When we introduced the renowned radiologist Prof. Dr Markus Düx and his innovative ultrasound method known as MRgFUS a while ago, many people were surprised. This is because this extremely gentle procedure makes it possible to successfully treat conditions and symptoms that can be very painful – and all without any surgical intervention. Consequently, many people became aware of the MRgFUS Center at Prof. Dr Markus Düx’s radiology practice, which, with its locations in Frankfurt and Königstein im Taunus, plays a pioneering role in this still novel method.
The first part of the discussion focused on applications and treatment methods using MRgFUS, such as for fibroids, painful facet joint osteoarthritis or bone tumors. We learnt that, technically speaking, highly focused ultrasound can generate heat of up to one hundred degrees Celsius, which is then directed at the target structure. With the help of MRI, the temperature development can be measured, and it is also possible to see exactly what energy is generated in the tissue. This allows tumors to be destroyed – and can trigger regeneration processes in cells, which can be very helpful in cancer therapies. Prof. Düx and his team in Frankfurt and Königstein use only MRgFUS therapies that are approved for clinical use in treating conditions such as osteoid osteomas: For these often tiny bone tumors, which mainly occur in children, the gentle ultrasound method is “the treatment of choice”, as Prof. Düx put it.
MRgFUS is now also being used successfully to treat prostate cancer – and it helps to overcome the blood-brain barrier. This follow-up article explores what this involves and the future prospects for this innovation. Dr Daniel Düx, who spent a year conducting research on the subject at Stanford University in California, also joined the video conference.
Leading Medicine Guide: Professor Düx, could you briefly outline once again what MRgFUS is actually about?
Prof. Dr Markus Düx: Certainly. MRgFUS stands for magnetic resonance-guided focused ultrasound therapy. This therapeutic method can replace surgical intervention for certain conditions. Highly focused ultrasound was already in clinical use in the 1990s, for example in urology, but purely on a physical basis and without MRI guidance. Magnetic resonance imaging allows us to measure temperatures. Although this has been known for a long time, the combination of these two techniques – creating a distinct therapeutic unit from MRI and focused ultrasound – is relatively new. This allows us to heat and destroy damaged tissue using high-energy ultrasound, rather than removing it invasively with a needle or scalpel.
Leading Medicine Guide: And can you also use this to treat prostate cancer?
Prof. Dr. med. Markus Düx: Exactly. We destroy early-stage prostate cancer using heat and MRI guidance. The probes, onto which the elements for generating the highly focused ultrasound are mounted, are kept small enough to be inserted via the rectum. Our system is currently the only one in Europe that inserts the ultrasound source via the rectum and, while the prostate is being treated with heat, displays the results – specifically the temperature distribution within the tumor and surrounding tissue – using MRI. In this way, ultrasound waves are directed into the prostate, where the tumor is destroyed.
Leading Medicine Guide: ... quite simply through heat.
Prof. Dr. med. Markus Düx: Through heat. These tumors can now be diagnosed very effectively using MRI; prostate cancer can be identified precisely, and with MRI-guided treatment it is usually possible to maintain a safe distance from healthy tissue without any problems. If, on the other hand, a prostate patient has to undergo surgery, they often have to deal with side effects such as incontinence and erectile dysfunction – there is a high risk of side effects that we men all fear. Even though surgical techniques are constantly improving, the risk is always present. If the neurovascular bundle in the prostate is damaged during surgery, patients often experience unwanted side effects and problems after the procedure. With MRI, we can see the neurovascular bundle clearly, so we can guide the MRgFUS therapy in such a way that we avoid the critical structures and effectively shield them from the heat. So we treat only the tumor from a safe distance and destroy it. At present, we are only carrying out this treatment for early-stage prostate cancer.
Leading Medicine Guide: Why is that?
Prof. Dr. med. Markus Düx: First of all, this type of cancer is very common. Almost one in two men develops prostate cancer. There are three of us sitting here now, and it is highly likely that one of us will develop prostate cancer at some point in our lives. Prostate cancers are common tumors that we usually do not die from. Men diagnosed with prostate cancer can certainly live to a ripe old age, but it is essential to diagnose and remove it early. With the help of MRI, prostate cancer is often detected at an early stage. This allows for early local treatment, in line with the saying ‘nip it in the bud’. Early-stage prostate cancer is almost always confined to the prostate, which justifies local thermal therapy. In the case of advanced cancer, there are often already lymph node or distant metastases, in which case local treatment no longer makes sense. An indicator of prostate cancer is an elevated PSA level.
Leading Medicine Guide: PSA level?
Prof. Dr. med. Markus Düx: PSA stands for prostate-specific antigen, which is a protein produced only by prostate cells. It is an important component of prostatic fluid, and small amounts of PSA can also be detected in the blood. If this level is elevated, we look for a cancer – and often find one using magnetic resonance imaging. If we then biopsy the cancer under MRI guidance, we can determine what stage it is at. Through early diagnosis, we can achieve successful treatment outcomes, ensuring that prostate cancer causes as few men as possible to suffer harm that leads to death. And of course, it is wonderful that patients can have such a tumor removed without surgery and therefore without side effects or scarring.
Determining the PSA level © jarun011 / AdobeStock
Leading Medicine Guide: But isn’t there also the option of radiotherapy?
Prof. Dr. med. Markus Düx: Radiotherapy for prostate cancer at an early tumor stage is usually like using a sledgehammer to crack a nut. Radiotherapy causes side effects; for example, bowel problems can arise years later – or lifelong bladder infections that flare up time and again. MRgFUS is a very good alternative here, because the tumor is destroyed using heat in a single treatment. The tumor is no longer present, side effects are the exception, and should the cancer reappear, it can of course be treated again with heat. This closes the loop, as we can also use MRI to monitor the scar in the prostate that forms after the heat treatment very effectively. The absence of tumor activity on MRI, combined with a drop in the PSA level, allows us to distinguish between a recurrence and a scar. This enables us to monitor the course of the disease and the outcome of the treatment.
Leading Medicine Guide: And how long does this MRgFUS treatment take?
Prof. Dr. med. Markus Düx: The treatment of prostate cancer takes three to four hours. It is a complex process, and the patient is under general anesthesia during the procedure. Patients then have a urinary catheter for two days – the treatment is carried out on an outpatient basis and patients go home with the catheter, usually with no side effects whatsoever. The catheter is left in place solely to prevent urinary retention. The ablation of the tumor causes the prostate to swell for a short time, which can compress the urethra and lead to urinary retention. The swelling usually subsides within two days, at which point the catheter is removed. The insertion of the urinary catheter is therefore purely prophylactic. Following treatment, the PSA level usually rises significantly, a sign that the tumor has been destroyed. Over the course of the following weeks, the PSA level returns to normal. The trend in the PSA level is an important marker that allows us to determine whether the tumor has been completely destroyed or whether a new tumor has developed. Of course, we also carry out MRI scans to provide patients with the necessary reassurance.
Leading Medicine Guide: How likely is it that you will actually detect such a carcinoma?
Prof. Dr Markus Düx: Very high! We have now reached a point where the diagnosis of prostate cancer via MRI is so reliable that we detect many cancers at an early stage. Just a few years ago, these would not have been detectable. This means that today we detect small cancers in the prostate that urologists cannot find at all using ultrasound. We have learnt a great deal in recent years and perfected MRI diagnostics of the prostate. This applies at least to the centers and radiology departments that carry out MRI scans of the prostate regularly, usually several times a day. We often see men with elevated PSA levels whose urologist has been unable to determine whether or not they have cancer. We are extremely precise in this regard, as studies also show: the rate of ruling out so-called significant prostate cancer is almost one hundred per cent; significant prostate cancers are those that require treatment, either through surgery or radiotherapy. However, we also diagnose most non-significant prostate cancers, i.e. early-stage cancers where the tumor is confined to the prostate. These cancers are the target for MRgFUS, where the tumor is destroyed by heat and a scar is monitored. From the perspective of many men, this is a far better alternative to active surveillance! With active surveillance, the cancer is monitored to see if it grows and becomes a significant cancer. So you keep checking the tumor on MRI scans and hope that it hasn’t changed. This can be gruelling over time.
Leading Medicine Guide: Why, then, is the procedure not standard practice in prostate treatment?
Prof. Dr Markus Düx: In the long term, we hope that our method will be approved as a service covered by health insurance – and that the statutory health system will reimburse these services at the outpatient level. However, there is still a long way to go, as we need more data for this, particularly in comparison with active surveillance. We know that sixty per cent of all men with early-stage prostate cancer (Gleason 6 and 7) do not develop a significant, treatable cancer over a ten-year period. That is why the concept of active surveillance exists. The cancer is monitored, and the aim is to identify those cancers that develop into significant cancer. These are treated, while the others are merely monitored. The idea behind focal therapy is that the number of significant cancers arising from early tumor stages can be significantly reduced. Ideally, a scar following focal therapy should be free of cancer cells; it follows that no significant cancer can develop from it. This is a different situation from simply monitoring a cancer, even if it is only at an early tumor stage. The likelihood of this cancer transforming is probably higher. However, this logic has yet to be proven; this requires comparative long-term studies, which do not yet exist. That is why MRgFUS treatment is not yet a standard in the treatment of prostate cancer for the foreseeable future! At the moment, we are still in the pioneering phase: we have demonstrated through studies that it works, and the approvals are in place. MRgFUS therapy for early-stage prostate cancer has now also been approved by the FDA in the USA. As we know, the hurdles for approving a new treatment method there are very high. That alone shows that our MRgFUS procedure has great potential – but it is not widely available. Partly because there are too few devices.
Leading Medicine Guide: There aren’t enough devices?
Prof. Dr. med. Markus Düx: HIFU therapy for prostate cancer has been around for a long time and is used by urologists in individual cases. Monitoring heat treatment with HIFU via real-time MR thermometry is a completely different ball game. To do this, you need a system like our MRgFUS, in which the highly focused ultrasound is integrated into the MRI. The technical and equipment requirements are enormous, and consequently so are the costs. Many centers are reluctant to make the investment, particularly as reimbursement for each case must be clarified individually. It is just like with other innovations in medicine: every beginning is difficult, and we have to overcome the hurdles. But I believe in its success, as I can see the results directly on the MRI scan and thus demonstrate the difference compared to a standard HIFU treatment. We can prove that we reach eighty degrees within the tumor because we measure and visualize the temperature via the MRI. This is the only way to systematically destroy the cells. We already know from our data that in around seventy per cent of treatments we have to adjust the parameters to adapt the therapy to the nature of the prostate tissue and achieve homogeneous, complete tumor necrosis. If you only reach fifty degrees in the tissue, the tumor survives and grows again. This is what happens, in a nutshell, with standard HIFU treatment.
Leading Medicine Guide: So HIFU treatment is not MRgFUS?
Prof. Dr. med. Markus Düx: Yes and no! HIFU is the process of generating heat. HIFU stands for high-intensity focused ultrasound, which many urologists use. However, it lacks MR monitoring – and therefore temperature measurement. Consequently, it is not possible to verify what is actually achieved. A defined amount of energy is delivered, and one hopes that the tumor is completely destroyed. However, this is often not the case: we make adjustments during HIFU treatments in almost seventy per cent of all cases. The prostate is usually very heterogeneous – scarring, benign tissue growths, inflammation, calcifications, and cancer cells alongside well- or poorly-perfused tissue repeatedly alter heat sensitivity. We must take this into account during treatment and regularly adjust the temperature parameters to achieve a good result. To do this, we need feedback on the temperature distribution within the tissue, and we need it while the treatment is still in progress! That is MRgFUS! We destroy the tumor completely and can see or measure this immediately. We can see where heat is generated throughout the prostate and can thus tailor the treatment precisely. At the same time, we monitor sensitive structures such as the neurovascular bundle to ensure that no undesirable side effects of prostate treatment occur.
Leading Medicine Guide: Why, then, aren’t there many more of these devices?
Prof. Dr. med. Markus Düx: This type of treatment for prostate tumors is still in its infancy. The FDA in the US has only recently approved MRgFUS for the treatment of prostate cancer patients, based on convincing study data. It is also the case that you have to be convinced of this approach – and you need a high degree of enthusiasm. In hospitals, cost factors are always calculated, and MRgFUS cannot yet be costed. But we believe in this technology of the future – my son Daniel included. We need to further develop the technology, and we need to offer it. And that is exactly what we want to do. It can make a huge difference. Acceptance of MRgFUS will come later.
Leading Medicine Guide: Through research work too, of course.
Prof. Dr Markus Düx: Exactly. There are quite different studies underway at Stanford University in California. That is the world’s largest MRgFUS center. But my son can tell you more about that.
Dr Daniel Düx: Even while studying medicine, I used to watch my father perform the treatments and then decided to go where the broadest spectrum of research on MRgFUS exists. Then came the offer to spend a year in the US and take part in MRgFUS therapies there. Stanford University has the world’s largest cohort of patients who have received MRgFUS treatment for a desmoid tumor. These are rare, aggressively growing soft tissue tumors that are often neither operable nor responsive to other therapies. I had been given the opportunity to participate in the scientific evaluation of this unique collection of cases. Such patients also exist in Germany, but there are no treatment options of this kind available. The therapies my father mentioned are all carried out at Stanford. In addition, there are MRgFUS treatments in the field of neurology, an area in which a great deal of research is being conducted at Stanford.
Leading Medicine Guide: MRgFUS in neurology?
Dr Daniel Düx: The procedure is already just as well established in neurology in the USA as, for example, the treatment of uterine fibroids is in Germany – specifically in relation to tremors. This refers to the tremor suffered by people with Parkinson’s disease, for instance. MRgFUS is, of course, also a symptomatic therapy in this field. At Stanford, MRgFUS is frequently used for this condition: it is effective in treating the symptoms of Parkinson’s disease and other essential tremor disorders that impair quality of life.
Leading Medicine Guide: How so?
Dr Daniel Düx: Tremors are usually treated with medication. The problem is that such medications have a high rate of side effects. Over time, increasingly higher doses are required, and the medication eventually loses its effectiveness. And it is not just hand tremors that limit people; many can only eat through a straw and can barely speak. This often leads to complete isolation. With MRgFUS, it is possible to selectively heat the area of the brain where the tremors in Parkinson’s are triggered, thereby alleviating the symptoms.
Leading Medicine Guide: Heat in the brain?
Dr Daniel Düx: Initially, only a small amount of heat. The problem is that this center is located quite centrally in the brain. If you try to stimulate this center with a needle, you have to pass through many structures, and you have to be very careful and exercise appropriate caution. MRgFUS, on the other hand, is something quite different: you pass the ultrasound through the brain, and only the point where the tremor originates is destroyed by heat. In fact, most people no longer experience any tremors at all after such treatment. It is wonderful to see how happy and relieved the patients are afterward.
Prof. Dr Markus Düx: This procedure is performed while the patient is fully conscious. So the patients are always awake.
Dr Daniel Düx: Exactly. They also need to be awake because the patients provide constant feedback: Is there still any tremor? Are there any side effects? We start with low temperatures, at which we only stimulate without destroying anything, but the effect lasts for a quarter of an hour. This is what makes the therapy so safe, because we only create a permanent lesion once we are absolutely certain we have the correct site. This is how the tremor is effectively treated.
Prof. Dr Markus Düx: The blood-brain barrier can also be opened using MRgFUS. A lot of research is being done on this at Stanford too.
Dr Daniel Düx: That is another fascinating topic. We were just talking about this: if drugs only take effect at high doses, it is because of the fairly impermeable blood-brain barrier. This means that the exchange between the blood and the brain is limited, which is why brain tumors cannot be treated as effectively with chemotherapy – because these drugs do not penetrate the brain well. To get past this barrier, one would have to choose a dosage that the patient could not tolerate.
Leading Medicine Guide: And where does MRgFUS come into play?
Dr Daniel Düx: Small air bubbles can be transported into the brain via the bloodstream, which are then made to vibrate in the area of the tumor using MRgFUS. These vibrations specifically open the blood-brain barrier for up to 24 hours, allowing drugs to penetrate and take effect within the tumor. This enables chemotherapeutic agents to be administered to the brain in low doses. Studies have shown that this works particularly well for brain tumors with a poor prognosis. This has enormous therapeutic and diagnostic relevance. It also allows mental health conditions to be treated with drugs where the active ingredients enter the brain due to the temporary opening of the blood-brain barrier. Many patients do not take these drugs at all because of the severe side effects – this method could therefore be a solution with great potential.
Prof. Dr Markus Düx: Many more indications will be added in the future – for example, to increase the effectiveness of drugs in inoperable pancreatic tumors. It will become clear over the next few years how else we can use MRgFUS. We are absolutely convinced that great successes await us here. Of course, we must wait until studies actually confirm all the benefits we are convinced of.
Leading Medicine Guide: When highly specialized doctors like yourself are so committed, success shouldn’t be long in coming.
Prof. Dr Markus Düx: You can see it in the patients: almost all of the treatments are outpatient procedures. You can see it immediately, especially in children! When a benign tumor in the hip joint, such as an osteoid osteoma, causes severe pain and restricted movement, we can use ultrasound to destroy the tumor. Without any X-rays, without a scalpel or disfiguring scars! We see the effect immediately after treatment! Children don’t feign symptoms, and as soon as they leave our therapy center, we can already see a completely different gait, as the pain is no longer there. In some cases we can cure the condition, in many others we can only alleviate the symptoms, at least for a certain period of time – this often helps patients a great deal, and the good thing about MRgFUS is that the treatments can be repeated. MRgFUS is a method that shows results in a short time with virtually no side effects.
Leading Medicine Guide: Which is, of course, an incentive.
Prof. Dr. med. Markus Düx: Certainly. Many patients come back. If, for example, we manage to temporarily relieve people’s back pain – then the patients return when the pain reappears. You don’t need an injection or a needle, and you achieve significant results. That’s the great thing about the method – for me as a therapist too.
Dr Daniel Düx: You mustn’t forget that we also treat very rare tumors with MRgFUS, which often grow near nerves. This causes severe pain and muscle weakness. Until a few years ago, these tumors were treated surgically. I worked in surgery for just under two years and saw this first-hand: a great deal of tissue is often removed during such operations. If such tumors can be removed non-invasively, that is a major advance. And if MRgFUS allows us simply to ensure that chemotherapy drugs can be administered in smaller doses, thereby minimizing side effects, this is a huge advantage, particularly for young patients.
Leading Medicine Guide: We would like to thank you very much for the interview – and wish you every success in seeing MRgFUS successfully applied in many more areas.
Further information is available on the profile page of Prof. Dr Markus Düx. You can also contact this renowned specialist directly via this page.
