J.J. O. Barentsz O. BarentszHoofd-wetenschap Radiologie RUNMCHoofd-wetenschap Radiologie RUNMC

Innovatieve imaging biedt grote kansen voor betere diagnostiek- entherapeutische produkten,

j.barentsz@rad.umcn.nl

Missie

• Patiënt helpen door wetenschappelijk onderzoek: verbetering radiologische diagnostiek

• Bench-to-clinic-to-population: translationeel onderzoek

• Betere diagnose → effectievere therapie

Focus

• Richting: - Ontwikkelingen vanuit de kliniek- Inzichten vanuit fundamenteel onderzoek

• Niches opzoeken• Mogelijkheden om ons heen benutten

Focus: kanker (RUCO)• Prostaat: 1/6 mannen • Borst kanker: 1/8 vrouwen

• Dikke darm kanker

• Hoofd-hals tumoren

Learning ObjectivesMulti-modality MRI

1. High resolution 1. High resolution T2-wT2-w.: .: anatomyanatomy

2. 2. DDiffusioniffusion WWeightedeighted IImaging: maging: functionfunction

3. 3. HHydrogenydrogen MR-SMR-Spectroscopy: pectroscopy: functionfunction

4.4. DDynamic ynamic CContrast ontrast EEnhanced:nhanced: functionfunction

Learning ObjectivesMulti-modality MRI: anatomy

1 mm1 mm

• Brownian movement of water• DWI: cell density, extracellular space, tortuosity,

integrity of cellular membranes & extent of glandular tissues

Tightly packed cellular tissue Organised glandular tissueWell organised tissue

Multi-modality MRI: DWI

DWI:DWI: PCa restricted H PCa restricted H22O movementO movement

Multi-modality MRI: function

MRS:MRS: PCa PCa Choline/Citrate ratio Choline/Citrate ratio ↑↑

Multi-modality MRI: function

Multi-modality MRI: vascularity

DCE MRI: DCE MRI: PCaPCa increased vascular permeabilityincreased vascular permeability

Clinical questions in PCa

1. Determine aggression

2. Improve detection & localization

3. Improve local staging

4. Detect small nodal metastases

5. Detect recurrences / follow up

Clinical questions in PCa

1. Determine aggression

2. Improve detection & localization

3. Improve local staging

4. Detect small nodal metastases

5. Detect recurrences / follow up

What is the association betweeen What is the association betweeen dogsdogs and and prostate cancersprostate cancers??

Dogs and Prostate

BenignBenign

Gleason 3

Dogs and Prostate

c. T. Hambrock

Intermediate aggressiveIntermediate aggressive

Gleason 4c. T. Hambrock

Dogs and Prostate

c. T. Hambrock Gleason 5

Dogs and ProstateHighly aggressiveHighly aggressive

At random TRUS prostate At random TRUS prostate biopsiesbiopsies

→ → 64%64% accuracy to accuracy to predict predict truetrue GS GS

Narain et al. Prostate 2001; Antumes et al. Arch Path Lab Med 2008

Gleason Score Gleason Score (GS) generally used (GS) generally used predictorpredictor of of aggressivityaggressivity

HOWEVERHOWEVER

Clinical problem

Therefore using TRUS biopsy GS can result in inappropriate therapy

Pearson Pearson CorrelationCorrelation

r = r = 0.73 0.73

p <p < 0.01 0.01

DWI: Non-invasive aggression determination

Hambrock Radiology accepted p.r.

DWI: ADC-value versus Gleason score

Clinical questions in PCa

1. Determine aggression

2. Improve detection & localization

3. Improve local staging

4. Detect small nodal metastases

5. Detect recurrences / follow up

Introduction localization aggression local nodes recurrence/FU

70 yr: 5x neg. biopsies (30 cores) PSA 33 ng/ml

Case

Next step ?

Localization: saturation biospy?

Introduction Local Nodes Fusion

70 yr: 6x neg. biopsies (54 cores) PSA 33 ng/ml

Case

Next step ?

Saturation biopsy Saturation biopsy (24 cores)(24 cores)

Case

MR Guided biopsy

Manual Manual biopsy gunbiopsy gun and and confirmationconfirmation scan of scan of correct correct needle positionneedle position

3T MR-biopsy

Highly aggressive cancer Highly aggressive cancer (4+4)(4+4)

3T MR-biopsy

MRGB vs multi-session TRUS

3T MR guided biopsy

Multi-modality MR imaging

- guiding biopsy with - guiding biopsy with MRI-TRUS fusionMRI-TRUS fusion Accurate Tissue Accurate Tissue Sampling Sampling byby

with TRUS – MR (ADCmap) fusion

Hit the most aggressive lesion

Learning Objectives

MR-robotMR-robot with guided with guided remote remote control?control?

MR-guided biopsy

MIRIAM Project

Improved Localization → Focal therapy

1. IMRT dominant prostatic lesion

2. HD-Brachy

3. Cryotherapy

4. Thermo ablation

5. High Frequency US ablation

IMRT : high dosis to DIL

van Lin IJROBP 2006IMRT: Partial boost to 90 Gy

Clinical questions in PCa

1. Determine aggression

2. Improve detection & localization

3. Improve local staging

4. Detect small nodal metastases

5. Detect recurrences / follow up

3T ERC-MRI: 2 mm close to NVB

TT

Clinical questions in PCa

1. Determine aggression

2. Improve detection & localization

3. Improve local staging

4. Detect small nodal metastases

5. Detect recurrences / follow up

Detecting nodal metastasis:some challenges

• Imaging (CT, MRI , PET)- Less invasive- Inaccurate size criterion- Size limitation

• Surgery (PLND)- Invasive, costly- Limited in coverage

Vincent van GoghSorrowing old man

NanoparticleContrast

(Combidex / Sinerem)

MR Lymphography

MRL

Nodal involvement

USPIOUSPIO

prepre-USPIO-USPIO

nn

mm

ppost-USPIOost-USPIO

Patient-to-patient correlationPatient-to-patient correlation (n=375) (n=375) MDMDCTCT MRL MRL accuracy accuracy 86% 86% → → 9191%% specificity specificity 97%97% → → 9393%% sensitivity sensitivity 34% 34% → → 93%93%NPVNPV 89% 89% → → 9797%%

Probability of Probability of correct diagnosiscorrect diagnosis: : MRL MRL 91%91% Surgery + CT Surgery + CT 89%89%

Dutch study: 13 centres

Heesakkers, Lancet Oncology 2008

IMRT planning

• Accurate mapping of positive MRL nodes for IMRT has the potential:

- to reduce toxicity in normal tissue

- allows higher doses on the positive nodes

Case • 60 yr; initial PSA60 yr; initial PSA 6 6; Gleason ; Gleason 4+34+3

• Dec 2005: Da Vinci Px: Dec 2005: Da Vinci Px: T3B N1 Mx R+ T3B N1 Mx R+ • Feb 2006: PSA Feb 2006: PSA 0.220.22

Do weneed to treat Do weneed to treat both areasboth areas??

• March 2005March 2005 Combidex/Sinerem MRI: Combidex/Sinerem MRI:

Case

Case • 60 yr; initial PSA60 yr; initial PSA 6 6; Gleason ; Gleason 4+54+5

• Dec 2005: Da Vinci Px: Dec 2005: Da Vinci Px: T3BN1Mx T3BN1Mx • Feb 2006: PSA Feb 2006: PSA 0.220.22

• March 2005March 2005 Combidex/Sinerem MRI: Combidex/Sinerem MRI: → → ADT + ADT + 4D-IG-IMRT4D-IG-IMRT

Case 1

Case • PSAPSA: : Nov 06:Nov 06: 0.00060.0006

Apr 07:Apr 07: 0.0030.003 July 07: Stop ADTJuly 07: Stop ADT

• PSAPSA:: Aug 07:Aug 07: <0.01*<0.01*March 08:March 08: <0.003<0.003March 09:March 09: <0.003<0.003March 09:March 09: <0.01*<0.01*

Combidex/Sinerem MRI November 2009

Case

March 2006 November 2009

Case 1

Clinical questions in PCa

1. Improve detection & localization

2. Determine aggression

3. Improve local staging

4. Detect small nodal metastases

5. Detect recurrences / follow up

• Plain film and CT show Plain film and CT show bone bone destruction destruction

Bone involvement

• Scintgraphy shows increased Scintgraphy shows increased bone bone metabolism metabolism

MRI showsMRI shows bone marrowbone marrow itselfitself

bone scan: se 46% sp 32% bs+X: se 63% sp 64%

MRI: se 100% sp 88%

Bone scan, PET/CT, or MRI?

Lecouvet JCO 2007Lecouvet JCO 2007

T1-w. MRIT1-w. MRI DWI-MR DWI-MR

Computers:Computers:Visualize MR imagesVisualize MR imagesPharmacokinetic analysisPharmacokinetic analysisMRS analysisMRS analysisStructured reportingStructured reportingCADCAD

5454

CADx – Computer aided diagnosis

Samenwerking (met Industrie)

• MR-geleide MR-geleide RobotRobot (U-Twente) (U-Twente)

• Minimaal invasieveMinimaal invasieve behandelingen behandelingen

• ContrastContrast middelen middelen (Magnamedics) (Magnamedics)

• CComputer omputer AAssisted ssisted DDiagnosis (Meavis)iagnosis (Meavis)

Innovaties van Beeldvorming

• Maakt Maakt PCa screeningPCa screening mogelijk: mogelijk:- MRI als- MRI als PSA PSA ↑↑

• Spoort Spoort meest agressieve PCameest agressieve PCa op op → → optimale behandeling optimale behandeling

• Toont Toont exact exact dede uitbreiding uitbreiding buiten buiten prostaat aan prostaat aan → optimale behandeling → optimale behandeling

Confectiewerk: “behandeling op maat!”

Implementatie van Zorgverbetering

• UUniversitair niversitair PProstaatkanker rostaatkanker SSneldiagnostiek en neldiagnostiek en BBehandeladvies ehandeladvies CCentrum entrum

Topdiagnose en advies < 1 week

Vragen?Wetenschap blijft Teamwork:Wetenschap blijft Teamwork:Debats, Fütterer, Hambrock, Heerschap, Debats, Fütterer, Hambrock, Heerschap, Heijmink, Hoeks, Huisman, Litjes, Heijmink, Hoeks, Huisman, Litjes, Scheenen, Vos, Yakar, Scheenen, Vos, Yakar,

Witjes, van Oort, van Lin, HulsbergenWitjes, van Oort, van Lin, Hulsbergen

UT, RUNMC, XiVent MedicalDemcom, Siemens

Magnamedics