Section IV: Multiparametric MRI (mpMRI)
A. T1-Weighted (T1W) and T2-Weighted (T2W)
Both T1W and T2W sequences should be obtained for all prostate MR exams. T1W images are used primarily to determine the presence of hemorrhage within the prostate and seminal vesicles and to delineate the outline of the gland. T1W images may also useful for detection of nodal and skeletal metastases, especially following intravenous administration of a gadolinium-based contrast agent (GBCA).
T2W images are used to discern prostatic zonal anatomy, assess abnormalities within the gland, and to evaluate for seminal vesicle invasion, EPE, and nodal involvement.
On T2W images, clinically significant cancers in the PZ usually appear as round or ill-defined hypointense focal lesions. However, this appearance is not specific and can be seen in various conditions such as prostatitis, hemorrhage, glandular atrophy, benign hyperplasia, biopsy related scars, and after therapy (hormone, ablation, etc.).
The T2W features of TZ tumors include non-circumscribed homogeneous, moderately hypointense lesions (“erased charcoal” or “smudgy fingerprint” appearance), spiculated margins, lenticular shape, absence of a complete hypointense capsule, and invasion of the urethral sphincter and anterior fibromuscular stroma. The more features present, the higher the likelihood of a clinically significant TZ cancer.
TZ cancers may be difficult to identify on T2W images since the TZ is often composed of variable amounts of glandular (T2-hyperintense) and stromal (T2-hypointense) tissue intermixed with each other, thus demonstrating heterogeneous signal intensity. Areas where benign stromal elements predominate may mimic or obscure clinically significant cancer.
Both PZ and TZ cancers may extend across anatomical boundaries. Invasive behavior is noted when there is extension within the gland (i.e. across regional parts of the prostate), into the seminal vesicles, or outside the gland (EPE).
1. Technical Specifications
T2W
Multiplanar (axial, coronal, and sagittal) T2W images are usually obtained with 2D RARE (rapid acquisition with relaxation enhancement) pulse sequences, more commonly known as fast-spinecho (FSE) or turbo-spin-echo (TSE). In order to avoid blurring, excessive echo train lengths should be avoided.
• Slice thickness: 3mm, no gap. Locations should be the same as those used for DWI and DCE
• FOV: generally 12-20 cm to encompass the entire prostate gland and seminal vesicles
• In plane dimension: ≤ 0.7mm (phase) x ≤0.4mm (frequency)
3D axial acquisitions may be used as an adjunct to 2D acquisitions. If acquired using isotropic voxels, 3D acquisitions may be particularly useful for visualizing detailed anatomy and distinguishing between genuine lesions and partial volume averaging effects. However, the soft tissue contrast is not identical and in some cases may be inferior to that seen on 2D T2W images, and the in-plane resolution may be lower than their 2D counterpart.
T1W
Axial T1W images of the prostate may be obtained with or without fat suppression using spin echo or gradient echo sequences. Locations should be the same as those used for DWI and DCE, although lower spatial resolution compared to T2W may be used to decrease acquisition time or increase anatomic coverage.
2. PI-RADS Assessment for T2W
Score Peripheral Zone (PZ)
1 Uniform hyperintense signal intensity (normal)
2 Linear or wedge-‐shaped hypointensity or diffuse mild hypointensity, usually indistinct margin
3 Heterogeneous signal intensity or non-‐circumscribed, rounded, moderate hypointensity – Includes others that do not qualify as 2, 4, or 5 4
4 Circumscribed, homogenous moderate hypointense focus/mass confined to prostate and <1.5 cm in greatest dimension
5 Same as 4 but ≥1.5cm in greatest dimension or definite extraprostatic extension/invasive behavior
Score Transition Zone (TZ)
1 Homogeneous intermediate signal intensity (normal)
2 Circumscribed hypointense or heterogeneous encapsulated nodule(s) (BPH)
3 Heterogeneous signal intensity with obscured margins – Includes others that do not qualify as 2, 4, or 5 4
4 Lenticlular or non-‐circumscribed, homogeneous, moderately hypointense, and <1.5 cm in greatest dimension
5 Same as 4, but ≥ 1.5cm in greatest dimension or definite extraprostatic extension/invasive behavior
B. Diffusion-Weighted Imaging (DWI)
Diffusion-weighted imaging (DWI) reflects the random motion of water molecules and is a key component of the prostate mpMRI exam. It should include an ADC map and high b-value images.
The ADC map is a display of ADC values for each voxel in an image. In most current clinical implementations, it uses two or more b-values and a monoexponential model of signal decay with increasing b-values to calculate ADC values. Most clinically significant cancers have restricted/impeded diffusion compared to normal tissues and, thus, appear hypointense on grey-scale ADC maps. Although ADC values have been reported to correlate inversely with histologic grades, there has been considerable overlap between BPH, low grade cancers, and high grade cancers. Furthermore, ADC calculations are influenced by choice of b-values and have been inconsistent across vendors. Thus, qualitative visual assessment is often used as the primary method to assess ADC. Nevertheless, ADC values, using a threshold of 750-900 μm2/sec, may assist differentiation between benign and malignant prostate tissues in the PZ, with ADC values below the threshold correlating with clinically significant cancers.
“High b-value” images utilize a b-value between >1400 sec/mm2. They display preservation of signal in areas of restricted/impeded diffusion compared with normal tissues, which demonstrate diminished signal due to greater diffusion between application of gradients with different b-values. Compared to ADC maps alone, conspicuity of clinically significant cancers is sometimes improved on high b-value images, especially in those adjacent to or invading the anterior fibromuscular stroma, in a subcapsular location, and at the apex and base of the gland. High b-value images can be obtained in one of two ways: either directly by acquiring a high b-value DWI sequence (requiring additional scan time), or by calculating (synthesizing) the high b-value image by extrapolation from the acquired lower b-value data used to create the ADC map (potentially less prone to artifacts because it avoids the longer TEs required to accommodate the strong gradient pulses needed for high b-value acquisitions). As the bvalue increases, the signal-to-noise ratio (SNR) decreases, so that the optimum high b-value may be dependent on magnetic field strength, software, and manufacturer. Thus, there is no currently widely accepted optimal “high b-value”, but if adequate SNR permits, b-values of 1400- 2000 sec/mm2 or higher seem to be advantageous.
1. Technical Specifications
Free-breathing spin echo EPI sequence combined with spectral fat saturation is recommended.
• TE: ≤ 90 msec; TR : > 3000 msec
• Slice thickness: ≤4mm, no gap. Locations should match or be similar to those used for T2W and DCE
• FOV: 16-22 cm
• In plane dimension: ≤ 2.5mm phase and frequency
• Echotrain length: 50-60 with parallel imaging factor of 2 For ADC maps, if only two b-values can be acquired due to time or scanner constraints, it is preferred that the lowest b-value should be set at 50-100 sec/mm2 and the highest should be 800-1000 sec/mm2. Additional b-values between 100 and 1000 may provide more accurate ADC calculations and estimations of extrapolated high b-value images (>1400 sec/mm2).
Information regarding perfusion characteristics of tissues may be obtained with additional bvalues ranging from 0 to 500 sec/mm2,
2. PI-RADS Assessment of DWI Signal intensity
Signal intensity in a lesion should be visually compared to the average signal of “normal” prostate tissue in the histologic zone in which it is located.
Score Peripheral Zone (PZ) or Transition Zone (TZ)
1 No abnormality (i.e. normal) on ADC and high b-‐value DWI
2 Indistinct hypointense on ADC
3 Focal mildly/moderately hypointense on ADC and isointense/mildly hyperintense on high b-‐value DWI.
4 Focal markedly hypontense on ADC and markedly hyperintense on high b-‐value DWI; <1.5cm in greatest dimension
5 Same as 4 but ≥1.5cm in greatest dimension or definite extraprostatic extension/invasive behavior
3. Caveats for DWI
• Findings on DWI should always be correlated with T2W, T1W, and DCE.
• Due to technical issues, units of signal intensity have not been standardized across different MRI scanners and are not analogous to Hounsfield units of density on CT. As a result, there are no standardized “prostate windows” that are applicable to images obtained from all MRI scanners. Clinically significant cancers have restricted/impeded diffusion and should appear as hypointense on the ADC map. It is strongly recommended that ADC maps from a particular scanner are set to portray clinically significant prostate cancers so that they appear markedly hypointense on ADC maps, and they should be consistently viewed with the same contrast (window width and level) settings. Guidance from radiologists who have experience with a particular vendor or scanner may be helpful.
• Color-coded maps of ADC may assist in standardization of viewing and assessing images from a particular scanner or vendor, but they will not obviate the concerns with reproducibility of quantitative ADC values.
• Benign findings and some normal anatomy (e,g. calculi and other calcifications, areas of fibrosis or dense fibromuscular stroma, and some blood products, usually from prior biopsies) may exhibit no or minimal signal on both T2W and ADC because there is insufficient signal. However, in contrast to clinically significant prostate cancers, these entities will also be markedly hypointense on all DWI images.
• Some BPH nodules in the TZ are not clearly encapsulated, and they may exhibit hypointensity on ADC maps and hyperintensity on high b-value DWI. Although morphologic features may assist assessment in some cases, this is currently a recognized limitation of mpMRI diagnosis.
An encapsulated, circumscribed, round nodule in the PZ is likely an extruded BPH nodule, even if it is hypointense on ADC. PIRADS Assessment Category for this finding should be 2.
C. Dynamic Contrast-Enhanced (DCE) MRI
DCE MRI, is defined as the acquisition of rapid T1W gradient echo scans before, during and after the intravenous administration of a low molecular weight gadolinium-based contrast agent (GBCA). As with many other malignancies following bolus injection of a GBCA, prostate cancers often demonstrate early enhancement compared to normal tissue. However, the actual kinetics of prostate cancer enhancement are quite variable and heterogeneous. Some malignant tumors demonstrate early washout, while others retain contrast longer. Furthermore, enhancement alone is not definitive for clinically significant prostate cancer, and absence of early enhancement does not exclude the possibility.
DCE should always be closely inspected for focal early enhancement. If found, then the corresponding T2W and DWI images should be carefully interrogated, as subtle lesions which may be small but clinically significant cancers, may initially be missed. However, most published data show that the added value of DCE over and above the combination of T2W and DWI is modest. Thus, although DCE is an essential component of the mpMRI prostate examination, in PI-RADSv2, its role in determination of PI-RADS Assessment Category is secondary to T2W and DWI.
DCE is positive when there is enhancement that is focal, earlier or contemporaneous with enhancement of adjacent normal prostatic tissues, and usually corresponds to a suspicious finding on T2W and/or DWI. Positive enhancement in a lesion usually occurs within 10 seconds of the appearance of the injected GBCA in the femoral arteries (depending on temporal resolution used to acquire the images, injection rate, cardiac output, and other factors).
The most widely available method of analyzing DCE is direct visual assessment of the individual DCE time-points at each slice location by either manually scrolling or using cine mode. Visual assessment of enhancement may be improved with fat suppression or subtraction techniques (especially in the presence of blood products that are hyperintense on pre-contrast enhanced T1W). Visual assessment of enhancement may also be assisted with a parametric map which color-codes enhancement features within a voxel (e.g. slope and peak). However, any suspicious finding on subtracted images or a parametric map should always be confirmed on the source images.
Considerable effort has gone into “curve typing” (i.e. plotting the kinetics of a lesion as a function of signal vs. time). However, there is great heterogeneity in enhancement characteristics of prostate cancers, and at present there is little evidence in the literature to support the use of specific curve types. Another approach is the use of compartmental pharmacokinetic modeling, which incorporates contrast media concentration rather than raw signal intensity and an arterial input function to calculate time constants for the rate of contrast agent wash-in (Ktrans) and wash-out (kep). Commercial software programs are available that produce “maps” of Ktrans and kep and may improve lesion conspicuity. Although pharmacodynamic (PD) analysis may provide valuable insights into tumor behavior and biomarker measurements for drug development, the PI-RADS Steering Committee believes there is currently insufficient peer reviewed published data or expert consensus to support routine adoption of this method of analysis for clinical use.
Thus, for PI-RADS v2, a “positive” DCE MRI lesion is one where the enhancement is focal, earlier or contemporaneous with enhancement of adjacent normal prostatic tissues, and corresponds to a finding on T2W and/or DWI. In the TZ, BPH nodules frequently enhance early, but they usually exhibit a characteristic benign morphology (round shape, well circumscribed). A “negative” DCE MRI lesion is one that either does not enhance early compared to surrounding prostate or enhances diffusely so that the margins of the enhancing area do not correspond to a finding on T2W and/or DWI.
1. Technical Specifications
DCE is generally carried out for several minutes to assess the enhancement characteristics. In order to detect early enhancing lesions in comparison to background prostatic tissue, temporal resolution should be <10 seconds and preferably <7 seconds per acquisition in order to depict focal early enhancement. Fat suppression and/or subtractions is recommended. Although either a 2D or 3D T1 gradient echo (GRE) sequence may be used, 3D is preferred.
• TR/TE: <100msec/ <5msec
• Slice thickness: 3mm, no gap. Locations should be the same as those used for DWI and DCE
• FOV: encompass the entire prostate gland and seminal vesicles
• In plane dimension: ≤2mm X ≤2mm
• Temporal resolution: ≤15sec (<7sec is preferred)
• Total observation rate: >2min • Dose: 0.1mmol/Kg standard GBCA or equivalent high relaxivity GBCA
• Injection rate: 2-3cc/sec starting with continuous mage data acquisition (should be the same for all exams)
2. PI-RADS Assessment for DCE
Score Peripheral Zone (PZ) or Transition Zone (TZ) for DCE
(-) no early enhancement, or diffuse enhancement not corresponding to a focal finding on T2 and/or DW or focal enhancement corresponding to a lesion demonstrating features of BPH on T2WI
(+) focal, and; earlier than or contemporaneously with enhancement of adjacent normal prostatic tissues, and; corresponds to suspicious finding on T2W and/or DWI
Caveats for DCE
• DCE should always be interpreted with T2W and DWI; Focal enhancement in clinically significant cancer usually corresponsds to focal findings on T2W and/or DWI.
• DCE may be helpful when evaluation of DWI in part or all of the prostate is technically compromised (i.e. Assessment Category X) and when prioritizing multiple lesions in the same patient (e.g. all other factors being equa, the largest DCE positive lesion may be considered the index lesion).
• Diffusely positive DCE is usually attributed to inflammation (e.g. prostatitis). Although infiltrating cancers may also demonstrate diffuse enhancement, these are uncommon and usually demonstrate an abnormality on the corresponding T2W and/or DWI.
• There are instances where histologically sparse prostate cancers are intermixed with benign prostatic tissues. They may be occult on T2W and DWI, and anecdotally may occasionally be apparent only on DCE. However, these are usually lower grade tumors, and the enhancement might, in some cases, be due to concurrent prostatitis.