Background

In the last decade, increasing numbers of people have become interested in the diagnostic efficacy of newer US techniques and the multiparametric (mp) approach in determining the function of mpUS, either as a diagnostic imaging test that may complement mpMRI or as a supplement to a biopsy.¹ mpUS combines different US exams, such as grayscale US, Doppler US, elastography, and contrast-enhanced (CE) US. Similar to the development of mpMRI, a combination of these US-based modalities could potentially enhance diagnostic performance. More recently, high resolution micro-US has emerged as a promising tool for the diagnosis of prostate cancer (PCa). mpUS and micro-US have gained interest in urology and radiology, especially in prostate imaging and targeting.^2-5

Brightness Mode Transrectal US

Traditional brightness mode (B-mode) or grayscale US imaging has limitations in detecting PCa because backscatter signals from PCa and normal prostate may be similar. The main PCa detection method has historically been B-mode sonographic imaging. It offers real-time images and is the most popular, affordable, and readily available medical imaging.⁶ However, conventional B-mode transrectal (TR) US alone has a low sensitivity and specificity that ranges from 40% to 50% for PCa detection.²

Doppler US

Doppler US detects the increased microvascular density associated with PCa angiogenesis. Color Doppler (CD) US converts the blood flow measurements into an array of colors to show the speed and direction of blood flow through the vessel. Vascular characteristics of the malignant and benign lesions are markedly different and consistent with vascular and tissue remodeling known to be associated with tumor growth. Isoechoic lesions are easily missed on grayscale TRUS, especially when they are small in size. In CDUS, the pulsatility of microvessels can be accurately measured, and the increased tissue perfusion reveals potential foci of PCa, improving the accuracy of TRUS.⁷ Power Doppler US is even more sensitive than CDUS in detecting blood flow, although it does not provide information about the direction of blood flow. Power Doppler US has not demonstrated superior PCa detection, despite being more sensitive than CDUS at detecting slow blood flow with a negative predictive value of 96% but a positive predictive value of 57% for predicting positive biopsy.⁸ CDUS is more sensitive to high-grade large lesions in which the feeding vessels are more prominent.

Elastography

US elastography is an imaging technique capable of mapping tissue stiffness of the prostate. It is known that prostatic cancer tissue is often more rigid than benign tissue. Strain elastography and shear-wave elastography are the 2 most frequently used types of elastography in the prostate.⁹ Prostate elastography may be used as an additional tool to locate tumors and to guide biopsies, by identifying stiffer lesions. Morris et al used a dense acoustic radiation force push method, which is simpler to use to check the entire gland before a biopsy because it provides a better shear wave signal—to—noise ratio than commercially available shear-wave elastography systems. It standardizes tissue stiffness measurement and enables increased accuracy of suspicious lesions.¹⁰

CEUS

CEUS involves intravenous injection of gas-filled microbubble contrast agents to patients to evaluate perfusion within the small microvessels (40 μm) and enhance visualization of structures of interest.¹¹ CEUS exhibits a diagnostic accuracy of 83.7%, a sensitivity of up to 79.3%, and a positive predictive value of up to 91.7%. Adding CEUS-guided targeted biopsy to a 12-core systematic biopsy significantly improves cancer detection rates.¹² During focal therapy, CEUS enables quick intraoperative visualization of the ablated region with precise margins, indicating the adequacy of treatment.¹³

Micro-US

Micro-US is a high-resolution imaging technique that utilizes a 29 MHz system compared to 9-12 MHz conventional TRUS.¹⁴ Micro-US showed good reliability in identifying PCa index lesions. In the context of index lesion detection, micro-US exhibits a sensitivity of 76.5%, specificity of 76.6%, negative predictive value of 85.6%, positive predictive value of 64.1%, and accuracy of 76.6%. These performance metrics are comparable to those of mpMRI, which has a sensitivity of 65.1%, specificity of 93.4%, negative predictive value of 83.2%, positive predictive value of 84.3%, and accuracy of 81.8%.¹⁵ The advantages of micro-US include clinic-based real-time TRUS imaging performed by urologists, real-time high-resolution imaging of PCa lesions, and avoidance of contrast. Micro-US is a less expensive and more convenient alternative diagnostic tool that may either overcome the ever-growing burden on MRI scanning and reporting or be used in combination with mpMRI to improve detection of PCa.¹⁶ Similar to the PI-RADS (Prostate Imaging—Reporting & Data System) grading system used for mpMRI, a specific grading scheme called PRI-MUS (Prostate Risk Identification Using Micro-US) ranging from 1 to 5 is used for objective grading on micro-US. Lesions with a PRI-MUS score of 3 or higher are recommended for targeted biopsy. The risk of clinically significant cancer on biopsy increases by about 10% for each unit of increase in PRI-MUS score.^17,18 The limitations of micro-US include the limited availability of a specific US machine, limited depth of penetration due to its ultrahigh frequency, operator dependency, and learning curve in grading using PRI-MUS score. The Table summarizes the differences of various US techniques in PCa detection.

mpUS and Micro-US vs mpMRI

Today, the TRUS prostate fusion-guided biopsy in conjunction with mpMRI is an effective and valuable method for detecting clinically significant PCa.¹⁹ According to the CADMUS trial,^20,21 mpUS consisting of B-mode, real-time elastography, color Doppler, and intravenous microbubble CEUS scans detected 11.1% more patients who would be referred for a biopsy, despite finding 4.3% fewer clinically significant PCas than mpMRI. It may be used instead of mpMRI as the initial test if mpMRI is not readily available or the patient is not fit for MRI (eg, claustrophobia, magnetic resonance—incompatible intracorporeal metals, and poor renal function). The limited interobserver agreement, significant training in interpretation and reporting of mpUS, and the need of specific equipment pose challenges in widespread application of mpUS. A real-time targeted biopsy is possible in most MRI lesions because they are usually visible at micro-US.²² Using both micro-US and mpMRI would increase the detection of clinically significant PCas compared to using each test alone.^21,23 Data from the ongoing randomized OPTIMUM study in comparing micro-US, mpMRI, and combined micro-US and mpMRI is awaited.²⁴ Further standardization in mpUS and the optimal combination of mpUS modalities will be needed to maximize its benefits.