Background information
Anamnestic information prior to MRI of the prostate
PSA
Determination of the serum prostate-specific antigen (PSA) value is an established
method for the early detection of prostate cancer. It is recommended in the S3 guidelines
for men starting at age 45. The probability of the presence of prostate cancer increases
as the PSA value increases. The PSA value, possibly also the ratio between the free
and total PSA value and, if available, information regarding the PSA curve and PSA
doubling time should be specified for every MRI examination [1].
Previous biopsies
A biopsy results in hemorrhage in the parenchyma. This has low signal intensity on
the T2w image and high signal intensity on the T1w image. A hemorrhage thus changes
the initial images of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted
imaging (DWI). The changes can be detectable many months after biopsy and can complicate
tumor detection. Therefore, the time at which the biopsy was performed should be indicated
[2]. Moreover, the number of biopsy specimens and the biopsy site, if available, should
be specified [1].
Histological results
With a previously negative prostate biopsy, the probability of a tumor diagnosis in
a new systematic biopsy decreases. Prostate MRI for tumor detection in combination
with a targeted biopsy can increase the detection rate in these cases. Therefore,
prostate MRI is particularly useful after a previous negative biopsy. In the case
of a positive biopsy, the number of positive core biopsies, the location of the positive
core biopsies, the Gleason grade of the tumor, and, if available, the size/infiltration
of the tumor in the core biopsy specimen should be specified. Therefore, a correlation
with the MRI finding is possible. On the one hand, the presence of additional tumor
foci can be detected and on the other hand it can be determined whether the present
biopsy was representative.
Additional information
Hormone therapy: The prostate is an androgen-sensitive organ. Hormone therapy results
in decreased activity of the gland function. MRI shows a reduction in prostate volume
and signal reduction of the gland on the T2w image. Delineation of the prostate zones
is more difficult or impossible. The effects of hormone therapy complicate tumor detection
on the T2w image and in DWI. Tumors are typically significantly smaller under hormone
therapy. The effects of hormone therapy on the prostate and also on prostate cancer
are typically noticeable after only 4 weeks of treatment [3].
Therapy with 5-alpha reductase inhibitors: During treatment with 5-alpha reductase
inhibitors, the volume of the prostate decreases with a volume reduction of the peripheral
zone and the transitional zone [4].
Radiotherapy: After radiotherapy, zonal structuring is eliminated and the peripheral
zone has low signal intensity. A volume reduction often occurs over the course. The
contour and the neurovascular bundle can be emphasized and the bladder wall and rectal
wall can be thickened [5]
[6].
Hematospermia: The changes correspond to those in hemorrhage after biopsy but are
less diffuse and are often also detectable in the seminal vesicle [7].
Clinical prostatitis and information regarding the treatment of prostatitis: Prostatitis
can show similar changes as in carcinoma of the prostate on MRI and can therefore
be difficult to differentiate from carcinoma. Prostatitis often shows extensive changes
without the displacement of structures and can be detected on the basis of a band-like,
wedge-shaped, diffuse rather than focal appearance. There are also overlaps in the
evaluation of DWI, DCE-MRI and 1H-MR spectroscopy (1H-MRS). Prostatitis typically shows low diffusion restriction, a low signal amplitude,
and no rapid decrease in signal enhancement after peak enhancement in DCE-MRI [8].
Previous operations in the small pelvis: Transurethral resection (TUR-P) of benign
prostate hyperplasia (BPH) leaves a typical defect in the central zone. The remaining
peripheral zone usually has mildly reduced signal intensity. Since BPH nodules occasionally
develop again in the periphery, the time at which TUR-P was performed and information
regarding treatment success, if available, is helpful. Rectal resection and rectal
amputation as well as extensive repeat local treatment of bladder tumors can change
the prostate and the tissue surrounding the prostate.
Creatinine and eGFR
When using gadolinium-containing contrast agent in DCE-MRI, factors concerning the
patient and properties of the contrast agent must be taken into consideration. The
Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency
(EMA) evaluated the risk for gadolinium-containing contrast agents and the occurrence
of nephrogenic systemic fibrosis (NSF). This evaluation provides the basis for the
application recommendations of the European Society for Urogenital Radiology (ESUR).
The following risk classes for gadolinium-containing contrast agents and patients
were defined [9]: high risk: gadodiamide, gadopentetate dimeglumine and generics, gadoversetamide;
medium risk: gadobenate dimeglumine, gadofosveset trisodium, gadoxetate disodium;
low risk: gadobutrol, gadoteridol, gadoterate-meglumine. High-risk contrast agents
are contraindicated in patients with a GFR < 30 ml/min and in patients requiring dialysis.
Determination of the serum creatinine (eGFR) and a clinical evaluation, possibly via
questionnaire, are absolutely necessary [9]. Substances with an average or low risk should only be used with caution in patients
with an eGFR < 30 ml/min. It is not absolutely necessary to determine renal function.
If the serum creatinine was not determined, renal function should be recorded on the
questionnaire. The administered contrast agent dose should never be higher than 0.1 mmol/kg
body weight per examination and patient [9].
Examination scheduling and preparation
Time of examination
Bleeding into the prostate after a preceding biopsy can be detected for months in
the MRI examination and affects the ability to evaluate the examination. In the case
of MRI with the indication for tumor detection or active monitoring, a minimum time
of 6 weeks with respect to biopsy should be observed. In the case of MRI for local
tumor staging in histologically verified carcinoma, examination can be performed sooner
in order to provide the patient with definitive therapy as quickly as possible. MRI
to search for tumors can be performed at any time.
Antispasmodic
To improve image quality and to reduce artifacts caused by bowel movement, one to
two ampoules of butylscopolamine (20 – 40 mg) can be applied in fractionated doses
if not contraindicated. Alternatively, intravenous administration of one ampoule of
glucagon (1 mg) under consideration of the contraindications is possible. However,
there are no guidelines or studies verifying a clear improvement in the image quality
and diagnostic accuracy of prostate MRI as a result of the administration of an antispasmodic
[10]
[11]
[12].
Emptying the rectum
Air in the rectum can result in artifacts, particularly in the case of DWI. To reduce
these artifacts, patients should be required to empty the rectum and bladder prior
to examination. If significant air in the rectum is detected in the planning sequences,
decompression of the rectum via a rectal tube can be advantageous [12]. Enemas or laxatives should not be administered since these increase intestinal
peristalsis and can intensify artifacts.
Abstinence
Sexual abstinence on the part of the patient for 3 – 5 days can ensure greater filling
and thus better delineation of the seminal vesicle particularly in T2w sequences.
A clear advantage of a defined period of abstinence prior to MRI regarding the detection,
localization, and staging of prostate cancer has not yet been shown.
Examination protocol
The goal of the protocol should be the reliable detection and localization of significant
carcinomas of the prostate with a volume ≥ 0.5 ml and the detection of extracapsular
growth incl. infiltration of the seminal vesicle. For detection, MRI of the prostate
is useful both in the primary and the secondary indication since it was able to be
shown that targeted biopsy maximizes the detection rate of areas suspicious for carcinoma
on MRI in addition to systematic TRUS-guided biopsy [13]
[14]
[15].
A standardized protocol ensures comparability (e. g. during active monitoring) and
avoids unnecessary duplicate examinations. A combination of T2w imaging, DWI, and
DCE-MRI provides the highest diagnostic accuracy [16]. Studies that were not able to show a statistically significant advantage for the
use of DCE-MRI for detection were recently published [17]
[18]. Since the available data is still insufficient in our opinion, DCE-MRI should continue
to be used. For the diagnosis of local relapse after radiotherapy, MRI seems more
suitable than nuclear medicine methods for the detection of a recurrence near the
bladder.
Morphological T2w TSE/FSE sequences
T2w imaging via high-resolution T2w turbo spin echo (TSE) or fast spin echo (FSE)
sequences provides the basis for MRI of the prostate [19]. The sensitivity regarding prostate cancer detection varies in the literature between
36 % and 95 % which primarily depends on the cohort that was examined. To evaluate
the diagnostic quality of T2w imaging as a function of tumor size, it was shown in
a study with histological large-area sections that morphological T2w imaging alone
is not able to reliably rule out carcinoma foci smaller than 10 mm [20]. Therefore, morphological MRI must be supplemented by functional techniques. Carcinomas
are hypointense in T2w imaging. The differentiation between prostatitis and prostate
cancer can be difficult in the peripheral zone. In the transitional zone differentiation
particularly with respect to stromal hyperplasia, which is also hypointense, is difficult.
Nevertheless, T2w imaging is the most important sequence for detecting carcinomas
in the transitional zone. The differentiation criterion here is primarily the architectural
distortion followed by size [12]. Morphological T2w sequences are decisive for determining the location of focal
lesions. A targeted biopsy can be performed on this basis in the next step. In the
case of non-cognitive fusion techniques, the transverse T2w DICOM dataset can be used
for automatic fusion [21].
DWI, DCE-MRI, 1H-MRS
DWI: Carcinomas of the prostate with increased cell density decrease the size of the
interstitial space and displace, compress, or destroy the glandular ducts. This limits
the free particle mobility that can be detected with DWI [22].
DWI is typically comprised of images with single-shot-echo-planar-imaging (SSEPI)
sequences with a low diffusion-weighted gradient (b-value between 0 and 150 s/mm2) and at least one high diffusion-weighted gradient (b-value between 800 and 1500 s/mm2). Higher b-values have been used with varied results. With a mono-exponential function,
the so-called apparent diffusion coefficient (ADC) can be determined using the particular
image datasets with the low and the high b-value for each image point and the numerical
value can be shown with color coding [22].
In DWI, healthy prostate tissue shows a high signal at low b-values and significant
signal reduction at high b-values. The ADC values qualitatively show the significant
signal difference. Carcinomas of the prostate with a low percentage of water and limited
particle mobility show a low signal at a low b-value and a constant to significantly
increasing signal at a high b-value. The ADC values qualitatively show the minimal
signal difference. A low ADC value is quantitatively present. There is a correlation
between the increasing biological aggressiveness of carcinomas of the prostate and
the decreasing ADC value in DWI [23].
The sensitivity and specificity of DWI alone for the detection of carcinoma of the
prostate are specified in a current meta-analysis including a total of 1204 patients
as 62 % and 90 %, respectively [24]. In a meta-analysis including a total of 698 patients with a previous negative prostate
biopsy, the average sensitivity of DWI for detecting a carcinoma of the prostate is
38 % and the average specificity is 95 % [25]. The test quality parameters are slightly better for the combination of T2w images
with DWI than for T2w images alone [26].
Under external radiotherapy of the prostate, the ADC value in carcinomas of the prostate
increases significantly but does not change substantially in healthy prostate tissue
[27].
DCE-MRI: DCE-MRI includes the fast acquisition of T1w sequences after bolus application
of a gadolinium-containing contrast agent and is established in clinical oncology
as a biomarker [28]. DCE-MRI should always be interpreted in combination with DWI and T2w imaging which
is facilitated by the use of the same slice thicknesses. DCE-MRI significantly increases
the accuracy of tumor detection and lesion evaluation and DCE-MRI increases the sensitivity
for tumor detection particularly in the peripheral zone [29]
[30]. A high temporal resolution (at least 9 seconds) is a requirement for being able
to measure the rapid enhancement of contrast agent in the prostate [31]. DCE-MRI is essential particularly for diagnosing recurrence after prostatectomy
or radiotherapy [32].
1H-MRS: Three-dimensional 1H-MRS can localize carcinomas of the prostate as part of MRI examination [33]. Results of T1w/T2w imaging and 1H-MRS that are consistently suspicious for prostate cancer indicate the presence of
cancerous prostate tissue with a probability of approximately 50 % (positive predictive
value) with the important differential diagnosis of focal circumscribed prostatitis.
Conversely, results of T1w/T2w imaging and 1H-MRS that are consistently negative indicate the presence of healthy prostate tissue
with a probability of approximately 95 % (negative predictive value) with the differential
diagnosis of diffuse prostatitis [34]. The sensitivity and specificity of 1H-MRS combined with individual MRI sequences were 58 % and 93 %, respectively, for
the detection of carcinoma of the prostate in a current meta-analysis of 14 studies
including a total of 698 patients with a previous negative prostate biopsy [25]. The ability to differentiate between healthy and cancerous prostate tissue is fundamentally
maintained with 1H-MRS even after treatment of the prostate (e. g. hormone therapy, radiotherapy, cryotherapy)
[33].
T1w TSE/FSE sequence
The T1w sequence is used to evaluate bone and lymph nodes. For morphological detection
of pathological lymph nodes, it is useful to visualize the entire pelvis from the
aortic bifurcation to the pelvic floor. Bone marrow metastases of prostate cancer
are hypointense and focal in T1w sequences. It is important to observe that spin-echo
or fast spin-echo and TSE or FSE sequences are used since gradient echo sequences
distort the bone marrow signal and can thus mask bone marrow metastases. For the prostate,
a T1w sequence is also useful for detecting post-biopsy or inflammatory bleeding.
This has a hyperintense appearance in T1w sequences and can thus be effectively delimited
from the surrounding tissue [2].
Endorectal coil
In MRI examinations with a field strength of 1.5 T, the application of a combined
endorectal body phased-array coil is superior to the exclusive use of a phased-array
coil without an endorectal coil with respect to image quality and local staging [26]. By using a combined endorectal body phased-array coil, the sensitivity and the
positive predictive value for the detection of prostate cancer could be increased
in individual studies even in 3 T MRI examinations [27]. The sole use of a body phased-array coil at 3 T as widely used in practice is justified
by the good detection of significant tumors [28]. Use of the combined endorectal body phased-array coil at 3 T can improve local
staging, particularly the evaluation of extracapsular growth [35]. When using an endorectal coil, it should be filled with air. To reduce susceptibility
artifacts, the balloon for spectroscopy can be filled with distilled water or Fomblin
Med 08 (Solvay, Brussels, Belgium) as an alternative to air. However, using Fomblin
for this purpose in Germany represents an off-label use.
Further sequences
The contrast properties of T2w 3D-TSE/FSE sequences (multiecho sequences with variable
flip angles) for the detection of prostate cancer compared to T2w 2D-TSE sequences
have not been sufficiently studied. However, a study with a low case number could
not show inferiority of the 3 D sequence compared to the classic 2 D sequence for
the detection and the staging of a carcinoma of the prostate in the peripheral zone
[36]. Therefore and due to the increased susceptibility to motion artifacts, this sequence
should not be used to detect prostate cancer. A higher diagnostic accuracy of the
3 D sequence regarding extracapsular extension could be shown in a further study regarding
local staging also with a low number of cases [37]. Due to the isotropic voxels, the 3 D sequence can however be advantageous for fusion
with other imaging methods (in particular ultrasound).
Complex techniques of diffusion-weighted imaging take into consideration the microstructural
complexity of prostate cancer [38]. Intravoxel incoherent motion imaging (IVIM) takes into consideration the multiexponential
behavior of the diffusion signal at different b-values and the influence of the perfusion
components of the signal at low b-values. Diffusion kurtosis imaging (DKI) takes into
consideration the kurtosis of the tissue which refers to the deviation from the Gaussian
distribution [39]. These complex diffusion models are a current topic of research. The currently available
data do not show a significant advantage of these methods compared to classic diffusion
weighting and should therefore not be used for diagnosis at this time [39].
Further techniques, such as diffusion tensor imaging, BOLD imaging, MR elastography
and T2 mapping, are also currently under development and should therefore not be used
outside of studies.
MRI-guided in-bore biopsy
The most accurate MRI-guided biopsy method for histological confirmation of MRI lesions
is targeted biopsy in the MRI tube [40]. Possible accesses described in the literature are transrectal, transperineal, and
transgluteal. MRI (in-bore) biopsy should be performed under local anesthesia. The
use of a gel anesthesia was associated in a transrectal setting with a low level of
pain (VAS 1 – 2 in 297/297 patients) [40].
Studies show high detection rates both for patients without a previous biopsy and
with a negative prior biopsy [14]
[41]
[42]. MRI (in-bore) biopsy can be performed alternatively to MRI/US fusion biopsy in
the secondary indication [41]. As an alternative to MRI-guided biopsy methods, MRI/US fusion biopsy and cognitive
ultrasound biopsy can be used. MRI (in-bore) and fusion-based biopsy methods tend
to be superior to simple cognitive biopsy [43]. However, valid prospective comparison data is not currently available [44].
Laboratory
Conventional coagulation testing with International Normalized Ratio (INR), activated
partial thromboplastin time (aPTT), and thrombocyte number is a poor predictor of
the intraoperative bleeding risk and is not capable of detecting the most common blood
coagulation disorders (von Willebrand factor deficiency and thrombocyte dysfunction)
[45]. A standardized questionnaire for recording bleeding history, prior operations and
traumas, familial bleeding diathesis, and coagulation-inhibiting medication is therefore
essential. Coagulation testing is mandatory in the case of the suspicion of a coagulation
disorder given a positive bleeding history or if the patient is taking oral anticoagulants.
A biopsy in the case of clinical signs of an acute urinary tract infection, such as
burning during urination, should be avoided.
Anticoagulants
The taking of acetylsalicylic acid (ASS) during a surgical intervention increases
the risk of a bleeding complication by the factor of 1.5 without increasing the fatality
rate [46]. The current guidelines of the European Society of Cardiology recommend continued
periinterventional administration of ASS at a dose of 100 mg p. o. [47]. In patients with implanted coronary stents, a prostate biopsy – as an elective
intervention – should only take place after dual thrombocyte aggregation inhibition
(ASS + ADP antagonist (clopidogrel)) has ended and monotherapy with ASS has begun
[48].
A prostate biopsy under vitamin K antagonists (Marcumar) requires interdisciplinary
consideration. It is recommended to discontinue anticoagulation therapy if possible.
A subtherapeutic INR is achieved between four and seven days after discontinuation
[48]. In principle, a biopsy of the prostate can however also be performed while taking
a vitamin K antagonist.
Antibiotics
Based on the recommendations of the S3 guidelines for transrectal ultrasound-guided
biopsy in carcinoma of the prostate, it is recommended to perform transrectal MRI
biopsy with antibiotic prophylaxis. It was able to be shown that antibiotic prophylaxis
significantly lowers the rate of bacteriuria after core biopsy as a possible surrogate
parameter for an infection [49]. The typically lower number of core biopsy specimens in MRI biopsy may also contribute
to a lower infection rate. Quinolones are the antibiotic of choice in transrectal
biopsy [50]. In recent years an increase in infectious complications after prostate biopsy has
been described [51].