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Improved magnetic resonance imaging (MRI) may aid detection of prostate cancer

Posted By Harvard Prostate Knowledge On March 10, 2009 @ 2:06 pm In Diagnosis,Prostate Knowledge,Screening,Treatments | Comments Disabled

Until recently, most professionals have been skeptical that magnetic resonance imaging (MRI) could be used on a widespread basis to diagnose or stage prostate cancer with any degree of reliability, and therefore help with making treatment decisions. One analysis of scientific literature published from 1984 to 2000 found that MRI was able to predict the stage of prostate cancer accurately anywhere from 50% to 92% of the time, depending on the facility and the skill of the radiologist. In other words, MRI staging was sometimes no better than a coin toss (see “Reason for skepticism,” below). Actual detection of tumors also depended largely on the skill and experience of the radiologist, and whether or not an endorectal coil was used to make the image clearer.

Reason for skepticism

American Urological Association. Prostate-Specific Antigen (PSA) Best Practice Policy. Oncology 2000;14:267–72. PMID: 10736812.

Engelbrecht MR, Jager GJ, Laheij RJ, et al. Local Staging of Prostate Cancer Using Magnetic Resonance Imaging: A Meta-Analysis. European Radiology 2002;12:2294–302. PMID: 12195484.

But MRI technology has substantially improved in the past few years, and some experts believe it may be time to reevaluate its use in guiding treatment decisions. A new generation of MRI devices and additional technological advances (contrast enhancement and special processing) are being used together — in select imaging centers — to generate amazingly clear images of the prostate.

In these images, even tiny areas of cancer can be revealed in color, enabling radiologists to determine exactly where a tumor is located in the prostate gland. The technology is so new that published data are sparse — yet promising. One study found the new techniques have a 95% accuracy rate (see “New generation MRI,” below). You can also see several examples of new generation images in Figures 1 and 2 below. Here, Dr. Rofsky, of Harvard’s Beth Israel Deaconess Medical Center, talks more about the new MRI technology, which patients might benefit from it, and the relative advantages and disadvantages of MRI as compared with other imaging modalities.

New generation MRI

Bloch BN, Furman-Haran E, Helbich TH, et al. Prostate Cancer: Accurate Determination of Extracapsular Extension in Prostate Cancer Using High Spatial Resolution Dynamic Contrast Enhanced and T2-W Magnetic Resonance Imaging – Initial Results. Radiology 2007;245:176-185. PMID: 17717328.

Bloch BN, Lenkinski RE, Helbich TH, et al. Prostate Postbrachytherapy Seed Distribution; Comparison of High-Resolution, Contrast-Enhanced, T1- and T2-Weighted Endorectal Magnetic Resonance Imaging Versus Computed Tomography: Initial Experience. International Journal of Radiation Oncology, Biology, Physics 2007;69,70-78. PMID: 17513062.

Bloch BN, Rofsky, NM, Baroni RH, et al. 3 Tesla Magnetic Resonance Imaging of the Prostate with Combined Phased-Array and Endorectal Coils; Initial Experience. Academic Radiology 2004;11:863–867. PMID: 15288036.

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. Journal of Urology 2005;174:2158–63. PMID: 16280755.

Rosen Y, Bloch BN, Lenkinski RE, et al. 3T MR of the Prostate: Reducing Susceptibility Gradients by Inflating the Endorectal Coil with a Barium Sulfate Suspension. Magnetic Resonance in Medicine 2007;57:898–904. PMID: 17457870.

Sella T, Schwartz LH, Swindle PW, et al. Suspected Local Recurrence After Radical Prostatectomy: Endorectal Coil MR Imaging. Radiology 2004;231:379–85. PMID: 15064390.

Sosna J, Pedrosa I, DeWolf WC, et al. MR Imaging of the Prostate at 3 Tesla: Comparison of an External Phased-Array Coil to Imaging with an Endorectal Coil at 1.5 Tesla. Academic Radiology 2004;11:857–862. PMID: 15354305.

Yuen JS, Thng CH, Tan PH, et al. Endorectal Magnetic Resonance Imaging and Spectroscopy for the Detection of Tumor Foci in Men with Prior Negative Transrectal Ultrasound Prostate Biopsy. Journal of Urology 2004;171:1482–6. PMID: 15017203.

New options in MRI technology

MRIs can be done with or without an endorectal coil. What is the advantage or disadvantage of including an endorectal coil?

An endorectal coil in MRI functions a bit like a television antenna. It’s a thin wire, covered with a small inflated balloon and inserted into the rectum. Once the MRI device is turned on, the coil receives the magnetic waves, which we will analyze with a computer to gain information about the magnetic properties of a particular tissue. The closer the coil is to the target tissue, the stronger the signal. (The fundamentals of MRI technology are explained in “MRI basics“, below.)

The disadvantage of an endorectal coil is that it can be uncomfortable. Fortunately, most people are able to cope with this. We routinely inject a muscle relaxant to help muscles in the rectal wall relax a little and improve comfort. We can also offer some patients mild sedation, to ease anxiety.

What other new MRI technology is available, and why do you think it improves prostate cancer diagnosis and staging?

After Beth Israel Deaconess Medical Center purchased the 3T scanner with funding by a generous philanthropist, we produced very good images of the prostate gland using traditional coils placed on top of the body. But we had a great opportunity to improve the images even further since two of our colleagues at Beth Israel Deaconess Medical Center were among the researchers who developed the original endorectal coil while they were at the University of Pennsylvania — Dr. Robert Lenkinski, now vice chair of Radiology and director of Radiology Research at Beth Israel Deaconess Medical Center, and professor of radiology at Harvard Medical School, and Dr. Herbert Kressel, currently radiologist in chief at Beth Israel Deaconess Medical Center and the Miriam H. Stoneman Professor of Radiology at Harvard Medical School. I talked with them and suggested that we develop a coil specifically for use in a 3T scanner. We worked with a medical device company and developed an endorectal coil that is appropriate for the 3T scanner. When we looked at the first few images created using this new coil, we realized that this was going to be a game changer.

Why was that?

The combination of the more powerful scanner and endorectal coil, along with improvements in contrast-enhanced imaging, produced a degree of anatomic detail we hadn’t seen before.

The higher the strength of the magnet, the clearer the image?

That’s correct. One way to understand the importance of a higher tesla value is that a more powerful magnet creates a stronger signal, which we can use to construct a much higher spatial resolution in the image.

MRI basics

  • MRI uses the electromagnetic properties of hydrogen molecules to collect information about organs and other tissues and converts this to an image.
  • Cancerous tissue has a different set of magnetic properties than surrounding normal tissue. MRI is able to capture these differences.
  • Ionizing radiation, which is the type used to generate an x-ray or CT scan, carries some risk because too much exposure to this form of radiation can potentially damage a person’s genetic material. But MRI does not involve ionizing radiation, so there is no danger with single or repeat exposures.
  • An MRI exam takes 45 minutes to a little over an hour.
  • Before undergoing an MRI, your doctor will ask whether you have any electronic or metal medical devices in your body, such as a heart pacemaker or any metallic clips, pins, or screws. These precautions are necessary because the MRI magnet is so powerful that it could interfere with a pacemaker or displace some implanted clips.
  • An MRI magnet is measured in units of tesla (T), in honor of Nikola Tesla, a renowned physicist and electrical engineer who was very interested in magnetic fields. MRI magnets generally function between 0.5T and 3T. Most diagnostic work over the past few years has been at 1.5T.

Can you talk more about contrast-enhanced imaging, and how this has improved recently?

Radiologists can make an MRI image clearer by using contrast media, which have their own magnetic properties. That’s why some people receive an injection of a contrast medium, or what is sometimes called a “dye,” before undergoing an MRI. For a brief time, as the contrast material passes through tissues of interest, it will alter the magnetic properties of that tissue, depending on the amount and rate of absorption. And that gives us a great deal of information to characterize tissue.

The problem is that contrast enhancement is difficult to do because it requires that you collect images so rapidly that you lose some degree of spatial resolution in the process. But researchers in Europe and Israel have been collaborating on ways to solve this problem. While he was at the University of Vienna, Dr. B. Nicolas Bloch developed an improved approach to contrast-enhanced imaging of the prostate that provides better spatial resolution. He did initial work in collaboration with Dr. Hadassa Degani, a phenomenal researcher at the Weizmann Institute of Science, who was working with breast tissue. Dr. Bloch has since become a radiology clinician researcher at Beth Israel Deaconess Medical Center, where he’s perfected those techniques and is applying them to MRI imaging of the prostate using the 3T scanner.

Figure 1: Using contrast-enhanced 3T MRI to guide prostate biopsy

The patient whose prostate is pictured here had an elevated PSA, indicating that he might have prostate cancer. But several biopsies guided by traditional imaging technology came back negative, meaning they did not reveal cancer. The images below show why endorectal MRI with contrast enhancement can provide better guidance.

1A: This image was produced by a typical endorectal MRI with contrast enhancement. The MRI shows no suspicious areas or distinguishing features, which doctors use to guide a prostate biopsy. In such cases, the sampling is random — and in this patient’s case, missed the cancer.

1B: This image was taken from the same angle as Figure 1A, but used 3T endorectal MRI with contrast enhancement and a color-coding technique. The cancer shows up clearly in red (partly because of angiogenesis, the formation of multiple leaky blood vessels that feed a tumor). Normal blood vessels are shown as thin red lines near the rectum, and normal prostate tissue is seen in blue.

The yellow arrow points to an area in the anterior portion of the prostate, which is not normally sampled during random biopsy. When contrast-enhanced 3T MRI was used to guide the biopsy, doctors were able to sample the suspicious area, and found cancer — providing the patient and his doctors with crucial information to make treatment decisions.

So the images displayed in Figures 1 (above) and 2 (below) were produced by combining the new MRI technology with this improved contrast-enhancement technique?

Correct. And once again, working with researchers at the Weizmann Institute, we developed a color-coded technology where cancer shows up as red, and that really simplifies the evaluation. In traditional imaging, it’s possible to miss small clusters of cancer because the features are so subtle. But if you see it in red, it really jumps out at you.

Figure 2: Detecting cancer recurrence after radical prostatectomy

In a typical ultrasound image, the prostatic bed (the area that remains after the prostate is removed) usually appears as a sea of gray. Because other tissues and organs shift position after prostatectomy, to fill up the space where the prostate was once located, the anatomical landmarks are hard to interpret with ultrasound. There are no distinguishing features that would suggest where the prostate used to be, or where a recurrence of malignant growth may be located. Without such guidance, the biopsy is likely to be negative, and it will not be clear whether the patient should be treated.

In a color-coded contrast-enhanced endorectal MRI shown above, the cancer shows up clearly as red, while normal tissue is blue and green. This MRI was used to direct a biopsy that sampled the cancer, providing guidance for treatment decisions.

Do you also use MR spectroscopy? If so, could you explain what that is?

MR spectroscopy provides a way to look at specific chemical properties within a particular tissue. And so we can actually get information about molecular structures and metabolites, providing us with much more detail about the prostate gland itself. We’re combining many MRI “looks” at the prostate, in order to obtain unique information and then use all that information together to formulate a clearer picture of what’s going on in an individual’s prostate gland.

And as a result you’re providing better diagnostic information?

By using high-resolution contrast-enhanced imaging, we believe that we are able to stage prostate cancers much better. We can give patients specific information about the extent of their disease. And certainly that will help men and their doctors make more informed treatment decisions.

What are the advantages and disadvantages of ultrasound imaging of the prostate gland, versus MRI?

The advantage of ultrasound is that it’s readily available and, from the hospital’s perspective, a less expensive technology to purchase. However, this technology has its limits. For example, when ultrasound is used to guide a prostate biopsy, it enables the doctor to locate the prostate gland for gross placement of the needle, but ultrasound provides no reliable information about where cancer might be. As a result, the biopsy consists of a random sample of areas within the prostate.

In MRI, especially with this new technology, we can actually show where cancer may exist within the prostate gland. That enables a doctor to do purposeful — rather than random — sampling of the prostate.

How accurate is this new MRI technology?

We did a study, now in press, with a side-by-side comparison of an MRI image and its corresponding pathology slide. So we basically tried to slice the gland in pathology exactly how we “sliced” the gland when it was in the patient. This is known as the “whole mount” technique for pathology. We orient the prostate during pathology, so that it matches the way the gland was oriented during imaging, and we slice it exactly the way the individual image slices were obtained in the MRI. In that way, we try to repeat what happened in the imaging session with the pathology specimens.

In our latest publication, we had an accuracy rate of 95%. So in other words, 95% of the time the stage that we predicted using MRI before surgery was confirmed afterward when the gland was sent to pathology. This is important because understaging occurs alarming regularity in prostate cancer. Nationally, as many as 40% to 50% of men initially thought to have early-stage cancer will find out later that they have more extensive disease – although this varies by institution.

Which patients might benefit

When is MRI recommended for men with prostate cancer?

Men who are most commonly referred to our center have had a prostate biopsy that reveals cancer, but some other aspect of the diagnostic workup raises questions about the extent or aggressiveness of the cancer. For instance, maybe the PSA level or biopsy indicates that cancer is aggressive, but nothing can be felt on a digital rectal exam. In this type of situation, an MRI can help to resolve the issue.

So you’re trying to provide some additional information that might affect a treatment decision?


What are some other situations where MRI is helpful?

One of the more useful applications of MRI is in locating cancer that has not shown up on a biopsy. This can be very helpful to a man who has not yet been diagnosed with prostate cancer despite having an elevated PSA and continued biopsies that come back as being “negative,” meaning there is no evidence of cancer. The urologist thinks that cancer is present, but can’t find it based upon the biopsy results. Often men are referred to us after they have several negative biopsies. We can use MRI to advise the urologist where to target the biopsy needle, so that the doctor samples the area where we have the highest degree of suspicion that cancer exists.

And we’ve learned that often those patients who have a PSA that continues to increase, and are thus suspected of having cancer, yet whose biopsies come back negative, have cancer in locations that are poorly sampled in a routine ultrasound-guided biopsy. Many tumors we detect are located in the anterior portion of the prostate, in front of the urethra, toward the pelvic bones. These cancers cannot be seen with ultrasound and are extremely hard to hit with a biopsy needle. Virtually the only way to identify and diagnose these tumors is with MRI.

Other cancers are found low down, at what is known as the apex of the gland, or very high up, in the base. We’re working in conjunction with urologists right now, to use MRI to improve our ability to find these elusive cancers.

How do you answer critics who have not kept up with developments in this field and remember MRI of the prostate as being no better than a coin flip, and who believe that this may be a total waste of time and energy?

I would answer them by saying that it’s a whole new world, with new technology, and new insights, and to close your patients off to this emerging technology is a great disservice. There are many new possibilities, and many of those will be in the published literature over the next year, as our data are published. So you’ve got to believe in the clever, creative, and dedicated people out there who can move the field forward.

When to consider a prostate MRI

Studies indicate that MRI may be helpful in the following situations. The best images are obtained when using an endorectal coil.

  • You have a PSA that continues to increase, but an ultrasound-guided prostate biopsy does not reveal cancer; an MRI may be able to better pinpoint a suspicious area for a more targeted biopsy and increase the likelihood of finding cancer if it is there.
  • Different elements of your diagnostic workup are in conflict (for instance, your PSA level is high, but your Gleason score is 3 plus 3 and cancer is found in only 1 of 12 biopsy specimens); an MRI can better determine size of the tumor and whether it has extended beyond the capsule.
  • For large palpable tumors, MRI can rule out cancer that extends beyond the prostate itself.
  • If your PSA rises following prostate cancer treatment, MRI can be used to identify any cancerous tissue in the periprostatic bed (the area in the pelvis where the prostate was once located), which indicates a local recurrence.
  • MRI may provide better guidance about where to target radiation therapy.

Additional uses under investigation

How might this technology be used in the future?

We’re working toward performing biopsies directly through MRI guidance, probably by superimposing MRI information onto an ultrasound image. In this way, we could maximize benefits of MRI in identifying areas to target during biopsy, to increase the chances that cancer is sampled.

Many men are undergoing active surveillance, which means that their cancer has been diagnosed, but they are monitoring its progression before undergoing treatment. Have you had any experience with whether MRI could help such men to monitor cancer progression?

That’s another area we’re studying. But we’ve already been following individual men, on a case-by-case basis, who are undergoing serial MRIs at Beth Israel Deaconess Medical Center because they are undergoing active surveillance. In some of those patients, we’ve actually seen the cancer grow in size.

We think that in the future MRI may offer an opportunity to follow these patients without asking them to undergo biopsies. Instead, MRI might be able to provide an objective measure of whether cancer is remaining dormant, or whether it’s growing. We are accumulating data on that. Of course, this is still at the research stage. But I believe that one day we’ll be able to use MRI to categorize some tumors as being very slow-growing, with a good option for active surveillance, while identifying others that may transition into aggressive cancer. And hopefully we’ll be able to identify those patients early, perhaps even before a PSA bump is detected.

Are there any differential MRI appearances according to the Gleason score of the prostate cancer, as finally determined by pathology?

We have preliminary data provided by MR spectroscopy that a particular chemical profile is related to the Gleason score. As part of our research, we hope to use MR spectroscopy to gauge aggressiveness of a tumor to add yet another dimension to information provided by the Gleason score. A Gleason score is helpful, but it provides just one way to measure tumor aggressiveness; there are times when men with low Gleason scores have aggressive tumors. So we hope to use MRI and MR spectroscopy to provide other ways to characterize a tumor.

For more information

If someone reading this interview decides he wants an MRI, but his hospital does not have the sophisticated equipment we’ve been discussing, what should he do?

Anyone is welcome to contact Beth Israel Deaconess Medical Center.* Many patients are referred to us for imaging, and then return to their own urologist. In those instances I do ask to speak to the referring urologist or medical oncologist or radiation oncologist, because I want to know how the information will be used and I want to ensure continued follow-up of patients who have undergone imaging at our center. However, I do encourage patients from other hospitals to see another member of our comprehensive team, so they can benefit from more than just our imaging expertise.

*Note: To find out if you should consider asking for a referral, see “When to consider a prostate MRI,” above.

What other hospitals have a comparable technology?

Our specific approach is pretty unique to us right now. In terms of 3T imaging systems that are performing endorectal prostate imaging, I’d be surprised if there are more than 20 in the world doing it in a meaningful fashion at the moment. But the systems are proliferating quickly.

Originally published March 2009; last reviewed April 7, 2011.

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