Seminar article
Clinical application of a 3D ultrasound-guided prostate biopsy system

https://doi.org/10.1016/j.urolonc.2011.02.014Get rights and content

Abstract

Objectives

Prostate biopsy (Bx) has for 3 decades been performed in a systematic, but blind fashion using 2D ultrasound (US). Herein is described the initial clinical evaluation of a 3D Bx tracking and targeting device (Artemis; Eigen, Grass Valley, CA). Our main objective was to test accuracy of the new 3D method in men undergoing first and follow-up Bx to rule out prostate cancer (CaP).

Materials and methods

Patients in the study were men ages 35–87 years (66.1 ± 9.9), scheduled for Bx to rule out CaP, who entered into an IRB-approved protocol. A total of 218 subjects underwent conventional trans-rectal US (TRUS); the tracking system was then attached to the US probe; the prostate was scanned and a 3D reconstruction was created. All Bx sites were visualized in 3D and tracked electronically. In 11 men, a pilot study was conducted to test ability of the device to return a Bx to an original site. In 47 men, multi-parametric 3 Tesla MRI, incorporating T2-weighted images, dynamic contrast enhancement, and diffusion-weighted imaging, was performed in advance of the TRUS, allowing the stored MRI images to be fused with real-time US during biopsy. Lesions on MRI were delineated by a radiologist, assigned a grade of CaP suspicion, and fused into TRUS for biopsy targeting.

Results

3D Bx tracking was completed successfully in 180/218 patients, with a success rate approaching 95% among the last 50 men. Average time for Bx with the Artemis device was 15 minutes with an additional 5 minutes for MRI fusion and Bx targeting. In the tracking study, an ability to return to prior Bx sites (n = 32) within 1.2 ± 1.1 mm SD was demonstrated and was independent of prostate volume or location of Bx site. In the MRI fusion study, when suspicious lesions were targeted, a 33% Bx-positivity rate was found compared with a 7% positivity rate for systematic, nontargeted Bx (19/57 cores vs. 9/124 cores, P = 0.03).

Conclusion

Use of 3D tracking and image fusion has the potential to transform MRI into a clinical tool to aid biopsy and improve current methods for diagnosis and follow-up of CaP.

Introduction

“The discovery that would have the greatest impact on our field would be the development of accurate imaging of tumor within the prostate.” —Patrick C. Walsh [1].

Imaging prostate cancer (CaP), while in a curable state, has proven elusive, despite a half-century of interest and effort. Virtually all major cancers can be easily imaged within the organ of origin, but not CaP. Thus, diagnosis of CaP is often fortuitous, materializing only when systematic biopsy, which is usually driven by an elevated PSA level, is positive [2]. However, recent developments in magnetic resonance imaging (MRI) technologies—3 Tesla magnets and a multi-parametric approach—have led to a promising advance in prostate cancer imaging. Moreover, fusion of ultrasound and MRI by a new technology appears capable of bringing those images to the patient for biopsy guidance.

Challenges to imaging cancer within the prostate include (1) histologic similarity of cancer and benign tissue in many cases, (2) heterogeneity of prostate tissue in aging men, (3) decreasing volumes of CaP found today as a result of early biopsy stimulated by PSA levels, and (4) limited resolving power of available imaging devices. Systematic biopsy often detects insignificant cancers [3], which cannot reliably be distinguished by available biomarkers [4], and treatment decisions based on biopsy alone may be problematic. Overtreatment of localized CaP has been increasingly recognized [5], and active surveillance is gaining traction as a first choice for many men judged to have ‘low-risk’ CaP [6], [7]. In two groups especially—men undergoing active surveillance and those with elevated PSA levels but negative biopsies—the ability to image CaP within the prostate (or exclude it) could help clarify characteristics of the underlying pathology.

Recent advances in magnetic resonance imaging may soon alter the landscape of CaP diagnosis. As detailed below, MRI has evolved to yield images within the prostate that are approaching a considerable degree of diagnostic accuracy [8], [9], [10], [11]. The increased accuracy is attributable to machines that employ powerful 3 Tesla magnets, diffusion weighted imaging, and dynamic contrast enhancement. However, direct prostate biopsy within MRI machines is largely restricted to research institutions [8]. We tested a new device (Artemis; Eigen, Grass Valley, CA), which allows biopsy site tracking in ultrasound and fusion of real-time ultrasound with MRI. FDA approval [510(k)] was granted to the manufacturer in May 2008, but testing to date has been entirely on phantoms. We became early adopters of this technology, hoping to increase accuracy of prostate tissue sampling by recording biopsy sites and incorporating multi-parametric MRI detail into the site selection process. Development of the new technology at UCLA has involved an integrated collaboration between urology, radiology, pathology, and biomedical engineering. The program goals are to improve accuracy of prostate biopsy, to develop a method for visual follow-up and tissue sampling of ‘low risk’ lesions and, potentially, to aid in focal therapy. Herein we present an initial experience with the device, based on studies in the first 218 men who underwent 3D systematic biopsy in 2009–2010, 47 of whom underwent MRI/TRUS fusion biopsy.

Section snippets

Magnetic resonance imaging of prostate cancer

Magnetic resonance imaging has been used to evaluate the prostate and surrounding structures for nearly a quarter century [12]. Initially, investigators utilized the increased signal-to-noise ratio from the use of endorectal coils to study T1- and T2-weighted imaging (T2WI) and spectroscopic imaging for local staging [13], [14], [15], [16]. Standard T2-weighted imaging provides excellent resolution, but does not discriminate cancer from other processes with acceptable accuracy [17], [18].

MR technique and interpretation

In our current work, we utilize multiparametric MRI (T2WI, DWI, and DCE) to prospectively assess likelihood of prostate cancer, and to improve CaP detection through biopsy. A transabdominal coil is used (1) to minimize patient discomfort and (2) because with multiparametric techniques, the endorectal approach does not appear necessary for detection and grade stratification [8], [52]. Imaging is performed on a Siemens TrioTim Somatom 3T (Siemens Medical Solutions, Malvern, PA) magnet with

Clinical evaluation of targeted biopsy

The Artemis device is a 3D ultrasound-guided prostate biopsy system [53] that provides tracking of biopsy sites within the prostate [54]. The device software also allows stored MRI images to be electronically transferred and fused with real-time ultrasound, allowing biopsy needles to be guided into targets. The current version of this device evolved from a prototype built at the Robarts Research Institute in London, Ontario, Canada (Fig. 2) [53]. At Robarts Research, an affiliate of the

Delineation of suspicious areas

Suspicious areas, or regions of interest (ROI), were located on each MR parameter during interpretation, and a suspicion index (image grade) was assigned to each (Table 2). The ROI was then delineated in multiple 1–3 mm slices on the axial T2-weighted images using a contour tool in a DICOM reader (OsiriX [58]). A smooth 3D model of the ROI was then formed, and spatial coordinates of the model were output to a text file. This process was repeated for each suspicious area, resulting in a 3D model

Biopsy technique

Biopsy was performed using a conventional spring-loaded gun and 18 ga needles. A preliminary cleansing enema and prophylactic quinolone antibiotic were used. Procedures began with the patient in left lateral decubitus position, using a conventional ultrasound probe and machine (Hitachi Hi-Vision 5500 [Hitachi Medical Systems America, Twinsburg, OH], 7.5 MHz end-fire) to image the prostate transrectally in transverse and longitudinal views. After a preliminary scan, the prostate was anesthetized

Biopsy tracking accuracy

Clinical accuracy of 3D biopsy tracking was tested in 11 consecutive men, undergoing TRUS/Bx to rule out prostate cancer [54]. Locations of each biopsy site were recorded by the device and displayed on the digital model, as described above. The ultrasound probe was then removed, detached, and cleaned, while patients remained on the procedure table. The probe was then reinserted, and a new 3D scan of the prostate was performed, and prior biopsy sites were recalled. The subsequent scan was used

Targeted biopsy with MR fusion

Accuracy of biopsy targeting was tested by comparing histologic results of targeted vs. systematic biopsy. Biopsy data were obtained on 47 men, in which 65 suspicious areas, or targets, were identified and biopsied. These men also underwent 12-core systematic biopsy. Of these men, 30 were found to have CaP. The high rate of positivity was likely due to the inclusion of men on active surveillance (18 men). Targeted biopsies were found to be more likely to reveal cancer than non-targeted biopsies

Comment

Technologies to improve accuracy of prostate biopsy are rapidly emerging. In selecting and following men for active surveillance, the new technologies are particularly compelling. In the future, men considering focal therapy may also benefit from improved biopsy accuracy. We have described an initial clinical experience with a new 3D ultrasound device, which allows biopsy-site tracking for future recall and fusion of MRI targets with real-time ultrasound. While promising, these early

Acknowledgments

The authors thank Elizabeth Hamilton, LVN for her clinical assistance. This work was supported in part by grants from the Steven C. Gordon Family Foundation, the Beckman Coulter Foundation, and the Jean Perkins Foundation. Co-author JH is supported by UCLA SPORE in Prostate Cancer, Prostate Cancer Foundation Challenge Award and Creativity Award, and Department of Defense Prostate Cancer Research Program.

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