Evaluation of prostate cancer detection using micro-ultrasound versus MRI through co-registration to whole-mount pathology.

Micro-ultrasound has recently been introduced as a low-cost alternative to multi-parametric MRI for imaging prostate cancer. Early clinical studies have demonstrated promising results; however, robust validation via comparison with whole-mount pathology has yet to be achieved. Due to micro-ultrasound probe design and tissue deformation during scanning, it is difficult to accurately correlate micro-ultrasound imaging planes with ground truth whole-mount pathology slides. In this study, we developed a multi-step methodology to co-register micro-ultrasound and MRI to whole-mount pathology. The three-step process had a registration error of 3.90 ± 0.11 mm and consists of: (1) micro-ultrasound image reconstruction, (2) 3D landmark registration of micro-ultrasound to MRI, and (3) 2D capsule registration of MRI to whole-mount pathology. This process was then used in a preliminary reader study to compare the diagnostic accuracy of micro-ultrasound and MRI in 15 patients who underwent radical prostatectomy for prostate cancer. Micro-ultrasound was found to have equivalent performance to retrospective MRI review for index lesion detection (91.7% vs. 80%), while demonstrating an increased detection of tumor extent (52.5% vs. 36.7%) with similar false positive regions-of-interest (38.3% vs. 40.8%). Prospective MRI review had reduced detection of index lesions (73.3%) and tumor extent (18.9%) but improved false positive regions-of-interest (22.7%) relative to micro-ultrasound and retrospective MRI. Further evaluation is needed with a larger sample size.

Inter-reader Agreement for Prostate Cancer Detection Using Micro-ultrasound: A Multi-institutional Study.

Background and objective: Micro-ultrasound (MUS) uses a high-frequency transducer with superior resolution to conventional ultrasound, which may differentiate prostate cancer from normal tissue and thereby allow targeted biopsy. Preliminary evidence has shown comparable sensitivity to magnetic resonance imaging (MRI), but consistency between users has yet to be described. Our objective was to assess agreement of MUS interpretation across multiple readers. Methods: After institutional review board approval, we prospectively collected MUS images for 57 patients referred for prostate biopsy after multiparametric MRI from 2022 to 2023. MUS images were interpreted by six urologists at four institutions with varying experience (range 2-6 yr). Readers were blinded to MRI results and clinical data. The primary outcome was reader agreement on the locations of suspicious lesions, measured in terms of Light's κ and positive percent agreement (PPA). Reader sensitivity for identification of grade group (GG) ≥2 prostate cancer was a secondary outcome. Key findings and limitations: Analysis revealed a κ value of 0.30 (95% confidence interval [CI] 0.21-0.39). PPA was 33% (95% CI 25-42%). The mean patient-level sensitivity for GG ≥2 cancer was 0.66 ± 0.05 overall and 0.87 ± 0.09 when cases with anterior lesions were excluded. Readers were 12 times more likely to detect higher-grade cancers (GG ≥3), with higher levels of agreement for this subgroup (κ 0.41, PPA 45%). Key limitations include the inability to prospectively biopsy reader-delineated targets and the inability of readers to perform live transducer maneuvers. Conclusions and clinical implications: Inter-reader agreement on the location of suspicious lesions on MUS is lower than rates previously reported for MRI. MUS sensitivity for cancer in the anterior gland is lacking. Patient summary: The ability to find cancer on imaging scans can vary between doctors. We found that there was frequent disagreement on the location of prostate cancer when doctors were using a new high-resolution scan method called micro-ultrasound. This suggests that the performance of micro-ultrasound is not yet consistent enough to replace MRI (magnetic resonance imaging) for diagnosis of prostate cancer.

A Comparative Evaluation of Multiparametric Magnetic Resonance Imaging and Micro-Ultrasound for the Detection of Clinically Significant Prostate Cancer in Patients with Prior Negative Biopsies.

BACKGROUND: The diagnostic process for prostate cancer after a negative biopsy is challenging. This study compares the diagnostic accuracy of micro-ultrasound (mUS) with multiparametric magnetic resonance imaging (mpMRI) for such cases. METHODS: A retrospective cohort study was performed, targeting men with previous negative biopsies and using mUS and mpMRI to detect prostate cancer and clinically significant prostate cancer (csPCa). RESULTS: In our cohort of 1397 men, 304 had a history of negative biopsies. mUS was more sensitive than mpMRI, with better predictive value for negative results. Importantly, mUS was significantly associated with csPCa detection (adjusted odds ratio [aOR]: 6.58; 95% confidence interval [CI]: 1.15-37.8; p = 0.035). CONCLUSIONS: mUS may be preferable for diagnosing prostate cancer in previously biopsy-negative patients. However, the retrospective design of this study at a single institution suggests that further research across multiple centers is warranted.

Development of a microultrasound-based nomogram to predict extra-prostatic extension in patients with prostate cancer undergoing robot-assisted radical prostatectomy.

OBJECTIVES: To develop a microultrasound-based nomogram including clinicopathological parameters and microultrasound findings to predict the presence of extra-prostatic extension and guide the grade of nerve-sparing. MATERIAL AND METHODS: All patients underwent microultrasound the day before robot-assisted radical prostatectomy. Variables significantly associated with extra-prostatic extension at univariable analysis were used to build the multivariable logistic model, and the regression coefficients were used to develop the nomogram. The model was subjected to 1000 bootstrap resamples for internal validation. The performance of the microultrasound-based model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). RESULTS: Overall, 122/295 (41.4%) patients had a diagnosis of extra-prostatic extension on definitive pathology. Microultrasound correctly identify extra-prostatic extension in 84/122 (68.9%) cases showing a sensitivity and a specificity of 68.9% and 84.4%, with an AUC of 76.6%. After 1000 bootstrap resamples, the predictive accuracy of the microultrasound-based model was 85.9%. The calibration plot showed a satisfactory concordance between predicted probabilities and observed frequencies of extra-prostatic extension. The DCA showed a higher clinical net-benefit compared to the model including only clinical parameters. Considering a 4% cut-off, nerve-sparing was recommended in 173 (58.6%) patients and extra-prostatic extension was detected in 32 (18.5%) of them. CONCLUSION: We developed a microultrasound-based nomogram for the prediction of extra-prostatic extension that could aid in the decision whether to preserve or not neurovascular bundles. External validation and a direct comparison with mpMRI-based nomogram is crucial to corroborate our results.

MicroSegNet: A deep learning approach for prostate segmentation on micro-ultrasound images.

Micro-ultrasound (micro-US) is a novel 29-MHz ultrasound technique that provides 3-4 times higher resolution than traditional ultrasound, potentially enabling low-cost, accurate diagnosis of prostate cancer. Accurate prostate segmentation is crucial for prostate volume measurement, cancer diagnosis, prostate biopsy, and treatment planning. However, prostate segmentation on micro-US is challenging due to artifacts and indistinct borders between the prostate, bladder, and urethra in the midline. This paper presents MicroSegNet, a multi-scale annotation-guided transformer UNet model designed specifically to tackle these challenges. During the training process, MicroSegNet focuses more on regions that are hard to segment (hard regions), characterized by discrepancies between expert and non-expert annotations. We achieve this by proposing an annotation-guided binary cross entropy (AG-BCE) loss that assigns a larger weight to prediction errors in hard regions and a lower weight to prediction errors in easy regions. The AG-BCE loss was seamlessly integrated into the training process through the utilization of multi-scale deep supervision, enabling MicroSegNet to capture global contextual dependencies and local information at various scales. We trained our model using micro-US images from 55 patients, followed by evaluation on 20 patients. Our MicroSegNet model achieved a Dice coefficient of 0.939 and a Hausdorff distance of 2.02 mm, outperforming several state-of-the-art segmentation methods, as well as three human annotators with different experience levels. Our code is publicly available at https://github.com/mirthAI/MicroSegNet and our dataset is publicly available at https://zenodo.org/records/10475293.

Is multiparametric MRI always needed in biopsy-naïve patients with abnormal digital rectal examination? A single-institutional experience combining clinical and micro-ultrasonography-based factors to optimize prostate cancer detection.

PURPOSE: To assess the diagnostic performance of microultrasound-targeted biopsy (microUSTBx) and systematic biopsy (SBx) in detecting clinically significant prostate cancer (csPCa) among men with abnormal digital rectal examination (DRE) and suspicious lesions at multiparametric magnetic resonance imaging (mpMRI), and to compare the diagnostic performance of this approach with a mpMRI-guided targeted biopsy (MTBx) plus SBx-based strategy. METHODS: Biopsy-naïve men with suspicious lesions at mpMRI and abnormal DRE were prospectively evaluated between October 2017 and January 2023. csPCa detection rate by microUSTBx plus SBx and MTBx plus SBx was assessed and then compared by McNemar's test. The added value of prostate-specific antigen density (PSAd) was also evaluated. RESULTS: Overall, 182 biopsy naïve men were included. MicroUSTBx plus SBx achieved comparable detection rate to MTBx plus SBx in diagnosis of ciPCa and csPCa (ciPCa: 9.3% [17/182] vs 10% [19/182]; csPCa: 63% [114/182] vs 62% [113/182]). MicroUSTBx outperformed MTBx (ciPCa: 5.5% [10/182] vs 6.0% [11/182]; csPCa: 57% [103/182] vs 54% [99/182]). Using microUSTBx plus SBx would have avoided 68/182 (37%) unnecessary mpMRI, while missing only 2/116 (1.7%) csPCa. The decision curve analysis of suspicious microUS plus PSAd ≥ 0.15 ng/ml showed higher net benefit in the ability to identify true positives and reduce the number of unnecessary prostate biopsy in this subcategory of patients. CONCLUSIONS: The combination of microUSTBx and SBx showed equal diagnostic performance to an mpMRI-based approach in biopsy-naïve patients with an abnormal DRE. The combination of this approach with PSAd maximize the diagnostic accuracy while lowering the need for unnecessary biopsies.

Adaptation of a Clinical High-Frequency Transrectal Ultrasound System for Prostate Photoacoustic Imaging: Implementation and Pre-clinical Demonstration.

OBJECTIVE: High-frequency, high-resolution transrectal micro-ultrasound (micro-US: ≥15 MHz) imaging of the prostate is emerging as a beneficial tool for scoring disease risk and accurately targeting biopsies. Adding photoacoustic (PA) imaging to visualize abnormal vascularization and accumulation of contrast agents in tumors has potential for guiding focal therapies. In this work, we describe a new imaging platform that combines a transrectal micro-US system with transurethral light delivery for PA imaging. METHODS: A clinical transrectal micro-US system was adapted to acquire PA images synchronous to a tunable laser pulse. A transurethral side-firing optical fiber was developed for light delivery. A polyvinyl chloride (PVC)-plastisol phantom was developed and characterized to image PA contrast agents in wall-less channels. After resolution measurement in water, PA imaging was demonstrated in phantom channels with dyes and biodegradable nanoparticle contrast agents called porphysomes. In vivo imaging of a tumor model was performed, with porphysomes administered intravenously. RESULTS: Photoacoustic imaging data were acquired at 5 Hz, and image reconstruction was performed offline. PA image resolution at a 14-mm depth was 74 and 261 µm in the axial and lateral directions, respectively. The speed of sound in PVC-plastisol was 1383 m/s, and the attenuation was 4 dB/mm at 20 MHz. PA signal from porphysomes was spectrally unmixed from blood signals in the tumor, and a signal increase was observed 3 h after porphysome injection. CONCLUSION: A combined transrectal micro-US and PA imaging system was developed and characterized, and in vivo imaging demonstrated. High-resolution PA imaging may provide valuable additional information for diagnostic and therapeutic applications in the prostate.

Micro-ultrasound based characterization of cerebrovasculature following focal ischemic stroke and upon short-term rehabilitation.

Notwithstanding recanalization treatments in the acute stage of stroke, many survivors suffer long-term impairments. Physical rehabilitation is the only widely available strategy for chronic-stage recovery, but its optimization is hindered by limited understanding of its effects on brain structure and function. Using micro-ultrasound, behavioral testing, and electrophysiology, we investigated the impact of skilled reaching rehabilitation on cerebral hemodynamics, motor function, and neuronal activity in a rat model of focal ischemic stroke. A 50 MHz micro-ultrasound transducer and intracortical electrophysiology were utilized to characterize neurovascular changes three weeks following focal ischemia elicited by endothelin-1 injection into the sensorimotor cortex. Sprague-Dawley rats were rehabilitated through tray reaching, and their fine skilled reaching was assessed via the Montoya staircase. Focal ischemia led to a sustained deficit in forelimb reaching; and increased tortuosity of the penetrating vessels in the perilesional cortex; with no lateralization of spontaneous neuronal activity. Rehabilitation improved skilled reaching; decreased cortical vascularity; was associated with elevated peri- vs. contralesional hypercapnia-induced flow homogenization and increased perilesional spontaneous cortical neuronal activity. Our study demonstrated neurovascular plasticity accompanying rehabilitation-elicited functional recovery in the subacute stage following stroke, and multiple micro-ultrasound-based markers of cerebrovascular structure and function modified in recovery from ischemia and upon rehabilitation.

A current role status of micro-ultrasound imaging in prostate cancer diagnosis.

 Recently diagnostic field in medicine was enriched by advances in ultrasonography (US) technology, which led to establishment of novel modalities, one of which is micro-ultrasound. Results demonstrated by early studies have been promising, simultaneously rising a question if those new modalities could become an alternative in diagnosis of prostatic carcinoma (PCa). To answer this question, several studies have been conducted where micro-ultrasound have been compared to standard diagnostic tools, such as conventional TRUS or mpMRI. Nevertheless, new technology presents with some limitations, which include inconsistent results, necessity for specialized equipment, need of training for investigators to understand the findings, and external validation. In this publication, we have identified studies that provided evaluation of the accuracy and efficiency of the micro-ultrasound technology. Additionally, analysis of the results provided a better understanding of the novel imaging tool when compared standard modalities in diagnosis of PCa. Increasing number of studies demonstrated that micro-ultrasound carries high detection rate of PCa and clinically significant prostatic cancer (csPCa), suggesting a similar performance to mpMRI and even showing superiority over conventional TRUS. Recent studies have also showed that micro-ultrasound takes active role in improving the detection of csPCa and guidance for prostate biopsy (PBx) as well as further treatment. Moreover, certain practical aspects such as lower costs, decreased waiting time, real-time imaging and application of the imaging tool for patients that are not suitable for mpMRI (contrast allergy, prosthetics etc.) are significant advantages. Analysis of the results still does not provide clear answer whether micro-ultrasound outperforms mpMRI. Further studies are necessary in order to completely understand the potential of this new technology.

Assessing cancer risk in the anterior part of the prostate using micro-ultrasound: validation of a novel distinct protocol.

PURPOSE: To develop and validate a micro-ultrasound risk score that predicts the likelihood of significant prostate cancer in the anterior zone. METHODS: Patients were enrolled from three expert institutions familiar with micro-ultrasound. The study was conducted in two phases. First, the PRI-MUS anterior score was developed by assessing selected prostate videos from patients who subsequently underwent radical prostatectomy. Second, seven urology readers with varying levels of experience in micro-ultrasound examination evaluated prostate loops according to the PRI-MUS anterior score. Each reader watched the videos and recorded the likelihood of the presence of significant cancer in the anterior part of the prostate in a three-point scale. The coherence among the readers was calculated using the Fleiss kappa and the Cronbach alpha. RESULTS: A total of 102 selected prostate scans were used to develop the risk assessment for anterior zone cancer in the prostate. The score comprised three categories: likely, equivocal, and unlikely. The median (IQR) sensitivity, specificity, positive predictive value, and negative predictive value for the seven readers were 72% (68-84), 68% (64-84), 75% (72-81), and 73% (71-80), respectively. The mean SD ROC AUC was 0.75 ± 2%, while the Fleiss kappa and the Cronbach alpha were 0.179 and 0.56, respectively. CONCLUSION: Micro-ultrasound can detect cancerous lesions in the anterior part of the prostate. When combined with the PRI-MUS protocol to assess the peripheral part, it enables an assessment of the entire prostate gland. Pending external validation, the PRI-MUS anterior score developed in this study might be implemented in clinical practice.

The diagnostic accuracy of micro-ultrasound for prostate cancer diagnosis: a review.

PURPOSE: Micro-UltraSound (microUS) is a new imaging modality capable of identifying and targeting suspicious areas, which might further increase the diagnostic yield of prostate biopsy (PBx). Aim of this review is to provide insights into the usefulness of microUS for the sub-stratification of prostate cancer (PCa), clinically significant PCa (i.e., any Gleason score ≥ 7 PCa; csPCa) along with non-organ-confined disease in patients undergoing PBx. METHODS: A PubMed literature search was performed using keywords: prostate cancer diagnosis, prostate cancer diagnosis surveillance, systematic biopsy, target biopsy, micro-ultrasound, and prostate risk identification using micro-ultrasound. RESULTS: MicroUS could significantly improve multiparametric magnetic resonance imaging (mpMRI) findings by adding valuable anatomical and pathological information provided by real-time examination. Furthermore, microUS target biopsy could replace systematic biopsy in clinical practice by reducing the detection of clinically insignificant (ciPCa) and increasing that of csPCa. Finally, microUS may be useful in predicting the presence of non-organ confined PCa before radical prostatectomy and it could also be an effective add-on tool for patient monitoring within the active surveillance program. CONCLUSION: MicroUS may represent an attractive step forward for the management of csPCa as a complementary or alternative tool to mpMRI. Nevertheless, further longitudinal studies are warranted, and the strength of the evidence is still suboptimal to provide clear recommendations for daily clinical practice.

Comparative Assessment of Different Ultrasound Technologies in the Detection of Prostate Cancer: A Systematic Review and Meta-Analysis.

The present study aimed to assess the diagnostic test accuracy of different ultrasound scanning technologies in the detection of prostate cancer. A systematic search was conducted using the Cochrane Guidelines for Screening and Diagnostic Tests. We performed a systematic search in the international databases PubMed, Medline, Ovid, Embase and Cochrane Library. Searches were designed to find all studies that evaluated Micro-US, mpUS, SWE and CEUS as the main detection modalities for prostate cancer. This study was registered with Research Registry of systematic review and meta-analysis. The QUADAS-2 tool was utilized to perform quality assessment and bias analysis. The literature search generated 1376 studies. Of these, 320 studies were screened for eligibility, with 1056 studies being excluded. Overall, 26 studies with a total of 6370 patients met the inclusion criteria. The pooled sensitivity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.66 (95% CI 0.54-0.73) 0.73 (95% CI 0.58-0.88), 0.82 (95% CI 0.75-0.90), 0.85 (95% CI 0.76-0.94) and 0.87 (95% CI 0.71-1.03), respectively. Moreover, the pooled specificity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.56 (95% CI 0.21-0.90), 0.78 (95% CI 0.67-0.88), 0.76 (95% CI 0.65-0.88), 0.43 (95% CI 0.28-0.59) and 0.68 (95% CI 0.54-0.81), respectively. In terms of sensitivity, substantial heterogeneity between studies was detected (I2 = 72%, p = 0.000 < 0.05). In relation to specificity, extreme heterogeneity was detected (I2 = 93%, p = 0.000 < 0.05). Some studies proved that advanced ultrasound modalities such as mpUS, Micro-US, shear-wave elastography, contrast enhanced and micro-ultrasound are promising methods for the detection of prostate cancer.

Diagnostic accuracy of multiparametric MRI- and microultrasound-targeted biopsy in biopsy-naïve patients with a PI-RADS 5 lesion: a single-institutional study.

PURPOSE: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (MRI)- and microultrasound (microUS)-guided targeted biopsy (TBx) in detecting prostate cancer (PCa) and clinically significant (cs) PCa among men with Prostate Imaging Reporting and Data System (PI-RADS 5) lesions and to compare this combined TBx (CTBx) strategy with CTBx plus systemic biopsy (SBx). METHODS: One hundred and thirty-six biopsy-naïve patients with PI-RADS 5 lesion at multiparametric MRI undergoing CTBx plus SBx were retrospectively evaluated. Analysis of diagnostic performance of microUS-TBx, MRI-TBx, CTBx, SBx and combined CTBx plus SBx was performed. Cost (downgrade, upgrade and biopsy core) to effectiveness (detection rate) was compared. RESULTS: CTBx achieved a comparable detection rate to CTBx plus SBx in diagnosis of PCa and csPCa (PCa: 78.7% [107/136] vs 79.4% [108/136]; csPCa: 67.6% [92/136] vs 67.6% [92/136]; p > 0.05) and outperformed SBx (PCa: 58.8% [80/136]; csPCa: 47.8% [65/136]; p < 0.001). Using CTB would have avoided 41.1% (56/136) unnecessary SBx, without missing any csPCa. The rate of any upgrading or csPCa upgrading was significantly higher by SBx than by CTBx [33/65 (50.8%) vs 17/65 (26.1%) and 20/65 (30.8%) vs 4/65 (6.15%), respectively, p < 0.05]. Considering csPCa detection rate, microUS showed high sensitivity and positive predictive value (94.6%, 87.9%, respectively), with lower specificity and negative predictive value (25.0% and 44.4%, respectively). At multivariable logistic regression models, positive microUS was identified as an independent predictor of csPCa (p = 0.024). CONCLUSIONS: A combined microUS/MRI-TBx approach could be the ideal imaging tool for characterizing primary disease in PI-RADS five patients, allowing SBx to be avoided.

Embedding new technology into clinical ultrasound practice: Is role extension for sonographers the key to improving patient pathways?

Introduction: MicroUS is a new imaging technique that may have potential to reliably monitor prostate disease and therefore release capacity in MRI departments. Firstly, however, it is essential to identify which healthcare staff may be suitable to learn to use this modality. Based on previous evidence, UK sonographers may be well placed to harness this resource. Topic: Currently, there is sparse evidence on the performance of MicroUS for monitoring prostate disease but early findings are encouraging. Although its uptake is increasing, it is believed that only two sites in the UK have MicroUS systems and only one of those uses just sonographers to undertake and interpret this new imaging technique. Discussion: UK sonographers have a history of role extension dating back several decades and have proven repeatedly that they are reliable and accurate when measured against a gold standard. We explore the background of UK sonographer role extension and postulate that sonographers are best placed to adopt and embed new imaging techniques and technology into routine clinical practice. This is of particular importance given the dearth of ultrasound focussed radiologists in the UK. To effectively introduce challenging new work streams, multi-professional collaboration in imaging, alongside sonographer role extension, will ensure precious resources are maximised thus ensuring optimum patient care. Conclusion: UK sonographers have repeatedly demonstrated reliability in many areas of role extension in various clinical settings. Early data indicate that the adoption of MicroUS for use in prostate disease surveillance may be another role suited to sonographers.

TRUSformer: improving prostate cancer detection from micro-ultrasound using attention and self-supervision.

PURPOSE: A large body of previous machine learning methods for ultrasound-based prostate cancer detection classify small regions of interest (ROIs) of ultrasound signals that lie within a larger needle trace corresponding to a prostate tissue biopsy (called biopsy core). These ROI-scale models suffer from weak labeling as histopathology results available for biopsy cores only approximate the distribution of cancer in the ROIs. ROI-scale models do not take advantage of contextual information that are normally considered by pathologists, i.e., they do not consider information about surrounding tissue and larger-scale trends when identifying cancer. We aim to improve cancer detection by taking a multi-scale, i.e., ROI-scale and biopsy core-scale, approach. METHODS: Our multi-scale approach combines (i) an "ROI-scale" model trained using self-supervised learning to extract features from small ROIs and (ii) a "core-scale" transformer model that processes a collection of extracted features from multiple ROIs in the needle trace region to predict the tissue type of the corresponding core. Attention maps, as a by-product, allow us to localize cancer at the ROI scale. RESULTS: We analyze this method using a dataset of micro-ultrasound acquired from 578 patients who underwent prostate biopsy, and compare our model to baseline models and other large-scale studies in the literature. Our model shows consistent and substantial performance improvements compared to ROI-scale-only models. It achieves [Formula: see text] AUROC, a statistically significant improvement over ROI-scale classification. We also compare our method to large studies on prostate cancer detection, using other imaging modalities. CONCLUSIONS: Taking a multi-scale approach that leverages contextual information improves prostate cancer detection compared to ROI-scale-only models. The proposed model achieves a statistically significant improvement in performance and outperforms other large-scale studies in the literature. Our code is publicly available at www.github.com/med-i-lab/TRUSFormer .

Non-Invasive Imaging Modalities in Intravesical Murine Models of Bladder Cancer.

Bladder cancer (BCa) is the sixth most prevalent cancer in men and seventeenth most prevalent cancer in women worldwide. Current treatment paradigms have limited therapeutic impact, suggesting an urgent need for the investigation of novel therapies. To best emulate the progression of human BCa, a pre-clinical intravesical murine model is required in conjunction with existing non-invasive imaging modalities to detect and evaluate cancer progression. Non-invasive imaging modalities reduce the number of required experimental models while allowing for longitudinal studies of novel therapies to investigate long-term efficacy. In this review, we discuss the individual and multi-modal use of non-invasive imaging modalities; bioluminescence imaging (BLI), micro-ultrasound imaging (MUI), magnetic resonance imaging (MRI), and positron emission tomography (PET) in BCa evaluation. We also provide an update on the potential and the future directions of imaging modalities in relation to intravesical murine models of BCa.

Robotically controlled three-dimensional micro-ultrasound for prostate biopsy guidance.

PURPOSE: Prostate imaging to guide biopsy remains unsatisfactory, with current solutions suffering from high complexity and poor accuracy and reliability. One novel entrant into this field is micro-ultrasound (microUS), which uses a high-frequency imaging probe to achieve very high spatial resolution, and achieves prostate cancer detection rates equivalent to multiparametric magnetic resonance imaging (mpMRI). However, the ExactVu transrectal microUS probe has a unique geometry that makes it challenging to acquire controlled, repeatable three-dimensional (3D) transrectal ultrasound (TRUS) volumes. We describe the design, fabrication, and validation of a 3D acquisition system that allows for the accurate use of the ExactVu microUS device for volumetric prostate imaging. METHODS: The design uses a motorized, computer-controlled brachytherapy stepper to rotate the ExactVu transducer about its axis. We perform geometric validation using a phantom with known dimensions and compare performance with magnetic resonance imaging (MRI) using a commercial quality assurance anthropomorphic prostate phantom. RESULTS: Our geometric validation shows accuracy of 1 mm or less in all three directions, and images of an anthropomorphic phantom qualitatively match those acquired using MRI and show good agreement quantitatively. CONCLUSION: We describe the first system to acquire robotically controlled 3D microUS images using the ExactVu microUS system. The reconstructed 3D microUS images are accurate, which will allow for future applications of the ExactVu microUS system in prostate specimen and in vivo imaging.

Diagnostic performance of microUltrasound at MRI-guided confirmatory biopsy in patients under active surveillance for low-risk prostate cancer.

BACKGROUND: Active surveillance (AS) represents a standard of care of low-risk prostate cancer (PCa). However, the identification and monitoring of AS candidates remains challenging. Microultrasound (microUS) is a novel high-resolution imaging modality for transrectal ultrasonography (TRUS). We explored the impact of microUS TRUS and targeted biopsies in mpMRI-guided confirmatory biopsies. METHODS: Between October 2017 and September 2021, we prospectively enrolled 100 patients scheduled for MRI-guided confirmatory biopsy at 1 year from diagnosis of ISUP 1 PCa. TRUS was performed using the ExactVu microUS system; PRI-MUS protocol was applied to identify suspicious lesions (i.e., PRIMUS score ≥ 3). All patients received targeted biopsies of any identified microUS and mpMRI lesions and complementary systematic biopsies. The proportion of patients upgraded to clinically significant PCa (defined as ISUP ≥ 2 cancer; csPCa) at confirmatory biopsies was determined, and the diagnostic performance of microUS and mpMRI were compared. RESULTS: Ninety-two patients had a suspicious MRI lesion classified PI-RADS 3, 4, and 5 in respectively 28, 16, and 18 patients. MicroUS identified 82 patients with suspicious lesions, classified as PRI-MUS 3, 4, and 5 in respectively 20, 50, and 12 patients, while 18 individuals had no lesions. Thirty-four patients were upgraded to ISUP ≥ 2 cancer and excluded from AS. MicroUS and mpMRI showed a sensitivity of 94.1% and 100%, and an NPV of 88.9% and 100%, respectively, in detecting ISUP ≥ 2 patients. A microUS-mandated protocol would have avoided confirmatory biopsies in 18 patients with no PRI-MUS ≥ 3 lesions at the cost of missing four upgraded patients. CONCLUSIONS: MicroUS and mpMRI represent valuable imaging modalities showing high sensitivity and NPV in detecting csPCa, thus allowing their use for event-triggered confirmatory biopsies in AS patients. MicroUS offers an alternative imaging modality to mpMRI for the identification and real-time targeting of suspicious lesions in AS patients.

Side-specific, Microultrasound-based Nomogram for the Prediction of Extracapsular Extension in Prostate Cancer.

Background: Prediction of extracapsular extension (ECE) is essential to achieve a balance between oncologic resection and neural tissue preservation. Microultrasound (MUS) is an attractive alternative to multiparametric magnetic resonance imaging (mpMRI) in the staging scenario. Objective: To create a side-specific nomogram integrating clinicopathologic parameters and MUS findings to predict ipsilateral ECE and guide nerve sparing. Design setting and participants: Prospective data were collected from consecutive patients who underwent robotic-assisted radical prostatectomy from June 2021 to May 2022 and had preoperative MUS and mpMRI. A total of 391 patients and 612 lobes were included in the analysis. Outcome measurements and statistical analysis: ECE on surgical pathology was the primary outcome. Multivariate regression analyses were carried out to identify predictors for ECE. The resultant multivariable model's performance was visualized using the receiver-operating characteristic curve. A nomogram was developed based on the coefficients of the logit function for the MUS-based model. A decision curve analysis (DCA) was performed to assess clinical utility. Results and limitations: The areas under the receiver-operating characteristic curve (AUCs) of the MUS-based model were 81.4% and 80.9% (95% confidence interval [CI] 75.6, 84.6) after internal validation. The AUC of the mpMRI-model was also 80.9% (95% CI 77.2, 85.7). The DCA demonstrated the net clinical benefit of the MUS-based nomogram and its superiority compared with MUS and MRI alone for detecting ECE. Limitations of our study included its sample size and moderate inter-reader agreement. Conclusions: We developed a side-specific nomogram to predict ECE based on clinicopathologic variables and MUS findings. Its performance was comparable with that of a mpMRI-based model. External validation and prospective trials are required to corroborate our results. Patient summary: The integration of clinical parameters and microultrasound can predict extracapsular extension with similar results to models based on magnetic resonance imaging findings. This can be useful for tailoring the preservation of nerves during surgery.

Micro-Ultrasound: Current Role in Prostate Cancer Diagnosis and Future Possibilities.

Prostate Cancer (PCa) is the second most common cancer in men. Population screening using prostate specific antigen (PSA) blood test and digital rectal exam (DRE) is recommended by the NCCN, EAU and other prominent clinical guidelines. While MRI is the recommended initial test in men at risk for PCa, micro-Ultrasound (MicroUS) is a novel high resolution ultrasound technology that has shown promise in PCa detection. This article provides a narrative review of the studies to date which have been conducted to evaluate the functionality and efficacy of MicroUS within the patient care pathway for prostate cancer. A total of 13 relevant publications comparing detection of csPCa between MicroUS and mpMRI were selected. An amount of 4 publications referring to use of MicroUS for other indications were found. Each publication was evaluated for risk of bias and applicability using the Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool. The studies reviewed conclude that MicroUS detection rates for clinically significant prostate cancer diagnosis are comparable to the detection rates of mpMRI guided biopsy procedures. While the existing literature indicates that MicroUS should replace conventional TRUS for prostate imaging and biopsy, it is not yet clear whether MicroUS should be used on its own or in conjunction with mpMRI for augmenting prostate cancer detection. The ongoing OPTIMUM trial will provide evidence on how best to utilize this new technology. Early data also suggest this flexible new imaging modality has a place in local staging and active surveillance of prostate cancer as well as in bladder cancer staging.