A Cognitive Fusion-guided Prostate Biopsy Using Multiparametric Magnetic Resonance Imaging and Transrectal Ultrasound

Summary

Prostate biopsy is the gold standard diagnostic method for prostate cancer. Cognitive fusion-guided prostate biopsy, which combines transrectal ultrasound with pre-measured MRI parameters, improves biopsy accuracy and enhances the detection rate of clinically significant prostate cancer.

Abstract

Traditional transrectal ultrasound (TRUS)-guided prostate biopsy has limited sensitivity and specificity, particularly for detecting early-stage prostate cancer, due to a lack of precise lesion targeting. An improved cognitive fusion-guided prostate biopsy method has been developed to enhance lesion targeting by integrating three parameters of prostate multiparametric MR (mpMRI) images into TRUS images. Prostate mpMRI measurement is initially performed to obtain three key parameters: the rotation angle (α), the distance from the rectal wall (X), and the distance from the prostate apex (Y). These parameters are then cognitively applied in real-time, TRUS-guided prostate needle biopsy to detect target lesions. This improved transperineal cognitive fusion biopsy method enhances diagnostic accuracy, improves reproducibility, and reduces reliance on operator experience. Clinical application in 423 patients demonstrated a prostate cancer detection rate of 73.5%, with 62.9% classified as clinically significant cancers. Compared with equipment-intensive methods such as MRI-ultrasound fusion biopsy, this approach is cost-effective, practical, and well-suited for broader clinical adoption. Additionally, the method's flexibility supports integration with other imaging techniques, such as ⁶⁸Ga-PSMA PET/CT, further improving detection rates for patients with high-risk prostate cancer.

Introduction

Prostate cancer is a major global health concern, with an estimated 1,466,680 new cases and 396,792 deaths reported worldwide in 2022. Prostate cancer is the second most common cancer and the fifth leading cause of cancer death among men¹. By 2040, the number of new prostate cancer cases is projected to rise to 2.9 million, with deaths expected to reach 700,000². Early diagnosis and standardized treatment are crucial for improving survival rates in patients with prostate cancer, and prostate biopsy remains the gold standard for early diagnosis.

Since 1968, transrectal ultrasound (TRUS) has been an important tool for guiding prostate biopsies. However, the sensitivity and specificity of TRUS-guided prostate biopsies are limited by 65-74% and 40-57%³, respectively, particularly in detecting early-stage or small-volume lesions⁴. To overcome these limitations, multiparametric MRI (mpMRI) has emerged as a superior imaging technique, providing more detailed evaluations of prostate tissue and improved localization of clinically significant prostate cancer. Compared with traditional TRUS-guided biopsy, mpMRI can more accurately identify suspicious lesions within the prostate and improve the precision of targeted biopsies^5,6.

Several MRI-guided prostate biopsy techniques have been developed, leveraging the enhanced diagnostic capabilities of prostate mpMRI. These techniques include MRI-targeted prostate biopsy, MRI-transrectal ultrasound fusion prostate biopsy, and cognitive fusion-guided prostate biopsy^7,8. MRI-targeted prostate biopsy is performed directly inside the MRI scanner, allowing real-time image guidance during biopsy. This technique offers excellent lesion localization; however, it is costly and time-consuming due to the prolonged imaging and procedural requirements. MRI-transrectal ultrasound fusion prostate biopsy combines MR images and real-time TRUS images via specialized software, making it complex and costly.

In contrast, cognitive fusion-guided prostate biopsy involves clinicians memorizing lesion locations from MR images and mentally integrating this information with real-time TRUS during biopsy. This technique requires no additional equipment, making it simple, cost-effective, and highly suitable for clinical adoption. However, cognitive fusion-guided prostate biopsy is highly dependent on the clinician's experience, and the process of lesion localization relies entirely on memory and judgment, which results in reduced reproducibility and limits its broader application. To address these challenges, an improved transperineal cognitive fusion biopsy method was developed by integrating three key parameters from prostate mpMR images with TRUS. This method is highly reproducible, easy to perform, and well suited for widespread clinical implementation, offering significant support for the accurate diagnosis of prostate cancer. This paper details the protocol and clinical utility of this standardized approach, highlighting its potential to improve prostate cancer detection in routine practice.

Protocol

This study involving human participants was conducted in accordance with the principles outlined in the Declaration of Helsinki. Written informed consent was obtained from all participants prior to their inclusion in the study. The inclusion and exclusion criteria were carefully defined to ensure participant safety and the suitability of the procedure.

1. Patient selection

1. Set the following inclusion criteria for patient selection: prostate-specific antigen (PSA) > 10 ng/mL; presence of a suspicious prostate nodule detected by digital rectal examination (DRE), irrespective of PSA level; suspicious lesions identified via transrectal ultrasound (TRUS), MRI, or PSMA PET/CT, regardless of the PSA level; PSA levels between 4 and 10 ng/mL accompanied by f/tPSA < 0.16, and/or PSA density (PSAD) > 0.15 ng/mL², and/or PSA velocity (PSAV) > 0.75 ng/ml annually; abnormal results from other prostate-related tests, such as elevated prostate health index (PHI) or positive urinary prostate cancer antigen 3 (PCA3) results.
2. Exclude participants from the study based on the following criteria: acute infection or fever during the study period; hypertensive crisis; decompensated heart failure; severe bleeding disorders; poorly controlled or unstable comorbidities such as hypertension or diabetes; severe anal or rectal conditions, including advanced internal/external hemorrhoids or significant rectal/anal pathology; severe immunosuppressive state; severe psychological disorders or participants unwilling or unable to cooperate with the procedure.

2. Determining the three-dimensional coordinates of the lesion on mpMRI

1. Thoroughly review the T2-weighted imaging (T2WI, Figure 1A), diffusion-weighted imaging (DWI, Figure 1B), and apparent diffusion coefficient (ADC, Figure 1C) maps of multiparametric MRI (mpMRI) scans to identify the prostate lesions.
   NOTE: Consultation with a radiologist may be necessary to confirm the location of the lesion prior to biopsy.
2. Use a point approximately 7 mm from the anterior rectal wall as the vertex. Draw one line through the body's midline, which can be determined by the pubic symphysis or the bulbous urethra. Draw another line through the center of the lesion. The angle between these two lines is the angular displacement, recorded as α (Figure 2A).
   NOTE: This angle α is used to determine how much the ultrasound probe is rotated to align with the lesion during biopsy.
3. Measure the distance from the center of the lesion to the rectal serosal surface on the T2WI sequence and record it as X (Figure 2A).
   NOTE: Distance X is used to guide the needle insertion point during biopsy and determine the location where the biopsy needle is inserted relative to the rectum.
4. Measuring the Distance from the Apex of the Prostate (Y) Create a plane that passes through both the center of the vertex of the α angle and the center of the lesion via a DICOM viewer with MPR (multiplanar reconstruction) or another slice function. Measure the distance from the lesion to the apex of the prostate in this plane and record it as Y (Figure 2B).
   NOTE: The distance Y is critical for determining the depth of needle penetration; it corresponds to the depth the biopsy needle needs to reach during biopsy.

3. Patient preparation and imaging

1. Place the patient in the lithotomy position. Position the buttocks at the exact center edge of the examination table. Both legs are symmetrically supported in the leg rests.
2. Retract the scrotum upward and fully expose the perineal region.
3. Disinfect the perineal area with povidone-iodine (iodophor) and drape the area, leaving the procedural site accessible.
4. Subcutaneously inject 1% lidocaine for local anesthesia at the projection of the prostate's largest transverse plane on the perineal skin.
5. Gently insert the biplane transrectal ultrasound (TRUS) probe into the rectum. Position the probe at a 45° upward angle relative to the anus.
   NOTE: The anesthesia insertion point is typically 1.5 cm from the anus (Figure 3).
6. Inject 1% lidocaine into the levator ani muscle, prostatic capsule, and apex of the prostate via ultrasound guidance in the sagittal plane to ensure adequate anesthesia during the biopsy.

4. TRUS and cognitive fusion

1. Align the ultrasound probe with the midline by locating a plane on the transverse ultrasound image that closely matches the lesion's position from the T2WI transverse image on the mpMRI. Once identified, hold the probe steady, and freeze the ultrasound image at this cross-sectional level.
   NOTE: Ensure that the sagittal plane of the ultrasound probe is aligned with the body's midline. In the standard lithotomy position, the sagittal plane of the probe is typically positioned directly overhead.
2. Freeze the image and use the center of the probe as the vertex to measure the α angle on ultrasound. Align one edge of the α angle with the central guide line on the transverse ultrasound image (Figure 4A).
   NOTE: The location of the other edge of the α angle, which corresponds to the position of the lesion on the ultrasound image.
3. Unfreeze the image and rotate the probe until the central guide line of the transverse ultrasound image aligns with the position of the lesion identified on MRI. Hold the probe steady without further rotation once the rotation to the α angle is achieved.
4. Position the ultrasound probe in the lesion plane by advancing the probe horizontally along the rectum until the linear array ultrasound probe displays the prostate image, after rotating the probe to the correct α angle.
   NOTE: The current image displayed corresponds to the plane of the lesion as determined by the previous MRI measurements (Figure 4B).
5. Measure the distance from the rectal serosal surface to the location corresponding to the previously measured X value on MRI, confirming the insertion point for the biopsy needle.
6. Measure the distance from the apex of the prostate to the location corresponding to the previously measured Y value on MRI in the direction parallel to the rectum, ensuring the correct depth for the biopsy needle insertion (Figure 4B).
   NOTE: These X and Y measurements confirm that the probe is correctly aligned with the lesion on the ultrasound image, allowing for precise targeting during biopsy.

5. Targeted biopsy

1. Insert the biopsy needle along the needle guide line corresponding to the distance from the rectum (measured as X on the ultrasound image) under sagittal plane ultrasound guidance using the linear array probe.
2. Adjust the needle depth according to the previously measured Y value, which represents the distance from the apex of the prostate. Perform 2-3 targeted biopsy cores in the lesion area once the correct depth is reached (Figure 4B).
3. Repeat the above steps for each target lesion if multiple lesions are identified.
   NOTE: It is crucial to maintain the stability of the ultrasound probe, and the X and Y coordinates must be applied accurately for each biopsy site throughout the procedure. To ensure precision and reduce hand movement, it is recommended to use an ultrasound probe support arm for assistance.

6. Systematic biopsy

1. Take one biopsy core from the apex, midline, and base in both the peripheral and central zones of the left lobe of the prostate.
2. Adjust the probe position and take one core each from the apex, midline, and base in both zones; then, repeat the process on the right lobe of the prostate.
   NOTE: It is advised to collect a total of 12 cores during the systematic biopsy.

7. Completion

1. Gently remove the TRUS probe from the rectum to avoid any discomfort after biopsy.
2. Clean the perineal and rectal areas with sterile wipes to remove any residual gel or blood.
3. Place each biopsy core into prelabeled containers with appropriate preservatives. Mark each container with the patient's information and biopsy site.
4. Transport the labeled containers with biopsy cores to the Pathology Lab for histopathological analysis.

Results

In this case, the cognitive fusion-guided prostate biopsy accurately identified a clinically significant prostate cancer lesion. This lesion was indicated by MRI in the left apex of the prostate with a maximum diameter of approximately 6 mm and a PI-RADS score of 4, suggesting a high likelihood of clinically significant prostate cancer.

The pathologic diagnosis of this biopsy lesion was prostatic acinar adenocarcinoma with the following details (Figure 5):

Discussion

MRI-guided biopsy (MRI-GB) is a cornerstone of targeted prostate biopsy and includes MRI-targeted biopsy (MRI-TB), MRI-transrectal ultrasound fusion biopsy (FUS-TB), and cognitive fusion biopsy (COG-TB). MRI-TB achieves high diagnostic accuracy through real-time MR imaging, with an overall cancer detection rate of 80% and a clinically significant cancer detection rate of 55%⁹. However, its high cost and operational complexity limit its widespread use. FUS-TB combines MRI precision with real-time u...

Materials

Name	Company	Catalog Number	Comments
5% Povidone-Iodine Solution	Chengdu Yong'an Pharmaceutical Co., Ltd.	H51022885	For disinfection of the surgical area
10% Neutral Buffered Formalin Fixative	Guangzhou Vigrass Biotechnology Co., Ltd.	24010506	For fixing biopsy tissue
AccuCARE Transperineal Solutions	CIVCO Medical Instruments Co., Inc	620-119	For supporting the probe
Injection syringe (20 mL)	Shandong weigao group medical polymer Co., LTD	20211001	For local anesthesia
Lidocaine	Hubei Tiansheng Pharmaceutical Co., Ltd.	H42021839	Diluted with saline to 1% for local anesthesia
MRI 3.0T	Philips	Ingenia	For prostate examination
RadiAnt DICOM Viewer	Medixant	V2024.1	For reading prostate MRI, outlining lesions, measuring distances, and angles
Single-use Biopsy Needle MC1820	Bard Peripheral Vascular, Inc.	REHU3231	For needle biopsy sampling
Single-use Sterile Needle 0.7 x 80 TWLB	Zhejiang Kangdeli Medical Devices Co., Ltd.	C20230923	For local anesthesia
Sodium chloride injection	Southwest pharmaceutical Co., LTD	H50021610	For diluting lidocaine
Ultrasound	BK Medical	bk3000-01	For guiding prostate biopsy