PROSTATE MPMRI AND TRUS/MRI FUSION BIOPSY: A REVIEW
Sam Borofsky, MD
*Baris Turkbey, MD
Sheil Shah, DO
Harold Frazier, MD
Myles Taffel, MD
The George Washington University Hospital, Washington DC
*Molecular Imaging Program, NCI, NIH, Bethesda, MD
Disclosure Statement
The authors of this exhibit have no
conflicts of interest to disclose.
Goals and Objectives
Discuss current and changing paradigms in the urologists’ diagnosis of prostate cancer
The fundamentals of starting a multiparametric prostate program will be discussed, with an emphasis on the needs of referring urologists.
Multiparametric MRI (mpMRI) of the prostate gland will be reviewed.
The latest advancements in MRI/TRUS fusion biopsy will be discussed. Various software packages, and the benefits of each will be analyzed.
Prostate mpMRI in the News
Prostate Cancer Diagnosis
Current standard of care in diagnosing prostate cancer
Screening patients with serum PSA and digital rectal
examination (DRE).
Beginning at age 40 for high risk patients (African American men,
men with first degree relative diagnosed with prostate cancer below
age of 65)
Beginning at age 50 for general population (men at average risk with
>10 year life expectancy)
Concern arises if PSA is elevated (above 4.0 ng/mL, or
PSA velocity > 0.75 ng/mL/year) or the DRE is abnormal.
Subsequently, a biopsy is usually performed.
PCA3 mRNA is utilized as adjunct by some urologists.
This novel test improves sensitivity and specificity
compared to PSA (67% and 71%).
Carter HB, et al. Longitudinal evaluation of prostate-specific antigen levels in men with and without
prostate disease. JAMA. 1992 Apr 22-29;267(16):2215-20.
Vlaeminck-Guillem V et al. Urinary PCA3 to predict prostate cancer in a cohort of 1015 patients. Prog
Urol. 2015 Dec;25(16):e1-8
Prostate Cancer Diagnosis: Biopsy
Standard systematic biopsy
12 core biopsies sampling posterior portion of
prostate gland
As standard biopsy needle only extends 17 mm into
the prostate, tumors in the anterior gland are often
missed.
Example of prostate cancer in a
69 year old man with PSA of 10.6
and previous negative biopsy.
Lesions in the anterior transition
zone (arrows), are often missed
by standard systematic biopsy.
The dashed line demarcades
anterior/posterior gland division,
beyond which standard biopsy
often fails to sample
Djavan B. Virtual prostate biopsy and biopsy simulation: lessons to be learned. BJU Int. 2013 Nov;112(7):876-7. doi:
10.1111/bju.12023. PubMed PMID: 24118952.
PIRADS version2.0. http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/PIRADS/PIRADS%20V2.pdf
Prostate Cancer Diagnosis
Systematic random 12-core biopsy
– Limited sensitivity of only 53%.
– Systematic biopsy has resulted in
overdiagnosis of low grade,
indolent disease (up to 50% of
randomly biopsied cancer may be
clinically insignificant)
– These limitations have led to an
increasing utilization of
multiparametric MRI (mpMRI).
Cooperberg MR, Broering JM, Kantoff PW, Carroll PR. Contemporary trends in low risk prostate cancer: risk assessment and treatment. J Urol. 2007 Sep;178(3 Pt 2):S14-9. Epub 2007 Jul 20. PubMed PMID: 17644125; PubMed Central PMCID: PMC2987559. Siddiqui MM, 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 Jan 27;313(4):390-7.
Small lesions are susceptible to false negative biopsies, due to random sampling error. This 55 year old patient presented with a PSA of 4.3, and previous systematic biopsy showing low volume Gleason 3+3 in the right peripheral zone. Following targeted mpMRI/TRUS fusion biopsy, this lesion (arrows) was found to represent Gleason 4+4 prostate cancer, which was not detected during systematic biopsy.
Prostate mpMRI: Indications
Prostate cancer diagnosed on biopsy, patient at low risk for advanced disease
and/or metastases (PSA ≤10 and Gleason ≤6 and clinical stage T1 or T2a)
ACR Appropriateness criteria rating: 5
Prostate cancer diagnosed on biopsy patient at intermediate risk for locally
advanced disease and metastases (PSA 10-20 or Gleason 7 or clinical stage T2b)
ACR Appropriateness criteria rating: 7
Prostate cancer diagnosed on biopsy patient at high risk for locally advanced
disease and metastases (PSA ≥20 or Gleason 8-10 or clinical stage T2c or higher)
ACR Appropriateness criteria rating: 8
Multiple negative prostate biopsies, but there is concern for prostate cancer based
upon rising or persistently elevated serum markers suggestive of cancer.
ACR Appropriateness criteria rating: 7
ACR Appropriateness Criteria Rating Scale:
1,2,3 Usually not appropriate
4,5,6 May be appropriate
7,8,9 Usually appropriate
Eberhardt et al. PROSTATE CANCER —American College of Radiology ACR Appropriateness Criteria.
Prostate Cancer — Pretreatment Detection, Staging, and Surveillance.
Fundamentals of mpMRI Program: Components
Hardware
MRI Scanner 1.5 Tesla versus 3.0 Tesla
± Endorectal Coil (ERC)
Guided Biopsy MRI guided cognitive biopsy
Operator directs TRUS biopsy to
area of abnormality on mpMRI by
visual estimation
MRI/TRUS fusion biopsy mpMRI findings digitally overlaid
on real-time TRUS images for
targeted biopsy
In bore direct MRI biopsy
Example of MRI/TRUS fusion biopsy system in NIH
Interventional Urology Suite. mpMRI data is
transferred to workstation, which then fuses with real-
time ultrasound equipment with the aid of an
electromagnetic field generator (EM-FG) for tracking
and image registration
Cornud F, Brolis L, Delongchamps NB, Portalez D, Malavaud B, Renard-Penna R, Mozer P. TRUS-MRI image
registration: a paradigm shift in the diagnosis of significant prostate cancer. Abdom Imaging. 2013 Dec;38(6):1447-63.
doi: 10.1007/s00261-013-0018-4. Review. PubMed PMID: 23860771.
Pinto P(2015). MRI-US Fused Imaging in Prostate Cancer: Targeted Biopsy vs. Standard Biopsy vs. Template Biopsy.
Retrieved from http://www.grandroundsinurology.com/prostate-cancer-peter-a-pinto-biopsy-comparison/
Fundamentals of mpMRI Program: Components
Software
Diagnostic Component:
mpMRI image analysis software (Hitachi/Eigen Profuse, Philips/Invivo DynaCAD)
Intervention Component:
Cognitive Biopsy
MRI/TRUS fusion biopsy
In bore MRI biopsy
Example of Hitachi/Eigen ProFuse mpMRI
software. Entire prostate gland is semi-
automatically segmented (green outline). Two
lesions are outlined by green and yellow circles
(region of interest/ROI 1 and 2), for targeting on
subsequent fusion biopsy
Artemis for MRI Fusion Targeted Biopsy Solutions. http://www.hitachi-
aloka.com/products/artemis/urology/mri-fusion-targeted-biopsy-solutions
Magnetic Field Strength
1.5 Tesla
Benefits
Less susceptible to metallic
artifact
Decreased cost
Can be used in select
patients who contain
implanted devices deemed
unsafe for 3T MRI
Disadvantages
Endorectal coil usually
required
Lower signal to noise ratio,
particularly problematic with
high b-value diffusion
weighted imaging (DWI)
3 Tesla
Benefits
Higher signal to noise ratio
Improved sensitivity in detection
of prostate cancer
3T is recommended by
PIRADS steering committee
Diagnostic images can be
obtained without ERC
Disadvantages
More susceptible to metallic
artifacts
Increased cost
Increased RF energy deposition
Magnetic Field Strength
Example of the same patient undergoing MRI at 1.5 Tesla with endorectal coil (ERC) on
left and 3.0 Tesla without ERC on right. The patient had a PSA of 6.9, and a previous
positive systematic biopsy. Images obtained at higher magnetic field show improved
signal and contrast resolution, despite lack of endorectal coil. There is improved
conspicuity of two lesions in the prostate (arrows). Note presence of motion artifact in
image obtained with ERC, due to rectal peristalsis
A B
Endorectal Coil
Benefits:
Increases signal to noise
ratio in prostate gland
Improves detection of
prostate cancer,
particularly small lesions
(76% vs 45% sensitivity)
Aids DWI and improves
temporal resolution of DCE
sequences
Disadvantages:
Discomfort
Susceptibility and motion
related artifacts
Increased Cost
Increased Exam Time
Turkbey B, Merino MJ, Gallardo EC, Shah V, Aras O, Bernardo M, Mena E, Daar D, Rastinehad AR, Linehan WM, Wood BJ, Pinto PA, Choyke
PL. Comparison of endorectal coil and nonendorectal coil T2W and diffusion-weighted MRI at 3 Tesla for localizing prostate cancer: correlation
with whole-mount histopathology. J Magn Reson Imaging. 2014
MEDRAD MR eCoil™ https://www.imaxeon.com/products/MR/pages/MR_Coils.aspx
Endorectal Coil
Examples of different agents within ERC: MRI at 1.5 Tesla with barium insufflated endorectal coil (A). MRI at 3.0 Tesla with perfluorocarbon (PFC) compound (B).
A B
mpMRI: Technique
Multiparametric prostate MRI combines
anatomic T2 Weighted images with
functional and physiologic assessment using
diffusion weighted imaging (DWI) and
dynamic contrast enhanced (DCE) MRI.
The combination of these sequences have
led to substantial improvements in the
detection of clinically significant cancer
PIRADS version2.0. http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/PIRADS/PIRADS%20V2.pdf
mpMRI: Anatomic T2 Weighted Imaging
Example of T2 Weighted imaging in a patient with a normal prostate MRI. Peripheral Zone (asterisks), anterior fibromuscular stroma (S), prostate capsule (arrowheads), prostatic urethra (arrows), and neurovascular bundles (NV). Note hypointense signal from PFC gas within endorectal coil.
mpMRI: Technique
Example of mpMRI in a 61 year old man with serum PSA of 22.64 ng/mL T2WI show
a focal hypointense lesion in the right peripheral zone (arrow), with corresponding
restricted diffusion on ADC map and B2000 DWI, as well as early hyper-enhancement
on DCE-MRI. Interpreting all sequences simultaneously increases the confidence in
identifying this PIRADS 5 lesion.
T2W MRI
ADC map b=2000 DWI
DCE MRI
PiRADS 2.0 Score: • T2W MRI=5 • DW MRI=5 • DCE MRI=+ • Overall PiRADS score=5. Targeted biopsy showed 4+4 disease
T2W MRI
ADC map b=2000 DWI
DCE MRI
Example: 61 year old man with serum PSA of 22.64 ng/mL
Fundamentals of mpMRI Program: Components
Intervention Component:
mpMRI data uploaded to TRUS
fusion software system with lesions
demarcated by radiologist.
Ultrasound data is then linked to
fusion system for biopsy with targets
visualized on ultrasound screen
Vendors:
Most Common:
Uronav
Artemis
Less frequently utilized in US
Koelis/Urostation (France)
Hitachi/HI-RVS (Japan)
Geoscan/BioJet
Example of Philipis/Invivo Uronav software. Top images show
realt-time TRUS image acquisition. Bottom left images shows
axial T2 weighted image of mpMRI dataset, which can be used
for real-time coordination during fusion biopsy.
UroNav patient brochure. http://www.invivocorp.com/wp-content/uploads/2015/11/UroNav_Brochure.pdf
MRI/TRUS Fusion: Spatial Registration
Registration of TRUS and mpMRI with a navigation device.
Spatial coordinates linked by communication between a receiver
on/near TRUS probe and tracking device placed close to patient
Planning phase: at least three anatomic landmarks paired between MRI
and TRUS
Guiding phase: MR guided navigation of real-time TRUS scanning
Cornud F, Brolis L, Delongchamps NB, Portalez D, Malavaud B, Renard-Penna R, Mozer P. TRUS-MRI image registration: a paradigm shift
in the diagnosis of significant prostate cancer. Abdom Imaging. 2013 Dec;38(6):1447-63. doi: 10.1007/s00261-013-0018-4. Review. PubMed
PMID: 23860771.
Artemis for MRI Fusion Targeted Biopsy Solutions. http://www.hitachi-aloka.com/products/artemis/urology/mri-fusion-targeted-biopsy-
solutions
Example of landmark
based registration
between mpMRI and
TRUS (red circles)
Organ Based Registration
Registration of TRUS and mpMRI which accounts for prostate deformation (from
ERC, pressure US transducer)
Software tracks the prostate gland itself, rather than the US probe
Planning phase: 3D acquisition of prostate volume, followed by:
Uses multiple point registration and elastic 3D organ based registration, in
addition to standard three point landmark based registration
Organ based registration are optional packages offered some vendors
Cornud F, Brolis L, Delongchamps NB, Portalez D, Malavaud B, Renard-Penna R, Mozer P.
TRUS-MRI image registration: a paradigm shift in the diagnosis of significant prostate cancer.
Abdom Imaging. 2013 Dec;38(6):1447-63. doi: 10.1007/s00261-013-0018-4. Review. PubMed PMID: 23860771.
Example of spatial/rigid registration (A) as
described by Cornud et al. Three point
registration does shows inaccurate registration
in the presence of any prostate deformation.
Algorithms can compensate for this using
organ based/elastic registration(B)
MRI/TRUS Fusion Biopsy – Uronav
Philips/Invivo UroNav: Planning phase: 2D TRUS acquisition to
construct 3D volume. Registration is done manually by software (non-rigid registration)
Electromagnetic navigation sensor attached to ultrasound transducer. A stationary navigation system is placed above the patient in order to track probe. Fusion software helps guide operator to pre-delineated lesions based on mpMRI.
Pros: Can integrate with existing ultrasound
software (left)
Technique familiar to urologist due to use of endocavitary US probe (right)
Easy to adjust for patient motion
Cons More susceptible to prostate deformation
Less accurate probe tracking compared to robotic system
Requires manual calibration of ultrasound images
Sensor on TRUS probe, which is
tracked by using a small
electromagnetic field generator (white
box placed above or below surgical
field)
UroNav patient brochure. http://www.invivocorp.com/wp-
content/uploads/2015/11/UroNav_Brochure.pdf
MRI/TRUS Fusion Biopsy – Uronav
Example of UroNav fusion biopsy. Top, realtime TRUS biopsy,
with red circle segmented prostate. Bottom, mpMRI T2 weighted
image with previously delineated lesion/ROI.
UroNav patient brochure. http://www.invivocorp.com/wp-
content/uploads/2015/11/UroNav_Brochure.pdf
MRI/TRUS Fusion Biopsy – Artemis
Hitachi/Eigen- Artemis:
3D Semi-robotic prostate navigation system. Needle and TRUS probe tracked by angle-sensing devices built into each joint of the arm.
Planning phase: 2D mode US scanning renders 3D image, which is segmented and registered to mpMRI data set with previously segmented prostate and lesions
Pros: Automatic, Fast, Rigid and Elastic Image
Fusion
Remote center of motion, minimizing prostate deformation that occurs during standard TRUS guided biopsy
Cons:
Registration requires total patient immobility
Operator must learn a new technique to operate device
Marks L, Young S, Natarajan S. MRI–ultrasound fusion for guidance of targeted prostate
biopsy. Current opinion in urology. 2013;23(1):43-50. doi:10.1097/MOU.0b013e32835ad3ee.
MRI/TRUS Fusion Biopsy – Artemis
Example of MRI/TRUS fusion biopsy. Top left, bottom left real-time
ultrasound, top right, segmented mpMRI with lesions delineated with ROIs.
Bottom right, 3D model of prostate with previously delineated ROIs
Artemis for MRI Fusion Targeted Biopsy Solutions. http://www.hitachi-aloka.com/products/artemis/urology/mri-
fusion-targeted-biopsy-solutions
MRI-TRUS Fusion: The Cost?
Health Systems/Urologists/Radiologists without the technology are increasingly losing patients to competitors
Acquisition of MRI/TRUS fusion systems come at significant expense to hospital, with reported costs ranging between $200,000 and $300,000.
Difficult to recoup capital costs:
MRI/TRUS fusion does not have an independent CPT code, and is currently only reimbursed to same extent as a standard biopsy.
Fusion biopsies are usually acquired in conjunction with standard sextant biopsies. Thus, overall procedure time is generally increased with no change in reimbursement.
de Rooij M, Crienen S, Witjes JA, Barentsz JO, Rovers MM, Grutters JP. Cost-effectiveness of magnetic resonance (MR)
imaging and MR-guided targeted biopsy versus systematic transrectal ultrasound-guided biopsy in diagnosing prostate
cancer: a modelling study from a health care perspective. Eur Urol. 2014
Lee SM. Prostate diagnosis adds MRI to ultrasound for clearer view. www.SFGate.com 2014.
Jesitus J. MRI guiding future of prostate cancer diagnosis. Urology Times. 2014.
MRI-TRUS Fusion: The Cost?
Potential to offset costs:
Patients who undergo mpMRI may not undergo biopsy if no lesion is found.
Although conventional biopsies are often still being acquired in addition to targeted lesions, the decrease in repeat biopsies leads to less specimens submitted for pathology review.
Decreased prostatectomy on low-risk patients
A recent European study suggested the cost of mpMRI and TRUS/fusion to be comparable to the current standard of care
de Rooij M, Crienen S, Witjes JA, Barentsz JO, Rovers MM, Grutters JP. Cost-effectiveness of magnetic
resonance (MR) imaging and MR-guided targeted biopsy versus systematic transrectal ultrasound-guided
biopsy in diagnosing prostate cancer: a modelling study from a health care perspective. Eur Urol. 2014
Lee SM. Prostate diagnosis adds MRI to ultrasound for clearer view. www.SFGate.com 2014.
Jesitus J. MRI guiding future of prostate cancer diagnosis. Urology Times. 2014.
Conclusion
mpMRI with MRI/TRUS fusion systems
are increasingly utilized tools to aid in the
detection, localization, and risk
stratification of patients with prostate
cancer.
These techniques represent significant
advantages over the longstanding tools of
serum PSA and systematic biopsy.
References and Correspondence
• Carter HB, Pearson JD, Metter EJ, Brant LJ, Chan DW, Andres R, Fozard JL, Walsh PC. Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease.
JAMA. 1992 Apr 22-29;267(16):2215-20.
• Djavan B. Virtual prostate biopsy and biopsy simulation: lessons to be learned. BJU Int. 2013 Nov;112(7):876-7. doi: 10.1111/bju.12023. PubMed PMID: 24118952.
• Vlaeminck-Guillem V, Devonec M, Champetier D, Decaussin-Petrucci M, Paparel P, Perrin P, Ruffion A. Urinary PCA3 to predict prostate cancer in a cohort of 1015 patients. Prog Urol. 2015
Dec;25(16):e1-8. doi: 10.1016/j.purol.2015.10.006. Epub 2015 Nov 14. PubMed PMID: 26586639.
• PIRADS V2. http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/PIRADS/PIRADS%20V2.pdf
• Siddiqui MM, 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 Jan
27;313(4):390-7.
• Mendhiratta N, Meng X, Rosenkrantz AB, et al. Pre-Biopsy MRI and MRI-Ultrasound Fusion-Targeted Prostate Biopsy in Men with Previous Negative Biopsies: Impact on Repeat Biopsy
Strategies. Urology. doi:http://dx.doi.org/10.1016/
• Salami SS, Ben-Levi E, Yaskiv O, et al. In patients with a previous negative prostate biopsy and a suspicious lesion on MRI, is a 12-core biopsy still necessary in addition to a targeted
biopsy? BJU Int 2015; 115:562–570v
• UroNav patient brochure. http://www.invivocorp.com/wp-content/uploads/2015/11/UroNav_Brochure.pdf
• Pepe P(1), Garufi A(2), Priolo G(2), Pennisi M(3). Can MRI/TRUS fusion targeted biopsy replace saturation prostate biopsy in the re-evaluation of men in active surveillance? World J Urol.
2015 Dec 23. [Epub ahead of print]
• Artemis for MRI Fusion Targeted Biopsy Solutions. http://www.hitachi-aloka.com/products/artemis/urology/mri-fusion-targeted-biopsy-solutions
• D'Amico, R. Whittington, S.B. Malkowicz, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized
prostate cancer. JAMA. 1998 Sep 16;280(11):969-74.
• Mufarrij P, Sankin A, Godoy G, Lepor H. Pathologic outcomes of candidates for active surveillance undergoing radical prostatectomy. Urology 2010; 76:689–692.
Mendhiratta N, Rosenkrantz AB, Meng X, et al. Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy in a Consecutive Cohort of Men with No Previous Biopsy:
Reduction of Over Detection through Improved Risk Stratification. J Urol 2015. doi:10.1016/j.juro.2015.06.078
Eberhardt et al. PROSTATE CANCER —American College of Radiology ACR Appropriateness Criteria. Prostate Cancer — Pretreatment Detection, Staging, and Surveillance.
Lee SM. Prostate diagnosis adds MRI to ultrasound for clearer view. www.SFGate.com 2014
Jesitus J. MRI guiding future of prostate cancer diagnosis. Urology Times. 2014.
de Rooij M, Crienen S, Witjes JA, Barentsz JO, Rovers MM, Grutters JP. Cost-effectiveness of magnetic resonance (MR) imaging and MR-guided targeted biopsy versus systematic
transrectal ultrasound-guided biopsy in diagnosing prostate cancer: a modelling study from a health care perspective. Eur Urol. 2014
Turkbey B, Merino MJ, Gallardo EC, Shah V, Aras O, Bernardo M, Mena E, Daar D, Rastinehad AR, Linehan WM, Wood BJ, Pinto PA, Choyke PL. Comparison of endorectal coil and
nonendorectal coil T2W and diffusion-weighted MRI at 3 Tesla for localizing prostate cancer: correlation with whole-mount histopathology. J Magn Reson Imaging. 2014
Cornud F, Brolis L, Delongchamps NB, Portalez D, Malavaud B, Renard-Penna R, Mozer P. TRUS-MRI image registration: a paradigm shift in the diagnosis of significant prostate cancer.
Abdom Imaging. 2013 Dec;38(6):1447-63. doi: 10.1007/s00261-013-0018-4. Review. PubMed PMID: 23860771.
Pinto P(2015). MRI-US Fused Imaging in Prostate Cancer: Targeted Biopsy vs. Standard Biopsy vs. Template Biopsy. Retrieved from http://www.grandroundsinurology.com/prostate-cancer-
peter-a-pinto-biopsy-comparison/
Address Correspondence to:
Samuel Borofsky
The George Washington University Hospital
Department of Radiology
900 23rd St NW