PI-RADS v2.1 (https://www.acr.org/-/media/ACR/Files/RADS/Pi-RADS/PIRADS-V2-1.pdf?la=en) was introduced in 2019, and at the time of writing is the most current version.

Anatomical Zones of the Prostate Gland as seen on MRI²

Sector Map

https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/PI-RADS

Implication of PI-RADS Assessment Scores

Basic Scoring approach in Each Zone

Derived from PI-RADS V2.1 manual pages 11-14¹; specific scoring criteria for the PZ and TZ are included in the dedicated sections later in this document

• Peripheral Zone – DWI is the primary sequence for scoring; DCE relevant for DWI score of 3
• Transition Zone – T2W is the primary sequence for scoring; DWI relevant for T2W scores of 2 or 3
• Central Zone – No discrete scoring criteria, assess for focal early enhancement and/or asymmetry on DWI and T2W
• AFS – Apply TZ or PZ scoring criteria depending on perceived most likely zone of lesion origin

Specific Situations: Category Upgrades

PI-RADS v2.1 Scoring: DWI for Peripheral Zone or Transition Zone

DWI assessment should occur on the “high” b-value images (b ≥ 1400 s/mm²)
Adapted from the PI-RADS V2.1 Manual¹

PI-RADS v2.1 Scoring: DCE for Peripheral Zone

Scrolling through both the raw DCE and subtraction DCE images is helpful
Adapted from the PI-RADS V2.1 Manual¹

Example 1 – What PI-RADS score would you assign to this lesion?

Example 2 – What PI-RADS score would you assign to this lesion?

Example 3 – What PI-RADS score would you assign to this lesion?

Example 4 – What PI-RADS score would you assign to this lesion?

Example 5 – What PI-RADS score would you assign to this lesion?

Benign Peripheral Zone Abnormalities

Prostatitis, Post-inflammatory Scar, and Focal Prostate Atrophy

• Clarification of clinical and radiologic terminology
  • Clinically, the term “prostatitis” signifies either acute or chronic infection/inflammation of the prostate gland, sometimes with associated pain, recurrent UTI, and/or fluctuating PSA³
  • As opposed to clinically defined prostatitis, the MRI finding commonly reported as “prostatitis” or “sequelae of prostatitis” most often reflects areas of parenchymal signal abnormality related to⁴:
  1. Post-inflammatory scar from prior prostatitis, often subclinical
  2. Active acute or chronic prostatitis
  3. Focal prostate atrophy, a common benign pathologic finding sometimes associated with inflammation 
• Imaging features of post-inflammatory/inflammatory lesions^4–6
  • Range of appearances from characteristically benign to indistinguishable from cancer, typically with some degree of signal abnormality on T2, DWI, and DCE.^4–6
  • Features more typical of post-inflammatory/inflammatory findings include: wedge-shaped/linear morphology (following the normal glandular ductal drainage patterns), patchy/ill-defined appearance, striated appearance, lobar or diffuse distribution (as opposed to a focal lesion), associated volume loss, and milder diffusion abnormality.^4–6
  • Equivocal cases may be accompanied by a PI-RADS assessment.
• BCG-related granulomatous prostatitis
  • Can produce diffuse or focal signal abnormalities that are sometimes indistinguishable from cancer
  • Typical appearance includes T2 hypointensity and ADC hypointensity, with either isointensensity or hyperintensity on DWI⁷
  • Rim-enhancement with central hypoenhancement, when present, is characteristic and may suggest the diagnosis in the context of prior BCG therapy.⁸
  • When suspected, options for further assessment include biopsy for confirmation or short interval follow-up MRI after antibiotic therapy.

Typical Morphologic Features of Sequelae of Prostatitis

Wedge-shaped/linear morphology, striated appearance on T2W images, regional/lobar distribution, volume loss

Example 1	Example 2
Imaging Findings: Lesion in the left posterolateral mid-apical peripheral zone with mild wedge-shaped restricted diffusion, and a striated appearance on T2-weighed images. PI-RADS 2. Final Diagnosis:Sequelae of prostatitis	Imaging Findings: Lesion in the right posterolateral mid peripheral zone with marked restricted diffusion, homogeneous T2 hypointensity in a lobar distribution, and positive DCE. PI-RADS 5 by imaging criteria. Pathology (targeted biopsy): Benign prostate tissue. Final Diagnosis: Likely sequelae of prostatitis

Example 3	Example 4
Imaging Findings: Lesion in the left posterolateral mid peripheral zone with moderate restricted diffusion, suggestion of wedge-shaped T2W hypointensity, and positive DCE. Note the associated volume loss compared to the contralateral PZ. Appearance may represent prostatitis though biopsy was performed for confirmation. Pathology (targeted biopsy): Benign prostate tissue. Final Diagnosis: Sequelae of prostatitis	Imaging Findings: Lesion in the right posteromedial/posterolateral mid peripheral zone with marked restricted diffusion, homogeneous T2 hypointensity, and rim-enhancement on DCE. PI-RADS 4 by imaging criteria though likely BCG granuloma given rim-enhancement and hx of BCG therapy. Pathology/Final Diagnosis: BCG-related granulomatous prostatitis.

Extruded/Ectopic BPH Nodules

• While BPH largely arises in the TZ, nodules may less commonly either protrude exophytically into the PZ or arise ectopically in the PZ; in practice, both of these processes are often referred to as “extruded BPH”^1,5,9.
• Imaging features of extruded BPH: similar to BPH in the TZ, appearance may span the range from typical (circumscribed, heterogeneous, encapsulated) to atypical (homogeneous and non-encapsulated) BPH, the latter of which may be indistinguishable from cancer when in the PZ^1,5,9.
• Categorized as PI-RADS 2 when outside the TZ but have characteristic imaging findings of BPH¹

Example of Extruded BPH

Imaging Findings: Lesion in the right posterolateral base peripheral zone with mild/moderate restricted diffusion, circumscribed heterogeneous T2W signal with encapsulation, and positive DCE. PI-RADS 2 (Extruded BPH).

Post-biopsy Hemorrhage

• T1-hyperintense signal (as seen on pre-Gad) that may persist for several months after biopsy (due to anticoagulant effect of citrate produced by normal prostate).
• Interface with tumor visualization^4,5,9
  • Tumor may be less conspicuous on a background of hemorrhage-related T2 hypointense signal.
  • Intrinsic T1 hyperintensity obscures assessment for enhancement on DCE, and subtraction images (post-Gad minus pre-Gad) must be carefully reviewed.
  • ADC map can identify areas of marked diffusion restriction suspicious for tumor, while hemorrhage is typically either non-restricting or mildly restricting
  • Hemorrhage exclusion sign: Areas of tumor are commonly spared from hemorrhage-related intrinsic T1 hyperintensity, which may facilitate lesion delineation

Example of Post-biopsy Hemorrhage (with “hemorrhage exclusion sign”)

Markedly diffusion restricting lesion involving both the bilateral posteromedial mid peripheral zones, positive for cancer on recent biopsy. Note intrinsic T1 hyperintense hemorrhage in the peripheral zones bilaterally (yellow arrows), which spares the area of the lesion. The lesion enhanced avidly on DCE.

PI-RADS v2.1 Scoring: T2W for Transition Zone

Adapted from the PI-RADS V2.1 Manual

PI-RADS v2.1 Scoring: DWI for Transition Zone or Peripheral Zone

Adapted from the PI-RADS V2.1 Manual

How do Transition zone adenocarcinomas differ from Peripheral Zone Cancers?

• Biology
  • Tend to be lower grade and more likely organ-confined than PZ cancer, though larger in size on average¹⁰
  • Have a higher predilection for being located anterior and inferior in the gland, with tendency for early extension into the anterior fibromuscular stroma^11–13
• Imaging detection^10–14
  • MRI has lower accuracy and higher interobserver variability for TZ compared to PZ cancers, largely owing to the confounding effect of BPH¹²
  • Lesion morphology and texture on T2W imaging are the primary factors used for PI-RADS categorization, with features more typical of cancer including: Lenticular shape, non-circumscribed margins, and/or homogeneous, moderate T2W hypointensity.
  • Stromal BPH can demonstrate both marked restricted diffusion and early intense enhancement on DCE similar to cancer. When T2W morphology is equivocal, disproportionality of diffusion restriction and enhancement within a lesion compared to neighboring BPH can help raise suspicion.
  • Both DWI and DCE are very helpful for improving lesion conspicuity and prompting further interrogation on T2W images, and DWI has been shown to improve sensitivity for cancer detection in the TZ compared to T2W alone¹⁴.
• Tissue diagnosis
  • TZ lesions can be challenging to detect by transrectal biopsy or physical exam, given anterior predilection; therefore, MRI is crucial in directing targeted biopsy, and the anterior TZ deserves scrutiny in cases with negative prior biopsy but rising PSA¹².
  • Very anterior and apical lesions are typically easier to target by MRI-guided transperineal biopsy, which can be considered based on MRI findings and/or prior negative transrectal biopsy¹⁵.

Example 1 – What PI-RADS score would you assign to this lesion?

Example 2 – What PI-RADS score would you assign to this lesion?

Example 3 – What PI-RADS score would you assign to this lesion?

Example 4 – What PI-RADS score would you assign to this lesion?

Example 5 – What PI-RADS score would you assign to this lesion?

What is the central zone?^1,4,5,9,16

• T2 hypointense tissue surrounding the ejaculatory ducts at the prostatic base that atrophies and becomes less conspicuous with age
• Normal CZ can sometimes demonstrate T2W and DWI characteristics similar to cancer, though should not demonstrate early enhancement
• Cancers rarely originate in the CZ (1-5%), and much more often involve it secondarily from the adjacent PZ or TZ

How do you score central zone lesions in PI-RADS?¹

• PI-RADS v2.1 does not stipulate specific criteria for scoring CZ lesions, but rather suggests that focal early enhancement and/or asymmetry on DWI and T2W images may indicate the presence of PCa
• If a cancer secondarily involves the CZ, scoring can applied to the zone from which the lesion most likely arises

Example 1 – Normal Central Zone

Example 2a – How would you characterize this finding?

Example 2b – How would you categorize this finding?

Extraprostatic Extension (EPE)

Anatomic Principles

• Prostate does not actually have a true capsule, but the terms “capsule” or “outer prostate margin” are frequently used to refer to a condensed band of prostatic stroma along the gland periphery, sometimes visible as a thin T2 hypointense line¹⁷
• EPE = tumor beyond the prostatic capsule/margin
• Certain areas of the gland have a higher propensity for EPE due to anatomic factors (see table below); drawing attention to tumor contact in these locations is helpful, even if there is no frank EPE by imaging^18,19

Locations with higher risk of EPE

Posterolateral base	Apex	Anterior fibromuscular stroma	Central zone and base of seminal vesicles
Early perineural spread along penetrating branches from the neurovascular bundles	Capsule deficient in this location, facilitating spread into striated muscle of external sphincter	Capsule less defined in this location, facilitating anterior EPE of TZ cancers	No capsule surrounding the intraprostatic course of ejaculatory ducts or base of seminal vesicles, providing a route for EPE (including directly into the seminal vesicles)

Imaging Assessment

• MRI has Se ~ 60% and Sp ~ 90% for EPE²⁰.
• MRI plays a role in identifying definite extraprostatic extension or drawing attention to areas at risk of microscopic EPE, which may relate to surgical planning¹⁷.
• T2W images are often useful for assessing EPE, as they provide sharp depiction of the prostate border; DCE can also be a helpful adjunct.
• In the absence of frank EPE, one or more indirect signs (see table below) increases likelihood of EPE at pathology²¹, especially in an area of anatomic weakness.

Direct Sign	Indirect Signs
Frank EPE: tumor extension beyond prostatic margin into periprostatic fat or adjacent structures	Broad capsular contact: > 10-15 mm tumor contact with prostatic margin; sensitive but not specific	Contour bulge: smooth convex protrusion of prostatic margin overlying tumor	Contour irregularity	Neurovascular bundle asymmetry

Example 1	>Example 2
Imaging Findings: Frank EPE at the right posterolateral base.	Imaging Findings: Frank EPE at the posterior base, best seen on coronal T2W images. Multiplanar assessment is helpful.

Example 3	Example 4
Imaging Findings: Broad capsular contact at the posterolateral base without frank EPE. Pathology: Positive for EPE.	Imaging Findings: Broad capsular contact at the posterolateral mid gland without frank EPE. Similar appearance as Example 3. Pathology: Negative for EPE

Example 5	Example 6
Imaging Findings: Bulging of the prostate border and broad capsular contact along the left posterolateral mid to basal gland, without frank EPE. Based on these findings, left neurovascular bundle was removed at surgery. Pathology: Positive for EPE.	Imaging Findings: Irregularity along the right posterolateral prostate border, evident both on T2W and DCE, without frank EPE. Based on these findings, right neurovascular bundle was removed at surgery. Pathology: Positive for EPE.

Seminal Vesicle Invasion (SVI)

Mechanisms of Seminal Vesicle Invasion

Direct spread along ejaculatory duct into SV	EPE through adjacent capsule, with secondary invasion of SV	Discontinuous tumor deposit in SV (uncommon)

Imaging Assessment

• MRI has Se ~ 60% and Sp ~ 95% for SVI²⁰
• SVI manifests as focal or diffusely abnormal signal (T2 hypointensity, restricted diffusion, hyperenhancement) along the SV lumen or wall¹.
• T2W imaging, particularly the coronal and sagittal planes, is often useful due to sharp anatomic definition. DWI and DCE are adjunctive.
• Scrutinize the base of the seminal vesicle for abutment even if there is no frank SVI, as this finding has an association with SVI at pathologic assessment²².

Example 1

Imaging Findings: Foci of T2 hypointensity, restricted diffusion, and enhancement in the caudal left SV (white arrows), and to a lesser extent in the right SV (yellow arrows). Note the T2 hypointense tumor signal clearly extending into the left SV on the Sag T2W images, with effacement of the normal tapered T2 hyperintense SV base. Findings indicate bilateral SVI, left greater than right. Path: Bilateral SVI

Example 2	Example 3
Imaging Findings: T2-hypointense tumor signal abutment of the base of the left SV without frank SVI. Tapering of the SV base remains sharply defined. Multiplanar T2W assessment is helpful. Path: Abutment of SV base, without SVI.	Imaging Findings: T2-hypointense tumor signal abuts of the base of the right SV without frank SVI. In the coronal plane, note the preserved T2-hyperintense of the SV base (yellow arrow), which cleanly tapers into the ejaculatory duct (blue arrow), with immediately adjacent T2 hypointense tumor signal (dashed white arrows). Path: Right SVI. Teaching Point: Abutment on imaging may turn out to be invasion at path.

Example 4	Example 5
Imaging Findings: Frank extraprostatic tumor secondarily invades the mid-portion of the right SV.	maging Findings: Primary lesion is in the left posteromedial/posterolateral basal peripheral zone. Two separate foci of restricted diffusion and intense focal enhancement are seen in the left and right SV, indicating discontinuous SVI. Path: Bilateral SVI. Teaching point: Focal SV implants separate from the primary lesion can uncommonly occur. Additionally, the findings were less conspicuous on T2W images, and multisequence assessment of the SV on T2W, DWI, and DCE may improve sensitivity for SVI.

Clinical Significance of Extraprostatic Extension and Seminal Vesicle Invasion

• EPE (stage T3a) and SVI (stage T3b) worsen prognosis and increase risk of biochemical recurrence²³
• Relevance to surgeons²⁴
  • EPE and SVI increase risk of a positive surgical margin (R1) – most common locations for positive margin also happen to be areas most prone to EPE (posterolateral base, apex)
  • Can impact decision regarding nerve sparing, if EPE seen in region of neurovascular bundle
• Relevance to radiation oncologists²⁵
  • MRI is a useful tool for identifying EPE/SVI prior to definitive radiation therapy, given absence of a prostatectomy specimen
  • EPE and SVI may triage patients respectively to “high risk” or ”very high risk” disease by NCCN classification, which may impact management via:
    • Longer duration of androgen deprivation therapy
    • Possible modification of the radiation plan (e.g. nodal irradiation, brachytherapy)

Clinically relevant anatomic landmarks should be scrutinized once a focal prostatic lesion is identified. Multiplanar assessment on T2W imaging is useful, as some relationships may not be evident in the axial plane.

External Urethral Sphincter^18,24,26

• Anatomic and imaging principles
  • External urethral sphincter (EUS) = striated muscle primarily encircling the membranous urethra, appearing as T2 hypointense periurethral signal just caudal to the prostatic apex
  • Muscle fibers blend with prostatic apex to form an indistinct interface with deficient “capsule”, facilitating tumor spread^18,26
  • Tumor signal extending caudal to the apical prostatic margin along the urethra implies EUS invasion
  • Broad tumor abutment of the caudal apical prostatic margin also increases risk of microscopic EUS involvement²⁴
• Surgical Relevance
  • EUS preservation at prostatectomy relates to continence, and frank EUS invasion may impact prostatectomy plans²⁴
  • Abutment of the apical prostatic margin/EUS should be scrutinized, even in the absence of frank EUS invasion.

Normal External Urethral Sphincter

T2-hypointense periurethral band of signal, just beyond the prostatic apex

Example 1

Findings: T2-hypointense tumor signal (white arrows) extends beyond the apical prostatic margin (yellow arrow), seen best in the coronal plane Path: Positive distal surgical margin at the left apex

Bladder Neck

• Anatomic and imaging principles
  • Bladder neck = tapered portion of the bladder at its junction with the urethra and prostate, which contains the bulk of the internal urethral sphincter muscle
  • Common to have prostatic tissue protrude into the bladder neck in the setting of BPH
  • Tumor signal extending into the very T2 hypointense signal of the detrusor muscle implies bladder neck invasion; broad abutment should also be scrutinized, even in the absence of frank invasion²⁴.
• Surgical relevance
  • Some degree of bladder neck preservation during prostatectomy may relate to continence²⁷
  • Bladder neck invasion or abutment on imaging may impact the surgical plan

Normal Bladder Neck

Normal circumferential T2 hypointense bladder neck signal above the prostatic base (white arrows) Some protrusion of intermediate to mildly T2 hyperintense prostatic/BPH tissue into the bladder neck is common (black arrow)

Example 1	Example 2
Findings: T2 iso-to-hypointense, diffusion restricting tumor signal replacing some of the normal T2 hypointense detrusor muscle in the bladder neck, consistent with frank bladder neck invasion. Path/Surgery: Wide bladder neck dissection was performed based on MRI findings, resulting in a negative surgical margin.	Findings: Large diffusion-restricting anterior base TZ lesion. Tumor signal abuts the bladder neck (white arrow) without frankly replacing the normal T2 hypointense detrusor signal, best seen in the sagittal plane. Path/Surgery: Careful anterior bladder neck dissection undertaken, with negative surgical margin. Microscopic bladder neck invasion seen at pathology.

Neurovascular Bundles

• Anatomic and imaging principles
  • Nerve fibers that contribute substantially to erectile function are organized most densely adjacent to the posterolateral prostatic capsule (though sometimes spread more fan-like across a larger area), and along with adjacent venous branches are collectively termed the neurovascular bundle (NVB)^24,28
  • NVBs are variably visualized on MRI²⁹, but typically appear as a cluster of punctate/linear T2-hypointense foci at approximately 5 and 7 o’clock; the MRI-visible structures are likely predominantly small venous branches, though this allows one to infer the likely location of more densely concentrated periprostatic nerve fibers.
  • Asymmetric irregular prominence of a NVB adjacent to an area of PZ tumor suggests NVB involvement, particularly if EPE is present
  • Indirect signs of EPE (broad abutment, contour bulge, contour irregularity) adjacent to the expected area of the NVB (5 and 7 o’clock) are important to mention, particularly at the prostatic base, where there is a high rate of perineural spread along penetrating nerve fibers (“superior pedicle” of nerve fibers enters gland at this location)^11,24
• Surgical Relevance
  • Radical prostatectomy commonly involves bilateral “nerve-sparing”, where both the NVBs and adjacent fascia are preserved, relating to erectile function²⁴
  • Frank NVB involvement by tumor or direct/indirect signs of EPE near the NVB may impact decision regarding nerve-sparing²⁴

Normal Neurovascular Bundle	Example of NVB Involvement
Normal neurovascular bundle is visualized as a cluster of punctate/linear T2-hypointense foci (yellow arrow)	Findings: Large right base PZ lesion with asymmetric T2 hypointense thickening along the right NVB (yellow arrow), with corresponding restricted diffusion. Note the normal contralateral NVB (black arrow). Surgery/Path: Right NVB resected at surgery. Path positive for EPE.

Anterior Fibromuscular Stroma

• Anatomic and imaging principles
  • Anterior fibromuscular stroma (AFS) = band of non-glandular fibromuscular tissue blanketing the anterior surface of the prostate, contiguous with the muscle fibers of the EUS inferiorly (“EUS apron”) and detrusor superiorly (“detrusor apron”)¹⁸
  • Variably visualized as a symmetric T2 hypointense band anterior to the TZ, with mild or no restricted diffusion and either no enhancement or low-level delayed enhancement on DCE³⁰
  • When inconspicuous, the location of the AFS is inferred as being along the anterior-most margin of the gland
  • Anterior TZ lesions have a striking propensity for AFS involvement; therefore, tumor that appears centered in the AFS is most often related to an underlying anterior TZ lesion¹¹
  • AFS invasion is suggested when tumor directly extends into a well-visualized AFS, or when tumor abuts the anterior prostatic margin (even if AFS is not discretely visualized)
  • Lesions involving the AFS and abutting and anterior gland have a higher risk of anterior EPE, due to relative anatomic weakness in this location¹⁹
• Surgical relevance
  • AFS invasion and/or anterior prostate border abutment may modify the surgical plan with regard to sparing of anterior periprostatic supporting tissues³¹

Normal AFS	Normal AFS
Prominent but normal AFS with typical signal characteristics, including symmetric T2 hypointensity, lack of restricted diffusion, and lack of enhancement on DCE	Example of a normal AFS that is visible but less conspicuous

Example 1

Findings: Asymmetric T2 hypointense signal along the left anterior gland centered in the AFS with associated marked restricted diffusion and intense enhancement on DCE. PI-RADS 5. Path: Gleason 9 prostate cancer. Teaching point: Asymmetry, marked restricted diffusion, and intense enhancement in the region of the AFS should raise concern for tumor rather than prominent AFS.

PSA Density

• Definition:
  • Quotient of serum PSA level (on closest date available to MRI) divided by the prostate gland volume.
  • Volume (ml) may be estimated using ellipsoid volume calculation (CC x AP x TRV x 0.52)

    

• Concept
  • Corrects PSA for size of gland, given that a larger gland would be expected to have a higher PSA
  • PSA density > 0.1-0.15 ng/ml² increases the pre-test probability of clinically significant prostate cancer, though is not entirely sensitive or specific^32,33.
• Interface with MRI
  • Abnormally elevated PSA density should heighten suspicion for clinically significant prostate cancer
  • May impact urologist’s decision of whether or not to perform biopsy^32,33

1. PI-RADS Manual, Version 2.1, 2019.
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18. Vilanova JC (Joan C., Catalá V, Algaba F, Laucirica O. Atlas of Multiparametric Prostate MRI : With PI-RADS Approach and Anatomic-MRI-Pathological Correlation.
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20. de Rooij M, Hamoen EHJ, Witjes JA, Barentsz JO, Rovers MM. Accuracy of Magnetic Resonance Imaging for Local Staging of Prostate Cancer: A Diagnostic Meta-analysis. Eur Urol. 2016;70(2):233-245. doi:10.1016/j.eururo.2015.07.029
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