Chris Wallis: Hello, and thank you for joining us for our UroToday discussion on the third part in our series assessing what urologists need to know about multiparametric MRI with a focus on targeted biopsy. I'm Chris Wallis, an assistant professor in the division of urology at the University of Toronto. With me today is Zach Klaassen, an assistant professor in the division of urology at the Medical College of Georgia. This is a citation for the publication upon which the presentation is based. As we know, high level evidence demonstrates a multi-parametric MRI with targeted biopsy are able to increase the detection of clinically significant disease compared to performing systematic biopsy alone. At the same time, and perhaps more importantly, we can decrease the detection of clinically insignificant prostate cancer, reducing over diagnosis and treatment. Although multiparametric MRI is accurate in detecting and localizing suspicious clinically significant lesions, pathological confirmation is still necessary to confirm the cancer diagnosis, assess aggressiveness in planned treatment. Thus, the objective of this talk is describe the advantages and disadvantages and discuss challenges of visual cognitive targeted biopsies, software assisted MRI-TRUS fusion biopsies, and direct in-bore MRI targeted biopsies.

MRI targeted biopsy, regardless of approach, has in common that the multiparametric MRI information is analyzed and used to target one or more biopsy needles into a region of the prostate suspicious for tumor. Suspicious lesions identified on the MRI can be targeted under direct ultrasound or MRI guidance. And in the coming slides, we're going to go through three different approaches including a cognitive fusion, MRI-TRUS fusion, and direct in-bore MRI-guided biopsy. The first approach to be adopted is the cognitive MRI ultrasound fusion. In this approach, the ultrasound operator directs the biopsy needle towards the suspicious lesion that was identified on the MRI. The performing operator cognitively correlates the MRI findings with the realtime TRUS ultrasound images to sample the identified region of interest. Anatomical landmarks can be used as internal fiducials, and examples, as highlighted in the figures here, include BPH nodules, cysts or calcifications, gland contours, the location of the seminal vesicle or the urethra.

There are, however, disadvantages of this approach as biopsy accuracy may be limited, particularly in patients where there's an absence of internal fiducials. This may be even more notable for patients with small lesions, anteriorly located lesions, or those at the apex or base of the prostate where TRUS biopsy is known to be somewhat challenging. Additionally, there's no image confirmation that a biopsy was performed accurately because the cognitive biopsy does not allow for tracking and recording of biopsy and target coordinates. Additionally, differences in patient positioning and the use of a rectal ultrasound probe can distort the anatomy and result in sampling error. However, there are a number of important advantages. The first of these is that there's no need for a specialized and often expensive registration software, so it enables the use of a biopsy approach that allows targeting more widespread in generalizable.

Additionally, the performing operator can combine targeted biopsy with systematic TRUS biopsy seamlessly in one session. In terms of the role of a cognitive fusion, it appears to be most useful for sampling large lesions or diffuse abnormalities located in the peripheral zone of the prostate. In many countries, there's an inability to access expensive fusion equipment and cognitive MRI fusion-guided biopsy is potentially a first step to improve biopsy accuracy and leverage the real benefits of i. The next approach is MRI-TRUS fusion biopsies, and in this approach software-based platforms use previously obtained MRI information fused with realtime TRUS images. Importantly, these are performed in different sessions such that the MRI may be presegmented before the biopsy is performed.

Owing to deformations of the prostate that occur with transrectal ultrasound, adjustments are needed to adequately fuse the different imaging sets. And some software packages, as we'll discuss in coming slides, offer elastic image registration algorithms that allow for the surface contour to be matched between the MRI and the TRUS images. There are, as highlighted here, a number of platforms that offer fusion biopsy approaches. Some of these are rigidly registered and others, as we just alluded to, allow for elastic registration to capture deformation of the prostate. At this point in time, I'm going to hand it over to Zach to walk us through the remainder of MRI-TRUS fusion and discuss in-bore MRI biopsy as well.

Zach Klaassen: Thanks so much, Chris. So with regards to MRI fusion, it's important to understand the procedural steps for image registration. First off, the prostate MRI images must be acquired and the lesion must be assessed. Secondly, the prostate outline in suspicious legions are segmented on multiparametric MRI and uploaded into the ultrasound equipment, and this is often the T2 weighted images. Thirdly, image registration takes place by either contouring the prostate boundaries or using internal fiducials as markers. With regards to fine-tuning registration and movement tracking, to reduce registration inaccuracies a landmark as close to the region of interest as possible is chosen for image coupling. After the images are fused, there should be a cognitive enhancement by the operator who continuously performs mental verifications of the correct orientation of the probe relative to the prostate in the region of interest. As we can see here on the right, this is a cyst next to a PI-RADS 5 lesion and the cyst is being used as a marker for identifying this PI-RADS 5 lesion.

Movement tracking is done by a small electromagnetic track and field generator in combination with a sensor on the ultrasound probe. MR and TRUS images are then displayed side by side for cognitive monitoring of the registration and biopsy procedure. There are several disadvantages and advantages for fusion MR-guided biopsy that the authors list. With regards to disadvantages, this approach is more time consuming than cognitive MR-guided biopsy and expensive to implement into clinical practice. Additionally, it requires expensive coupling software and adequate training to correctly use the equipment. There are several advantages to this approach, it's a relative ease of implementation, lower cost and less time needed than the more expensive in-bore MRI-guided biopsy. Additional sampling of biopsy cores are able to be performed in the same session as systematic sampling.

With regards to the overall role for fusion MR-guided biopsy, the authors note that this should be the primary workhorse for prostate biopsy, the advantages of improved detection of clinically significant prostate cancer using multiparametric MRI targeted biopsy, better accuracy and better reliability compared to cognitive MR-guided biopsy, in combination with the advantage of being easy to use in the outpatient setting, make this the ideal first option for MR-guided biopsies. Moving to our final MRI-guided biopsy approaches is the in-bore MR-guided biopsy. This also uses multiparametric visualization in directing the biopsy needle. Although multiparametric MRI is used for both diagnostic and for needle guidance, acquisition of the diagnostic multiparametric MRI and in-bore MRI-guided biopsy are done in separate sessions.

With regards to procedural steps for the MR-guided in-bore biopsy, first the patients are placed headfirst and prone in the scanner with a rectally inserted needle guide as we can see here in this picture on the right. Secondly, axial T2 weighted images and diffusion weighted images are obtained to reproduce the previously determined location of the lesion. Third, to direct the needle towards a lesion, a physician needs to walk into the MR scanner room and move the patient partially out of the magnet in order to readjust the needle guide and new images are then required. We can see here on this figure on the right in panel A, the needle is going in. It's clearly not quite directed towards this PI-RADS 5 lesion in the prostate, but with adjustments we can see the needle is then directed towards the appropriate lesion. And finally, it's important to note that this procedure may have to be done several times, particularly if several target lesions are biopsied.

With regards to disadvantages and advantages of the in-bore MR-guided biopsy, the first disadvantage is that it requires at least 30 to 60 minutes per procedure and depends on how many lesions are biopsied. Secondly, there are scheduling difficulties and there's also a steep learning curve for this approach. With regards to advantages for in-bore MR-guided biopsy, it's likely the most accurate approach and it's also able to direct the needle towards the area within the suspicious lesion with the lowest ADC value, which likely correlates with the most aggressive part of the tumor. The role of in-bore MR-guided biopsy, this should be used for selected cases in which fusion MR-guided biopsy may be more challenging. Furthermore, it's also used for very small suspicious lesions and in cases where the coupling system of the fusion MR-guided biopsy fails, or when there's a high clinical suspicion for clinically significant prostate cancer, fusion or cognitive MR-guided biopsy is negative, or these approaches show insignificant prostate cancer.

In conclusion, fusion MR-guided biopsy should be the first choice in prostate cancer biopsy, which is suited for most patients. Direct in-bore MR-guided biopsy is used in selected difficult cases and is mainly used as a problem solver in patients with a negative fusion MR-guided biopsy outcome and a persistent high suspicion for clinically significant prostate cancer. Finally, cognitive MR-guided biopsy seems to be best used for sampling larger lesions and diffuse processes. Thank you very much for your attention and we hope you enjoyed this UroToday discussion of targeted biopsy in the setting of multiparametric MRI.