PAPERS AND POSTERS
Below is a select listing of published peer-reviewed clinical papers and scientific posters citing the ExactVu micro-ultrasound system for prostate imaging and guided biopsy. Multiple posters and papers can be requested. Select all that are applicable and submit at the bottom of the page.
PAPER
Comparison of conventional transrectal ultrasound, magnetic resonance imaging, and micro-ultrasound for visualizing prostate cancer in an active surveillance population: A feasibility study
Gregg Eure1, Daryl Fanney2, Jefferson Lin1, Brian Wodlinger3, Sangeet Ghai4 1 Urology of Virginia, Virginia Beach, Virginia 2 MRI & CT Diagnostics, Virginia Beach, Virginia 3 Exact Imaging, Markham, Ontario 4 Joint Department of Medical Imaging, University of Toronto, University Health Network, Mount Sinai Hospital, Women's College Hospital, Toronto General Hospital, Toronto, ON, Canada
Can Urol Assoc J 2018 August 30; Epub ahead of print.
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ABSTRACT
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

PAPER
Diagnosis and treatment of urethrocavernous fistula presenting as urethral bleeding
Amy M. Pearlman, Daniel B. Rukstallis, Ryan P. Terlecki; Wake Forest Baptist Health
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ABSTRACT
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

PAPER
High-Frequency Quantitative Ultrasound for Imaging Prostate Cancer Using a Novel Micro-Ultrasound Scanner
Daniel Rohrbach*, Brian Wodlinger, Jerrold Wen, Jonathan Mamou*, Ernest Feleppa*; * Lizzi Center for Biomedical Engineering, Riverside Research, New York, NY 10038, USA; Exact Imaging, Markham, Ontario, Canada
Ultrasound in Medicine & Biology, Available online 4 April 2018
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ABSTRACT
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

SCIENTIFIC POSTER
Comparison Between the Diagnostic Accuracy of High Resolution Micro-Ultrasound Versus Multiparametric MRI in the Detection of Prostate Cancer: Preliminary Results from a Single-Institutional Ongoing Prospective Trial
Lughezzani G1, Ma_ei D1, Lazzeri M1, Colombo P2, Lista G1, Cardone P1, Hurle R1, Casale P1, Saita A1, Bu_ N1, Guazzoni G1.Departments of Urology1 and Pathology2; 1Istituto Clinico Humanitas IRCCS, 2Humanitas Clinical and Research Center, Rozzano, Italy
Late-Breaking Scientific Poster, EAU (European Association of Urology) 2018, Copenhagen, Denmark
    
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ABSTRACT
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™ (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.


SCIENTIFIC POSTER
Initial Results Comparing 29 MHz Micro-Ultrasound with Multi-Parametric MRI for Targeted Prostate Biopsy: Relative Sensitivity to Clinically Significant Prostate Cancer
Astobieta A, Sanchez A, De la Cruz I, Pereira JG, Gamarra M, Urdaneta F, Mora G , Ibarluzea G. Urología Clínica, IMQ, Bilbao, Spain
Scientific Poster, EAU (European Association of Urology) 2018, Copenhagen, Denmark
    
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ABSTRACT
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

SCIENTIFIC POSTER
Comparison Between the Diagnostic Accuracy of Micro-Ultrasound Versus Multiparametric MRI in the Detection of Prostate Cancer: Preliminary Results from a Single-Institutional Ongoing Prospective Trial
Lughezzani G1, Ma_ei D1, Lazzeri M1, Colombo P2, Lista G1, Cardone P1, Hurle R1, Casale P1, Saita A1, Bu_ N1, Guazzoni G1.
Departments of Urology1 and Pathology2; 1Istituto Clinico Humanitas IRCCS, 2Humanitas Clinical and Research Center, Rozzano, Italy
Scientific Poster, 10th International Symposium On Focal Therapy And Imaging In Prostate And Kidney Cancer, 2018, Noordwijk, The Netherlands
    
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ABSTRACT
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.

SCIENTIFIC POSTER
Assessment of the Diagnostic Accuracy of Micro-Ultrasound for the Detection of Clinically Significant Prostate Cancer: Results from a Single-Institutional Preliminary Experience
Lughezzani G1, Ma_ei D1, Lazzeri M1, Colombo P2, Lista G1, Cardone P1, Hurle R1, Casale P1, Saita A1, Bu_ N1, Guazzoni G1. Departments of Urology1 and Pathology2, Istituto Clinico Humanitas IRCCS, Humanitas Clinical and Research Center, Rozzano, Italy
Scientific Poster, 10th International Symposium On Focal Therapy And Imaging In Prostate And Kidney Cancer, 2018, Noordwijk, The Netherlands
    
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ABSTRACT
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.

PAPER
Suspicious findings on micro-ultrasound imaging and early detection of prostate cancer
Sangeet Ghai1, Theodorus Van der Kwast2; 1Joint Department of Medical Imaging, University of Toronto, University Health Network - Mount Sinai Hospital-Women's College Hospital, Toronto General Hospital, Toronto, ON, Canada; 2 Department of Pathology, Toronto General Hospital, Toronto, ON, Canada
Urology Case Reports, January 2018 Volume 16, Pages 98–100
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ABSTRACT
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

SCIENTIFIC POSTER
Comparison of Conventional TRUS, MRI and Micro-Ultrasound for Visualizing Prostate Cancer in an Active Surveillance Population: A Feasibility Study
G. Eure1, D. Fanney2, J. Lin1, B. Wodlinger3, S. Ghai4 1 Urology of Virginia, Virginia Beach, Virginia 2 MRI & CT Diagnostics, Virginia Beach, Virginia 3 Exact Imaging, Markham, Ontario 4 Joint Department of Medical Imaging, University of Toronto, University Health Network - Mount Sinai Hospital-Women's College Hospital, Toronto General Hospital, Toronto, ON, Canada
Scientific Poster, ESUI (European Association of Urology’s Section of Urological Imaging) 2017, Barcelona, Spain
    
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ABSTRACT
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.


SCIENTIFIC POSTER
Correlating Micro-Ultrasound Sonographic Features and PRI-MUS™ Ranking of Prostate Cancer Lesions with Underlying Histo-pathology
Jefferson Lin, Brian Wodlinger, Theresa McGrath, Gregg Eure, Urology of Virginia, Virginia Beach, Virginia; Exact Imaging, Markham, Ontario, Canada
Scientific Poster, ESUI (European Association of Urology’s Section of Urological Imaging) 2017, Barcelona, Spain
    
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ABSTRACT
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.


SCIENTIFIC POSTER
Feasibility Study for Avoiding or Postponing Biopsy using Improved Imaging: Negative Predictive Value of Micro-Ultrasound for Subjects with Low PSAD
Astobieta A, Sanchez A, De la Cruz I, Pereira JG, Gamarra M, Urdaneta F, Mora G , Ibarluzea G. Urología Clínica Bilbao. Clínica IMQ Zorrotzaurre. Bilbao. Spain
Scientific Poster, ESUI (European Association of Urology’s Section of Urological Imaging) 2017, Barcelona, Spain
    
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ABSTRACT
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.


SCIENTIFIC POSTER
Initial Results Comparing 29 MHz Micro-Ultrasound with Multi-Parametric MRI for Targeted Prostate Biopsy: Relative Sensitivity to Clinically Significant Prostate Cancer
Astobieta A, Sanchez A, De la Cruz I, Pereira JG, Gamarra M, Urdaneta F, Mora G , Ibarluzea G. Urología Clínica Bilbao. Clínica IMQ Zorrotzaurre. Bilbao. Spain
Scientific Poster, ESUI (European Association of Urology’s Section of Urological Imaging) 2017, Barcelona, Spain
    
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ABSTRACT
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.


SCIENTIFIC POSTER
Promising initial results of semi-automated quantitative-ultrasound-based (QUS) algorithm for assessment of prostate cancer using a novel 29 MHz micro-ultrasound
Daniel Rohrbach, Brian Wodlinger, Jerrold Wen, Jonathan Mamou, Ernest Feleppa
Scientific Poster, ESUI (European Association of Urology’s Section of Urological Imaging) 2016, Milan, Italy
    
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ABSTRACT
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.

SCIENTIFIC POSTER
High resolution micro-ultrasound of the prostate, PRI-MUS™ protocol guidance along with clinical variables: Combined approach for reducing unnecessary biopsies
Wodlinger B, Ghai S, Eure G, Fradet V, Hyndman ME, McGrath T, Pavlovich CP
Scientific Poster, ESUI (European Association of Urology’s Section of Urological Imaging) 2016, Milan, Italy
    
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ABSTRACT
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

PAPER
Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification
Ghai S, Eure G, Fradet V, Hyndman ME, McGrath T, Wodlinger B, Pavlovich CP.
J Urol. 2016 Aug;196(2):562-9.
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ABSTRACT
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

SCIENTIFIC POSTER
Assessing Cancer Risk in 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the PRI-MUS (prostate risk identification using micro-ultrasound) protocol
Scientific Poster #P050, ESUI (European Association of Urology’s Section of Urological Imaging) 2015, Barcelona, Spain
    
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ABSTRACT
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.

PAPER
High-resolution transrectal ultrasound: pilot study of a novel technique for imaging clinically localized prostate cancer
Pavlovich CP, Cornish TC, Mullins JK, Fradin J, Mettee LZ, Connor JT, Reese AC, Askin FB, Luck R, Epstein JI, Burke HB.
Urol Oncol. 2014 Jan;32(1):34.e27-32. doi: 10.1016/j.urolonc.2013.01.006.
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ABSTRACT
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



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