Multiparametric magnetic resonance imaging (MRI) has provided a method for visualizing prostate cancer. MRI-ultrasonography fusion allows prostate biopsy to be performed quickly, on an outpatient basis, using the transrectal technique. Targeted biopsies are more sensitive for detection of prostate cancer than nontargeted, systematic biopsies and detect more significant prostate cancers and fewer insignificant cancers than conventional biopsies. A negative MRI scan should not defer biopsy. Two groups who will especially benefit from targeted prostate biopsy are men with low-risk lesions in active surveillance and men with increased prostate-specific antigen levels and previous negative conventional biopsies.
Key points
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Reliable imaging of prostate cancer within the organ has been elusive; however, over the past few years, use of multiparametric magnetic resonance imaging (MRI) has begun to allow visualization of many organ-confined prostate cancers. The new imaging modality and its offshoot, targeted biopsy, offer the promise of a major transformation in management of this disease.
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By aiming a biopsy needle at MRI regions of interest, a physician can now obtain tissue directly from suspicious lesions (ie, targeted prostate biopsy), rather than by blindly sampling the organ.
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Use of MRI images to guide prostate biopsy is accomplished by image fusion and may be performed in 1 of 3 ways: by direct in-bore MRI-MRI fusion; by cognitive fusion, using ultrasonography (US) guidance to sample suspicious areas on MRI; and by MRI-US fusion, using a device made for the purpose.
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MRI-US fusion devices, such as the Artemis (Eigen-Hitachi, Grass Valley, CA) or UroNav (Invivo-Philips, Gainesville, FL), allow the urologist to use sophisticated MRI images to guide prostate biopsy in an outpatient clinic setting; the procedure is contextually similar to that performed by most urologists for the past several decades.
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Targeted prostate biopsy, via MRI-US fusion, (1) allows diagnosis of serious tumors not found with conventional biopsy; (2) helps to avoid detection of insignificant tumors; (3) provides a method for repeat biopsy of specific tumor-bearing sites for men in active surveillance; and (4) creates an opportunity for study of focal therapy.
Introduction
For nearly a century, digital rectal examination was the only tool available to aid in tissue sampling for diagnosis of prostate cancer (CaP). With the advent of ultrasonography (US) in the 1980s, physicians had a new modality for directing biopsy needles in real time. Originally developed by Stamey, the US-guided, transrectal sextant method became widely adopted. Since that time, additional samples are taken (usually totaling 12) and local anesthesia has been added, but otherwise the random, systematic procedure of the 1980s has remained largely unchanged. Saturation biopsy has been advocated but may increase detection of insignificant cancers, and it typically requires general anesthesia.
Thus, CaP is the only important solid malignancy diagnosed by blind biopsy of the organ (ie, without tumor visualization). Some 50% of cancers detected by this method may not be of clinical significance. In addition, systematic biopsies are poor at sampling lesions in the anterior, midline, and apex of the prostate. This situation can lead to underdiagnosis of important lesions in these regions. Further, almost one-third of currently detected cancers are reclassified from original biopsy Gleason score to a higher score on final pathology.
Groundwork for a change in this schema was established with the observation that some CaP lesions could be visualized with magnetic resonance imaging (MRI). As MRI usage became widely disseminated, and as the technology improved, the value of MRI to diagnose (and stage) CaP became increasingly apparent. The advent of MRI coincided with decreasing volume of CaP at diagnosis. In an earlier time, when CaP usually presented as a palpable mass, US imaging could detect many lesions. Because of early prostate-specific antigen (PSA) screening, most newly diagnosed CaP is nonpalpable, and US usually fails to visualize a lesion. Thus, use of MRI to identify suspicious prostate lesions fills an important void, helping to identify regions of interest and enable targeted biopsy.
Introduction
For nearly a century, digital rectal examination was the only tool available to aid in tissue sampling for diagnosis of prostate cancer (CaP). With the advent of ultrasonography (US) in the 1980s, physicians had a new modality for directing biopsy needles in real time. Originally developed by Stamey, the US-guided, transrectal sextant method became widely adopted. Since that time, additional samples are taken (usually totaling 12) and local anesthesia has been added, but otherwise the random, systematic procedure of the 1980s has remained largely unchanged. Saturation biopsy has been advocated but may increase detection of insignificant cancers, and it typically requires general anesthesia.
Thus, CaP is the only important solid malignancy diagnosed by blind biopsy of the organ (ie, without tumor visualization). Some 50% of cancers detected by this method may not be of clinical significance. In addition, systematic biopsies are poor at sampling lesions in the anterior, midline, and apex of the prostate. This situation can lead to underdiagnosis of important lesions in these regions. Further, almost one-third of currently detected cancers are reclassified from original biopsy Gleason score to a higher score on final pathology.
Groundwork for a change in this schema was established with the observation that some CaP lesions could be visualized with magnetic resonance imaging (MRI). As MRI usage became widely disseminated, and as the technology improved, the value of MRI to diagnose (and stage) CaP became increasingly apparent. The advent of MRI coincided with decreasing volume of CaP at diagnosis. In an earlier time, when CaP usually presented as a palpable mass, US imaging could detect many lesions. Because of early prostate-specific antigen (PSA) screening, most newly diagnosed CaP is nonpalpable, and US usually fails to visualize a lesion. Thus, use of MRI to identify suspicious prostate lesions fills an important void, helping to identify regions of interest and enable targeted biopsy.
Advent of MRI for diagnosis of CaP
Among the first to show that CaP could be imaged by MRI was Hricak, in 1983. Subsequent advances in magnet strength and the availability of multiparametric studies have made MRI the imaging modality of choice for diagnosis of CaP ( Fig. 1 ). The established parameters of multiparametric MRI (mp-MRI) are T2-weighted images (T2WI), dynamic contrast enhancement (DCE), and diffusion-weighted imaging (DWI). As the limitations of PSA testing to diagnose CaP have become increasingly apparent, the importance of a visual representation of the tumor has become compelling. Accurate imaging of CaP and the offshoot, targeted biopsy, contain the seeds for a major change in management of the disease.
Current use of MRI for diagnosis of CaP
Either pelvic phased array or endorectal coils (ERC) may be used when performing mp-MRI of the prostate. ERC may improve definition of the prostate capsule, but does not seem critical for characterization of intraprostatic lesions. Thus, because of patient discomfort and increased procedure time, the endorectal approach is not routinely used for diagnostic purposes. Likewise, to identify regions of interest and guide biopsy, spectroscopy adds little and is not generally used. Three-Tesla magnets provide higher signal-to-noise ratios and shorter acquisition times than 1.5 T; both have been used successfully to define cancer within the prostate.
mp-MRI
mp-MRI incorporates several different imaging modalities: T2WI, DWI, and DCE to best assess potential lesions in the prostate. Fig. 2 shows an example of CaP visualized in all 3 modalities.
T2WI produces an anatomic image based on the transverse relaxation time after magnetically aligning a tissue to an external magnetic field. T2WI provides the best tissue contrast for the detection, localization, and staging of CaP, which has shorter T2 than normal tissue. However, other processes such as inflammation and prostatic hyperplasia can also shorten T2, and additional parameters are necessary to increase the specificity of T2WI.
DWI provides a measure of the Brownian motion of water molecules and is an essential component of mp-MRI. At body temperature, the mobility of water is primarily dependent on the molecular environment such as cell size and microstructure. DWI is a good indicator for CaP, because free motion of water is generally restricted within cancerous tissue. The slope of change of the received signal, based on the degree of diffusion weighting, is called the apparent diffusion coefficient (ADC) and creates quantitative maps of molecular mobility. By measuring the hydrodynamic environment of tissue using DWI, the specificity of CaP detection is improved compared with T2WI alone. In creating the University of California at San Francisco (UCLA) score for MRI suspicion, DWI is doubly weighted, as discussed later.
DCE uses T1-shortening contrast to evaluate tumor vascularity and adds value to diagnosis of suspicious lesions. For this method, rapidly repeated imaging is performed during the dynamic administration of intravenous contrast. Increased microvascular density and breakdown of capillary walls within tumors can lead to increased contrast arrival (washin) and dispersion (washout).
MRI-identified regions of interest are scored to help determine the likelihood of cancer in that area. Different scoring systems have been proposed, but all rely on the 3 parameters outlined earlier. The UCLA scoring system is shown in Table 1 . Image score is determined by assigning an image-grade number (left column) to each parameter; ADC value is assigned double weighting. For example, if a region of interest was moderately dark on T2WI (ie, a grade 3), had an ADC value of 0.7 mm 2 /s (ie, a grade 4), and had a DCE showing moderately abnormal enhancement (ie, a grade 3), the overall score would be (3 + 8 + 3)/4 = 3.5. The score is rounded up if the region of interest is in the peripheral zone, in this case giving it a score of 4, and rounded down if the region is in the transition zone, in this case giving it a score of 3. The higher the score, the more likely cancer is present in the region of interest. The PI-RADS (Prostate Imaging Reporting and Data System) scoring system, which is similar to the UCLA scoring system, has recently been proposed as an industry standard.
| Image Grade | T2WI | ADC (mm 2 /s) | DCE |
|---|---|---|---|
| 1 | Normal | >1.2 × 10 −3 | Normal |
| 2 | Faint decreased signal | 1.0–1.2 × 10 −3 | Mildly abnormal enhancement |
| 3 | Moderately dark nodule | 0.8–1.0 × 10 −3 | Moderately abnormal enhancement |
| 4 | Intensely dark nodule | 0.6–0.8 × 10 −3 | Highly abnormal enhancement |
| 5 | Dark nodule with mass effect | <0.6 × 10 −3 | Profoundly abnormal enhancement |
a The higher the score, the greater the level of suspicion. Regions of interest with scores of 1 and 2 are no more likely to contain cancer than normal tissue and are not usually targeted. A score of 5 indicates cancer in most cases.
b Although both the ESUR PI-RADS and UCLA reporting systems are standardized, there are two main differences: (1) ESUR PI-RADS uses qualitative evaluation of diffusion imaging, whereas the UCLA system uses the quantitative ADC based on a series of cases all using the same scanner platform and pulse sequence parameters, and (2) ESUR PI-RADS weights the T2 appearance, diffusion, and perfusion equally, whereas the UCLA reporting system weights diffusion twice as much as the other two.
Image fusion
Image fusion is the process of combining information from 2 or more images into a single image ( Fig. 3 ), with the intent that the resulting image provides more information than any input image alone. Image fusion, as an aid to prostate biopsy targeting, refers to the superimposition of prostatic images (stored MRI images and real-time US images) to create a three-dimensional (3D) reconstruction, on which biopsy work is performed. The fused image result gives the operator the tumor-detecting value of MRI with the ease of use of US. Fusion devices ( Table 2 ) allow the operator to electronically bring MRI to the US biopsy suite, to fuse MRI and US images into a 3D reconstruction, and under real-time US guidance, to aim the biopsy needle at suspicious regions of interest seen on MRI. Performance of the biopsy is operationally similar to that performed by urologists for several decades.
| Manufacturer/Trade Name | US Image Acquisition | Biopsy Route | Tracking Mechanism | Year of FDA Approval | Comments |
|---|---|---|---|---|---|
| Philips/UroNav | Manual US sweep from base to apex | Transrectal | External magnetic field generator | 2005 | Prospective targeting, integrated with existing US device, freehand manipulation |
| Eigen/Artemis | Manual rotation along fixed axis | Transrectal | Mechanical arm with encoders | 2008 | Prospective targeting, stabilized TRUS probe |
| Koelis/Urostation | Automatic US probe rotation | Transrectal | Real-time TRUS-TRUS registration | 2010 | Retrospective targeting, real-time elastic registration |
| Hitachi/HI-RVS (real-time virtual sonography) | Real-time biplanar TRUS | Transrectal or transperineal | External magnetic field generator | 2010 | Prospective targeting, integrated with existing US device |
| BioJet/Jetsoft/GeoScan | Manual US sweep in sagittal | Transrectal or transperineal | Mechanical arm with encoders; uses stepper | 2012 | Prospective targeting, rigid registration |
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Evolution and Immediate Future of US Screening Guidelines
Decision Making and Prostate Cancer Screening
The Epidemiology and Clinical Implications of Genetic Variation in Prostate Cancer
Management of an Increasing Prostate-Specific Antigen Level After Negative Prostate Biopsy
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