Urologic Oncology: Seminars and Original Investigations
Seminar articleClinical application of a 3D ultrasound-guided prostate biopsy system
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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