1. Applications of MRI in the diagnosis,
treatment and follow up of prostate
cancer
Matthew Buck
2. Prostate Cancer
• Second most common cause of cancer mortality in
males
• 1 in 8 males in UK
• Increases with age
• Risk factors include: ethnicity, family history, and
poor diet
• 70% in peripheral zone, 25% transitional zone and
5% central zone
• Clinically significant and clinically insignificant
(Cancer Research UK, 2015; Linton and Catto, 2013; Matikane et al., 2010)
3. Anatomy
A B
C D
(PI-RADS V2, 2015)
Key
A: Sagital
B: Cornonal
C: Axial Base
D: Axial Apex
PZ: Peripheral zone
CZ: Central zone
TZ: Transitional zone
US: Urethral sphincter
AFS: Anterior
fibromuscular stroma
a- anterior
p- posterior
l- lateral
m- medial
4. Staging
Stage I- Too small to see on scans Stage II- Completely inside prostate gland
Stage III- Broken through capsule Stage IV- Spread to other organs
5. Diagnosis
Digital Rectal Exam (DRE)
• Has a low specificity and low sensitivity
• Large amount of inter-observer variability
and dependent on clinical experience
Prostate Specific Antigen (PSA)
• Presence in blood indicates a disruption
in blood-prostate barrier
• PSA< 10 ng/ ml = low risk
• PSA 10-20 ng/ ml = intermediate risk
• PSA>20 ng/ ml = high risk
Trans rectal ultrasound (TRUS)
• Allows measurement of gland volume
Biopsy
• TRUS or tans-perineal
• Targeted to suspicious lesions or
peripheral zone
• Risk of bleeding or infection
Gleeson Score
• Assessment of cancerous cells
• Graded 1-5 based on growth patterns
• >7 = high risk
(Cancer Research UK, 2015; Linton and Catto, 2013; EAU, 2015)
6. MRI vs. CT vs. PET
MRI
• Visualization of organ-
confined or extra-
prostate spread
• Tumour location
• Extracapsular spread
• Seminal vesicle invasion
• Bone mets
CT
• Good for nodes and
distant disease
• Poor visualization of
the prostate gland
• Useful in MRI
contraindicated
• Quick scan time
• Ionising radiation
• Not recommended to
low or medium risk
patients (NICE, 2014)
PET
• Good for metastatic
boney deposits.
• Poor visualization of
the prostate gland
• Ionising radiation
• Not recommended in
routine clinical practice
(NICE, 2014)
(NICE, 2014; Lipton and Catto, 2013)
7. MRI Prep
• Use of Anti-spasmodic (e.g. buscopan)
• Empty bowels
• Consider scanning prone
• Recent biopsy may be contra-indicated
• Refrain from ejaculation for 3 days prior
(Gunderson & Tepper, 2015; PI- RADS V2, 2015)
8. Endorectal coil vs. Phased array coil
• Increased SNR
• Allows for more spatial resolution
imaging and better image quality of
low SNR sequences
• Better for larger patients
• More time consuming
• Poor patient tolerance
• Possible gland deformity
• Inflation of ERC balloon causes
magnetic field inhomogeneity
• Contraindication such as prior rectal
surgery, IBD, Latex allergy
• 16 channel phased array coil can
provide sufficient SNR
• Less time consuming
• Less traumatic for patients
• Cheaper
(NICE, 2014; PI-RADS, 2015; Grand et al, 2012)
9. Axial Pelvis
T1
• Nodular enlargement
• Loss of nodal sinus fat
• Bone metastasis
T2
• Nodal involvement
• Renal obstruction
• Large FOV
• 5mm slice thickness
(Mankad et al, 2011; PIRADS, 2015)
10. Axial Prostate
T1
• Presence of hemorrhage
within prostate and seminal
vesicles
T2
• Assess abnormalities
• Seminal vesicle involvement
• Nodal involvement
• Extra-prostatic extension
• Used for TZ lesion
measurement
• Small FOV- 120-200 mm (PI-RADS, 2015)
• 3 mm slices
(Mankad et al, 2011; PI-RADS, 2015)
11. T1 Axial T2 Axial
Biopsy related residual hemorrhage
in right mid-peripheral zone
Large left mid-peripheral
zone lesion
(Sankineni et al., 2014)
12. Sagittal and Coronal
Sagittal
• Evaluate prostate anatomy
• Localisation of ER coil
• Highlights invasion into bladder
• Large FOV to survey of lumbar
spine and retroperitoneal for
pathologies if suspected
• Used in PROMIS trial and HIFU
trial
Coronal
• Evaluate prostate anatomy
• Identify T2 bright and T2 dark
anatomy
• Assessment of apex and base of
prostate
• Bladder and seminal vesicle
assessment
Performing multi planar imaging is required for accurate
measurement of the prostate gland (PI-RADS V2)
(Grand et al., 2012; PI-RADS V2, 2015)
14. DWI
• Diffusion weighted imaging
• Assesses Brownian motion of molecules
• Clinically significant cancers have restricted diffusion
• Should include ADC
• B-values acquired from 50 to 2000
• High b-value can help visualize clinically significant cancers
• Achieved by high b-value sequence or extrapolation from low b-value data
• Primary sequence for PZ lesion measurement
• Overlap with BPH and low grade tumour
• Computed b-value can produce multiple b values from DWI with at least
two different b-values
• High b-values have reduced SNR and increased SAR
(Bittencourt et al., 2014; PI-RADS, 2015; Ueno, et al., 2014)
16. DCE MRI
• Dynamic contrast enhanced
• T1 scans before pre, during and post gadolinium
• 2D or 3D- 3D imaging preferred
• Ca prostate will often have early enhancement compared to
normal tissues and rapid wash out
• May detect smaller, significant cancers
• Secondary to T2 and DWI in PI-RADS assessment
• Fat suppression can improve visualisation of enhancement
• Direct visual assessment or parametric mapping
(PI-RADS, 2015; Bard, 2008; Sankineni et al., 2014)
19. Spectroscopy
• Prostate Ca has a high Choline content
• Combined with T2- sensitivity 91% specificity 95% (Murphy et al., 2013)
• FOV voxel size is too large therefore small tumors may not be
sampled
• Inoperative in the fat
• Inflammation and post treatment artifacts detrimental
• Specificity for low grade cancer 44% (Lemaitre et al., 2008)
• PI-RADS V2 does not recommend for routine imaging
(Bard, 2009; Lemaitre et al., 2008; Murphy et al., 2013; Carroll et al., 2006)
20. Departmental Protocols
Standard Protocol
• Buscopan administered
• Localiser
• T2 sag localiser
• T1 axial large FOV
• T2 coronal small FOV
• T2 axial small FOV
• DWI axial - b50 b400 b1000
• DWI axial - b1400
• T1 dynamic post contrast
PROMIS Protocol
• Localiser
• T2 3 plane localiser
• T2 coronal small FOV
• T2 sagittal small FOV
• T2 axial small FOV
• DWI axial - b0 b150 b500 b1000
• DWI axial - b1400
• T1 dynamic vibe
21. Prostate Carcinoma
MR features in PZ are:
• A low T2 signal intensity mass
• Diffusion restriction
• Elevated choline peaks on MRSI
• Early contrast wash-in and wash-out on DCE.
• Mass effect on the adjacent capsule
MR features in TZ are:
• On T2WI, area with homogenous low signal intensity, ill-defined
margins, lenticular shape and absence of a capsule and invasion of
the AFS
• Diffusion restriction with ill-defined margins
• Asymmetric rapid contrast wash-in and wash out
• Elevated choline peaks
(PI-RADS, 2015; Yu et al, 2014)
22. Mimics of Prostate Carcinoma
Chronic Pancreatitis
• No contour deformity or mass effect
on adjacent normal tissue
• Decreased T2 signal but DWI signal is
often less than prostate ca
• Mild contrast wash-in and wash-out
on DCE
Hypertrophic nodules
• Well defined margins; rounded or
spherical
• Rapid contrast wash-in and wash-out
on DCE
Focal changes related to prior
radiation
• Lack of significant diffusion
restriction
• No rapid wash-in or wash-out on DCE
• No elevation of choline peaks
Benign prostatic hyperplasia (BPH)
• Found in TZ but can extrude to PZ
• Glandular nodes have Moderate T2
hyper-intensity
• Encapsulated with round nodules and
circumscribed margins
• Stroma nodules have T2 hypo-intensity
• On DCE, Prostate Ca has stronger
enhancement with earlier peak
time (p< 0.05).
• ADCs are higher in BPH than prostate ca
(Yu et al., 2014; PI-RADS, 2015; Ren et al., 2007)
23. Role of MRI in treatment and follow-
up of Prostate Ca
• External beam radiation therapy (EBRT) and Brachytherapy are used in
patients with tumour extension beyond prostatic capsule and in patients
opting for primary or salvage treatment
• T2WI has a higher soft tissue contrast than CT and Transrectal US , as it
provides more accurate identification and localisation of the tumour and gives
more accurate delineation of irradiation field and decreases dose to
periprostatic tissues and urethra.
• Brachytherapy prostate Ca patients only to be imaged at 1.5T, due to artifact
from gold beads
• However, radiotherapy can cause diffuse T2 signal
• T2 imaging is limited by loss of zonal anatomy glandular atrophy and fibrosis
• Low signal T2, low signal ADC and rapid wash out on DCE
• DCE has better sensitivity (72%) than T2 (38%) for localisation of recurrent
prostate cancer (Haider et al., 2008)
• MRS can be added to examination to aid diagnosis as elevated choline levels
with absence of citrate suggest recurrent prostate carcinoma
(Westphalen et al.,2008,;Murphy et al., 2013, Haider et al., 2008; Yu et al., 2014)
24. References
American Journal of Urology. (2015). PI-RADS V2 Prostate imaging- reporting and data system. ACR
Bard, R. L. (2009). Dynamic contrast enhanced MRI. Berlin: Springer
Bhavsar, A. & Verma, S. (2014). Anatomic imaging of the prostate. BioMed Research International. doi:
10.1155/2014/728539
Bittencourt, L. K. Attenberger, U. I. Lima, D. Strecker, R. de Oliverira, A. Schoenberg, S. O. … & Hausmann, D. (2014).
Feasibility study of computed vs measured high b- value (1400 s/mm²) diffusion-weighted MR images of
the prostate. World Journal of Radiology, 6(6). 374-380. doi: 10.4329/wjr.v6.i6.374
Cancer Research UK. (2015). Prostate cancer mortality statistics. Cancer Research UK. Retrieved January 10th 2016
form:http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/prostate-
cancer/mortality
European Association of Urology. (2015). Guidelines to prostate cancer. EAU. Arnhem. Mottet, N.
Grand, D. J. Mayo-Smith, W. W. Woofield, C. A. (2012). Practical body MRI: protocols, applications and image
interpretation. New York: Cambridge University Press
Gunderson, L. L. & Tepper, J. E. (2015). Clinical radiation oncology. (4th Ed.). China: Elsevier
Haider, M. A. Chung, P. Sweet, J. Toi, A. Jhaveri, K. Menard, D. … & Milosevic, M. (2008). Dynamic contrast enhanced
MRI for localisation of recurrent prostate cancer after after external beam radiotherapy. Internation
Journal of Radiation Oncology. 70(2). 425-430. doi:10.1016/j.ijrobp.2007.06.029
25. References
Korobkin, A. Serova, N. Ustyuzhanin, I. Korobkova, G & Voskanyan, A. (2014).
Diagnostic value of modern MRI technique. ECR. Doi: 10.1594/ecr2014/C-1482
Linton, K. D. & Catto, J. W. F. 2013. Prostate cancer, Renal and Urological Surgery II. 31(10). 516-522
Mankad, K. Hoey, E. Lakkaraju, A. Bhuskute, N. (2011). MRI of the whole body: an illustrated guide to common
pathologies. Florida: Hodder Arnold
Murphy, G. Haider, M. Ghai, S. & Sreeharsaha, B. (2013). The expanding role of MRI in prostate cancer. American
Journal of Radiology, 201. 1229-1239. doi. 10.2214/AJR.12.10178
National Institute for Health and Care Excellence. (2014). Prostate Cancer: Diagnosis and Management. London.
NICE.
Ren, J. Huan, Y. Wang, H. Chang, Y. –J. Zhao, H. –T. Ge, Y. –L. … & Yang, Y. (2008). Dynamic contrast enhanced MRI of
benign prostatic hyperplasia and prostatic carcinoma: correlation with angiogenesis. Clinical Radiology. 63.
153-159. doi:10.1016/j.crad.2007.07.023
Sankineni, S. Osman, M. & Choyke, P. L. (2014). Functional MRI in prostate cancer detection. Bio-Med Research
International. doi: 10.1155/2014/590638
National Institute for Health and Care Excellence. (2014). Prostate Cancer: Diagnosis and Management. London.
NICE.
26. References
Ueno, Y. Takahashi, S. Ohno, Y. Kitajima, K. Yui, M. Kassai, Y. Kawakami, F. … & Sugimura, K. (2014). Computed
diffusion-weighted MRI for prostate cancer detection: the influence of the combinations of b-values.
British Journal of Radiology. 88(1048). doi. 0.1259/bjr.20140738
Westphalen, A.C. McKenna, D. A. Kurhanewicz, J. & Coakley, F.V. (2009). Role of MRI and MRI spectroscopic
imaging before and after radiotherapy for prostate cancer. Journal of Endourology, 24(4). 789-794
10.1089/end.2007.9822
Yu, J. Flucher, A. S. Turner, M. A. Cockrell, C. H. Cote, E. P. & Wallace, T. J. (2014). Prostate cancer and its
mimics at multiparametric prostate MRI. British Institute of Radiology, 87(1037)
doi. 10.1259/bjr. 20130659
Editor's Notes
Prostate cancer is the second most common cause of death from cancer in males in the western world after lung cancer (Linton and Catto, 2013).
Increases with age: in UK 36% of cases were diagnosed in men over 75 and only 1% were diagnosed in under 50s (Cancer Research UK, 2015)
Ethnicity: Black males are more at risk than Caucasian males (Cancer research UK, 2015)
Family history: 85% of cancers are sporadic but familial or hereditary cancer are more common in younger patients. There is a greater risk if immediate family is diagnosed and risk is inversely proportional to age. (Matikane et al, 2010)
Many candidates genes for prostate cancer susceptibility have been identified for example hereditary prostate cancer (HPC-1), and there is increased risk in men who carry BRCA-1 and BRCA-2 genes (Linton and Catto, 2013)
Poor diet: High fat, high red meat and low vegetable intake will increase risk of prostate cancer. Higher intake of foods with antioxidants reduces risk
70% of cancer occur in the peripheral zone, 25% in the transitional and only about 5% in the central zone
Key: A- Sagital B- Coronal C- Axial view at the base of the gland- the upper third of the prostate D- Axial view at the apex of the gland- the lower third of the gland
PZ- peripheral zone CZ- Central zone TZ- Transitional zone US- Urethral sphincter AFS- Anterior fibromuscular stroma
a- anterior p- posterior l- lateral m- medial
The peripheral zone is the larger zone and consists of approx. 70% of the glandular tissue it contains numerous ductal and aciner elements.
The central zone is located at the base of the gland and contain 25% of the glandular tissue
The transitional zone consists of two small lobes of glandular tissue that contain only 5% of the glandular tissue.
Anterior fibromuscular stroma is composed of fibrous and smooth muscle tissues, and no glandular tissue. (Bhavsar and Vermer, 2014)
T1 tumours are too small to be viewed on scans or felt during DRE– they may be discovered with needle biopsy, after finding a raised PSA Level
T2 tumours are completely inside the prostate gland and are divided into 3 smaller groups
T2a – The tumour is in only half of one of the lobes of the prostate gland
T2b – The tumour is in more than half of one of the lobes
T2c – The tumour is in both lobes but is still inside the prostate gland
T3 tumours have broken through the capsule (covering) of the prostate gland but have not spread into other organs – they are divided into 2 smaller groups
T3a – The tumour has broken through the capsule (covering) of the prostate gland
T3b – The tumour has spread into the seminal vesicles
T4 tumours have spread into other body organs nearby, such as the rectum (back passage), bladder, muscles or the sides of the pelvic cavity
To reduce motion artifact from bowel peristalsis, anti-spasmodic agent can be used, as long as there are no contraindications
If an endo-rectal coil is going to be used. The presence of stool in the rectum will interfere with placement. Also stool in the rectum can induce artificial distortion in DWI sequences are reduce image quality. It may be worth considering a minimal preparation enema be administered prior to the exam. However this may increase likelihood of peristalsis.
If there is air within the rectum, it may worth considering perform the examination with the patient in a prone position, to improve separation from the prostate and the rectum. However this may increase breathing related motion of the prostate (Gunderson and Tepper, 2015)
Post biopsy changes, such as hemorrhage and inflammation can be detrimental to prostate interpretation and a delay of at least 6 weeks between biopsy and MRI scan is recommended. However, if the aim of the exam is to test for clinically significant cancers, it will be present in other locations than just the hemorrhagic sight. Thus, scanning does not need to be delayed in this situation.
Refraining from ejaculation for 3 days prior to the examination will maintain maximum distention of the seminal vesicles. However there has not been reliable proof that this benefits the assessment for clinically significant cancer.
T1 images are used to determine the prescience of hemorrhage with the prostate and seminal vesicles and to outline the gland. At least one T1 sequence, should be performed for hemorrhage assessment (Barentz et al, 2012)
T2 images are used to assess the prostatic zonal anatomy and assess the abnormalities with the gland. It is used to evaluate seminal vesicle invasion, EPE and nodal involvement
Slice thickness of 3mm with no gap
A 57 year old with Gleason score 4+5 on multiple cores undergoing post biopsy staging MRI
T2 Sagittal and coronal of T4 stage patient, Sagittal shows cancer invasion of the bladder (arrowed) and Coronal shows invasion into the seminal vesicles (arrowed)
(Murphy et al., 2013)
Diffusion weighted imaging assess the random motion of water molecules (Brownian motion) and is a key component of prostate MRI.
It should be accompanied by Apparent Diffusion Coefficient (ADC) which will come in a range of b-values. These should come in range of low-b values and high b-values.
Cancerous tissue will appear hyper-intense on DWI and hypo-intense on ADC.
B-values greater than 1400 are considered high b-values and can help with the visualisation of clinically significant tumors. Especially those adjacent to anterior fibromuscular stoma or at the apex or base of the gland.
High b-values can be achieved by either having a high DWI sequence, which will increase scan time or by extrapolating data from low b-value data. Taking data from low b-values would be less prone artifacts because high DWI sequences have longer TEs and require stronger gradient pulses.
As the b-values increase, SNR decreases. Optimal b-values varies due to different magnetic field strengths and differences in equipment and software.
ADC is the primary tool for measuring PZ lesions
Although ADC values can correlate to histologic grades, there is overlap between BPH, low grade and high grade tumour.
Axial T2 weighted image of an 88 year old patient. T2 image shows a focal hypointense lesion in posterolateral left peripheral zone. Measured b vales depicts suspected lesion with varying degrees of contrast to the prostate background. B values from 0 to 1400. ADC value possible lesion is low.
Dynamic contrast enhancement should always be included in a MRI prostate examination. It is a rapid T1 GRE scan before, during and post gadolinium contrast.
Prostate cancer often demonstrates early enhancement compared with normal tissues and should therefore be closely assessed for signs of early enhancement. However prostate enhancement may be variable and heterogeneous, i.e. some malignancies will display early wash out whilst others retain contrast for longer.
DCE is positive if there is enhancement that is focal and corresponds to suspicious findings on T2 and DWI. Therefore, in PI-RADS assessment, DCE is secondary to T2 and DWI.
Assessment can be done via direct visual assessment or they can be assisted using a parametric map. Visualisation of enhancement can be improved by using fat suppression techniques.
Positive DCE MRI lesion is one with focal enhancement and corresponds to T2 or DWI appearances. BPH nodules enhance early but are round in shape and well circumscribed.
Dynamic contrast enhanced scan in axial plane in patient with prostatic cancer. Lesion (arrowed) enhances early in the right periphery zone of right lobe
Apical right focal lesion
Phased array coil used, no bowel prep, no clearing bowels, no refraining from ejaculation.
Large FOV axial- ST-6mm – FoV- 350mm
Coronal small Fov- st- 4mm- fov- 200mm
Small FOV axial- ST- 3mm fov- 200mm
DWI- FOV- 200mm, st- 4mm
DWI b1400- FOV- 320mm, st- 5mm
T1 post contrast- 1 slab, 26 slices, fat sat
No spectroscopy
PZ Prostate Ca features:
A low signal intensity with mass effect on the adjacent capsule on T2 images
Low signal intensity on ADC, often correlating with with Gleason scores such that lower ADC values correlate with higher Gleason scores
Elevated choline peaks on MRSI
Focal enhancement with early contrast wash-in and wash-out on DCE.
TZ prostate Ca features are more challenging to detect and diagnose as MR signal intensity characteristics of a normal TZ and carcinoma often overlap.
Findings most predictive of extracapsular extension on MRI are focal irregular capsular bulging, asymmetry of neurovascular bundles and obliteration of rectoprostatic angle
Chronic pancreatitis- decreased T2 but not as much as PCa
The average ADCs (× 10−3 mm2/sec) were 1.05 (95% CI: 0.97, 1.11), 1.27 (95% CI: 1.20, 1.33), and 1.73 (95% CI: 1.64, 1.83), respectively, in CG carcinoma, SH foci, and GH foci (Otto et al, 2010)
T2WI high soft tissue contrast allows for;
Depiction of zonal anatomy of the prostate
The extent of neoplastic disease
Periprostatic structures
Transrectal US imaging is routinely used as a guide for gold seed placement, but for optimal distribution of of radiation to specific targets is often impossible.
MRI provides better delineation of the tumour and peri-prostatic structures than CT does
Findings most predictive of extracapsular extension on MRI are focal irregular capsular bulging, asymmetry of neurovascular bundles and obliteration of rectoprostatic angle
