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Editorials |
1 From the Radiological Society of North America, 820 Jorie Blvd, Oak Brook, IL 60523. Received January 5, 2007; final version accepted January 8. Address correspondence to B.C.L. (e-mail: blentle{at}shaw.ca).
In real life, research is dependent on the human capacity for making predictions that are wrong, and on the even more human gift for bouncing back to try again. This is the way the work goes.Lewis Thomas (1)
As a species, we seem to be fond of reflection at signal times in life. The New England Journal of Medicine, at the dawn of this millennium, published a listing of what its editors considered to be the notable medical advances of the preceding millennium—and, of note, imaging was included (2). There have also been recent publications documenting those scientific questions that remain unanswered at the dawn of the 21st century. The journal Science celebrated its 125th anniversary by featuring "125 Questions: What Don't We Know?"—a fascinating list of problems capable of being addressed by the scientific method (3,4). A former editor of Nature similarly published a monograph entitled What Remains to be Discovered (5). The text is based on the Pegram Lectures at Brookhaven National Laboratory.
Kennedy and Norman (3), in introducing "What Don't We Know?" in Science, pointed out that the essay was not "a forecast of what science might achieve" but might be thought of as a survey of scientific ignorance, while Siegfried (4), in introducing the questions, described them as "opportunities to be exploited."
These attempts do, of course, contain an oxymoron (in that they concern the knowability of the unknown). Moreover, in the progress of scientific discovery during recent centuries, investigators who changed the course of science often did so without a specific goal in mind. Röntgen was not aware of x-rays when he was experimenting with cathode rays any more than Einstein was primarily dissatisfied with Newtonian mechanics in arriving at his theory of relativity. In one case, serendipity was at work, in the other, a singularly powerful imagination.
Nevertheless, if it is conceded that some fundamental paradigm shifts in science are unlikely to be anticipated, it may be helpful on occasion to take stock of the progress of research in groups of related disciplines. The result may be both a benchmark for science in evolution and a potential inspiration for the individual investigator looking for her or his next challenge.
The radiologic sciences as applied to the study and treatment of human disease are at a watershed. After decades of growth based on the introduction of new technologies (computed tomography [CT], magnetic resonance [MR] diagnosis, positron emission tomography [PET], image-guided treatments, hybrid technologies, etc), it seems we are approaching what we now understand to be limits to the physical energies that can be used to interrogate tissue. Whether this will prove to be the case or not is a moot point. Now is therefore an appropriate juncture at which to take stock of research in the radiologic sciences as applied to medicine and where it is headed conceptually.
At this same time, the Research and Education (R&E) Foundation of the Radiological Society of North America is approaching its 25th anniversary. It occurred to the Board of Trustees of the Foundation that, as part of an initiative to focus the attention of the membership of the Society on the role and importance of research in the future care of patients and on the practice of the radiologic specialties, it might be a useful and even thought-provoking exercise to challenge members to contribute to a listing of some of the relevant questions our disciplines might hope to answer with research in the radiologic sciences over the next 1 or 2 decades.
Submissions were invited at the R&E Foundation's 25 Questions Web site, and, during the course of 9 months, 89 submissions were received from 56 contributors. After review and merger and consolidation for overlapping questions, 25 questions were finally selected. This result is reported here with acknowledgments given to the most important people—those contributing to each question. We also thank the other contributors whose ideas did not quite make the list.
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Will functional imaging, in the context of image fusion, lead to tumors being treated as metabolic entities rather than simply as masses, thus allowing a firmer distinction to be made between benign and malignant lesions and the relative effectiveness of their treatment?
Joe Y. Chang, MD, PhD
Caroline Chiles, MD
Peter Choyke, MD
Ronald H. Gottlieb, MD, MPH
Edward Graves, PhD
Jon A. Jacobson, MD
Billy W. Loo, Jr, MD, PhD
How might we detect asymptomatic vascular lesions and then synthesize this information into a risk estimation that will allow us to predict and thus prevent the occurrence of vascular events in those most at risk?
Mark Hiatt, MD, MBA
Stephen Zink, MD
Can the delivery of site-specific or receptor-based drug and gene therapies, as well as their effectiveness, be imaged and measured while exploiting the genetic characterization and risk stratification data provided by the Human Genome Project to optimize the development of novel imaging agents?
Barry B. Goldberg, MD
Ronald H. Gottlieb, MD, MPH
Ravi S. Prasad, MD
Kitt Shaffer, MD, PhD
Might we devise methods to determine the effect of imaging on the morbidity and mortality of specific population groups and therefore evaluate the cost-utility of diagnostic imaging in specific contexts?
Deborah Baumgarten, MD, MPH
Are there fundamentally different ways from those now used to evaluate, view, process, and diagnose disease by using the extremely large and increasingly highly resolved multidimensional imaging data sets that medical imaging now produces? Moreover, can this process use the world's database of normative data and normal variants, as well as the evidentiary basis of medical practice, to produce a practical but informed diagnostic outcome while optimizing radiologist productivity by using computer decision support? May these tools be used to measure radiologist performance, as well as reduce physician error, while enhancing the role of the radiologist as consultant in applying diagnostic algorithms?
Walter E. Drane, MD
Ronald H. Gottlieb, MD, MPH
Gowthaman Gunabushanam, MD
Curtis P. Langlotz, MD, PhD
Levon N. Nazarian, MD
J. Kevin Smith, MD, PhD
May the precision of radiation dose delivery be exploited in combination with systemic treatments to synergistically treat local cancers, as well as their regional metastases? Might we gain some insight into the mechanisms of action of such treatments by a better understanding of the molecular determinants—for example, those that allow some lymphomas to be controlled with a radiation dose as low as 20 Gy, while other tumors may require doses in excess of 70 Gy?
Scott R. Floyd, MD, PhD
Eduardo G. Moros, PhD
Peter Choyke, MD
Can the radiolabeling of potential pharmaceuticals be used to measure and image the kinetics and in vivo biodistributions of the molecules in question and thus accelerate drug discovery and development while lowering the costs of clinical trials?
Peter Choyke, MD
Is it possible to develop imaging techniques to identify, by using noninvasive means, microscopic cancers at the stage of single cells or small clusters of malignant cells, either in the organ of origin or remote from the primary tumor—thereby improving the chance of cure?
Peter Choyke, MD
Christopher Ian Flowers, MBBS
Can percutaneous radiofrequency and noninvasive focused ultrasound energies, with or without other measures, be harnessed to effectively cure localized, early stage diseases and alleviate the pain and suffering caused by more advanced disease?
J. Kevin Smith, MD, PhD
Is it possible to use imaging tools to determine important clinical information noninvasively? For example, which patients with prostate cancer will either benefit from therapy or may be safely observed, and which lesions (eg, those in the kidney) need biopsy? Similarly, is it possible to target biopsies more effectively by using image guidance? Not least, can molecular markers be imaged, at the preclinical and clinical or early clinical stages of disease, to identify different cell types in order to spare some patients the need for biopsy?
Peter Choyke, MD
Ronald H. Gottlieb, MD, MPH
Deborah Levine, MD
Jonathan B. Kruskal, MD, PhD
John Stuart To, MD
Joan C. Vilanova, MD
Might reliable methods of image-guided measurements of tumor perfusion and angiogenesis be applied to tumors to measure response to therapy and, moreover, might these or other markers then be used to assess treatment response in the short term, allowing the early introduction of alternative treatment protocols in patients not responding?
Abraham H. Dachman, MD
Barry B. Goldberg, MD
Jon A. Jacobson, MD
Sheela D. Konda, MD, PhD
Is it appropriate for radiology to evolve from a "diagnostic" specialty to a "prognostic" specialty involving a synthesis of risk markers from imaging and other data to provide a global risk profile for patients and thus predict patient outcomes? How shall we measure the cost-utility of such strategies?
Walter E. Drane, MD
Ronald H. Gottlieb, MD, MPH
Might there be physical principles or energies or even behaviors of subatomic particles that we have not yet exploited for medical imaging and that will be the technologies of the future? Equally, in the context of radiation therapy, will more cost-effective proton/ion therapy systems such as those using laser-plasma accelerators replace electron/photon therapy systems to become the treatment modality of choice for radiation oncology?
Barbara Y. Croft, PhD
Ronald H. Gottlieb, MD, MPH
Charlie Ma, PhD
Antonio Carlos A. Westphalen, MD
Will functional imaging be used to image neural activity at greater temporal resolution to link diseases of brain structure and organization with abnormalities in brain function, leading to insights into matters as diverse as neuroses, psychoses, autism, behavioral disorders, the psychopathic mind, and even the nature and purpose of dreams?
Marilyn Goske, MD
Christopher Hess, MD, PhD
Stephen E. Jones, MD, PhD
Elizabeth A. Krupinski, PhD
Srikanth Narayanaswamy, MBBS, MRCPCH
How may we best integrate and display radiologic imaging data with all the other data into the electronic patient record, and will all these data actually improve diagnosis and treatment without causing information overload? Will it then be possible to overcome all the barriers to privacy, as well as business competition, data content, and redundancy, to seamlessly allow imaging data to flow with the patient, not the institution?
Walter E. Drane, MD
Elizabeth A. Krupinski, PhD
Can the sensation of pain and its determinants be imaged and localized anatomically as pathophysiologic events—either centrally or peripherally or both?
Josh B. Moosikasuwan, MD
What are the potential consequences of the now widespread increases in exposure to ionizing radiation from medical applications such as multidetector CT and PET/CT examinations? Moreover, what is the effect of the increasing use of ionizing radiation in diagnosis on the public health, and how much of such an effect, if any, is acceptable to society? Might this be a factor in the future use of alternative technologies employing smaller quantities of or no ionizing radiation, and do we need to know more certainly that MR imaging examinations carry no risk?
Vikas Gulani, MD, PhD
Eoin C. Kavanagh, MD
Martin R. Prince, MD, PhD
Might we develop standardized terms for use in radiology that are universally adopted as well as effectively linked to other patient findings, thus creating a lexicon to describe a patient's clinical status and potential disease states? Will this lead to the traditional narrative radiology report or consultation being replaced with graphic data that incorporate images from several sources, as well as integrating other relevant clinical data?
Peter Choyke, MD
Andrew Dwyer, MD
Ronald H. Gottlieb, MD, MPH
Will personalized medicine be based on imaging, and, in that context, as the use of image-guided therapeutic procedures continues to grow, how may we foster the further development of radiologists as health care providers rather than merely as consultants?
Gary J. Becker, MD
Levon N. Nazarian, MD
Might imaging be used to detect and quantitate early articular cartilage or bone damage or deterioration, both structural and biochemical, as a basis for improved management of disorders of the bone and joint?
Jon A. Jacobson, MD
Brian C. Lentle, MD
Is it possible to better select (on the basis of newly defined skills) and educate radiology residents, bearing in mind that in the future the need for lifelong learning may involve simulation, as well as hands-on, interactive, or entirely online learning in continuing medical education and professional development? Equally, might there be a leadership role for radiology in the curricula of medical schools, something that is important both in its own right as well as in resident selection? At the same time, can we develop methods of learning for adults in an increasingly complex educational, technical, and research environment that can be reconciled with the need for individuals to spend adequate time with their family, be responsive to the needs of society, and participate in the public affairs?
Judith Korek Amorosa, MD
Richard B. Gunderman, MD, PhD, MPH
Kitt Shaffer, MD, PhD
Barbara Weissman, MD
Is it possible to identify and spatially localize the stem cells of solid tumors?
Ernest M. Scalzetti, MD
Might there be a future role for medications, such as an angiogenic factor, to be delivered locally in patients with lower extremity arterial disease so that such medications might induce the formation of collateral vessels, and can this effect be imaged?
Zubin N. Balsara, MD
Are there current applications of CT that would be better performed by using operator-independent, multitransducer ultrasonographic examinations?
Neville Irani, MD
Are there new MR imaging techniques that might improve the spatial, temporal, and spectroscopic resolution of MR imaging to allow high-resolution spatial-temporal, functional, and metabolic imaging in practical examination times, and is it possible to develop an "all-in-one" diagnostic and therapeutic MR imaging contrast agent for diagnosing, characterizing, and treating tumors or other diseases?
J. Kevin Smith, MD, PhD
Robert M. Steiner, MD
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The listing is not intended to be prescriptive in terms of future directions, and it will, we hope, rapidly become outdated. At the same time, it is important to recognize in this context the need to provide for paradigm shifts that cannot be readily anticipated, as suggested above. Indeed, there is discussion in the physics community, as an example, about the need for small but finite amounts of research support to be available to encourage investigation in contexts that are of extremely high risk in possibly overturning fundamental concepts or yielding no return at all but are potentially of high gain in terms of moving a discipline to a new plane (7).
Alfonso X of Castile, a medieval musician and patron of astronomy, commented that, "if the Lord Almighty had consulted me before embarking upon creation I would have recommended something simpler" (8). Nature indeed is complex in ways Alfonso X could not even begin to have imagined. The diversity and complexity of the questions speaks to that. The secrets of nature are not easily disclosed, and that is part of the wonder at the natural world we can share.
It might be of interest to measure correlation coefficients between this list and journal publications in the radiologic sciences during the next decade or two. Perhaps it will be more important, however, if the list makes each of us take stock of what we do, how we might do it better, and what potential each of us has to advance radiologic science either at the bench or in our support for research—both in our individual departments and in the societies we support. Not least, it may lead us to reflect on how fortunate we are to have had a small part to play in the growth of our amazing disciplines. The R&E Foundation invites reader comments on the results of the 25 Questions Project. Comments may be sent to the Foundation by e-mail at R&EFoundation@rsna.org, and they will be shared with the R&E Foundation Board of Trustees.
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