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.
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

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.

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


ExactVu™ micro-ultrasound system is available for sale in the European Union (CE Mark), the United States (FDA 510(k) clearance), and in Canada (Health Canada license).