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The History of X-Rays and Their Use in Diagnostic Medicine Isla McInnes Perspectives On Medical Advances SSC May 2011 (word count: 3279) The discovery of x-rays by Wilhelm Röntgen (1845-1923) on 8th November 1895 in the German city of Würzburg, brought about the age of medical diagnostic imaging.[1] Holding the Chair of Physics at Würzburg University,[2] he had already written 48 scientific papers before this.[3] At the time he was working to understand the properties of electric currents being passed through a vacuum tube,[4][5] and it was these experiments which lead to the discovery of a “new kind of ray”.[1] Entire books have been written on the history of x-rays, but in this essay I am going to focus on the story of the discovery and the particular use in diagnostic medicine. I will explore its development, the people it involved and the impact on medicine and society. THE FOUNDATION IS SET By the 1890s, the three things needed for the production of a radiograph had been discovered through the work of scientists like Guericke, Hauksbee and Faraday: a vacuum, a source of electricity and an emulsion sensitive to the rays.[4] Cathode rays were discovered by J.W.Hittorf (1824-1914) in Bonn in 1869. As a student he was studying the fluorescence on the internal glass wall of an energised vacuum tube; he observed that when an object was put in front of the cathode, a shadow was cast on the tube wall.[4] The nature of these rays was of great interest throughout the scientific community, and many scientists became involved in the search. One of the most famous is the British physicist Sir William Crookes (1832-1919), who in addition to his vital research, developed a more efficient design of vacuum tube – the Crookes tube, which was used by Röntgen in his experiment.[4] Another important figure is Philipp Lenard (1862-1947) who began working with cathode rays in 1888; he designed the experiment which Röntgen would later replicate. An important development was of the “Lenard window” which maintained the vacuum in a tube, but let the cathode rays pass out - allowing them to be studied outside of the discharge tube.[6] In his experiments, he used pentadecylparatolylketone coated screens, which although respond to cathode rays are not sensitive to x-rays; therefore although he would have produced them, he did not detect them or distinguish them as a different type of ray.[4] In retrospect, many others working in this field probably came across x-rays. One example of this is Crookes returning a box of photographic plates claiming there was a manufacturing error, however it is now thought that they had been altered by exposure.[5] Lenard's contribution to x-ray discovery was however recognised; he was and is often jointly credited with Röntgen.[4] The experiments and technological developments of these men and scientists in their field paved the way for discovery of x-rays. THE DISCOVERY In the last few months of 1895 Röntgen began to work on electric currents in vacuum tubes and on cathode rays. As he was reproducing Lenard's experiment, he noticed not only what was happening within the tube, but what was happening outside of it.[4][5] With the room in darkness, and the tube completely covered with black paper (to prevent sunlight affecting the experiment); he observed that a photographic plate covered in barium platinocyanide (a fluorescent material which was not used by most scientists before him) placed in the path of the rays from the tube became illuminated, even out with the range of cathode rays.[2][5] With these differing behaviours, he determined that the invisible rays causing the illumination must be different from cathode rays.[1] On investigating this phenomenon, he discovered that other objects such as wood, thick books and metal sheets were all penetrated by these rays.[5] The only exception to this was lead which blocked the rays completely, a fact which would be later utilised in protection.[1] Whilst holding some material between the tube and the photographic plate, he noted the outline of his hand, and more significantly the difference in ray absorption between bone and soft tissue.[1][5] When he was later asked what he thought at the time he replied “I did not think, I investigated”[4] This was a characteristic of Röntgen which made him determined to understand his discovery completely, and he spent the next several weeks systematically conducting further experiments, verifying his results and learning all he could. He believed reputation to be based on professional integrity and was in part worried that his colleagues would think he had “really gone crazy”. [3][4] “The left hand of Anna Roentgen”[7] One of the first radiographs ever taken was of the hand of Röntgen's wife, with 15 minutes of exposure on 22 December 1895. Upon seeing it she commented “I have seen my death!”[7] This is an interesting comment, as to see inside one's body was a suggestion of ill health, and the image of the skeleton is often used as a symbol and omen of death.[4] This belief was held by the majority of society in Victorian era Europe and America. Because of this, when Röntgen gave his only public demonstration of x-rays[5], he insisted on Alfred von Kolliker (chairman of the society) to keep on his wedding rings, as a radiograph was made of his hand. This was not only to show differences in absorption of materials but to make the picture seem more “human”.[4] The successful and continued use of x-rays helped to diminish this, and meant that later diagnostic techniques did not have to overcome this resistance from the public.[5] THE NEWS SPREADS After first presenting his work to the Physical-Medical Society of Würzburg[3], he then published an article in January 1896 titled “A New Kind of Ray”,[1] naming them x-rays because of their unknown nature[1]; this was the first of only three articles he wrote about his discovery.[5] He sent papers and prints of his early radiographs to a few friends and colleagues, including Sir Arthur Schuster in Manchester and Lord Kelvin in Glasgow[5 ]who was “astonished and delighted”[8] at the discovery. The scientific community's response to the discovery of these x-rays or “Röntgen rays” occurred quickly although it was varied. However the medical implications were realised immediately.[5] The equipment to replicate Röntgen's experiment was widely available, which together with his refusal to patent the idea and make any profit from it, allowed the technology to quickly be reproduced across western Europe and North America.[9] They were quickly used in medical diagnosis, with the first clinical radiograph being taken as early as 7th January 1896[1] and expansion from imaging of bones to stones, foreign bodies and even internal organs quickly took place.[4] By allowing doctors to “see” inside their patients without opening them up, the impact on diagnosis was huge – surgeons did not need to go in blindly in an operation, procedures which before may not have been possible could now be performed, assessment of health could be improved and the management of fractures advanced, as only a few examples.[4][5] Demonstrations and lectures became widespread and helped to spread information of the discovery.[4] Teaching hospitals began to establish x-ray departments, the first of which was at Glasgow Royal Infirmary, set up by John McIntyre who was running the electrical department and associated with Lord Kelvin.[8] In many areas of Britain the medical profession were not in charge of x-rays in early years, as most doctors did not have good working knowledge of the science behind them. There were many physicist-physician collaborations in this time, which although short-lived, was important in the development of medical radiology. As time went on, more specialised radiographers began to emerge, and it became a more established branch of medicine.[5] As of September 2010 in Scotland 21.9% of the Allied Health Professionals are radiographers, and there are 286 consultant radiologists.[10] Hundreds of papers were written on the subject in 1896, exhibiting the many disciplines and people involved with the study and application of x-rays.[3] The first journal of radiology (which eventually became British Journal of Radiology[5]) was established in April 1986 in London, and in the following year the Roentgen Ray Society was also established here.[9] These helped to define radiology as an individual science; there are now several societies and journals dedicated to radiology alone. The most influential publications in Britain are considered to be Arthur Stanton's translation of Röntgen's paper in Nature on 16th January 1896; a radiograph of Alan Swinton's hand in Nature a week later; and Rowland's articles in BMJ throughout 1896.[5] These was seen as proof by those in Britain who had been sceptical at the original claims, and as such were key in changing views of both doubting scientists and medical professionals. The news of the discovery reached the British public in the first week of January through a Vienna newspaper, whose editor's son was allowed to view the paper Röntgen had sent his old friend Professor Exner.[5] The reaction of the general public is interesting; there was incredulity and delight, but also scepticism, fear and anxiety at what this new scientific discovery would mean; many did not fully understand it.[1] News coverage, public lectures and public demonstrations increased the knowledge of x-rays and their potential uses. The satirical magazine Punch published many infamous cartoons aptly expressing the feelings of the British public at the time.[5] Bizarre claims began to crop up, including the idea that they were the “philosopher's stone” and could turn metal into gold.[5] One enterprising company in London took advantage of the public's fear that the discovery would aid Peeping Toms and produced “X-Ray Proof” underwear for ladies.[1] As knowledge and practice of x-rays began to increase, these misconceptions died down along with the initial excitement over x-rays.[4] Röntgen was given numerous honours, though he rarely travelled to receive them in person due to his private lifestyle. In several cities streets were named for him, he was given prizes, medals, honorary doctorates, membership to learned societies and was the first person to win the Nobel Prize in Physics in 1901.[2] The bestowing of all these awards shows how important both the man and the discovery was thought of by the scientific community and the world-wide public. DEVELOPMENTS As with most new technology there were several limitations to x-rays: taking a 3D image and imposing it on a 2D surface meant that it could be difficult to determine structures and precise locations; the lack of differentiation between soft tissues; safety questions began to be raised over the lack of protection and the exposure times to both patient and doctor; and the lower power of the apparatus meaning long exposure times and difficult images.[5][11] The cause of many of the earlier injuries was due to the lack of protection of the radiationemitting tube or the screen, and many early radiographers suffered due to their occupation. The common practice of using the practitioner's hand to test the apparatus and hand-held equipment meant that many had to have their hands amputated or died from radiation-induced illness.[5] The British X-Ray and Radium Protection Committee came into being in April 1921 (disbanded in 1952) after years of informal discussions about the safety of radiology and the need for protection, and published guidelines for use of x-rays and radium.[11] Since then there has been significant developments in technology and practice, to ensure that x-ray use is kept as safe as possible. This coupled with the dramatically reduced exposure times means that the danger has been significantly reduced. There will however always be risks associated with using ionising radiation; though these have helped bring about developments in other technologies, as doctors looked for new and safer ways to investigate patients, such as ultrasound and MRI.[5] War was an important stimulus in the development of x-rays. It lead not only to more specialised radiologists, but the equipment being used became more refined - it was more portable and compact (particularly necessary in the battlefield) and it was more powerful – and it was safer due to reduced exposure times.[9] Being able to determine where a bullet was in a patient was a significant advantage to the army surgeons, and would have helped safe hundreds of lives.[5] A major development in radiology is of the use of contrast medium or “dyes” in conjunction with x-rays. The first documented use of a contrast agent used was soon after Röntgen's discovery, in January 1896 by a physicist Haschek and a physician Lidenthal in Vienna. They performed the first arteriogram by injecting calcium carbonate into the brachial artery of a cadaver then exposing to x-rays for 57 minutes. The first visceral angiogram was of the kidneys by the physicist Hicks at Sheffield University in February 1896.[5] In December 1896 Walter Cannon was working at Harvard University and discovered that when bismuth salts were fed to animals, their intestinal tract could be clearly differentiated from the other soft tissues on fluorescent screen when x-rayed.[1][5] He developed this, replacing bismuth with safer barium – inventing the “Barium Swallow” which by 1904 was being used in patients.[5] This became a key gastrointestinal diagnostic procedure, though it has been largely superseded by endoscopy. Sickard and Forestier working in the early 1920's injected a mixture of iodine and poppy seed oil (lipiodol) which enabled the production of a good quality bronchography.[3] From this beginning, the use of iodine as an agent has carried on up to the present. In 1923 a group from The Mayo Clinic published the first scientific paper on intravenous urography with sodium iodide.[5] Egas Moniz was working on contrast agents after Sickard and Forestier's success, and experimented to obtain a carotid arteriography, for diagnosis and location of cerebral tumours. His first successful procedure was a 30% solution of sodium iodide on young man with pituitary tumour in July 1927.[5] Over the next few decades pharmaceutical companies and individual scientists attempted to refine agents to produce better pictures and to reduce toxicity. In the early 1950's, research by Wallingford reduced the toxicity of the current agents by altering the chemical structure. This was furthered a few years later by Hoppe and Laren, and these compounds became the standard for the next 30 years.[5] Torsten Almen, a Swedish radiologist, theorised that the high osmolality of the contrast agents was the cause of the renal toxicity. Although at first met with much rejection, his paper was eventually published and his ideas were developed commercially with the production of the first non-ionising low-osmolality contrast media (LOCM). Due to its expense, it was mainly used for myelography. Second generation agents were produced which were more stable, less toxic and cheaper and are still the contrast medium of choice.[5] This is an example of the close relationship between scientific discovery and advancements in medicine. By using the fact that different atomic weights cast different shadows, contrast media allows doctors to visualise organs and blood vessels more clearly than with x-rays alone (where it is difficult to differentiate between soft tissues).[9] The issue with only being able to view a 2D image was addressed with the development of the x-ray technique of Axial/Classical Tomography (tomography meaning “slice imaging”). An image is formed when the x-ray source and the detector move in a coupled manner; each ray joining the source pivots around a single point in an “in-focus” plane. Rays are still passed through other planes, however the structures in these “out-of-focus” planes are blurred out by the movement of the apparatus. Many scientists were independently working on developing the technique during the 1920's-1930's, and its inventor has been debated to a great extent; an important pioneer was Bernard Zeidses des Plantes whose equipment formed an early commercial basis.[5] This method was used heavily in dental practice (for imaging of the jaw and its joints), neurology (giving more detail on the internal structures of the brain) as well as other medical disciplines. Again there is no definitive answer to who invented the next breakthrough – Computerised Tomography (CT). In 1967 an engineer and computer expert, Godfrey Hounsfield thought to develop a way of building up 3D body images.[1] The practical invention of the technique is also credited to Allan Cormack who had been working on the theory since 1956;[5] they share the Nobel Prize for Physiology or Medicine in 1979.[12] X-rays are used to take thousands of cross-sectional pictures through a patient's body, with the source and detector moving in relation to the patient. They are then processed by a computer to be shown in a series, able to be manipulated for analysis. Routine clinical CT came into being in 1972, within a few years there were hundreds of scanners the world over, and it is still regularly used today.[5] It was considered the greatest leap since the initial discovery of xrays. Later developments enabled the images to be coloured by the computers.[5] Classical tomography has virtually disappeared, but the development of 3D technology has lead the way for the application to medicine of different technologies in the same manner. CT lead to PET scanning (positron emission tomography) which began development in the late 1950's, using radioactive emissions in the study of brain disorders, which was revolutionary in physiology, oncology and neurology.[5] Nuclear Magnetic Resonance had been developed many years before, following the second world war, for the study of chemical compounds, but because of new x-ray methods, the idea to apply it to medicine occurred – Magnetic Resonance Imaging (MRI) the latest great leap in diagnostic imaging.[1][5] Even with these new methods, simple x-rays and CT have important roles in diagnostics and so are set to remain still for a significant time. The use of x-rays in medicine has not only been in diagnosis but in therapeutics and in screening. Therapeutic use began shortly after Röntgen's discovery, and this is a field which has undone a great deal of development.[5] In the past, chest x-rays were used as a screening test for TB. Currently the NHS runs screening programmes using x-rays including DEXA scanning for osteoporosis and routine mammographies for detection of breast cancer. The latter was established in 1988, introduced through evidence that screening could reduce mortality by up to 30%.[13] These programmes incorporate many areas of medicine, showing just how integrated radiology has become. CONCLUSION In the space of just over a hundred years – a relatively short time given medicine itself has been around for thousands of years – radiology has emerged and developed into an important part of medicine. The story of their discovery and the achievements of early pioneers are fascinating and show just how far we have come. It is a young discipline, but its significant impact on diagnostic medicine cannot be denied. Few people will go their entire lives without being exposed to x-rays; whether through diagnosis, therapy, work or another individual. From its beginning, the non-invasive nature of x-rays have helped doctors to diagnose, understand and manage their patients, and they are still used in almost every medical speciality. It has also had significant influence on society; helping to show the importance of screening for pathology, and to change the belief that seeing into the body was a “bad thing”. It is interesting to think that when first discovered x-rays were thought by many to be potentially devious, yet only a few decades later “x-ray vision” was considered a superpower. Its early limitations as well as clinical needs brought about developments in technology and practice which have continued to advance into the present day. By showing the world the benefits of imaging, they helped bring about the development of other technology into clinical practice, such as ultrasound from SONAR technology, PET and MRI. And although new technologies have since been developed, xrays are still – and I believe will be for a significant time - a fundamental tool for diagnosticians. REFERENCES [1] Porter R. The Greatest Benefit To Mankind. 1st Edition. London: Harper Collins; 1997. [2] The Nobel Foundation. Wilhelm Conrad Röntgen – Biography. No date [cited 2011 May 5]. Available from: http://nobelprize.org/nobel_prizes/physics/laureates/1901/rontgenbio.html [3] McCurley JM. The Contribution of Fundamental Discovery to the Emergence of Nuclear Medicine as a Discipline. Radiographics. 1995; 15: 1243-1259. [4] Burrows EH. Pioneers And Early Years - A History Of British Radiology. 1st Edition. Alderney: Colophon Limited; 1986. [5] Thomas AMK, editor. The Invisible Light – 100 Years of Medical Radiology. 1st Edition. UK: Alden Press Limited; 1995. [6] The Nobel Foundation. Philipp Lenard – Biography. No date [cited 2011 May 11]. Available from: http://nobelprize.org/nobel_prizes/physics/laureates/1905/lenardbio.html [7] Wellcome Trust. The Left Hand of Anna Roentgen. c2010 [created 2010 Aug 13; cited 2011 May 5]. Available from: http://wellcometrust.wordpress.com/2010/08/13/wellcomeimage-of-the-month-the-left-hand-of-anna-roentgen/ [8] Calder JF. The History of Radiology In Scotland 1896-2000. 1st Edition. Edinburgh: Dunedin Academic Press; 2001. [9] Bodley R. A century of medical imaging. Paraplegia. 1995; 33: 685-686. [10] ISD Scotland. NHS Scotland Workforce Information. c2010 [updated 2010 Dec 14; cited 2011 May 12]. Available from: http://www.isdscotland.org/isd/5238.html [11] Spear FG. The British X-Ray and Radium Protection Committee. BJR. 1953; 26: 553554. [12] The Nobel Foundation. The Nobel Prize in Physiology or Medicine 1979. No date [cited 2011 May 11]. Available from: http://nobelprize.org/nobel_prizes/medicine/laureates/1979/ [13] ISD Scotland. Breast Screening. c2010 [updated 2011 Mar 8; cited 2011 May 12]. Available from: http://www.isdscotland.org/isd/1623.html