The last several decades have seen remarkable advances in the clinical neurosciences, with some of the most remarkable achievements related to neuroimaging. Given the current depth of knowledge about the brain, it is difficult to appreciate that barely 300 years ago this organ was almost a complete mystery, particularly as to its function. While the brain has been recognized as an “organ” since antiquity, no functional role was ascribed to it until the early 1600s, when Descartes placed the “soul” in one of its small parts, the pineal gland.[1] Prior to this intriguing, but erroneous, concept, much more functional importance had been attributed to the fluid in the ventricles than to the brain itself. Descartes’ non-scientific attribution was, fortunately, quickly followed by the much more rigorous description of the structure of the brain by Thomas Willis in 1664.[2] While Willis’ application of the scientific method to the brain was seminal, the primitive scientific tools available at the time limited his direct observations to anatomy, and gross anatomy at that, which in and of itself does not convey function. Despite little direct evidence, Willis began to argue that mental functions reside in the brain, as do certain diseases such as epilepsy. The scientific tools necessary to prove his assertions by actual observation of physiology, molecular biology, and other “functional” aspects of the brain were still several centuries away.

The title of this book refers to two components – science and imaging. Science, by usual definitions, has two aspects: a body of knowledge and a methodology. The former is the organized body of information that we have gained about ourselves and our environment by rigorous application of the latter. The scope of the scientific body of knowledge is vast; indeed, it is the total knowledge we have of our universe and everything in it. However, there is a restriction on this knowledge: it must have been derived through the scientific method. This carefully circumscribed method uses observation and experimentation in a logical and rational order to describe and explain natural phenomena. Scientific imaging, which is the specific topic of this presentation, likewise has two aspects: it is a body of knowledge – knowledge gained from the application of imaging – and a scientific methodology to answer scientific questions. While both of these elements, knowledge and methodology, are equally important, this book will focus on the methodological aspects of scientific imaging. However, this methodology will be extensively illustrated by examples from the commensurate body of knowledge. Hopefully the reader will be able to appreciate not only how to make and analyze a scientific image, but also what might be learned by doing so.

Having defined the universe and nature, introduced concepts of imaging portions thereof, and outlined how to make such an image, let us now address the issue of how to analyze an image. Imaging is not necessarily science. The ancients imaged the heavens for eons, but performed no science. Instead, they fantasized animals and mythical creatures in the heavens and created the constellations (Figure 3.1). The ancients practiced non-scientific astrology, not scientific astronomy. Perhaps the first example of modern scientific imaging was Galileo's discovery and description of the moons of Jupiter in 1610 (Figure 1.25). Galileo used a new imaging tool, the telescope, which improved the imaging capabilities of the naked eye by increasing spatial resolution. This technology allowed him to image previously invisible, small, faint objects in the vicinity of the even-then known planet of Jupiter. At this point Galileo had performed novel imaging, but not science. He had a choice as to what to do with this new information. He could have mythologized the images he saw and empirically filled the telescopic sky with more fantastic creatures. Fortunately, he chose the heretofore unorthodox scientific approach. Instead of imagining monsters, he used his new imaging tool to make localized measurements of energy (visible light) in the spatial vicinity of Jupiter over time (several weeks). He exquisitely displayed these observations with simple images – drawings. Importantly, he then applied the scientific method to first hypothesize and then prove mathematically that these faint light signals were from four previously unknown moons.