Jean Michel Correas, prostate cancer use of multiparametric ultrasound imaging for management, jfim ifupi milan 2018

1. Pr JM Correas MD PhD
Paris-Descartes University & Department of Adult Radiology, Necker University Hospital
Ecole Supérieure de Physique et Chimie Industrielles, Paris Tech,
Institut Langevin (CNRS UMR 7587) & INSERM ERL 979
Paris France
Prostate cancer: use of multiparametric ultrasound
imaging for management
1st Italian-French Update Imaging – IFUPI
Advanced Multiparametric Imaging - How to use in daily practice
MILAN March 23-24 2018
www.jfim.org

2. Conflict of Interest:
- Toshiba MS: expert and lecturer
- Philips US: expert and lecturer
- SuperSonic Imagine: expert and lecturer
- Hitachi MS: expert and lecturer
- Bracco SA: expert and lecturer, principal investigator of
BR1-127 and SonoCap protocol
- Guerbet SA: expert and lecturer, principal investigator of
NsSafe and Secure protocol, lecturer
jean-michel.correas@aphp.fr

3. The prostate cancer
• Most common diagnosed malignancy in men (besides skin cancer)
Incidence > 200/100000 men/Y
• 2nd leading cause of cancer death in men
• Evolution: slight decrease in the incidence
annual death rate & mortality: slight ⇓
BUT
strong 5-year survival rate increase
(30% in 25 Y; 98%)
• PCa: stiff lesion (DRE) and hypervascular (dynamic-MRI)
Mottet N.et al. EAU–ESTRO–SIOG Guidelines
on Prostate Cancer. Part 1:
Screening, Diagnosis, and Local Treatment with
Curative Intent. Eur Urol. 2016 Aug 25

4. • Limited performance of all dg tests (PSA, TRUS, MRI, biopsy)
• PSA: Non specific elevation (PCa, BPH, prostatitis…)
20% of PCa => PSA< 4 ng/ml
• TRUS limited sensitivity (30-50%) for PCa detection
Normal TRUS => not delay prostate biopsies if abnormal DRE/PSA
Limitation of diagnostic tests
Conventional TRUS
(Necker; 105 pat. MRI + biopsy correlation Se 32% Sp 88% PPV 38% NPV 85%)

5. • MRI: MP imaging (T2w, diffusion,DCE-MRI, spectroscopy)
=> a major tool for cancer detection and staging significant PC
- High detection rate (Se 58-96%) and NPV (63-98%)*
- BUT low specificity (23-87%) and limited accuracy (44-87%)
- Additional limitations: cost, availability, tolerance
biopsy guidance with fusion
Limitation of diagnostic tests
Multi-Parametric MRI
*Fütterer JJ, et al. Can Clinically Significant Prostate Cancer
Be Detected with Multiparametric Magnetic Resonance
Imaging? A Systematic Review of the Literature.
Eur Urol (2015), http://dx.doi.org/10.1016
** Le JD, et al. Multifocality and Prostate Cancer Detection
by Multiparametric Magnetic Resonance Imaging: Correlation
with Whole-mount Histopathology.Eur Urol. 2014 Sep 22

6. • Prostate biopsies:
- systematic posterior sextant biopsies in PZ with
various sampling protocols (12 cores)
- additional targeted biopsies on US/MRI abnormalities
- provide diagnosis of cancer and grade (Gleason score)
- BUT false negative rate of 17-21%
positive biopsy rate 30-60% depending on PSA values
- Additional limitations:
cost (procedure, pathology, complications, gal anesthesia),
tolerance and complications (bleeding, infection)
in some cases: hospitalization, general anesthesia…
Limitation of diagnostic tests
Prostate biopsies
Matlaga BR J Urol 2003; Djavan BJ Urol 2001

7. Shear Wave Elastography
Principles
STEP 1
Radiation Force:
Shear wave generation by
inducing local excitation
STEP 2
UltraFast Imaging:
Shear wave propagation is
captured with planes waves
7
STEP 3
Quantification
processing:
From velocity movie to
elasticity
Total time: 20 ms
Acquisition speeds of up to 20 000 Hz
MultiWave™ Interaction

8. Prostate US elastography
Performing acquisition
• SWE elastography:
- Prostate preset, “PEN” option, scale 70 kPa
- set SWE window on transverse plane
- avoid any pressure on the probe
- wait until stabilization of signals (2-3 sec)
- scan entire gland from base to apex
- suspicious lesion: hypoechogenic + increased stiffness (red)
calculation of elasticity in ROI (mean, SD, min, max) and ratio
- store digital cineloop for review (up to 5 min) and review
It is possible to calculate again stiffness values and ratios on still frames
even after the end of the examination

9. Prostate elastography
Normal pattern
• SWE elastography:
- PZ: homogeneous encoding
with blue and green colors
(soft tissue)
- TZ:
before BPH: PZ, CZ & ZC soft
with elasticity< 30 kPa
with BPH: CZ & TZ heterogeneous
pattern 30 – 180 kPa
Calcifications => stiff area

10. Prostate elastography
SWE cancer pattern
• SW elastography:
- heterogeneous stiff area coded
in red in PZ
- with stable signals

11. Pathology: inflammation except in nodule biopsied=> 8 mm cancer Gleason 7
Prostate elastography
SWE cancer pattern

12. Prostate elastography
SWE performance prior to random/targeted biopsy
• Random biopsy overall SWE performance: Acc 70 - 96%, SE
92-96% (except for Woo et al.), and Spe 83 - 99% higher than
those of SE
• PCa Stiffness much higher than normal tissue stiffness
(p<0.0001) and ìstiffness linked to ìGleason Score
1.Barr RG, Memo R, Schaub CR. Shear wave ultrasound elastography of the prostate: initial results. Ultrasound quarterly. Mar 2012;28(1):13-20.
2.Ahmad S, Cao R, Varghese T, Bidaut L, Nabi G. Transrectal quantitative shear wave elastography in the detection and characterisation of prostate cancer. Surgical endoscopy. Sep
2013;27(9):3280-3287.
3.Woo S, Kim SY, Cho JY, Kim SH. Shear wave elastography for detection of prostate cancer: a preliminary study. Korean journal of radiology : official journal of the Korean Radiological
Society. May 2014;15(3):346-355.
4.Correas JM, Tissier AM, Khairoune A, et al. Prostate Cancer: Diagnostic Performance of Real-time Shear-Wave Elastography. Radiology. Apr 2015;275(1):280-289.
5.Boehm K, Budaus L, Tennstedt P, et al. Prediction of Significant Prostate Cancer at Prostate Biopsy and Per Core Detection Rate of Targeted and Systematic Biopsies Using Real-Time
Shear Wave Elastography. Urologia internationalis. Jun 3 2015.

13. • Prostate ADK: 41 ± 43 kPa (r=2.9 ± 1.1) vs adenomatous hyperplasia
vs focal prostatitis: 29 ± 19 kPa (r=1.17 ± 0.6)
• Ratio cut-off value for highest NPV:
stiffness= 35 kPa / elasticity ratio= 1.5
Prostate elastography
SWE performance
P< 0.0001
Correas et al. Radiology 2015

14. ROC curve for sextant SWE
(AUC 0.95)
Prostate elastography
SWE performance
ROC curve for patient SWE
(AUC 0.80)

15. Prostate elastography
SWE improving biopsy guidance
• Prospective bicentric study (Dr Barr Ohio, USA & Dr Correas Paris, France)
• Population: 184 men (66 ± 7 Y) + PSA level (7.4 ± 6.5 ng/ml)
state-of-the art prostate imaging using AixPlorer (SSI, France)
• Pathology: 12 systematic biopsies + 2-6 targeted biopsies
Significant prostate cancer define as positive core length≥ 2mm and Gleason≥ 6
- Lesions: 132 detected at conventional US/ pathology
- 56 cancers / 76 benign lesions (hyperplasia/ focal prostatitis)
• Cancer detection rate:
- Systematic biopsies: 1709 including 213 positive cores (12%)
- Targeted biopies: 275 including 110 positive cores (40%)

16. • TR CEUS: under evaluation
- preliminary experience Levovist®
- can improve cancer detection
- improved detection rate of
targeted biopsies
CE-TRUS imaging
Ragde Prostate 1997; Rifkin RSNA 1997
Eckersley RSNA 1998; Bogers Urology 1999
Halpern AJR 2002; Frauscher J Urol 2002
Roy J Urol 2003

17. • TR CEUS: under evaluation
- can improve cancer detection
- targeted biopsies to abnormal enhancement => detection rate 50%
higher/ systematic biopsies
- transient arterial enhancement
• TR CEUS acquisition
- stabilize transducer at the most suspicious level
- set acoustic power, gain, focal zone
- avoid pressure on PZ
- SonoVue®: 2x 2.4 mL bolus inj.
Halpern RSNA 2003;
Mitterberger Prostate 2007
CE-TRUS
prostate imaging

18. CE-TRUS prostate imaging
Difference between PCa and non-PCA nodules p-value
1 WiPI wash-in perfusion index (WiAUC/RT) 1.172e-12
2 PE peak enhancement [a.u] 1.511e-12
3 WiRxWoR wash-in and wash-out product 3.204e-11
4 WiR wash-in rate 4.687e-11
5 WoR wash-out Rate 1.254e-10
6 WiAUC wash-in area under the curve 1.989e-07
7 WiWoAUC wash-in and wash-out AUC 3.208e-05
8 WoAUC wash-out AUC 0.0001412
9 RT rise time [sec] 0.006359
10 TTP time to peak 0.01048
11 FT fall time (TO – TTP) 0.01255
12 mTTl mean transit time local (mTT – TI) 0.7433
Master Dr M Skendi

19. • Due to microbubble detection
- resonance freq. (1-2 MHz) below transducer transmit freq.
- transducer focalization (PZ against transducer)
- subjective assessment
• Due to prostate gland vascularity
- limited vascularity of prostate gland
- high vascularity of TZ compared to PZ
- poor enhancement of FMZ (attenuation)
• Due to prostate cancer vascularity
- all PC are not highly perfused
- PC hypervascularity highly transient
- PC and normal tissue rapidly iso-enhanced
- lack of delayed phase
CE-TRUS prostate imaging limitations

20. Recent improvements
• 3D-SWE
• CE-TRUS with dispersion mode
• 3D-CEUS
• Automatic fusion with mp-MRI

21. Potential additional value of 3D-SWE
● Standardized acquisition (B-mode, PDUS and SWE…)
● One single acquisition for complete prostate SWE assessment
● Combined evaluation of 3D-SWE to 3D-B mode and 3D-PDUS
● Improved stiffness assessment in the coronal plane
● Improved staging: sub-capsular lesions, seminal vesicle
extension
● Improved performance (significant PCa detection,
nodule characterization)

22. 3D-Prostate
Image Processing
● B-mode, PDUS and SWE processed
● MPR calculated directly on the
AixPlorer US system at the end of
examination
● Axial, coronal and transverse MPR
with 16 planes covering entire
prostate with and without color info.
● Thickness rendering: max
Thickness slice: 2.2 mm
Interslice gap: 0 mm

23. Coronal Planes
Reconstructions of Multislice Views of
3D Bmode and 3D SWE
Tranverse Planes Sagittal Planes

24. PZ left (normal)
PZ right (cancer)
Mode (most frequently occurring value)
Sigma (dispersion)
PZ right PZ left
WiR parametric image
WiR histogram (PZ)
Courtesy Pr Tranquart & Dr P Frinking
Bracco Research
( )2
expMode M S= −
( )( )2 2
exp 2 exp( ) 1Sigma S M S= + −
CE-TRUS: dispersion mode
Statistical analysis of wash-in rate

25. CE-TRUS: dispersion mode
Statistical analysis of wash-in rate
• Sensitivity 90%
• Specificity 70%
• Positive Predictive value 45%
• Negative Predictive value 95%
PZ K
(Gleason≥7)
NK
SP+ 29 24 53
SP- 3 56 59
Total nodules 32 80 112
Master Dr M Skendi

26. 70 year-old man, normal DRE, volume 30 mL
- 2010: BPH resection <5% cancer G6 PSA 3 ng/ml => active surveill.
- 2011 PSA 6.1 ng/ml => MRI: right lateral apex PiRads III 6 mm
diffuse heterogeneous PZ in T2
G 6 G 7 G 8 SWEBmode MRI
8mm

35. 70 year-old man, normal DRE, volume 30 mL
- 2010: BPH resection <5% cancer G6 PSA 3 ng/ml => active surveill.
- 2011 PSA 6.1 ng/ml => MRI: right lateral apex PiRads III 6 mm
diffuse heterogeneous PZ in T2
G 6 G 7 G 8 SWEBmode MRI
8mm
36/52
10/20

36. • Automatic fusion procedure (OmniTrax® detection)
- fusion available information provided by MRI
- with all US modalities: conventional / CEUS / 3D
- independent from patient mvts
- ultrafast and reliable
MR-US Fusion Imaging

37. Bmode + dCPI:
One suspicious target
60 YO man; PSA 13.3 ng/ml (no previous data);
no previous US study
SWE:
Large lesion

38. Mid Section
60 YO man; PSA 13.3 ng/ml (no previous data); no previous US study
SWE CEUS

39. Abb. 6 PI-RADS-Klassifikation für MR-Spektroskopie.
Standardisiertes MRT Befundschema Prostata
Name: _________________________
Datum:
PSA:
Vorherige Biopsie:
Vorherige MRT:
PI-RADS: 1-benigne; 2-wahrscheinlich benigne; 3-unklar; 4-wahrscheinlich maligne, 5 – hochwahrscheinlich maligne
Einzelscoring:
Gesamtbeurteilung PI-RADS:
Regio PI-RADSSummeMRSDCEDWIT2
Abb. 7 Standardisiertes MRT-Befundschema Prostata, PI-RADS.
DokumentwurdezumpersönlichenGebrauchheruntergeladen.VervielfältigungnurmitZustimmungdesVerlages.
G 7
G 7
Positive Biopsies Gleason 7
Right Lobe
MRIG 6 G 7 G 8 SWEBmode
T2
60 YO man; PSA 13.3 ng/ml (no previous data)
- mp-MRI prior to biopsy: 1 nodule at he apex and mid part of the prostate
G 7
G 7
1
G 7
G 7
DCE
DWI

40. MP-US
of the
prostate

41. MP
-
IRM
Elastography
MR-spectroscopy
T2w MR sequence B-mode anatomy
Diffusion MR sequence
Perfusion Imaging
MP
-
US
Fusion Imaging
mp-IRM & mp-US
3D/4D Imaging
Vascular Imaging
Perfusion Imaging

42. Conclusion
• Limited performance of
conventional TRUS
• mp-US: SWE + CEUS: US modalities that allow stiffness
and perfusion assessment for:
- characterization of area/nodule detected at MRI/US/CDUS/ ECUS
- detection of a suspicious area
- targeted biopsy guidance
- fusion with all modalities to MRI
• Future perspectives:
- volumetric SWE (3D/4D) with MPR
automatic fusion to mp-MRI (only with SWE)
=> focal therapy?
Work-in Progress SuperSonic Imagine