1. Dr Mohit Goel
JRIII
20/9/14
AND RECENT ADVANCEMENTS
Imaging Prostate Cancer: A Multidisciplinary Perspective
Advancements in MR Imaging of the Prostate: From Diagnosis to Interventions
A clinically relevant approach to imaging prostate cancer: review.
2. CT does not provide sufficient soft-tissue contrast beyond size assessment of
the prostate. Although CT is valuable in the evaluation of pelvic
lymphadenopathy and bone metastases, MR imaging and bone scanning have
been found superior in their assessment.
3. Prostate is divided from superior to inferior into the base (just
below the urinary bladder), the midgland, and the apex.
In the axial plane, the prostate is divided into four zones:
(a)the anterior fibromuscular stroma, which contains no glandular
tissue;
(b)the transition zone surrounding the urethra, which contains
5% of the glandular tissue;
(c)the central zone, which contains 20% of the glandular tissue; &
(d)the outer peripheral zone, which contains
70%–80% of the glandular tissue.
The volume of the peripheral zone increases
from the base to the apex of the gland.
4. Ninety-five percent of prostate cancers are adenocarcinomas that
develop from the acini of the prostatic ducts.
Thus, prostate cancers arise in the glandular tissue, with about 70%
originating in the peripheral zone, 25% in the transition zone, and 5%
in the central zone.
At imaging, the transition zone cannot be separated from the central
zone; therefore, these two zones are often referred to together as the
central gland.
11. The prostate does not have a true capsule, only an outer band of
concentric fibromuscular tissue that is an inseparable component
of the prostatic stroma..
The outer-layer “capsule” is most apparent posteriorly and
posterolaterally; it is seen at MR imaging as a thin layer of tissue
that is dark on T2WI.
The capsule is an important landmark for assessment of
extraprostatic tumor extension, since irregularities, bulges, and
disruptions of the capsule are signs of tumor invasion or spread
outside the confines of the prostate.
12. The periprostatic neurovascular bundles course posterolateral to
the prostate bilaterally.
They are well seen at imaging at the 5-o'clock and 7-o'clock
positions in reference to the prostate .
At the apex and base, the nerve bundles send penetrating
branches through the capsule, which provide a route for
extraprostatic tumor extension.
14. Transrectal US is primarily used to guide prostate biopsies, but
new developments in microbubble contrast agents offer the
possibility of improving prostate cancer detection by detecting
tumor angiogenesis.
When prostate cancer is suspected, the diagnostic test of choice is
a systematic needle biopsy with US guidance.
Cores are typically obtained from six areas, or sextants, of the
peripheral zone: left and right apex, left and right midgland, and
left and right base.
Cancer, depending on its size, grade, and location, usually appears
hypoechoic relative to the normal peripheral zone of the prostate
15.
16. Many cancers detected at biopsy are not visible at US (low
sensitivity) and many hypoechoic areas do not prove to be
malignant at biopsy (low specificity); therefore, transrectal US
alone, without the addition of biopsy, has limited value in the
detection of cancer.
The criteria for identifying extracapsular extension (ECE) on
transrectal US scans are bulging or irregularity of the capsule
adjacent to a hypoechoic lesion.
The length of the contact of a visible lesion with the capsule is also
associated with the probability of ECE.
17.
18. Seminal vesicle invasion (SVI) is heralded by a visible extension of a
hypoechoic lesion at the base of the prostate into a seminal vesicle
or by echogenic cancer within the normally fluid-filled seminal
vesicle.
Asymmetry of the seminal vesicles or solid hypoechoic masses
within the seminal vesicles are indirect indicators of disease
extension.
TRUS continues to play an important role in therapy. Worldwide,
TRUS is the modality of choice for directing brachytherapy seeds
into the prostate.
Cryotherapy of the prostate also requires US guidance as does
high-intensity focused ultrasound, which, coupled with US
targeting, is used for focal ablation of prostate cancers.
19. New treatment approaches such as hyperthermia, photodynamic
therapy, direct injection of oncolytic viruses, tumor vaccines, and
gene therapy also depend on transrectal US for easy access to
cancers of the prostate.
Future developments in transrectal US include the use of
microbubble contrast agents and targeted imaging.
20. it has virtually no role in prostate cancer
detection or primary tumor staging.
The major role of CT is in the nodal
staging of prostate cancer.
CT has been used to monitor bone
metastases, but bone scanning and MR
imaging are superior to CT in the
diagnosis of bone metastases.
Lytic and blastic bone metastases will
commonly be visible at CT.
21. Reduced diffusion of water in prostate cancer has been attributed to
the increased cellularity of malignant lesions, with reduction of the
extracellular space and restriction of the motion of a larger portion
of water molecules to the intracellular space.
Therefore, diffusion-weighted imaging provides an important
quantitative biophysical parameter that can be used to differentiate
benign from malignant prostate tissue.
22. DWI is effective in detecting recurrent disease after radiation
therapy or surgery. Subtle changes in apparent diffusion
coefficient detected on DWI images are indicative of recurrent
disease in patients with increasing PSA levels after treatment.
DWI improves detection of nodal disease with the use of
lymphotropic superparamagnetic nanoparticles as a contrast agent
at MR imaging. The nanoparticles are taken up by circulating
macrophages, which then traffic to the normal nodal tissue.
The inability of malignant nodes to take up the agent provides
tissue contrast within the lymph node and allows detection of
metastases, even in nodes that do not meet the standard size
criteria for metastasis.
23. MR spectroscopy provides important information about the biochemical and
metabolic environment of the tissue, it is increasingly being used as a biomarker
for detection of cancers, including prostate cancer.
MR spectroscopy of the prostate requires use of multivoxel volume selection
techniques
Citrateis found in fairly high concentrations in healthy prostate
epithelium and prostatic fluid; it is found in low concentrations
elsewhere in tissue.
The normal prostate has an MR spectrum with a prominent citrate
peak at 2.6 ppm, which is usually seen as a doublet with occasional
visualization of small additional side peaks.
A decreased citrate level is found in prostate cancer, as well as in
prostatitis and hemorrhage.
24. Choline is represented at 3.2 ppm.
Owing to increased cell membrane turnover and increased cell
surface compared with cell volume in cellular tumors, choline
concentrations are increased in prostate cancer.
Increased choline signal or concentration is considered the
spectroscopic hallmark of cancer; however, it has also been found
in benign conditions of the prostate such as prostatitis.
An increase in the choline-to-citrate ratio or the (choline +
creatine)/citrate ratio is often used as a marker of malignancy in
prostate cancer and increases the specificity of diagnosis; however,
it is most reliable in the peripheral zone.
25.
26.
27.
28. BPH shows significant overlap with the findings of prostate cancer.
In addition, prostatitis has previously been found to be able to
mimic prostate cancer.
This leads to possible significant difficulty in distinguishing prostate
cancer from prostatitis and stromal BPH, especially in the transition
zone.
When combined with anatomic imaging, MR spectroscopy has been
found to increase the accuracy of tumor volume estimation in
prostate cancer.
29. DCE MR imaging is an advanced prostate imaging modality that allows
derivation of parameters that are closely related to microvascular
properties and angiogenesis in tissues.
In prostate cancer, increased tumor vascularity leads to early
hyperenhancement (higher and earlier peak enhancement than in
normal tissue) and to rapid washout of contrast material from the
tumor, in comparison with normal prostate tissue.
Microvascular alterations and neovascularity are in general most
severe in prostate cancer, in comparison with other processes in the
prostate such as BPH or prostatic intraepithelial neoplasia.
30. The normal prostate is a vascular organ, and so rapid injections with
rapid scanning are needed to detect angiogenesis in a lesion.
Typically, a full dose (0.1 mmol/kg) of gadolinium chelate is injected
at 3 mL/sec, and serial 3D acquisitions are obtained every 2–5
seconds through the prostate.
Cancers often demonstrate early nodular enhancement before the
rest of the parenchyma and early washout of signal intensity. This
pattern is highly predictive of prostate cancer but is not
pathognomonic.
Some prostate cancers are mildly or moderately hypervascular and
thus are not detectable with this method.
Combining dynamic contrast-enhanced MR imaging and 3D proton
spectroscopy may prove helpful in tumor localization when T2-
weighted images are inconclusive for a tumor focus.
32. In prostate cancer, there is early, rapid, and intense enhancement
with quick washout of contrast material.
The presence of washout is highly indicative of prostate cancer,
even in the absence of low T2 signal intensity.
33. Criteria for extracapsular extension or seminal vesicle invasion at
DCE MR imaging include:
1. abnormally high or asymmetric peak enhancement,
2. contrast agent washout, and
3. short onset time and
4. Short time to peak enhancement.
In the case of extracapsular extension, these findings are detected
near the neurovascular bundle or rectoprostatic angle, broadly
abutting the capsule, or in an extracapsular location.
34.
35. On T2WI, the normal peripheral zone has homogeneous high signal intensity and
the central gland has variable amounts of intermediate signal intensity, which is
often replaced by well-circumscribed hyperplastic nodules of BPH.
36.
37.
38.
39.
40. A series of studies in the late 1980s established that prostate cancer
is characterized by low T2 signal intensity replacing the normally
high T2 signal intensity in the peripheral zone.
However, the presence of decreased T2 signal intensity in the
peripheral zone is of limited sensitivity because some prostate
tumors are isointense.
This finding is also of limited specificity because there are other
possible causes of low T2 signal intensity in the peripheral zone,
including hemorrhage, prostatitis, scarring, atrophy, and effects of
radiation therapy, cryosurgery, or hormonal therapy.
Postbiopsy hemorrhage may hamper tumor detection. The imaging
appearance depends on the length of time between the biopsy and
MR imaging. A delay of 6–8 weeks is recommended.
41.
42. Prostate cancer arising in the transition zone poses additional
imaging difficulties because of the heterogeneity of signal intensity
in the central gland.
Findings supporting the diagnosis of a transition zone tumor
include :
1. a homogeneous low-signal-intensity region in the transition
zone,
2. poorly defined or spiculated lesion margins,
3. lack of a low-signal-intensity rim (seen commonly in association
with benign adenomatous nodules),
4. interruption of the surgical pseudocapsule (transition zone–to–
peripheral zone boundary of low signal intensity),
5. urethral or anterior fibromuscular stromal invasion, and
6. lenticular shape
43.
44.
45. The most important aspect of local staging is differentiation between
organ-confined disease (stage T1 or T2) and early advanced disease
in the form of extracapsular extension or seminal vesicle invasion
(stage T3).
46.
47. Criteria for extracapsular extension include:
1. Asymmetry of the neurovascular bundle,
2. Tumor encasement of the neurovascular bundle,
3. A bulging prostatic contour,
4. An irregular or spiculated margin,
5. Obliteration of the rectoprostatic angle,
6. Capsular retraction,
7. A tumor-capsule interface of greater than 1 cm, and
8. A breach of the capsule with evidence of direct tumor extension
50. The features of seminal vesicle invasion at endorectal MR imaging
include:
1. disruption or loss of the normal architecture of the seminal
vesicle
2. focal low signal intensity within and along the seminal vesicle,
3. enlarged low-signal-intensity ejaculatory ducts & seminal
vesicle,
4. obliteration of the angle between the prostate and the
seminal vesicle, and
5. demonstration of direct tumor extension from the base of the
prostate into and around the seminal vesicle
51.
52.
53. It has no role in prostate cancer detection or local staging;
however, bone scanning continues to be the mainstay of diagnosis
of initial spread of cancer to bone – BONE METS.
A focal area of increased tracer uptake, usually in the axial
skeleton, related to host osteoblastic bone response to tumor
invasion.
However, other causes of altered marrow signal intensity (eg,
infection, infarction, trauma) can mimic metastatic disease at MR
imaging.
54.
55. Radionuclide bone scanning can also be used to assess the
response to treatment, as uptake usually decreases after
chemotherapy, hormone therapy, or radiation therapy if a response
is obtained.
In patients with prostate and breast cancer, a “flare” phenomenon
may be observed, where uptake initially increases after
chemotherapy or hormone therapy, peaking at 6 weeks after
treatment as bone turnover increases as part of the healing
process.
Care must be taken in this situation to avoid mistaking apparent
new lesions for areas of new metastatic disease, when subtle
changes were in fact present in prior studies.
56. Single photon emission computed tomographic (SPECT)
SPECT studies of the skeleton have been shown to be more
sensitive in the detection of metastatic disease than planar images
alone.
This technique has particular utility in the evaluation of the spine in
patients with low back pain who present for evaluation of possible
metastatic disease.
Sites of abnormal uptake may be localized to the vertebral body or
posterior elements, leading to other radiologic techniques for
confirmation.
Combined SPECT/CT, a recent development, adds anatomic
information to SPECT.
58. PET uses compounds labeled with positron-emitting radioisotopes to
detect pathologic processes.
It is performed with the glucose analogue fluorine 18 (18F)
fluorodeoxyglucose (FDG).
Cancers have increased metabolism and utilize the less-efficient
glycolytic pathway, both of which lead to increased glucose analogue
uptake.
PET/CT demonstrate tumor location in the prostate bed and to
better assess pelvic lymph node disease.
FDG has limitations with regard to distinguishing tumors from
inflammation. Future applications of PET will therefore involve new
tracers, which are currently under clinical investigation
59.
60.
61. The fundamental impetus for the migration to higher static magnetic
field strengths lies in an increased SNR and increased spectral
resolution.
In comparison with 1.5-T imaging, improvements in spatial or
temporal resolution and in patient comfort—when no endorectal
coil is used—are possible.
Imaging without endorectal coils is feasible at 3 T and helps
decrease patients’ reluctance to undergo an uncomfortable and
invasive examination.
At 3 T, however, if endorectal coils are used, significant
improvements in localization and staging of prostate cancer have
been reported.
62. Voxel sizes for 3-T MR spectroscopy is smaller then 1.5-T MR
spectroscopy.
Smaller voxel sizes are desirable to reduce volume averaging of
tumors with periprostatic fat, the seminal vesicles, postbiopsy
hemorrhage, or periurethral tissues.
DWI is another low-SNR technique that benefits from higher field
strengths, allowing higher-quality imaging and higher spatial
resolution.
In summary, detection, localization, and staging of prostate cancer
benefit from the higher achievable spatial resolution and increased
SNR at 3 T, as tissue interfaces are better visualized and lower-
contrast structures are better identified.
63. Because MR imaging provides more detailed anatomic images of
the prostate than does transrectal US and because it has been
shown to be the most accurate imaging modality for localization of
prostate cancer, MR imaging–based guidance offers the possibility
of more precise targeting.
Real-time virtual sonography is a technique in which the MR
imaging dataset is coregistered to landmarks during the US
examination, so that a needle can be placed sonographically.
However, experience with this technique is currently limited.
Transrectal MR imaging–guided prostate brachytherapy can also
be performed in a closed-bore 1.5-T imaging unit.
65. Robotic prostate biopsy promises high accuracy and is a topic of
intense research. This robot can perform biopsies and
automatically place brachytherapy seeds in the prostate.
zonal anatomy in the sagittal plane and corresponding axial sections from the
base (1), midgland (2), and apex (3). Note the anterior fibromuscular stroma (red), peripheral zone (pink), central zone (yellow), and transition zone (blue).
Sag T2WI -three sections –base, midgland & apex.
Base- The anterior fibromuscular stroma (arrow) consists of nonglandular tissue and appears dark. Note the symmetric homogeneous muscular stroma layer (arrowheads) in the posterior prostate base.
Midprostate- homogeneously bright peripheral zone (arrowheads) surrounding the central gland (white arrows), neurovascular bundles at the 5-o’clock and 7-o’clock positions (black arrows).
Apex- homogeneous peripheral zone (arrowheads) surrounding the urethra (U). Note that the volume of the peripheral zone increases from the base to the apex.
CG = central gland (central zone and transition zone), PZ = peripheral zone
CG = central gland (central zone and transition zone), PZ = peripheral zone, FS = anterior fibromuscular stroma, NV = neurovascular bundle, V = verumontanum
CG = central gland (central zone and transition zone), PZ = peripheral zoneV = verumontanum
restricted diffusion in tumor
T2-weighted image with voxel on normal prostatic tissue (green) and cancer (purple).
Normal (green) and abnormal (purple) MR spectra corresponding to regions of interest show elevated choline and creatine (Ch + Cr) to citrate (Ci) ratio.
CI = citrate, CH = choline, PA = polyamine
Abnormal spectra (elevated choline and decreased citrate level) suspicious (SC) or very suspicious (VC) for prostate cancer are seen in voxels containing tumor (*). A = artifact, ED = ejaculatory duct, H = healthy prostate tissue, ND = nondiagnostic.
Section in midgland shows healthy prostate tissue throughout peripheral zone as evidenced by high signal intensity on T2-weighted image with corresponding spectra demonstrating normal high citrate peaks (eg, arrow) and low or absent choline peaks (eg, arrowhead).
(b) Adjacent inferior section shows a tumor focus in left peripheral zone, seen as low-signal-intensity area (arrow) within the surrounding high-signal intensity peripheral zone.
52-year-old man with biopsy-proven adenocarcinoma. Perfusion images and MR spectroscopy was also performed.
T2WI- shows a well-defined heterogeneously bright hyperplastic nodules in the central prostate. Note the discrete dark margins of the junction of the central gland and the peripheral zone pseudocapsule (arrows).
Color map from computer-assisted diagnosis analysis of DCE (dynamic contrast enhanced) MR imaging data shows a ROI marking the left hyperplastic nodule of BPH.
Kinetic curve (percentage of enhancement over time) from DCE MR imaging data shows a washout pattern of enhancement in the BPH tissue included in the ROI
MR spectroscopy shows a high citrate (Ci) peak and a low choline (Ch) peak in the benign tissue of BPH.
Prostate cancer in a 72-year-old man Endorectal MRI of the prostate at 3.0 T
Axial T2WI of the prostatic apex shows a hypointense nodule (arrow) in the right side of the apex.
Sagittal T2WI shows the dark nodule in the prostatic apex (arrow). Note the intact, well-defined, thin, dark prostatic capsule (arrowhead).
Coronal T2WI shows the hypo-intense spiculated nodule (arrow). This is a typical morphology for prostate cancer.
AxialADC map shows restricted diffusion
(e) Color map from DCE MR imaging shows that the area of highest permeability (arrow) is in the region of prostate cancer
(f) Kinetic curve (percentage of enhancement over time) from DCE MR imaging shows a washout pattern of enhancement, typical of malignancy
Transverse, (b) coronal, and (c) sagittal unenhanced T2WI demonstrate a low-signal-intensity area (arrow) in the peripheral zone of right posterolateral midgland and apex. Tumor appears confined to the gland, as outer margin in all planes is smooth.
(a) T2WI shows a voxel of interest (square) in the left peripheral zone. Although the left peripheral zone is enlarged compared with the right peripheral zone, it has no focal dark areas. There are patchy dark abnormalities in the right peripheral zone. (b) MR spectroscopic spectrum from the voxel of interest shows a markedly elevated level of choline (Cho) (arrow) that is almost equal to the citrate (Ci) peak. Elevation of choline level with a decrease in citrate level is the spectral signature of prostate cancer. (c) Color DCE MR map shows a large area of high permeability (Ktrans) occupying the entire left peripheral zone (arrows). (d) Axial image from a SPECT study with 111In-labeled prostate monoclonal antibody shows avid uptake in the entire left prostate (arrow), a finding compatible with a large-volume prostate cancer. As seen in this case, some aggressive prostate cancers, even of large volume, may appear isointense on T2-weighted images; thus, morphologic imaging alone may not be able to show these tumors. Functional MR imaging—MR spectroscopy and DCE MR imaging—as well as antibody imaging accurately depicted this large prostate cancer.
MR images show large tumor(t)in the transition zone and tumor bulging with interruption of very low-signalintensity anterior fibromuscular stroma by slightly higher signal intensity tumor, suggestive of anterior ECE (arrow)
Prostate cancer of the transition zone in a 52-year-old man
Axial & Sagittal T2WI shows ill-defined homogeneous dark infiltration of the central gland (arrows).
Axial color DCE MR map shows a large area of high permeability (Ktrans) (red areas) in the transition zone.
Kinetic curve shows typical washout pattern in the transition zone tumor.
MR spectroscopic spectrum shows a high choline (Cho) peak typical of prostate cancer.
Axial T2WI at the level of the prostate base shows confluent dark signal intensity replacing a large volume of the left peripheral zone, with extraprostatic tumor extension (arrow) involving the left neurovascular bundle.
Axial T2WI at the level of the midgland shows the extracapsular extension of the tumor, with encasement of the left neurovascular bundle (arrow).
Axial T1WI shows good definition of the prostatic contour and the extracapsular tumor extension on the left into the bright periprostatic fat. Note the obliterated left neurovascular bundle (arrow) in comparison with the intact right neurovascular bundle (arrowhead).
MR images with corresponding spectroscopic data show large low-signal-intensity lesion in the right side of peripheral zone with a focal bulge (arrowhead) and obliteration of the rectoprostatic angle (arrow) in addition to broad (>1 cm) capsular contact. Findings are indicative of extracapsular extension.
Transverse image shows a dominant tumor (arrow) at the right base; loss of normal contour and irregular bulging are evidence of extracapsular disease. There is direct tumor extension into both seminal vesicles (arrowheads) on (b) transverse and (c) corresponding coronal images, seen as mild enlargement of the involved seminal vesicles and low-signal-intensity tissue replacing normal thin walls and obliterating the lumen.
(d) Sagittal image shows seminal vesicle invasion (arrow) and adjacent tumor extending into extracapsular space between urinary bladder and seminal vesicle.
Coronal T2WI shows concentric wall thickening of the left seminal vesicle (arrows) and dark tumor extending along the left seminal vesicle, findings compatible with seminal vesicle invasion.
Sagittal T2WI shows continuity of the dark tumor, which extends from the left base into the left seminal vesicle (arrows).
99mTc methylene diphosphonate bone scans show numerous foci of increased uptake in the axial skeleton, indicating widespread osseous metastatic disease
PET/CT scans of osseous metastasis in the posterior element of thoracic spine. (a) Coronal FDG PET scan shows focal increased activity in left posterior spine (arrow). (b) Transverse PET/CT overlay scan shows that focal lesion corresponds to metabolically active bone metastasis in the posterior vertebra (arrow).
MR imaging–compatible biopsy device. The device (top left) has an endorectal probe (arrow), a needle guide (arrowhead), and a set of dials (D), which allow the needle to be directed to the target on the basis of input from the targeting software (bottom left). The software provides the necessary angles for probe rotation, needle angulation, and needle depth (bottom right). The dials are adjusted manually by the operator on the basis of software calculations derived from prebiopsy targeting MR images. The patient is placed in the prone position (top right) with endorectal placement of the biopsy probe (arrow at bottom right).
MR imaging–compatible prostate intervention robotic device. The device can operate in the gantry of an MR imaging unit alongside the patient in the decubitus position and can be actuated remotely.