PROSTATE MPMRI AND TRUS/MRI FUSION BIOPSY: A · PDF fileDjavan B. Virtual prostate biopsy and biopsy simulation: lessons to be learned. ... content/uploads/2015/11/UroNav_Brochure.pdf

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)


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)


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 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/


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


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.


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


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

[email protected]

http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/PIRADS/PIRADS V2.pdf

http://www.grandroundsinurology.com/prostate-cancer-peter-a-pinto-biopsy-comparison/











