An odd tumor of the pancreas, held in the hand, a death-the history of watery profuse diarrhea. Why, what, how? That was the gross pathology of discovery, a window to disease. The year was 1958, the pathologist, my father Duke, giving another discovery in medicine to the world[i]. A discovery made from the history, and the course of the disease, combined with information gleaned post mortem-holding in hand the organs, weighing the pancreas, observing the masses and finally looking under the microscope…A syndrome described…Verner-Morrison syndrome-yet what was it and why? WDHA[ii], pancreatic cholera[iii]…An islet cell tumor…Vasoactive intestinal peptide was discovered, a molecular cause determined. Now the gene sequence is analyzed. Going deeper and deeper into the root cause of disease is what we do, and when we think we might understand, we realize there is yet another layer of knowledge to gain.
Today we stand at the intersection of genetics and radiology: radiogenomics. We are the de facto gross pathologists of the age, wielding our imaging scalpels to cut through the body swiftly to diagnose, to treat and to follow. As medical knowledge explodes, we are there to discover, to guide and to direct therapy. Often it is we who first discover a mass-but is it cancer or not? We use now tried and true guidelines to decide further action. Is that pancreatic tumor big or small, cystic or solid, enhancing or not, single? Multiple? Encasing the vessels? With this knowledge in-hand decisions are made and care given, often a biopsy obtained. If we don’t think the results are what we expect. We say go back, get more tissue, do it again! What if we know not only the cell type but the genetic expression of the tumor? Could we help more? Give better guidance? What if we could combine the big picture we see with ever more specific data-delving into not only the pathology but beyond, into specific expressions of tumor genetics? Not only to see the gross pathology but to combine magnetic resonance spectroscopy, molecular imaging, microscopic pathology and genetic information. What a powerful tool this could be-taking imaging and cancer treatment to the next level, many steps beyond Virchow, beyond WDHA and into the new world of radiogenomics, correlating genetic information with radiology images.
Imagine starting with a breast MR, swooping down to see the digital pathology slide, and yet again through higher and higher powered resolution and more—down to the sub-cellular level.
A Google maps for the body… Yesterday we had gross pathology, a surgical specimen or an autopsy, yielding an organ to hold in the hand, to weigh and to dissect. Next the pathologic glass slide, carefully prepared, stained and ready to examine. These findings, in the setting of the patient’s history, their signs and symptoms, gave us the basis to diagnose and treat. Today we have gone digital—and have replaced the touch and feel of the organs with the dynamic non-invasive gross pathology—the CT scan, the MRI…We have added functional molecular imaging, MR spectroscopy, fusion imaging…The virtual microscope, first invented at Hopkins in 1997[iv], gave us a digital version of the glass slide. Today this technology allows us to zoom in and out, and to move through a block of tissue, virtually. Now we are able to add the genetic information, in a “mark-up”—placing it in three-dimensional space. We know that combining genetic information about tumors and their radiologic appearance adds valuable information[v] and that MR spectroscopy is more powerful when combined with molecular genomics[vi]. This is the beginning of an information explosion, and we must prepare as imagers and physicians to lead our medical colleagues through this journey.
As those most able to visualize and integrate imaging data, radiologists are uniquely poised on the edge of the new imaging frontier, where placing genetic information in three-dimensional space is now possible…disease rediscovered…Combining information across modalities, then going down to the next level of resolution, then the next, will yield a wealth of knowledge. Using our current understanding of disease, based on centuries of science, while leveraging state-of-the-art advances, will bring us to the cutting edge of patient care, providing novel and personalized therapies. As imagers we will be able to see and monitor these interventions in a new way—personalized radiology of the future, here today. Let us seize this opportunity as imagers, and take it to the next level. What do you think?