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Research Projects / P17: Ultrasound-MRI Fusion for Targeted Diagnosis of Prostate Cancer

Ultrasound-MRI Fusion for Targeted Diagnosis of Prostate Cancer: Use of Artemis Device to Evaluate Organ-Confined Lesions

 
 UCLA Health System video detailing targeted prostate biopsy using MRI-Ultrasound Fusion

 Leonard S. Marks, MD
CASIT Investigator
Professor of Urology

Shyam Natarajan, Ph.D
CASIT Researcher
Department of Biomedical Engineering

OVERVIEW:
ProstateFall 2010—Recent advances in MRI technology now offer the promise of visualizing localized Prostate Cancer (CaP). Unlike all other major cancers, CaP has proven difficult to image when still localized. Our mission here is to try to bring prostate imaging to clinical utility, using the new Artemis device to convert MRI findings into a practical guide for the patient. In a biopsy, a potentially lethal CaP lesion may be difficult to distinguish from one of the small insignificant cancers, which are far more prevalent than the lethal ones. That distinction is important, since the former should be treated, while the latter can be simply observed ("Active Surveillance"). Improved CaP imaging and targeted biopsy will help resolve the dilemma.

For further information, or to schedule a consultation regarding
targeted prostate biopsy at UCLA: Call 310-794-3070 or E-mail: lmarks@mednet.ucla.edu

INTRODUCTION:
Professor of Pathology, Urology, and Oncology at the Johns Hopkins Medical Institutions
Dr. Jonathan Epstein
Today's challenge of localized CaP is diagnosis and treatment of clinically-important tumors. Diagnosis is
Chair of Dept. of Pathology at Wayne State University School of Medicine
Dr. Wael A. Sakr
hindered by lack of an accurate screening test; the foibles of PSA testing are by n ow well-known.  Several new tests for prostate cancer, such as PCA3 and proPSA, are on the horizon and appear promising, but are not yet fully validated or approved.   

Thus, at present approximately four men must undergo biopsy to find one with cancer, and not all cancers found are clinically important. Frequency of the unimportant tumors was defined by Sakr and the tissue characteristics described by Epstein and colleagues in the 1990s. Tumor volume is also a critical factor, with lesions less than 0.5 ml unlikely to cause harm.  At least half of all prostate cancers diagnosed today are believed to be innocuous; some men with 'low-risk' CaP now undergo active surveillance, rather than immediate surgery or radiation therapy. Others may in the future be candidates for focal therapy (a la breast tumor lumpectomy).

However, in the U.S. alone, an estimated 32,000 men will die from CaP in 2010. Therefore, a number of CaP cases diagnosed today are destined to kill. Some of the potentially lethal CaP cases are recognized by tissue features and can be treated promptly with curative therapies. Others will appear of low risk initially, but either become progressive over time or may actually be more extensive than the biopsy indicates, i.e., the 'tip of the iceberg.' A method to visualize and track CaP lesions while localized would be a major advance. According to Patrick C. Walsh of Johns Hopkins University, in a recent State of the Art lecture:

"To the young people here, if you want to make a substantial contribution to medicine for this decade and maybe for the century, address yourself to the problem of imaging cancer within the prostate gland."
—PCW, Whitmore Lecture, 2008 AUA Meeting


PROSTATE BIOPSY THEN AND NOW:
Prostate biopsy is the only proven method to diagnose CaP. The evolution of prostate biopsy over the past century is shown in the chart below. Remarkably, little has changed since Stamey and colleagues introduced the trans-rectal ultrasound guided technique (TRUS) in the mid-1980s. The major difference is that local anesthesia is now used and an increased number of cores are now obtained. Otherwise, in an era of rapid change in all aspects of medicine, the prostate biopsy is not much different today than it was several decades ago.    

Thus, advent of Artemis, an electronic imaging device—to aid systematic and targeted prostate biopsy, to guide and record biopsy locations, and to fuse MRI images with real-time ultrasound—has been received with keen interest. The manufacturer of the Artemis device, Eigen Corp. of Grass Valley, CA was granted FDA approval to market the product in May, 2008.

Modified Timeline from Silletti et al - Prostate Biopsy: Past, Present, and Future
Modified from Silletti et al, "Prostate Biopsy: Past, Present, and Future."

THE ARTEMIS DEVICE:
Prototype | Robarts Research Artemis | Eigen Corp
Artemis was the Greek goddess of the hunt; the name has been applied to convey the cancer-hunting mission of the new device. The concept of the device derives from work over the past decade at Robarts Research Institute in London, Ontario, Canada, under the direction of Aaron Fenster, Ph.D. At Robarts, a prototype was built and described in 2008. The Eigen Corp. has licensed the patents from Robarts and obtained marketing rights.   The current commercial version of Artemis is shown here and is likely to undergo changes (i.e., upgrades in hardware & software, miniaturization) in the future.

The Artemis device consists of 3 main parts: a tracking arm, a monitor, and a work station. In brief, a conventional ultrasound unit is used to image the prostate trans-rectally. The tracking arm attaches to the ultrasound probe, allowing a capture of the scanned prostate by the processor. From the ultrasound feed, a 3D reconstruction of the prostate is created on the monitor in a near-realtime manner.

Prostate biopsy is performed systematically using built-in sites, or, targeted biopsy may be perf ormed, if areas of interest are known. MRI studies, obtained in advance, may be loaded into the device for fusion with the ultrasound images, allowing areas of interest on the MRI to become TRUS-guided targets. Targets and biop

Ultrasound showing biopsy
targets after MRI Fusion
Artemis model showing
targeted biopsies
sy sites are captured and stored within the 3D model and may be used for future re-call.

MRI, particularly multi-modal MRI using a 3 Tesla magnet, may identify some prostate tumors not apparent with TRUS. An example is shown here. Thus, we have adopted a practice of obtaining MRI with diffusion-weighted imaging and dynamic contrast enhancement prior to selected biopsy procedures. In the Artemis, fusion of the stored MRI images with the real-time TRUS images often provides a target for prostate biopsy, as in the example shown.


TARGETED PROSTATE BIOPSY AT UCLA:
The Artemis device was approved by the U.S. FDA in May, 2008 and a few weeks later was exhibited at the Annual Meeting of the American Urological Association in Orlando, FL, where we first learned of it. At UCLA over the next several months, an evaluation of the device potential was undertaken, culminating in detailed discussions between the UCLA Urology Department and the Eigen Corp.  A test-site agreement was drawn; and an Artemis device was delivered to Clark Urology Center on March 23, 2009.

The work flow of Artemis-guided TRUS biopsy, from patient selection to final diagnosis, as currently practiced at UCLA, is shown here:

A presentation of the initial Artemis experience at UCLA, establishing the biopsy-tracking accuracy of the device, was
presented at the Annual Meeting of the American Urological Association, San Francisco, CA, May, 2010.

As of August, 2010, more than 150 men have had an Artemis-guided prostate biopsy at UCLA. 

Who Should Have a Targeted Prostate Biopsy?:
Because at this time availability is limited for targeted biopsy, we are currently recommending it for men who are suspected of having prostate cancer, but whose tests have been inconclusive, e.g., men with:

  • Persistent, unexplained PSA elevation, or
  • Prior negative biopsy, or
  • Increased prostate cancer gene expression (PCA3 urine test), or
  • Apparent low-risk prostate cancer interested in Active Surveillance.

All targeted biopsies are performed in the UCLA Clark Urology Center on an outpatient basis.

INVESTIGATORS:
At UCLA, a coordinated, multi-disciplinary effort has been organized to advance the understanding and application of targeted prostate biopsy. Further, world-class advisors (Fenster, Barentsz) from Canada and Holland have generously donated time and energy to the mission. In addition, scientists from Eigen Corp. (Kumar, Narayanan) are also actively involved.

Members of this team and their roles are shown below:

 

Leonard S. Marks, MD
CASIT Medical Investigator
Department of Urology
Research: Targeted Prostate Biopsy
lmarks@mednet.ucla.edu
 

Shyam Natarajan, MS
CASIT Researcher
Department of Biomedical Engineering
Research: MRI/TRUS Fusion, Embedded Systems, Signal Processing 
shyam@ucla.edu

 

Steven Raman, MD
Department of Radiology
Research: Interpretation of MRI
sraman@mednet.ucla.edu

 

Daniel Margolis, MD
Department of Radiology
Research: Interpretation of MRI
dmargolis@mednet.ucla.edu

 


Malu Macairan
Department of Urology
Research coordination
mmacairan@mednet.ucla.edu

  Jiaoti Huang, MD, PhD
Department of Pathology
Research: Whole mount histology
jiaotihuang@mednet.ucla.edu
 

Aaron Fenster, PhD
Robarts Research Institute,
University of Western Ontario,
London, Ontario, CA
Advisor / Collaborator: Ultrasound, Artemis usage, & MRI Fusion
afenster@imaging.robarts.ca

  Jelle Barentsz, MD
Department of Radiology
Radboud University, Nijmegen, NL
Advisor/Collaborator: MRI
j.barentsz@rad.umcn.nl
 

Dinesh Kumar, PhD
Eigen Corporation
Image Engineering
Dinesh.kumar@eigen.com

Ram Narayanan, PhD
Eigen Corporation
Software Engineering
Ram.narayanan@eigen.com

KEY REFERENCES:

  1. Sonn, G.A., et al. "Targeted biopsy in the detection of prostate cancer using an office based magnetic resonance ultrasound fusion device." Journal of Urology 189: 86, 2013
  2. Marks, L.S., et al. "MRI-ultrasound fusion for guidance of targeted prostate biopsy." Current Opinion in Urology, 2013 
  3. Natarajan, S., et al. "Clinical application of a 3D ultrasound-guided prostate biopsy system." Urologic Oncology 29: 334, 2011
  4. T.A. Stamey, et al. "Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer." Cancer. 1993 Feb 1;71(3 Suppl):933-8.
  5. J. I. Epstein, et al. "Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer." Journal of A.M.A. 1994 Feb 2;271(5):368-74
  6. W.A. Sakr, et al. "Age and racial distribution of prostatic intraepithelial neoplasia."
    Eur.Urol. 1996;30(2):138-44
  7. J. Bax, et al. "Mechanically assisted 3D ultrasound guided prostate biopsy system." Med. Phys. 2008 Dec;35(12):5397-410
  8. L.S. Marks, et al; Presentation at Annual Meeting
    American Urological Association, 2010
  9. T. Hambrock, et al. "Magnetic resonance imaging guided prostate biopsy in men with repeat negative biopsies and increased prostate specific antigen."  J.Urol. 2010 Feb;183(2):520-7
  10. A.K. Singh, et al. "Initial clinical experience with real-time transrectal ultrasonography-magnetic resonance imaging fusion-guided prostate biopsy." BJU International 2008 Apr;101(7):841-5
  11. B. Turkbey, et al. "Documenting the location of prostate biopsies with image fusion."
     BJU International, 2010 (e-pub, ahead of print)

For further information or to schedule a consultation regarding targeted prostate biopsy at UCLA,
call (310) 794-3070 or E-mail: lmarks@mednet.ucla.edu

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Website created by: Susan Ly, sly.mednet@ucla.edu.