Imaging: a discovery tool in obstetrics and gynecology

Sir Robert Hutchison. Imaging is now, more than ever, a powerful instrument for scientific discovery that has, and will continue to change the practice of medicine. Our society (ISUOG) and this journal were founded at a crucial time in the evolution of obstetrics and gynecology, when the information provided by imaging with ultrasonography had not yet found a natural venue for scientific discourse. Diagnostic imaging had been traditionally conducted in departments of radiology. In the early days, the pioneers of ultrasonography in obstetrics and gynecology courageously traded the forceps and scalpel for a seemingly less glamorous tool: an ultrasound transducer1-46. This choice demanded vision to conceive what ultrasonography could become, creativity to solve the challenges of a developing technology, imagination to discern normal from abnormal anatomy in the early images, and perseverance in the face of those who forecasted: ‘forget it, it will never work!’ (a personal communication from a famous professor of anatomy). For centuries, imaging was the domain of the artist. The challenge of displaying a three-dimensional object on a two-dimensional surface is one of the oldest problems in art, and one for which there is no unique solution47. This task is also that of ultrasonography. While art moved from realism to abstraction, ultrasonography evolved in the opposite direction; Pablo Picasso, in a series of eleven drawings, demonstrated that it was possible to represent the essence of a bull with a few lines defining the creature—an elegant ‘compression algorithm’ (Figure 1). In contrast, the pioneers of obstetrical ultrasonography had to see a fetal head and measure the biparietal diameter from only two echoes displayed in images obtained by the amplitude mode (A-mode) (Figure 2)9, 48. Technology has since made it possible for prenatal imaging with ultrasonography to evolve to ‘realism’ (Figure 3)41, 44, 49. Pablo Picasso's representation of the essence of a bull (1922). Reproduced with permission. © Succession Picasso/DACS 2005. The biparietal diameter (BPD) by A-mode ultrasonography. Three-dimensional rendered images of the fetal face. (a) Surface rendered mode. (b) Same volume dataset rendered using the maximum intensity projection mode to demonstrate the facial bones. Our discipline consists of the visual display of anatomy and pathology and, therefore, is grounded in the oldest of all basic sciences: gross anatomy. It is not difficult to understand why physiology and experimental pathology would have seemed more attractive to members of our scientific community in the latter part of the 20th century. Yet, scientists and artists alike have revered the dictum that ‘form follows function’. While made popular by the American architect Louis Sullivan50, the roots of this idea are present in the Origin of the Species, as Darwin reflected on the evolutionary forces that resulted in differences in anatomical shapes to ensure adequate function in various environments51. The most fundamental advance in biology in the 20th century was the elucidation of the structure of DNA52, which launched the molecular age and eventually led to the completion of the Human Genome Project53, 54. Watson and Crick acknowledged that they could not have solved the problem of the structure of DNA, and hence the genetic code, without an image. This image, the X-ray crystallography of DNA obtained by Rosalind Franklin, contained the critical data suggesting a double helical structure55. Therefore, biochemistry was informed by the study of form. The most powerful and useful imaging technique in obstetrics and gynecology has been ultrasonography, hence the name of our society and our journal. Ultrasonography has provided information about anatomy, growth and pathology. Also, it has been a rich source of functional information. For example, Doppler interrogation of the umbilical arteries can identify placental disease56-58, Doppler of the uterine arteries identifies patients at risk for the development of pre-eclampsia/small for gestational age fetuses31, Doppler of the middle cerebral artery can be used to identify cerebral blood flow redistribution and fetal anemia59-62, and Doppler of the venous system provides evidence of cardiac failure63-73. Science is grounded in the observation and measurement of object properties47. Imaging instruments and modalities (e.g. the microscope, the telescope, the X-ray machine, magnetic resonance imaging (MRI), and even a simple photographic camera) extend the range of natural vision and make it possible to observe and measure properties that may not be accessible by natural means47. For example, ultrasonography depicts images based upon the composition of tissues, which alter the propagation and reflection of sound. However, there are other means of examination of the same structures in obstetrics and gynecology. Figure 4 shows images of the Milky Way, obtained by exploiting different object properties74, 75. Obstetrics and gynecology has used radiography, ultrasonography and MRI to examine different object properties and, indeed, an immediate challenge is to merge information derived from the examination of the same structure, but derived from the interrogation of different object properties. For example, it is now possible to merge information from computerized tomography (gross anatomy) with positron emission tomography (biochemistry and physiology) from the same subject76-79. Thus, anatomy and physiology are no longer divorced. For example, while MRI is widely used for anatomical imaging, functional MRI (fMRI) provides information about oxygen consumption. When an area of the brain is hyperactive, oxygenated blood is delivered, and this can be recorded with fMRI. In adults, this technology is being used to address questions that were once considered outside the realm of the imaging specialist. Functional MRI has the potential to change society's approach to truth verification and lie detection80-83. In an experimental paradigm designed to examine the differences between truthful answers and deception, Langleben et al.80 found that subjects who gave truthful answers demonstrated increased activity in the visual and motor cortex, while those who were deliberately deceptive showed activation in areas of the anterior cingular cortex which have been thought to monitor error and attention. The authors concluded that it took more mental energy to lie than to tell the truth. While the interpretation of these fascinating experiments remains controversial, neuroscientists continue to move ahead, trying to detect imaging patterns associated with good humor84, false or truthful memories85, active suppression of memory86 and violent criminal behavior87, as well as mood disorders88. Imaging can also be used to monitor the response to therapy89. A new discipline, neuroeconomics, has emerged, and companies are allegedly using this technology to assess the preferences of prospective consumers (Coke or Pepsi?)90. In the fetus, this technology has been used to identify the areas of the brain that are active after acoustic or visual stimulation91-94. We expect that with technological advances we will be able to understand neurodevelopment of the fetal brain and details of the biology of cognition. Images of the Milky Way obtained by the National Aeronautics and Space Administration (NASA)74 by exploiting four object properties: (a) light within the visible spectrum; (b) gamma rays; (c) radio waves; and (d) the infrared spectrum. Image 4a reproduced with permission of A. Mellinger75, University of Potsdam, Germany. The major new frontiers in imaging are molecular, functional, cellular and genetic imaging95. It is now possible to use non-invasive imaging to monitor complex events at the cellular and subcellular levels. For example, we have used ultrafast microscopy to record changes in oscillations in the level of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), calcium waves and reactive oxygen metabolites by neutrophils and monocytes of normal pregnant women and those with pregnancy complications96, 97. We have been able to gain fundamental insights about the physiology of the immune system during pregnancy that had eluded studies based on physiologic and biochemical changes alone. It is now possible to tag bacteria with fluorescent probes and monitor their progress as they invade the host, while examining the host response to microbial invasion98, 99. The potential for non-invasive molecular imaging to reveal important and relevant mechanisms of disease in reproduction is now more real than ever. What does this all mean? I believe that our society needs to commit itself to imaging in obstetrics and gynecology and reproductive sciences rather than restrict itself to ultrasonography. While we have informally done this by providing a scientific forum in our annual congress and having our journal welcome other imaging modalities, I think that the time has come to be explicit. I propose that we encourage and embrace all imaging modalities providing information about the fundamental nature of reproductive processes, improved diagnosis, prognosis and treatment of our patients. This will require more than a change in title. A deliberate commitment of our leadership and the recognition that ‘imaging in reproduction’ is as important as our traditional subspecialties will be needed. This new effort will require a multidisciplinary curriculum. The financial and healthcare policy implications of this endeavor are formidable. If bringing ultrasound machines into departments of obstetrics and gynecology was a challenge, the implementation of training programs of imaging in reproduction will tax our imagination, skills, and resolve. What are the risks of not undertaking this challenge? Ultrasonography has contributed more than any other tool to improve the care of patients in obstetrics and gynecology. If we do not embrace the new imaging technologies, we will not be able to meet the expectations of our patients and the obligation that we have contracted with society as fiduciaries of the healthcare of women and their unborn children. The following material is available from the Journal homepage: http://www.interscience.wiley.com/jpages/0960-7692/suppmat/index.html (restricted access) The Ian Donald Lecture, delivered by Roberto Romero. The PowerPoint presentation contains specific instructions for downloading the audio and video clips. 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