A Facility for Magnetic Resonance–Guided Radiation Therapy David A. Jaffray,*,†,‡,§,║ Marco C. Carlone, PhD,*,† Michael F. Milosevic, MD,*,† Stephen L. Breen, PhD,*,† Teodor Stanescu, PhD,*,†,║ Alexandra Rink,*,†,║ Hamideh Alasti,*,† Anna Simeonov, MSc,*,† Michael C. Sweitzer, M(Eng),¶ and Jeffrey D. Winter, PhD# Magnetic resonance (MR) imaging is routinely employed in the design of radiotherapy (RT) treatment plans for many disease sites. It is evident that tighter integration of MR imaging into the RT process would increase confidence in dose placement and facilitate the integration of new MR imaging information (including anatomical and functional imaging) into the therapy process. To this end, a dedicated MR-guided RT (MRgRT) facility has been created that integrates a state-of-the-art linear accelerator delivery system, high-dose rate brachytherapy afterloader, and superconducting MR scanner to allow MR-based online treatment guidance, adaptive replanning, and response monitoring while maintaining the clinical functionality of the existing delivery systems. This system is housed within a dedicated MRgRT suite and operates in a coordinated fashion to assure safe and efficient MRgRT treatments. Semin Radiat Oncol 24:193-195 C 2014 Published by Elsevier Inc.
System Design he “system” defines a dedicated 320-m2 magnetic resonance (MR)-guided radiotherapy (RT) (MRgRT) facility (Fig. A) that satisfies the American College of Radiology MR safety guidelines and allows a rail-mounted 1.5-T MR scanner to operate in 3 different suites: (1) MR-simulation—Siemens Espree 1.5-T, 70-cm bore, and contrast injector, (2) MRgBT— MR-guided brachytherapy (Nucletron, MicroSelectron highdose rate (HDR), Ir-192, 10 Ci), and (3) MRgRT—MR-guided
T
*Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. †Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. ‡Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. §Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. ║Techna Institute, University Health Network, Toronto, Ontario, Canada. ¶Varian Medical Systems, Palo Alto, CA. #IMRIS, Minneapolis, MN. The employers of D.A.J., M.C.C., M.F.M., S.L.B., T.S., H.A., and A.S. have a codevelopment agreement with IMRIS, Inc. D.A.J.'s employer has a sponsored research agreement with Elekta Inc. M.S. is an employee of Varian Medical Systems, Inc. J.D.W. is an employee of IMRIS, Inc. Address reprint requests to D.A. Jaffray, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. E-mail: David. [email protected]
http://dx.doi.org/10.1016/j.semradonc.2014.02.012 1053-4296/& 2014 Published by Elsevier Inc.
external-beam RT (Varian, TrueBeam, 6 MV, 1400 MU/min). The facility is structured under the premise that the high field of the MR can be located in any 1 of the 3 suites, and hence these are considered “zone 4” (i.e., restricted access and strong MR field) by the American College of Radiology guidelines. A “zone 2” (screening room) limits access to the facility with the HDR, linear accelerator, and MR scanner control areas located in a common extended “zone 3” (restricted access). The 2 treatment suites can operate with or without the MR scanner present.
MR-Simulation MR imaging for purposes of simulation and treatment planning can be performed in the dedicated central MR-simulation suite without interfering with the adjacent treatment suites. In addition to standard 1.5-T coils, the system is equipped with a dedicated oncology coil set for extended field-of-view imaging of the head and neck, as well as, high-performance pelvic imaging. The coils integrate with the RT-specific flat table top and are identical to those to be used in the MRgRT room.
Magnetic Resonance–Guided Brachytherapy A set of automated shielding doors (6.4-cm Pb) allows the MR scanner to enter the MRgBT to permit MR imaging of the patient located on a dedicated OR table. Patient positioning is 193
D.A. Jaffray et al.
194
Screening room
Zone 2
MR Control Console
Zone 3
MRgBT Console
Zone 3
MRgRT Console
Zone 3
MRgBT Suite
Zone 4
MR Simulation
Zone 4
MRgRT Suite
Zone 4
Rail System for Magnet 1.5T Espree MR Varian TrueBeam Pedestal for Modified Couch 5G Line
View from MRgRT
Figure (A) Floor plan and safety zones of the MR-guided RT facility at the Princess Margaret Cancer Centre showing brachytherapy, imaging, and external-beam RT suites. (B) Photograph of the accelerator and MR scanner in the facility. The magnet is advanced on the rail system into the MRgRT suite, and the patient is positioned via a modified treatment couch. At nearest approach, the magnet to linear accelerator isocenter distance is 3.1 m.
facilitated by the short (125 cm), wide (70 cm) bore of the magnet. MR imaging is possible during applicator and needle placement; however, the MR must be withdrawn and doors closed before connecting the HDR afterloader to the implant. The room includes an “radio frequency isolation equipment room” to allow MR-incompatible equipment (ie, HDR, C-arm, and ultrasound) to remain energized during MR-based procedures. In addition, a MR-compatible template system is also employed to support MR-guided HDR for prostate cancer.1
Magnetic Resonance–Guided Radiotherapy Online MR-guided external-beam radiation delivery is achieved through the coordinated movement of the MR scanner, linear accelerator, and a modified treatment couch. A set of radiation shielding doors (20.3-cm Pb) opens to allow the MR scanner to advance over the patient who has been moved 3.1 m (Fig. B) between linac isocenter and in-room MR-imaging isocenter. The linear motion of the magnet is a safety design element to avoid patient-magnet collision risks. Additional safety components include a magnet motion “dead man switch” and various interlocks between the linear accelerator, magnet mover, and shielding systems. The linear accelerator is equipped with both megavoltage (portal) and kilovoltage imaging (rad, fluoro, and cone-beam computed tomography [CT]). MR images are routed through an image calibration system that corrects for reproducible variations (rigid) in MR imaging geometry and converts them to the treatment reference frame. These images are then routed to the RT Picture Archiving and Communication System system or image registration or planning system or both. Corrections are routed through the treatment console to allow rigid corrections in patient position based on MR-MR registration. The movement of the patient from MR imaging to treatment position and the withdrawal of the magnet is targeted for less than 90 seconds with current performance at approximately
120 seconds. This time delay is comparable to the typical time interval between cone-beam CT images being acquired and beam-on in our institution ( 80 seconds). Generating artifactfree MR images while maintaining the linear accelerator in state of “beam-on readiness” requires a set of radio frequency isolation doors that separate the accelerator from the scanner during imaging. Upon completion of MR imaging and correction, the linear accelerator is capable of delivering noncoplanar, IMRT and volumetric modulated arc therapy (VMAT) deliveries at high-dose rates (6 MV; 1400 MU/min). The potential for online planning is evident and requires additional disease-specific development. In addition, the integration of the MR information with the kilovoltage imaging capabilities will provide opportunities for real-time monitoring during radiation delivery. It should also be noted that the MR scanner can also be deployed after treatment as part of a scheduled regimen of MR-based response assessment.
Planned “First-in-Human” Applications The clinical motivations for the facility include increased precision and accuracy of image-guided RT, online adaptation, and MR-based response assessment during RT with the patient in the treatment position.
Increase Accuracy and Precision The use of the system in paraspinal stereotactic body RT should be straightforward with the potential for direct visualization of the spinal cord with the patient in the treatment position and will enhance overall treatment quality and safety. Liver lesion visualization is challenging with cone-beam CT, and the addition of online MR imaging, including MR cine motion assessment,2 will provide greater confidence in target
Facility for MR-guided radiation therapy localization and possibly allow a reduction in planning target volume margins. In addition, current efforts in intraprostatic boost with either HDR brachytherapy or VMAT external-beam delivery will also be facilitated through the use of anatomical and functional MR imaging approaches to improved target localization.
Online or Off-Line Adaption Previous investigations by our group and others have highlighted the potential for adaptation using MR imaging.3,4 The MRgRT and MRgBT platforms will be applied in gynecologic cancer to assure target coverage with minimized normal tissue irradiation. Daily online MR imaging of tumor and normal tissue with the patient in the treatment position, linked to strategic replanning, and adaptation to account for systematic changes in tumor size, shape, or position have the potential to substantially enhance cure rates and reduce toxicity. Other clinical applications of this paradigm include head and neck cancer, preoperative sarcomas, and esophageal cancer and extend to brachytherapy for cancer of the cervix, prostate, and other sites, where real-time MR-guided positioning of applicators and needles will improve target coverage and conformality.
Response Assessment Based on previous experience, it is challenging for patients to complete frequent (eg, daily or weekly) image-based response assessments during a course of RT, especially when this requires separate or protracted visits to accommodate separate machine bookings. Acquiring these images as an integrated part of their treatment will contribute to our understanding of patient-specific response, including morphologic and functional (diffusion weighted imaging and dynamic contrastenhanced) changes.5-7 Initial disease sites that will be studied include cervix, head and neck, prostate, liver, and esophageal cancer. It is important to note that the MRgRT linear accelerator is identical to others in our program allowing patients to be periodically transferred to the MRgRT unit for MR-based response studies (eg, once per week).
Key Strengths The key strengths include high-quality MR imaging for online treatment guidance; high-performance radiation delivery (VMAT, noncoplanar) including real-time x-ray
195 guidance; avoidance of magnetic field–induced perturbations in delivered radiation dose; secondary validation of corrections using cone-beam CT; use of existing radiation commissioning standards; reliability and ongoing improvements associated with conventional RT and MR systems; and the capability for use without the magnetic field present. With respect to MRgBT, key strengths include MR imaging during applicator or catheter placement and optional use of MR and MR-compatible brachytherapy devices. A key strength of the combined facility is the ability to support MR-simulation activities before either BT or external-beam treatments to establish appropriate MR imaging sequences. A key limitation is the lack of real-time MR imaging during radiation delivery; however, the clinical relevance of this shortcoming is unclear.
Development Phase and Commercial Deployment The development of the system has been ongoing for the past 24 months with clinical deployment possible in Q2 of 2014. With regard to the commercial status of the system, Health Canada clearance for all components is expected in the next 18 months.
References 1. Menard C, Susil RC, Choyke P, et al: MRI-guided HDR prostate brachytherapy in standard 1.5 T scanner. Int J Radiat Oncol Biol Phys 59 (5):1414-1423, 2004 2. Kirilova A, Lockwood G, Choi P, et al: Three-dimensional motion of liver tumors using cine-magnetic resonance imaging. Int J Radiat Oncol Biol Phys 71(4):1189-1195, 2008 3. Stewart JMP, Lim K, Brock KK, et al: Automated weekly online replanning for IMRT of cervix cancer. Int J Radiat Oncol Biol Phys 72(suppl 1):S18, 2008 4. Potter R, Kirisits C, Fidarova EF, et al: Present status and future of highprecision image guided adaptive brachytherapy for cervix carcinoma. Acta Oncol 47(7):1325-1336, 2008 5. Foltz WD, Wu A, Chung P, et al: Changes in apparent diffusion coefficient and T2 relaxation during radiotherapy for prostate cancer. J Magn Reson Imaging 37(4):909-916, 2013 6. Eccles CL, Haider EA, Haider MA, et al: Change in diffusion weighted MRI during liver cancer radiotherapy: Preliminary observations. Acta Oncol:1-10, 2009 7. Lim K, Chan P, Dinniwell R, et al: Cervical cancer regression measured using weekly magnetic resonance imaging during fractionated radiotherapy: Radiobiologic modeling and correlation with tumor hypoxia. Int J Radiat Oncol Biol Phys 70(1):126-133, 2008
System Design he “system” defines a dedicated 320-m2 magnetic resonance (MR)-guided radiotherapy (RT) (MRgRT) facility (Fig. A) that satisfies the American College of Radiology MR safety guidelines and allows a rail-mounted 1.5-T MR scanner to operate in 3 different suites: (1) MR-simulation—Siemens Espree 1.5-T, 70-cm bore, and contrast injector, (2) MRgBT— MR-guided brachytherapy (Nucletron, MicroSelectron highdose rate (HDR), Ir-192, 10 Ci), and (3) MRgRT—MR-guided
T
*Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. †Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. ‡Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. §Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. ║Techna Institute, University Health Network, Toronto, Ontario, Canada. ¶Varian Medical Systems, Palo Alto, CA. #IMRIS, Minneapolis, MN. The employers of D.A.J., M.C.C., M.F.M., S.L.B., T.S., H.A., and A.S. have a codevelopment agreement with IMRIS, Inc. D.A.J.'s employer has a sponsored research agreement with Elekta Inc. M.S. is an employee of Varian Medical Systems, Inc. J.D.W. is an employee of IMRIS, Inc. Address reprint requests to D.A. Jaffray, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. E-mail: David. [email protected]
http://dx.doi.org/10.1016/j.semradonc.2014.02.012 1053-4296/& 2014 Published by Elsevier Inc.
external-beam RT (Varian, TrueBeam, 6 MV, 1400 MU/min). The facility is structured under the premise that the high field of the MR can be located in any 1 of the 3 suites, and hence these are considered “zone 4” (i.e., restricted access and strong MR field) by the American College of Radiology guidelines. A “zone 2” (screening room) limits access to the facility with the HDR, linear accelerator, and MR scanner control areas located in a common extended “zone 3” (restricted access). The 2 treatment suites can operate with or without the MR scanner present.
MR-Simulation MR imaging for purposes of simulation and treatment planning can be performed in the dedicated central MR-simulation suite without interfering with the adjacent treatment suites. In addition to standard 1.5-T coils, the system is equipped with a dedicated oncology coil set for extended field-of-view imaging of the head and neck, as well as, high-performance pelvic imaging. The coils integrate with the RT-specific flat table top and are identical to those to be used in the MRgRT room.
Magnetic Resonance–Guided Brachytherapy A set of automated shielding doors (6.4-cm Pb) allows the MR scanner to enter the MRgBT to permit MR imaging of the patient located on a dedicated OR table. Patient positioning is 193
D.A. Jaffray et al.
194
Screening room
Zone 2
MR Control Console
Zone 3
MRgBT Console
Zone 3
MRgRT Console
Zone 3
MRgBT Suite
Zone 4
MR Simulation
Zone 4
MRgRT Suite
Zone 4
Rail System for Magnet 1.5T Espree MR Varian TrueBeam Pedestal for Modified Couch 5G Line
View from MRgRT
Figure (A) Floor plan and safety zones of the MR-guided RT facility at the Princess Margaret Cancer Centre showing brachytherapy, imaging, and external-beam RT suites. (B) Photograph of the accelerator and MR scanner in the facility. The magnet is advanced on the rail system into the MRgRT suite, and the patient is positioned via a modified treatment couch. At nearest approach, the magnet to linear accelerator isocenter distance is 3.1 m.
facilitated by the short (125 cm), wide (70 cm) bore of the magnet. MR imaging is possible during applicator and needle placement; however, the MR must be withdrawn and doors closed before connecting the HDR afterloader to the implant. The room includes an “radio frequency isolation equipment room” to allow MR-incompatible equipment (ie, HDR, C-arm, and ultrasound) to remain energized during MR-based procedures. In addition, a MR-compatible template system is also employed to support MR-guided HDR for prostate cancer.1
Magnetic Resonance–Guided Radiotherapy Online MR-guided external-beam radiation delivery is achieved through the coordinated movement of the MR scanner, linear accelerator, and a modified treatment couch. A set of radiation shielding doors (20.3-cm Pb) opens to allow the MR scanner to advance over the patient who has been moved 3.1 m (Fig. B) between linac isocenter and in-room MR-imaging isocenter. The linear motion of the magnet is a safety design element to avoid patient-magnet collision risks. Additional safety components include a magnet motion “dead man switch” and various interlocks between the linear accelerator, magnet mover, and shielding systems. The linear accelerator is equipped with both megavoltage (portal) and kilovoltage imaging (rad, fluoro, and cone-beam computed tomography [CT]). MR images are routed through an image calibration system that corrects for reproducible variations (rigid) in MR imaging geometry and converts them to the treatment reference frame. These images are then routed to the RT Picture Archiving and Communication System system or image registration or planning system or both. Corrections are routed through the treatment console to allow rigid corrections in patient position based on MR-MR registration. The movement of the patient from MR imaging to treatment position and the withdrawal of the magnet is targeted for less than 90 seconds with current performance at approximately
120 seconds. This time delay is comparable to the typical time interval between cone-beam CT images being acquired and beam-on in our institution ( 80 seconds). Generating artifactfree MR images while maintaining the linear accelerator in state of “beam-on readiness” requires a set of radio frequency isolation doors that separate the accelerator from the scanner during imaging. Upon completion of MR imaging and correction, the linear accelerator is capable of delivering noncoplanar, IMRT and volumetric modulated arc therapy (VMAT) deliveries at high-dose rates (6 MV; 1400 MU/min). The potential for online planning is evident and requires additional disease-specific development. In addition, the integration of the MR information with the kilovoltage imaging capabilities will provide opportunities for real-time monitoring during radiation delivery. It should also be noted that the MR scanner can also be deployed after treatment as part of a scheduled regimen of MR-based response assessment.
Planned “First-in-Human” Applications The clinical motivations for the facility include increased precision and accuracy of image-guided RT, online adaptation, and MR-based response assessment during RT with the patient in the treatment position.
Increase Accuracy and Precision The use of the system in paraspinal stereotactic body RT should be straightforward with the potential for direct visualization of the spinal cord with the patient in the treatment position and will enhance overall treatment quality and safety. Liver lesion visualization is challenging with cone-beam CT, and the addition of online MR imaging, including MR cine motion assessment,2 will provide greater confidence in target
Facility for MR-guided radiation therapy localization and possibly allow a reduction in planning target volume margins. In addition, current efforts in intraprostatic boost with either HDR brachytherapy or VMAT external-beam delivery will also be facilitated through the use of anatomical and functional MR imaging approaches to improved target localization.
Online or Off-Line Adaption Previous investigations by our group and others have highlighted the potential for adaptation using MR imaging.3,4 The MRgRT and MRgBT platforms will be applied in gynecologic cancer to assure target coverage with minimized normal tissue irradiation. Daily online MR imaging of tumor and normal tissue with the patient in the treatment position, linked to strategic replanning, and adaptation to account for systematic changes in tumor size, shape, or position have the potential to substantially enhance cure rates and reduce toxicity. Other clinical applications of this paradigm include head and neck cancer, preoperative sarcomas, and esophageal cancer and extend to brachytherapy for cancer of the cervix, prostate, and other sites, where real-time MR-guided positioning of applicators and needles will improve target coverage and conformality.
Response Assessment Based on previous experience, it is challenging for patients to complete frequent (eg, daily or weekly) image-based response assessments during a course of RT, especially when this requires separate or protracted visits to accommodate separate machine bookings. Acquiring these images as an integrated part of their treatment will contribute to our understanding of patient-specific response, including morphologic and functional (diffusion weighted imaging and dynamic contrastenhanced) changes.5-7 Initial disease sites that will be studied include cervix, head and neck, prostate, liver, and esophageal cancer. It is important to note that the MRgRT linear accelerator is identical to others in our program allowing patients to be periodically transferred to the MRgRT unit for MR-based response studies (eg, once per week).
Key Strengths The key strengths include high-quality MR imaging for online treatment guidance; high-performance radiation delivery (VMAT, noncoplanar) including real-time x-ray
195 guidance; avoidance of magnetic field–induced perturbations in delivered radiation dose; secondary validation of corrections using cone-beam CT; use of existing radiation commissioning standards; reliability and ongoing improvements associated with conventional RT and MR systems; and the capability for use without the magnetic field present. With respect to MRgBT, key strengths include MR imaging during applicator or catheter placement and optional use of MR and MR-compatible brachytherapy devices. A key strength of the combined facility is the ability to support MR-simulation activities before either BT or external-beam treatments to establish appropriate MR imaging sequences. A key limitation is the lack of real-time MR imaging during radiation delivery; however, the clinical relevance of this shortcoming is unclear.
Development Phase and Commercial Deployment The development of the system has been ongoing for the past 24 months with clinical deployment possible in Q2 of 2014. With regard to the commercial status of the system, Health Canada clearance for all components is expected in the next 18 months.
References 1. Menard C, Susil RC, Choyke P, et al: MRI-guided HDR prostate brachytherapy in standard 1.5 T scanner. Int J Radiat Oncol Biol Phys 59 (5):1414-1423, 2004 2. Kirilova A, Lockwood G, Choi P, et al: Three-dimensional motion of liver tumors using cine-magnetic resonance imaging. Int J Radiat Oncol Biol Phys 71(4):1189-1195, 2008 3. Stewart JMP, Lim K, Brock KK, et al: Automated weekly online replanning for IMRT of cervix cancer. Int J Radiat Oncol Biol Phys 72(suppl 1):S18, 2008 4. Potter R, Kirisits C, Fidarova EF, et al: Present status and future of highprecision image guided adaptive brachytherapy for cervix carcinoma. Acta Oncol 47(7):1325-1336, 2008 5. Foltz WD, Wu A, Chung P, et al: Changes in apparent diffusion coefficient and T2 relaxation during radiotherapy for prostate cancer. J Magn Reson Imaging 37(4):909-916, 2013 6. Eccles CL, Haider EA, Haider MA, et al: Change in diffusion weighted MRI during liver cancer radiotherapy: Preliminary observations. Acta Oncol:1-10, 2009 7. Lim K, Chan P, Dinniwell R, et al: Cervical cancer regression measured using weekly magnetic resonance imaging during fractionated radiotherapy: Radiobiologic modeling and correlation with tumor hypoxia. Int J Radiat Oncol Biol Phys 70(1):126-133, 2008
