Secondary Logo

Journal Logo

MRI–ultrasound fusion for guidance of targeted prostate biopsy

Marks, Leonarda; Young, Shelenaa; Natarajan, Shyamb

doi: 10.1097/MOU.0b013e32835ad3ee
ROBOTICS: Edited by Jim Hu
Free

Purpose of review Prostate cancer (CaP) may be detected on MRI. Fusion of MRI with ultrasound allows urologists to progress from blind, systematic biopsies to biopsies, which are mapped, targeted and tracked. We herein review the current status of prostate biopsy via MRI/ultrasound fusion.

Recent findings Three methods of fusing MRI for targeted biopsy have been recently described: MRI–ultrasound fusion, MRI–MRI fusion (‘in-bore’ biopsy) and cognitive fusion. Supportive data are emerging for the fusion devices, two of which received US Food and Drug Administration approval in the past 5 years: Artemis (Eigen, USA) and Urostation (Koelis, France). Working with the Artemis device in more than 600 individuals, we found that targeted biopsies are two to three times more sensitive for detection of CaP than nontargeted systematic biopsies; nearly 40% of men with Gleason score of at least 7 CaP are diagnosed only by targeted biopsy; nearly 100% of men with highly suspicious MRI lesions are diagnosed with CaP; ability to return to a prior biopsy site is highly accurate (within 1.2 ± 1.1 mm); and targeted and systematic biopsies are twice as accurate as systematic biopsies alone in predicting whole-organ disease.

Summary In the future, MRI–ultrasound fusion for lesion targeting is likely to result in fewer and more accurate prostate biopsies than the present use of systematic biopsies with ultrasound guidance alone.

aDepartment of Urology, David Geffen School of Medicine

bCenter for Advanced Surgical and Interventional Technology, University of California, Los Angeles, Los Angeles, California, USA

Correspondence to Leonard Marks, MD, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, 10945 Le Conte Avenue, PVUB 3361, Los Angeles, CA 90095, USA. E-mail: lmarks@mednet.ucla.edu

Back to Top | Article Outline

INTRODUCTION

Prostate biopsy to diagnose or exclude cancer is currently performed an estimated one million times annually in the USA [1]. Nearly all are performed by the transrectal, ultrasound-guided technique, which was introduced some 25 years ago by Hodge and colleagues [2]. Using this technique, tissue cores are obtained under ultrasound guidance systematically throughout the prostate, a method shown in 1989 to be just as accurate as when the operator used ultrasound to aim at a nodule [3]. The Stamey technique was performed without knowing the tumour location within the prostate (i.e. a blind biopsy), but it was still a major advance over older methods in which biopsy needles were guided only by the examining finger. The systematic method gained widespread adoption, and prostate cancer (CaP) became the only major cancer, in which diagnosis is now routinely made by blind biopsy of the organ.

However, many of the currently performed prostate biopsies yield misleading information. Microfocal ‘cancers’ of little clinical significance are frequently detected [4], whereas the incidence of falsely negative biopsies, that is serious tumours not detected, may in first-time biopsies be as high as 35% [5]. Part of the problem may be that the average index CaP is smaller today than it was in the 1980s, making serious cancers more difficult to detect [6]. Further, as 12 cores are now routinely obtained, compared with six cores previously, overdetection of small, indolent tumours has become problematic [7]. Up to 50% of currently detected CaP cases may not be clinically relevant [4]. Conversely, 28 000 deaths are expected this year from CaP; thus, early detection of clinically significant CaP would very likely save many lives.

Box 1

Box 1

MRI of the prostate, particularly if performed with multiparametric imaging, is capable of detecting clinically relevant CaP [8▪▪]. Accuracy parameters are not yet clear, but for the first time, localized CaP may in many cases be identified, measured, selectively sampled and treated, or if appropriate, followed [9▪▪]. Potentially, many such cancers may be observed and resampled in active surveillance programmes, or perhaps in the future, focally ablated. The ability to visualize some CaP on MRI has brought the opportunity to use those images as targets for needle biopsy by incorporating (i.e. fusing) MRI into a needle-aiming or targeting method [10▪▪].

Back to Top | Article Outline

USE OF MRI TO VISUALIZE PROSTATE CANCER

The first published report, in which MRI was used to visualize CaP within the organ, was probably that of Hricak et al. [11]. In that 1983 report, the authors showed, using an MRI unit with a magnet operating at 0.35 T, that malignant prostate tissue had a higher intensity signal than surrounding benign tissues. They concluded that the ‘greatest potential (of prostate MRI) seems to be its capability to detect pathology confined to the gland’ [11].

Since that time, magnets have become stronger, resolution has improved dramatically and multiparametric enhancements, such as diffusion-weighted imaging and dynamic contrast studies, have become available. In a study of men with prior negative biopsies and persistently elevated PSA levels, Hoeks et al. [9▪▪] – working with multiparametric MRI, a machine with a 3-T magnet, and a body coil (not endorectal) – detected twice as many cancers with targeted biopsy as others have reported with conventional ultrasound guidance (detection rate of 41 vs. 18%). In this large series (N = 265), 87% of the MRI-detected tumours found on biopsy were important cancers. Conversely, using MRI-targeted biopsy, the detection rate of insignificant cancers, that is those that would best be left undetected, should be lower than with systematic blind biopsy [12▪]. Further, when MRI findings have been correlated with pathologic findings, tumour localization appears to be significantly better with MRI than with digital rectal examination (DRE) or blind biopsy [13]. In the detection of CaP, multiparametric MRI appears superior to all other imaging modalities evaluated to date.

Back to Top | Article Outline

METHODS OF MRI-GUIDED PROSTATE BIOPSY

Three methods of MRI guidance are available for performance of targeted prostate biopsy: cognitive fusion, in which the ultrasound operator simply aims the biopsy needle at the prostate area where the reviewed prior MRI demonstrates a lesion; direct MRI-guided biopsy, performed within an MRI tube; and software coregistration of stored MRI with real-time ultrasound, using a fusion device. Each method has its advantages and disadvantages. To date, no prospective comparison of the three methods has been made.

Cognitive fusion is simple, quick and requires no additional equipment beyond the MRI and a conventional transrectal ultrasound (TRUS) facility. Specialized training beyond conventional TRUS biopsy is not required for the ultrasound operator. In the comprehensive review of Moore et al. [10▪▪], cognitive fusion was used in some 22 separate studies. Although data are limited, cognitive fusion does appear to yield improved accuracy over conventional systematic, blind biopsy.

Disadvantage of cognitive fusion is the potential for human error in the extrapolation from MRI to TRUS without an actual overlay.

Direct MRI-guided biopsy is performed ‘in-bore’, that is within the MRI tube, by a radiologist, who fuses a prior MRI demonstrating a lesion with a contemporaneous MRI to confirm biopsy needle localization. The transrectal route is employed. After each biopsy sample, the patient is rescanned to confirm localization. Typically, only a few targeted cores are taken; systematic sampling is not performed. A large experience with in-bore biopsy has been published by the Barentsz group at Radboud University in Nijmegen, the Netherlands [9▪▪]. The advantages of this method are the limited number of cores taken, the exact localization of the biopsy and the reduced detection of insignificant tumours. The disadvantages of this method include the time and expense required, including the in-bore time and the two MRI sessions necessary to obtain the biopsy specimens. Further, as only suspicious lesions are sampled, tissues with a ‘normal’ appearance on MRI are not obtained, which is problematic, as any false-negative aspects of prostate MRI are not yet known.

The third method for MRI guidance of prostate biopsy is MRI–TRUS fusion. In this method, the operator images the prostate using ultrasound, as performed for the past several decades; while thus viewing the prostate, the MRI of that prostate, which is performed beforehand and stored in the device, is fused with real-time ultrasound using a digital overlay, allowing the target(s), previously delineated by a radiologist, to be brought into the aiming mechanism of the ultrasound machine. The fusion results in creation of a three-dimensional reconstruction of the prostate, and on the reconstructed model, the aiming and tracking of biopsy sites occurs. The disadvantage of this method is that it is indirect, involves use of an additional device and requires specialized operator training. The advantage is that it can be performed within minutes in an outpatient clinic setting under local anaesthesia, using techniques familiar for several decades. Results using a fusion device are very promising.

Back to Top | Article Outline

MRI–ULTRASOUND FUSION TECHNOLOGIES

Image fusion is the process of combining relevant information from two or more images into a single image, which is more informative than either of the images separately. In medical usage, MRI–ultrasound image fusion is a product of the last decade, first in central nervous system applications [14] and subsequently in prostate brachytherapy [15]. In 2002, Kaplan et al. [16] in Boston performed MRI–ultrasound fusion for targeted prostate biopsy, thereby establishing the concept that ‘this technique has the potential to increase the yield of the biopsy procedure’. In 2007, researchers at the National Cancer Institute, working in collaboration with scientists from Philips Research North America and Traxtal, Inc., showed in five patients that MRI–ultrasound fusion for targeted prostate biopsy was not only possible, but it could also be quick and accurate [17].

Technologies to perform image fusion are evolving rapidly. As of this writing, five devices providing MRI–ultrasound fusion for targeted prostate biopsy have been approved by the US Food and Drug Administration (FDA), all via the 510(k) route (Table 1). The Philips/PercuNav system (Royal Philips Electronics, Amsterdam, the Netherlands) has undergone more years of clinical testing than the others; development has been entirely done at the NCI. This system employs an external magnetic field generator to perform biopsy site localization and tracking. Among the first 101 men undergoing MRI–TRUS fusion biopsy with this system, CaP detection correlated with the degree of suspicion on MRI [18▪▪]. Cancer was detected in nearly 90% of cases, in whom a highly suspicious lesion on MRI was targeted. In this work, targeted biopsies were twice as likely to show cancer as systematic biopsies. The Hitachi HI-RVS system (Hitachi Medical Systems America, Inc., Twinsburg, Ohio, USA) also employs magnetic field localization; clinical experience with this system is limited [19,20].

Table 1

Table 1

The Urostation (Koelis, Grenoble, France) has been studied extensively by Ukimura et al. [21▪▪]; in a preclinical study, ability of this system to navigate to targets within prostate phantoms was highly accurate. Similar to the in-bore biopsies, confirmation of needle location with Urostation is retrospective, that is the biopsy is taken and then the scan is made to confirm placement position. At the 2012 American Urology Association meeting, Ukimura presented a body of clinical work with the Koelis device, showing that tumour localization was highly accurate and that progression of lesions in men undergoing active surveillance could be determined by targeted biopsy.

Work with the Artemis device (Eigen, Grass Valley, California, USA) began at the University of California, Los Angeles (UCLA) in 2009, soon after the FDA approval [22▪▪]; a multiyear National Institutes of Health (NIH)-supported evaluation is in progress.

The Artemis device differs from the others in that it incorporates a robot-like mechanical arm used to scan and digitize the prostate; the needle and probe positions are tracked by angle-sensing devices (encoders) built into each joint of the arm. A prototype of the device was developed in the laboratories of Professor Aaron Fenster et al. at Robarts Research Institute in London, Ontario, California, USA [23]. In Figure 1, the Robarts prototype and the commercially available Artemis device v2.0 are shown. The essential components of the device, as described by Bax et al.[23], are as follows:

  1. Passive mechanical components for guiding, tracking and stabilizing the position of a commercially available end-firing transrectal ultrasound transducer;
  2. Software components for acquiring, storing and reconstructing in real-time a series of two-dimensional ultrasound images into a three-dimensional ultrasound image; and
  3. Software that displays a model of the three-dimensional scene to guide and record the biopsy core locations three-dimensionally.
FIGURE 1

FIGURE 1

These generic software features are also employed by all other prostate fusion devices.

A summary of the working experience with the Artemis device at UCLA Clark Urology Center is shown in Table 2. In brief, a multidisciplinary team was assembled in early 2009 to try to bring MRI/TRUS fusion biopsy to clinical utility. A urologist, a radiologist expert in prostate MRI, a prostate pathologist and a biomedical engineer were included. NIH grant support (R01) was received via an industry/academic collaborative channel, and imaging scientists from Eigen were also involved. The Artemis device was delivered in March 2009, and its clinical usage commenced in September 2009. Early clinical application of the device at our institution has been detailed previously by Natarajan et al. [22▪▪]. An online video explains rationale and methods of the work (YouTube: ‘UCLA BIOPSY’). In a subsequent publication, results of the first 171 men undergoing a MRI/TRUS fusion biopsy at UCLA are detailed [24▪▪]. Results of that study are summarized in Table 3.

Table 2

Table 2

Table 3

Table 3

Back to Top | Article Outline

PATIENT EXAMPLES

In the following patient examples, the value of MRI/ultrasound-targeted prostate biopsy is illustrated.

Back to Top | Article Outline

Anterior prostate cancer

A 60-year-old man was referred to UCLA because eight sets of conventional ultrasound-guided biopsies over a 10-year period were all negative, despite serum PSA level increasing from 4 to 50 ng/ml over that period of time. Prostate volume was 64 ml. mpMRI revealed the lesion causing increased PSA (Fig. 2a–c). Targeted biopsy, using MRI–ultrasound fusion, confirmed the diagnosis of a large, high-grade anterior CaP (Fig. 2d and e) [25].

FIGURE 2

FIGURE 2

Anterior CaPs, while once thought to be rare, accounted for more than 80% of tumours found on saturation biopsy in one recent study [26]. The growing concern about ‘evasive anterior tumours’, and the role MRI can play in diagnosis, were addressed recently by Lawrentschuk et al. [27]. When anterior tumours become large (pT3), the likelihood of a positive surgical margin appears to increase substantially [28]. Thus, early diagnosis of anterior tumours has important clinical implications. MRI/ultrasound fusion biopsy provides visualization and access to anterior tumours not possible with conventional biopsy, especially in large prostates.

Back to Top | Article Outline

Active surveillance

A 70-year-old man was enrolled into the UCLA Active Surveillance programme after an early Artemis-guided biopsy (systematic, nonfusion) showed a small amount of well differentiated CaP. Six months later, a confirmatory biopsy was performed using MRI/ultrasound fusion, targeting a high-grade lesion seen on MRI; the prior positive site was also targeted. The target and the prior positive sites were near each other on MRI, as shown in the Artemis imagery (Fig. 3). Fusion biopsy revealed extensive Gleason 3+4 = 7 CaP in multiple cores obtained from the target and a lesser amount of Gleason 3+3 = 6 CaP in the prior positive site. Patient was counselled to proceed with active treatment; he elected brachytherapy.

FIGURE 3

FIGURE 3

The confirmatory, or first surveillance biopsy, is considered the most important follow-up study in men entering active surveillance [29]. In such cases, information derived from PSA testing is of limited value, compared with that gained via repeat biopsy [30]. Among six large programmes reviewed by Dall’era et al.[29], the confirmatory biopsy showed absence of cancer in 24–50% of cases, grade progression in 2.5–28% of cases and no change in 42–61% of cases. Barzell et al.[31▪] showed recently that, when confirmatory biopsy was performed via a transperineal template mapping technique (28–34 cores, general anaesthesia), disease reclassification to a clinically important status occurred much more frequently than when conventional TRUS-guided biopsy was used. Many important cancers in such cases can be identified by MRI [32]. Thus, using MRI/ultrasound fusion and targeted biopsy, confirmatory results, which are comparable with those obtained with template biopsy, may potentially be obtained in a clinic setting under local anaesthesia [24▪▪].

Back to Top | Article Outline

CONCLUSION

Multiparametric MRI (3 T) holds great promise of prospectively identifying clinically important cancer within the prostate. Targeted biopsy through magnetic resonance guidance or MRI–ultrasound fusion offers a way to localize and sample suspected cancers with precision. Image fusion using specialized devices offers the practicing urologist an accurate and efficient way to diagnose and manage CaP in an office-based setting. Biopsy results obtained with the fusion devices compare favourably with results obtained with template perineal biopsy performed under general anaesthesia in the operating room. In the future, MRI/ultrasound fusion technology may be used for targeting and following lesions appropriate for focal therapy.

Back to Top | Article Outline

Acknowledgements

The project described was supported by Award Number R01CA158627 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the NIH. Additional support was provided by the Beckman Coulter Foundation, the Jean Perkins Foundation and the Steven C. Gordon Family Foundation.

Back to Top | Article Outline

Conflicts of interest

There are no conflicts of interest.

Back to Top | Article Outline

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 100).

Back to Top | Article Outline

REFERENCES

1. Welch HG, Fisher ES, Gottlieb DJ, Barry MJ. Detection of prostate cancer via biopsy in the Medicare-SEER population during the PSA era. J Natl Cancer Inst 2007; 99:1395–1400.
2. Hodge KK, McNeal JE, Stamey TA. Ultrasound guided transrectal core biopsies of the palpably abnormal prostate. J Urol 1989; 142:66–70.
3. Hodge KK, McNeal JE, Terris MK, Stamey TA. Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol 1989; 142:71–74.discussion 4–5.
4. Cooperberg MR, Broering JM, Kantoff PW, Carroll PR. Contemporary trends in low risk prostate cancer: risk assessment and treatment. J Urol 2007; 178:S140–S149.
5. Taira AV, Merrick GS, Galbreath RW, et al. Performance of transperineal template-guided mapping biopsy in detecting prostate cancer in the initial and repeat biopsy setting. Prostate Cancer Prostatic Dis 2010; 13:71–77.
6. Stamey TA, Caldwell M, McNeal JE, et al. The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J Urol 2004; 172:1297–1301.
7. Stamey TA, Freiha FS, McNeal JE, et al. Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer 1993; 71:933–938.
8▪▪. Barentsz JO, Richenberg J, Clements R, et al. ESUR prostate MR guidelines 2012. Eur Radiol 2012; 22:746–757.

Current clinical guidelines for multiparametric prostate MRI.

9▪▪. Hoeks CM, Schouten MG, Bomers JG, et al. Three-tesla magnetic resonance-guided prostate biopsy in men with increased prostate-specific antigen and repeated, negative, random, systematic, transrectal ultrasound biopsies: detection of clinically significant prostate cancers. Eur Urol 2012 [Epub ahead of print].

A study showing the ability to diagnose and track clinically important CaP in patients with prior negative biopsies using magnetic resonance guidance.

10▪▪. Moore CM, Robertson NL, Arsanious N, et al. Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur Urol 2012 [Epub ahead of print].

A comprehensive review on studies utilizing MRI to target CaP either through direct guidance, cognitive fusion or software fusion.

11. Hricak H, Williams RD, Spring DB, et al. Anatomy and pathology of the male pelvis by magnetic resonance imaging. AJR Am J Roentgenol 1983; 141:1101–1110.
12▪. Hoeks CM, Barentsz JO, Hambrock T, et al. Prostate cancer: multiparametric MR imaging for detection, localization, and staging. Radiology 2011; 261:46–66.

A review on prostate MRI techniques and a discussion on how to effectively utilize MRI in cancer detection.

13. Mullerad M, Hricak H, Kuroiwa K, et al. Comparison of endorectal magnetic resonance imaging, guided prostate biopsy and digital rectal examination in the preoperative anatomical localization of prostate cancer. J Urol 2005; 174:2158–2163.
14. Schlaier JR, Warnat J, Dorenbeck U, et al. Image fusion of MR images and real-time ultrasonography: evaluation of fusion accuracy combining two commercial instruments, a neuronavigation system and a ultrasound system. Acta Neurochir (Wien) 2004; 146:271–276.discussion 6–7.
15. Reynier C, Troccaz J, Fourneret P, et al. MRI/TRUS data fusion for prostate brachytherapy. Preliminary results. Med Phys 2004; 31:1568–1575.
16. Kaplan I, Oldenburg NE, Meskell P, et al. Real time MRI-ultrasound image guided stereotactic prostate biopsy. Magn Reson Imaging 2002; 20:295–299.
17. Singh AK, Kruecker J, Xu S, et al. Initial clinical experience with real-time transrectal ultrasonography-magnetic resonance imaging fusion-guided prostate biopsy. BJU Int 2007; 101:841–845.
18▪▪. Pinto PA, Chung PH, Rastinehad AR, et al. Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging. J Urol 2011; 186:1281–1285.

A comprehensive clinical study involving MRI–ultrasound fusion biopsy of the prostate using an electromagnetic tracking device.

19. Miyagawa T, Ishikawa S, Kimura T, et al. Real-time virtual sonography for navigation during targeted prostate biopsy using magnetic resonance imaging data. Int J Urol 2010; 17:855–860.
20. Ukimura O, Hirahara N, Fujihara A, et al. Technique for a hybrid system of real-time transrectal ultrasound with preoperative magnetic resonance imaging in the guidance of targeted prostate biopsy. Int J Urol 2010; 17:890–893.
21▪▪. Ukimura O, Desai MM, Palmer S, et al. 3-Dimensional elastic registration system of prostate biopsy location by real-time 3-dimensional transrectal ultrasound guidance with magnetic resonance/transrectal ultrasound image fusion. J Urol 2012; 187:1080–1086.

A phantom study evaluating MRI–ultrasound fusion biopsy with the Urostation, a registration-based biopsy tracking device.

22▪▪. Natarajan S, Marks LS, Margolis DJ, et al. Clinical application of a 3D ultrasound-guided prostate biopsy system. Urol Oncol 2011; 29:334–342.

Description of a system for grading lesions on prostate MRI and initial clinical results from targeted prostate biopsy.

23. Bax J, Cool D, Gardi L, et al. Mechanically assisted 3D ultrasound guided prostate biopsy system. Med Phys 2008; 35:5397–5410.
24▪▪. Sonn GA, Natarajan S, Margolis DJA, et al. Targeted biopsy in the detection of prostate cancer using an office-based MR-US fusion device. J Urol (in press).

A clinical study on 171 patients involving MRI–ultrasound fusion biopsy of the prostate using a mechanical tracking device.

25. Rosset A, Spadola L, Ratib O, Osiri X. An open-source software for navigating in multidimensional DICOM images. J Digit Imag 2004; 17:205–216.
26. Mabjeesh NJ, Lidawi G, Chen J, et al. High detection rate of significant prostate tumours in anterior zones using transperineal ultrasound-guided template saturation biopsy. BJU Int 2012; 110:993–997.
27. Lawrentschuk N, Haider MA, Daljeet N, et al. ‘Prostatic evasive anterior tumours’: the role of magnetic resonance imaging. BJU Int 2010; 105:1231–1236.
28. Hossack T, Patel MI, Huo A, et al. Location and pathological characteristics of cancers in radical prostatectomy specimens identified by transperineal biopsy compared to transrectal biopsy. J Urol 2012; 188:781–785.
29. Dall’era MA, Albertsen PC, Bangma C, et al. Active surveillance for prostate cancer: a systematic review of the literature. Eur Urol 2012 [Epub ahead of print].
30. Adamy A, Yee DS, Matsushita K, et al. Role of prostate specific antigen and immediate confirmatory biopsy in predicting progression during active surveillance for low risk prostate cancer. J Urol 2011; 185:477–482.
31▪. Barzell WE, Melamed MR, Cathcart P, et al. Identifying candidates for active surveillance: an evaluation of the repeat biopsy strategy for men with favorable risk prostate cancer. J Urol 2012; 188:762–767.

A study showing that conventional TRUS biopsy misses clinically important cancer in patients on active surveillance.

32. Margel D, Yap SA, Lawrentschuk N, et al. Impact of multiparametric endorectal coil prostate magnetic resonance imaging on disease reclassification among active surveillance candidates: a prospective cohort study. J Urol 2012; 187:1247–1252.
Keywords:

MRI–ultrasound fusion; prostate cancer; prostate imaging; targeted biopsy

© 2013 Lippincott Williams & Wilkins, Inc.