Title and Logo

Rinckside
ISSN 2364-3889

Rinck PA.
MR Imaging: Quo Vadis?
Rinckside 2019; 30,3: 5-8.



Read the Print Edition
(pdf)


Also published in two parts as:
Maverinck –
MR Imaging: Quo Vadis?
and: What lies ahead for MRI contrast agents?
22 and 28 May 2019.
Aunt Minnie Europe


The version published in Aunt Minnie Europe was shortened and edited by AME.


This column is based
on a lecture given to
an invited audience
in Milan, Italy,
in October 2018
and as the Opening Lecture at
Contrast-Enhanced Biomedical Imaging –
Standing at the Crossroads:
40 Years of
MR Contrast Agents

in Mons, Belgium,
in May 2019.



MR Imaging: Quo Vadis?

uring the second part of the twentieth century, four new medical imaging modalities were established aside of conventional x-ray (Roentgen) imaging: ultrasound, computed tomography, radioisotope imaging and magnetic resonance imaging. These were great and exciting steps forward in science and medicine.

Paul C. Lauterbur, the fa­ther of MRI, died more than a decade ago. Interestingly, he didn't believe too much in high-tech medicine and re­fused at the end of his life to undergo dialy­sis when his kid­neys were failing. Nobody and noth­ing would persuade him. He lived another two years and nine months – without machines and medical terror. Thirty years ago I might not have understood this decision, both as a human being and as a medical doctor; today I do.


Instrumentation

MR imaging became a clinical tool in the 1980s and has not much changed since the turn of the millennium; the technique re­mained the same, although the appearance of the machines might be different and hard- and software became more sophisticated.

Diagnostic imaging with magnetic resonance has developed into a stable technology and is an important part of medicine and the health consumer market. There is a wide range of machines, offered by numerous hardware manufacturers.

Today, there are approximately 50,000 whole-body MR machines worldwide. Most machines per country are found in the United States, followed by Japan, in the meantime also China, Germany, Brazil, Italy, and South Korea. To provide suffi­cient medical care for a population, 12 to 15 ma­chines per one million inhabitants suffice. In coun­tries with over-saturated markets there is a high risk of overuse and abuse of MR imaging.

Despite the commercial availability of 3.0 Tesla equipment for more than 15 years, the majority of routine imaging is done at 1.5 T; about two thirds of all machines in the United States and Europe operate at this field strength. Gradient strength is already at its limit, imaging at higher fields is of unproven general advantage and patients suffer from the noise of 3T machines and unpleasant side effects at ultra-high fields [1]. There is also a lack of reliable, non-biased out­come studies on which field strengths and technologies are best suited for routine and everyday clinical imaging. The hard­ware industry and other circles block such studies.

ruler black

Novel developments introduced by non-medical actors may even lead to actual reduction in patient well-being.

ruler black

People from out­side medical care (in this case, in­dustry representatives and health administrators) have become more influen­tial and fi­nally taken over decision-making. The users, the radiologists, are often simply pushed aside. Medicine is being increasingly commercial­ized with limited respect for the human factor. Novel developments introduced by non-medical actors may even lead to actual reduction in patient well-being.


Cultural Differences

The cultures of these markets are different. Chinese MR sites, for instance, are less scientific or – better – pseudo-scientific players, but rather more patient and diag­nostic focused. Of course, these countries are also consumer markets which reflects in their structure.

As mentioned before, in Europe and North America, one finds 15-18% 3 Tesla machines and about 66% 1.5 Tesla ma­chines; in China the percentages are approxi­mately 8% 3 Tesla, 45% 1.5 Tesla, and nearly 50% lower than 1.5 Tesla – a far healthier distribution for routine diagnostic necessities.


Changes within Societies

The human factor plays a major role in the changes occurring in radiology: A new generation of radiologists starts climbing the career ladder. Many of them grew up pampered in comfort and affluence, exposed to the digital revolution in a period when average quality of school and university educa­tion declined. They lack critical insight. Attached to playing computer games, digital imaging technologies are extremely attractive to them. On the other hand, lower working hours and higher salaries are also important to them.

During the last twenty years the generation gap has deepened to a chasm, and both younger medical doctors and older ones complain about of a mutual lack of comprehension of their respective worlds. The suitability of candidates for the existing, partly very demanding health system is de­creasing. By many sociologists and psy­chologists they are seen as a possible threat to the existing sta­ble society and workplace structures [2]. On a global scale, in particular for the operation of specialized MR equipment, radiologists will partly be replaced by medical doctors from other disciplines, e.g., by oncologists, neuroscientists and nuclear medicine specialists.

It is interesting to see that the sales representa­tives of some companies seem to have reacted to these changes, but not company management and developers – it’s easier to deal with the existing present that with an unknown future. Companies target their potential younger customers with completely different marketing methods than twenty years ago.

Another important point is the change of age distribution in the population in Japan and numerous European countries. This different patient clientèle requires adaptation of MR machines and examinations.


Simplistic Academic Research

Research, fashions and hypes are a fundamental element of MR equipment and contrast agent sales not only in Europe and North America. The credo of "publish or perish" has left a ter­rible battlefield in the papers on MR imaging. Checking the contents of radiological journals of the last 30 years shows that few learned pa­pers are relevant. Studies reveal that 90% and 95% were simply wrong, sense- and useless; still, they have influenced the use of magnetic resonance and medicine at large. This will not change in the near future, because climbing the entire career ladder in Europe and North America is based on this spiel – as well as major commercial interests, for instance, the annual congresses of the European Society of Radiology and the MR societies [3, 4].

Fashions which came and went again during the last 35 years were, for instance, MR spectroscopy – the combination of high-resolution imaging and depiction of metabolism. MRS has more or less disappeared from the stage: Here today, gone tomorrow ...

Another idea in the earliest times of MRI, even before, was tissue characterization by in vivo relaxation time measure­ments. This was 40 years ago and the methods had gone out of date already in the mid-1980s: they didn’t work in a clinical environment. More than 20 years later they were re-invented as “MR fingerprinting” and “biomarkers”. Even dressed in new clothes they cannot be validated in independent trials and are mostly inadequate and deficient in precision and accuracy [5, 6]. Still companies jump on this bandwagon because they don't have anything novel to offer. Outdated ideas are repacked and sold with marketing gags as revolutionary developments. Here today, gone tomorrow.

Functional MR imaging (fMRI) was invented in the early 1990s, followed by MR tractography and the 1-billion-euro Connectome Project [7]. All are prone to disappoint. The most common software packages for (fMRI) analysis resulted in false-positive rates of up to 70%. These results question the valid­ity of some 40,000 published fMRI studies and may have a large impact on the interpretation of neu­ro-imaging results [8]. Here today, gone tomorrow ...

Many people believe that numbers (data) are the truth. Many people do not understand how the numbers were acquired and what they stand for. Nature, biology and medicine are more complex and don't care much about numbers.

For decades the euphoria over new offspring techniques of MRI has been reliably followed by disillusionment. Exaggerations are and were widespread. There has been progress but much of the trust of the people who actually count on the developers and researchers was lost. They were taken on a constant roller coaster ride into nowhere. For some time, new developments in MR imag­ing have been merely apps and gadgets.

The latest hype, an exploding volcano, is “artificial intelligence”. AI will come on the MR market; it’s business value is enormous. But AI is mindless, lacks consciousness and curiosity. These are fundamental flaws which can’t be overcome, distinguishing it from real intelligence. The human mind must be critical; artificial intelligence won't be. The human mind is able to consider, reconsider and doubt. AI won't. But human laziness will rely on it anyway. Let’s see what happens to it.

Still, it’s not a disruptive technology for MRI, but just another still very immature app [9].


Disruptive Technologies

However, real disruptive technologies will hit MR imaging as well as contrast agent use and development, for in­stance ultrasound and in vitro tests. Soon we will have cheap smartphone-size ultrasound equipment that will revolutionize and shuffle the imaging market. Most likely, we will be moving to­wards earlier diag­nosis and management, wherever possible, which implies ultrasound, op­tical or some other sort of high spatial resolution imaging technique, but not, for instance, ultra-high field MRI.

Manufacturers are first and foremost interested in money; this is their raison d'être, the purpose that justifies their existence – and, basically, there is nothing to criticize about it. The manufacturers are increasingly faced with the question whether new ideas have any clinical and commercial relevance. They still can try to invent some “relevance”. In general, MR research will move away from developing new pulse sequences or new coils; this will even hold for academic research, perhaps with the exception of superconducting materials.


MR Contrast Agents

What will be the clinical need for imag­ing agents when in vitro diagnostics will begin to pro­vide useful information? If you know the patient has xxx from their in vitro analysis what is the role of imag­ing and what type of imaging will provide the clini­cal manage­ment information needed?

I have been involved in MR contrast agents since 1981, for nearly 40 years. The main question is if there is room for a new agent today or in the future – and if so, how and why – when the remaining Gd chelates are so uni­versal in terms of their application. Gadolinium extra-cellular fluid agents are the only ones that have grown into a realistic market size. Thus, it will be extremely dif­ficult to develop a new MR contrast agent that fulfills unsatisfied clinical needs and has a large enough range of application to justify development.

The disaster of the nephrogenic systemic fibrosis (NSF) has left deep scars in the industry. Still, gadolinium agents are safe contrast agents when properly applied, far safer than, for instance, x-ray contrast agents. I believe it's unlikely that you can find some­thing better than Gd that ticks all the boxes in terms of applications, higher safety profile and po­tential market size. Getting the market to embrace a new agent will be a slow process as radiologists are conservative and it will take years to grow the markets [10, 11].

As we have seen, for instance, with Novartis, the era of mass production in the pharmaceutical industry is claimed to be over: so-called “personalized medicine” is replacing “one-size-fits-all” pills. I doubt if this holds for contrast agents. It will be difficult to isolate unmet clinical needs, and the cost and approval processes are exorbitant. Today's contrast agents on the market were developed for field strengths below 2 Tesla; their relaxivity diminishes with increasing magnetic field strength. In the unlikely case that imaging will be performed at ultra-high fields of 7 Tesla or even higher, new classes of contrast agents must be developed for research applications, mostly for animal experiments. Again, costs will be prohibitive.

An interesting approach to new paradigms and elements is the production and distribution of already approved agents that were withdrawn from the market before the gadolinium phobia, such as Mn-DPDP for pancreas, liver, and cardiac applications and ferumoxtran for the enhancement of metastases. In these cases approval is relatively simple and distribution might be efficient even by small companies. Thus, new “old” players have entered and will enter the market. Gone yesterday, back here today?


spaceholder blue

Additional Commentaries and References

1. Rinck PA. MR safety update: Why we may not need a 20-Tesla MRI machine. Rinckside 2016; 27,6: 13-15.
2. Rinck PA. Generation Y and the future of radiology. Or: Is Generation Y outsourcing cerebral activities to smartphones? Rinckside 2012; 23,7: 13-15.
3. Rinck PA. A new paradigm for medical papers. Or: Why we need less trash and more substantial papers. Rinckside 2014; 25,2: 3.
4. Rinck PA. The calamity of medical and radiological publications. Rinckside 2015; 26,8: 21-22.
5. Rinck PA. Relaxing times for cardiologists. Rinckside 2015; 26,2: 3-5.
6. Rinck PA. MR fingerprinting returns to radiology – and hopefully disappears again. Rinckside 2015; 26,5: 13-14.
7. Rinck PA. Mapping the biological world. Rinckside 2017; 28,7: 13-15.
8. Rinck PA. Debacles mar “Big Science” and fMRI research. Rinckside 2016; 27,7: 17-18.
9. Rinck PA. Some reflections on artificial intelligence in medicine. Rinckside 2018; 29,5: 11-13.
10. Rinck PA. Gadolinium – will anybody learn from the debacle? Rinckside 2015; 26,9: 23-26.
11. Rinck PA. Paradigm and element shift in MR contrast agent applications. Rinckside 2017; 28,1: 1-2.

See also: Rinck PA. Contrast Agents. in: Rinck PA. Magnetic Resonance in Medicine. A Critical Introduction. 12th ed. BoD, Norderstedt, Germany. 2018. ISBN 978-3-7460-9518-9. pp. 231-255.


spaceholder blue003 spaceholder blue003

VirtualCampus

00-f1

00-f2

00-f3

00-f4

00-f1

00-f2

00-f3

00-f4

00-f1

00-f2

00-f3

00-f4

00-f1

00-f2

00-f3

00-f4

00-f1

00-f2

00-f3

00-f4

00-f1

00-f2

00-f3