Advances in MR Advances in MR Imaging of PROSTATE Imaging of PROSTATE

CANCERCANCER

Demetri Papadatos, MD, FRCPCDemetri Papadatos, MD, FRCPC

Abdominal Imaging RadiologistAbdominal Imaging RadiologistDirector, Abdominal Imaging FellowshipDirector, Abdominal Imaging Fellowship

Director, Percutaneous Radiofrequency AblationDirector, Percutaneous Radiofrequency AblationThe Ottawa HospitalThe Ottawa Hospital

PROSTATE CANCERPROSTATE CANCER

Most common malignancy of men in USMost common malignancy of men in USafter skin cancerafter skin cancer

At autopsy, prostate cancer is found in At autopsy, prostate cancer is found in 30% of men at age 50 30% of men at age 50 almost 90% at age 90almost 90% at age 90

About one in six men will be diagnosed with About one in six men will be diagnosed with prostate cancer during lifetimeprostate cancer during lifetime However, only 1 / 34 will die of the diseaseHowever, only 1 / 34 will die of the disease

PROSTATE CANCERPROSTATE CANCER

Many cancers are indolent, Many cancers are indolent,

show no signs of clinical show no signs of clinical growthgrowth

Despite the long latent period, Despite the long latent period,

second commonest cause of cancer second commonest cause of cancer death in American men over age 55death in American men over age 55

ETIOLOGY - RISK FACTORSETIOLOGY - RISK FACTORS

All men are at a risk of developing prostate cancer.All men are at a risk of developing prostate cancer.

AgeAge : Greatest risk factor : Greatest risk factor risk increasing significantly after 50 yrsrisk increasing significantly after 50 yrs

Family historyFamily history: Men with affected father or brother at increased : Men with affected father or brother at increased riskrisk

ACA Recommendation to start screening 10 yrs ACA Recommendation to start screening 10 yrs earlierearlier

compare to general populationcompare to general population

Genetic FactorsGenetic Factors – abnormal genes in 10 % – abnormal genes in 10 % but genetic testing is not available yetbut genetic testing is not available yet

Race:Race: more frequent and aggressive in African American men more frequent and aggressive in African American men

Environmental and dietary factorsEnvironmental and dietary factors

HISTOPATHOLOGICAL TYPESHISTOPATHOLOGICAL TYPES

More than 95% of prostatic malignancies More than 95% of prostatic malignancies are are adenocarcinomas adenocarcinomas

Rarely, a squamous or transitional cell Rarely, a squamous or transitional cell neoplasm neoplasm

Very rarely sarcomaVery rarely sarcoma

SCREENINGSCREENING

Routine Screening is offeredRoutine Screening is offered Men > 50 yrsMen > 50 yrs With a life expectancy of at least 10 yrsWith a life expectancy of at least 10 yrs

Screening consists of :Screening consists of : Digital rectal examination Digital rectal examination Serum PSA levelsSerum PSA levels

PSA (Prostatic Specific Antigen)PSA (Prostatic Specific Antigen)

Secreted into blood stream by the prostate Secreted into blood stream by the prostate glandgland

It’s routine use for screening has lead an It’s routine use for screening has lead an exponential rise in prostate cancers, which exponential rise in prostate cancers, which are being detected much earlierare being detected much earlier

Elevated PSA = non specificElevated PSA = non specific

Also seen in benign prostatic hypertrophy Also seen in benign prostatic hypertrophy (BPH)(BPH)

and prostatitis (benign conditions)and prostatitis (benign conditions)

If PSA elevatedIf PSA elevated

Repeat PSA level a few weeks later Repeat PSA level a few weeks later when probable occult prostatitis has resolvedwhen probable occult prostatitis has resolved

Calculate PSA Density (PSA/gland volume) Calculate PSA Density (PSA/gland volume) increases PSA specificityincreases PSA specificitytransrectal ultrasound (TRUS) = gland transrectal ultrasound (TRUS) = gland

volumevolume+ ? Nodules+ ? Nodules

Free PSAFree PSA increases PSA specificityincreases PSA specificity

Low in CALow in CA Elevated in benign prostatic hypertrophy (BPH)Elevated in benign prostatic hypertrophy (BPH) If < 25 % of PSA is free – worrisome for cancerIf < 25 % of PSA is free – worrisome for cancer

DIAGNOSISDIAGNOSIS

Diagnosis of prostate carcinoma is usually made Diagnosis of prostate carcinoma is usually made by TRUS-guided core biopsy.by TRUS-guided core biopsy.

However, can have +ve/rising PSA but –ve biopsiesHowever, can have +ve/rising PSA but –ve biopsies

DilemmaDilemma

Do these patients have prostate cancer ???Do these patients have prostate cancer ???

If so, why are the biopsies negative ???If so, why are the biopsies negative ???

Transrectal Ultrasound (TRUS)Transrectal Ultrasound (TRUS)and Biopsy (Bx)and Biopsy (Bx)

TRUS can assess gland volume (PSAD) TRUS can assess gland volume (PSAD) and detect nodulesand detect nodules

However, nodules may or may not represent cancerHowever, nodules may or may not represent cancer

Therefore, perform multiple biopsies in attempt to Therefore, perform multiple biopsies in attempt to find the suspected cancerfind the suspected cancer

TRUS is used to guide needle placement for TRUS is used to guide needle placement for biopsiesbiopsies

TRUS BxTRUS Bx

Systematic approach needed during biopsy session Systematic approach needed during biopsy session in order to maximize the yieldin order to maximize the yield

Number and location of biopsies variesNumber and location of biopsies varies

Trend is to increase the number of biopsies obtained Trend is to increase the number of biopsies obtained

Some cancers are located in nodules seen on TRUSSome cancers are located in nodules seen on TRUS

However, more aggressive cancer may be located However, more aggressive cancer may be located elsewhere and not visible on TRUSelsewhere and not visible on TRUS

Malignant prostatic nodules tend to look hypoechoic (dark)Malignant prostatic nodules tend to look hypoechoic (dark)and demostrate increased vascularityand demostrate increased vascularity

EXTENDED BIOPSY PROTOCOLSEXTENDED BIOPSY PROTOCOLS

Traditionally, a six biopsy protocol was used Traditionally, a six biopsy protocol was used

Insufficient, tumours being missed and undergraded Insufficient, tumours being missed and undergraded

In particular, midline and apicolateral PZ tumours were In particular, midline and apicolateral PZ tumours were missed missed

8 -10 biopsies improve diagnostic yield by 20–30% over 8 -10 biopsies improve diagnostic yield by 20–30% over traditional number of biopsiestraditional number of biopsies

Some centers recommend 24 biopsies (12 per side)Some centers recommend 24 biopsies (12 per side)to get +ve diagnosisto get +ve diagnosisto accurately grade the tumorto accurately grade the tumor

PATHOLOGYPATHOLOGYGleason GRADEGleason GRADE and and Gleason ScoreGleason Score

Gleason Grade Gleason Grade 1=Low …….. 1=Low …….. 5=High5=High

GLEASON SCOREGLEASON SCORE

A grade is assigned to the 2 largest foci of cancerA grade is assigned to the 2 largest foci of cancer

These 2 grades are added together to yield the These 2 grades are added together to yield the Gleason scoreGleason score (eg. Grade 3 + Grade 4 = Score of (eg. Grade 3 + Grade 4 = Score of 7) 7)

Gleason Score varies between 2 and 10Gleason Score varies between 2 and 10

The higher the Gleason score – more aggressive The higher the Gleason score – more aggressive tumortumor

NB: Score of 7 (3+4 vs 4+3)NB: Score of 7 (3+4 vs 4+3)

GLEASON SCOREGLEASON SCORE

2-6 = Low Risk

7 = Intermediate risk

8-10 = High risk

My prostate biopsy was positive, My prostate biopsy was positive, now what ?now what ?

Surgery only proven curative treatmentSurgery only proven curative treatment Only tumor confined to prostate is curableOnly tumor confined to prostate is curable Surgery = HIGH morbidity/complications Surgery = HIGH morbidity/complications

urinary incontinence + sexual impotenceurinary incontinence + sexual impotence Need reliable staging tool to predict who will Need reliable staging tool to predict who will

benefit from surgerybenefit from surgery Before the advent of accurate staging with Before the advent of accurate staging with

imaging, nomograms were developedimaging, nomograms were developed

CLINICAL NOMOGRAMSCLINICAL NOMOGRAMS Originally designed to help Originally designed to help predict predict the STAGEthe STAGE (as determined after surgery) and best course of (as determined after surgery) and best course of

treatment. treatment.

"Partin tables" "Partin tables" originally developed by 2 urologists originally developed by 2 urologists

(Alan W. Partin and Patrick C. Walsh)(Alan W. Partin and Patrick C. Walsh) based on accumulated data from hundreds of patients based on accumulated data from hundreds of patients

treated for prostate cancertreated for prostate cancer

Most recent version of the Most recent version of the Partin TablesPartin Tables, released in 2001, released in 2001 based on data from 5000 patients based on data from 5000 patients underwent radical prostatectomy at Johns Hopkins underwent radical prostatectomy at Johns Hopkins

Can be used to determine pre test probabability of Can be used to determine pre test probabability of unresectable disease and decide if surgery is worth the unresectable disease and decide if surgery is worth the potential complicationspotential complications

ROLE OF MRIROLE OF MRI

MR can detect cancer but is not MR can detect cancer but is not recommended as an initial screening tool recommended as an initial screening tool (PSA, DRE, TRUS Bx)(PSA, DRE, TRUS Bx)

However However ? +ve PSA but –ve biopsy ? +ve PSA but –ve biopsy

Does this patient have cancer ???Does this patient have cancer ??? MR helps target repeat biopsy to suspicious areasMR helps target repeat biopsy to suspicious areas

Local Staging (to determine best treatment)Local Staging (to determine best treatment)

WHO NEEDS MRI STAGINGWHO NEEDS MRI STAGING

Most patients with prostate CA have indolent Most patients with prostate CA have indolent cancercancer

Will unlikely need any form of treatment Will unlikely need any form of treatment

during their lives as cancer will never during their lives as cancer will never

manifest clinicallymanifest clinically

High (+/- intermediate) risk groupsHigh (+/- intermediate) risk groups

( ie significant chance of tumor progression)( ie significant chance of tumor progression)

WHO NEEDS MRI STAGINGWHO NEEDS MRI STAGING

Staging MR would be cost effective if Staging MR would be cost effective if performed performed

ONLY in the subgroup of patients withONLY in the subgroup of patients with

Palpable tumorPalpable tumor PSA > 10PSA > 10 At least 50 % positive cores for At least 50 % positive cores for

malignancy malignancy High Gleason grade and score High Gleason grade and score

IMAGING THE PROSTATE GLANDIMAGING THE PROSTATE GLAND Currently imaging at 1.5 Tesla scanner is Currently imaging at 1.5 Tesla scanner is

recommendedrecommended

Endorectal /Surface Coil MRI combination is best Endorectal /Surface Coil MRI combination is best for anatomic detailfor anatomic detail High SNR High SNR High spatial resolution of 0.5 mmHigh spatial resolution of 0.5 mm

5 MR techniques will be discussed today5 MR techniques will be discussed today

T2 Weighted ImagingT2 Weighted Imaging Dynamic contrast enhanced MRI (DCE-MRI)Dynamic contrast enhanced MRI (DCE-MRI) MR Spectroscopic Imaging (MRSI)MR Spectroscopic Imaging (MRSI) Diffusion weighted Imaging (DWI)Diffusion weighted Imaging (DWI) Lymphotropic Nanoparticle-enhanced MRI (Ferumoxtran-Lymphotropic Nanoparticle-enhanced MRI (Ferumoxtran-

10)10)

NORMAL ANATOMYNORMAL ANATOMY

ANATOMY OF THE GLANDANATOMY OF THE GLAND

Glandular (acinar) and nonglandular elements Glandular (acinar) and nonglandular elements

I - I - Glandular prostateGlandular prostate 1- Outer components1- Outer components

Central zone (CZ)Central zone (CZ)Peripheral zones (PZ)Peripheral zones (PZ)

2- Inner components 2- Inner components Periuretheral glandsPeriuretheral glandsTransitinal zone (TZ) (BPH)Transitinal zone (TZ) (BPH)

II - II - Nonglandular portionsNonglandular portions Prostatic urethra Prostatic urethra Anterior fibromuscular band Anterior fibromuscular band

ABNORMAL GLANDABNORMAL GLAND

DISTRIBUTION OF PROSTATE DISTRIBUTION OF PROSTATE CANCER CANCER

Tumor location:Tumor location: 70 % in Peripheral Zone, PZ 70 % in Peripheral Zone, PZ 20 % in Transition Zone, TZ 20 % in Transition Zone, TZ 10 % in Central Zone, CZ10 % in Central Zone, CZ Central gland most difficult to localize Central gland most difficult to localize

cancercancer

because of overlapping signal intensitybecause of overlapping signal intensity

with normal gland / hypertrophy with normal gland / hypertrophy

LOCAL STAGING - IMPORTANCELOCAL STAGING - IMPORTANCE

Accurate tumor staging is essential to determine Accurate tumor staging is essential to determine appropriate treatment (ie is curative surgery an appropriate treatment (ie is curative surgery an option ?)option ?)

Extracapsular Extension (ECE)Extracapsular Extension (ECE)Seminal Vesicle Invasion (SVI)Seminal Vesicle Invasion (SVI)Bladder/Rectal InvasionBladder/Rectal InvasionLymph Node MetastasesLymph Node Metastases

Only carcinomas confined within the prostate gland, Only carcinomas confined within the prostate gland, are potentially curable by radical prostatectomyare potentially curable by radical prostatectomy

Staging usually classified using TNM classificationStaging usually classified using TNM classification

TNM CLASSIFICATIONTNM CLASSIFICATIONPrimary tumor (T)Primary tumor (T)TX:TX: Primary tumor cannot be assessed Primary tumor cannot be assessedT0:T0: No evidence of primary tumor No evidence of primary tumor

T1: Clinically inapparent tumor not palpable nor visible by imagingT1: Clinically inapparent tumor not palpable nor visible by imagingT1a: Tumor incidental histologic finding in <5% of tissue resectedT1a: Tumor incidental histologic finding in <5% of tissue resectedT1b: Tumor incidental histologic finding in >5% of tissue resectedT1b: Tumor incidental histologic finding in >5% of tissue resectedT1c: Tumor identified by needle biopsy (eg, because of elevated PSA)T1c: Tumor identified by needle biopsy (eg, because of elevated PSA)

T2: Tumor confined within prostateT2: Tumor confined within prostateT2a: Tumor involves < 50% of 1 lobeT2a: Tumor involves < 50% of 1 lobeT2b: Tumor involves > 50% of 1 lobeT2b: Tumor involves > 50% of 1 lobeT2c: Tumor involves both lobesT2c: Tumor involves both lobes

T3: Tumor extends through the prostate capsuleT3: Tumor extends through the prostate capsuleT3a: Extracapsular extension (unilateral or bilateral) T3a: Extracapsular extension (unilateral or bilateral) ECEECET3b: Tumor invades seminal vesicle(s) T3b: Tumor invades seminal vesicle(s) SVISVI

T4: Tumor is fixed or invades adjacent structures other than seminal T4: Tumor is fixed or invades adjacent structures other than seminal vesiclesvesicles: : bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wallbladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall

TNM CLASSIFICATIONTNM CLASSIFICATIONRegional lymph nodes (N)Regional lymph nodes (N)

Regional lymph nodesRegional lymph nodes are the nodes of the are the nodes of the true pelvistrue pelvis Distant lymph nodesDistant lymph nodes are outside the true pelvis are outside the true pelvis

NX: Regional lymph nodes were not assessedNX: Regional lymph nodes were not assessed N0: No regional lymph node metastasisN0: No regional lymph node metastasis N1: Single regional lymph node (inside the pelvis) < 2 cm N1: Single regional lymph node (inside the pelvis) < 2 cm N2: One or more regional lymph nodes, largest > 2 cm but < 5 cmN2: One or more regional lymph nodes, largest > 2 cm but < 5 cm N3: One or more regional lymph nodes, largest > 5 cmN3: One or more regional lymph nodes, largest > 5 cm

Distant metastasis (M)Distant metastasis (M)

MX: Distant metastasis cannot be assessed (not evaluated by any MX: Distant metastasis cannot be assessed (not evaluated by any modality)modality)

M0: No distant metastasisM0: No distant metastasis M1: Distant metastasisM1: Distant metastasis M1a: M1a: Non-Regional lymph node(s)Non-Regional lymph node(s) M1b: Bone(s)M1b: Bone(s) M1c: Other site(s) with or without bone diseaseM1c: Other site(s) with or without bone disease

STAGING OBJECTIVESSTAGING OBJECTIVES

To confirm organ-confined diseaseTo confirm organ-confined diseaseradical surgical prostatectomyradical surgical prostatectomy could be offered could be offered without adjuvant radiation therapy.without adjuvant radiation therapy.

If disease is largely organ-confined with small volume If disease is largely organ-confined with small volume periprostatic or seminal vesicle spread, periprostatic or seminal vesicle spread, radical radical radiotherapyradiotherapy can still be offered can still be offered with / without pelvic nodal irradiation orwith / without pelvic nodal irradiation or with / without adjuvant hormonal therapywith / without adjuvant hormonal therapy

To confirm clinically suspected apical tumor or extent To confirm clinically suspected apical tumor or extent of LN metastases which will affect of LN metastases which will affect radiotherapy radiotherapy marginsmargins..

TIMING FOR MRITIMING FOR MRI

MRI should be delayed at least 4-8 weeks after biopsyMRI should be delayed at least 4-8 weeks after biopsy

Post biopsy hemorrhage may hamper tumor detection Post biopsy hemorrhage may hamper tumor detection in in

the glandthe gland

May result in under or overestimation of tumor May result in under or overestimation of tumor presence presence

and local extentand local extent

MR “exclusion sign”: cancers are resistant to the MR “exclusion sign”: cancers are resistant to the development of post biopsy hemorrhagedevelopment of post biopsy hemorrhage

LOCAL STAGINGLOCAL STAGING

T STAGINGT STAGING

ORGAN CONFINED DISEASEORGAN CONFINED DISEASE

Primary tumor – TNM Stage of T2 or lessPrimary tumor – TNM Stage of T2 or less

Suitable for radical surgerySuitable for radical surgery

Nerve sparing radical surgery if neurovascular bundles are Nerve sparing radical surgery if neurovascular bundles are clearclear

Clinical estimation of the organ confined disease is Clinical estimation of the organ confined disease is based on clinical nomograms which takes into accountbased on clinical nomograms which takes into account

PSAPSA DREDRE Gleason scoreGleason score

MR imaging has been shown to have an incremental value MR imaging has been shown to have an incremental value additive to clinical nomogramsadditive to clinical nomograms

EXTRACAPSULAR EXTENSION - EXTRACAPSULAR EXTENSION - ECEECE

MRI SIGNS OF ECEMRI SIGNS OF ECE

Assessed on AXIAL & CORONAL imagesAssessed on AXIAL & CORONAL images

Contour deformity with step off or Contour deformity with step off or angulated marginangulated margin

Irregular bulge or capsule retractionIrregular bulge or capsule retraction Capsular breach & direct tumor extensionCapsular breach & direct tumor extension Obliteration of rectoprostatic angleObliteration of rectoprostatic angle Asymmetry of neurovascular bundlesAsymmetry of neurovascular bundles

SEMINAL VESICLE SEMINAL VESICLE INVASIONINVASION

MRI SIGNS OF SEMINAL VESICLE MRI SIGNS OF SEMINAL VESICLE INVASION (SVI)INVASION (SVI)

Combined AXIAL, SAGITAL & CORONAL Combined AXIAL, SAGITAL & CORONAL images images

facilitates detection of SV invasionfacilitates detection of SV invasion

Contiguous low SI from base of gland in SVContiguous low SI from base of gland in SV

Extension of soft tissue along ejaculatory Extension of soft tissue along ejaculatory ductsducts

Asymmetric decrease in SI of SVAsymmetric decrease in SI of SV

Decreased conspicuity of SV wall on T2WIDecreased conspicuity of SV wall on T2WI

BLADDER & RECTAL BLADDER & RECTAL INVASIONINVASION

T2WI – SENITIVITY AND T2WI – SENITIVITY AND SPECIFICITYSPECIFICITY

Varies widely for cancer detectionVaries widely for cancer detection

Without endorectal coilWithout endorectal coil Sensitivity : 45 %Sensitivity : 45 % Specificity : 73 %Specificity : 73 %

With Endorectal coilWith Endorectal coil Sensitivity : 77 - 91 %Sensitivity : 77 - 91 % Specificity : 27 - 61 %Specificity : 27 - 61 %

How do we increase specificity ?How do we increase specificity ?

Keep Endorectal Coil MRI T2 imagingKeep Endorectal Coil MRI T2 imaging(high sensitivity) and add:(high sensitivity) and add:

Contrast-enhanced MRI (CE-MRI)Contrast-enhanced MRI (CE-MRI)

MR Spectroscopic Imaging (MRSI)MR Spectroscopic Imaging (MRSI)

Diffusion-weighted MRI (DWI)Diffusion-weighted MRI (DWI)

DYNAMIC CONTRAST DYNAMIC CONTRAST ENHANCED MRI – DCE MRIENHANCED MRI – DCE MRI

WHY TUMORS ENHANCE WHY TUMORS ENHANCE DIFFERENTLY THAN NORMAL DIFFERENTLY THAN NORMAL

TISSUESTISSUES

Cancers results in tumor angiogenesisCancers results in tumor angiogenesis

Increased no. of vessels Increased no. of vessels

Increased permeability of vesselsIncreased permeability of vessels

Increased interstitial tissue spaceIncreased interstitial tissue space

DCE MRIDCE MRI

Fast GRE seq. can scan entire vol. of gland Fast GRE seq. can scan entire vol. of gland in few secondsin few seconds

Various perfusion parameters are Various perfusion parameters are electronically extracted according to time electronically extracted according to time seq.seq.

Relative peak enhancement is most reliable Relative peak enhancement is most reliable perfusion parameter for cancer detectionperfusion parameter for cancer detection

Improves specificity compared to T2W scansImproves specificity compared to T2W scans

Tumors can be detected with higher Tumors can be detected with higher accuracy but it does not improve stagingaccuracy but it does not improve staging

DCE MRI - IMPROVEMENT IN DCE MRI - IMPROVEMENT IN DETECTION RATES DETECTION RATES

Peripheral zone cancersPeripheral zone cancers Sensitivity : 96 % Sensitivity : 96 % Specificity: 97 %Specificity: 97 %

Compared to 75 % and 53 % respectively on Compared to 75 % and 53 % respectively on T2WIT2WI

Not tested in multi institutional trialsNot tested in multi institutional trials

Suffers from lack of uniformly accepted analytic Suffers from lack of uniformly accepted analytic method method

Still of unproven benefit as per ACR guidelinesStill of unproven benefit as per ACR guidelines

DCE MRI – Analysis of data DCE MRI – Analysis of data

3 methods of analysis3 methods of analysis

Qualitative Qualitative Easier Easier

Look at curvesLook at curves

Semi-Qualitative Semi-Qualitative Average Average

Parameters from curvesParameters from curves

Quantitative Quantitative Complicated Complicated

Mathematical ModellingMathematical Modelling

MR SPECTROSCOPY - MR SPECTROSCOPY - MRSMRS

SPECTROSCOPY – NORMAL SPECTROSCOPY – NORMAL SPECTRAL ANALYSISSPECTRAL ANALYSIS

3D proton MR spectroscopic metabolic 3D proton MR spectroscopic metabolic mapping of the entire gland is possible mapping of the entire gland is possible with a resolution of 0.24 ml per voxel. with a resolution of 0.24 ml per voxel.

Proton MR spectroscopy displays Proton MR spectroscopy displays concentrations of citrate, creatine, and concentrations of citrate, creatine, and choline metabolites found in the prostate choline metabolites found in the prostate gland and cancer. gland and cancer.

Normal Normal prostateprostate tissue contains high tissue contains high levels of citrate -higher in the PZ than in levels of citrate -higher in the PZ than in the central gland. the central gland.

SPECTROSCOPY – SPECTRAL SPECTROSCOPY – SPECTRAL ANALYSISANALYSIS

Healthy peripheral-zone voxels typically have Healthy peripheral-zone voxels typically have

diagnostic levels of Cit with (Cho + Cr)/Cit diagnostic levels of Cit with (Cho + Cr)/Cit ratios ratios

less than 0.5 less than 0.5

Because of the proximity of the choline and Because of the proximity of the choline and

creatine peaks at 1.5-T MR unit two peaks creatine peaks at 1.5-T MR unit two peaks cannot be separatedcannot be separated

TUMOR VOLUMETUMOR VOLUME

TUMOR VOLUMETUMOR VOLUME

There is an association between primary There is an association between primary tumor volume and local extent of disease, tumor volume and local extent of disease, progression, and survivalprogression, and survival

A review of a large number of prostate A review of a large number of prostate cancers in surgical and autopsy specimens cancers in surgical and autopsy specimens showed showed Capsular penetrationCapsular penetration Seminal vesicle invasion and Seminal vesicle invasion and Lymph node metastases Lymph node metastases

usually found only with tumors larger than 1.4 ccusually found only with tumors larger than 1.4 cc

TUMOR VOLUMETUMOR VOLUME

Another study - ECE in 18 % with vol. < 3 cc Another study - ECE in 18 % with vol. < 3 cc 79% with volume > 3 cc79% with volume > 3 cc

Tumor volume – significant predictor of ECETumor volume – significant predictor of ECE

Bx, TRUS and T2-MRI disappointing in Bx, TRUS and T2-MRI disappointing in volume estimationvolume estimation

MRS provides more accurate volume MRS provides more accurate volume estimationestimation

ROLE OF SPECTROSCOPY IN ROLE OF SPECTROSCOPY IN ESTIMATING TUMOR VOLUMEESTIMATING TUMOR VOLUME

Relative tumor volume is determined on MRSRelative tumor volume is determined on MRS ( counting the voxels containing abnormal ( counting the voxels containing abnormal

spectra )spectra )

Improves Dx of ECE for both experienced and less Improves Dx of ECE for both experienced and less experienced readerexperienced reader

Decrease inter observer variability – further Decrease inter observer variability – further studies required to assure improvement in the studies required to assure improvement in the performance of truly inexperienced readerperformance of truly inexperienced reader

MR SPECTROSCOPY - MRSMR SPECTROSCOPY - MRS

Technically demanding and time consumingTechnically demanding and time consuming

Improvement in diagnostic accuracy and Improvement in diagnostic accuracy and staging have been reported but not proved staging have been reported but not proved in multi institutional trials in multi institutional trials

ACR clinical trial is currently underwayACR clinical trial is currently underway

Currently cannot be considered as routine Currently cannot be considered as routine diagnostic tooldiagnostic tool

Diffusion-weighted Imaging (DWI)Diffusion-weighted Imaging (DWI)

DiffusionDiffusion is the process of thermally is the process of thermally induced random molecular displacement – induced random molecular displacement – Brownian motionBrownian motion

Diffusion properties of tissues are related Diffusion properties of tissues are related Amount of tissue water Amount of tissue water Tissue permeabilityTissue permeability

Cancer tends to have restricted diffusion Cancer tends to have restricted diffusion due to due to High cell densities High cell densities Abundant intracellular membranesAbundant intracellular membranes

DWIDWI

ADVANTAGESADVANTAGES Short acquisition time Short acquisition time High contrast resolution between tumor and High contrast resolution between tumor and

normal tissuenormal tissue No need for endorectal CoilNo need for endorectal Coil

DISADVANTAGESDISADVANTAGES Poor spatial resolutionPoor spatial resolution Potential risk of image distortion by post biopsy Potential risk of image distortion by post biopsy

HgHg

LOCAL STAGING LOCAL STAGING

N STAGINGN STAGING

ABNORMAL NODESABNORMAL NODES

Early metastases can occur in small nodesEarly metastases can occur in small nodes

Size and shape of nodes inaccurate for Size and shape of nodes inaccurate for stagingstaging

ABNORMAL NODESABNORMAL NODES

Rounded configuration Rounded configuration

Short axis > 10 mm if oval, > 8 mm if round Short axis > 10 mm if oval, > 8 mm if round

T1 OR T2 SI – not helpfulT1 OR T2 SI – not helpful

Enhancement suggestive of metastatic lymph nodeEnhancement suggestive of metastatic lymph node

SHORTCOMINGS- NODAL STAGINGSHORTCOMINGS- NODAL STAGING

Normal sized nodes - contain cancer Normal sized nodes - contain cancer as micro metastasesas micro metastases

Enlarged nodes may be reactiveEnlarged nodes may be reactive

DETECTION OF ABNORMAL LYMPH DETECTION OF ABNORMAL LYMPH NODESNODES

Neither CT nor MRI is accurate as laparoscopic nodal Neither CT nor MRI is accurate as laparoscopic nodal dissectiondissection

Initial step prior to radical prostatectomy remains Initial step prior to radical prostatectomy remains nodal dissectionnodal dissection

MR is at least as accurate as CT in nodal stagingMR is at least as accurate as CT in nodal staging

If good chance the prostate cancer has already spread If good chance the prostate cancer has already spread to the lymph nodes to the lymph nodes laparoscopic laparoscopic lymph node lymph node

dissectiondissection is a minimally invasive procedure to begin with is a minimally invasive procedure to begin with

Lymphotropic NanoparticlesLymphotropic Nanoparticles

ULTRASMALL SUPER PARAMAGNETIC MR ULTRASMALL SUPER PARAMAGNETIC MR contrast agents taken up by macrophagescontrast agents taken up by macrophages

Distributes to LNs throughout the body Distributes to LNs throughout the body Injected intravenously and imaged 24 hrs laterInjected intravenously and imaged 24 hrs later +++ susceptibility effect on T2* MR images+++ susceptibility effect on T2* MR images Cannot enter tumor (no macrophages)Cannot enter tumor (no macrophages) Can differentiate normal/reactive lymph nodes Can differentiate normal/reactive lymph nodes

from malignant onesfrom malignant ones Iron based contrast agents not approved by Iron based contrast agents not approved by

FDAFDA(Ferumoxtran-10)(Ferumoxtran-10)

Future trendsFuture trends

3T MRI3T MRI Increased SNRIncreased SNR Increased spatial resolutionIncreased spatial resolution ? Assessment of microscopic disease? Assessment of microscopic disease ? Need for Endorectoil Coil? Need for Endorectoil Coil

Standardized technique for CE-MRI with Standardized technique for CE-MRI with availability of vendor softwareavailability of vendor software

Approval of Approval of Lymphotropic Nanoparticles for accurate nodal staging

Thanks to:Thanks to:

Arifa SadafArifa Sadaf

Radiology, Radiographics and AJRRadiology, Radiographics and AJR

Researchers who develop Prostate MRResearchers who develop Prostate MR

Thank YouThank You