revisions to the original thermal therapy plan based on the monitored progress of the thermal therapy in order to ensure that all of the cancer tissue has been ablated. For example, the computing system 300 may identify the areas of the target site that have been ablated (e.g., using MR thermometry) and compare the ablated areas to the target site as a whole. The computing system 300 may then display non-ablated areas to the user (e.g., via the displays 306a and/or 306b) and output coordinates for adjusting the placement of the needle guide 216 and/or the laser system 232 for ablating the remaining areas.
The construction and arrangement of the systems and methods as shown in the various exemplary embodiments are illustrative only. Although only a few embodiments have been described in detail in this disclosure, many modifications are possible (e.g., variations in sizes, dimensions, structures, shapes and proportions of the various elements, values of parameters, use of materials, colors, orientations, etc.). For example, the position of elements may be reversed or otherwise varied and the nature or number of discrete elements or positions may be altered or varied. Accordingly, all such modifications are intended to be included within the scope of the present disclosure. The order or sequence of any process or method steps may be varied or re-sequenced according to alternative embodiments. Other substitutions, modifications, changes, and omissions may be made in the design, operating conditions and arrangement of the exemplary embodiments without departing from the scope of the present disclosure.
Although a specific order of method steps may be described, the order of the steps may differ from what is described. Also, two or more steps may be performed concurrently or with partial concurrence. Such variation will depend on the software and hardware systems chosen and on designer choice. All such variations are within the scope of the disclosure. Likewise, software implementations could be accomplished with standard programming techniques with rule based logic and other logic to accomplish any connection steps, processing steps, comparison steps, and decision steps.
The present disclosure contemplates methods, systems and program products on any machine-readable media for accomplishing various operations. The embodiments of the present disclosure may be implemented using existing computer processors, or by a special purpose computer processor for an appropriate system, incorporated for this or another purpose, or by a hardwired system. As described herein, embodiments within the scope of the present disclosure include program products comprising machine-readable media for carrying or having machine-executable instructions or data structures stored thereon. Such machine-readable media can be any available media that can be accessed by a general purpose or special purpose computer or other machine with a processor. By way of example, such machine-readable media can comprise RAM, ROM, EPROM, EEPROM, CD-ROM or other optical disk storage, magnetic disk storage, other magnetic storage devices, solid state storage devices, or any other medium which can be used to carry or store desired program code in the form of machine-executable instructions or data structures and which can be accessed by a general purpose or special purpose computer or other machine with a processor. When information is transferred or provided over a network or another communications connection (either hardwired, wireless, or a combination of hardwired or wireless) to a machine, the machine properly views the connection as a machine-readable medium. Thus, any such connection is properly termed a machine-readable medium. Combinations of the above are also included within the scope of machine-readable media. Machine-executable instructions include, for example, instructions and data which cause a general purpose computer, special purpose computer, or special purpose processing machines to perform a certain function or group of functions.
For the purpose of this disclosure, the term “coupled” means the joining of two members directly or indirectly to one another. Such joining may be stationary or moveable in nature. Such joining may be achieved with the two members or the two members and any additional intermediate members being integrally formed as a single unitary body with one another, or with the two members or the two members and any additional intermediate members being attached to one another. Such joining may be permanent in nature or may be removable or releasable in nature.
The breadth of the present invention is not to be limited to the examples provided and/or the subject specification, but rather only by the scope of claim language associated with this disclosure.
This application is a continuation of U.S. patent application Ser. No. 15/894,190, filed Feb. 12, 2018, which is incorporated by reference herein in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 15894190 | Feb 2018 | US |
| Child | 18229085 | US |
