Micro-Ultrasound Guided Transperineal Prostate Biopsy: A Clinic-Based Procedure

The methods described are based on experience at the University of Florida (UF). The protocol and acquisition of data were approved by the University Institutional Review Board (IRB). Indications for prostate biopsy included a suspicious digital rectal exam (DRE), prostate-specific antigen (PSA) elevation, or another biomarker abnormality (i.e., 4K, ExoDx). The protocol is described for a right-handed surgeon.

1. Micro-ultrasound probe preparation

1. Disinfect the probe as per the micro-ultrasound "System Operation and Safety Manual"¹¹.
2. Place around 20 mL of acoustic gel at the end of the probe cover, and remove bubbles. Place a needle guide on the probe, and place the probe cover over the probe (Figure 1A).
   NOTE: Bubbles are removed by rotating the probe cover with lube as with a foxtail toy. The centrifugal force displaces the lubrication distally while moving the bubbles proximally.
3. Place a rubber band around the probe neck below the piezoelectric crystals to prevent gel leakage.
4. Set up the biopsy equipment as per the surgeon's preference.
   NOTE: The setup used in this study is demonstrated in Figure 1B.

2. Patient positioning and anesthesia

1. Position the patient in the lithotomy position with the anus at the edge of the bed. Provide head support and a genital drape to improve comfort and privacy (Figure 1C).
   NOTE: At UF, stirrups for lithotomy positioning are preferred.
2. Place 10 mL of 2% viscous lidocaine gel into the rectum as previously described¹².
   1. Ensure patient comfort and the preparation of the necessary materials during this time.
3. Adjust the bed height so that the anus is at the level of the surgeon's elbow.
4. Instruct the patient to elevate their scrotum and expose the perineum (Figure 1C).
5. Using acoustic gel, perform a digital rectal exam. Note palpable abnormalities for staging and biopsy targeting.
6. Change gloves, and sterilize the perineal skin with betadine or chlorhexidine from the base of the scrotum to below the anus.
7. Anesthetize the perineal soft tissue at the 10 o'clock and 2 o'clock positions, starting around 10-15 mm from the anus (Figure 1D).
   NOTE: Begin with a 2 inch 25 G needle containing 1% lidocaine with 1:100,000 epinephrine and 8.4% sodium bicarbonate solution mixed in a 1:10 ratio (1 mL of NaHCO₃: 10 mL of lidocaine). This is, hereafter, referred to as "lidocaine."
8. Insert the needle parallel to the rectum, and inject lidocaine as the needle is advanced. Place around 3 mL of lidocaine in the soft tissue between the skin and Colles' fascia and 2 mL between the Colles' fascia (Figure 2A).
   ​NOTE: For efficiency, the above step is performed in a blind fashion; however, early in one's experience, consider utilizing ultrasound guidance as patient anatomy differs with pelvic shape, gluteal musculature, and obesity.

3. Micro-ultrasound diagnosis

1. Lubricate the probe, gently insert it into the rectum, and advance until the mid-prostate is centered on the viewing monitor.
   NOTE: Follow the contour of the sigmoid by directing the probe tip downward (toward the sacrum) once beyond the anal sphincter. Using this technique, the bladder base can be visualized with minimal discomfort. Failing to direct the probe downward will cause pain.
2. Optimize the micro-ultrasound image settings.
   1. Grasp the imaging probe in the left (non-dominant) hand at the thickest portion of the probe. Pitch and lift the probe upward so that the base of the prostate receives the greatest pressure from the piezoelectric crystals. The pitching and lifting motion will compress the rectum and optimize visualization (Figure 1C).
   2. Adjust the time-compensated gain (TCG) sliders into a gentle reverse "C" or "J" shape until there is a uniform gray scale across the image.
   3. Adjust the master gain dial so that the lateral edges of the prostate are well visualized yet the center of the prostate is not too bright.
      NOTE: The lateral prostate is acoustically darker than the mid gland as fewer reflected ultrasound waves return at an angle.
   4. Ensure no bubbles or rectal mucus are causing a shadow.
      NOTE: At UF, the default settings are utilized for dynamic range, depth, and focus; however, these can be adjusted as per surgeon preference.
   5. Select an image preset (Small, Medium, Large, and Extra-Large) that enables the visualization of the prostate with minimal anterior prostatic fat.
      NOTE: Details of the image optimization and Micro-US operation are available in the Micro-US "System Operation and Safety Manual"¹¹.
3. Perform a prostate volume calculation by pressing the Dual/Transverse button, performing a prostate sweep, and then measuring the sagittal length and reconstructed axial height and width.
4. Rotate the probe until the urethra is visualized. The visualization of the urethra is best at the bladder, neck, and prostate apex. Place the probe parallel to the midline so the bladder neck and urethra are visible in the same plane (yaw neutral).
5. Press the Angle Reset on the Micro-US touch screen to zero the probe accelerometer.
6. Place the right hand at the proximal portion of the probe where the probe meets the electrical cord. The left hand slides under the probe neck, supporting the upward pitch position (Figure 1C).
7. Tell the patient to hold still; in one motion, sweep from the right lateral prostate border (clockwise) through the prostate to the left edge, taking ~25 s. Press the Cine Loop button to record the sweep.
   ​NOTE: Separate sweeps of the apex and base are often required for prostates larger than 50 mL. It is best practice to record a sweep that visualizes the transition zone and a sweep on the Small setting to visualize the peripheral zone.

4. Diagnostic evaluation

1. Evaluate the transition zone for PRI-MUS lesions.
2. Once the transition zone has been evaluated, switch to the Small image setting, and evaluate the peripheral zone for PRI-MUS lesions.
   NOTE: Consider practicing using the free Micro-US diagnostic library to gain experience with identifying and grading PRI-MUS lesions¹¹.
3. Note the location of the encountered regions of interest (ROI) by recording the center angle and the angles at which the ROI is first and last visible.
   NOTE: At UF, these angles are called out by the surgeon and recorded in the operative notes by staff in the biopsy suite.
4. If utilizing fusion software, load a pre-biopsy annotated MRI, and press the Mid-line button while visualizing the urethra (Figure 2B).

5. Prostate anesthesia

1. Using a 6 inch 20 G needle, puncture the skin at the previously anesthetized biopsy tract, and advance the needle to the levator ani under Micro-US visualization (Figure 2A).
2. Place 3 mL of the local anesthetic into the levator ani muscle complex (Figure 2A).
3. Advance the 20 G needle into the peri-apical triangle (bounded by the urethra medially, the levator ani laterally, and the Denonvilliers' fascia posteriorly). Inject 5-7 mL of lidocaine into the peri-apical triangle (Figure 2A).
   ​NOTE: The lateral aspect of the dorsal venous complex (DVC) drapes into the periapical triangle; thus, aspirate before the lidocaine injection. Appropriate anesthesia will hydrodissect between the prostate capsule and Denonvilliers' fascia.

6. Prostate biopsy

1. Insert a 14 G angiocatheter or 15 G metal coaxial needle (access needle) through the previously anesthetized tract to within 5-10 mm of the prostate apex. Pass the access needle above the anal sphincter and through or medial to the levator ani. Customize the distance between the access needle and the rectum according to the ROI location.
2. Sample the entire prostate using a needle location 5 mm above the rectum and 15°-20° from the mid prostate plane where the urethra is visible (Figure 1D, 10 o'clock and 2 o'clock positions).
3. Rotate the probe so that the insonation plane visualizes the access needle, and advance the biopsy gun until the biopsy needle tip becomes visible at the end of the access needle.
4. Rotate the probe to visualize the biopsy target (either the ROI or systematic core), and then rotate back to visualize the biopsy needle tip. Adjust the needle trajectory toward the target by adjusting the biopsy gun external to the patient.
5. Advance the needle under vision, and complete small 3°-10° probe rolls (micro rolls) to guide the needle tip into the intended target. Only advance the biopsy needle while visualizing the tip to prevent overshooting the intended target.
   NOTE: It is necessary to withdraw the biopsy needle if making larger movements toward a target. In this technique, the probe is kept parallel to the urethra rather than parallel to the needle ("yawing"). Preserving the biopsy angle relative to the urethra allows an accurate reconstruction of the cancer location and maximizes patient comfort. The most challenging portion of this technique is visualizing the needle when uncoupled from the insonation plane. In our experience instructing residents, fellows, and other physicians, the muscle memory required to implement the technique requires around 3 h of practice. Consider practicing on a prostate phantom or simulator¹³ to build the requisite muscle memory before a biopsy. Performing this technique initially on an anesthetized patient will ease the transition to a clinic-based practice.
6. Before obtaining a biopsy sample, roll it to the urethra, and ensure the angle is within 1°-2° of the 0° position. Record the angle position for each biopsy throw by capturing a frame or cine loop.
   NOTE: By convention, right-sided (counterclockwise) rotation is indicated by a positive angle, while left-sided (clockwise) rotation is characterized by a negative angle.
7. Begin by obtaining three biopsy cores distributed through the ROI (Figure 2C).
8. Consider performing a transperineal systematic biopsy (Figure 3). For efficiency, begin systematic biopsies ipsilateral to the ROI. If the ROI is anterior, lower the coaxial needle to improve the systematic biopsy sampling of the peripheral zone.
   ​NOTE: This study performed a 14-core systematic biopsy (Figure 3). A systematic biopsy can likely be skipped in these instances: 1) systematic cores overlapping a previously sampled ROI, and 2) small prostates where a single throw samples the apex and base. Utilizing this template, apical biopsies are obtained by beginning the throw at the apical prostate capsule. Base biopsies are obtained by starting the throw in the mid gland.

7. Procedure end

1. After acquiring all the biopsies, remove the coaxial needle and ultrasound probe.
2. Hold pressure on the perineum with a towel for 1-5 min until puncture site hemostasis is achieved.
3. Assist the patients to a seated position and, after 1 min, a standing position.
4. Counsel the patients to expect transient hematuria and hematospermia.
5. Prescribe patients with baseline restricted urinary stream alpha-blockers to be filled as needed.