Multi -parametric MRI in prostate cancer practice … internal structure and un -sharp margins 5...

Anwar PadhaniAnwar [email protected]@stricklandscanner.org.uk

Mount Vernon Cancer CentreMount Vernon Cancer Centre

LondonLondon

MultiMulti--parametric MRI in prostate parametric MRI in prostate

cancer practice made easycancer practice made easy

OutlineOutline

�� To briefly illustrate the expanded role of functional MRI techniTo briefly illustrate the expanded role of functional MRI techniques ques

in clinical practicein clinical practice

�� Diffusion weighted MRI (DWDiffusion weighted MRI (DW--MRI) MRI)

�� MR spectroscopic imaging (MR spectroscopic imaging (11HH--MRSI) MRSI)

�� Dynamic contrast enhanced MRI (DCEDynamic contrast enhanced MRI (DCE--MRI)MRI)

�� To demonstrate in practice how structured reporting using scorinTo demonstrate in practice how structured reporting using scoring g

schema can aid in communicating imaging findings back to schema can aid in communicating imaging findings back to

surgeons / oncologistssurgeons / oncologists

•Sciarra A, et al. Advances in magnetic resonance imaging: how they are changing the

management of prostate cancer. European Urology 2011; 59: 962-77

•Hoeks CM, et al. Prostate cancer: multiparametric MRI for detection, localization, and

staging. Radiology 2011; 261 – in press

•Padhani AR. Integrating multiparametric prostate MRI into clinical practice. Cancer Imaging

2011 - in press

IntroductionIntroduction

�� High field 3T MRI presents new exciting opportunities for promotHigh field 3T MRI presents new exciting opportunities for promoting ing

men's prostatic healthmen's prostatic health

�� Advanced MRI tools enable us to tackle new indications in the Advanced MRI tools enable us to tackle new indications in the

prostate cancer patients journeyprostate cancer patients journey

�� Raised PSA/PCa3 with negative TRUS biopsies Raised PSA/PCa3 with negative TRUS biopsies

�� Active surveillance patients Active surveillance patients –– enables appropriate patient selectionenables appropriate patient selection

�� Move into new areas of established disease Move into new areas of established disease

�� To identify poor prognosis tumours and guide focal therapies to To identify poor prognosis tumours and guide focal therapies to dominant dominant

intraprostatic lesionsintraprostatic lesions

�� Improved ability to tackle transition zone tumorsImproved ability to tackle transition zone tumors

�� Integration/ relative weighting/ communication of complex biologIntegration/ relative weighting/ communication of complex biological ical

information is a major bioinformatics challenge information is a major bioinformatics challenge

0++++++++++++0+++++++++++DCE-MRI

0+++++++++++++++++++++++DW-MRI

0++++++0+++++++++++MRSI

0++++++0000+0+MRI

biopsy

++++++++++++++++++++++++++++++++++Morphol

ogy

Contribution made by MRI techniques$

Define extent

of relapsed

disease and

complication

s (C)

Requirement

s for local

palliation (C)

Define

extent of

local

disease

and

absence

of

metastase

s (C)

Identify site

and volume

of recurrence

(C)

Detect active

disease in

absence of

significant

PSA rise (R)

Treatment

verification

(R)

Define

volume

and extent

of residual

disease (R)

Define

extent of

nodal &

distant

metastases

(C)

Requirement

s for local

palliation (C)

Confirm

confinement to

pelvis (C)

Nodal mapping

(C/R)

Define

dominant

lesion location

and size (C/R)

Detect

adverse

features (C)

Target pelvic

nodal

dissection (C)

Confirm

organ

confine

ment (C)

Docume

nt size

and

location(

C)

Depict

lesion

aggressi

veness

(C/R)

TNM

stage

(C)

Define

domina

nt

lesion

(C)

Define

lesion

aggressi

veness

(C/R)

Therapy

plannin

g (C)

Define

tumour

location and

size for

targeted

biopsy (C)

Clinical

(C) or

Research

(R)

require

ments

Disease is not

localised and

salvage is

impossible

Disease is

localised

and

salvage is

possible

Significant

rise in serum

PSA

Rare to use

imaging in

this role

(Serum PSA

surveillance)

Usually

after focal

therapies

Usually

hormonal

therapy ± RT

Usually

includes

neoadjuvant

hormonal

therapy

Organ confined

disease

No metastases

Organ

confinement

No tumour at

prostatic

apex

No

metastases

Small

volume

Low

aggressi

veness

Cancer

presenc

e

confirm

ed by

biopsy

Raised PSA

with negative

TRUS biopsy

or biopsies

Clinical

scenario

External beam

radiotherapy

to prostate ±

pelvic nodes

Ablative

therapies

(HIFU, PDT,

cryotherapy

brachytherapy)

Surgery

PalliativeLocal

salvage

PalliativeCurative intentInitial

observat

ion

(active

surveilla

nce)

→ Treatment of relapsed

disease

→

Suspect

relapse

→

Surveillance

of treated

disease

→

Monitoring

effectivene

ss of

therapy

→ Treatment of initial disease→

Stage

known

cancer

→ Suspect

cancer

Clinical

Journey

begins

here

Prostate cancer patient journey & contribution of MRI to careProstate cancer patient journey & contribution of MRI to care

Advanced MRI tools available for Advanced MRI tools available for

clinical practice clinical practice -- 20102010

Tool (abbreviation)Tool (abbreviation) Biological property depictedBiological property depicted

Diffusion MRI (DWI, Diffusion MRI (DWI,

DWDW--MRI)MRI)Extent of gland formation, cellular density, Extent of gland formation, cellular density,

necrosis and perfusionnecrosis and perfusion

Spectroscopy (MRSI)Spectroscopy (MRSI) Cell membrane turnover/energetics and Cell membrane turnover/energetics and

replacement of normal glandular tissuesreplacement of normal glandular tissues

Dynamic contrast Dynamic contrast

enhanced (DCEenhanced (DCE--MRI)MRI)Blood flow and vascular permeabilityBlood flow and vascular permeability

Prostate cancer Prostate cancer

localisation with dynamic localisation with dynamic

MRI and spectroscopy MRI and spectroscopy

Futterer, J. J. et al. Radiology 2006;

241:449-458

Peripheral zonePeripheral zone

Central GlandCentral Gland

MPKS = DCEMPKS = DCE--MRI scoreMRI score

T2W

MRSI

DCE-MRI

All

The multiparametric MRI challengeThe multiparametric MRI challenge

Pre RxPre Rx

Post antibioticsPost antibiotics

Post LHPost LH--RHaRHa

Post HIFUPost HIFU

T2WT2W b800b800 ADCADC DCEDCE--SubSub TumTum--MRSIMRSI PZPZ--MRSIMRSI Mean curveMean curve

Essential communication elementsEssential communication elements

�� Scoring systems that indicate likelihood of a Scoring systems that indicate likelihood of a

““significant cancersignificant cancer”” being presentbeing present

-- LikertLikert--like 5like 5--grade scoring systems*grade scoring systems*

» Score 1: clinically significant disease is highly unlikely to be present

» Score 2: clinically significant cancer is unlikely to be present

» Score 3: the presence of clinically significant cancer is equivocal

» Score 4: clinically significant cancer is likely to be present

» Score 5: clinically significant disease is highly likely to be present

�� Structured reporting using a graphical interfaceStructured reporting using a graphical interface

-- Matches prostate anatomyMatches prostate anatomy

*Dickinson L, et al. MRI for the detection, localisation, and characterisation of prostate cancer: recommendations from a European consensus meeting. Eur

Urol. 2011; 59:477-94

What is clinically What is clinically

significant cancer?significant cancer?

�� A tumor that poses a significant A tumor that poses a significant

risk to the health of an risk to the health of an

individual. Depends onindividual. Depends on

-- Aggressiveness of the tumorAggressiveness of the tumor

-- Life expectancy (period of risk)Life expectancy (period of risk)

�� No universally accepted No universally accepted pathologic criteriapathologic criteria

�� Definition often used* Definition often used*

-- Tumor volume > 0.5 ml and/or Tumor volume > 0.5 ml and/or

-- Gleason pattern 4 or 5 and/or Gleason pattern 4 or 5 and/or

-- ExtracapsularExtracapsular diseasedisease

* Bott SR, et al. The index lesion and focal

therapy: an analysis of the pathological

characteristics of prostate cancer. BJU Int 2010;

106: 16071611. From MFrom M KaravitakisKaravitakis et al. et al. Prostate Cancer and Prostate Cancer and

Prostatic DiseasesProstatic Diseases (2011) (2011) 14,14, 4646––5252

T2T2--weighted MRIweighted MRI

�� Excellent at depicting internal prostatic anatomyExcellent at depicting internal prostatic anatomy

�� Best for more advanced disease presentationsBest for more advanced disease presentations

�� Signal intensity of Signal intensity of tumorstumors appears to correlate with appears to correlate with

grade*grade*

�� Better at depicting dense cellular (dense) cancers Better at depicting dense cellular (dense) cancers

than sparse infiltrating disease**than sparse infiltrating disease**

* Wang L. et al. Radiology 2008; 246:168-176

** Langer DL, et al. Radiology 2008; 249:900-908

Score*Score* Peripheral zone appearancesPeripheral zone appearances illustrationsillustrations

1 1 -- clinically clinically

significant disease significant disease

is highly unlikely is highly unlikely

Normal PZ with uniform high signal intensityNormal PZ with uniform high signal intensity

2 2 –– clinically clinically


is unlikely is unlikely

Linear, wedge shaped or geographic nonLinear, wedge shaped or geographic non--focal focal

areas of low SI, usually not well demarcatedareas of low SI, usually not well demarcated

3 3 -- indeterminate indeterminate Appearances not in categories 1/2 or 4/5Appearances not in categories 1/2 or 4/5



is likely is likely

Low signal (dark grayLow signal (dark gray--black) intensity focus/mass, black) intensity focus/mass,

well defined lesion confined to prostatewell defined lesion confined to prostate



is highly likely is highly likely

Low signal intensity mass, with invasive features Low signal intensity mass, with invasive features

including including extracapularextracapular or seminal vesicle invasion, or seminal vesicle invasion,

mass effect on capsule including bulgingmass effect on capsule including bulging

* Subtract 1 if significant haemorrhage in area of abnormality* Subtract 1 if significant haemorrhage in area of abnormality

Score*Score* Transition zone appearancesTransition zone appearances illustrationsillustrations


significant disease is significant disease is

highly unlikely highly unlikely

TZ containing stromal & glandular TZ containing stromal & glandular

hyperplasia/adenoma with well defined margins. No hyperplasia/adenoma with well defined margins. No

low SI nodules or lenticular lesionslow SI nodules or lenticular lesions



unlikely unlikely

Round shaped low SI lesions with a smooth margins. Round shaped low SI lesions with a smooth margins.

Lenticular shaped, band like low SI in midline or around Lenticular shaped, band like low SI in midline or around

central adenomacentral adenoma

3 3 -- indeterminate indeterminate Appearances not in categories 1/2 or 4/5Appearances not in categories 1/2 or 4/5



likely likely

Lenticular shaped anterior low SI lesion without Lenticular shaped anterior low SI lesion without

capsule invasion.capsule invasion.

““charcoalcharcoal”” sign: homogeneous low SI lesion with loss sign: homogeneous low SI lesion with loss

of internal structure and unof internal structure and un--sharp marginssharp margins



highly likely highly likely

Lenticular or round mass with bulge / irregularity / Lenticular or round mass with bulge / irregularity /

retraction of the anterior prostate capsule.retraction of the anterior prostate capsule.

Irregular, infiltrating mass destroying TZ architecture, Irregular, infiltrating mass destroying TZ architecture,

invading adjacent PZ/SV/bladderinvading adjacent PZ/SV/bladder

* Subtract 1 if significant haemorrhage in area of abnormality* Subtract 1 if significant haemorrhage in area of abnormality

Limitations of T2Limitations of T2--weighted MRIweighted MRI

�� Tumour volume is underestimated and locations are not well Tumour volume is underestimated and locations are not well

depicteddepicted

–– Not all tumours are visibleNot all tumours are visible

–– Transition zone tumours not well seen (30% of cancers)Transition zone tumours not well seen (30% of cancers)

–– False positivesFalse positives: scars, BPH, prostatitis, hemorrhage & treatment : scars, BPH, prostatitis, hemorrhage & treatment

effectseffects

�� Restricted ability to distinguish localized (T2) from early T3 Restricted ability to distinguish localized (T2) from early T3

(advanced) disease(advanced) disease

→→ great staging variability (37great staging variability (37--96%)96%)

�� Important biologically characteristics are not well depictedImportant biologically characteristics are not well depicted

–– Tumour volume, location, histological grade, vascularisation, hyTumour volume, location, histological grade, vascularisation, hypoxia, poxia,

proliferation rate, proliferation rate, perineuralperineural invasion invasion

T2W b1000

ADC

T2W b1000

ADC

Park BK et al. Investigative Radiology

2007; 24:842-847

Qualitative assessmentQualitative assessment ––

hyperintensity in high bhyperintensity in high b--value imagesvalue images

Quantitative assessmentQuantitative assessment –– ADC valueADC value

DWDW--MRI pathological correlationsMRI pathological correlations

3T images

ADCs for tumors with different D’Amico clinical risk scores in the whole prostate

Turkbey B et al. Radiology 2011;258:488-495

©2011 by Radiological Society of North America

ADCs for tumors with different Gleason scores in the whole prostate

Distinguishing tumour from T2Distinguishing tumour from T2--shine throughshine through(look for hyperintensity on (look for hyperintensity on veryvery high bhigh b--value images)value images)

b0b0 b750tb750t

b900tb900t b1100tb1100t b1400tb1400t

ADC 0ADC 0--750t750t

For some moderate grade tumours it is necessary to have very higFor some moderate grade tumours it is necessary to have very high bh b--valuesvalues

Where is the tumour?Where is the tumour?

Scoring system for DWScoring system for DW--MRI (PZ)MRI (PZ)

TZ criteria to be decidedTZ criteria to be decided

ClassClass DescriptionDescription b1000b1000 ADCADC



is highly unlikely is highly unlikely

No reduction in ADC compared to normal

glandular tissue / no increase in signal on

high b-value images (≥b1000)



is unlikely is unlikely

Diffuse, hyperintensity on ≥b1000 image with

low ADC; No focal features - linear, triangular

or geographical features allowed

3 3 -- indeterminate indeterminate Diffuse unilateral hyperintensity on

≥b1000 image with diffuse low ADC (no

focal features)



is likely is likely

Focal area(s) of reduced ADC but

isointense SI on high b-value images

(≥b1000)



is highly likely is highly likely

Focal area/mass of hyperintensity on the

high b-value images (≥b1000) with

reduced ADC

CaCaCaCa

CaCa

CaCa

CaCa

CaCa

PINPIN

PINPIN

PINPIN

PINPIN

ROC curves show Az values for DCE-MRI (MPKS)

and MRS for localization of prostate tumors with

volumes of >0.5 cm3

Futterer JJ, et al. Radiology 2006;241:449-458

washout

kep – rate constant

Ktrans – transfer constant

ve – leakage space

Bloch BN, et al.Bloch BN, et al.

Radiology. 2007; Radiology. 2007;

245(1):176245(1):176--85.85.

N = 32

Validating DCEValidating DCE--MRI for prostate cancer MRI for prostate cancer

localisation and staginglocalisation and staging

Scoring scheme for DCEScoring scheme for DCE--MRI curvesMRI curves

Symmetry and focalness are assess on the basis of corresponding normal tissue (PZ/TZ)Subtract 1 from TZ lesions – because normal BPH is hypervascular

Curve score

Symmetry &

focalnessscore

Total score

1 -

Definite benign (1)

2

Asymmetry or focal

(+1)

3

2

Asymmetry & focal (+2)

4

3

Asymmetry or focal

(+1)

4

3

Asymmetry & focal (+2)

Definite malignant (5)

Rising PSA Rising PSA ––negative biopsy x 2negative biopsy x 2

�� 56 56 yoyo raised serum PSA level raised serum PSA level and 2 negative TRUSand 2 negative TRUS�� 1/12 ICU following TRUS1/12 ICU following TRUS

�� 8 mm nodule in the left PZ with 8 mm nodule in the left PZ with washwash--out curve out curve

�� Low ADC values within the Low ADC values within the nodule. The lesion is not seen nodule. The lesion is not seen on the b900 image because of on the b900 image because of persistent high signal intensity persistent high signal intensity of the peripheral zone. of the peripheral zone.

�� ADC map does not depict all ADC map does not depict all intraprostatic lesions intraprostatic lesions –– misses misses the small, Gleason 6 tumour focithe small, Gleason 6 tumour foci

June

08

4/54/5

4/5

2/5

5/55/5

Threshold metabolite approach Threshold metabolite approach vsvs classifier systems classifier systems

Jung, J. A. et al. Jung, J. A. et al.

Radiology 2004; Radiology 2004;

233:701233:701--708708

Futterer, J. J. et al.

Investigative Radiology

2007;42: 116–122

1 – Def Ben 2 - PB 3 - intermediate 4 - PM 5 – DM – Def Malig

Overlap of Overlap of choline:citratecholine:citrate ratios ratios

between malignant and between malignant and

benign/normal tissuesbenign/normal tissues

IMAPS data IMAPS data –– ask ask ArendArend HershapHershap

Courtesy of Courtesy of ArendArend HerrshapHerrshap -- NimegenNimegen

Integration, reporting and Integration, reporting and

communicationcommunication�� Structured reporting method via graphical interface to match Structured reporting method via graphical interface to match

prostate anatomyprostate anatomy

�� AnteriorAnterior--posterior border 1.7cm from the rectal wall (average length posterior border 1.7cm from the rectal wall (average length

of core biopsy needle)of core biopsy needle)

�� Use sUse scoring system that indicates the likelihood of a coring system that indicates the likelihood of a

““significant cancersignificant cancer”” being presentbeing present

�� Assign scores per prostate/ sector/ lesion (max 5 lesions)Assign scores per prostate/ sector/ lesion (max 5 lesions)

�� Dominant cancer focus makes up to 90% of the cancer volume and Dominant cancer focus makes up to 90% of the cancer volume and

80% of small foci have tumour volumes < 0.5 ml80% of small foci have tumour volumes < 0.5 ml

�� Give a putative TNM stageGive a putative TNM stage

�� Take account of patient history and symptoms, serum PSA, Take account of patient history and symptoms, serum PSA,

DRE findings, concomitant medications (particularly antiDRE findings, concomitant medications (particularly anti--

androgens) and time since TRUS biopsyandrogens) and time since TRUS biopsy

Active surveillanceActive surveillance –– baseline (Dec 2008)baseline (Dec 2008)

PSA 5.3ng/ml; TRUS PSA 5.3ng/ml; TRUS -- small foci of Gleason 3+3 plus prostatitis in PZ; TRUS missed asmall foci of Gleason 3+3 plus prostatitis in PZ; TRUS missed anterior gland tumor (ADC 835 nterior gland tumor (ADC 835 µµmm22/s)/s)

TRUS biopsy only = Gleason 3+3 on left side with prostatitisTRUS biopsy only = Gleason 3+3 on left side with prostatitis

PZ: T2W =3/5; DWI =2/5

DCE = 3/5; MRSI =1/5

Ant TZT2W =2/5; DWI =4/5

DCE =5/5; MRSI =1/5

Active surveillance Active surveillance –– post antibiotics (Dec 2009)post antibiotics (Dec 2009)

PSA 5.8ng/ml; enlarging anterior gland tumor (ADC 835PSA 5.8ng/ml; enlarging anterior gland tumor (ADC 835→ 583 583 µµmm22/s) with decreased flow in PZ /s) with decreased flow in PZ

PZ: T2W =3/5; DWI =2/5

DCE = 2/5; MRSI =1/5


DCE =5/5; MRSI =1/5

PostPost--androgens, preandrogens, pre--HIFU (Oct 2010)HIFU (Oct 2010)

Smaller anterior gland tumor (ADC 1355 Smaller anterior gland tumor (ADC 1355 µµmm22/s) with decreased flow & marked metabolic atrophy/s) with decreased flow & marked metabolic atrophy

PZ: T2W =3/5; DWI =2/5

DCE = 1/5; MRSI =ND


DCE =4/5; MRSI =ND

ChallangesChallanges

�� Ability to display, coAbility to display, co--register, segment, fuse, and register, segment, fuse, and

analyse every tool in an integrated single workspace analyse every tool in an integrated single workspace

would be ideal would be ideal

�� Methods for dealing with missing functional datasets Methods for dealing with missing functional datasets

(not obtained, corruption, artefacts) are needed(not obtained, corruption, artefacts) are needed

�� Relative weighting of individual tests requires further Relative weighting of individual tests requires further

researchresearch

�� LocalizationLocalization: : DWDW--MRI MRI >> T2W T2W = = DCEDCE--MRI MRI >> MRSI ???MRSI ???

�� Aggressiveness:Aggressiveness: DWDW--MRI MRI == MRSI MRSI >> T2W T2W >> DCEDCE--MRI ???MRI ???

Multi -parametric MRI in prostate cancer practice … internal structure and un -sharp margins 5...

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Transcript of Multi -parametric MRI in prostate cancer practice … internal structure and un -sharp margins 5...