Purpose:
Micro-ultrasound is a novel high resolution ultrasound technology aiming to improve prostate imaging and, consequently, the diagnostic accuracy of ultrasound-guided prostate biopsy. Micro-ultrasound–guided prostate biopsy may present comparable detection rates to the standard of care multiparametric magnetic resonance imaging-targeted prostate biopsy for the diagnosis of clinically significant prostate cancer. We aimed to compare the detection rate of micro-ultrasound vs multiparametric magnetic resonance imaging-targeted prostate biopsy for prostate cancer diagnosis.

Materials and Methods:
We performed a systematic review and meta-analysis of diagnostic accuracy studies comparing micro-ultrasound–guided prostate biopsy to multiparametric magnetic resonance imaging-targeted prostate biopsy as a reference standard test (PROSPERO ID: CRD42020198326). Records were identified by searching in PubMed®, Scopus® and Cochrane Library databases, as well as in potential sources of gray literature until November 30th, 2020.

Results:
We included 18 studies in the qualitative and 13 in the quantitative synthesis. In the quantitative synthesis, 1,125 participants received micro-ultrasound–guided followed by multiparametric magnetic resonance imaging-targeted and systematic prostate biopsy. Micro-ultrasound and multiparametric magnetic resonance imaging-targeted prostate biopsies displayed similar detection rates across all prostate cancer grades. The pooled detection ratio for International Society of Urological Pathology Grade Group ≥2 prostate cancer was 1.05 (95% CI 0.93–1.19, I2=0%), 1.25 (95% CI 0.95–1.64, I2=0%) for Grade Group ≥3 and 0.94 (95% CI 0.73–1.22, I2=0%) for clinically insignificant (Grade Group 1) prostate cancer. The overall detection ratio for prostate cancer was 0.99 (95% CI 0.89–1.11, I2=0%).

Conclusions:
Micro-ultrasound–guided prostate biopsy provides comparable detection rates for prostate cancer diagnosis with the multiparametric magnetic resonance imaging-guided prostate biopsy. Therefore, it could be considered as an attractive alternative to multiparametric magnetic resonance imaging-targeted prostate biopsy. Nevertheless, high quality randomized trials are warranted to corroborate our findings.

Introduction
Magnetic Resonance Imaging (MRI) has emerged as the most accurate diagnostic tool, showing a high sensitivity in the diagnosis of clinically significant prostate cancer (csCaP). However only a minority of patients with a PI-RADS 3 lesion at multiparametric magnetic resonance imaging (MRI) are diagnosed with csCaP. The aim of the current study was to assess whether high resolution micro-ultrasound (microUS) could help in sub-stratifying the risk of csCaP in this specific population.

Material and methods
We retrospectively analyzed the records of 111 consecutive patients scheduled for a prostate biopsy with at least 1 PI-RADS 3 lesions at MRI. We excluded patients with a PIRADS >3 lesion, even if they had a coexisting PIRADS 3 lesions. MicroUS was performed in all patients before prostate biopsy by an operator blind to MRI results. The Prostate Risk Identification using MicroUS (PRI-MUS) protocol was used to assess the risk of CaP and csCaP. All patients received both targeted and systematic biopsies. The primary endpoint was to determine the diagnostic accuracy of microUS in detection of csCaP in patients with a PI-RADS 3 lesion at MRI. Specifically, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of microUS were determined. Multivariable logistic regression models (MLRMs) were fitted to identify predictors of CaP. The diagnostic accuracy was reported as area under the receiver operator characteristic (ROC) curve.

Results
Overall, 43 patients (38.7%) harboured CaP and 22 (20%) csCaP. MicroUS showed a high sensitivity and negative predictive value (100%), while its specificity and positive predictive value were 33.7% and 27.2%, respectively. Among patients without lesions at microUS, 25 (83.3%) did not harbour CaP, while 5 (16.7%) patients were diagnosed with a Gleason score 6 CaP, with no patients harbouring csCaP. Using microUS, the csCaP detection would have remained 100%, while reducing the detection of insignificant CaP of a 23.8% extent (n = 5). In MLRMs, lesion identified at microUS and continuously-coded PSAd were independent predictors of CaP. The accuracy of a model including PRI-MUS score, digital rectal examination (DRE), PSA density, age and family history was 0.744 (95% CI: 0.645 – 0.843).

Conclusion
In our single-institutional retrospective study, microUS was potentially capable to stratify the presence of CaP in patients with an equivocal MRI. Further prospective studies on larger populations are needed to validate our results.

Keywords
Prostate cancerDiagnosisPi-Rads 3Prostate biopsyTargeted biopsiesMultiparametric MriMicro-ultrasound

We read with great interest the article by Klotz et al discussing high-resolution micro-ultrasound and multiparametric magentic resonace imaging (mpMRI) for prostate cancer detection, recently published in the Canadian Urological Association Journal.1 We would like to congratulate the authors on the honest analysis of their multicentric data; it is always difficult to retrieve scientific information from many centers, which almost always use different protocols when managing patients. We have become strong supporters of micro-ultrasound and we believe this new technology has the potential to become the first-level test for patients with a clinical suspicion of prostate cancer

N/A

Background:
Multiparametric magnetic resonance imaging (MRI) represents the gold standard for the diagnosis of clinically significant prostate cancer (csPCa). The search for alternative diagnostic techniques is still ongoing.

Objective:
To determine the accuracy of microultrasound (microUS) for the diagnosis of csPCa within prospectively collected cohort of patients with a suspicion of prostate cancer (PCa) according to MRI.

Design, setting, and participants:
A total of 320 consecutive patients with at least one Prostate Imaging Reporting and Data System (PIRADS) ≥3 lesion according to MRI were prospectively enrolled.

Intervention:
All patients received microUS before prostate biopsy using the ExactVu system; the Prostate Risk Identification using microUS (PRI-MUS) protocol was used to identify targets. The urologists were blinded to MRI results until after the microUS targeting was completed. All patients received both targeted (based on either microUS or MRI findings) and randomized biopsies.

Outcome measurements and statistical analysis:
The sensitivity and specificity of microUS to determine the presence of csPCa (defined as at least one core with a Gleason score ≥7 PCa) were determined. Multivariable logistic regression analysis was fitted to determine the predictors of csPCa.

Results and limitations:
Clinically significant PCa was diagnosed in 116 (36.3%) patients. The sensitivity and negative predictive value of microUS for csPCa diagnosis were 89.7% and 81.5%, while specificity and positive predictive value were 26.0% and 40.8%, respectively. A combination of microUS-targeted and randomized biopsies would allow diagnosing the same proportion of csPCa as that diagnosed by an approach combining MRI-targeted and randomized biopsies ( n = 113; 97.4%), with only three (2.6%) csPCa cases diagnosed by a microUS-targeted and three (2.6%) by an MRI-targeted approach. In a logistic regression model, an increasing PRI-MUS score was an independent predictor of csPCa ( p ≤ 0.005). The main limitation of the current study is represented by the fact that all patients had suspicious MRI.

Conclusion:
Microultrasound is a promising imaging modality for targeted prostate biopsies. Our results suggest that a microUS-based biopsy strategy may be capable of diagnosing the great majority of cancers, while missing only few patients with csPCa.

Patient summary:
According to our results, microultrasound (microUS) may represent an effective diagnostic alternative to magnetic resonance imaging for the diagnosis of clinically significant prostate cancer, providing high sensitivity and a high negative predictive value. Further randomized studies are needed to confirm the potential role of microUS in the diagnostic pathway of patients with a suspicion of prostate cancer.

Keywords:

1. Prostate cancer, Diagnosis, Prostate biopsy, Targeted biopsies, Multiparametric magnetic resonance imaging, microultrasound

References:

1. Department of Urology, Humanitas Clinical and Research Center, Rozzano, Italy

Only a decade ago there were insufficient imaging options for the detection and local staging of prostate cancer. However, the introduction of multiparametric magnetic resonance imaging (mpMRI) has advanced a much-needed tool for this scope of application. The possibilities and limitations of mpMRI have been well studied. Imaging must be acquired and evaluated using a standardized protocol (the latest version of PI-RADS). Sensitivity has been shown to increase with higher grades and larger tumors and while the detection rate on a per patient basis is relatively high, the per-lesion detection rate is far inferior. Various specialists have attempted to elevate the use of transrectal ultrasound, a tool frequently used by all urologists. Encouragement for this idea comes from a recently introduced system of high frequency transrectal ultrasound. The level of evidence supporting its use in the detection and staging of prostate cancer is not comparable to mpMRI yet, but initial prospective studies indicate good potential. The sensitivity of microultrasound and mpMRI for clinically significant prostate cancer ranges from 94-100% and 88-90%, respectively. Further areas of application, such as local staging for prostate and bladder cancer, are currently being evaluated. In summary, microultrasound presents a promising technology for further improving urological imaging and allows for the possibility of returning prostate cancer imaging to urologists. This review will summarize the current scientific basis for the use of microultrasound in the detection of prostate cancer.

Keywords:
Diagnostic imaging, Prostatic neoplasms, Ultrasonography

INTRODUCTION:
High-resolution micro-ultrasound has the capability of imaging prostate cancer based on detecting alterations in ductal anatomy, analogous to multiparametric magnetic resonance imaging (mpMRI). This technology has the potential advantages of relatively low cost, simplicity, and accessibility compared to mpMRI. This multicenter, prospective registry aims to compare the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of mpMRI with high-resolution micro-ultrasound imaging for the detection of clinically significant prostate cancer.

METHODS:
We included 1040 subjects at 11 sites in seven countries who had prior mpMRI and underwent ExactVu micro-ultrasound-guided biopsy. Biopsies were taken from both mpMRI targets (PI-RADS >3 and micro-ultrasound targets (PRIMUS >3). Systematic biopsies (up to 14 cores) were also performed. Various strategies were used for mpMRI target sampling, including cognitive fusion with micro-ultrasound, separate software-fusion systems, and software-fusion using the micro-ultrasound FusionVu system. Clinically significant cancer was those with Gleason grade group ≥2.

RESULTS:
Overall, 39.5% were positive for clinically significant prostate cancer. Micro-ultrasound and mpMRI sensitivity was 94% vs. 90%, respectively (p=0.03), and NPV was 85% vs. 77%, respectively. Specificities of micro-ultrasound and MRI were both 22%, with similar PPV (44% vs. 43%). This represents the initial experience with the technology at most of the participating sites and, therefore, incorporates a learning curve. Number of cores, diagnostic strategy, blinding to MRI results, and experience varied between sites.

CONCLUSION:
In this initial multicenter registry, micro-ultrasound had comparable or higher sensitivity for clinically significant prostate cancer compared to mpMRI, with similar specificity. Micro-ultrasound is a low-cost, single-session option for prostate screening and targeted biopsy. Further larger-scale studies are required for validation of these findings.

Keywords:

1. Prostate cancer, Imaging, High resolution micro ultrasound, MRI, Pi-RADS

References:

1. University of Toronto
2. Insituto Clinicao Humanitas, Rozzano, Italy
3. Instituto Clinico Humanitas, Rozzano, Italy
4. Urología Clínica, Clínica IMQ Zorrotzaurre
5. Urología Clínica, Clínica IMQ Zorrotzaurre
6. Polyclinique Reims-Bezannes, Bezannes
7. Charité Universitätsmedizin Berlin
8. Ordensklinikum Linz, Barmherzige Schwestern Linz
9. Groupe Urologie Saint-Augustin, Bordeaux
10. Institut Mutualiste Montsouris, Paris
11. Glickman Urological Institute, Cleveland Clinic, Cleveland
12. Carolina Urologic Research Center, Myrtle Beach, SC
13. Urology of Virginia, Virginia Beach

Background:
Although multiparametric magnetic resonance imaging (mpMRI) revolutionized the implementation of prostate biopsies, a considerable amount of clinically significant prostate cancer (csPCa) is missed when performing mpMRI-targeted biopsies only. Microultrasound (micro-US) is a new modality that allows real-time targeting of suspicious regions.

Objective:
To evaluate micro-US of the prostate with real-time targeting of suspicious regions in patients suspected to have prostate cancer (PCa).

Design, setting, and participants:
We examined 159 patients with prior mpMRI and suspicion of PCa with micro-US in the period from February to December 2018. Micro-US lesions were documented according to the prostate risk identification for micro-US (PRI-MUS) protocol, and were blinded to the mpMRI results and targeted independently of the mpMRI lesions.

Outcome measurements and statistical analysis:
The main outcomes were cancer detection rate, additional detection of csPCa, and International Society of Urological Pathology (ISUP) grade group upgrading via micro-US.

Results and limitations:
PCa was found in 113/159 (71%) men, with 49% (78/159) having clinically significant cancer (csPCa; ISUP ≥ 2). Micro-US–targeted biopsies resulted in a higher ISUP grade group than the nontargeted biopsies in 26% (42/159), compared with both nontargeted and MRI-targeted biopsies in 16% (26/159). In 17% (27/159) of patients, targeted mpMRI–guided biopsy was negative with cancer identified in the micro-US–guided biopsy, of whom 20 had csPCa. The comparison with only MRI-positive patients is the main limitation of this analysis.

Conclusion:
Our data show an added benefit of micro-US in addition to mpMRI-targeted biopsies in a population of men at risk of PCa. A novel biopsy protocol with solely targeted biopsy with micro-US and mpMRI seems possible, replacing conventional ultrasound and omitting standard systematic biopsies.

Patient summary:
In this report, we looked at the performance of microultrasound in the setting of diagnosing prostate cancer. We found that microultrasound is a good addition to magnetic resonance imaging (MRI) of the prostate and presents an alternative for men who may not undergo MRI.

Keywords:

1. Prostate biopsy, Microultrasound, Target biopsy, Multiparametric magnetic resonance imaging, Prostate cancer

References:

1. Charité—University Medicine Berlin, Berlin, Germany

OBJECTIVES:
To evaluate the ability of high-frequency (29 MHz) transrectal micro-ultrasound (microUS) as a second-look examination after biparametric MRI (bp-MRI) and to reidentify focal lesions seen on diagnostic MRI and to detect new ones

METHODS:
A total of 118 consecutive men (mean age, 66±13 [SD] years; range, 49-93 years) with a mean prostate-specific antigen level of 11±19 (SD) ng/mL (range, 2-200 ng/mL) and at least one focal lesion (MRI+) with a score >2 on bp-MRI were included. Of these, 79/118 (66.9%) were biopsy-naïve and 102/118 (86.5%) had non-suspicious rectal examination. All patients had MRI-directed microUS-guided biopsy using a 29-MHz transducer. All lesions visible on micro-ultrasound (microUS+) were targeted without image fusion, which was only used for MRI+/microUS- lesions. Significant prostate cancer (sPCa) was defined by a Gleason score ≥7 or a maximum cancer core length >3 mm.

RESULTS:
A total of 144 focal prostatic lesions were analyzed, including 114 (114/144, 79.2%) MRI+/microUS+ lesions, 13 MRI+/microUS- lesions (13/144, 9%), and 17 MRI-/microUS+ lesions (17/144, 11.8%). Significant PCa was detected in 70 MRI+/microUS+ lesions (70/114, 61.4%), in no MRI+/microUS- lesion (0/13, 0%), and in 4 MRI-/microUS+ lesions (4/17, 23.5%). The sensitivity and specificity of microUS on a per-patient and a per-lesion basis were 100% (95% CI, 84.9-100%) and 22.8% (95% CI, 12.5-35.8%) and 100% (95% CI, 85.1-100%) and 22.6% (95% CI, 12.3-36.2%), respectively.

CONCLUSION:
MicroUS, as a second-look examination, may show promise to localize targets detected on bp-MRI.

Keywords:

1. Biopsy; Magnetic resonance imaging; Prostatic neoplasms; Ultrasonography

References:

1. Department of Radiology, Clinique de l'Alma, Paris, France. francois.cornud@imagerietourville.com.
2. Department of Radiology, Hôpital Cochin, Assistance Publique Hôpitaux Paris, AP-HP, Paris, France. francois.cornud@imagerietourville.com.
3. Department of Radiology, Clinique de l'Alma, Paris, France.
4. Department of Urology, Clinique St Jean de Dieu, Paris, France.
5. Department of Urology, Clinique Turin, Paris, France.
6. Department of Urology, Clinique de l'Alma, Paris, France.
7. Department of Radiology, Hôpital Cochin, Assistance Publique Hôpitaux Paris, AP-HP, Paris, France.
8. Université de Paris Descartes Paris V, Paris, France.
9. Centre de Pathologie, Amiens, France

High resolution micro-ultrasound (micro-u/s) is a novel technology that permits visualization of lesions suspicious for prostate cancer. The resolution of 70 μ, that of a prostatic duct, means that alterations in ductal anatomy and cellular density are readily apparent. Initial experience in multiple centers comparing it to mpMRI suggests that the sensitivity for clinically significant prostate cancer is comparable or superior. Specificity is comparable or mildly reduced. Micro-u/s is an inexpensive, accessible and convenient alternative to mpMRI for imaging and diagnosing prostate cancer.
Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Keywords:

1. High resolution micro ultrasound; Prostate cancer; Prostate imaging; Prostate ultrasound

References:

1. Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, USA. Electronic address: Laurence.klotz@sunnybrook.ca.

PURPOSE:
We compared cancer detection rates in patients who underwent magnetic resonance imaging cognitive guided micro-ultrasound biopsy vs robotic ultrasound magnetic resonance imaging fusion biopsy for prostate cancer.

METHODS:
Among 269 targeted biopsy procedures 222 men underwent robotic ultrasound magnetic resonance imaging fusion biopsy and 47 micro-ultrasound biopsy. Robotic ultrasound magnetic resonance imaging fusion biopsy was performed using the transperineal Artemis™ device while micro-ultrasound biopsy was performed transrectally with the high resolution ExactVu™ system. Random biopsies were performed in addition to targeted biopsy in both modalities. Prostate cancer detection rates and concordance between random and target biopsies were also assessed.

RESULTS:
Groups were comparable in terms of age, prostate specific antigen, prostate volume and magnetic resonance PI-RADS (Prostate Imaging Reporting and Data System) version 2 score. The micro-ultrasound biopsy group presented fewer biopsied cores in random and target approaches. In targeted biopsies micro-ultrasound biopsy cases presented higher detection of clinically significant disease (Gleason score greater than 6) than the robotic ultrasound magnetic resonance imaging fusion biopsy group (38% vs 23%, p=0.02). When considering prostate cancer detection regardless of Gleason score or prostate cancer detection by random+target biopsies, no difference was found between the groups. However, on a per core basis overall prostate cancer detection rates favored micro-ultrasound biopsy in random and targeted scenarios. In addition, the PRI-MUS (Prostate Risk Identification Using Micro-Ultrasound) score yielded by micro-ultrasound visualization was independently associated with improved cancer detection rates of clinically significant prostate cancer.

CONCLUSION:
In our initial experience micro-ultrasound biopsy featured a higher clinically significant prostate cancer detection rate in target cores than robotic ultrasound magnetic resonance imaging fusion biopsy, which was associated with target features in micro-ultrasound (PRI-MUS score). These findings reinforce the role of micro-ultrasound technology in targeted biopsies.

Keywords:

1. biopsy; high-intensity focused; magnetic resonance imaging; prostatic neoplasms; transrectal; ultrasound

References:

1. Institut Mutualiste Montsouris, Paris, France.
2. Hospital Israelita Albert Einstein, São Paulo, Brazil.
3. Hospital Cardiopulmonar, Bahia, Brazil.
4. Hospital Universitari Germans Trias I Pujol, Badalona, Spain.
5. IRCCS Ospedale San Raffaele, Milan, Italy.

PURPOSE:
To assess the prostate cancer (PCa) detection accuracy of transperineal prostate biopsy using mpMRI/Ultrasound Fusion Targeted Biopsy (TBX) and Micro-Ultrasound (micro-US) during the same procedure. Micro-US is a new high-resolution imaging system that allows real-time targeted biopsy.

METHODS:
194 consecutive patients underwent transperineal prostate biopsies using real-time targeted Micro-US (ExactVuTM) and TBX (BiopSee®) in the same procedure, from February 2018 - September 2019. Biopsies were performed using a transperineal needle guide attached to the 29MHz High resolution Micro-US transducer.

RESULTS:
The overall positive rate was 56% (108) for PCa and 42% (81) for csPCa (GG>1), adding Micro-US and MRI detected significantly more csPCa than systematic biopsy (SBX) (p<0.001). Micro-US found 12/108 (11%) PCa that were missed by all other techniques and 11 (92%) were csPCa. Both PI-RADS and PRI-MUS were strong predictors of csPCa in a Logistic Regression Model (AUC = 0.76). For PSA>4, PI-RADS>3 there was an improvement in detection rate between PRI-MUS 4 and PRI-MUS 5 (52% GG>1 to 92% GG>1). No fever or clinical infection was observed, 17 (8.7%) patients presented minor complications (Clavien Dindo I).

CONCLUSION:
This is the first study using a transperineal approach for Micro-ultrasound guided biopsy and mpMRI fusion biopsy. The results show a high accuracy for PCa and csPCA diagnosis, without infectious complications. The proposed method should be validated in large randomized clinical trials.

Keywords:

1. Fusion Biopsy; Multiparametric magnetic resonance imaging; Prostate Cancer; Transperineal Prostate Biopsy; micro-US; micro-ultrasounds; targeted biopsies.

References:

1. Department of Urology, Instituto Cirugía Urológica Avanzada (ICUA), Madrid, Spain.

PCa is a disease with a wide range of tissue patterns and this adds to its classification difficulty. Moreover, the data source heterogeneity, i.e. inconsistent data collected using different machines, under different conditions, by different operators, from patients of different ethnic groups, etc., further hinders the effectiveness of training a generalized PCa classifier. In this paper, for the first time, a Generative Adversarial Network (GAN)-based three-player minimax game framework is used to tackle data source heterogeneity and to improve PCa classification performance, where a proposed modified U-Net is used as the encoder. Our dataset consists of novel high-frequency ExactVu ultrasound (US) data collected from 693 patients at five data centers. Gleason Scores (GSs) are assigned to the 12 prostatic regions of each patient. Two classification tasks: benign vs. malignant and low-vs. high-grade, are conducted and the classification results of different prostatic regions are compared. For benign vs. malignant classification, the three-player minimax game framework achieves an Area Under the Receiver Operating Characteristic (AUC) of 93.4%, a sensitivity of 95.1% and a specificity of 87.7%, respectively, representing significant improvements of 5.0%, 3.9%, and 6.0% compared to those of using heterogeneous data, which confirms its effectiveness in terms of PCa classification.

Background:
Prostate cancer is a frequently diagnosed malignant solid tumor in men. The accuracy of diagnosis is becoming increasingly important. This meta-analysis evaluated the accuracy of micro-ultrasound in the diagnosis of clinically significant prostate cancer.

Methods:
We searched PubMed, Embase, Web of Science, and Cochrane Library databases to recruit studies in English. The quality assessment of diagnostic accuracy studies-2 protocol was used to evaluate the literature quality. Publication bias was analyzed using Deeks’ funnel plot asymmetry test. We calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and 95% confidence interval (95% CI) for studies of micro-ultrasound imaging for prostate cancer. The results were assessed by the summary receiveroperating characteristic curve (SROC). Ultimately, a univariable meta-regression and subgroup analysis, Fagan plot, and a likelihood matrix were conducted.

Results:
A total of seven studies containing 769 patients were included in this meta-analysis. Micro-ultrasound had a pooled sensitivity, specificity, DOR, and an area under the SROC of 0.91, 0.49, 10, and 0.82, respectively. Based on these findings, micro-ultrasound has superior ability to diagnose clinically significant prostate cancer.

Conclusion:
Micro-ultrasound is a more convenient and cost-effective method in realtime imaging during the biopsy procedure in detecting clinically significant prostate cancer. Although micro-ultrasound has shown promising results, more clinical data and comprehensive analysis are still needed.

Keywords:

1. micro-ultrasound, clinically significant prostate cancer, diagnostic accuracy, biopsy, ExactVu, meta-analysis

Background:
The PRI-MUSTM (Prostate Risk Identification for Micro-Ultrasound) protocol was developed in 2016 to identify suspicious areas
seen by the ExactVu™ micro-ultrasound imaging platform. While a retrospective validation was performed, no prospective validation has been
published in the peer-reviewed literature. Further, this protocol was developed for the peripheral zone and it is unclear whether the accuracy to
predict clinically significant cancer is uniform throughout the gland.

Methods:
399 prostate biopsies were performed in 372 patients using the ExactVu micro-ultrasound system (Exact Imaging, Markham, Canada)
from January 2018 to May 2019 at the Ordensklinikum Linz (Linz, Austria). Subjects had a median PSA of 6.7 (IQR 4.5-11.2) ng/mL and 30% had
positive DRE. Suspicious areas were assessed in real-time using PRI-MUS and a TRUS biopsy was performed in the same session under microultrasound
guidance. Biopsies were carried out by 5 providers and results from pathology were then compared with the image findings.

Results:
Biopsy pathology confirmed a cancer diagnosis in 60% of patients, with 42% of patients harboring Grade Group (GG) > 1 cancer.
The PRI-MUS protocol had an area under the receiver-operator characteristic (AUC) of 0.76 for predicting GG>1 cancer in the peripheral zone.
This accuracy varied between 0.68-0.83 depending on prostate region, with highest accuracy in the prostate apex and lowest accuracy in the base.
Anterior targets were sampled but generally not assigned a PRI-MUS score as the system is currently only validated in the peripheral zone, still, in
the 33/737 anterior samples assigned a PRI-MUS score AUC was 0.80.

Conclusion:
Micro-ultrasound and the PRI-MUS protocol are useful tools to detect cancer and appear to maintain strong diagnostic value
throughout the prostate. This technology holds promise for reducing the high false-negative rate of prostate biopsy, without relying on multimodality,
multi-specialty solutions like mpMRI.

Keywords:
Exact Imaging; mpMRI; ultrasound; Micro-ultrasound; Biopsy; Prostate cancer

PURPOSE:
This report presents our early experience at Cleveland Clinic replacing conventional ultrasound with a novel 29 MHz
high-resolution micro-ultrasound system for both systematic sampling and real-time targeting of suspicious regions during
prostate biopsy. The added value of micro-ultrasound and MRI over systematic biopsy is presented.

METHODS:
Sixty-seven consecutive subjects (January–August 2018) from our prospective database who underwent prostate
biopsy using the micro-ultrasound system were included. 19/67 had prostate MRI imaging available. MRI targets were
sampled using the UroNav fusion system. Patients had a median PSA of 5.37 ng/mL (IQR 4.13–8.74).

RESULTS:
38/67 (56.7%) subjects were positive for prostate cancer. In six of these cases, systematic biopsy was negative with
only micro-ultrasound targeted samples detecting cancer. In two other cases, patients were upgraded from Grade Group 1
to Grade Groups 4 and 2 based on micro-ultrasound targets. Micro-ultrasound targets detected cancer in two subjects where
MRI was negative (Grade Groups 3 and 2). MRI targets alone did not change the overall diagnosis of any subjects. Switching
biopsy guidance to real-time micro-ultrasound increased detection rate on prostate biopsy from 44.8% (30/67) to 56.7%
(38/67), a relative increase of 26.7%.

CONCLUSION:
High-resolution micro-ultrasound identified clinically significant cancer that would have, otherwise, been missed
by both MRI fusion and systematic biopsy and was useful in both biopsy naïve and repeat negative patients. Early results
from this small, single-center cohort are promising, particularly given the ease with which micro-ultrasound can replace the
conventional ultrasound in standard prostate biopsy procedures.

KEYWORDS:
Micro-ultrasound · Prostate cancer · TRUS · Biopsy · Systematic · Targeted · mpMRI · ExactVu

Multiparametric magnetic resonance imaging (mpMRI) and MRI/ultrasound (US) fusion targeted biopsies are an increasingly popular alternative to randomized biopsies, but adoption of this technique has been limited owing to its additional costs and complexity. High-resolution micro-ultrasound (micro-US) is a real-time US-based imaging modality that allows real-time targeted prostate biopsies using the Prostate Risk Identification Using Micro-Ultrasound risk identification protocol. We compared the diagnostic accuracy of micro-US targeted biopsies (index test) and MRI/US fusion targeted biopsies (reference standard test) in detecting clinically significant prostate cancer (csPC), defined as Gleason ≥7 disease, in a prospectively collected cohort of 104 patients with suspected PC defined according to prostate-specific antigen, digital rectal examination, and the presence of at least one Prostate Imaging-Reporting and Data System ≥3 lesion at mpMRI. PC was diagnosed in 56 patients (54%) and csPC in 35 (34%). Micro-US sensitivity for csPC detection was 94%, with 33/35 csPC cases correctly identified. The negative predictive value was 90%, while the positive predictive value was 40% and the specificity was 28%. Of the 61 targeted zones concordant between micro-US and mpMRI, 24 were csPC. Discordant targeted lesions led to csPC discovery by micro-US in three cases and mpMRI in four cases. Both techniques missed one case for which csPC was diagnosed by systematic biopsies only.

Keywords:
Prostate cancer, Diagnosis, Prostate biopsy, Multiparametric magnetic resonance imaging, Micro-ultrasound, PRI-MUS

We describe our experience with four patients undergoing cryotherapy for treatment of prostate cancer. Micro-ultrasound was utilized in conjunction with standard transrectal ultrasound to intraoperatively assess lesions. In addition, the results were compared to preoperative mpMRI in several patients. The use of micro-ultrasound has been evaluated in clinical trials to include real-time imaging in the clinic for biopsies and fusion with prior mpMRI. We evaluated the technique in men with known prostate cancer undergoing cryoablation. Micro-ultrasound has the potential to replace the current clinical methods for targeted prostate biopsies and improve intraoperative monitoring.

Keywords:
Exact Imaging; mpMRI; Conventional ultrasound; Micro-ultrasound; Biopsy; Prostate cancer

Abbreviations:
mpMRI: Multiparametric Magnetic Resonance Imaging; PSA: Prostate Specificantigen; PIRADS v2: Prostate Imaging and Reporting
Data System Version 2; TRUS: Trans-Rectal Ultrasound

 

BACKGROUND:
Magnetic resonance imaging (MRI) has been proposed as a staging tool for bladder cancer (BC), but its use has been limited by its high costs and limited availability. Micro-ultrasound is a novel technology capable of providing high-resolution images of the prostate.

OBJECTIVE:
To test the feasibility of high-resolution micro-ultrasound in patients diagnosed with BC and its ability to differentiate between non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC).

DESIGN, SETTING, AND PARTICIPANTS:
This is an observational prospective study performed in 23 patients with a diagnosis of primary BC scheduled for an endoscopic treatment.

SURGICAL PROCEDURE:
Micro-ultrasound was performed before transurethral resection of bladder tumor using the ExactVu system with an EV29L 29-MHz side-fire transducer (Exact Imaging, Markham, Canada).

MEASUREMENTS:
Micro-ultrasound was performed before transurethral resection of bladder tumor using the ExactVu system with an EV29L 29-MHz side-fire transducer (Exact Imaging, Markham, Canada).

RESULTS AND LIMITATIONS:
Micro-ultrasound was accurate in differentiating the three layers of the bladder wall in all cases. Bladder cancers were clearly identified as heterogeneous structures protruding from the normal bladder wall. In 14 cases the lesions appeared confined to the lamina propria, and in all cases NMIBC was confirmed by the final pathological report. In the other patients, the lesions seemed to extend into the muscular layer, but MIBC was confirmed in five out of seven cases (71.4%) from the pathologist. The small sample size was the main limitation of the current study.

CONCLUSIONS:
Our findings showed that micro-ultrasound is able to differentiate the bladder wall layers and identify the bladder cancer stage. Further studies with a larger population and imaging correlation with MRI are warranted before its introduction in clinical practice.

PATIENT SUMMARY:
In this report, a new imaging technique was tested for the characterization of bladder cancer. Micro-ultrasound appears to be feasible and capable of discriminating between superficial and invasive tumors.

KEYWORDS:
Bladder cancer, Staging, Muscle-invasive bladder cancer, Non-muscle-invasive bladder cancer, Micro-ultrasound, High-resolution ultrasound

INTRODUCTION:
Active Surveillance monitoring of prostate cancer is unique in that most patients have low grade disease which is not well visualized by any common imaging technique. High-resolution (29 MHz) micro-ultrasound is a new real-time modality which has been demonstrated to be sensitive to significant prostate cancer and effective for biopsy targeting. This study compares micro-ultrasound imaging with MRI and conventional ultrasound for visualizing prostate cancer in active surveillance.

METHODS:
9 patients on active surveillance were imaged with mpMRI prior to biopsy. During the biopsy procedure, imaging and target identification was first performed using conventional ultrasound, then using micro-ultrasound. The mpMRI report was then un-blinded and used to determine cognitive fusion targets. Using micro-ultrasound, biopsy samples were taken from targets in each modality, plus 12 systematic samples.

RESULTS:
mpMRI and micro-ultrasound both demonstrated superior sensitivity to Gleason Sum 7 or higher cancer compared to conventional ultrasound (p=0.02 McNemar’s test). Micro-ultrasound detected 89% of clinically significant cancer, compared to 56% for mpMRI.

CONCLUSIONS:
Micro-ultrasound may provide similar sensitivity to clinically significant prostate cancer as mpMRI, and visualized all significant mpMRI targets. Unlike mpMRI, micro-ultrasound is performed in the office, in real-time during the biopsy procedure, and so is expected to maintain the cost-effectiveness of conventional ultrasound. Larger studies are needed before these results may be applied in a clinical setting.

KEY WORDS:
Prostate cancer, micro-ultrasound, MRI, PRI-MUS, PI-RADS, Active Surveillance

Urethrocavernous fistula is rarely reported, though should be considered within the differential diagnosis for men who present with urethral bleeding, particularly at time of erection. Ultrasonography with concomitant intracavernosal injection can be considered to confirm the diagnosis. Here we report a case of urethrocavernous fistula in a 48 year old man without preceding traumatic event.

Keywords:
Erectile dysfunction, Urethral bleeding, Urethrocavernous fistula

Currently, biopsies guided by transrectal ultrasound (TRUS) are the only method for definitive diagnosis of prostate cancer. Studies by our group suggest that quantitative ultrasound (QUS) could provide a more sensitive means of targeting biopsies and directing focal treatments to cancer-suspicious regions in the prostate. Previous studies have utilized ultrasound signals at typical clinical frequencies, i.e., in the 6-MHz range. In the present study, a 29-MHz, TRUS, micro-ultrasound system and transducer (ExactVu micro-ultrasound, Exact Imaging, Markham, Canada) was used to acquire radio frequency data from 163 patients immediately before 12-core biopsy procedures, comprising 1956 cores. These retrospective data are a subset of data acquired in an ongoing, multisite, 2000-patient, randomized, clinical trial (clinicaltrials.gov NCT02079025). Spectrum-based QUS estimates of effective scatter diameter (ESD), effective acoustic concentration (EAC), midband (M), intercept (I) and slope (S) as well as envelope statistics employing a Nakagami distribution were used to train linear discriminant classifiers (LDCs) and support vector machines (SVMs). Classifier performance was assessed using area-under-the-curve (AUC) values obtained from receiver operating characteristic (ROC) analyses with 10-fold cross validation. A combination of ESD and EAC parameters resulted in an AUC value of 0.77 using a LDC. When Nakagami-µ or prostate-specific antigen (PSA) values were added as features, the AUC value increased to 0.79. SVM produced an AUC value of 0.77, using a combination of envelope and spectral QUS estimates. The best classification produced an AUC value of 0.81 using an LDC when combining envelope statistics, PSA, ESD and EAC. In a previous study, B-mode-based scoring and evaluation using the PRI-MUS protocol produced a maximal AUC value of 0.74 for higher Gleason-score values (GS >7) when read by an expert. Our initial results with AUC values of 0.81 are very encouraging for developing a new, predominantly user-independent, prostate-cancer, risk-assessing tool.

Keywords:
Prostate cancer; Quantitative micro-ultrasound; High frequency; Quantitative ultrasound; QUS

The ExactVu™ Micro-Ultrasound system is a new high resolution imaging system for visualizing the prostate and has been FDA, CE, and Health Canada approved for visualization and biopsy of the prostate. The PRI-MUS™ (Prostate Risk Identification for Micro-Ultrasound) protocol has previously been demonstrated to correlate with risk of prostate cancer and severity of cancer. Here we present a case where a healthy 50 year old subject with no known risk factors volunteered to test the ExactVu system and was found to harbour multiple PRI-MUS 3–5 lesions. This prompted PSA testing, biopsy and eventual diagnosis of significant prostate cancer. Comparative MRI and Micro-ultrasound images of index lesion are illustrated where the MRI lesion was visualized as a PI-RADS 3 - - and the micro-ultrasound identified the lesion at a PRI-MUS™ 5 - - which was correlated to the Gleason 7 (4+3) pathology. Due to its ease of use, real-time nature, cost-effectiveness comparable to conventional ultrasound, and its comprehensive risk identification protocol (PRI-MUS), micro-ultrasound has the potential to be a powerful screening and targeting tool for urologists.

Keywords:
Prostate cancer, Micro-ultrasound, Prostate biopsy, PRI-MUS, Biomarkers

PURPOSE:
Conventional ultrasound systems operate at 6 to 9 MHz and serve as the standard of care to guide prostate biopsies. We present a protocol using a novel high resolution (29 MHz) transrectal prostate micro-ultrasound system. This protocol includes a scoring system to assess the risk of prostatic carcinoma and enable real-time targeted biopsies.

MATERIALS AND METHODS:
The ExactVu™ system is currently being used in a multisite, 2,000-patient, randomized clinical trial. Cine loops of 400 biopsies from this trial were used to create the PRI-MUS™ (prostate risk identification using micro-ultrasound) protocol and risk scale. Validation was performed in an independent, pathology blinded set of 100 cines. Three of the 5 investigators performing this validation were familiar with micro-ultrasound but naïve to the PRI-MUS protocol and they received only 1 hour of training.

RESULTS:
Each increase in risk score demonstrated a 10.1% increase (95% CI 9.3-10.8) in the probability of clinically significant cancer. The risk score also increased with Gleason sum and cancer length with a slope of 0.15 (95% CI 0.09-0.21) and 0.58 (95% CI 0.43-0.73), respectively. Sensitivity and specificity were 80% and 37%, respectively, and the mean ± SD ROC AUC was 60% ± 2%. The protocol was more accurate for detecting high grade disease (Gleason sum greater than 7) with a peak AUC of 74% (mean 66%).

CONCLUSIONS:
The new resolution of the micro-ultrasound platform paired with the PRI-MUS protocol shows promise for real-time visualization of suspicious lesions and targeting of biopsies. The improved performance of the protocol in more significant disease is consistent with the focus of the field on decreasing insignificant diagnoses and detecting high risk disease early.

KEYWORDS: biopsy; clinical protocols; diagnostic imaging; prostatic neoplasms; ultrasonography

OBJECTIVES:
To determine how high-resolution transrectal ultrasound (HiTRUS) compares with conventional TRUS (LoTRUS) for the visualization of prostate cancer.

METHODS AND MATERIALS:
Twenty-five men with known prostate cancer scheduled for radical prostatectomy were preoperatively imaged with both LoTRUS (5MHz) and HiTRUS (21MHz). Dynamic cine loops and still images for each modality were saved and subjected to blinded review by a radiologist looking for hypoechoic foci ≥ 5 mm in each sextant of the prostate. Following prostatectomy, areas of prostate cancer ≥ 5 mm on pathologic review were anatomically correlated to LoTRUS and HiTRUS findings. The accuracy of LoTRUS and HiTRUS to visualize prostate cancer in each sextant of the prostate and to identify high-grade and locally advanced disease was assessed. The McNemar test was used to compare sensitivity and specificity and paired dichotomous outcomes between imaging modalities.

RESULTS:
Among 69 sextants with pathologically identified cancerous foci at radical prostatecomy, HiTRUS visualized 45 and missed 24, whereas LoTRUS visualized 26 and missed 43. Compared with LoTRUS, HiTRUS demonstrated improved sensitivity (65.2% vs. 37.7%) and specificity (71.6% vs. 65.4%). HiTRUS's agreement with pathologic findings was twice as high as LoTRUS (P = 0.006). HiTRUS provided a nonsignificant increase in visualization of high-grade lesions (84% vs. 60%, P = 0.11).

CONCLUSIONS:
HiTRUS appears promising for prostate cancer imaging. Our initial experience suggests superiority to LoTRUS for the visualization of cancerous foci, and supports proceeding with a clinical trial in the biopsy setting.

NOTE: The high-resolution ultrasound system (“HITRUS”)used in this study is an alpha version of the Exact Imaging ExactVu™ micro-ultrasound system. “Imagistx” is the former name of Exact Imaging.

KEYWORDS:
Diagnosis; Prostate cancer; Radical prostatectomy; Sensitivity and specificity; Ultrasound

Introduction:
This study aims to compare the sensitivity, specificity, NPV and PPV of mpMRI with the novel high-resolution micro-ultrasound imaging modality. This approach offers the benefits of simplicity, a single intervention for imaging and biopsy, leveraging the low cost of ultrasound. Micro-ultrasound may be used to image suspicious lesions and target biopsies in real-time with or without additional MRI-based targets.

Methods:
8 institutions in Europe and the USA participating, totaling 784 subjects

All subjects received both mpMRI and ExactVu™ micro-ultrasound imaging.

mpMRI targets sampled per site preference:

• cognitive fusion with micro-ultrasound
• separate software-fusion system
• software-fusion using micro-ultrasound FusionVu™

Micro-Ultrasound targets and systematic samples taken using the ExactVu™ micro-ultrasound system.

Clinically significant cancer was any Gleason Sum > 6 and targeted samples were taken for PI-RADS™ > 2 or PRI-MUS™,1 > 2 lesions with at least 2 samples per lesion

Results:
40% of cases were positive for clinically significant PCa

mpMRI sensitivity 89% and NPV 75%
Micro-ultrasound sensitivity 94% and NPV 83% both higher (p<0.01)

• Micro-ultrasound less specific (19% vs 23% for mpMRI)
• PPV 44% for both

Conclusion:

• Micro-ultrasound is an attractive option for screening and targeted biopsy. Sensitivity and NPV appear superior to MRI, but specificity is mildly reduced.
• Further larger-scale studies are required for validation of these findings.

Authors:
¹Instituto Clinico Humanitas, Rozzano, Italy,
²Urología Clínica, Clínica IMQ Zorrotzaurre, Spain,
³Polyclinique Reims-Bezannes, Reims, France,
⁴Charité Universitätsmedizin Berlin, Berlin, Germany,
⁵Groupe Urologie Saint-Augustin, Bordeaux, France,
⁶Glickman Urological Institute, Cleveland Clinic, Cleveland, USA,
⁷Sunnybrook Hospital, Toronto, Canada,
⁸Urology of Virginia, Virginia Beach, USA,

References:

1. Ghai, S. et al., “Assessing Cancer Risk in Novel 29 MHz Micro-Ultrasound Images of the Prostate”, Journal of Urology, 2016 Aug;196(2):562-9

Introduction:
Clinically significant prostate cancer (csPCa) detection rate is improved by pre-biopsy MRI. MRI/ultrasound fusion biopsy shows some limitations in terms of procedure duration and lack of precision. In-bore MR-guided biopsy is not widely available. Very high frequency transrectal ultrasound (micro-ultrasound, MUS) could therefore compensate for these limitations.

Methods:

• Micro-ultrasound biopsy was performed using 29 MHz Micro-Ultrasound System ExactVu™ (Exact Imaging, Markham, Canada).
• MRI+/MUS+ lesions: MRI lesions visualized with micro-ultrasound, targeted by micro-ultrasound guidance, no fusion
• MRI+/MUS- lesions: MRI lesions not visualised with micro-ultrasound, targeted with fusion imaging
• MRI-/MRI+ lesions: Micro-ultrasound lesions not seen on MRI, targeted with micro-ultrasound guidance
• Any cancer with Gleason score ≥ 7 or cancer length > 3mm was considered csPCa

Results:
58 MRI lesions in 56 patients including 52/58 (90%) MRI+/MUS+ lesions

• 19% (10/52): PI-RADS 3, 20% (2/10) csPCa
• 60% (31/52): PI-RADS 4, 68% (21/31) csPCa
• 21% (11/52): PI-RADS 5, 91% (10/11) csPCa

6 MRI+/MUS- lesions, 4 in peripheral zone, 5 PI-RADS 3

• csPCa not found in the MRI+/MUS- group.

13 MRI-/MUS+ lesions

• 31% (4/13) csPCa, including 1 contralateral extension of index lesion and 3 remote nodules

Conclusion:

• Micro-ultrasound can localize PI-RADS>2 focal lesions, may be an alternative to MRI/US fusion
• Micro-ultrasound may aid in postponing biopsy for MRI+/MUS- PI-RADS 3 lesions (all negative for csPCa)

References:
1. Ghai S, Eure G, Fradet V, et al: Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J. Urol. 2016; 196: 562–569.

Introduction:
The introduction of the PSA test to screen men for prostate cancer (PCa) has led to an increase in the overdiagnosis of indolent PCa that can remain asymptomatic during a patient’s lifetime. Active Surveillance (AS) is the recommended management strategy for men with low-risk prostate cancer. We assess the role of micro-ultrasound and multiparametric MRI (mpMRI) in monitoring the progression of prostate cancer in men on AS according to the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria.

Objective: This study seeks to identify the potential of ExactVu™ Micro-Ultrasound System (Exact Imaging, Markham, Canada, Figure 1) as an additional tool for the management of Gleason 6 prostate cancer with Active Surveillance.

Methods:

1. 44 consecutive subjects +enrolled in PRIAS +Previous GS 6 (3+3)
2. 39 mpMRI [PI-RADS v2]
3. ExactVu™ micro-ultrasound + targeted biopsy
4. Pathology Assessment

Results:
Prostate cancer found in 126/178 (71%) patients

• For all PCa micro-ultrasound sensitivity was 84% and mpMRI was 72%.
• csPCa was found in 6/39 (15%) subjects with GS 3+4 or greater, targets from either modality alone would have found 5/6 of these with 1 small volume (3mm) discovered systematically near the Micro-ultrasound and MRI target (Table 1).
• 13/19 subjects were confirmed in GS 3+3 pathology by micro-ultrasound targets, while 9/19 were confirmed by MRI (Figure 4).
• 17/39 (44%) of subjects had non-suspicious imaging on at least one modality. No significant cancer was found in this population, suggesting biopsy may be avoidable (Figure 5).

Conclusion:
Micro-ultrasound and mpMRI evaluations performed similarly in the detection of csPCA, with Micro-ultrasound detecting more Gleason 6 PCa.

Incorporation of micro-ultrasound or mpMRI in Active Surveillance protocol could reduce the number of unnecessary repeat biopsies:

• Eliminating the need for biopsy in patients with benign findings
• Increase yield of csPCA detection in fewer biopsies

References:
1. Ghai S, Eure G, Fradet V, et al: Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J. Urol. 2016; 196: 562–569.

Introduction:
High-resolution micro-ultrasound is a novel 29 MHz ultrasound modality enabling real-time targeted prostate biopsies. This increase in resolution allows visualization of tissue characteristics which can be correlated with clinically-significant indications. Micro-ultrasound technology has been shown to be more sensitive to detect prostate cancer than conventional ultrasound and a viable, cost-effective clinical alternative to MRI for guiding and targeting prostate biopsies.

Objective: This work reviews a small case series of subjects who underwent radical prostatectomy (RP) following micro-ultrasound targeted biopsy and seeks to determine whether the micro-ultrasound images were predictive of extra-prostatic extension (EPE).

Methods:

• 16 subjects underwent RP following micro-ultrasound targeted biopsy.
• 18/32 prostate lobes had extra-prostatic extension (EPE) based on histopathology analysis of the RP specimen.
• ExactVu™ Micro-Ultrasound platform (Exact Imaging, Markham, Canada) was used to acquire images during real-time targeted biopsy procedure.
• Micro-ultrasound images were reviewed in all subjects to propose imaging features which might be predictive of EPE.

Results:

In 15/18 prostate lobes with EPE, interruption of the posterior capsule or a hypoechoic halo surrounding the prostate along anterior and/or apical border was observed in the lobe with EPE. In 10/11 lobes with a hypoechoic halo, the halo was either thick, irregular or both. Upon examination of prostate lobes with benign findings, suspicious imaging findings were absent in 13/14.

Conclusion:

• Micro-ultrasound imaging may be able to predict the presence of EPE.
• A “thick/irregular hypoechoic halo” on the anterior and/or apical prostate capsule appears to be increasingly correlated to the presence of EPE.
• More clinical data is required to corroborate this finding and more detailed examination of pathology specimens will be required to better interpret its meaning.

References:
1. Ghai S, Eure G, Fradet V, et al: Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J. Urol. 2016; 196: 562–569.

Background:
The PRECISION study was able to show that sole targeted fusion biopsy is superior to systematic biopsy. However, the combination of an MRI / US fusion biopsy with a systematic biopsy results in a maximized detection rate of significant carcinomas. The use of a micro-ultrasound system with improved resolution allows the evaluation of additional tumor-related foci, offering the option of further optimizing fusion biopsy.

Methods:
178 consecutive men presenting for prostate biopsy between February and December 2018

Biopsy using ExactVu™ 29MHz Micro-ultrasound system (Figure 1)

• Micro-ultrasound targets
• 10-core systematic samples
• MRI targets (sampled separately)

Analysis for added value of each biopsy strategy.

Results:
Prostate cancer found in 126/178 (71%) patients

• 88/178 (49%) GG > 1
• 42/178 (24%) GG > 3

Of the 159 cases with MRI results:

• MRI targets upgraded the Grade Group in 34 cases (21%) including 11 cases not found with micro-ultrasound (7%)
• Micro-ultrasound targets upgraded the Grade Group in 46 cases (29%) including 26 not found on MRI (16%)

Only in 5 cases (3%), systematic biopsy alone revealed evidence of significant prostate cancer

Conclusion:

• Micro-ultrasound leads to an improvement in diagnostic accuracy as a supplement to an MR fusion biopsy
• Future studies will examine whether an entirely targeted approach MRI+Micro-US is feasible and effective.

References:
1.Ghai S, Eure G, Fradet V, et al: Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J. Urol. 2016; 196: 562–569.

Background:
Patients often receive a higher Grade Group (GG) after radical prostatectomy (RP) than on prostate biopsy. This has implications for care since it implies that treatment decisions based on biopsy results underestimate the severity of disease. We investigate whether micro-ultrasound or mpMRI targeted biopsy better predict final GG after radical prostatectomy.

Methods:

• Rate of upgrading after radical prostatectomy compared for cases with MRI only and cases with MRI+Micro-Ultrasound
• ExactVu™ Micro-Ultrasound
  (Exact Imaging, Markham, Canada) used for micro-ultrasound guided biopsy including MRI target sampling and systematic biopsy.

Results:

• MRI-only group: 48/127 (38%) of subjects were upgraded by at least 1 GG
• Micro-Ultrasound group: 11/46 (24%) were upgraded
• Adding micro-ultrasound guidance to MRI and systematic biopsy lowered upgrading rate on radical prostatectomy (p<0.05)

Conclusion:

• Micro-ultrasound guidance appears to provide more accurate biopsy grading compared to commercial elastic MRI/US fusion systems and reduced upgrading on radical prostatectomy
• Larger prospective trials will be required to confirm this result

References:
1. Ghoi S, Eure G, Frodet V, et ol: Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J. Urol. 2016; 196: 562–569.

Introduction:
MRI-US fusion targeted biopsy is recommended in men with MRI visible lesions. For lesions not visible on MRI, or when fusion is inaccurate, the diagnostic performance of standard transrectal US is insuffi cient for prostate cancer lesions. This study aimed to evaluate the performance of a novel transrectal micro-ultrasound (micro-US) using high-frequency at 29 MHz (ExactVu™) with an embedded fusion software.

Methods:

• Retrospective analysis of consecutive men undergoing MRI-micro-US fusion targeted biopsy from May 2018 to March 2019.
• MRI lesions not visualised with micro-ultrasound, targeted with fusion imaging
• Standard US and micro-US was performed with suspicious lesions noted
• MRI-micro-US fusion targeted biopsy, followed by micro-US targeted biopsy, followed by random biopsy, as clinically indicated.
• Clinically significant disease: any Grade 4 and/or total cancer length ≥10mm.

Results:

• Significant disease was detected in 79 (53%), insignificant disease was detected in 14 (10%), no disease was detected in 55 (37%).
• Of the 88 posterior lesions PI-RADS ≥ 3, 66 (75%) were visible on micro-US.
• 36 MRI non-visible lesions were detected on micro-US: 9 (25%) harboured significant, 8 (22%) harboured insignificant disease and 19 (53%) were false positive.

Conclusion:

• This study suggests that combining micro-US with MRI fusion targeted biopsy might enhance the detection rate of significant disease.
• Most lesions are visible on micro-US, minimizing any error associated with incorrect MRI fusion.

References:
1. Ghai S, Eure G, Fradet V, et al: Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J. Urol. 2016; 196: 562–569

Background:
Multiparametric Magnetic resonance imaging (mpMRI) of the prostate has recently been recommended in the French guidelines for men suspected of harboring prostate cancer. However, MRI quality is inconsistent outside of large expert centers, and adds significant cost and complexity due to the multi-specialty, multi-visit nature of the pathway. A novel high-resolution 29 MHz micro-ultrasound offers real time targeting of biopsies of suspicious areas and enables the detailed visualization of cancer related prostate tissue characteristics. This study compares the performance of mpMRI and micro-ultrasound for the detection of prostate cancer.

Methods:

• 55 consecutive patients from our prospective biopsy database presenting with elevated PSA levels and an mpMRI prostate study were included
• All biopsies were performed using the ExactVu™ (Exact Imaging, Markham, Canada) Micro-Ultrasound System
• Each biopsy included micro-ultrasound targeted, mpMRI targeted, and systematic biopsy samples mpMRI targets were cognitively sampled.
• The PRI-MUS™ (prostate risk identification using micro-ultrasound) evidence-based protocol was used to characterize suspicions tissue under micro-ultrasound for targeting

Results:

• Biopsy histopathology confirmed cancer in 27/55 patients with 15/27 (55.6%) diagnosed with clinically significant cancer (csPCa, Grade Group>1)
• Micro-ultrasound sensitivity for csPCa 14/15 (93.3%) was superior to mpMRI 13/15 (86.7%)
• Negative Predictive Value for Micro-Ultrasound and mpMRI to csPCa were 11/12 (91.7%) and 11/18 (61.1%) respectively

Conclusion:

• Micro-ultrasound provided improved sensitivity to mpMRI for csPCa, suggesting it may be a more cost-efective, single specialty, diagnostic pathway for guiding prostate biopsies
• Improved sensitivity to smaller and lower-risk disease suggests opportunities for micro-ultrasound in active surveillance and imaging-based monitoring of prostate cancer

References:
1. Ghai S, Eure G, Fradet V, et al: Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J. Urol. 2016; 196: 562–569.

Introduction & Objectives:
Reducing unnecessary prostate biopsy procedures is an important clinical goal to minimize patient stress, minimize risk of infection and overtreatment, and reduce overall healthcare cost. Prostate imaging with mpMRI shows considerable utility in patient risk stratification however indeterminate or equivocal results pose a diagnostic challenge. Alternately, micro-ultrasound operates at high frequencies (29 MHz) and provides real-time, office-based imaging with high resolution (down to 70 microns) and may help guide evidence-based decision-making for indeterminate results.

This study seeksto identify the potential of micro-ultrasound as an additional risk stratification with patients who have equivocal mpMRI results.

Methods:

• Retrospective analysis was performed on 83 patients, each with MRI findings of maximum PI-RADS 3 (equivocal), across 7 international urological sites
• PRI-MUS™ (prostate risk identification using micro-ultrasound) protocol1 was used to identify suspicious regions, locate targets (PRI-MUS ≥ 3) and biopsies were performed using the ExactVu™ micro-ultrasound system (ExactVu™, Exact Imaging)
• Overall maximum PRI-MUS score for each subject was used to determine whether the case was non-suspicious (PRI-MUS 1 or 2), equivocal (PRI-MUS 3), or suspicious (PRI-MUS 4 or 5)
• Overall Gleason sum was used as a reference; however there was no standard biopsy procedure due to varying number of systematic and targeted samples

Results:
83 subjects were included, each with 1 biopsy

Overall detection rate was 55% (46/83) with 23% (19/83) csPCa (GG>1)

• Non-suspicious micro-ultrasound imaging reduced the risk of finding csPCa by more than half to 10% (1/10)
• Equivocal micro-ultrasound imaging provided little additional information with detection rate 17% (3/18)
• Suspicious micro-ultrasound imaging resulted 17% increase in detection rate to 27% (15/55) over mpMRI

Conclusions:
Micro-ultrasound imaging along with the PRI-MUS protocol appear to provide additional information in equivocal mpMRI cases.

Synergies between micro-ultrasound clinical risk indicators such as PSA or family history may help advise patients on the necessity of a biopsy.

Authors:
¹Martini Klinik, Prostate Cancer Center, University Hospital Hamurg, Germany,
²Instituto Clinico Humanitas, Rozzano, Italy,
³Urología Clínica , Clínica IMQ Zorrotzaurre, Spain,
⁴Polyclinicque les Bleuets, Reims, France,
⁵Glickman Urological Institute, Cleveland Clinic, Cleveland, USA,
⁶Urology of Virginia, Virginia Beach, USA,
⁷Joint Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada

References:

1. Ghai, S. et al., “Assessing Cancer Risk in Novel 29 MHz Micro-Ultrasound Images of the Prostate”, Journal of Urology, 2016 Aug;196(2):562-9

Introduction:
PRI-MUS™ (Prostate Risk Identification for Micro-Ultrasound) is an evidence-based risk assessment protocol1 developed to identify suspicious areas in the prostate as visualized during routine clinical scanning by high-resolution 29 MHz micro-ultrasound imaging. Multiple clinical studies have demonstrated the utility of the PRI-MUS protocol for characterizing tissue and helping to direct targeted prostate biopsies using micro-ultrasound. In this study we provide a prospective validation of PRI-MUS during its real-world clinical application.

This study tracks the performance of the PRI-MUS protocol after introducing the micro-ultrasound platform (ExactVu™, Exact Imaging, Markham, Canada) for targeted prostate biopsy into the Department of Urology at the Ordensklinikum Linz (Linz, Austria).

Methods:
• 399 consecutive subjects were examined by 5 urologists from January 2018 - May, 2019:

• Median age: 66 years (IQR: 59-73)
• Median PSA: 6.7 ng/mL (IQR: 4.5-11.2)

• Suspicious areas of the prostate were characterized in real-time using the PRI-MUS protocol. A targeted TRUS biopsy was then performed in the same session using the ExactVu™ micro-ultrasound system (Exact Imaging, Markham, Canada)

• Areas marked with a PRI-MUS ≥ 3 were considered targets.

Results:

• PRI-MUS accuracy ranged from 0.68-0.83 depending on anatomical area Accuracy highest in apex, lowest in base
• Anterior targets not often graded, but surprisingly accurate with AUC 0.80

Summary of Targeted Biopsy Results using Micro-Ultrasound:
160/399 (40%) of all patients were diagnosed with benign conditions, 71/399 (18%) were diagnosed with low grade prostate cancer with (Gleason = 6) and the remaining 168/399 (42%) were diagnosed with clinically significant cancer (Gleason > 6)

• 239/399 (60%) of the patients were diagnosed with PCa
• 168/239 (70%) of cancers were clinically significant (Gleason > 6)

Conclusion:
M icro-ultrasound and the PRI-MUS protocol are useful tools to detect cancer and are more accurate in the detection of clinically significant cancer. This technology holds promise for reducing the high false-negative rate of prostate biopsy, without relying on multi-modality, multi-specialty solutions like mpMRI. 

• Micro-ultrasound based PRI-MUS accuracy is relatively uniform across prostate areas, more study required in anterior and transition zones
• Micro-ultrasound provides a highly sensitive real-time targeting tool for prostate biopsies, thereby improving detection rates of csPCa at our clinic
• Exciting potential to reduce false-negatives without relying on multi-modality, multi-specialty solutions like mpMRI.

References:
1. Ghai S, Eure G, Fradet V, et al: Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J. Urol. 2016; 196: 562–569.

Introduction:
The low negative predictive value of conventional ultrasound leads to systematic biopsies, and a high rate of under-diagnosis. New recommendations include multi-parametric MRI (mpMRI) targeted biopsies. Here we compare the added diagnostic potential of mpMRI with new 29 MHz micro-ultrasound (micro-US), a novel technique enabling real-time targeting without the complexities, costs and challenges of performing MRI.

Methods:

• Prospective database study including 51 subjects presenting with elevated PSA or abnormal DRE undergoing prostate biopsy using ExactVu™ micro-ultrasound system (Exact Imaging, Markham, Canada)
• These subjects had also received mpMRI imaging which indicated targets for biopsy
• Each case was analyzed to determine whether mpMRI and/or micro-US targeted samples identified the highest Grade Group (GG) detected for the subject by any technique.

Results:

• Prostate cancer was identified in 27/5l (53%) subjects, and was clinically significant (GG 2) in 22/5l (43%)
• In l9/27 (70%) of all cancers and l6/22 (73%) GG 2 cancers, both micro-US and mpMRI targets identified the highest GG cancer
• mpMRI alone detected 3/27 (ll%, GGl,l,3) cancers which were not identified by micro-US
• Micro-US alone detected 3/27 (ll%, GG2,2,4) cancers which were not identified by mpMRI
• Systematic biopsies detected the highest GG in 2/27 (7%) patients, although in each case both mpMRI and micro-US had identified a lower GG region
• In patients without mpMRI, 2 had positive biopsies in areas identified by micro-US

Conclusions:
Image-based targeting of prostate biopsies added significant value with high rates of clinically significant cancer detection

With strong agreement between MRI and micro-US in most cases, micro-US may be a reasonable alternative to MRI for targeted biopsy

Introduction & Objectives:
Multi-parametric MRI (mpMRI) is growing as a screening approach for prostate cancer due to trials such as PROMIS and PRECISION demonstrating high sensitivity and negative predictive values.  Unfortunately, implementation of mpMRI programs is complicated in practice due to additional costs, complexity, learning curve, procedure time, and experience required for adequate interpretation and reproducible results.  Many men are also contraindicated to MRI due to concerns with renal function, claustrophobia, or ferromagnetic implants.  This work aims to compare the sensitivity and specificity of mpMRI with the novel high-resolution micro-ultrasound imaging modality, which maintains the workflow, simplicity and low cost of ultrasound and can be used to target biopsies in real-time without the need for MRI.

Material & Methods:
Data from 5 sites was aggregated, totaling 274 subjects presenting for ExactVu micro-ultrasound guided biopsy with available mpMRI studies.  Samples in all subjects were taken from mpMRI targets and micro-ultrasound targets, with up to 12 systematic samples filled in.  mpMRI targets were sampled cognitively at 4/5 sites using the micro-ultrasound system and with either a software-fusion system or cognitively using micro-ultrasound at the 5th site.  Clinically significant cancer was considered any Gleason Sum > 6 and targeted samples were taken for PI-RADS > 2 or PRI-MUS1 > 2 lesions.

Results:
mpMRI demonstrated strong sensitivity (84%), with slightly weaker NPV (69%).  Micro-ultrasound sensitivity (95%) and NPV (84%) were both higher. However, micro-ultrasound was considerably less specific (16% vs 25% for mpMRI) and both modalities showed a relatively poor PPV of 43%.

Conclusions:
Micro-ultrasound’s high sensitivity makes it an attractive option for both screening and targeted biopsy, even relative to the more widely studied mpMRI.  Further larger-scale studies are required to ensure these early results are repeatable.  The relatively lower specificity suggest micro-ultrasound is not yet able to exclude biopsy in as many men, though the higher sensitivity indicates the confidence may be higher in the men it does exclude.

Authors:
¹Instituto Clinico Humanitas, Rozzano, Italy,
²Urología Clínica , Clínica IMQ Zorrotzaurre, Spain,
³Polyclinicque les Bleuets, Reims, France,
⁴Glickman Urological Institute, Cleveland Clinic, Cleveland, USA,
⁵Urology of Virginia, Virginia Beach, USA,

References:

1. Ghai, S. et al., “Assessing Cancer Risk in Novel 29 MHz Micro-Ultrasound Images of the Prostate”, Journal of Urology, 2016 Aug;196(2):562-9

Introduction & Objectives: Although multiparametric MRI (mpMRI) is the most accurate tool in the detection of clinically significant Prostate Cancer (CsPCa), some limitations have reduced its use as a triage test. ExactVu is a real-time micro-ultrasound system capable of providing 300% higher resolution compared to conventional trans rectal ultrasound. Similarly to mpMRI in which PIRADS protocol has been developed to standardize the likelihood of PCa risk, a novel protocol of risk identification called PRI-MUS, is being developed to provide the same intended benefits for micro-ultrasound. The aim of our study was to evaluate the performance of ExactVu in the detection of CsPCa.

Methods: Patients with PCa diagnosed at fusion biopsy were imaged with ExactVu. CsPCa was defined as any Gleason Score ≥3+4. ExactVu examination was considered as positive when PRI-MUS score was ≥3. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operator characteristic (ROC) curve (AUC) were calculated.

Results: 57 patients out of 68 (84%) had a csPCa. A detailed list of clinical, radiological and pathological characteristics of patients is reported in table 1a. PRI-MUS score was correctly assessed in 57% of cases (table 1b). Regarding the detection of CsPCa (Fig. 1a), ExactVu's sensitivity, specificity, PPV, and NPV was 68%, 73%, 93%, and 31%, respectively and the AUC was 0.7 (95% CI 0.5-0.8). Detecting CsPCa in the transition/anterior zone (Fig. 1b) the sensitivity, specificity, PPV, and NPV was 45%, 66%, 83% and 25% respectively ant the AUC was 0.5 (95% CI 0.2-0.9). Accounting only the CsPCa located in the peripheral zone (Fig. 1c), sensitivity, specificity, PPV, and NPV raised up to 74%, 75%, 94%, 33%, respectively with AUC 0.75 (95% CI 0.5-0.9).

Conclusions: ExactVu provides high resolution of the prostatic peripheral zone and could represent a step forward in the detection of CsPCa in a triage setting.

Introduction & Objectives: Magnetic resonance imaging (MRI) is becoming an increasingly adopted imaging tool for the preoperative staging of patients with bladder cancer (BC). However, MRI is a costly and time-consuming exam and may be contraindicated in a non-negligible proportion of individuals. We test the hypothesis that a novel imaging modality, named high resolution micro-ultrasound could help to differentiate between patients with non-muscle invasive (NMIBC) vs. muscle-invasive cancer (MIBC).

Materials & Methods: This was an observational prospective investigative study performed from October 2017 to May 2018 in male and female patients, age > 18 years, with a diagnosis of primary or recurrent BC scheduled for an endoscopic treatment. The end-points of the current study were:

1. to test the feasibility of high resolution micro-ultrasound in BC patients;
2. to test its ability to differentiate between the three layers of a normal bladder wall (urothelium, lamina propria and muscolaris propria);
3. to test its accuracy in determining the presence/location of bladder lesions as well as the relationship between micro-ultrasound results and pathological staging. Micro-ultrasound imaging was performed before trans-urethral resection of cancers using the ExactVu™ system with an EV29L 29 MHz side-fire transducer (Exact Imaging, Markham, Canada). Images were acquired transvaginally in females and transrectally in males.

Results: The procedure was feasible in all 11 patients (9 females and 2 males). However, given to the current shape of the micro-ultrasound probe, the transvaginal route allowed a more precise exploration of the cranial portion of the bladder. Micro-ultrasound was capable of accurately differentiate the three layers of the bladder wall in all individuals. Bladder cancers were clearly visualized, appearing as heterogenous structures protruding from the normal bladder wall. In all 9 NMIBC cases, lesions were not disrupting or only focally disrupting the hyperintense line representing the lamina propria and this finding was concordant with final pathology, showing 8 pTa and 1 pT1 tumors. In the 2 cases where tumors were extending beyond this line into the muscular layer, the presence of MIBC was confirmed at final pathology.

Conclusions: Our preliminary findings showed that micro-ultrasound may be a feasible staging tool in patients with BC, and may be capable of accurately depicting the different bladder layers, determining the absence/presence of bladder wall infiltration. Further studies are needed to confirm our preliminary results in large prospectively collected cohorts and to evaluate the impact of this staging tool in the management of BC patients.

Introduction & Objectives: Targeted multi-parametric MRI(mpMRI) fusion biopsies are an increasingly popular alternative to random US-guided biopsies. High-resolution micro-ultrasound is a new real-time US-based imaging modality enabling real-time targeted prostate biopsies. We examined the efficacy of micro-ultrasound as a newly-found diagnostic approach to targeted biopsies and subsequently compared the diagnostic accuracy of micro-US and mpMRI within a prospectively collected cohort of patients with suspected prostate cancer (PCa).

Materials & Methods: The study population consisted of 179 consecutive patients with at least one suspicious lesion (PIRADSv2≥3) according to mpMRI who were enrolled within a prospective trial aimed at comparing the diagnostic accuracy of micro-ultrasound and mpMRI. The PRI-MUS™ (prostate risk identification using micro-ultrasound) risk identification protocol was used to identify targets on micro-ultrasound. The urologist, newly trained on performing the micro-ultrasound targeted-biopsies (ExactVu™ 29 MHz micro-ultrasound, Exact Imaging, Markham, Canada), was blinded to the mpMRI results until after the micro-ultrasound targeting was complete. All subjects received targeted biopsy (based on micro-ultrasound and mpMRI imaging) as well as systematic random biopsies. The overall presence of PCa and clinically significant (Gleason score≥7) PCa was assessed. Concordance between mpMRI and micro-ultrasound findings and biopsy results were determined.

Results: Mean patient age was 64.7 yrs and mean total PSA value was 8.2 ng/mL. Overall, 92 (51.4%) patients were in the repeat biopsy setting and DRE was suspicious in 43 (24.0%) patients. PCa detection rate was 56.5%, while csPCa detection rate was 38.0%. The proportion of patients with csPCa increased significantly according to PRI-MUS (from 16.7 to 41.0 and 60.5% for patients with a PRI-MUS score 3, 4 and 5 lesion, respectively; p<0.001), and to PIRADS score (from 17.9 to 39.0 and 54.8% in patients with a PIRADS score 3, 4 and 5 lesion, respectively; p=0.007). Micro-ultrasound csPCa sensitivity was 91.2% (62 out of 68 with csPCa having at least one lesion at micro-ultrasound). Negative predictive value was 82.4%, while positive predictive value was 42.8% and specificity was 25.2%. Overall, 111 concordant targeted zones between micro-ultrasound and mpMRI were identified, in which 50 were csPCa. Although presenting with suspicious lesions at both mpMRI and micro-ultrasound, 6 patients (5 in the initial biopsy setting) were diagnosed with csPCa by random cores only.

Conclusions: Micro-ultrasound is a promising new imaging modality for targeted prostate biopsies, enabling high sensitivity to detect PCa. This work suggests that micro-ultrasound may provide additional information regarding the presence or absence of csPCa in patients with suspected PCa according to mpMRI, and may further improve results over conventional ultrasound MRI/US fusion biopsy. Further studies are warranted to investigate how the new micro-ultrasound modality can best be leveraged within the prostate cancer diagnostic pathway.

Introduction & Objectives: While mpMRI has progressively gained an important role in the prostate cancer (PCa) diagnostic pathway, its widespread use in clinical practice is still limited by cost-effectiveness considerations. 29 MHz high resolution micro-ultrasound is a new imaging modality with resolution down to 70 microns. This study reports on our clinical experience after introducing micro-ultrasound into our prostate biopsy clinic.

Materials & Methods: Data on 286 consecutive patients imaged with the ExactVu micro-US system between October 2017 and September 2018 were prospectively collected. All patients were scheduled for prostate biopsy due to clinical suspicion of PCa. The PRI-MUS™ (prostate risk identification using micro-ultrasound) protocol was used to locate targets on micro-ultrasound (ExactVu™ 29 MHz micro-ultrasound, Exact Imaging, Markham, Canada). Lesions with a PRI-MUS score ≥3 were targeted. Patients were also subjected to systematic prostatic biopsies. The presence of overall PCa and of clinically significant PCa (defined as a Gleason score ≥7 cancer; csPCa) was determined and the diagnostic performance of microUS was assessed. Finally, logistic regression models (LRMs) were fitted to test the predictors of csPCa.

Results: Mean patient age was 64 yrs, mean total PSA was 9.0 ng/mL and mean prostate volume was 57.3 mL. Overall, 130 (45.5%) patients were in the repeat biopsy setting. Micro-ultrasound detected prostate lesions with a PRI-MUS score of 3, 4 and 5 in respectively 36 (12.6%), 133 (46.5%) and 66 (23.1%) patients, while in 51 (17.8%) individuals micro-ultrasound did not identify any target. Overall PCa and csPCa detection rates were 53.5% (n=133) and 36.0% (n=103). Micro-ultrasound provided high sensitivity, with 89.3% of patients (92/103) with csPCa having at least one PRI-MUS score ≥3 lesion. Similarly, negative predictive value was 82.3%, with 42 out of 51 patients with no micro-ultrasound targets receiving a benign diagnosis after systematic biopsy. Conversely, positive predictive value and specificity were significantly lower (40.0% and 22.9%), likely due to over-targeting. In univariable LRMs, patients with a PRI-MUS 4 or 5 lesions showed a 3.3- and a 9.3-fold higher risk of harbouring csPCa compared to those with a micro-ultrasound PRI-MUS ≤3 pattern (p≤0.001). These results were confirmed also in multivariable LRMs where, after adjustment for several confounders, patients with a PRI-MUS 4 or 5 lesions had respectively a 2.9- and 4.7-fold higher risk of harbouring csPCa (p≤0.018). Besides increasing PRI-MUS score, initial biopsy setting (OR: 2.3; p=0.022) and decreasing prostate volume (OR: 0.98; p=0.010) achieved the independent predictor status.

Conclusions: Micro-ultrasound is a promising new imaging modality showing high sensitivity to detect csPCa. In addition, the system appears to be capable of reliably excluding the presence of csPCa in the great majority of patients. Multi-institutional efforts are still needed to further support the adoption of this tool in the diagnostic pathway of patients with suspected PCa.

uspected PCa according to mpMRI, and may further improve results over conventional ultrasound MRI/US fusion biopsy. Further studies are warranted to investigate how the new micro-ultrasound modality can best be leveraged within the prostate cancer diagnostic pathway.

INTRODUCTION
We aimed to compare the cancer detection rates in patients who underwent Micro-ultrasound biopsy (MB) versus Robotic ultrasound-magnetic resonance imaging fusion biopsies (RFB) for PCa.

MATERIALS AND METHODS
Between February 2017 and September 2018, 451 biopsies were performed at our institution. We selected 271 patients that underwent target biopsy. In total 223 men underwent RFB, and 48 underwent MB. The study cohort was divided into two groups: robotic ultrasound-magnetic resonance imaging fusion biopsy (Group A) and micro-ultrasound biopsy (Group B). Micro-ultrasound imaging was performed using the high resolution ExactVu™ system ( Exact Imaging, Markham, Canada). RFB was performed using Artemis Device (Eigen, Grass Valley, CA). Biopsy samples were taken from targets in each modality, plus systematic samples.

There were no differences according to age (median: 66.9 years), PSA(median: 9.1 ng/mL), prostate volume(median: 54.4 g), and PIRADS (median: 3.96). There were no differences according to cancer detection rates except for target detection rates of clinically significant tumors. The prostate cancer detection rate was 67.7% (151) in group A and 62.5% (30) in group B (p=0.48). The detection of clinically significant cancer defined as patients with Gleason score greater or equal to 3+ 4 was 31.8%(71) in group A and 39.5% (19) in group B (p=0.31).

The clinically significant cancer detection rate of random biopsies were similar in group A and group B (21.5% vs. 22.91% respectively; p=0.83). Patients from Group B had higher clinically significant tumours detection in target biopsies (37.5% vs. 22.86%; p=0.035).

CONCLUSIONS
Our study suggests that micro-ultrasound biopsy may be comparable to RFB according to prostate cancer detection. Micro-ultrasound might play a role in cognitive fusion biopsies.

 

Objective:
To compare first generation high-frequency 29 MHz transrectal micro-ultrasound (“micro-US”) with conventional low-frequency 7–12 MHz transrectal ultrasound (“conv-US”) for the detection of clinically-significant prostate cancer (csPCA).

Methods:
1,676 men indicated for prostate biopsy and without known prostate cancer were randomized 1:1 to micro-US or conv-US guided biopsy at 5 sites in North America from 2013-16. Exactly 12-cores were taken transrectally from each subject, with each core taken either systematically or from a target near the systematic position. The trial was paused after 1,113 subjects to train investigators on the new PRI-MUS™ (Prostate Risk Identification using Micro-Ultrasound) protocol for micro-ultrasound targeting, developed using data from the first portion of the trial. csPCA was defined as any Gleason Grade Group > 1 and/or any core with > 50% cancer.

Results:
The per-patient detection rates of csPCA in the intent-to-treat (ITT) analysis did not differ between transrectal micro-ultrasound and conventional-ultrasound arms (34.6% (290/837) vs. 36.6% (307/839), respectively, p=0.21). However, the per-protocol analysis (PP) detection rate of csPCA was significantly greater with micro-US (43.7% (125/286) vs. 36.6% (301/823), p=0.02). After PRI-MUS training, sensitivity improved to 63.4% from 24.7% for micro-ultrasound (p<0.01), but at the cost of lower specificity (post-training for micro-ultrasound = 61.7%, conv-US = 89.5%), suggesting a learning curve to micro-ultrasound interpretation across all investigators. Unexpected prostate under-sampling was noted in the micro-ultrasound arm, where 65.8% of men had inadequate sampling of the prostatic apex, which explains the disparity in number of subjects between the ITT and PP groups.

Conclusions:
First generation transrectal micro-ultrasound with PRI-MUS achieved greater sensitivity to detect significant prostate cancers than conventional TRUS. Despite limitations of the first-generation instrument, when clinicians were instructed in micro-ultrasound image interpretation and used proper systematic biopsy technique with the experimental probe, greater cancer detection rates were achieved with the same number of biopsy samples. This work also represents the first prospective validation of a protocol for real-time lesion identification and biopsy targeting using micro-ultrasound (PRI-MUS™).  Additional studies are underway to refine use and application of this novel imaging technology.

Introduction and objectives:
Prostate cancer is the most common cancer in men worldwide. Detection technologies have improved in recent decades and as a result, more patients are diagnosed at early stages of the disease. Multiparametric Magnetic resonance imaging (mpMRI) of the prostate has recently been recommended in the French and European guidelines for men suspected of harboring prostate cancer. However, MRI quality is inconsistent outside of large expert centers, and adds significant cost and complexity due to the multi-specialty, multi-visit nature of the pathway.  A novel  high resolution 29 MHz micro-ultrasound offers real time targeting of suspicious areas. The 70-micron resolution provides a 300% improvement in resolution over conventional ultrasound and enables the detailed visualization of cancer related prostate tissue characteristics visible. This study compares the performance of mpMRI and micro-ultrasound for the detection of prostate cancer.

Materials and methods:
37 consecutive patients from our prospective biopsy database presenting with elevated PSA levels (range: 4.2 – 40 ng/mL, median 8.57 ng/mL) and an available mpMRI prostate study were included. Micro-ultrasound biopsy was performed using the ExactVuTM (Exact Imaging, Markham, Canada) micro-ultrasound system and included micro-ultrasound targeted, mpMRI targeted, and systematic biopsy samples. mpMRI targets were cognitively sampled.

Results:
Biopsy histopathology confirmed cancer in 17 out of 37 patients with 7/17 (41.2%) diagnosed with clinically significant cancer (ISUP>1). For clinically significant cancer, micro-ultrasound and mpMRI both provided an equal sensitivity of 6/7 (85.7%). Micro-ultrasound’s negative predictive value, specificity value and positive predictive value were calculated at 11/12 (91.7%), 11/30 (36.7%) and 6/25 (24%) compared to MRI calculated at 14/15 (93.3%), 14/30 (46.7%) and 6/22 (27.3%).
For all cancer, micro-ultrasound sensitivity and negative predictive value were 14/17 (82.4%) and 9/12 (75%). Specificity and positive predictive value were calculated at 9/20 (45%) and 14/25 (56%). While mpMRI scored 12/17 (70.6%) and 10/15 (66.7%) for sensitivity and negative predictive value, missing three subjects with prostate cancer. Specificity and positive predictive value for mpMRI were calculated at 10/20 (50%) and 12/22 (54.6%).

Conclusion:
For clinically significant prostate cancer, micro-ultrasound provided equivalent sensitivity to mpMRI, suggesting it may be a more cost-effective, single specialty, diagnostic pathway for guiding prostate biopsies.  The improved sensitivity to smaller and lower-risk disease suggests possible opportunities in the area of active surveillance and longitudinal imaging-based monitoring of prostate cancer patients.

Background:
Prostate Cancer is the most common cancer in men with 185,000 new cases of prostate cancer diagnosed in the United States every year. Diagnosis of this disease is complicated by the high false negative rate of the systematic biopsy procedure.  MRI/US-fusion provides a possible alternative to improving prostate cancer detection rates but requires multiple specialists, costly equipment, has a significant learning curve and requires longer procedure times. This report presents early experience at our institution using a novel 29 MHz micro-ultrasound system for prostate biopsy, allowing both standard systematic sampling as well as real-time targeting of suspicious regions during the biopsy procedure.

Methods:
45 consecutive subjects from the prospective biopsy database at the Cleveland Clinic from January to April 2018 who underwent prostate biopsy using the ExactVuTM (Exact Imaging, Markham, Canada) micro-ultrasound system were included. Patients had a median PSA of 12.7 ng/dl, and 18/45 had mpMRI performed prior to biospy. Biopsies were performed by 3 urologists, none of whom had any experience with micro-ultrasound before this study.

Results:
24/45 subjects were positive for prostate cancer (53.3%). In 3 of these cases, systematic biopsy was negative with only micro-ultrasound targeted samples detecting the cancer (3/24, 12.5%).  Two of the three subjects were diagnosed with clinically significant cancer with Gleason sums of 8 (4+4) and 7 (3+4). The remaining patient had a Gleason sum of 6 (3+3). Targeted sampling with ExactVu increased yield on prostate biopsy from 46.7% (21/45) to 53.3% (24/45), a relative increase of 14%.

Conclusion:
Prostate cancer is the second leading cause of cancer death among men. As such, there is a need to improve the accuracy of cancer detection and imaging overall. Our initial results with the ExactVu micro-ultrasound imaging platform suggest that it can increase detection rates of significant prostate cancers, potentially allowing earlier treatment and more accurate follow-up.  These encouraging results so soon after implementing this new modality reflect the short learning curve and suggest that similar results may be achievable across the general urology community.

Introduction & Objectives:
The novel high-resolution micro-ultrasound imaging modality has been previously demonstrated to provide high sensitivity to detect prostate cancer.  Multi-parametric MRI (mpMRI) is a more established imaging technique with a well-documented high sensitivity to detect prostate cancer.  mpMRI is thought to provide particular benefit in the anterior portion of the prostate which is often under-sampled on systematic biopsy.  This study aims to compare the locations where MRI and micro-ultrasound identify prostate cancer.

Material & Methods:
A prospective database was maintained of all subjects presenting for biopsy with the ExactVuTM micro-ultrasound system (Exact Imaging, Markham, Canada) at our center. All cases having both mpMRI and micro-ultrasound targets were included.  Targeted biopsy was performed cognitively and in real-time on mpMRI targets using the ExactVu system, and targeting was performed in real-time using direct visualization on micro-ultrasound targets.  All samples were labeled so that pathology results could be correlated back to the targeting modality and sample location.  Location of samples was recorded for left or right sides as Apical, Basal, Lateral, Anterior Zone, or Transition Zone.

Results:
180 subjects were enrolled, of whom mpMRI data was available in 104.  81 of these subjects had both mpMRI and micro-ultrasound targets (using the PRI-MUS™ risk identification protocol) for comparison with a total of 33 biopsy-positive targeted lesions with Gleason Sum > 6.  mpMRI found 3/3 total significant lesions in the anterior and transitions zones while micro-ultrasound found 2/3.  mpMRI also showed a benefit at the lateral margin, finding 7/8 significant lesions compared to 4/8 for micro-ultrasound.  Micro-ultrasound showed comparative benefit at the base of the prostate, finding 3/3 positive lesions while mpMRI found 2/3.  Both modalities found differing lesions at the apex, 14/19 (73%) for mpMRI and 16/19 (84%) for micro-ultrasound.  Overall, mpMRI and micro-ultrasound found a similar number of significant lesions, 26/33 (79%) and 25/33 (76%) respectively.

Conclusions:
mpMRI and micro-ultrasound found a similar number of lesions positive for significant prostate cancer, however the sites of these cancers differed.  Micro-ultrasound performed well in the anterior and transition zones even though the PRI-MUS protocol for risk assessment does not cover these areas.  While mpMRI found more lesions in these areas, many revealed insignificant prostate cancer.  mpMRI appears to be more useful at the lateral margins of the prostate, while micro-ultrasound was more sensitive to cancer at the base.  Both modalities found independent cancers at the apex of the prostate, indicating that they may provide independent information even in areas where both are sensitive.

References:

1. Ghai, S. et al., “Assessing Cancer Risk in Novel 29 MHz Micro-Ultrasound Images of the Prostate”, Journal of Urology, 2016 Aug;196(2):562-9

Introduction & Objectives:
Micro-Ultrasound is a new, high resolution ultrasound for targeted prostate biopsies which operates at 29MHz, providing a 300% improvement in resolution down to 70 microns.  A number of centers have published initial evidence that this new micro-ultrasound technology is more sensitive to detect prostate cancer and should replace conventional TRUS, in addition to being a viable, cost-effective alternative to mpMRI for targeting prostate biopsies.  This work summarizes our initial experience implementing micro-ultrasound at our centre.

Material & Methods:
A prospective database was maintained for all micro-ultrasound biopsies including patient risk factors such as PSA and DRE status, detailed data on lesions detected by pre-biopsy mpMRI, and biopsy pathology.  All patients received a targeted biopsy via micro-ultrasound of lesions detected by mpMRI or micro-ultrasound, as well as systematic biopsy.  

Results:
87 Micro-ultrasound biopsies were performed between September  2017 and May  2018, with mpMRI report and pathology results available in 52 cases.  Sensitivity to detect clinically significant prostate cancer (Gleason ≥7) was similar for both mpMRI and micro-ultrasound at 76% (13/17) and 82% (14/17) respectively.  Interestingly, combining mpMRI and micro-ultrasound targets resulted in 94% (16/17) sensitivity with only 1 patient diagnosed due to systematic samples (a 15% Gleason 3+4).  Specificity was somewhat lower with micro-ultrasound than mpMRI (20% vs 40%), possibly due to the early learning curve.    All 3 false negative cases for micro-ultrasound were within the first 17 cases (14 complete records); in the 38 cases with complete records since then, no false negatives have occurred.  Sensitivity was 100% for micro-ultrasound in this group (82% for mpMRI), while specificity was similar to overall at 15%.

Conclusions:
A perfect diagnostic tool would have high sensitivity and specificity, however for prostate biopsy our main concern is not determining whom to biopsy as this is already well-established using standard risk nomograms, but rather how to reduce the high false negative rate of the standard TRUS biopsy procedure.  Micro-ultrasound appears to offer a high sensitivity which may succeed in reducing false negative biopsies.  Initial learning curve appears short, though we expect the relatively low specificity to improve over time as more is learned about normal anatomical variants.

Background:
In the last few years, mpMRI and MRI/ultrasound (US) fusion biopsies have been increasingly adopted as a possible alternative to random US-guided biopsies in patients with suspected PCa. However, the widespread use of this diagnostic strategy has been limited by cost-effectiveness, workflow considerations and by studies suggesting that mpMRI may miss a significant proportion of cancers, especially in the initial biopsy setting. High resolution micro-ultrasound is a new real-time ultrasound-based imaging modality with resolution down to 70 microns. We compared the diagnostic accuracy of micro-ultrasound and mpMRI within a prospectively collected cohort of patients with suspected PCa.

Methods:
Data on 60 consecutive patients who were scheduled for a MRI/US fusion biopsy due to the presence of at least one suspicious (PIRADS score ≥3 lesion) at mpMRI were prospectively collected. Prior to MRI/US fusion biopsy, all patients were imaged with the ExactVu™ 29 MHz micro-ultrasound system and eventually subjected to micro- ultrasound targeted biopsies by a urologist blinded to mpMRI results. The PRI-MUS™⁽ⁱ⁾ (prostate risk identification using micro-ultrasound) protocol was used to locate targets (defined as a PRI-MUS score ≥3 lesion) on micro- ultrasound. For the scope of the study, besides micro-ultrasound and MRI fusion biopsies, all patients also received random biopsy (mean 7.2 cores). The overall presence of PCa and the presence of clinically significant PCa (defined as a Gleason score ≥7 PCa; csPCa) was assessed. Concordance rate between mpMRI and micro- ultrasound findings and biopsy results were determined.

Results:
Median patient age was 64 years (range 46-78) and median total PSA was 7.0 ng/mL (range 0.65-20). The majority of patients (n=35, 58.3%) have already undergone at least one previous prostate biopsy. Overall, 17 (28.3%) had a PIRADS 3 lesion at mpMRI, while 28 (46.7%) and 9 (15.0%) had PIRADS 4 and 5 lesions, respectively. No PI-RADS score was given in the remaining 6 cases. Prostate cancer and csPCa detection rate were respectively 53.3% (n=32) and 30.0% (n=18). Micro-US did not identify any suspicious lesion in 13 (21.7%) patients. Of these, 6 patients were confirmed as having a negative histology at biopsy, while 6 individuals harboured clinically insignificant PCa. In those patients where a micro-ultrasound lesion was detected, the concordance rate between micro- ultrasound and mpMRI was fairly good (37 out of 59 lesions; 62.7%). Only 7/22 discordant lesions were positive for significant cancer and in 5/7 micro-ultrasound for a separate lesion of significant cancer in the same subject. Relative to mpMRI and systematic biopsy, the sensitivity and negative predictive value of micro- ultrasound in detecting csPCa were 83% and 80% respectively, while its specificity was 28.6%. The sensitivity of mpMRI relative to micro- ultrasound and systematic biopsy was similar at 85%.

Conclusions:
According to our preliminary experience, micro-ultrasound appears to be a valuable tool that may provide additional information regarding the presence or absence of csPCa in patients with suspected PCa according to mpMRI. Future studies evaluating and comparing the diagnostic accuracy of micro-ultrasound and mpMRI may help to further refine our ability to detect csPCa.

^[1] 1. Ghai S, Eure G, Fradet V, et al: Assessing Cancer Risk on Novel 29 MHz Micro-ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J. Urol. 2016; 196: 562–569.

Introduction & Objectives:
Prostate cancer (PCa) lacks a reliable diagnostic imaging technique as conventional ultrasound has poor sensitivity and MRI demonstrates significant inter-reader variability and may not be able to see smaller aggressive lesions. MRI also adds additional costs, procedural complexity, and has a significant learning curve. High resolution micro-ultrasound, a novel modality with 70 micron resolution, allows visualization of the prostate in real time and can be used to perform targeted biopsies of suspicious lesions in a simple, cost and time-effective manner. The PRI-MUS™ (prostate risk identification using micro-ultrasound) protocol¹ was used to assess micro-ultrasound images, while PI-RADS™ v2 was used for mpMRI.

Methods:
To compare the diagnostic accuracy of Micro-Ultrasound and mpMRI in detecting clinically significant prostate cancer:

• 79 patients presenting for prostate biopsy were imaged with mpMRI and then biopsied using micro-ultrasound (ExactVu™, Exact Imaging)
• mpMRI targets were blinded until micro-ultrasound lesions had been recorded
• Sensitivity of each modality to clinically significant cancer (G7+) was compared

Results:
Sensitivity of micro-ultrasound was significantly higher than mpMRI in both the per zone (p<0.001) (Table 2) and per patient (p=0.001) analysis (Table 3). Specificity was lower (40% micro-ultrasound vs. 91% mpMRI), though this is expected to be less of an issue as final diagnosis is determined by pathology. The high sensitivity should ensure all suspicious samples are collected at time of biopsy for proper pathological analysis

Conclusion:

• Micro-ultrasound shows promising relative sensitivity and NPV for detecting clinically significant prostate cancer when compared to mpMRI
• The small sample size and retrospective nature of this work prevents a definite conclusion from being drawn; larger studies are warranted

Background:
In the last few years, mpMRI and MRI/ultrasound (US) fusion biopsies have been widely adopted as an alternative to random US-guided biopsies in patients with suspected PCa. However, the widespread use of this diagnostic strategy has been limited both by cost-effectiveness considerations and by studies suggesting that mpMRI may miss a significant proportion of cancers, especially in the initial biopsy setting. Micro-Ultrasound is a new ultrasound-based imaging modality with resolution down to 70 microns. We compared the diagnostic accuracy of micro-US and mpMRI within a prospectively collected cohort of patients with suspected PCa.

Methods:
Data on 24 consecutive patients who were scheduled for a MRI/US fusion biopsy due to the presence of at least one suspicious (PIRADS score ≥3 lesion) at mpMRI were prospectively collected. Prior to MRI/US fusion biopsy, all patients were imaged with the ExactVu™ micro-ultrasound system and eventually subjected to micro-US targeted biopsies by a urologist blinded to mpMRI results. The PRI-MUS™ protocol was used to locate targets (defined as a PRI-MUS score ≥3 lesion) on micro-US. For the scope of the study, besides micro-ultrasound and MRI fusion biopsies all patients received also a standard 12-core random biopsy. The overall presence of PCa and the presence of clinically significant PCa (defined as a Gleason score ≥7 PCa; csPCa) was assessed. Concordance rate between mpMRI and micro-ultrasound findings and biopsy results were determined.

Results:
Median patient age was 64 years (range 52-75) and median total PSA was 7.0 ng/mL (range 2.2-17). The majority of patients (n=16, 66.6%) have already undergone at least one previous prostate biopsy. Overall, 11 (45.8%) had a PIRADS 3 lesion at mpMRI, while 8 (33.3%) and 5 (20.8%) had PIRADS 4 and 5 lesions, respectively. Prostate cancer and csPCa detection rate were respectively 58.3% (n=14) and 25% (n=6). Micro-US did not identify any suspicious lesion in 7 (29.1%) out 24 patients. Of these, 5 patients were confirmed as having a negative histology at biopsy, while 2 individuals harboured clinically insignificant PCa. In those patients where a micro-US lesion was detected, the concordance rate between micro-US and mpMRI was fairly good (13 out of 17 lesions; 76.5%). Of the 4 discordant cases, 1 patient showed a GS 3+4 tumor located in the transitional zone at MRI/US fusion biopsy, 2 patients harbour a clinically insignificant PCa and 1 was negative both at fusion and random biopsies. The sensitivity and negative predictive value of micro-ultrasound in detecting csPCa was 100%, while its specificity was 38.8%, result that may be attributed to the initial phase of the learning curve.

Conclusions:
According to our preliminary experience, micro-ultrasound appears to be a valuable tool that may provide additional information regarding the presence or absence of csPCa in patients with suspected PCa according to mpMRI. Future studies evaluating and comparing the diagnostic accuracy of micro-ultrasound and mpMRI may help to further refine our ability to detect csPCa.

Background:
Prostate cancer (PCa) is the most prevalent cancer among European men. While mpMRI has progressively gained an important role in the PCa diagnostic pathway , its widespread use in clinical practice is still limited by cost-effectiveness considerations. In addition, it has been shown that mpMRI may miss a significant proportion of cancers especially in the initial biopsy setting. Micro-ultrasound is a new ultrasound-based imaging modality with resolution down to 70 microns, a 300% improvement over conventional ultrasound. This study reports on our first two weeks after introducing micro-ultrasound into our prostate biopsy clinic.

Methods:
Data on the first 36 patients at our institution imaged with the ExactVu™ micro-ultrasound system were prospectively collected. All patients were scheduled for prostate biopsy due to clinical suspicion of PCa (abnormal DRE or elevated PSA). The PRI-MUS protocol1 was used to locate targets on micro-ultrasound, and these targets were compared to biopsy pathology. Lesions with a PRI-MUS score ≥3 were targeted. The presence of clinically significant PCa (defined as a Gleason score ≥7 cancer) was determined.

Results:
Mean age of patients was 64.2 ± 6.7 years and mean total PSA was 8.1 ± 4.4 ng/mL. Overall, 344 biopsy samples were taken from 36 patients. Overall micro-ultrasound detected prostate lesions with a PRI-MUS score of 3, 4 and 5 in respectively 2 (5.5%), 12 (33.3%) and 13 (36.1%) patients, while in 9 (25.0%) individuals micro-ultrasound did not identify any target. Micro-ultrasound targets provided high sensitivity with 89% of patients (8/9) with GS ≥7 disease having at least 1 positive target. Negative predictive value was also 89% with 8 out of 9 patients with no micro-ultrasound targets receiving a benign diagnosis after systematic biopsy. Not surprisingly, in our preliminary experience, positive predictive value and specificity were lower (30% and 30%), likely due to over-targeting while we become more comfortable with the new tissue detail this modality offers. Retrospective analysis on the single false negative patient revealed a lesion missed during the case. Including this lesion as a target would bring the sensitivity and NPV of micro-ultrasound up to 100%.

Conclusions:
Micro-ultrasound is a promising new imaging modality showing high sensitivity to detect csPCa. In addition, the system appears to be capable of reliably excluding the presence of csPCa in the great majority of patients even in our initial experience. Future efforts aimed at outlining our learning curve and comparing the diagnostic accuracy of this technique to that of mpMRI are warranted.

Purpose:
Active Surveillance monitoring of prostate cancer is unique in that most patients have low grade disease which is not well visualized by any common imaging technique. High-resolution (29 MHz) micro-ultrasound is a new real-time modality which has been demonstrated to be sensitive to significant prostate cancer and effective for biopsy targeting. This study compares micro-ultrasound imaging with MRI and conventional ultrasound for visualizing prostate cancer in active surveillance.

Materials and Methods:
9 patients on active surveillance were imaged with mpMRI prior to biopsy. During the biopsy procedure, imaging and target identification was first performed using conventional ultrasound, then using micro-ultrasound. The mpMRI report was then un-blinded and used to determine cognitive fusion targets. Using micro-ultrasound, biopsy samples were taken from targets in each modality, plus 12 systematic samples.

Results and Limitations:
mpMRI and micro-ultrasound both demonstrated superior sensitivity to Gleason Sum 7 or higher cancer compared to conventional ultrasound (p=0.02 McNemar’s test). Micro-ultrasound detected 89% of clinically significant cancer, compared to 56% for mpMRI.

Conclusions:
Conclusion: Micro-ultrasound may be more sensitive to clinically significant prostate cancer than mpMRI, and visualized all significant mpMRI targets. Unlike mpMRI, micro-ultrasound is performed in the office, in real-time during the biopsy procedure, and so is expected to maintain the cost-effectiveness of conventional ultrasound. Larger studies are needed before these results may be applied in a clinical setting.

Introduction & Objectives:
The PRI-MUS™ (prostate risk identification for micro-ultrasound) protocol was developed to identify suspicious regions of the prostate using micro-ultrasound imaging in order to enable better targeting of prostate biopsies, and to reduce false negatives in the prostate biopsy procedure. While this protocol has been validated using an independent data set1, it would provide additional support if there was a basis for the imaging findings in the histology of the underlying tissue. Since the resolution of micro-ultrasound is substantially improved over conventional ultrasound (down to 75μm), it is reasonable to expect that the imaging findings would bear a closer link and visual appearance to the cellular and ductal structure identified in pathology.

Material & Methods:
20 images of micro-ultrasound guided biopsies from the Exact Imaging clinical trial (clinicaltrials.gov NCT02079025) were selected as being clear examples of particular PRI-MUS sonographic features. These images were taken immediately preceding biopsy using the ExactVu™ micro-ultrasound system (Exact Imaging Inc., Markham, Canada), allowing a direct comparison between the image and pathology. A detailed pathological review of the resulting biopsy sample was performed and the resulting pathology features were correlated to the identified imaging features.

Results:
Strong correlation was found for many of the features investigated. Of the 20 samples which received detailed analysis, 2/2 samples with the ductal “Swiss Cheese” PRI-MUS feature were found to contain mixed benign glands and ducts on pathology. Similarly, 4/5 cases marked with Echogenic “Cauliflower” were found to contain densely packed cancer, and 3/3 cases marked with “Finger-like shadowing” contained dense cribiform cancer. 3/4 cases marked with “Bright Echoes” contained comedonecrosis on pathological analysis, and 3/3 cases marked with “Smudgy texture” contained corpora amylacea mixed with dense or intermediate grade cancer. Finally, 3/3 cases marked with corpora amylacea were demonstrated to contain that finding on pathology.

Conclusions:
While these findings are preliminary and will need to be repeated with a larger, blinded dataset with multiple pathology and PRI-MUS readers, the strong correlation suggests a biophysical basis for the sonographic changes observed in the prostate. This correlation between pathology and micro-ultrasound imaging will be important to further our development of the PRI-MUS protocol, and perhaps to track cancer progression as well as estimate grade of disease.

Background:
Prostate cancer is one of the only solid cancers without a reliable diagnostic imaging technique. With improved imaging and characterization of suspicious prostatic tissue, urologists could potentially reduce over-diagnosis by performing only targeted biopsy in men with low risk factors where suspicious lesions are seen. A novel high resolution micro-ultrasound imaging modality enables 70 micron resolution of prostatic tissues, and along with the support of the PRI- MUS™ (prostate risk identification using micro-ultrasound) protocol, may provide the improved negative predictive value required to determine a stratification protocol for avoiding or delaying biopsies in target patient cohorts.

Methods:
41 consecutive subjects with suspicion of prostate cancer due to elevated PSA / abnormal DRE were evaluated at our institution. All subjects underwent a transrectal micro-ultrasound guided biopsy using the ExactVu™ micro-ultrasound platform (Exact Imaging Inc, Markham, Canada). The investigator performing the microultrasound exam scored each of the 12 extended sextant zones of the prostate plus any targeted areas of interest using the PRI-MUS protocol. After micro-ultrasound scoring, a biopsy was performed under micro-ultrasound guidance. The sensitivity of the modality was then compared to pathology results, defining a PRI-MUS 3 or above as a target and GS7+ as significant cancer. The subject’s prostate volume and PSA were also collected. The data was then retrospectively analyzed to evaluate the Negative Predictive Value of the modality.

Results:
The total NPV of micro-ultrasound to predict benign pathology samples for the 41 patients (488 samples) was 91.54%. Excluding subjects with higher PSAD increased the NPV as expected. When limiting the PSAD to 0.25ng/mL cc the NPV rose to 94.17%. This included 24 subjects, if targeted samples alone had been taken, diagnosis would have changed in only 1 subject. Selecting instead the common clinical threshold of 0.15ng/mL cc resulted in a similar NPV of 94.29% including 8 patients (19.5% of the population).

Conclusions:
After removing high risk patients based on PSAD, the per-sample NPV of the micro-ultrasound modality improved. A combination of novel biomarkers and the novel micro-ultrasound imaging may be more effective at safely avoiding biopsy, or restricting to targeted biopsy in low risk patients. This would result in fewer biopsies performed and a reduction in possible biopsy-related morbidities such as sepsis . The results from this analysis are not conclusive since the population is too small but proves promising for future’s studies as more research is needed.

Background:
Prostate cancer is one of the only solid cancers without a reliable diagnostic imaging technique. Conventional ultrasound has poor resolution and sensitivity. MRI involves complicated workflows and operations, and demonstrates significant variability. A novel 70-micron resolution micro-ultrasound modality allows clinicians to visualize the prostate in real time and differentiate suspicious sections of the prostate to allow targeted biopsies. This modality offers a potential urology-centered solution for targeted prostate biopsies.

Methods:
35 consecutive subjects with elevated PSA / abnormal DRE where evaluated at our institution. Two techniques for targeting regions suspicious for prostate cancer where compared: multiparametric MRI (mpMRI) and the novel high resolution transrectal micro-ultrasound. Subjects first underwent an mpMRI imaging session using the PIRADS v2 protocol. After the MRI report was prepared, the subject returned for transrectal ultrasound guided biopsy using the ExactVu™ micro-ultrasound platform (Exact Imaging Inc, Markham, Canada). The investigator performing the micro-ultrasound scan was blinded to the MRI report until after they had scored each of the 12 zones of the prostate plus any targeted areas of interest using the PRI- MUS™ (prostate risk identification using micro-ultrasound) protocol1. After scoring, the targeted and systematic biopsies were performed under micro-ultrasound guidance. mpMRI targets were acquired using cognitive fusion. Targets for PI-RADS 3 or PRI-MUS 3 and above were considered suspicious. The sensitivity of each modality to clinically significant cancer (GS7+) was then compared based on biopsy pathology on a per zone and per patient basis. McNemar’s test was used to determine statistical significance.

Results:
21 patients had clinically significant prostate cancer with a total of 64 affected zones. mpMRI correctly predicted 15/64 zones (23%) and 12/21 of the patients (57%). Micro-ultrasound correctly predicted 47/64 zones (73%) and 20/21 patients (95%). This resulted in a 91% NPV and a 73% sensitivity in the per zone analyses and a 95% sensitivity in the per patient level for micro-ultrasound. MRI demonstrated a 87% NPV and a 23% sensitivity on the per zone analyses and a 57% sensitivity on the per patient analysis. Sensitivity of micro-ultrasound was significantly (p<0.01) improved over MRI in a per zone basis and a trending to significance on the per patient analysis (p=0.01).

Conclusions:
The micro-ultrasound modality shows promising results for relative sensitivity and NPV in detecting clinically significant prostate cancer when compared to mpMRI. The small sample size prevents a definite conclusion from being drawn, however this work suggests that larger studies are warranted.

Intro and Purpose:
Diagnosis of prostate cancer is performed via transrectal or transperineal-guided ultrasound (TRUS) imaging. No technology is available that reliably detects cancerous regions in the prostate for guiding biopsies, which contributes to false-negative diagnoses and unnecessary biopsies. Quantitative ultrasound (QUS)-based algorithms have potential for detecting cancerous prostate tissue. Conventional TRUS systems used for biopsies operate in the 6 – 9 MHz range. Recent technological advances have led to development of a novel micro-ultrasound system operating at far higher frequencies (29 MHz) enabling ultrafine resolution of the prostate. This preliminary study investigated incorporating our QUS approaches in the micro-ultrasound scanner for identifying cancerous regions in the prostate.

Methods:
RF (radio frequency) data from 67 patients (532 biopsy cores) were acquired using a 29 MHz micro-ultrasound system (ExactVu™ micro-ultrasound, Exact Imaging, Canada). These retrospective data are a subset acquired in an ongoing 2,000-patient clinical trial (clinicaltrials.gov NCT02079025) and consists of 75 biopsy samples with pathology-determined Gleason Sums (GS) of 7 and above (positive) and 457 biopsy samples with negative biopsy results (negative). Before each biopsy, 2D RF data in the longitudinal biopsy plane were acquired using a linear array. For each RF data set, power spectra were computed along the biopsy needle trace using a sliding 1 mm2 ROI. Spectra from the set of ROIs were averaged and normalized by a reference spectrum computed from RF data acquired from a calibration phantom. A linear model was fit to the normalized spectra and QUS estimates of midband (M), intercept (I) and slope (S) were calculated. The QUS estimates were used to train linear discriminant classifiers (LDC). Classifier performance was assessed using area under the curve (AUC) values obtained from receiver operating characteristic (ROC) analyses with leave-one-out cross validation.

Results:
When the three QUS parameters (I, M, and S) were used alone for classification, the AUC values respectively were 0.66, 0.61 and 0.55. No single parameter provided higher accuracy than the QUS I value. When all parameters were used for classification, then an AUC value of 0.74 was obtained. Conclusion: In a previous study, a prostate-cancer risk identification protocol using micro-ultrasound (PRI-MUS™) was introduced to provide a subjective scoring system for assessing prostate-cancer likelihood. This study demonstrated a peak AUC value of 0.74 for higher GS values (GS > 7) when read by participating urologists. Our software-based results with AUC values of 0.74 are very encouraging for developing an incremental prostate-cancer risk-assessing tool to further leverage the high resolution micro-ultrasound images. Further testing approaches involving additional QUS estimates are underway to improve the classification performance.

References:

• Ghai, S. et al., “Assessing Cancer Risk in Novel 29 MHz Micro-Ultrasound Images of the Prostate”, Journal of Urology, 2016 Aug;196(2):562-9.

Intro & Objectives:
Diagnosis of prostate cancer relies on transrectal ultrasound (TRUS)-guided biopsy of the prostate however given poor specificity of screening and insufficient resolution of conventional ultrasound, many men undergo this procedure unnecessarily. A novel 29 MHz high resolution micro-ultrasound (ExactVu™ micro-ultrasound, Exact Imaging, Toronto, Canada) has been developed to significantly increase the spatial resolution and tissue differentiation of TRUS. Combining patient screening data with real-time visualization of the prostate (quantified using PRI-MUS™, Prostate Risk Identification for Micro-Ultrasound1 risk scores) may permit leaving lower risk sections of the prostate, or entire patients with uniformly low risk glands, un-biopsied without significantly increasing the procedure’s false negative rate.

Material & Methods:
Cine loops of 300 micro-ultrasound TRUS biopsies were examined from an ongoing 2,000 patient multi-center clinical trial (clinicaltrials.gov NCT02079025). Patients were undergoing TRUS biopsy for suspicion of cancer due to elevated PSA and/or abnormal DRE. Two investigators marked PRI-MUS scores on the micro-ultrasound images to differentiate suspicious tissue from characteristically benign tissue for all 300 loops, while blinded to pathology. 200 of these loops were a training set, and histograms of patient age, DRE result, and PSA were examined for each PRI-MUS risk level to determine pre-screening viability for potentially benign cases. Conditions were identified for lower-risk individuals and/or areas of the prostate and applied to the 100-loop test set.

Results:
In the 100 sample test set (45 with clinically-significant cancer), each investigator would have eliminated 11 biopsies while maintaining a per-core sensitivity of 96% by applying age, DRE, and PSA to the PRI-MUS protocol. 3 of these 22 samples were positive for cancer via pathology. One was a low-risk GS 6 lesion. Another was a GS 9 lesion which would have been identified by surrounding high-PRI-MUS score samples. The third was a small GS 7 lesion at 35% core length which would have been missed. In total, diagnosis of cancer and grade of the index lesion would have been changed in 1 of the 100 subjects for investigator 1, and in none of the 100 subjects for investigator 2. This suggests an overall per-subject sensitivity of 98.7% (specificity 19.4%) and NPV of 95.5% (PPV 47.0%).

Conclusions:
This mini study suggests that the combination of clinical variables and micro-ultrasound may allow better targeting of biopsies and avoidance of sampling certain low-risk areas of the prostate in low-risk individuals. This technique could be done live during the biopsy procedure and requires no additional equipment or personnel, assuming that a micro-ultrasound system and the PRI-MUS protocol is employed for biopsy guidance.

References:

• Ghai, S. et al., “Assessing Cancer Risk in Novel 29 MHz Micro-Ultrasound Images of the Prostate”, Journal of Urology, Paper In Press: June 2016

Introduction & Objectives:
Conventional transrectal ultrasound systems operate at 6-9 MHz and serve as standard of care for guiding prostate biopsies. We have developed a novel high resolution micro-ultrasound system (29 MHz) to image and target prostate cancer during transrectal biopsies. The purpose of this study is to establish a protocol (PRI-MUS, or prostate risk identification using micro-ultrasound) for standardizing analysis of prostate images from the micro-ultrasound system. PRI-MUS includes an evidence-based scoring system to assess the risk of prostatic carcinoma.

Material & Methods:
Cine loops of 200 transrectal ultrasound-guided (TRUS) biopsies were examined from an ongoing multi-center clinical trial of high-resolution TRUS vs standard TRUS for detection of clinically significant prostate cancer using the novel 29 MHz ExactVu™ system (Exact Imaging, Toronto, Canada). Subjects were undergoing TRUS biopsy for suspicion of cancer due to PSA elevation and/or abnormal DRE. Investigators used the initial image set, with pathology results available, to agree on standardized features to describe each image. A further 200 cine loops from the same trial were then read by the same investigators but blinded to pathology to assess correlation with biopsy results. An independent set of 100 cine loops, again blinded to pathology, was used for validation. 3 of the 5 investigators who performed this blinded validation were familiar with the ExactVu™ system but naïve to the PRI-MUS protocol and received only 1 hour of PRI-MUS training.

Results:
Ten sonographic features associated with pathologically confirmed malignant or benign tissue were identified during initial review; 6 were significant when tested on the blinded data set. These features were incorporated into a 5-level risk scale; from “Very Low” (mean relative risk 0.28) to “Very High” (1.99) risk for clinically significant prostate cancer. Validation results showed an AUC of 0.60 ± 0.02 over 5 independent reviewers. Each reviewer’s ability to detect clinically significant cancer using PRI-MUS was significant at the p<0.1 level, and overall with p=0.0001.

Conclusions:
The resolution of the micro-ultrasound platform, paired with the PRI-MUS protocol, shows significant promise in aiding real-time visualization of prostate cancer. This objective and reliable imaging protocol may be useful in facilitating targeted biopsies, with an accuracy similar to that seen historically using only T2-weighted anatomical MRI. This is a first implementation of a risk assessment protocol on high-resolution micro-ultrasound images in men undergoing biopsy for suspicion of prostate cancer and will require ongoing refinement, including expansion to a multi-parametric approach incorporating functional scans for optimal diagnostic accuracy and a more direct comparison with MRI-based PI-RADS.