MRI Fusion Biopsy in Turkey

MR fusion biopsy is an advanced diagnostic biopsy method in which magnetic resonance imaging and ultrasound are used simultaneously, enabling suspicious lesions, especially in the prostate, to be sampled with high accuracy. It increases diagnostic accuracy with targeted tissue sampling and reduces unnecessary sampling.

The procedure of how MR fusion biopsy is performed is based on combining previously obtained multiparametric MR images with ultrasound during the procedure. Suspicious areas are marked with the help of software, and with real-time guidance, the needle is advanced directly into the target tissue, thus minimizing systematic errors.

Among the advantages of MR fusion biopsy are the high rate of detecting clinically significant cancer foci and the reduction of overdiagnosis of low-risk lesions. In addition, obtaining more accurate results with fewer samples increases patient comfort while also reducing the risks of complications.

The evaluation of who MR fusion biopsy is performed on is made in the presence of elevated PSA, suspicious digital rectal examination findings, or ongoing clinical suspicion despite previous negative biopsies. Especially in the need for repeated biopsy, the targeted approach provides significant clinical benefit.

Why Was There a Need for a New Method, MR Fusion Biopsy Technology, in the Diagnosis of Prostate Cancer?

Prostate diseases, which are among the leading issues concerning men’s health, become part of many people’s lives in one way or another with advancing age. This organ, about the size of a chestnut and located just below the bladder, is by nature quite prone to enlargement or cellular changes with age. For many years, modern medicine had a standard roadmap for detecting prostate cancer. A high Prostate Specific Antigen level in the blood, in other words, the PSA test as we all know it, or an unusual hardness felt during a digital physical examination constituted the first steps of the diagnostic process. When these suspicions arose, ten or twelve tissue samples were taken from different areas of the prostate under standard ultrasound guidance.

However, this traditional method had a very fundamental weak point that was psychologically quite exhausting for patients. Although standard ultrasound devices showed the outer contour and size of the prostate very well, they were inadequate in distinguishing dangerous cancer cells in the internal structure of the organ from completely innocent and healthy tissues. Cancerous tissues often appeared on the ultrasound screen in the same color and structure as healthy tissues. We can compare this situation to trying to find a specific object by feeling around in a pitch-dark room. Since physicians could not see where the cancer was, they were taking samples from certain regions of the prostate at standard intervals with an approach called “blind” or systematic.

It was exactly this blind approach that caused clinically significant cancers, that is, cancers that truly threaten the patient’s health and require urgent treatment, to be missed at a rate of one quarter. The biopsy needle could pass just a few millimeters away from the cancerous tumor and take a completely healthy piece of tissue. As a result, the report came back clean, but the patient’s PSA value measured in the blood continued to rise. This uncertainty caused patients to experience stress lasting for months and sometimes years, forcing them to lie on that table again and again and undergo repeated biopsies. Moreover, because the diagnosis was delayed, that valuable early stage of the disease in which it could be treated could be missed. All these deficiencies made it necessary to develop a much smarter and more technological method that would focus only on the suspicious point and be able to make a “pinpoint shot.”

What Are the Main Reasons for Using MR Fusion Biopsy Instead of Standard Methods?

Thanks to developing imaging technologies, a much more precise and reliable system that saves patients from this exhausting uncertainty has been brought into the world of medicine. The main features that make this innovative technology, which closes the gaps of the old methods, preferred are as follows:

• Millimetric precision
• High accuracy
• Targeted approach
• Early diagnosis
• Personalized mapping
• Fewer tissue samples
• Low complication

These basic advantages have completely changed the rules of the game in medical practice. If there is a suspicious area in the patient’s prostate, this system projects that area onto the screen like a glowing target. Thus, instead of unnecessarily taking dozens of pieces from the healthy parts of the prostate, it becomes possible to direct the procedure directly and only to that point that poses danger. Seeing the target clearly reduces the number of tissues to be taken, while at the same time increasing the quality of the specimen sent to the laboratory. This certainty in diagnosis eliminates that heavy psychological burden in the form of “Do I have cancer that just could not be found?” and gives patients confidence. In addition, thanks to the clarity of the target, the possibility of the biopsy needle damaging the nerves or vessels around the prostate is also minimized.

What Is Multiparametric MR and How Does It Distinguish Cancerous Tissue Before MR Fusion Biopsy?

At the heart of the fusion procedure lies Multiparametric Magnetic Resonance (Mp-MR), an extremely advanced imaging system. We can think of standard MR scans as static photographs that only show the inside of the body. However, “multiparametric” MR analyzes the organ not only as a physical structure but also as a dynamic system that lives, is supplied with blood, and has moving cells. We can think of this device as a huge and highly capable radar; it measures not only the outside of the building, but also the movement inside the rooms, the plumbing, and the density of the walls at the same time.

In order to obtain this tremendous detail, the device is operated with different settings and different imaging types (sequences). The first of these is anatomical images. At this stage, called T1- and T2-weighted sequences, a high-resolution map of the prostate is produced, so to speak. The inner region of the prostate (transitional zone) and the outer region (peripheral zone) are examined in detail, and whether the membrane surrounding the outside of the organ is intact is checked. Especially in people with benign prostatic enlargement, the inside of the organ takes on a highly complex and nodular structure. T2 images identify the first suspicions by detecting architectural distortions within this complex structure.

The second and most striking stage is the function called Diffusion-Weighted Imaging (DWI). A large part of the human body is made up of water, and these water molecules are in constant microscopic motion within tissues. However, because cancer cells multiply uncontrollably and very rapidly, they create a tremendous crowd and a cellular “traffic jam” in the area where they are located. This congestion prevents water molecules from moving freely in that region. The MR device detects these crowded areas where the water cannot move and becomes trapped. In the images, these areas appear as bright, eye-catching focal points and provide one of the strongest clues to the presence of cancer.

The third stage is Dynamic Contrast-enhanced examination. Cancerous tumors need blood in order to be nourished and grow, and for this purpose they build extremely irregular, strange new vascular networks around themselves. When a harmless contrast agent (medication) is administered to the patient through the vein, the MR device follows the journey of this agent within the prostate second by second. Those irregular vascular networks formed by cancerous tissues absorb the agent much faster than healthy tissues and then expel it again very quickly. Thanks to this difference in vascularization, the borders of the suspicious target are clearly drawn. When all these three different pools of information are brought together, where the cancerous tissue is, how large it is, and even its estimated degree of aggressiveness become largely clarified.

What Is the PI-RADS Score That Affects the Decision for MR Fusion Biopsy and How Is the Scoring Done?

All these complex MR images and mathematical data obtained must be simplified and translated into a universal language so that a clear decision can be reached in the patient’s diagnostic process. This common language, which enables radiologists and urologists all over the world to reach the same conclusion from the same report, is called PI-RADS (Prostate Imaging-Reporting and Data System). If a suspicious spot, that is, a lesion, is seen in the prostate as a result of the multiparametric MR scan, the radiology specialist gives this spot a risk score between 1 and 5 by blending all the data.

Comparing this scoring system to the colored weather warnings used by meteorology will make the subject very easy to understand. The aim is both to prevent unnecessary panic and to ensure that the right precautions are taken on time if a real storm is approaching. The scores do not directly prove the presence of cancer, but they show the statistical strength of the probability of finding a clinically significant cancer. When scoring is done, fine details such as where the lesion is located in the prostate, whether its borders are irregular, its size, and the degree of water restriction in the diffusion images are used. For example, a large spot located in the outer region of the prostate, with unclear borders and very high cellular density, will automatically receive a higher danger score.

Which PI-RADS Scores Are Taken Into Consideration When Deciding on MR Fusion Biopsy in Patients?

The main scores included in the conclusion section of the radiology report and determining the next step of treatment or diagnosis are as follows:

• PI-RADS 1
• PI-RADS 2
• PI-RADS 3
• PI-RADS 4
• PI-RADS 5

These scores are the basic milestones that draw the roadmap between the doctor and the patient. When PI-RADS 1 and PI-RADS 2 scores are obtained, this is an extremely reassuring picture. The probability of there being cancer in the patient at a level that would pose a clinical danger is quite low. If the PSA value measured in the blood is not very high and there is no strong genetic history of cancer in the family, a biopsy is generally not considered necessary. The patient is only taken into routine follow-up with periodic blood tests and examinations.

The PI-RADS 3 score is the most caution-requiring “gray zone” of the process. It expresses a moderate suspicion of cancer; that is, the lesion does not appear completely innocent, but it also does not exhibit a definite cancer character. At this point, personalized medicine comes into play. All personal factors such as the patient’s age, the overall size of the prostate, whether the patient has had prostate inflammation (infection), and whether a biopsy has been performed before are placed on the scale. If suspicion outweighs reassurance, a biopsy decision can be made to clarify this gray area.

PI-RADS 4 and PI-RADS 5 scores constitute the high-risk group in which alarm bells are ringing. While the probability of cancer is very high in PI-RADS 4, in PI-RADS 5 the presence of cancer is almost certain and there may even be a possibility that this tissue has spread beyond the prostate. When any of these scores is reported, MR Fusion Biopsy directed at those lesions must definitely be planned without delay and the structure of the tissue must be examined pathologically.

What Are the Main Methods Used in MR Fusion Biopsy Application?

After the map of suspicious spots is created by MR, the most difficult stage begins: directing the needle with full accuracy to the target on this map. Different techniques have been developed over the years to perform this procedure. There are three main approaches, and although all of them serve the same purpose, they show major differences in terms of accuracy rates and application comfort.

The first method is the Cognitive, that is, Mental Fusion technique. In this method, no high-level technological device is used. The physician who will perform the procedure examines the patient’s MR images on the computer screen in detail and visualizes in three dimensions where the tumor is located in the prostate. Then they place the classic ultrasound probe on the patient and try to direct the needle to the suspicious area, relying entirely on their own memory and the map created in their mind. This method does not bring any additional equipment cost to the hospital and can be applied very quickly. However, it depends entirely on the spatial perception, manual skill, and experience of the person performing the procedure. If the targeted tumor is very small, such as three or four millimeters, hitting that area with only mental estimation is quite difficult and the margin of error is high.

The second method is the biopsy performed directly inside the MR device (In-Bore). As the name suggests, this procedure is not performed in a standard outpatient room but inside the tunnel of that huge MR device in the hospital’s radiology unit. While the patient lies face down inside the device, the radiologist gradually directs the needle toward the tumor by looking directly at the MR screen under real-time MR images. It is almost perfect in terms of visual accuracy because the moment the needle enters the very center of the target can be monitored instantly. However, this procedure is quite burdensome for patients. It may take between half an hour and one and a half hours, it is necessary to remain motionless inside a huge magnet, and taking backup samples from other areas of the prostate for control purposes is technically very difficult. In addition, its cost is quite high.

The third method, and the one accepted today as the gold standard in the medical world, is software-assisted smart fusion systems. In this technology, those detailed digital images taken in the MR unit are transferred via a special flash drive or hospital network to the high-level ultrasound device in the biopsy room. Thanks to its incredible software, this device overlays the static MR photographs with real-time ultrasound images with millimetric precision. The two different images appear on a single screen like a three-dimensional and moving hologram. The suspicious cancer focus is marked on the screen as a colored and distinct target. The tip of the needle is also followed on this screen in real time. Thus, without the need for any human estimation or mental fatigue, the shot is made directly at that colored target on the screen.

How Do Software-Assisted Smart MR Fusion Biopsy Devices and Navigation Systems Work?

Behind the success of software-assisted devices lie the image-matching, that is, “registration” algorithms. Combining an MR image with ultrasound is like reading books written in two different languages at the same time and making a perfect translation. There are two different software models that make this possible:

The simpler model is called “Rigid Registration.” This system considers the prostate as if it were a solid wooden ball that never changes shape. It takes the MR image and directly pastes it onto the ultrasound image. However, the human body is not rigid. During the biopsy, when the ultrasound probe comes into contact with the tissue and applies pressure, the prostate stretches like a sponge, changes shape, and shifts right and left. Since rigid systems do not take this stretching into account, deviations of a few millimeters may occur in the target.

The most advanced technology devices used today (such as Artemis, Koelis, UroNav, BioJet) use the “Elastic Registration” system. This system knows that organs are alive and flexible. When the prostate is subjected to pressure and changes shape during the biopsy, the artificial intelligence and mathematical models inside the software instantly bend, stretch, and recalculate the MR image in accordance with this change. We can compare this to the smart navigation systems in cars; even if you take a wrong turn or your car slides, the GPS system instantly recalculates the route and keeps you locked onto the target. Some of these devices have electromagnetic sensors, while others have robotic arms, and they completely prevent the needle from deviating by damping even the millimetric vibrations that occur when the patient breathes during the procedure.

For Which Patient Groups Is It Especially Vital to Undergo MR Fusion Biopsy?

Although it is a wonderful technology, this procedure is not a routine step for every prostate patient. However, for individuals with certain special clinical scenarios, it is a vital necessity. The patient groups for whom this method is indispensable are as follows:

• Those whose PSA value shows a continuous upward trend
• Those whose first biopsy came back clean but whose suspicions continue
• Those who receive a PI-RADS score of 3 and above
• Those in whom a suspicion of a mass is detected during physical examination
• Those with a family history of aggressive prostate cancer
• Those being followed under an active surveillance protocol

Especially patients who have previously undergone traditional biopsy, have been told “the result is clean, there is no cancer,” but whose blood values never improve are the group that benefits most from this technology. Tumors growing insidiously in the farthest or front (anterior) parts of the prostate, which classical needles could not reach, have generally been missed in these patients. Fusion technology directly sheds light on these hidden dark areas and reveals the danger.

In addition, the situation is also very critical for patients under “active surveillance.” Sometimes patients have cancer cells that grow so slowly and are so harmless that treatment is postponed to protect the patient from the possible side effects of surgery, and the patient is placed under close follow-up. However, if the first diagnosis was made with the old blind method, the actual dangerous type of cancer hidden in another corner of the prostate may have been missed. By scanning the entire prostate with fusion biopsy, it is clarified without leaving any room for doubt whether it is truly an innocent cancer or whether urgent surgery is needed.

Should the MR Fusion Biopsy Procedure Be Performed Through the Intestine or Through the Skin?

The choice of the route through which the needle will enter the body in order to reach the prostate is at least as important as the software used in terms of patient comfort and post-procedural safety. From past to present, biopsies have generally been performed through the route called Transrectal (TR), that is, through the anus and the final part of the large intestine. The advantage of this method is that it is a technically more familiar, quickly applicable, and short procedure. However, it carries a very large disadvantage: the inside of the intestines is naturally full of trillions of bacteria. Every time the biopsy needle takes a sample, it passes through the intestinal wall and can directly carry some of these bacteria into the prostate tissue, and even into the blood. No matter how strong the antibiotics used are, after this method serious infections, high fever, and sepsis requiring hospitalization can be seen in a certain percentage of patients.

In recent years, the modern medical world and current health guidelines have turned toward the Transperineal (TP) method, which is a much safer route. In this method, the needle does not come into contact with the intestines at all. The entry point is the clean skin region called the “perineum,” located between the scrotum and the anus. Before the procedure, this region is completely sterilized with special solutions just like a surgical field.

The most tremendous advantage of the transperineal method for patients is that it reduces the risk of intestine-based infection almost to zero. The patient does not experience fear of fever or severe infection after the procedure. Its second major advantage is ease of access. While reaching the upper and front regions of the prostate, which we can call the “attic” of the prostate, is physically very difficult through the intestinal route, entering through the skin provides equal and easy access to every millimeter of the prostate. Especially in patients with a large prostate, hitting the target becomes much easier.

What Should Patients Pay Attention to Before and After MR Fusion Biopsy?

When the biopsy day arrives, proper preparation and anesthesia planning are essential for the process to be comfortable and trouble-free. Since the fusion procedure is a technology based on millimetric calculations, it is mandatory for the patient to remain completely motionless throughout the procedure. If the patient strains slightly or startles because of pain, that delicate fused map may shift. Therefore, today, deep sedation (a light sleep state) or full anesthesia methods, in which the patient feels and remembers nothing, are frequently preferred. Before the procedure, if the patient uses blood thinners, they must definitely be stopped under doctor supervision to prevent the risk of bleeding, and antibiotics prescribed for protective purposes must be used as described.

After the procedure is completed, patients can walk back to their homes or workplaces on the same day. During the recovery process, while the prostate tissue repairs itself, some expected side effects may occur. The following are situations that patients should not panic about and that are considered completely normal:

• Pinkish urine
• Blood in semen
• Mild aching
• Rectal tenderness
• Frequent urination
• Temporary weakness
• A feeling of fullness while sitting

These are the process of the body eliminating micro-bleeding and edema caused by small needle entries. Bleeding in the urine usually disappears within a few days by drinking plenty of water. Seeing dark brown or rust-colored blood in the semen may last longer; even if this continues for weeks, it poses no medical danger whatsoever.

On the other hand, there are also some serious warning signs that may indicate the response of the immune system or possible rare complications and require urgent medical support without delay. These emergency symptoms are as follows:

• High fever
• Severe chills
• Inability to urinate
• Bleeding with clots
• Sharp pain
• Nausea
• Severe weakness

Especially within the first few days after the procedure, a fever exceeding 38 degrees and cold sweating may be a signal that the infection has entered the bloodstream. Likewise, the inability to urinate at all despite the bladder being full because blood clots have blocked the urinary tract also requires an urgent intervention, namely catheter placement. Fortunately, thanks to modern techniques performed through the skin, such frightening situations are now encountered very rarely.

What Do MR Fusion Biopsy Success Rates Tell Us?

This wonderful opportunity offered by medicine is not just a clinical assumption; it has an indisputable superiority proven by very large-scale international studies involving thousands of patients. In studies carried out at the world’s most respected medical centers (for example, the PRECISION study, one of the best-known largest studies), the old method and the new generation fusion method were compared head to head. The results obtained are quite striking.

Compared to the old standard methods, MR Fusion Biopsy increases the success of detecting cancers that are aggressive enough to truly endanger the patient’s life by an average of 30 to 40 percent. This means saving the lives of hundreds of patients who were previously sent home after being told “clean” even though a growing danger was actually inside them. Even better, this technology also reduces the rate of finding insignificant cancer cells that grow very slowly, would not cause any complaints throughout the patient’s life, and can be likened to “turtle”-speed cancers similar to age spots. Thanks to this, the number of patients who were unnecessarily labeled with cancer after biopsy and subjected to major surgeries has been significantly reduced.