Clinical Trial Protocol: Developing an Image Classification Algorithm for Prostate Cancer Diagnosis on Three-dimensional Multiparametric Transrectal Ultrasound

Introduction and hypothesis: The tendency toward population-based screening programs for prostate cancer (PCa) is expected to increase demand for prebiopsy imaging. This study hypothesizes that a machine learning image classification algorithm for three-dimensional multiparametric transrectal prostate ultrasound (3D mpUS) can detect PCa accurately. Design: This is a phase 2 prospective multicenter diagnostic accuracy study. A total of 715 patients will be included in a period of approximately 2 yr. Patients are eligible in case of suspected PCa for which prostate biopsy is indicated or in case of biopsy-proven PCa for which radical prostatectomy (RP) will be performed. Exclusion criteria are prior treatment for PCa or contraindications for ultrasound contrast agents (UCAs). Protocol overview: Study participants will undergo 3D mpUS, consisting of 3D grayscale, 4D contrast-enhanced ultrasound, and 3D shear wave elastography (SWE). Whole-mount RP histopathology will provide the ground truth to train the image classification algorithm. Patients included prior to prostate biopsy will be used for subsequent preliminary validation. There is a small, anticipated risk for participants associated with the administration of a UCA. Informed consent has to be given prior to study participation, and (serious) adverse events will be reported. Statistical analysis: The primary outcome will be the diagnostic performance of the algorithm for detecting clinically significant PCa (csPCa) on a per-voxel and a per-microregion level. Diagnostic performance will be reported as the area under the receiver operating characteristic curve. Clinically significant PCa is defined as the International Society of Urological grade group ?2. Full-mount RP histopathology will be used as the reference standard. Secondary outcomes will be sensitivity, specificity, negative predictive value, and positive predictive value for csPCa on a per-patient level, evaluated in patients included prior to prostate biopsy, using biopsy results as the reference standard. A further analysis will be performed on the ability of the algorithm to differentiate between low-, intermediate-, and high-risk tumors. Discussion and summary: This study aims to develop an ultrasound-based imaging modality for PCa detection. Subsequent head-to-head validation trials with magnetic resonance imaging have to be performed in order to determine its role in clinical practice for risk stratification in patients suspected for PCa

Clinical Trial Protocol: Developing an Image Classification Algorithm for Prostate Cancer Diagnosis on Three-dimensional Multiparametric Transrectal Ultrasound

Introduction and hypothesis: The tendency toward population-based screening programs for prostate cancer (PCa) is expected to increase demand for prebiopsy imaging. This study hypothesizes that a machine learning image classification algorithm for three-dimensional multiparametric transrectal prostate ultrasound (3D mpUS) can detect PCa accurately. Design: This is a phase 2 prospective multicenter diagnostic accuracy study. A total of 715 patients will be included in a period of approximately 2 yr. Patients are eligible in case of suspected PCa for which prostate biopsy is indicated or in case of biopsy-proven PCa for which radical prostatectomy (RP) will be performed. Exclusion criteria are prior treatment for PCa or contraindications for ultrasound contrast agents (UCAs). Protocol overview: Study participants will undergo 3D mpUS, consisting of 3D grayscale, 4D contrast-enhanced ultrasound, and 3D shear wave elastography (SWE). Whole-mount RP histopathology will provide the ground truth to train the image classification algorithm. Patients included prior to prostate biopsy will be used for subsequent preliminary validation. There is a small, anticipated risk for participants associated with the administration of a UCA. Informed consent has to be given prior to study participation, and (serious) adverse events will be reported. Statistical analysis: The primary outcome will be the diagnostic performance of the algorithm for detecting clinically significant PCa (csPCa) on a per-voxel and a per-microregion level. Diagnostic performance will be reported as the area under the receiver operating characteristic curve. Clinically significant PCa is defined as the International Society of Urological grade group ≥2. Full-mount RP histopathology will be used as the reference standard. Secondary outcomes will be sensitivity, specificity, negative predictive value, and positive predictive value for csPCa on a per-patient level, evaluated in patients included prior to prostate biopsy, using biopsy results as the reference standard. A further analysis will be performed on the ability of the algorithm to differentiate between low-, intermediate-, and high-risk tumors. Discussion and summary: This study aims to develop an ultrasound-based imaging modality for PCa detection. Subsequent head-to-head validation trials with magnetic resonance imaging have to be performed in order to determine its role in clinical practice for risk stratification in patients suspected for PCa

Use of contrast-enhanced ultrasound in the assessment of uterine fibroids: a feasibility study

Contrast-enhanced ultrasound (CEUS) is an innovative ultrasound technique capable of visualizing both the macro- and microvasculature of tissues. In this prospective pilot study, we evaluated the feasibility of using CEUS to visualize the microvasculature of uterine fibroids and compared CEUS with conventional ultrasound. Four women with fibroids underwent gray-scale ultrasound, sonoelastography and power/color Doppler scans followed by CEUS examination. Analysis of CEUS images revealed initial perfusion of the peripheral rim, that is, a pseudo-capsule, followed by enhancement of the entire lesion through vessels traveling from the exterior to the interior of the fibroid. The pseudo-capsules exhibited slight hyper-enhancement, making a clear delineation of the fibroids possible. The centers of three fibroids exhibited areas lacking vascularization, information not obtainable with the other imaging techniques. CEUS is a feasible technique for imaging and quantifying the microvasculature of fibroids. In comparison with conventional ultrasound imaging modalities, CEUS can provide additional diagnostic information based on the microvasculature

Ultrasound

Clinical ultrasound (US) or sonography is an imaging modality using high frequency sound waves typically between 1 and 20 MHz. US pulses are created in transducers, often piezo-electrical crystal, which converts changes of thickness of the crystal into sound waves by alternating applying voltage. In brachytherapy, transrectal ultrasound (TRUS) probes are commonly used. They can be used for prostate and anal cancers, as well as, with some restrictions, for gynecological brachytherapy treatments. US is extensively used for diagnostic purposes in oncology. The high image resolution and good soft-tissue contrast allow for assessment of different oncologic sites such as abdominal or pelvic tumors, breast cancer, or various lymph node regions. For selected indications, US is considered equal or even superior to computed tomography (CT) or magnetic resonance imaging (MRI). The ultrasound contrast agents (UCA) used in contrast-enhanced ultrasound (CEUS) imaging consist of small bubbles of gas encapsulated in biocompatible shell, which resonate when excited by US waves at certain frequencies

Multiparametric ultrasound: evaluation of greyscale, shear wave elastography and contrast-enhanced ultrasound for prostate cancer detection and localization in correlation to radical prostatectomy specimens

Abstract Background The diagnostic pathway for prostate cancer (PCa) is advancing towards an imaging-driven approach. Multiparametric magnetic resonance imaging, although increasingly used, has not shown sufficient accuracy to replace biopsy for now. The introduction of new ultrasound (US) modalities, such as quantitative contrast-enhanced US (CEUS) and shear wave elastography (SWE), shows promise but is not evidenced by sufficient high quality studies, especially for the combination of different US modalities. The primary objective of this study is to determine the individual and complementary diagnostic performance of greyscale US (GS), SWE, CEUS and their combination, multiparametric ultrasound (mpUS), for the detection and localization of PCa by comparison with corresponding histopathology. Methods/design In this prospective clinical trial, US imaging consisting of GS, SWE and CEUS with quantitative mapping on 3 prostate imaging planes (base, mid and apex) will be performed in 50 patients with biopsy-proven PCa before planned radical prostatectomy using a clinical ultrasound scanner. All US imaging will be evaluated by US readers, scoring the four quadrants of each imaging plane for the likelihood of significant PCa based on a 1 to 5 Likert Scale. Following resection, PCa tumour foci will be identified, graded and attributed to the imaging-derived quadrants in each prostate plane for all prostatectomy specimens. Primary outcome measure will be the sensitivity, specificity, negative predictive value and positive predictive value of each US modality and mpUS to detect and localize significant PCa evaluated for different Likert Scale thresholds using receiver operating characteristics curve analyses. Discussion In the evaluation of new PCa imaging modalities, a structured comparison with gold standard radical prostatectomy specimens is essential as first step. This trial is the first to combine the most promising ultrasound modalities into mpUS. It complies with the IDEAL stage 2b recommendations and will be an important step towards the evaluation of mpUS as a possible option for accurate detection and localization of PCa. Trial registration The study protocol for multiparametric ultrasound was prospectively registered on Clinicaltrials.gov on 14 March 2017 with the registry name ‘Multiparametric Ultrasound-Study for the Detection of Prostate Cancer’ and trial registration number NCT0309123

Imaging of the dispersion coefficient of ultrasound contrast agents by Wiener system Identification for prostate cancer localization

Prostate cancer (PCa) is the most prevalent form of cancer in Western men; however, reliable tools for PCa detection and localization are lacking. Dynamic Contrast Enhanced Ultrasound (DCE-US) is a diagnostic tool that allows analysis of vascularization, by imaging an intravenously injected microbubble bolus. The localization of angiogenic vascularization associated with the development of tumors is of particular interest. Recently, methods aiming at estimating contrast dispersion to localize angiogenesis have shown promise. However, independent estimation of dispersion was not possible due to the ambiguity between dispersive and convective processes. Therefore, in this study we propose a new method that considers the vascular network as a dynamic linear system, whose impulse response can be locally identified by solving the Wiener-Hopf equations. To facilitate characterization, model-based parameter estimation is employed, permitting the determination of the apparent dispersion coefficient (D), velocity (v), and Péclet number (Pe) of the system. A preliminary clinical evaluation using data recorded from 10 patients shows that the proposed method can be applied effectively to DCE-US, and is able to locally characterize the hemodynamics in the prostate

Accurate validation of ultrasound imaging of prostate cancer: a review of challenges in registration of imaging and histopathology

As the development of modalities for prostate cancer (PCa) imaging advances, the challenge of accurate registration between images and histopathologic ground truth becomes more pressing. Localization of PCa, rather than detection, requires a pixel-to-pixel validation of imaging based on histopathology after radical prostatectomy. Such a registration procedure is challenging for ultrasound modalities; not only the deformations of the prostate after resection have to be taken into account, but also the deformation due to the employed transrectal probe and the mismatch in orientation between imaging planes and pathology slices. In this work, we review the latest techniques to facilitate accurate validation of PCa localization in ultrasound imaging studies and extrapolate a general strategy for implementation of a registration procedure

Transabdominal contrast-enhanced ultrasound imaging of the prostate

Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time-intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r(2) = 0.91 (r(2) > 0.75 for 78.6% of all prostate pixels) compared with r(2) = 0.91 (r(2) > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitorin