- Prostate cancer is one of the most common malignancies in men,
generally with a slow growth rate and early detection is essential for a complete treatment [1].
- The diagnosis is mainly based on digital rectal examination (DRE),
serum prostate specific antigen (PSA) and trans-rectal ultrasound (TRUS) guided systematic random prostate biopsy,
but cancer located outside the routine biopsy zone may be missed [1-3].
Currently,
an accurate detection and localization of prostate cancer can be done easily using multip-parametric MRI (mp-MRI) examination which is able to provide anatomical and functional information about prostate tissue [3,
4].
Multip-parametric MRI (mp-MRI) examination includes a combination of high-resolution T2-wi and at least two functional MRI techniques,
such as dynamic contrast-enhanced (DCE) MRI,
diffusion-weighted imaging (DWI) or proton spectroscopy imaging (MRSI) [2,
5].
- Based on our experience,
in this presentation we will refer to these acquisitions: T2-wi,
DCE MRI and DWI / ADC map.
Anatomy of the Prostate
- The anatomy of the prostate gland was based on the zonal compartment system developed by McNeal: periurethral tissue and transitional,
central and peripheral zones [1,
6].
According to this system,
prostate is divided into two compartments,
the central gland composed of a transitional zone and periurethral tissue,
and the peripheral gland composed of peripheral zone and central zone [1] (Fig. 1).
- The peripheral zone accounts over 70% of the glandular tissue [1,
7].
It is located posterior and lateral to the urethra and its ducts open into prostatic urethra distal to verumontanum [1,
7,
8].
About 70% of prostate cancers arise in the peripheral zone [1,
7,
8].
- The central zone accounts about 25% of the glandular tissue that surrounds the ejaculatory ducts and its ducts arise into the prostatic urethra close to the ejaculatory duct orifices [7,
8].
Carcinomas and other diseases are rarely present at this level [8].
- The transitional zone constitutes for 5% to 10% of the glandular prostate and its ducts arise into the postrolateral part of the prostatic urethra [1,
8].
Cellular proliferation in the transitional zone causes benign prostatic hyperplasia (BPH) [1,
8].
About 20% of prostate cancers are localized in the transitional zone [1].
- Periurethral zone consists of small ducts and acini which are not completely developed; it is located along the proximal urethral segment inside the preprostatic sphincter [8].
- The anterior fibromuscular stroma consists of nonglandular tissue; it covers the entire anterior surface of the prostate gland [8].
Conventional MRI
- T2-weighted MR imaging is optimal to characterize the anatomy of the prostate [1].
On T2-wi,
the peripheral zone has high signal intensity,
in contrast to the low signal intensity of the central and transitional zones,
in young male subjects [1,
9] (Fig. 2).
With increasing age,
the central gland is mainly composed of transition zone,
due to BPH,
which leads to the formation of adenomatous nodules [3,
5].
BPH appears as a well-defined and inhomogeneous area with intermediate signal intensity on T2-wi [3,
9].
The anterior fibromuscular stroma also appears as an area with low signal intensity on T2-wi [1].
- T2-w images are useful to detect prostate cancer in the peripheral zones,
which appears as an area of low signal intensity [1,
3,
5].
- Sometimes,
a focal area of low signal intensity located in the peripheral zone may represent a benign abnormalities such as chronic prostatitis,
atrophy,
scars,
post–radiation therapy fibrosis and changes after hormone deprivation therapy [1,
3].
Usually a benign lesion appears as an area of low-signal-intensity with a wedge shape and a diffuse distribution without mass [3,
10].
- Another limitation of this method is represented by cancer detection in the transitional and central zones,
because cancer and normal tissues have low signal intensity on T2-w images [1].
- Because T1-w contrast in the prostate is very low,
it is not possible to identified the different anatomic zones [1,
3].
T1-w images are mainly used to identify blood product,
usually after biopsy,
which leads to high signal intensity on T1-w images,
respectively low signal intensity on T2-w images [1,
3,
11].
Therefore,
the MRI examination should be avoided for 8 weeks after biopsy to reduce artifacts caused by hemorrhage [3,
12].
MR-dynamic contrast enhanced (DCE)
Principles
- This technique is based on tumor angiogenesis [1].
Genetic mutation caused by cancer leads to the production and release of angiogenic factors such as the vascular permeability factor or vascular endothelial growth factor in reaction to the presence of local hypoxia or lack of nutrients [1,
3,
13].
Therefore,
the number of vessels increases in cancerous tissue,
and these newly formed tumor vessels presents a higher permeability than do normal vessels because of weak integrity of the vessel wall [1,
13].
- Because the interstitial space is greater in cancerous tissue than in normal tissue,
there is a significant difference of contrast material concentration between the plasma and the interstitial space [1].
- This characteristic environment explain the enhancement pattern of cancerous tissue with earlier and faster enhancement and earlier contrast agent washout compared with surrounding normal prostate tissue [1,
13-16].
- This technique requires a rapid acquisition methods,
before,
during,
and after a fast bolus administration of low-molecular-weight gadolinium contrast media using an injection rate of 2–4 mL/s [13].
- IV-injected contrast media reaches to the tissue microvasculature and extravasate within seconds to the extravascular extracellular space,
leading to a fast brightening of signal on T1-w images [13].
The signal measured in cancerous tissue on DCE-MRI represents a combination of perfusion and permeability due to alterations in vascular permeability,
extracellular space,
and blood flow [13] (Fig. 3).
Image Acquisition
- DCE-MRI usually use 3D T1-w fast spoiled gradient-echo sequences to examine the prostate after the administration of a bolus of IV contrast agent [13].
The image sets are obtained repeatedly every 5 seconds for up to 5−10 minutes,
the aim is to detect early enhancement of the cancerous tissue,
but many centers use acquisition times up to 10 seconds with good results [13].
Image analysis
- The most common method of image analysis is the semi-quantitative,
based on the supposition that early and intense enhancement and washout is a predictor of malignancy [13].
- It is necessary to quantify the signal intensity changes represented by time-intensity (gadolinium concentration) curves analyzing the following parameters,
the first peak of enhancement,
integral area under the curves,
wash-in / wash-out gradient,
maximum signal intensity,
time-to-peak enhancement and start of enhancement [3,
13].
- In prostate cancer,
there is early intense enhancement and fast washout of contrast agent [13,
15,
17].
- After initial uptake,
three types of time-intensity curves can be seen,
persistent increase (type 1),
plateau (type 2) and decline after initial upslope (type 3) [13] (Fig. 4).
- The most suspicious for prostate cancer is type 3 of time-intensity curve,
especially if associated a focal asymmetric enhancing lesion [13].
- Kim et al.
analyzed the role of Parametric Imaging of the Wash-In Rate and T2-wi in the detection of prostate cancer [1,
18].
The sensitivity and specificity for cancer detection in the peripheral zone were significantly greater on parametric imaging of the wash-in rate (96% and 97%) than on T2-wi (75% and 53%); in the transitional zone,
the sensitivity for cancer detection was significantly greater on parametric imaging of the wash-in rate (96%) than on T2-wi (45%),
but the specificity is greater on T2-wi (73%) than on parametric imaging of the wash-in rate (51%) [18].
Diffusion-weighted Imaging (DWI)
- DWI is a fast and simple MR imaging technique in the detection and characterization of prostate cancer based on the random movement of water molecules in cancerous tissue [3,
5]. Movement of water molecules is limited in cancerous tissue or fibrosis and the images will show diffusion restriction appearing in high signal intensity on the high b-value images,
respectively low signal intensity on the apparent diffusion coeficient (ADC) maps [5].
- The prostate cancer appearance on ADC maps correlates well with tumor aggressiveness,
increasing the specificity of magnetic resonance examination [5,
19].
- b values between 500 and 800 sec/mm2 are typically used for prostate cancer,
but b values of 1000 and 2000 sec/mm2 may increase the detection of prostate cancer,
especially in the transition zone,
improving differential diagnosis between BPH and prostate cancer [3,
20,
21].
- Chiho Sato et al.
demonstrated that the ADC values of prostate cancer in the peripheral zone and transitional zone were significantly lower than the ADC values of benign tissue in the corresponding zone [22].
- Meltem Esen et al.
demonstrated the usefulness of ADC values in the differentiation of prostate cancer from normal prostate parenchyma and prostatitis using b values of 100,
600 and 1,000 s/mm2; the ADC values of prostate cancer group were significantly lower at b values of 600 and 1,000 s/mm2 [23].
ESUR prostate MR guidelines 2012
- In 2012,
a group of experts from the European Society of Urogenital Radiology (ESUR) developed a clinical guidelines for mp-MRI of the prostate with the aim to standardize the interpretation and to improve communication with clinical colleagues preferably using a structured reporting scheme [2,
5].
- For optimal MRI examination protocols have been proposed three protocols: “detection”,
“staging” for evaluating minimal extra-capsular extension and “node and bone” to assess nodal size and bone marrow metastases [2].
- European urologists and radiologists introduced a scoring system similar to that employed successfully by breast radiologists expert; this scoring system is named the Prostate Imaging Reporting and Data System (PI-RADS) based on mp-MRI examinations [2,
24].
- The PI-RADS score should be assessed for each acquisition included in the mp-MRI examination [2].
- The PI-RADS scoring system uses a five-point scale as follows [2,
5]:
-Score 1: clinically significant disease is highly unlikely to be present;
-Score 2: clinically significant cancer is unlikely to be present;
-Score 3: clinically significant cancer is equivocal;
-Score 4: clinically significant cancer is likely to be present;
-Score 5: clinically significant cancer is highly likely to be present.
- The criteria for each PI-RADS score are present in schematic form for each acquisition as follows: T2-wi in the peripheral zone (Fig. 5); T2-wi in the transition zone (Fig. 6); DCE MRI (Fig. 7); DWI / ADC map (Fig. 8).
- Extra-prostatic involvement should also be scored using the same scale range of 1 to 5 [2].
The criteria for PI-RADS score are shown in the following figure (Fig. 9); these include extra-capsular extension and infiltration of the seminal vesicles,
distal sphincter and bladder neck [2].
Local staging of prostate cancer
- Local staging of prostate cancer is based on primary tumor classification proposed by the American Joint Committee on Cancer [25]; this classification is shown in the following figure (Fig. 10).
- Local staging of prostate cancer is usually performed using T2-wi acquisition,
but mp-MRI may also improve prostate cancer staging [3].
- Jurgen J.
Fütterer et al.
demonstrated in a large prospective study with 99 patients that staging accuracy of the prostate cancer diagnostic was significantly improved when acquisitions T2-wi and DCE-MRI were combined [3,
17].
- Acquisition mp-MRI is also useful in differentiating stage T1 / T2 (tumor confined to prostate) to stage T3 (early advanced disease regarding extracapsular extension or seminal vesicle invasion) and is preferred to other imaging methods [26].