Barentsz
2-4-2011
Advances in Prostate
MR imaging
Learning
LearningObjectives
Objectives
• to show the potential of
new MR
MRII developments in PCa
Jelle Barentsz
Prostate MR Center of Excellence
Department of Radiology
Radboud University Nijmegen Medicaal Center
The Netherlands
• to illustrate this from a clinical
(radiation oncology)
oncology) perspective
[email protected]
Multi-parametic
Learning ObjectivesMRI
T2WI MRI: anatomy
1. High resolution T2
T2WI:
WI: anatomy
2. Diffusion Weighted Imaging: function
3. Hydrogen MR
MR--Spectroscopy: function
4. Dynamic Contrast Enhanced: function
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Barentsz
2-4-2011
c. Villiers
MRI: high soft tissue contrast
CT Image
Delineation of CTV
Additional Use of MRI
Delineation of CTV:
CT > MRI
MR Image
MR-anatomy of PCa
• Smaller CTV (6.5%(6.5%-34%)
• Inter
Inter--observer variability ↓ (~63%) at:
-
Apex :
↓↓↓↓
Base :
↓↓
SV :
↓
Mid--gland : Mid
Roach IJROPB 1996,
Rash IJROPB 1999,
Villiers,, Strahlenther Onko 2006
Villiers
PCa, hematoma, fibrosis, prostatitis: low SI
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Barentsz
2-4-2011
Patient 57 y, PSA 7; TRUS Bx: negative
T2WI: PCa anatomy
Your diagnosis?
1.
2.
3.
4.
normal
BPH
prostatitis
ventral TZ tumor
T2WI: Local Staging
T2WI: PCa anatomy
•
•
•
•
BPH: organised chaos
“Erased Charcoal drawing sign”
prostatectomy vs radiotherapy
decrease R+
nerve sparing
local therapy
3T ERC:
se 87% sp 96%
Futterer, Invest Radiol 2006, Heijmink, Radiology 2007
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Barentsz
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Multi-parametric MRI: DWI
DWI: ADC-value versus Gleason score
Pearson
Correlation
Organised galandular tissue
Tightly packed cellular tissue
r = 0.73
p < 0.01
DWI: PCa restricted H2O movement
Specificity, aggression!
DWI: ADC-value vs Gleason score
Hambrock,, Radiology, in press
Hambrock
Alvares,, Radiology, in press
Alvares
Multi-parametric MRI: DCE
DCE MRI: PCa increased vascular permeability
Sensitivity!!
Sensitivity
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Barentsz
2-4-2011
MR Spectroscopy
MR Spectroscopy
Metabolite ratio Cho + Cr
Cit
↑
Creatine
Citrate
0.37 / 0.64
For Ferrari drivers only?
MR Spectroscopy
Clinical Problems
•
PSA:: non specific marker :
PSA
>4 ng
ng/L:
/L: sens.:
sens.: 80%, spec
spec.:
.: 36%
•
DRE is not sensitive
- sens
sens.:
.: 37%
37%,, spec
spec.:
.: 91%
You need EXPERIENCE how to drive
Djavan J Urol (2001); Roehl J Urol (2002); Pepe Urol (2007), Schroeder JNCI (1998)
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Barentsz
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Problems: TRUS Bx
•
Clinically insignificant
cancers are identified by
chance
•
Important cancers are
incorrectly classified as
unimportant or are missed
•
36- 46% undergrading of
36Gleason score
Be aware!
EU Urologists are getting there
Sciarra, European Urology 2011
Multi-modality MRI:
MR-guided biopsy
Intraprostatic Localization Accuracy
Accuracy::
T2
T2--w :
70%
Jager AJR 1996; Scheidler Radiol 1999
DWI--MRI:
DWI
86%
Haider AJR 2007; Miao Eur J Rad 2007
H-MRS:
81%
Futterer Radiol 2006, Reinsberg AJR 2007
DCE-- MRI:
DCE
85%
Ito Br J Radiol 2003, Futterer Radiol 2006
Gleason score 4+3
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Barentsz
2-4-2011
3T MR-biopsy (n=68)
• After ≥2 - biopsies: TRUS is + in 5-19%
• MR-guided biopsy of TSR: + in 59% (40/68)
What is beyond
theObjectives
horizon?
Learning
1. Improvement of mpmp-MR directed
biopsy techniques
2. Active Surveillance, Screening
• with MR ~ 4 cores instead of ~ 12
3. Will mpmp-MRI replace Gleason?
• 57% anterior tumors
4. Focal therapy
• 93% (37/40) clinically significant tumors
nano--particles + DWI
5. Nodes:
Nodes: nano
Hambrock, J Urol 2010
What is beyond
theObjectives
horizon?
Learning
What is beyond
theObjectives
horizon?
Learning
1. Improvement of mpmp-MR directed
biopsy techniques
1. Improvement of mpmp-MR directed
biopsy techniques
2. Active Surveillance, Screening
2. Active Surveillance, Screening
3. Will mpmp-MRI replace Gleason?
3. Will mpMRI replace Gleason
Gleason?
?
4. Focal therapy
4. Focal therapy
5. Nodes: nano
nano--particles + DWI
5. Nodes:
Nodes: nanonano-particles + DWI
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Barentsz
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Biopsy with TRUS - mp-MRI fusion
Hit the most aggressive lesion
with TRUS – MR (ADCmap) fusion
Learning
FutureObjectives
Potential
MR-robot
First, diagnostic session
Case: 59 y.o., PSA 10, 3x negative TRUS sessions
T2
T2--weighted
• MR
MR--robot with MR guided remote control
DWI
DCE
TSR 2
8
Barentsz
2-4-2011
9
Barentsz
2-4-2011
What is beyond
theObjectives
horizon?
Learning
Perform biopsy
1. Improvement of mpmp-MR
MR--directed
biopsy techniques
2. Active Surveillance, Screening
Histopathology
Gleason 4+3
3. Will mpmp-MRI replace Gleason?
4. Focal therapy
5. Nodes:
Nodes: nanonano-particles + DWI
PZ PCa with focal
“hot spot” (Gl 4+3
4+3))
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Barentsz
2-4-2011
Focal therapy
Focal therapy
- Focal laser ablation
- HDR Brachytherapy / DIL IMRT
DWI with b values 0, 50, 600
ADC map showing restricted
diffusion
c. J. Feller, Palm Springs USA
Focal therapy
Focal therapy
Prostate Capsule
Target Area
Thermal Ablation
Damage Estimate
Laser Doses
Treatment #1
177s @ 8.00W
Visible Damage
10mm by 12mm
Animation – not in real-time
Treatment temperature map
Irreversible damage estimate
c. J. Feller, Palm Springs USA
T2 Pre-treatment Image
Irreversible damage estimate
Axial Images
Post-treatment MRI
Laser Fiber Trajectory
c. J. Feller, Palm Springs USA
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Barentsz
2-4-2011
Focal therapy
Marker fusion CT-MRI
Huisman Radiology 2005
- Focal laser ablation
- HDR Brachytherapy / DIL IMRT
inaccuracy < 1 mm
at periphery of prostate
f-MR-based DIL IMRT Planning
What is beyond
theObjectives
horizon?
Learning
1. Improvement of mpmp-MR
MR--directed
biopsy techniques
2. Active Surveillance, Screening
3. Will mpmp-MRI replace Gleason?
4. Focal therapy
5. Nodes: nano
nano--particles + DWI
IMRT: Partial boost to 90 Gy
van Lin IJROBP 2006
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Barentsz
2-4-2011
Pathway of spread
SVI
Detecting Nodal metastasis
in PCa
• Imaging (CT, MRI etc)
- Less invasive
- Inaccurate size
criterion
MRL detected in 41% patients
Positive nodes outside routine PLND
• Surgery (PLND)
- Invasive, costly
- Limited in coverage
Heesakkers et al Radiology 2009
Vincent van Gogh
Sorrowing old man
Dutch study: 13 centres
Fe
Fe--nanoparticles
(20 nm)
Ferumoxtran--10
Ferumoxtran
(Combidex/Sinerem))
(Combidex/Sinerem
Patient--toPatient
to-patient correlation
CT
accuracy
86%
specificity
97%
sensitivity
34%
NPV
89%
(n=375)
→
→
→
→
MRL
91%
91%
93%
93%
93%
93%
97%
97%
Probability of correct diagnosis:
diagnosis:
MRL
91%
PLND + CT 89%
Heesakkers et al Lancet Oncology 2008
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Barentsz
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Meijer, IJROPB in preparation
Post Px recurrence: MRL
Nodal Roach Formula: Low PPV
PSA ≥0.2
≥0.2 ng/ml
ng/ml 6 w. postop. + 1 higher value, or a single PSA ≥0.5 ng/ml;
ng/ml;
no bone metastases
•
•
•
72% (47/65) ≥1 ⊕ node, 6/275 nodes >1 cm
62%
62% had ≥1
≥1 ⊕ node with low PSA (<1.0
<1.0))
77% and 61% ≥1 ⊕ node in regions not in CTV for elective
pelvic irradiation by the RTOG
4. Many nodes are not in CTV
Deserno, IJROPB 2010
IMRT planning
IJROPB 2010
• Accurate mapping of
positive MRL nodes
for IMRT has the
potential:
- to reduce toxicity in
normal tissue
- allows higher doses
on the positive nodes
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Barentsz
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Case
• 60 yr;
yr; initial PSA 6; Gleason 4+3
• Dec 2005: Da Vinci Px
Px:: T3B N1 Mx R+
• Feb 2006: PSA 0.22
What treatment:
treatment: hormonal palliative
whole pelvic radiation
para--aortic nodes
para
nodes?
?
March 2005 Combidex/Sinerem MRI
Case
Case 1
• March 2005 Combidex/Sinerem MRI:
• 6 positive pelvic nodes
4D--IG
IG--IMRT:
IMRT: dose painting
→ ADT + 4D
c M Dattoli
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Barentsz
2-4-2011
But
Case
• PSA
PSA:: Nov 06:
Apr 07:
0.0006
0.003
Due to approval
problems,
development
of Combidex
is discontinued
July 07: Stop ADT
• PSA
PSA::
Aug 07:
March 08:
March 09:
March 10:
<0.01*
<0.003
<0.003
<0.01*
Combidex/Sinerem MRI November 2009
But there is hope: DWI? Ferumoxytol? P904?
DWI helps to find
bone and nodal metas
Future: ferumoxytol
ferumoxytol:: WIP
24 hrs post Combidex 24 hrs post ferumoxytol
c. S Bravo, Orlando
CTA
post ferumoxytol
post ferumoxytol + Gd
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Barentsz
2-4-2011
PSA Relapse: Imaging Protocol
• Bone:
DWI MRI of pelvis & spine
• Nodes:
Nanoparticle MRI (n.a.)
DWI MRI of pelvis & spine
• Local:
DCE
DCE-- and DWI MRI
Post-Brachy, PSA recurrence
bone + X: se 63% sp 64%
Post-Brachy, PSALearning
recurrence
(1.8)
Objectives
Post-Brachy, PSA recurrence
MRI: se 100% sp 88%
Spine and pelvis is enough
Lecouvet JCO 2007
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Barentsz
2-4-2011
Meijer, IJROPB in preparation
PSA Relapse: Imaging Protocol
• Bone:
DWI MRI of pelvis & spine
• Nodes:
Nanoparticle MRI (n.a.)
DWI MRI of pelvis & spine
• Local:
DCE- and DWI MRI
Future: MRL or 11C Choline PET/CT?
Post Px recurrence
recurrence:: MRL
Stephenson nomogram accurately predicted
⊕ MRL result →can be used to identify patients
for pelvic radiation
but
We need better imaging to decrease the CTV
Meijer, IJROPB 2010
Future: MRL or 11C Choline PET/CT?
MRL
• 151 positive nodes in 23/29 patients
mean size 4.9 mm*
11C
Choline PET/CT
• 34 positive nodes in 13/29 patients
mean size 8.4 mm*
* p<0.001 more and smaller nodes detected
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Barentsz
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Negative PET/CT:
post-RP (T3b N0 M0)
USPIO--MRI
USPIO
post Px
Choline PET/CT
DCE MRI!
PSA Relapse: Imaging Protocol
• Bone:
DWI MRI of pelvis & spine
• Nodes:
Nanoparticle MRI (n.a.)
DWI MRI of pelvis & spine
• Local:
DCE- and DWI MRI
Local post radiotherapy
recurrence: DCEDCE- MRI
T2
T2--w
DCE Ktrans
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Take home messages
• MRI is the best technique to show the
prostate and its tumor localization and
aggression
• MRI is a superior technique in showing
small nodal and bone metastates
• integration of Rth and MRI still needs a
lot of research but offers great potential
Thank you for your attention
Bomers, Debats, Fütterer,
Hambrock, Huisman,
Heijmink, Heerschap,
Hoeks, Scheenen, Yakar.
Hulsbergen, van Lin,
Hulsbergen,
van Oort, Witjes, Dattoli
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