Site Imaging Manual ACRIN 6701

Transcription

1 Site Imaging Manual ACRIN 6701 Repeatability Assessment of Quantitative DCE MRI and DWI: A Multicenter Study of Functional Imaging Standardization in the Prostate Version: Final Version 1.0 Date: 09 Oct 2012

2 Table of Contents Letter of Introduction... 3 ACRIN 6701 Study Schema OVERVIEW OF IMAGING REQUIREMENTS STUDY OBJECTIVES/SPECIFIC AIMS SCANNER QUALIFICATION DWI Phantom Scanning DCE MRI Phantom Scanning Qualification Review Phantom Re scan Qualifying Image Submission Participant Eligibility Inclusion Criteria Exclusion Criteria Participant Scheduling Participant Preparation Contrast Agent Administration Standardized Image Acquisition Protocols Image Submission TRIAD Image Transmittal Worksheet (ITW) Image Quality Control (QC) Local Site Review of Imaging Site Assessment Specific to MRI Scan Site Assessment Specific to MRI Scan Locally Determined Deficient Imaging Study ACRIN Core Laboratory Quality Control Technical Review Image Data Queries Central Diagnostic Review of MRI SCAN Imaging Forms Oct 2012 pg. 1 of 16

3 REFERENCES 17 APPENDIX I: DWI PHANTOM TEST INSTRUCTIONS APPENDIX II: DCE PHANTOM TEST INSTRUCTIONS APPENDIX III: MRI SCAN 1 IMAGING PROCEDURES APPENDIX IV: MRI SCAN 2 IMAGING PROCEDURES APPENDIX V: MRI IMAGE ACQUISITION PARAMETERS History of Revisions: 09 Oct 2012 pg. 2 of 16

4 Letter of Introduction Dear Imaging Staff, This Site Imaging Manual contains the image acquisition instructions for the ACRIN 6701 trial: Repeatability Assessment of Quantitative DCE MRI and DWI: A Multicenter Study of Functional Imaging Standardization in the Prostate. To successfully meet the study objectives, it is critical that the DCE MRI and DWI image datasets are acquired according to the imaging protocol detailed in this manual. Quality Control (QC) review of the images will be performed by the ACR Imaging Core Laboratory. This review will be performed in a timely fashion, as part of ACRIN standard operating procedures. If any protocol deviations or technical issues are identified during the review, an ACR Core Lab Imaging Technologist will contact your site to provide feedback expeditiously. This will allow your site to make any necessary adjustments early in the conduct of the study. The ACRIN 6701 Imaging Team wishes to thank you in advance for your diligence in adhering to the procedures described in this manual to ensure the integrity of the image data collected for the study. Please do not hesitate to contact the ACRIN 6701 Imaging Technologist (see contact information below) if you have any questions. Sincerely, Dena Flamini RT(R)(M)(MR) ACRIN 6701 Imaging Analyst American College of Radiology 1818 Market Street Suite 1600 Philadelphia, PA Phone: (215) Fax: (215) dflamini@acr.org 09 Oct 2012 pg. 3 of 16

5 ACRIN 6701 Study Schema 42 Day Maximum Timeline from Enrollment to Completion of Both MRI Scans Day #0 Eligibility/Enrollment: Calculate GFR for Renal Function ACRIN Web Registration Between 0 and 28 days later SOC Anatomic MRI plus Study Related DWI Scan and Gad Enhanced DCE MRI #1: MRI Between 0 and 28 Days after Enrollment Between 2 to 14 days later Study Related DWI Scan and Gad Enhanced DCE MRI #2: MRI Between 2 and 14 Calendar Days after MRI Scan #1 TREATMENT 09 Oct 2012 pg. 4 of 16

6 1.0 OVERVIEW OF IMAGING REQUIREMENTS DCE MRI and DWI Qualification TRIAD Installation Time Points for Trial Examinations Image Submission Data Queries Rescanning With Phantom for Maintenance Submit prior to site activation (for each scanner): Protocol Specific Application (PSA) Submission of phantom based DCE MRI and DWI qualification exams (acquired per the ACRIN 6701 standardized imaging protocol). Should be installed prior to study participant enrollment for secure, electronic submission of imaging to ACRIN. DCE MRI and DWI per standardized ACRIN 6701 acquisition protocol provided in this imaging manual: MRI/DWI/DCE MRI 1: between 0 and 28 days of enrollment (at time of standard of care anatomic MRI per institutional practice) MRI/DWI/DCE MRI 2: between 2 and 14 calendar days after MRI Scan #1 ACRIN 6701 imaging should be submitted electronically to the ACR Imaging Core Lab via TRIAD. All imaging should be submitted within 48 hours after acquisition and should include an Image Transmittal Worksheet (ITW). ACRIN will issue queries, as needed, based on QC review of imaging. The qualification phantoms must be rescanned prior to any subsequent participant scan if there are any substantive changes in scanner hardware or software during the trial. General Trial Requirements: 3T whole body MRI scanner Institutional expertise in prostate MRI (proven record of 50 prostate MRIs per year) Site must be able to utilize a torso array coil Site must be able to utilize a power injector The site must perform both study related DCE MRI and DWI examinations on the same MRI unit for the same participant using the same magnet configuration (manufacturer; field strength; coil) Site must submit all trial exams to ACRIN within 48 hours after acquisition NOTE: It may be helpful to keep a copy of this Manual in the imaging department, so all technologists involved in the image acquisition of ACRIN 6701 are privy to the protocol required imaging specifications. 09 Oct 2012 pg. 5 of 16

7 2.0 STUDY OBJECTIVES/SPECIFIC AIMS The Quantitative Imaging Biomarkers Alliance (QIBA) dynamic contrast enhanced magnetic resonance imaging (DCE MRI) committee is working to identify the limits of reproducibility of DCE MRI quantitative metrics critical for useful biomarker studies. The ACRIN 6701 trial will examine the QIBA DCE MRI profile claims regarding the repeatability of tumor DCE MRI, as well as repeatability of diffusion weighted imaging (DWI) metrics, and evaluate the performance of these metrics in human subjects with prostate tumors. In addition to implementing the imaging protocol, the trial will introduce site imaging personnel to proper procedures for magnet qualification, the selection of tumor bearing human subjects, and the implementation of the proper DCE MRI and DWI parameters in general oncologic MRI. Primary Hypothesis Within the context of a multi site clinical trial, the upper limits of the repeatability coefficient (RC) for DCE MRI metrics K trans and blood normalized initial area under the gadolinium curve (IAUCG90 bn ), and DWI metric D(t), using the whole prostate as a target lesion, can be demonstrated to be less than or equal to the pre specified values that signify the minimal detectable significant biologic change of each quantitative MRI metric. Hypothesis #1: The repeatability coefficient (RC) of the DCE MRI metric K trans, as measured by median pixel values of the whole prostate, is equal to or less than 22%. Hypothesis #2: The RC of the DCE MRI metric IAUGC90 bn (blood normalized initial area under the gadolinium curve between 0 and 90 seconds), as measured by median pixel values of the whole prostate, is equal to or less than 0.05 (in normalized units). Hypothesis #3: The RC of DWI metric D(t), as measured by median pixel values of the whole prostate, is equal to or less than 0.3 x 10 3 mm 2 /sec. 3.0 SCANNER QUALIFICATION Participation in the ACRIN 6701 requires that all sites adhere to standardized DCE MRI and DWI protocol parameters. The use of standard imaging guidelines is an essential component of clinical trials in which imaging plays a central role in the research endpoints. This is of particular importance in multicenter trials where equipment, personnel, and imaging acquisition protocols can vary significantly. Thus, the use of standardized imaging guidelines helps control the inter and intravariability inherent in multicenter imaging trials. The purpose of any imaging qualification process is to help ensure the trial imaging is of high quality and performed per the trial standardized acquisition protocol. To participate in the ACRIN 6701 trial, each site must qualify by first scanning the DWI and DCE MRI phantoms based on ACRIN 6701 phantom scanning protocols. Phantom scanning provides an opportunity to evaluate compliance 09 Oct 2012 pg. 6 of 16

8 with sample imaging acquisition protocols prior to participant recruitment and actual trial specific protocols. These qualification examinations will be reviewed by the ACR Imaging Core Lab for both protocol compliance and image quality; approval of the qualification exams is required prior to ACRIN 6701 site activation. Suboptimal image quality and/or imaging not performed per the trial standardized protocol can result in exclusion of the imaging exam(s) and/or the entire case from analysis. Therefore, routine QC and adherence to the ACRIN 6701 image acquisition protocol are of great importance, and sites will be asked to re scan using the phantoms should there be any substantive changes in hardware or software to the scanner during the conduct of the trial. 3.1 DWI Phantom Scanning Prior to site qualification, a DWI phantom test scan must be run. Sites will be provided with a DWI ice water phantom; this phantom consists of a 1.5 liter white plastic container with a sealed 75ml tube pre filled with distilled water. The design of this phantom allows for the measurement of apparent diffusion coefficient (ADC) values of a known temperature controlled fluid to confirm proper MRI system performance in acquisition of diffusion weighted (DW) imaging. Upon completion and approval of the DWI phantom qualification testing, sites are asked to keep the ice water phantom in the event that there is a need for DWI phantom testing re qualification. Please see Appendix I for detailed DWI phantom test scan parameters and instructions. 3.2 DCE MRI Phantom Scanning Prior to site qualification, a DCE phantom test scan must be run to assess MRI system performance. Sites will be provided a standardized multi compartment R1 phantom having inserts with T1 relaxation times spanning the ranges typically obtained in blood and in tissue. Sites are to retain the DCE phantom, until the ACR Imaging Core Lab has approved the submitted imaging; a Core Lab representative will then provide detailed shipping instructions. Please see Appendix II for detailed DCE phantom test scan parameters and instructions. 3.3 Qualification Review The qualification exam will be evaluated for image quality (e.g. artifacts, distortion, and signal to noise) and compliance with the standardized DCE MRI and DWI acquisition protocol. An ACR Imaging Core Lab Imaging Technologist will notify the site of the results of the qualification review via e mail. E mail documentation will include your site s Study Coordinator (SC), site PI, and lead technologist to inform the site team whether the qualifying exams have been approved or not. If the qualifying exams are not approved, required corrections for rescanning will be included in the e mail. NOTE: Approval of these qualifying exams is mandatory prior to your site registering a participant onto the ACRIN 6701 trial. 09 Oct 2012 pg. 7 of 16

9 3.4 Phantom Re scan If DWI or DCE MRI initial phantom scans are not approved after initial scanning and submission, phantom re scans (DWI or DCE MRI) will be required until parameters for approval are met for site qualification. Upon approval of both the DWI and DCE MRI phantom scans, no additional requalification is required unless one of the following conditions occurs: a. New scanner being introduced. A new scanner system, not ACRIN qualified via phantom assessment, is to be used for subsequent patient studies. b. Major changes to qualified scanner. A major change in scanner hardware or software occurs during the course of the study. This would include major software upgrades (i.e., a software upgrade that result in a new software primary version number) and changes to the coil system, gradient systems, or RF amplifier. Periodic minor updates to existing software versions are not considered major changes. c. Trial ongoing after one year. If active patient accrual and scanning are underway at one year after the date of the original approval of the phantoms for the trial, then requalification will be required, with replicate scanning of the DWI and/or DCE MRI phantoms. NOTE: We strongly encourage sites to use a single 3T MRI scanner for the entire study. However, a second 3T MRI scanner for use in this study may be necessary for some sites. In such cases, qualification via DWI and DCE MRI phantom scanning and approval is necessary for each scanner to be used in the study. ACRIN strongly encourages that all MRI scans for a given patient take place on the same scanner unless such is not feasible due to temporary scanner failure. 3.5 Qualifying Image Submission Phantom images in DICOM format are to be sent to the ACR Imaging Core Lab on Compact Disc (CD) or DVD. Please label the disk, in permanent marker, with the following information: Site Name Trial Name (ACRIN 6701) Date of Phantom Imaging (DD MMM YYY) Type of Phantom Imaging (e.g. DWI or DCE imaging) For questions related to DCE MRI/DWI phantom qualification, please send an to: imagearchive@acr.org. Enter ACRIN 6701 DCE MRI/DWI Qualification in the subject line. Ship All Qualification Imaging to: American College of Radiology 1818 Market St., Suite 1600 Philadelphia, PA Attn: ACRIN 6701 DCE MRI/DWI Qualification 09 Oct 2012 pg. 8 of 16

10 4.0 Participant Eligibility 4.1 Inclusion Criteria Men 18 years of age or older Diagnosis of prostate cancer by trans rectal ultrasound (TRUS) guided biopsy 28 to 90 days prior to enrollment Minimal tumor burden as defined by at least one of the following criteria: o One single core with 50% cancer burden and 5 mm tumor length o Two or more cores in the same prostate region, each with 30% cancer burden o Three or more cores positive for prostate cancer (of any magnitude of cancer burden) in the same prostate region o Gleason grade 7 or higher cancer burden o PSA 10 mg/ml 4.2 Exclusion Criteria Severe claustrophobia not relieved by oral anxiolytics per institutional standard practice Presence of MRI incompatible metallic objects or implanted medical devices in body (including but not limited to: non MRI compatible metal objects, cardiac pacemaker, aneurysm clips, artificial heart valves with steel parts, metal fragments in the eye or central nervous system) Renal failure, as determined by glomerular filtration rate (GFR) < 30 ml/min/1.73 m 2 based on a serum creatinine level obtained within 48 hours prior to enrollment Weight greater than that allowable by the MRI table, per local institutional practice Anti androgenic therapy within 30 days prior to enrollment Prior external beam, proton, or brachytherapy to the prostate Prior hip replacement or other major pelvic surgery 09 Oct 2012 pg. 9 of 16

11 5.0 Participant Scheduling Participants will undergo two 3T MRI studies for the trial. These quantitative MRI studies (DCE MRI and DWI) will be performed without the endo rectal coil. Sites are to follow local procedures for endorectal coil use during the first MRI, which should be the standard practice anatomical MRI. MRI SCAN 1 and MRI SCAN 2 must be completed no less than 2 calendar days (to ensure 24 hours for clearance of gadolinium) and no greater than 14 days apart, and both must be completed prior to treatment initiation. NOTE: The same MRI unit and configuration must be used for MRI SCAN 1 and MRI SCAN 2. The same contrast agent used for MRI SCAN 1 must be utilized for MRI SCAN Participant Preparation Prepare participant according to local standard practice, including any pre treatment for severe claustrophobia or anxiety. Confirm renal function sufficiency prior to imaging (egfr must be assessed within 48 hours prior to participant enrollment but does not have to be repeated for the trial as long as scheduling timelines do not deviate). Same size and placement of the intravenous catheter is recommended for both MRI scans. Each participant should have an intravenous catheter with a gauge no smaller than 20 gauge. Ideally, the injection site that was used for the initial exam (MRI SCAN 1) should be the same for all subsequent exams for that given patient (MRI SCAN 2) and any additional imaging that may be required to complete the trial protocol (see protocol Sections 8.3 and for details). Injection through a port a catheter or other permanent indwelling central catheter is not permitted. The participant will be placed supine in the magnet; arms at side are acceptable. The torso array coil should be placed about the pelvis per institutional standard practice. Landmark the participant at the level of the symphysis pubis Initiate imaging NOTE: If institutional standards require the use of endo rectal coil for anatomic imaging during MRI SCAN 1, this should be placed prior to imaging as per intuitional practice. See note regarding the use of endo rectal coil for anatomic imaging in Appendix III Part II. 7.0 Contrast Agent Administration Each participant should have an intravenous catheter (no smaller than 20 gauge), placed prior to imaging. Contrast agent should be administered in a dynamic fashion with a power injector at both test and re test time points. 09 Oct 2012 pg. 10 of 16

12 Contrast injection should begin seconds after the start of data acquisition. For the DCE (3D T1) sequence, gadolinium contrast agent should be administered intravenously at a dose of 0.1 mmol/kg body weight and rate of 2 ml/second, followed by a 20 ml saline flush, also at 2 ml/second. The type, amount, rate of injection, and site/gauge of IV should comply with the study guidelines and should be documented by the technologist on the MRI Scan Administration form. NOTE: The gadolinium agents MultiHance, Eovist, and Vasovist are NOT permitted to be used as a contrast agent for the subjects on this trial. Also, keep in mind that the same brand and dose of contrast, same IV site, and same rate of contrast and saline flush administration should be maintained for both the test and re test examinations. 8.0 Standardized Image Acquisition Protocols At each time point, the ACRIN 6701 imaging protocols will include a: Pre contrast T2 weighted sequence Pre contrast diffusion weighted imaging (DWI) SE EPI sequence Pre contrast T1 mapping sequence set Pre contrast coil ratio map sequence set Pre /post contrast T1 weighted dynamic contrast enhanced (DCE) sequence Please review the participant preparation description in Section 6.0 above and the following participant preparation instructions and acquisition parameters carefully as this imaging protocol may or may not align with your institution s standard prostate MRI protocol. NOTE: Additional imaging for clinical staging as per institutional routine may occur during MRI SCAN 1. See Appendices III V for time point specific exam sequences. 9.0 Image Submission 9.1 TRIAD All trial exams will be submitted to ACR Core Laboratory via TRIAD. TRIAD is a software application that ACRIN provides for installation on a site s PC. One or several computers of choice within the institutional firewall and on the institutional network may be equipped with TRIAD software; internet access is also required. The TRIAD application can then be configured as a DICOM destination on either scanner(s) and/or PACS system for direct network transfer of study related images into the TRIAD directory. When properly configured, the TRIAD software anonymizes, encrypts, and performs a lossless compression of the images before they are transferred to the ACRIN image archive in Philadelphia. Your site will need to communicate with their IT department for assistance with the initial steps outlined in the TRIAD Pre Installation Checklist (see Appendix VI) prior to scheduling TRIAD 09 Oct 2012 pg. 11 of 16

13 installation. Once equipment readiness has been determined, imaging personnel from ACRIN will coordinate installation and training for the software. The TRIAD Installation Guide and TRIAD Users Guide can be found online at To contact TRIAD Support call: or TRIAD 9.2 Image Transmittal Worksheet (ITW) All imaging should be submitted within 48 hours after acquisition and should include an Image Transmittal Worksheet (ITW). An Image Transmittal Worksheet (ITW) is used during the exam QC review to verify a complete transfer of images has been submitted to the ACR Imaging Core Lab. The ITW is completed in the Medidata/Rave data management system and upon the completion of this form, an will be automatically generated to the ACRIN Imaging Technologist to notify an image submission has taken place Image Quality Control (QC) 10.1 Local Site Review of Imaging Site Assessment Specific to MRI Scan 1 After completion of imaging for MRI SCAN 1, the study should be reviewed based on standard institutional practices for clinical image review and reporting. This assessment will include: Adequacy of endo rectal coil placement for anatomic imaging (if applicable) Proper placement and functional of torso array coils throughout all imaging sequences Removal of endo rectal coil (if applicable) and proper participant repositioning and landmarking prior to initiation of non endo rectal coil study imaging sequences Adequacy of anatomic imaging, especially the axial T2 weighted series, with: o proper anatomic prescription to include entire prostate and seminal vesicles o acceptable signal to noise ratio o absence of severe artifacts that would render the series clinically nondiagnostic Adequacy of DWI imaging, with: o proper acquisition parameters, including FOV, matrix, phase direction, slice thickness, and use of fat saturation o proper anatomic prescription to include entire prostate and seminal vesicles 09 Oct 2012 pg. 12 of 16

14 o proper number and choice of B values o acceptable signal to noise ratio o absence of severe artifacts that would render the series clinically nondiagnostic Adequacy of DCE MRI imaging, with: o proper acquisition parameters, including FOV, matrix, phase direction slice thickness, and slice number o proper anatomic prescription including full pelvic imaging with prostate located eccentrically in the inferior aspect of the slab to minimize arterial inflow o completion of all three aspects of the DCE MRI series: T1 mapping, coil ratio map, and dynamic gadolinium imaging, with proper choices of flip angle, signal averaging, and number of phases for each o correct choice of contrast agent type, dose, rate of injection, and timing of injection o acceptable signal to noise ratio o absence of severe artifacts that would render the series clinically nondiagnostic Site Assessment Specific to MRI Scan 2 After completion of imaging for MRI SCAN 2, the study should be reviewed based on standard institutional practices for clinical image review and reporting. This assessment will include: Proper placement and functional of torso array coils throughout all imaging sequences Adequacy of axial T2 weighted series for prostate localization Adequacy of pre coffee break DWI imaging, with: o proper acquisition parameters, including FOV, matrix, phase direction, slice thickness, and use of fat saturation o proper anatomic prescription to include entire prostate and seminal vesicles o proper number and choice of B values o acceptable signal to noise ratio o absence of severe artifacts that would render the series clinically nondiagnostic Correct implementation of the coffee break as evidenced by correct replacement of torso array coils, repeat landmarking and axial T2W imaging, repeat localizer imaging, and adequate temporal gap between the two DWI image sets (minimum of three minutes) Adequacy of post coffee break DWI imaging, with: 09 Oct 2012 pg. 13 of 16

15 o proper acquisition parameters, including FOV, matrix, phase direction, slice thickness, and use of fat saturation o proper anatomic prescription to include entire prostate and seminal vesicles o proper number and choice of B values o acceptable signal to noise ratio o absence of severe artifacts that would render the series clinically nondiagnostic Adequacy of DCE MRI imaging, with: o proper acquisition parameters, including FOV, matrix, phase direction slice thickness, and slice number o proper anatomic prescription including full pelvic imaging with prostate located eccentrically in the inferior aspect of the slab to minimize arterial inflow o completion of all three aspects of the DCE MRI series: T1 mapping, coil ratio map, and dynamic gadolinium imaging, with proper choices of flip angle, signal averaging, and number of phases for each o correct choice of contrast agent type, dose, rate of injection, and timing of injection o acceptable signal to noise ratio o absence of severe artifacts that would render the series clinically nondiagnostic Locally Determined Deficient Imaging Study If the standard practice anatomic sequences of MRI SCAN 1 are deemed suboptimal for clinical evaluation by the local site imaging team, the site PI/radiologist has the discretion to recommend repeat of one or more clinical imaging series during MRI SCAN 2. The endo rectal coil is not expected to be used for any imaging sequences during MRI SCAN 2. However, if the local site radiology investigator deems that re use of the endorectal coil per standard institutional practice for repeated clinical anatomic imaging is desirable, repeat endo rectal coil placement is allowed for this portion of MRI SCAN 2. The recommendation for re use of the endo rectal this should be adequately explained to the participant prior to MRI SCAN 2. Similarly, if the study specific DWI and/or the DCE MRI sequences of MRI SCANS 1 or MRI SCAN 2 are deemed technically inadequate or incomplete/not per protocol specifications, the site PI/radiologist and/or ACRIN has the option to recommend repetition of the deficient study sequences as a separate visit. Only willing participants will undergo additional imaging visits. Any participants unwilling to complete repeat imaging studies will be off study and will be replaced to meet trial accrual. 09 Oct 2012 pg. 14 of 16

16 Repeat imaging must adhere to the protocol specific imaging procedures and performed within 14 days of the non deficient imaging study. The site must appropriately document all cases in which deficient imaging led to repeat of imaging. Contact the trial s lead ACRIN data manager for assistance as needed ACRIN Core Laboratory Quality Control Technical Review Upon receipt of the images at the ACR Imaging Core Lab, an initial QC review will be conducted by a qualified ACRIN Imaging Technologist. The ACRIN Imaging Technologist will check for missing images/sequences, appropriate image anonymization, complete anatomical coverage of the prostate, adherence of all sequences to imaging protocol, and absence of image artifact. In cases where image sets are judged to be suboptimal ( technically inadequate ), the trial PI will be informed, and a replacement participant will be accrued from participating institution Image Data Queries If it is found during the QC review that the submitted exam has missing data or does not follow the protocol guidelines, detailed in this manual, the Medidata/Rave data management system will generate an auto query. Sites are expected to resolve data queries expeditiously. Queries not resolved within 7 business days will be sent to the ACRIN 6701 trial team for additional follow up Central Diagnostic Review of MRI SCAN 1 Prior to quantitative DWI and DCE MRI analysis, two central radiologists will each assess for the presence of visible tumor nodules. If central diagnostic evaluation of MRI SCAN 1 by either reader fails to reveal a definite or likely tumor nodule of 5 mm or greater, a replacement participant will be enrolled to the trial Replacement participants will be enrolled for any of the following reasons An enrolled participant does not complete all required imaging for MRI SCAN 1 and MRI SCAN 2 Either MRI SCAN 1 and/or MRI SCAN 2 is determined to be technically inadequate, and the inadequate imaging series cannot be obtained during a repeat visit. MRI SCAN 1 does not reveal at least one definite or probable tumor nodule 5mm or greater as determined by each of two independent central readers. Replacement participants will be accrued at the same participating site with the same vendor equipment, if the participant whose deficient imaging needs to be replaced (in order to maintain accrual of 10 participants to each vendor manufacturer). 09 Oct 2012 pg. 15 of 16

17 Participants with complete MRI SCAN 1 and MRI SCAN 2 imaging data sets, but whose MRI SCAN 1 does not define a dominant tumor nodule, will still be evaluated for the non tumor endpoints (e.g. whole prostate evaluation for DWI and DCE MRI) Imaging Forms There are 5 imaging forms that must be completed and submitted via the Medidata/Rave ecrf system for each DCE MRI and DWI exam. Image Transmittal Worksheet (ITW) Imaging Procedure form MRI Scan Administration MRI Imaging Assessment Anatomic MRI Imaging Assessment DWI/DCE MRI It is recommended that each of the above forms be made available, in hard copy format, for the Imaging Technologists to be completed during image acquisition when the requested information on these forms is most readily available. Worksheets of the data asked throughout the various imaging forms have been created to aid the technologist during imaging and are included in the appendices of this document. These Worksheets are meant to approximate the actual ACRIN 6701 screens in the Medidata EDC system (e.g. provide users of the EDC system with the questions asked on the forms within the system). Please note that these are worksheets and are only meant as a HELP TOOL for users who wish to know/prepare for the information content of the e CRFs prior to actually logging into the Medidata EDC system. Note: In the event these worksheets are used, they should be considered source documents and stored in the participant s medical record. Please do NOT submit the worksheets to ACRIN all participant and image related data must be provided electronically in the Medidata database and no hard copy forms/worksheets will be accepted. 09 Oct 2012 pg. 16 of 16

18 Appendix I Appendix I DWI Phantom Test Instructions MRI DWI Phantom Test Instructions Page 1 of 8 09 Oct 2012

19 Appendix I DWI PHANTOM TEST INSTRUCTIONS Objective: Measure apparent diffusion coefficient (ADC) values of a known temperature controlled fluid to confirm proper MRI system performance in acquisition of diffusion weighted (DW) images of the pelvis using a pelvis/torso array coil. DWI Ice Water Phantom Preparation Procedure: Once prepared, an ice water phantom requires approximately 1 hour to reach thermal equilibrium. Please plan on filling the phantom well in advance of scanning. Once at thermal equilibrium, the phantom will be usable for several hours. Do not dispose of foam insulation sleeves and zip lock plastic bag shipped with each phantom. 1. The phantom consists of a 1.5 liter white plastic container with a sealed 75 ml tube prefilled with distilled water. Leave the 75 ml tube sealed and affixed within the container. For phantom preparation, temporarily remove the container from the foam insulation sleeve and zip lock bag. 2. You will need a source of ice cubes or ice chips and a sink basin for phantom filling. The volume of ice cubes/chips required is approximately twice the volume of the white container. Fill the white container to the top with ice cubes/chips then add cold tap water and fill to the top the colder the water, the better. Loosely cap the phantom for an initial cool down period of approximately 10 minutes. 3. Depending on how cold your tap water is, much of the ice will melt relatively quickly. Therefore after 10 minutes, reopen the container and pack in more ice to replace the melted ice. Fill ice to the top allowing displaced water to overflow into the sink. The objective is to have ice cubes to the full depth of the phantom and the interstitial space filled with water and minimal air (Figure 1). Screw cap on tightly, dry off the phantom and inspect for leaks. 4. Put the phantom into a foam insulation sleeve with the container top toward the open end of the sleeve and seal the phantom in a zip lock bag. Set the phantom aside for an additional 50 minutes to allow the central tube to come to thermal equilibrium with the surrounding ice water. As long as there is adequate ice in the phantom, temperature will be controlled to near 0 C, thereby holding water within the tube at a MRI DWI Phantom Test Instructions Page 2 of 8 09 Oct 2012

20 Appendix I known diffusion coefficient. The phantom should be usable for several hours within the insulation sleeve. If desired, you can store the phantom in a refrigerator (not a freezer) to extend the usable time. 5. After scanning, simply empty the ice water down the drain but leave the central tube filled and sealed for use at a later date by following the same procedure. DWI Ice Water Phantom Scan Procedure: 1. Set up the DWI phantom in the center of the magnet table, placed upright as shown in Figure 2a. If appropriate for torso array coil imaging at your center, place posterior torso coil under the phantom first. 2. Place foam pads or blocks on sides of the phantom to support the anterior torso/pelvic coil (e.g. see Figure 2). If your system requires additional coil loading, place an appropriate loading coil adjacent to the phantom. Alternately, a torso type loading coil can be used. Finally place the anterior torso array coil as shown in Figure 2b. 3. Start a New Patient/Exam using the same patient entry convention normally used for pelvis (non ecoil) MRI exams (e.g. head first, supine ). 4. Keep phantom in the zip lock bag and insulation sleeve during the scan procedure to keep condensate off of MRI system components. 5. If required, wedge or tape the phantom using patient support pads to hold the phantom firmly in place with the water tube approximately vertical (e.g. parallel to anteriorposterior axis) as shown in Figure 1. Precise alignment is not required, although the phantom should be positioned roughly in the center of the magnet bore. Overview of Series Required for DWI QC Phantom Scanning: 1. Three plane scout/survey 2. Axial 3D T1 weighted spoiled gradient echo without fat suppression 3. Axial DWI using single shot echo planar imaging (EPI) at b values=0, 100, 600, 800s/mm 2. Note: A set of DWI containing all 4 b values is called one pass. MRI DWI Phantom Test Instructions Page 3 of 8 09 Oct 2012

21 Appendix I 4. Copy & Paste the DWI series and repeat to acquire a total of four passes in immediate succession in four consecutive series. Avoid changing scanner pre scan/hardware settings between these consecutive series. Details of Required Series: 1. Three plane scout/survey: Use site preferred body sequence as used for graphic prescription of subsequent series. 2. Axial 3D T1 weighted spoiled gradient echo without fat suppression: FOV = 320mm (A/P phase) x 320mm (R/L frequency) at 256 x 256 matrix. 3. Acquire 4mm slice thickness interpolated to 2mm. Acquire sufficient slices to cover 120mm in the superior/inferior direction. TR=4 10ms, TE=min, flip angle 10 o, single average, acquisition time <3min. 4. Axial single shot isotropic diffusion weighted single SE, echo planar imaging (EPI) by parameter settings listed in Table 1 below. One DWI pass should contain all 4 b values. Copy and paste the DWI series so that 4 consecutive passes are acquired in separate series. If the MRI system cannot acquire all b values in one series, see note in section (e) under Table 1. Note: Total scan time for DWI is approximately 4 passes x 3min/pass = 12min. MRI DWI Phantom Test Instructions Page 4 of 8 09 Oct 2012

22 Appendix I Table 1. DWI Ice Water Phantom SE EPI Scan Parameters DWI Single Shot SE EPI Single Echo Field Strength 3T DWI Sequence Single Shot SE EPI Single Echo Receiver Coil Torso/Pelvis Array FOV (mm) 320 RL x 260 AP Acquisition Matrix 160 RL x 128 AP *(a) Reconstruction Matrix 256 x 256 *(b) Orientation Axial (Foldover Phase AP; Freq RL) Number of Slices 27 Slice Thickness (mm) 5 mm Gap (mm) 0 TR (ms) >8000 TE (ms) Half scan, Partial Fourier, Frac NEX No *(a) Number of Gradient Directions 3 orthogonal axes *(c) Freq Enc Bandwidth (Hz/px) 1500 to 2500 *(d) Parallel Imaging Factor (e.g. SENSE) 2 b values (s/mm2) 0, 100, 600, 800 *(e) Number Signal Averages 2 Fat Suppression On *(f) Image Filtering (e.g. SCIC or CLEAR) Off (*) Notes a. Some systems may require half scan, partial Fourier, or fractional NEX in DWI scans. It is preferred to acquire the full phase encode matrix = 120 by setting halfscan/ partial fourier/fractional NEX to No or at least as close to 1 as possible. b. Interpolate image matrix to 256 x 256. Some systems may do this automatically. c. Acquire DWI along three orthogonal axes so that isotropic or trace diffusion weighted images are generated for each slice and b value. Tetrahedral or Gradient Overplus diffusion encoding schemes are allowed wherein combinations of X, Y, and Z gradients are applied simultaneously for each orthogonal DWI axis. Individual diffusion axes DW images are not required. Only the b=0 and DWI trace images at each b value are required. d. Frequency encoding bandwidth may not be under full operator control. If possible use maximum bandwidth, or equivalently minimum fat shift per pixel, or set within 1500 to 2500 Hz/pixel range. MRI DWI Phantom Test Instructions Page 5 of 8 09 Oct 2012

23 Appendix I e. It is preferred to acquire all four b values in a single series. The collection of all b values is called one pass. However, if on a particular MRI system it is not possible to acquire all four b values in one series, it is allowable to acquire these in three separate sequential series: b=0, 100 followed by b=0, 600 then b=0, 800. On such scanners, these three series constitute one pass. DO NOT allow TE to change (e.g. set OPTIMIZE TE to NO ), and do not allow the system to adjust hardware settings (e.g. transmit/receive gain) between DWI series. NOTE: The PHANTOM PROTOCOL CALLS FOR FOUR ACQUISITIONS AT EACH b VALUE. If the scanner acquires all b values in a single series, simply repeat the DWI in four sequential series (e.g. Scan #1 b=0, 100, 600, 800; Scan #2 b=0, 100, 600, 800) If the scanner can only acquire one b value pair per series, then perform 12 sequential scans in order: Scan #1 b=0, 100; Scan #2 b=0, 600; Scan #3 b=0, 800; Scan #4 b=0, 100; Scan #5 b=0, 600; Scan #6 b=0, 800; Scan #7 b=0, 100; Scan #8 b=0, 600; Scan #9 b=0, 800; Scan #10 b=0, 100; Scan #11 b=0, 600; Scan #12 b=0, 800. f. Use site preferred spectral fat suppression technique, such as SPAIR, but unlike protocol used on patients DO NOT USE the Inversion Recovery fat suppression technique STIR for DWI Phantom scans ADC Map Generation: Generate ADC maps for all slices using software tools available on the scanner. The ADC map should be derived from the full set of b values = 0, 100, 600, 800. If the system only acquired one pair of b values in each series, generate the ADC maps using the b value = 0, 800 pair. If possible, take a screenshot of a region of interest (ROI) drawn in a central tube region showing ROI size/location and resultant statistics (e.g. See Figure 3). The screenshot should be simply saved within the phantom examination for transfer to ACRIN as DICOM images. Site certification and QC calculations will be performed on ADC maps regenerated at ACRIN core labs; however screenshots are helpful to confirm proper image scaling and equivalence in ADC calculation routines. MRI DWI Phantom Test Instructions Page 6 of 8 09 Oct 2012

24 Appendix I Figure 1: MRI of DWI phantom ice water contents Figure 2: : (a) Position DWI phantom vertically on center of table with pads and/or coil load to support anterior component of torso/pelvic phased array coil, as shown in (b). MRI DWI Phantom Test Instructions 09 Oct 2012 Page 7 of 8

25 Appendix I Figure 3: Screen capture of ROI on ADC map Qualifying Image Submission Please label the disk, in permanent marker, with the following information: Site Name Trial Name (ACRIN 6701) Date of Phantom Imagingg (DD MMM YYY) Type of Phantom Imagingg (DWI) Do not de identify DWI phantom images. Submit all DWI phantom images, including screen shots, to the ACRIN Imaging Core Laboratory on Compact Disc (CD) or DVD. For questions related to DWI phantom qualification, please send an to: imagearchive@acr.org. Enter ACRIN 6701 DCE MRI/DWI Qualification in the subject line. Ship All Qualification Imaging to: American College of Radiology 1818 Market St., Suite 1600 Philadelphia, PAA Attn: ACRIN 6701 DCE MRI/DW WI Qualification MRI DWI Phantom Test Instructions 09 Oct 2012 Page 8 of 8

26 Appendix II Appendix II DCE Phantom Test Instructions MRI DCE Phantom Test Instructions 1 of 5 Appendix II 09 Oct 2012

27 Appendix II MRI DCE QIBA PHANTOM TEST INSTRUCTIONS Objective: This document provides information regarding the MRI DCE QIBA phantom tests. The QIBA MRI DCE phantom is not currently a commercially available phantom. This phantom will be provided by ACRIN to all sites for qualification testing purposes only. Preparing the QIBA DCE Imaging Sequence Templates: 1. Open a protocol or folder labeled ACRIN6701_DCE_templates. 2. Create an imaging series using the proper 3D spoiled gradient echo technique based on MRI manufacturer (see right column of Table 1 on of Appendix V). Enter the technical parameters for the DCE MRI imaging protocol into the imaging series. Refer to the parameters specified in the DCE MRI column in Table 1 of Appendix V of this manual. Temporarily set the number of signal averages (NEX/NSA) to one and the flip angle to 30. Note specific vendor required settings in Table 4 of Appendix V. (GE users: use Turbo=2 setting). Adjust parameters such as BW, phase matrix, FOV, and % phase FOV within the allowed ranges from Table 1 of Appendix V to ensure that the time for the sequence is between 5 and 8 seconds. You will need to reference this time later on when creating the full protocol. 3. Save this sequence as ACRIN6701_DCE_template_human in the DCE_template folder. This template will also be used to construct the human imaging sequence for the trial. 4. Make a copy of the ACRIN6701_DCE_template_human series and rename it as ACRIN6701_DCE_template_phantom 5. Open ACRIN6701_DCE_template_phantom and make the following changes to this sequence: a. Change imaging plane to coronal b. Set frequency direction to S/I and phase direction to R/L. c. Set frequency and phase FOV to 360 each. Percent phase FOV should be 100% d. Keep acquisition matrix unchanged, but set reconstruction matrix to 512 x 512 (Siemens users: check interpolate). e. Remove parallel imaging. f. Set number of slices to 26. g. Change slice thickness to 4.25mm. MRI DCE Phantom Test Instructions 2 of 5 Appendix II 09 Oct 2012

28 Appendix II Preparing the QIBA DCE Phantom Imaging Protocol: 1. Open a new folder/protocol for ACRIN6701_DCE_phantom. 2. Add localizer sequences for body imaging as per institutional standard. 3. Copy the series labeled ACRIN6701_DCE_template_phantom and paste into the phantom scanning protocol. 4. Open this series and make the following changes: a. Set number of acquisitions/signal averages to 4 b. GE users: set Turbo=0 5. Rename this series as ACRIN6701_Ph_VFA_flip_ Copy this series and change flip angle to 25. Siemens users: set acquisition properties to scan without further adjustment. 7. Rename this series as ACRIN6701_Ph_VFA_flip_ Make five additional copies of this series. Successively open each one, changing flip angle to 20, 15, 10, 5, 2 sequentially. Save each subsequent series as ACRIN6701_Ph_VFA_flipXXs where XX is 20, 15, 10, 05, and 02, for each series. 9. Make a copy of the ACRIN6701_Ph_VFA15_degree series. 10. GE users: open this series and change to Turbo=2 11. Save/rename this series as ACRIN6701_Ph_Ratio_map_Array_Coil 12. Make a copy of the ACRIN6701_Ratio_map_Array_Coil series 13. Open this and change to Body coil acquisition. Siemens users: add comment to technologist re coil change. 14. Save this series as ACRIN6701_Ph_Ratio_map_Body_Coil 15. Make a copy of the ACRIN6701_Ph_VFA_30_degrees series 16. Open this and make the following changes a. Change number of signal averages to 1. b. Change number of dynamic acquisitions based on previously noted time for the ACRIN6701_DCE_template_human acquisition, as indicated below: i seconds 65 acquisitions ii seconds 60 acquisitions iii seconds 50 acquisitions iv seconds 45 acquisitions c. GE users: set Turbo=2 and MPH option d. Siemens users: remove scan without further adjustment from acquisition properties. 17. Save series as ACRIN6701_Ph_Dynamic. MRI DCE Phantom Test Instructions 3 of 5 Appendix II 09 Oct 2012

29 Appendix II This completes the phantom protocol set up. Your MRI DCE QIBA phantom protocol should have the following series prepared, in the order shown: localizer (recommend 3 plane T1 Map 30 (tuned, with pre scan) T1 Map 25 (not tuned, no pre scan) T1 Map 20 (not tuned, no pre scan) T1 Map 15 (not tuned, no pre scan) T1 Map 10 (not tuned, no pre scan) T1 Map 5 (not tuned, no pre scan) T1 Map 2 (not tuned, no pre scan) Ratio map array coil Ratio map body coil Dynamic gadolinium (tuned, pre scan) QIBA DCE Phantom Preparation Procedure: 1. Use the surface array coil per your institutional routine for pelvic imaging (i.e. torsoarray) 2. Place the QIBA MRI DCE phantom in the center of the table, on top of the posterior elements of the torso array coil 3. Add the anterior torso array coil elements to the top 4. Landmark to the center of the phantom. Initiate localizer scanning. Once a satisfactory localizer imaging in the sagittal or axial plane is obtained, prescribe the coronal slab from a central slice. Continue remaining sequences, noting switch to body coil for the Ratio_map_Body_Coil series. QIBA DCE Phantom Scan Procedure T1 Mapping Series for DCE Body 1. Run the localizer scan to identify the phantom (may use either body coil or array coil for image reception). 2. Open the T1 map flip 30 series. Switch to array coil for image reception. 3. Prescribe the 3D slab in the coronal plane through the center of the phantom, centered in all 3 planes. Pre scan, as usual, for this series, then run. 4. Run the next T1 Map at 25, copying the position of the 3D slab from the previous series. DO NOT pre scan. 5. Run the next T1 Map at 20, copying the position of the 3D slab from the previous series. DO NOT pre scan. MRI DCE Phantom Test Instructions 4 of 5 Appendix II 09 Oct 2012

30 Appendix II 6. Run the 15, 10, 5, 2 T1 maps in the same manner as above without a pre scan. Body Coil Ratio Map Series 1. Run the Ratio_map_Array_Coil scan. 2. Run the Ratio_map_Body_Coil scan. Make sure to switch to body coil as receive coil. DO NOT run a pre scan. Dynamic Series 1. Switch back to array coil as receive coil. Run the DYNAMIC SCAN, copying the position of the 3D slab from the previous series. Pre scan is allowed for this series. MRI DCE Phantom Test Instructions 5 of 5 Appendix II 09 Oct 2012

31 Appendix III Appendix III MRI Scan 1 Human Imaging Procedures MRI Scan 1: Human Imaging Procedures 09 Oct 2012 Page 1 of 11 Appendix III

32 Appendix III MRI SCAN 1: Human Imaging Procedures Introduction The following is a guideline document depicting the patient preparation and order of imaging for ACRIN 6701 MRI Scan 1. Note that this document is divided in to three sections: 1. Part I: Anatomic imaging procedures for sites not using an endo rectal coil (ecoil) (see page 3) 2. Part II: Anatomic imaging procedures for sites using an endo rectal coil (ecoil) (see page 5) 3. Part III: Non ecoil DWI and DCE MRI imaging (all sites see page 8) Sites should determine whether they will follow Part I or Part II of the anatomic imaging procedures, then all sites should proceed to Part III after completion of either Part I or Part II. MRI Scan 1: Human Imaging Procedures 09 Oct 2012 Page 2 of 11 Appendix III

33 Appendix III Part I: Pre DWI and DCE MRI Imaging Procedures (For Institutions not Utilizing Endo rectal Coil (ecoil) for Anatomic Prostate Imaging) Note: Institutions utilizing ecoil for anatomic imaging during MRI 1 should skip to Part II Preparation 1. Document participant body weight on the MRI Scan Administration Form 2. Pre draw appropriate amount (0.1 mmol/kg) of protocol approved gadolinium and 20 ml normal saline into dual chamber power injector 3. Place intravenous line (20G or higher), preferably in right antecubital fossa, for gadolinium contrast administration, then document injection site and catheter size on the MRI Scan Administration Form 4. Place participant supine in MRI scanner; connect IV to power injector; and deploy scanner specific local torso array coils about pelvic region 5. Landmark participant at the level of the symphysis pubis Anatomic Image Acquisition 1. Perform pre contrast anatomic imaging as described below: Note: Minimal required imaging is listed below, but any pre contrast imaging series per institutional norms are permitted a. Localizer: per institutional routine. It is strongly recommended that a large FOV sagittal localizer is acquired for the planning of the DCE MRI acquisition. See Figures 1 & 2 on page 10 & 11 of this appendix for proper slab prescription. b. High resolution T1 weighted axial (or oblique axial) imaging: Scanning should be tailored to the prostate, with the appropriate use of FOV and image matrix values for high resolution prostate imaging. Use institutional norms for type of T1 scanning and other acquisition parameters. Note: Oblique axial imaging (i.e perpendicular to the posterior edge of the prostate) is acceptable if per institutional norms (see Figure 2, page 11). Use of standard or oblique scanning planes should be uniform throughout examination. c. High resolution T2 weighted axial (or oblique axial) imaging: MRI Scan 1: Human Imaging Procedures 09 Oct 2012 Page 3 of 11 Appendix III

34 Appendix III Utilization of identical scan prescription (FOV, slice thickness, slice locations) with that of T1 imaging is strongly encouraged. Note acceptable parameter ranges in Table 1 of Appendix V d. High resolution T2 weighted coronal (or oblique coronal) imaging: Utilization of oblique coronal imaging plane (i.e. parallel to the posterior surface of the prostate is acceptable). Utilize institutional norms for scanning parameters 2. Perform any additional standard of care pre gadolinium imaging per institutional norms. Possible imaging series may include: High resolution sagittal T2 imaging of the prostate Large FOV T1 and/or T2 imaging to document nodal or osseous metastatic disease Supplemental DWI with ecoil (per institutional norms) 3. Please proceed to Appendix III Page 8 for the DWI and DCE MRI imaging instructions, at the completion of the pre gadolinium imaging. MRI Scan 1: Human Imaging Procedures 09 Oct 2012 Page 4 of 11 Appendix III

35 Appendix III MRI SCAN 1: Imaging Procedures Part II: Pre DWI and DCE MRI Imaging Procedures (For Institutions Utilizing Endo rectal Coil (ecoil) for Anatomic Prostate Imaging) This portion of the imaging manual is for sites that choose to use ecoil for anatomic imaging of the prostate. Sites should use this section for imaging if their institutional norms for clinical exams of the prostate require the use of an ecoil at 3T imaging and the use of non ecoil exams would result in imaging not deemed to be acceptable for clinical staging per institutional standards. Note that even if an ecoil is normally utilized for anatomic and/or functional prostate imaging at 3T, sites should consider whether non ecoil anatomic imaging may produce clinically acceptable imaging, as this will improve patient throughput during this study. After completion of MRI Scan 1, sites may review the imaging and determine whether ecoil imaging for anatomic prostate evaluation may benefit the patient during MRI Scan 2. Sites that choose to use ecoil imaging for anatomic prostate evaluation should first perform ecoil based imaging, and then perform non ecoil DWI and DCE MRI study imaging. Preparation 1. Document participant body weight on the MRI Scan Administration Form 2. Pre draw appropriate amount (0.1 mmol/kg) of protocol approved gadolinium and 20 ml normal saline into dual chamber power injector 3. Place intravenous line (20G or higher), preferably in right antecubital fossa, for gadolinium contrast administration, then document injection site and catheter size on the MRI Scan Administration Form 4. Deploy endo rectal coil 5. Place participant supine in MRI scanner; connect IV to power injector; and deploy scanner specific local torso array coils about pelvic region 6. Landmark participant at the level of the symphysis pubis Anatomic Image Acquisition with ecoil 1. Perform pre contrast anatomic imaging as described below: Note: Minimal required imaging is listed below, but any pre contrast imaging series per institutional norms are permitted. a. Localizer: per institutional routine b. High resolution T1 weighted axial (or oblique axial) imaging: MRI Scan 1: Human Imaging Procedures 09 Oct 2012 Page 5 of 11 Appendix III

36 Appendix III Scanning should be tailored to the prostate, with the appropriate use of FOV and image matrix values for high resolution prostate imaging. Use institutional norms for type of T1 scanning and other acquisition parameters. Note: Oblique axial imaging (i.e perpendicular to the posterior edge of the prostate) is acceptable if per institutional norms (see Figure 2, page 11). Use of standard or oblique scanning planes should be uniform throughout examination. c. High resolution T2 weighted axial (or oblique axial) imaging: Utilization of identical scan prescription (FOV, slice thickness, slice locations) with that of T1 imaging is strongly encouraged. Note acceptable parameter ranges in Table 1 of Appendix V d. High resolution T2 weighted coronal (or oblique coronal) imaging: Utilization of oblique coronal imaging plane (i.e. parallel to the posterior surface of the prostate is acceptable. Utilize institutional norms for scanning parameters 2. Perform any additional standard of care pre gadolinium imaging per institutional norms. Possible imaging series may include: High resolution sagittal T2 imaging of the prostate Large FOV T1 and/or T2 imaging to document nodal or osseous metastatic disease Supplemental DWI with ecoil (per institutional norms) Note: DWI performed with ecoil is at the discretion of the imaging site PI. Scanning parameters for ecoil DWI series should be based on institutional norms and need not utilize study specific DWI parameters. Note that DWI imaging without ecoil, per study guidelines, must be performed even if ecoil DWI imaging is utilized. 3. Prepare for Non ecoil Anatomic Imaging Remove endo rectal coil from patient. Re place participant supine in MRI scanner; connect IV to power injector; and redeploy scanner specific local torso array coils about pelvic region MRI Scan 1: Human Imaging Procedures 09 Oct 2012 Page 6 of 11 Appendix III

37 Appendix III Landmark participant at the level of the symphysis pubis Non ecoil Anatomic Image Acquisition 1. Localizer: per institutional routine. It is strongly recommended that a large FOV sagittal localizer is acquired for planning the DCE MRI acquisition. See Figures 1 & 2 on pages 10 & 11 of this appendix. 2. T2 weighted axial (or oblique axial) imaging The utilization of oblique imaging planes is permitted (see Figure 2, page 11), but should be used uniformly throughout all portions of this section. Imaging should be sufficient to localize prostate for comparison with DWI and DCE MRI imaging. High resolution imaging is not required at this stage. Rapid T2 FSE imaging, such as SS FSE, HASTE, etc; is acceptable. 3. Please proceed to Appendix III Page 8 for the DWI and DCE MRI imaging instructions, at the completion of the pre gadolinium imaging. MRI Scan 1: Human Imaging Procedures 09 Oct 2012 Page 7 of 11 Appendix III

38 Appendix III MRI SCAN 1: Imaging Procedures Part III: DWI and DCE MRI Imaging Procedures (Non ecoil All sites) The following guidelines are for study required non ecoil DWI and DCE MRI imaging. These instructions should be followed by each imaging center after completion of either Part I or Part II of these instructions. DWI/DCE Image Acquisition Procedures 1. Perform Multi B value axial (or oblique axial) SE EPI DWI (with B values of 0, 100, 600, and 800 s/mm 2 )) The utilization of oblique imaging planes are permitted (see Figure 2, page 11), but should be used uniformly throughout all portions of this section. See Table 1 in Appendix V for detailed imaging instructions Certain scanner systems may not allow the use to run more than one non zero B value during DWI. If Multi B value DWI imaging is not permitted on your MRI system, this section should be run in three distinct series. Label series accordingly: o Series 1: B values 0 & 100 o Series 2: B values 0 & 600 o Series 3: B values 0 & Prescribe axial (or oblique axial) 3D volume for DCE MRI study: The utilization of oblique imaging planes is permitted (see Figure 2, page 11), but should be used uniformly throughout all portions of this section. Axial volume of 32 x 5mm slices must be prescribed; do not center imaging over the prostate. Rather, the prostate should be at the lower portion of the imaging volume to minimize vascular in flow affects. See Figures 1 & 2 on Pages 10 & 11 of this appendix for details regarding slab placement. Perform all series using same exam prescription. Do not perform pre scan/preparation between series; unless indicated otherwise See Table 1 of Appendix V for detailed imaging information. 3. DCE MRI Imaging Series: MRI Scan 1: Human Imaging Procedures 09 Oct 2012 Page 8 of 11 Appendix III

39 Appendix III Multi flip angle T1 mapping protocol (30, 25, 20, 15, 10, 5, 2 ) Array Body coil only imaging for receive coil bias field calculation Dynamic Enhanced Imaging Note on SAR: In the event of a SAR error the technologist should only make adjustments to the flip angle; please do not make any additional parameter adjustments. If, on a subject s initial scan, a SAR error requires dynamic enhanced imaging to be run at a flip angle less than 30 the flip angle adjustment should be noted and this parameter should be replicated, if possible, at all subsequent visits. 4. Contrast Administration for DCE Imaging The gadolinium agents MultiHance, Eovist, and Vasovist are NOT permitted for this study The same brand and dose of contrast, same IV site, and same rate of contrast and saline flush administration should be maintained for both the test and retest examinations. Contrast agent should be administered in a dynamic fashion beginning seconds after the start of the dynamic enhanced imaging. Contrast agent should be administered at a dose of 0.1 mmol/kg body weight and rate of 2 ml/second, followed by a 20 ml saline flush, also at 2 ml/second. Document the amount of contrast administered on the MRI Scan Administration Form 5. Post gadolinium imaging, per institutional norms, may be performed after completion of the dynamic enhanced imaging series. MRI Scan 1: Human Imaging Procedures 09 Oct 2012 Page 9 of 11 Appendix III

40 Appendix III Figure 1: DCE MRI Slab Prescription for Axial Imaging Scout View (Circle=Prostate C=eCoil) Correct Slab Placement Incorrect (Slab too thin) Incorrect (Slab set too low) MRI Scan 1: Human Imaging Procedures Appendix III 09 Oct 2012 Page 10 of 11

41 Appendix III Figure 2: DCE MRI Slab Prescription for Oblique Axial Imaging Scout View (Circle=Prostate C=eCoil) Correct Slab Placement Incorrect (Slab too thin) Incorrect (Slab set too low) MRI Scan 1: Human Imaging Procedures Appendix III 09 Oct 2012 Page 11 of 11

42 Appendix IV Appendix IV MRI Scan 2 Human Imaging Procedures MRI Scan 2: Human Imaging Procedures 09 Oct 2012 Page 1 of 7 Appendix IV

43 Appendix IV MRI SCAN 2: Imaging Procedures The following guidelines are for study required non ecoil DWI and DCE MRI imaging for ACRIN 6701 MRI Scan 2. Note that MRI Scan 2 is not for clinical use unless deemed necessary by the local site radiology PI. In such cases, the local site radiology PI should indicate to the MRI technologist prior to the examination which additional imaging should be performed. Specifically, endo rectal coil (ecoil) imaging should not be performed at this time unless explicitly indicated by the site PI to repeat non diagnostic anatomic imaging series obtained at the time of MRI Scan 1. Note: this MRI scan visit includes a coffee break where the technologist will be required to briefly remove the participant from the scan table. Preparation 1. Document participant body weight on the MRI Scan Administration Form 2. Pre draw appropriate amount (0.1 mmol/kg) of protocol approved gadolinium and 20 ml normal saline into dual chamber power injector 3. Place intravenous line (20G or higher), preferably in right antecubital fossa, for gadolinium contrast administration, then document injection site and catheter size on the MRI Scan Administration Form 4. Place participant supine in MRI scanner; and deploy scanner specific local torso array coils about pelvic region. Do not connect the participant to the power injector at this time. 5. Landmark participant at the level of the symphysis pubis Non ecoil Anatomic Image Acquisition 1. Localizer: per institutional routine. 2. T2 weighted axial (or oblique axial) imaging The utilization of oblique imaging planes is permitted (see Figure 2, page 7), but should be used uniformly throughout all portions of this section. Imaging should be sufficient to localize prostate for comparison with DWI and DCE MRI imaging. High resolution imaging is not required at this stage. Rapid T2 FSE imaging, such as SS FSE, HASTE, etc; is acceptable. 3. Additional pre gadolinium anatomic imaging series for clinical care (if required) may be MRI Scan 2: Human Imaging Procedures 09 Oct 2012 Page 2 of 7 Appendix IV

44 Appendix IV performed at this time. DWI/DCE MRI Image Acquisition Procedures 1. Perform Pre Coffee Break Multi B value axial (or oblique axial) SE EPI DWI (with B values of 0, 100, 600, and 800 s/mm 2)) The utilization of oblique imaging planes is permitted, but should be used uniformly throughout all portions of this section. See Table 1of Appendix V for detailed imaging instructions Certain scanner systems may not allow the user to run more than one non zero B value during DWI. If Multi B value DWI imaging is not permitted on your MRI system, this section should be run in three distinct series. Label series accordingly: o Series 1: B values 0 & 100 o Series 2: B values 0 & 600 o Series 3: B values 0 & Implement a Coffee Break Remove the participant from the MRI table for approximately 1 2 minutes Place participant supine on the MRI table Connect IV to power injector; and deploy scanner specific local torso array coils about pelvic region Landmarked at the level of the symphysis pubis. 3. Imaging Prior to Post Coffee Break DWI Series Localizer: per institutional routine. It is strongly recommended that a large FOV sagittal localizer is acquired for planning the DCE MRI acquisition (see Figure 2, page 7). T2 weighted axial (or oblique axial) imaging o The utilization of oblique imaging planes is permitted (see Figure 2, page 7), but should be used uniformly throughout all portions of this section. o Imaging should be sufficient to localize prostate for comparison with DWI and DCE MRI imaging. High resolution imaging is not required at this stage. Rapid T2 FSE imaging, such as SS FSE, HASTE, etc; is acceptable. 4. Perform Post Coffee Break Multi B value axial (or oblique axial) SE EPI DWI (with B MRI Scan 2: Human Imaging Procedures 09 Oct 2012 Page 3 of 7 Appendix IV

45 Appendix IV values of 0, 100, 600, and 800 s/mm 2)) The utilization of oblique imaging planes is permitted, but should be used uniformly throughout all portions of this section. See Table 1 in Appendix V for detailed imaging instructions Certain scanner systems may not allow the user to run more than one non zero B value during DWI. If Multi B value DWI imaging is not permitted on your MRI system, this section should be run in three distinct series. Label series accordingly: o Series 1: B values 0 & 100 o Series 2: B values 0 & 600 o Series 3: B values 0 & Prescribe axial (or oblique axial) 3D volume for DCE MRI study: The utilization of oblique imaging planes is permitted (see Figure 2, page 7), but should be used uniformly throughout all portions of this section. Axial volume of 32 x 5mm slices must be prescribed; do not center imaging over the prostate. Rather, the prostate should be at the lower portion of the imaging volume to minimize vascular in flow affects. See Figures 1 & 2 on Pages 6 & 7 of this appendix for details regarding slab placement. Perform all series using same exam prescription. Do not perform pre scan/preparation between series; unless otherwise indicated See tables in Appendix V for detailed imaging information. 6. DCE MRI Imaging Series: Multi flip angle T1 mapping protocol (30, 25, 20, 15, 10, 5, 2 ) Array Body coil only imaging for receive coil bias field calculation Dynamic Enhanced Imaging Note on SAR: In the event of a SAR error the technologist should only make adjustments to the flip angle; please do not make any additional parameter adjustments. If, on a subject s initial scan, a SAR error requires dynamic enhanced imaging to be run at a flip angle less than 30 the flip angle adjustment should be noted, and this parameter should be replicated, if possible, at all subsequent visits. MRI Scan 2: Human Imaging Procedures 09 Oct 2012 Page 4 of 7 Appendix IV

46 Appendix IV 7. Contrast Administration for DCE Imaging The gadolinium agents MultiHance, Eovist, and Vasovist are NOT permitted for this study The same brand and dose of contrast, same IV site, and same rate of contrast and saline flush administration should be maintained for both the test and retest examinations. Contrast agent should be administered in a dynamic fashion beginning seconds after the start of the dynamic enhanced imaging. Contrast agent should be administered at a dose of 0.1 mmol/kg body weight and rate of 2 ml/second, followed by a 20 ml saline flush, also at 2 ml/second. Document the amount of contrast administered on the MRI Scan Administration Form 8. Post gadolinium imaging, per institutional norms, may be performed after completion of the dynamic enhanced imaging series. MRI Scan 2: Human Imaging Procedures 09 Oct 2012 Page 5 of 7 Appendix IV

47 Appendix IV Figure 1: DCE MRI Slab Prescription for Axial Imaging Scout View (Circle=Prostate C=eCoil) Correct Slab Placement Incorrect (Slab too thin) Incorrect (Slab set too low) MRI Scan 2: Human Imaging Procedures Appendix IV 09 Oct 2012 Page 6 of 7

48 Appendix IV Figure 2: DCE MRI Slab Prescription for Oblique Axial Imaging Scout View (Circle=Prostate C=eCoil) Correct Slab Placement Incorrect (Slab too thin) Incorrect (Slab set too low) MRI Scan 2: Human Imaging Procedures Appendix IV 09 Oct 2012 Page 7 of 7