Acoustic Radiation Force Impulse (ARFI) Imaging for Targeted Prostate Biopsy
Phase: NA
Conditions: Prostate Cancer
Sponsor: Duke University

 
 
 
 
 
 
 
 
 
 
Acoustic Radiation Force Impulse (ARFI) Imaging for Targeted Prostate Biopsy 
 
Document Date: October 18, 2023 
 
NCT04607135 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Purpose of the Study 
  
The objective of the proposed study is to evaluate the feasibility of a new ultrasonic acoustic radiation 
force impulse (ARFI) elasticity imaging system with a custom-designed transducer and biopsy guide to 
provide imaging guidance and targeting during prostate needle biopsy. This study will be conducted in 
two parts. Part 1 will evaluate a new, custom designed ultrasound transducer and needle guide in 
performing systematic transrectal ultrasound-guided prostate biopsies, as is the current standard-of-
care. In addition to standard imaging, the new probe will be capable of ARFI measurements of tissue 
stiffness. Part 2 will evaluate the feasibility of targeted prostate biopsy guidance using ultrasound ARFI 
targeting as compared to ultrasound-MR fusion targeting in subjects electing to have ultrasound fusion-
MR targeted biopsy procedures. 
 
Background & Significance 
 
Prostate cancer is the most common cancer and the second leading cause of cancer death for American 
men. For men harboring occult aggressive cancers, early diagnosis is essential for better treatment and 
increasing survival rate. Although the current screening techniques (prostate-specific antigen (PSA) 
blood testing and digital rectal examination (DRE)) are moderately sensitive but lack specificity for 
cancer screening, resulting diagnostic biopsies have significant shortcomings. Transrectal ultrasound is 
currently used to provide biopsy guidance only; however, it has poor sensitivity and specificity for 
prostate cancer. Without a good imaging technique to guide the needle biopsy in prostate glands, only 
about 25% of tests are positive for cancer in more than 1 million prostate biopsies performed each year; 
the false negative rates range from 25-45% based on the first-time biopsy. Although studies have shown 
more biopsy cores can increase diagnostic accuracy, prostate needle biopsy is an invasive procedure for 
the patient associated with both pain and risks, such as infection, hematuria (blood in the urine), urinary 
retention, hematochezia (blood during bowel movement), and hematospermia (blood in the semen).  
More biopsy cores mean higher risk for the patient. Thus, improved needle biopsy procedures guided by 
ARFI imaging would be of great clinical benefit. 
 
Design & Procedures 
 
PART 1: The new ultrasound probe will be used in the same manner as current probes for standard-of-
care prostate biopsy using systematic sampling with transrectal ultrasound (TRUS) guidance. In addition 
to B-mode images during the procedure, ARFI images will be acquired immediately before each needle 
insertion, after needle insertion, and following needle removal in each sampled image plane. The 
additional time required for ARFI measurements will be approximately 5-10 minutes. 
 
PART 2: Three-dimensional ARFI images of the prostate will be acquired by sweeping the imaging plane 
through the prostate volume as in our current study of ARFI prostate imaging (Pro00006458), using the 
custom-designed ARFI-capable ultrasound probes. Image volume acquisition will take approximately 12 
minutes, and not more than 20 minutes. Display of these images will be in real-time, and immediately 
following the volume acquisition, the most suspicious targets (up to 3) in the gland will be identified. The 
ultrasound probe will be positioned to image the target in plane and two-four biopsy cores will be 
acquired per target – with ARFI and B-mode image data acquired from each targeting procedure. The 

ARFI ultrasound probe will be removed, and the standard ultrasound-MR fusion biopsy procedure will 
then proceed using the clinical ultrasound fusion-MR system. The additional time required to acquire 
the ARFI image volume and perform the ARFI-targeted biopsy cores is approximately 25-30 minutes 
 
Selection of Subjects 
  
PART 1: We will enroll patients scheduled for standard TRUS biopsy with suspected PCa.  
 
PART 2: We will enroll patients with suspected PCa who are scheduled to undergo an ultrasound fusion-
MR prostate biopsy. 
 
Due to the nature of PCa, this study is open to men only; women and children are excluded. It is open to 
members of all racial and ethnic groups. Patients will be recruited by the treating physician or a 
healthcare provider known to the patient at the time of consultation. 
 
Inclusion criteria: 
 
PART 1: Men with suspected PCa based on suspicious PSA or DRE, or abnormal radiological finding 
scheduled for standard TRUS prostate biopsy; 
PART 2: Men who are scheduled to undergo ultrasound fusion-MR prostate biopsy; 
Men who are willing to participate in the study; 
Subjects must freely sign informed consent to enroll in the study; 
18 years or older 
 
Assessing eligibility: eligibility for the study will be assessed, based upon the above criteria, by the 
participating urologist at the time of consultation. 
 
Exclusion criteria: 
 
Men who have had previous treatment for PCa including radiation, cryoablation, chemotherapy, 
surgery, high intensity focused ultrasound (HIFU), laser therapy or hormone therapy; 
Men who have had previous non-pharmacological invasive or minimally invasive treatment for benign 
prostatic hypertrophy (BPH) (i.e., TURP, TUMPT, WIT, TUNA, etc); standard pharmacological treatment 
of BPH is allowable; 
Men who are mentally impaired and cannot give written consent; 
Men with anomalies of the rectum 
 
Subject Recruitment and Compensation 
 
This study will be open to members of all demographic groups who meet the eligibility criteria. The 
study will be introduced to potential subjects by a healthcare provider known to them. If interested, 
someone from the research team will discuss the study with the potential subject. Potential subjects will 
be identified from the pool of adult male urology patients at clinic 1G, the Duke Cancer Center, the Duke 
Raleigh Urology clinic or referred from an outside facility which will provide sampling from a diverse 

patient population spanning all demographics in order to support equitable subject selection. Subjects 
will not receive any compensation. We will need to review protected health information such as name, 
history number, appointment date and physician, past cancer history, other past medical history and 
other protected health information (PHI) to determine study eligibility. This activity is used only to 
identify subjects, and information resulting from this activity will be used only to assess eligibility of 
subject. Once the subject has been assigned to the study and consent has been obtained, 
documentation of eligibility will be recorded. 
 
PART 1: Ten patients will be recruited for the first part of the study, which will evaluate the performance 
of a new, custom designed ultrasound probe and biopsy guide for systematic transrectal ultrasound 
guided prostate biopsies. 
 
PART 2: Up to 60 patients will be recruited per our existing NIH grant. 
 
Study Interventions 
 
PART 1: Participation will not affect the subjects’ standard clinical treatment in any way.  
 
PART 2: Two-four additional biopsy cores per target lesion will be acquired at suspicious positions 
identified by ARFI targeting. 
 
Risk/Benefit Assessment 
 
PART 1: If, as we expect, the B-mode image quality and biopsy guide performance of the new transducer 
and system are comparable or better than the current clinical TRUS system, there should be no 
increased risk to the patient from using the prototype system for standard systematic TRUS biopsy. If 
the imaging capabilities of the new ultrasound probe are insufficient as compared to the clinical 
ultrasound system, the attending physician will remove the new probe and use the clinical system to 
perform the required measurements and TRUS-guided biopsy. If necessary, this change would require 
approximately 5 minutes.  Per our current IRB protocol, the additional ARFI images that will be acquired 
in each image plane where a biopsy is taken are of minimal risk. The primary risk associated with ARFI 
measurements using the new ultrasound probe is slightly increased tissue heating that is within the FDA 
limits for ultrasound, and a theoretical risk of cavitation. There will be no direct benefit to the patients 
enrolled in this part of the study. 
 
PART 2: The primary risk associated with the second part of the study is the acquisition of two-four 
additional biopsy cores per target as compared to the number obtained during the standard-of-care 
ultrasound fusion-MR biopsy acquisitions. Actually, subjects may require fewer overall numbers of 
biopsy cores as abnormal areas of imaging (ARFI and MRI) will be targeted compared to standard, blind, 
non-targeted prostate biopsy.  Per our current IRB protocol (Pro00006458), while minimal, the primary 
risk associated with ARFI imaging is tissue heating, though temperature increases are below FDA limits 
for ultrasound measurements. There is also a theoretical risk of acoustic cavitation associated with the 
ARFI pulses, however, this is unexpected based upon the pulse MI and duration (Nightingale et. al, JUM, 
2015), and has not been observed in the over 200 ARFI/SWE imaging studies we have performed to 

date. The additional time required for the ARFI measurements and targeted biopsy procedure will 
extend the time the patient will receive anesthesia.  Additionally, this study will require a separate 
insertion of the ARFI probe in addition to the standard TRUS probe used for MRI targeted biopsy. The 
subject will benefit directly from the acquisition of two-four additional biopsy cores per ARFI target at 
suspicious positions identified by ARFI imaging. 
 
We consider the risks identified to be minimal, and we hypothesize that the ARFI technology has 
significant potential for improving the diagnostic accuracy of TRUS prostate biopsy. Thus, we consider 
this study to have a favorable benefit/risk ratio. 
 
Data Analysis & Statistical Considerations 
 
For the first part of the study, images acquired with the new ultrasound transducer will be evaluated 
qualitatively by the attending physician to determine if they are adequate for ultrasonic systematic 
biopsy sampling of the prostate.  ARFI images will also be obtained and will be analyzed off-line using 
existing methods to assess tissue stiffness, needle visualization, and changes in tissue stiffness following 
needle removal.  We expect b-mode ultrasound imaging and ARFI imaging capabilities to be comparable 
or superior to those we have obtained with the transducer/system we have been using under our 
current imaging protocol.   We plan to include up to 10 patients in this Part 1 study.  We do not plan to 
perform statistical analyses for this part because our goal is primarily to verify the functionality of the 
probe/system prior to initiating part 2. 
 
For the second part of the study, we will test the hypothesis that ARFI guided targeted biopsy provides a 
higher PCa detection rate than that reported for systematic TRUS biopsy. We will also compare ARFI-
targeted biopsy performance to that of MR-ultrasound fusion targeting by evaluating the biopsy cores 
obtained using each method with standard statistical tests to compare the length and grade of 
cancerous tissue in the cores.  Biopsies will be scored for clinically significant disease (CSD) using the 
same clinical standard as for TRUS biopsy (e.g., percent PCa per/core, Gleason score, Gleason Grade 
Group) and yield of CSD (i.e., number of cores containing CSD/total number of cores) for each biopsy 
method. In addition, the spatial location of the targeted cores within the prostate will be compared 
between ARFI and Ultrasound-MR fusion.    Assuming an ARFI imaging specificity for CSD of 70% (our 
preliminary data from Protocol Pro00006458 in patients receiving radical prostatectomy yielded 79% 
CSD from ARFI suspicious regions, and, 71% detection of all CSD present in the gland), and comparing to 
the systematic sampling TRUS PCa mean detection rate of 30% that has been well-established in the 
literature, inclusion of 35, 45, and 50 patients would achieve study powers of 80%, 90%, and 95%, 
respectively through a one-mean, one-sample equivalence test with a 30% testing margin and a 
standard deviation of up to 20% of the target ARFI imaging specificity. We plan to include 50 patients in 
this Part 2 study, plus 10 initial patients for early phase development and workflow integration (60 total 
in part 2).  
 
Direct personal identifiers in study records will not be disclosed outside of Duke University Health 
System. For records disclosed outside of Duke, subjects will be assigned a unique code number. 
 
 

Data & Safety Monitoring 
 
The Principal Investigator, Dr. Thomas Polascik, will be responsible for monitoring the safety of these 
studies. As previously described, we do not anticipate any adverse events. However, in the event that 
adverse events occur, they will be immediately reported in detail in writing to the Duke University 
Medical Center’s Institutional Review Board (IRB) in accordance with the re portable events policy. 
 
Data for this study, including relevant medical records such as prostate-specific antigen (PSA) level, 
biopsy results, and any available imaging studies (MR, prior ultrasound, etc.) will be analyzed at the 
completion of study enrollment. A code number will be assigned to each subject, which will be used for 
data analysis and result reporting. The patient name and history number will be recorded only in the 
electronic enrollment log, which will also have the unique code number. The patient consent forms will 
be stored in the office of the primary study coordinator, which is locked when the primary study 
coordinator is not present and is a restricted access area. The protected health information will not be 
reused or disclosed to any other person or entity, except as required by law, for authorized oversight of 
the research study.