Prostate Cancer Detection Using a Quantitative Screening MRI Protocol
Phase: NA
Conditions: Prostate Cancer
Sponsor: University of Illinois at Chicago

 
 
Prostate Cancer Detection Using a Quantitative Screening MRI Protocol 
Principal Investigator: 
Michael Abern MD, Assistant Professor of Urology, University of Illinois at Chicago 
Mabern1@uic.edu, 312-996-9330 
 
Co-Investigators: 
Karen Xie DO, Assistant Professor of Radiology, University of Illinois at Chicago 
Kejia Cai PhD, Assistant Professor of Radiology and Bioengineering, University of 
Illinois at Chicago 
Xiaohong Joe Zhou PhD, DABR, Professor of Radiology, Neurosurgery, and 
Bioengineering; Chief Medical Physicist; Director of 3T MR Research Program; Director 
of MR Physics, University of Illinois at Chicago 
Andre Kajdacsy-Balla MD PhD, Professor of Pathology, University of Illinois at Chicago 
Richard Magin PhD, Professor of Bioengineering, University of Illinois at Chicago 
Dr. Peter Gann MD MSc, Professor of Pathology, University of Illinois at Chicago 
 
Study Location(s): University of Illinois at Chicago Hospital and Ambulatory Clinics, 
University of Illinois at Chicago Advanced Imaging Center (3T Center for Magnetic 
Resonance Research) 
 
 
Version: 1.0 
Date: 1/24/2019 
 
 

TABLE OF CONTENTS 
Page 
Table of Contents ............................................................................................................ 2 
List of Abbreviations ........................................................................................................ 3 
1.0 Project Summary/Abstract ................................................................................... 4 
2.0 Background/Scientific Rationale ......................................................................... 5 
3.0 Objectives/Aims .................................................................................................... 7 
4.0 Eligibility ................................................................................................................ 8 
4.1 Inclusion Criteria ............................................................................................. 8 
4.2 Exclusion Criteria ............................................................................................ 8 
4.3 Excluded or Vulnerable Populations ............................................................. 8 
5.0 Subject Enrollment................................................................................................ 8 
6.0 Study Design and Procedures ............................................................................. 9 
7.0 Expected Risks/Benefits ..................................................................................... 10 
8.0 Data Collection and Management Procedures ................................................. 11 
9.0 Data Analysis ....................................................................................................... 12 
10.0 Quality Control and Quality Assurance ............................................................. 12 
11.0 Data and Safety Monitoring ................................................................................ 12 
12.0 Statistical Considerations .................................................................................. 12 
13.0 Regulatory Requirements ................................................................................... 13 
13.1 
Informed Consent ..................................................................................... 13 
13.2 
Subject Confidentiality ............................................................................. 13 
13.3 
Unanticipated Problems .......................................................................... 13 
14.0 References ........................................................................................................... 14 
Appendices ................................................................................................................... 16 
 
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LIST OF ABBREVIATIONS  
 
PCa  
 
Prostate cancer 
MRI 
 
 
Magnetic resonance imaging 
mpMRI 
 
Multiparametric MRI 
TRUS  
 
Transrectal ultrasound 
PSA  
 
Prostate specific antigen 
DRE  
 
Digital rectal examination 
AS 
 
 
Active surveillance 
GS 
 
 
Gleason score 
DWI  
 
Diffusion weighted imaging 
ADC  
 
Apparent diffusion coefficient 
DDC  
 
Distributed diffusion coefficient 
SEM  
 
Stretched exponential model 
FROC  
 
Fractional order calculus 
CEST  
 
Chemical exchange saturation transfer 
ROC  
 
Receiver operating curve 
AUC  
 
Area under the receiver operating curve 
SOC  
 
Standard of care 
H&E  
 
Hematoxylin and Eosin  
PBCG  
 
Prostate Biopsy Collaborative Group 
IPSS  
 
International Prostate Symptom Score 
SHIM  
 
Sexual Health Inventory for Men 
DICOM 
 
Digital Imaging and Communications in Medicine 
PI 
 
 
Primary Investigator 
IRB 
 
 
Institutional Review Board 
AIC 
 
 
Advanced Imaging Center 
 
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1.0 
Project Summary/Abstract 
Currently men with elevated prostate specific antigen (PSA) or abnormal digital rectal 
examination (DRE) undergo systematic sampling of the prostate with transrectal 
ultrasound (TRUS)-guided needle biopsies. PSA and DRE have low specificity for 
prostate cancer (PCa), and TRUS biopsies have an approximately 30% false negative 
rate. Whether a quantitative detection specfic magnetic resonance imaging (MRI) 
protocol improves PCa detection in biopsy naïve men is not adequately studied. 
This pilot study aims to test a novel detection specific MRI protocol which uses image 
collection and post-processing to assist the radiologist find areas of the prostate with 
increased suspicion for clinically significant cancer. Men with an MRI negative for 
cancer will undergo standard of care TRUS biopsies, and men with suspicious MRI 
lesions (as defined by our preliminary data) will undergo biopsies of these lesions in 
addition to systematic TRUS biopsies. We will compare the yield of significant PCa 
between systematic sampling and MRI determined areas of the prostate. 
 
  
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2.0 
Background/Scientific Rationale  
While there is concern for over-treatment of prostate cancer (PCa) it remains the 2nd 
leading cause of cancer death in U.S. men (1). This paradox is due in part to the 
accuracy limitations of current detection methods of serum prostate specific antigen 
(PSA) and digital rectal examination (DRE) screening, and the inability of current clinical 
information to discriminate indolent from aggressive tumors. Clinical patient 
characteristics including age, race, family history of PCa, DRE, and prior negative 
prostate biopsy history have been combined into a predictive calculator to guid biopsy 
decisions(2). Men found to have adequate suspicion for PCa require a tissue diagnosis. 
Standard PCa detection relies on 12-core transrectal ultrasound (TRUS) guided biopsy 
that samples anatomic zones of the prostate gland. Approximately 35% of men 
undergoing immediate radical prostatectomy (RP) for low grade PCa on standard 
biopsy will be found to have higher grade tumors in the pathologic specimen(3). 
Furthermore, between 30-38% of men with clinical suspicion for PCa and a negative 
standard biopsy will be diagnosed with PCa on re-biopsy(4). Finally, TRUS biopsy is an 
invasive procedure with a rate of sepsis as high as 2%, and this risk is proportional to 
the number of biopsy cores sampled(5). With a more precise method for early detection 
of the most aggressive tumors, men with indolent PCa could be spared treatment with 
its associated cost and morbidities and instead be managed conservatively with active 
surveillance (AS), while those with potentially lethal disease could be expediently 
referred for radiation or surgery with curative intent. 
Improved PCa detection may be particularly important for African American (AA) men, 
who are almost twice as likely to die from PCa as white men(1). A recent study of men 
with very low risk PCa based on clinical information who underwent immediate RP 
found that AA men were more likely to have adverse RP pathology and anteriorly 
located tumors not reached with standard TRUS prostate biopsies(6). In addition, two 
series of men selected for AS based on standard clinical information reported that AA 
men progressed to treatment faster than white men(7, 8). These data have questioned 
the safety of managing AA men with AS without more accurate risk stratification tools 
such as imaging. At UIC, over 60% of PCa cases diagnosed are in AA men. 
Standard TRUS imaging does not provide enough resolution to localize most PCa, 
much less provide information about its aggressiveness.  One promising approach to 
improve PCa detection and risk stratification is through advanced imaging such as 
magnetic resonance imaging (MRI).  In this setting an ideal imaging study would 
differentiate aggressive PCa from indolent PCa and benign processes such as 
hyperplasia (BPH) or inflammation as well as localize the aggressive PCa to reduce 
biopsy sampling error. Currently in the US, prostate mpMRI is approved for : 1) men 
with continued suspicion for PCa but negative TRUS biopsy or 2) for staging of known 
high risk PCa for treatment planning. The images from the mpMRI can be used for 
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targeted biopsies using TRUS/mpMRI imaging fusion to improve PCa detection(9). As 
such, there is interest in using mpMRI as a confirmatory test in men with elevated PSA 
and prior to the first biopsy to improve biopsy accuracy and potentially obviate the need 
for unnecessary “random” biopsies. A landmark study conducted in Europe, the 
PRECISION trial, recently reported that TRUS/mpMRI fusion biopsies in biopsy naive 
men with suspected PCa resulted in an increase in the absolute detection of clinically 
significant PCa of 12% in men randomized to mpMRI, despite 28% of the men in this 
group avoiding biopsy due to a negative study(10). These data are certainly compelling, 
but have yet to be replicated in a US population, and particularly in a high-risk group 
such as AA men. The implications in the US are significant as approximately 1 million 
TRUS biopsies are performed annually for known or suspected PCa(11). 
While MRI protocols are variable and evolving, the current recommended standard is 
combining T2-weighted anatomical imaging (T2WI) with two functional MRI techniques, 
typically diffusion-weighted images (DWI) and dynamic contrast enhanced images 
(DCE), together to create a multi-parameter MRI (mpMRI) study. A radiologist reviews 
the imaging and assigns a semi-qualitative suspicion of high grade PCa on a 1-5 Likert 
scale. This score, called the prostate imaging reporting and data system (PI-RADS), is 
an attempt to standardize mpMRI assessment and guide clinical management(12). 
ThePI-RADS has several limitations including modest inter-rater reliability(13, 14), and a 
false positive rate of as high as 88% of the PI-RADS 3 (indeterminate) scores (figure 1).   
Currently the same prostate MRI protocols are used for PCa detection in men with prior 
negative TRUS biopsies, staging of known PCa, and for suspected PCa local 
recurrence after treatment. As such, the protocol 
contains several imaging sequences such as T1 
weighted imaging to detect hemorrhage related to 
biopsy and DCE which is of limited value for PCa 
detection which add to the study time and 
cost(15). In addition, the fields of view of prostate 
MRI protocols are designed to show surrounding 
structures such as the pelvic lymph nodes for 
staging purposes which aren’t applicable to the primary PCa detection setting. These 
larger fields of view come at the expense of longer study times, and lower imaging detail 
in the prostate.  
Finally, current prostate MRI protocols are designed for qualitative assessment and PI-
RADS scoring. A detection specific protocol can be designed so that quantitative 
parameters can be measured as an adjunct to PI-RADS scoring. We hypothesize that 
quantitative tools for image assessment could benefit radiologists to further characterize 
indeterminate MRI studies, and to facilitate comparisons across patients, centers, and 
populations. 
Figure 1: Specificity of PI-RADS scoring in biopsy naive men 
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Our study explores 2 ways to improve mpMRI for 
PCa detection: 1) Developing an imaging protocol 
specifically designed for biopsy naïve men with 
suspected PCa and 2) improving utility of the 
collected images with quantitative image analysis 
tools as an adjunct to PI-RADS. DWI characterizes 
the Brownian movement of water molecules in 
tissues. Conventional DWI fits a line to data acquired 
using two strengths (b-values) of the magnetic 
diffusion gradient, the slope of which is the apparent 
diffusion coefficient (ADC) which can be used as a 
quantitative parameter. When compared to RP histology, ADC has a moderate inverse 
correlation with PCa grade(ref ADC and grade). With conventional DWI the calculation 
of ADC assumes a gaussian distribution of water molecule diffusion and tissue 
homogeneity which may oversimplify water motion in organs with complex tissue 
structures. A technique that more accurately determines water diffusion through tissues 
may better discriminate cancer grade. As such, we have tested stretched exponential 
(SEM) and kurtosis models of DWI with high b-values to determine the grade of PCa in 
31 men undergoing biopsy targeted to MRI lesions identified using standard PI-RADS 
scoring. We found accuracy as measured by area under the receiver operator curve 
(AUC) that is significantly improved over PI-RADS, the PBCG model, and modestly 
improved over conventional ADC (Figure 2). Therefore, we propose to prospectively use 
quantitative DWI as a biomarker to determine regions of the prostate suspicious for high 
grade PCa in biopsy naïve men. 
 
3.0 
Objectives/Aims 
 
This study aims to determine whether a detection specific MRI protocol with quantitative 
image analysis can improve high grade PCa detection in men with clinical suspicion and 
no prior biopsy. 
 
Aim 1: Design a PCa detection specific MRI protocol which will facilitate 
quantitative image analysis and reduce study time by ~50% 
  
Current prostate mpMRI protocols include image sequences and fields of view outside 
of the prostate gland and its immediate surrounding that are not useful for PCa 
detection. We will create a detection specific MRI protocol featuring: smaller fields of 
view zoomed to the prostate, T2 weighted imaging at multiple echo times, chemical 
exchange saturation transfer imaging (CEST), and DWI at higher b values (up to 4000) 
that will allow for quantitative prediction of high grade PCa. The exact imaging 
acquisition parameters can be found in Appendix 3. We expect this MRI protocol to 
Figure 2: Area under ROC for imaging and clinical 
biomarkers 
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reduce study (acquisition) time from approximately 45 minutes to 27 minutes, which will 
potentially lower cost and improve tolerance of the procedure. Significantly, we will omit 
DCE which will reduce the imaging time, and the risks associated with intravenous 
contrast including systemic fibrosis, and patient discomfort.  
 
Aim 2: Determine the accuracy of the novel MRI protocol for detection of high 
grade PCa 
 
50 men with clinical suspicion of PCa (elevated PSA and/or abnormal DRE) will be 
enrolled into a prospective protocol and will undergo detection protocol MRI described 
in Aim 1. Quantitative image analyses will be performed to generate SEM maps of DWI. 
Areas of suspicion for high grade PCa (GS ≥7) will be targeted for biopsy. Men with MRI 
with no areas of suspicion for high grade PCa will undergo standard of care 12 core 
TRUS biopsy. The primary endpoint will be the rate of detection of high grade PCa on 
the per patient and per biopsy core basis. Men with biopsy pathology negative for PCa 
will undergo standard of care (SOC) continued monitoring.  
 
 
4.0 
Eligibility 
 
Men with suspected PCa (elevated PSA and/or abnormal DRE) and no prior prostate 
biopsy will be identified in the UI Health Urology ambulatory clinics by the clinical 
research coordinator and study investigators.  
 
4.1 Inclusion Criteria 
• Adult men between 18 and 80 years of age 
• Suspected PCa as defined by elevated PSA ≥4 ng/mL and ≤20 ng/mL 
and/or abnormal DRE as determined by a physician 
• Abililty to provide informed consent 
 
4.2 Exclusion Criteria 
• Prior prostate biopsy 
• Prior diagnosis of PCa 
• MRI incompatible implanted medical devices or foreign bodies  
• Rectal anatomy incompatible with TRUS biopsy 
• Life expectancy <10 years as determined by the treating urologist  
 
4.3 Excluded or Vulnerable Populations 
• No vulnerable populations such as minors or incarcerated persons will be 
included in the study.  
 
 
5.0 
Subject Enrollment 
 
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The study investigators and clinical research coordinator will screen the scheduled 
encounters at the Urology clinics at UI Health for potentially eligible subjects meeting 
the inclusion criteria. No advertising materials will be used. No data will be collected 
from men screened but not enrolled. The clinical research coordinator will discuss the 
study risks and benefits and obtain informed consent separate from the study 
investigators to minimize coercion.  
 
5.0 
Study Design and Procedures 
 
This will be a single arm prospective clinical trial. Men with clinical suspicion for PCa but 
no prior prostate biopsy will be enrolled from the UI Health Urology clinics. All eligible 
men will be screened and enrolled by the clinical research coordinator. Enrolled men 
will undergo detection protocol MRI at the UIC Advanced Imaging Center (AIC) prior to 
diagnostic biopsy. The image acquisition parameters are listed in the Appendix 3.  The 
MRI will be processed by the study team and evaluated for areas suspicious for high 
grade PCa by a board certified clinical radiologist (Dr. Xie). Subjects with MRI with no 
suspicious areas for high grade PCa will undergo SOC 12 core TRUS biopsy. Subjects 
with MRI suspicious for high grade PCa will have 2-4 biopsies guided toward each 
suspicious lesion using MRI/TRUS fusion biopsies (maximum of 12 cores). All biopsies 
will undergo SOC histologic processing and interpretation in pathology. Biopsy results 
will be communicated to the patients by the Urologist performing the biopsy and all 
additional management will be SOC. This visit will signify the end of the study. See the 
study schema in Figure 4.  
 
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The primary outcome will be the rate of detection of high grade PCa on a per-patient 
and per biopsy core basis. The detection rate will be compared between patients with 
and without evidence of high grade PCa (GS ≥7) based on the detection protocol MRI. 
Secondarily we will analyze the accuracy of the individual MRI parameters including: T2 
imaging, ADC, the SEM parameters (DDC and α), the FROC parameters (µ, ∆, β), the 
Kurtosis model parameters (D, K), and PI-RADS score. 
 
 
7.0 
Expected Risks/Benefits 
 
The study intervention is the detection protocol MRI and all other aspects of the study 
are standard of care. The detection protocol MRI is a minimal risk procedure as it does 
not require intravenous contrast and does not expose the subject to ionizing radiation. 
Also, in contrast to the aforementioned PRECISION study, patients not found to have 
suspicion of PCa on the detection protocol MRI will undergo the SOC 12 core TRUS 
Figure 4: Study schema 
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prostate biopsy thereby resulting in no additional risk of a missed or delayed PCa 
diagnosis.  
 
The risks of the study are therefore mild anxiety due to the MRI examination itself, and 
violation of patient privacy due mishandling of protected health information.  
Anxiety related to the MRI study, if mild, may be treated with an oral anxiolytic by the 
primary investigator (Dr. Abern) or the patient’s primary care physician as is SOC. 
Severe anxiety precluding MRI without intravenous sedation or general anesthesia 
will be a reason to exclude a patient from the study. If this severe anxiety is discovered 
during the MRI, the study and the patient’s involvement in the research will be 
terminated. Health information will be secure in REDCap, principal investigator will 
allow access to key research personnel only.  
 
The benefits of the study may include: improved detection rate of high grade PCa and 
lower complication rates compared to standard TRUS 12 core biopsy,  If the detection 
protocol MRI has high negative predictive value, it is possible in the future that 
unnecessary prostate biopsies could be avoided in men with a negative study, thereby 
reducing the discomfort and infectious complications of the procedure. 
 
8.0 
Data Collection and Management Procedures 
 
To meet the study goals, clinical, imaging, and pathologic data will be collected 
prospectively. The co-investigators and other key personnel will have access to the 
identified data while the subject is on study. A REDCap database will be used to record 
all of the baseline and clinical data for each subject including: age (continuous in years), 
self reported race (white, black, Hispanic, other), family history of prostate cancer 
(positive or negative), serum PSA (continuous, in ng/mL), International Prostate 
Symptoms Score (IPSS: continuous), Sexual Health Inventory for Men score (SHIM: 
continuous). All source MRI images from the scanner as well as post-processed images 
will be collected in Digital Imaging and Communications in Medicine (DICOM) format. 
Image data will be stored on a password protected server and physically transported 
from the scanner to the post-processing workstation and to the radiologist workstation 
using an encrypted flash drive. Data from interpretation of the MRI images to be stored 
in REDCap will include: PI-RADS score (ordinal), number of lesions (ordinal), and the 
lesion mean, median, minimum and maximum for each quantitative MRI parameter if 
applicable. In addition, if applicable each lesion will be outlined on the T2 weighted 
image series by the radiologist for use at the time of biopsy.  At the time of biopsy the 
prostate volume (continuous, cubic centimeters), type of biopsy (standard or targeted), 
and number of biopsy cores obtained (ordinal) will be entered in REDCap. Pathology 
data to be collected and stored in REDCap includes: presence of any carcinoma 
(Boolean), number of biopsy cores involved with carcinoma (ordinal), location of positive 
biopsy cores (ordinal lesion number), and maximum GS of biopsies (categorical: 
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6,7,8,9, or 10). At the biopsy results visit, biopsy complications will be recorded in 
REDCap: hematuria persisting greater than 72 hours (boolean), urinary retention 
(boolean), infectious complication (boolean), All data will be de-identified for each 
subject after study visit #4 when the biopsy results are known. We anticipate 
approximately 1 year to meet the enrollment goals. At this time, a 3 month period for  
data analysis of the primary outcome is anticipated. After this time, the de-identifed data 
will be stored by the primary investigator (Dr. Abern) for potential use for secondary 
retrospective studies under separate IRB approval.  See Appendix 4 for the data flow 
diagram. 
 
 
9.0 
Data Analysis 
 
The data analysis will be performed on de-identified data by the primary investigator, Dr. 
Abern, who has extensive experience in the statistical analysis of PCa outcomes and 
biomarkers. Dr. Gann, a co-investigator who is a world expert in PCa biomarker study 
design and analysis, will provide analytical support and oversight. Statistical methods 
are outlined in section 12 below.  
 
10.0 Quality Control and Quality Assurance 
 
The quality of the MRI images will be assessed qualitatively by the scanner technician 
in the Advanced Imaging Center at the time of data acquisition. In addition, the source 
and processed images will be assessed for acceptable quality by the study radiologist 
(Dr. Xie). It is possible that a patient would need to undergo a repeat MRI if the data are 
not adequate for assessment for PCa. All pathologic analysis is subject to the UIC 
Department of Pathology clinical quality assurance procedures as is the current clinical 
SOC. 
 
 
11.0 Data and Safety Monitoring 
 
Privacy of protected health information will be maintained by minimizing identifiable 
patient data and maintaining this information in a secure database for use only by 
study investigators. All identifiers needed for the research will be kept in the secure 
REDCap server. Only de-identified data will be retrieved from the server in order to 
perform data analyses 
 
 
12.0 Statistical Considerations 
As this is a single arm pilot study, no power analysis is necessary. Based on the 
PRECISION study, we expect a high grade PCa detection rate of approximately 30% or 
in 17/50 subjects (10). The primary outcome will be the comparison of the rate of high 
grade PCa detection based on the 2 possible MRI outcomes: men undergoing standard 
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12 core TRUS biopsy (detection protocol MRI negative) versus men undergoing MRI 
targeted biopsy (detection protocol MRI positive for lesions). This will be analysed for 
statistical difference using the chi-square test. Each MRI quantitative parameter will be 
evaluated on a per lesion basis as a predictor of high grade PCa using ROC logistic 
regression and will be reported as AUC with 95% confidence intervals (CI). The 
Youden’s Index and 90% fixed sensitivity thresholds of each quanititative parameter will 
be reported. Combinations of MRI quantitative and clinical parameters will be combined 
into multinomial logistic regression models for which AUC with 95% CI will be reported. 
The AUC of the multi-parametric models will be compared iteratively for statistical 
differences using the likelihood ratio test. 
 
13.0 Regulatory Requirements 
13.1 Informed Consent  
Informed consent will be obtained by the clinical research coordinator, Ruben Sauer 
Calvo, in the Urology ambulatory clinics at UI Health. He is an experienced coordinator 
currently in this role for several other PCa studies at UI Health. He is a native Spanish 
speaker and will therefore be able to enroll Spanish speaking subjects using the 
translated consent form. Completed consent documents will be stored in a locked file 
cabinet in the coordinator’s office in the Urology administrative office in Clinical 
Sciences North Suite 515.  
13.2 Subject Confidentiality  
As this research is not funded by the NIH, a certificate of confidentiality is not required. 
That said, every effort will be taken to protect the confidentiality of the research 
subjects. The study investigators, as well as the other key personnel including graduate 
students performing the image post processing will have access to the data. The MRI 
and clinical data will maintain identifiers which is necessary to allow for MRI/TRUS 
fusion biopsy. After the biopsy result is reported, approximately 1 week after the biopsy 
procedure, the MRI DICOM data and REDCap clinical data will be de-identified. No data 
analysis will take place until the accrual target is met and the data has all been de-
identified.  
13.3 Unanticipated Problems 
Any unanticipated problems or protocol deviations will be reported to the IRB and the 
Cancer Protocol Review Committee within 5 business days using OVCR Form 0257. 
The form will be prepared by the coordinator or co-investigator that discovered the 
problem and will be reviewed and approved by the PI. 
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14.0 References 
 
1. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 
Jan;68(1):7-30. 
2. 
Ankerst DP, Straubinger J, Selig K, Guerrios L, De Hoedt A, Hernandez J, et al. 
A Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous 
Cohorts. Eur Urol. 2018 Aug;74(2):197-203. 
3. 
Epstein JI, Feng Z, Trock BJ, Pierorazio PM. Upgrading and downgrading of 
prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors 
using the modified Gleason grading system and factoring in tertiary grades. Eur Urol. 
2012 May;61(5):1019-24. 
4. 
Nelson AW, Harvey RC, Parker RA, Kastner C, Doble A, Gnanapragasam VJ. 
Repeat Prostate Biopsy Strategies after Initial Negative Biopsy: Meta-Regression 
Comparing Cancer Detection of Transperineal, Transrectal Saturation and MRI Guided 
Biopsy. PLoS One. 2013;8(2):e57480. 
5. 
Papagiannopoulos D, Abern M, Wilson N, O'Block N, Raff L, Coogan C, et al. 
Predictors of Infectious Complications after Targeted Prophylaxis for Prostate Needle 
Biopsy. J Urol. 2018 Jan;199(1):155-60. 
6. 
Sundi D, Kryvenko ON, Carter HB, Ross AE, Epstein JI, Schaeffer EM. 
Pathological Examination of Radical Prostatectomy Specimens in Men with Very Low 
Risk Disease at Biopsy Reveals Distinct Zonal Distribution of Cancer in Black American 
Men. The Journal of urology. 2014;191(1):60-7. 
7. 
Abern MR, Bassett MR, Tsivian M, Banez LL, Polascik TJ, Ferrandino MN, et al. 
Race is associated with discontinuation of active surveillance of low-risk prostate 
cancer: results from the Duke Prostate Center. Prostate Cancer Prostatic Dis. 2013 
Mar;16(1):85-90. 
8. 
Iremashvili V, Soloway MS, Rosenberg DL, Manoharan M. Clinical and 
demographic characteristics associated with prostate cancer progression in patients on 
active surveillance. J Urol. 2012 May;187(5):1594-9. 
9. 
Siddiqui M, Rais-Bahrami S, Turkbey B, et al. Comparison of mr/ultrasound 
fusion–guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate 
cancer. JAMA. 2015;313(4):390-7. 
10. 
Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, 
Vaarala MH, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N 
Engl J Med. 2018 May 10;378(19):1767-77. 
11. 
Halpern JA, Shoag JE, Artis AS, et al. National trends in prostate biopsy and 
radical prostatectomy volumes following the us preventive services task force guidelines 
against prostate-specific antigen screening. JAMA Surgery. 2017;152(2):192-8. 
12. 
Steiger P, Thoeny HC. Prostate MRI based on PI-RADS version 2: how we 
review and report. Cancer Imaging. [journal article]. 2016 April 11;16(1):9. 
13. 
Shankar PR, Kaza RK, Al-Hawary MM, Masch WR, Curci NE, Mendiratta-Lala M, 
et al. Impact of Clinical History on Maximum PI-RADS Version 2 Score: A Six-Reader 
120-Case Sham History Retrospective Evaluation. Radiology. 2018 Jul;288(1):158-63. 
14. 
Mussi TC, Yamauchi FI, Tridente CF, Tachibana A, Tonso VM, Recchimuzzi DR, 
et al. Interobserver Agreement and Positivity of PI-RADS Version 2 Among Radiologists 
with Different Levels of Experience. Acad Radiol. 2018 Sep 27. 
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15. 
Weinreb JC, Barentsz JO, Choyke PL, Cornud F, Haider MA, Macura KJ, et al. 
PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2. Eur Urol. 
2016 Jan;69(1):16-40. 
 
 
 
 
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APPENDICES 
 
Appendix 1: International Prostate Symptom Score questionnaire 
 
 
 
 
 
 
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Appendix 2: Sexual Health Inventory for Men questionnaire 
 
 
 
 
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Appendix 3: Detection protocol MRI imaging acquisition parameters 
 
Hardware: 
3 Tesla GE Discovery MR750 (GE Healthcare, Chicago, IL) 
Coil: 32-channel pelvic/cardiac phased-array 
 
Acquisition parameters: 
 
Imaging plane: axial 
Slice thickness: 3mm 
Number of slices: 10-15 (depending on prostate size) 
Field of view: 15cm x 15cm using FOCUS 
Matrix size: 256x192 
 
DWI 
b values: 0, 50, 100, 400, 700, 1000, 1300, 1600, 2000, 3000, 4000 s/mm2 
Averages:  
  b 0-1000:  1 
  b 1300-2000: 2 
  b 3000: 4 
  b 4000: 8 
Directions: 3 (x,y,z) 
TR/TE = 1538 ms/69.8 ms, 
Acquisition time ~3.5 minutes 
 
 
T2 Mapping 
TR: 1900 ms 
TE: 14, 28, 41, 55, 69, 83, 97, 110 ms 
Acquisition time ~ 5.6 minutes 
 
CEST 
Frequency selective saturation pulse at various amplitudes B1 (100 Hz), durations (2 s) 
Saturation frequencies: −5 to 5 ppm with 0.25 ppm step size,  ±20, and ±100 ppm 
Acquisition time ~ 18 min 
 
 
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Appendix 4: Data flow 
 
 
 
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