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The first volume of Cancer published in 1948 included 5 articles that addressed the diagnosis and treatment of lung cancer. The second issue of that volume itself contained 3 of those articles.1–3 Admittedly, the intent of those 3 articles was not imaging of this neoplasm. Clearly, however, the cluster of these articles informs us that the importance of this neoplasm was recognized even then, and it has become an even more pervasive health problem. Although chest radiography was not specifically a topic of those articles, in fact, chest films almost certainly were obtained for the patients who were reported in those studies. By 1948, the diagnostic utility and value of chest radiology had become a standard tool for the assessment of lung cancer. Taking the liberty of commenting on the important disease emphasized in those early reports, this report concentrates on the development of imaging for bronchogenic carcinoma.

Wilhelm Conrad Roentgen discovered what he named x-rays (after the unknown x from algebraic nomenclature) in November 1895. Almost miraculously, his 10-page publication was excerpted by a newspaper editor in Vienna who predicted that the ‘new light’ was being used to see fractured bones and foreign bodies within intact patients. This had not been done at the time of the newspaper account, but the report was circulated widely around the world, and it caught the attention and sparked the imagination of numerous physicists and physicians; within months, investigators in multiple countries were exposing patients to the new ray.4 Adjusting their gas-filled tubes, these early radiographers soon observed that the thorax was a particularly favorable site for their diagnostic work; air in the lungs offered a perfect contrast medium for the solid organs and lung pathology contained therein. Some of these observers soon understood that chest fluoroscopy or radiography surpassed physical diagnosis for many conditions in the thorax.

Five years after the general announcement of this historic discovery in what many consider the first textbook of clinical radiology, Dr. Francis Williams at Boston City Hospital devoted 255 pages of his 658-page book to the diagnosis of intrathoracic diseases.5 At that time, the diagnostic studies were carried out predominantly through fluoroscopy and were used predominantly for tuberculosis. Intrathoracic cancers apparently were not an important problem at the turn of the century, and only 20 pages of Dr. Williams's treatment of chest diseases were devoted to new growths and enlarged glands. In Chapter XII, he wrote “A new growth in the lung usually casts a marked shadow, and in the latter stages may fill up most of one side of the chest and thus render this side completely dark on the fluorescent screen. If, however, the new growth is recognized in its early stage, the shadow cast may be slight. In many cases an X-ray examination makes it evident without much question that we have to deal with a new growth”, even though “its presence was unsuspected by the usual methods.” Later, he noted that the X-ray examination “will aid us to make a more definite and an earlier diagnosis when it is a question of a new growth, than has hitherto been possible.”5 And, of course, he was correct, but not using fluoroscopy. In the early 1900s and 1920s, innovations in film construction and composition, film cassettes, x-ray tubes (the hot cathode x-ray tube of Coolidge in 1913), and better generators led to the conversion to chest radiography as the dominant chest imaging method.

With film technique, it was easier to store and compare information. Yet the presence of bronchogenic carcinoma as a major health problem still was not evident. Holmes and Ruggles, in the second edition of their popular textbook took, all of one-quarter of a page to describe the radiographic findings of the ‘rare’ primary malignancy of the lungs. They used an equal amount of space to report on the findings of metastatic malignancy to the lungs.6 In another notable textbook, this one solely about chest radiology, published in 1923, Wessler and Jaches devoted 22 pages to tumors of the lungs, 18 pages to metastatic disease of the lungs, 13 pages to tumors of the pleura, and 19 pages to mediastinal neoplasms; this in a book that totaled 560 pages.7 Like the book published by Dr. Williams 20 years earlier, much of the space in the book by Wessler and Jaches was taken up by descriptions of tuberculosis and other infections. However, although little interest was directed toward the subject of lung cancer at that time, the radiologic literature regarding chest films, describing the effects of bronchial obstruction and masses in the lungs, mediastinum, and pleural space, was advancing nicely. The ability to extract a large amount of information from the plain film was part of the radiologist's skill, which continued to improve with experience and research. One notable article published in 1918 by McMahon and Carman included a detailed description of the radiographic appearance of lung cancers, which they referred to as ‘rare tumors.’8 Over the next few decades, greater recognition of specific findings observed in bronchogenic carcinoma led to landmark publications that still are referenced today. For example, in 1925, Ross Golden reported a characteristic type of right upper lobe atelectasis indicating the presence of a bronchial obstructing neoplasm; the finding is known by his name, the S sign of Golden.9 Seven years later, in 1932, Henry Pancoast described the clinical and radiographic findings observed in patients with a superior sulcus tumor, now more commonly referred to as Pancoast tumor.10 After 1948, the number of lung cancer cases increased steadily and this caused radiologists to pursue a better understanding of the chest film findings of this disease. Leo Rigler and Henry Garland examined serial radiographs and commented on the slow growth of lung cancer and that, by the time tumors were observed on chest films, they were late in the life cycle of the neoplasm.11 In the 1950s, Rigler also wrote of the general appearance of bronchogenic carcinoma on plain films,12 whereas Liebow reported on the pathologic correlation of lung cancer with its appearance on chest films.13 Today, the plain chest radiograph remains the mainstay of preliminary lung cancer diagnosis.

Academic achievements in chest film interpretation would not have been possible without the many technical advancements and refinements in plain film imaging that have occurred since x-rays were discovered. Some of these came about surprisingly early in the history of radiology (eg, intensifying screens in 1896). Others have come about more recently. In the 1940s, plain films still were hand-processed and hung to dry (thus, the origin of the term ‘wet read’). In 1942, the first prototype automatic x-ray film processor was developed; and, by 1948, commercial units were common. In 1956, the first roller transport processor was introduced.14 These innovations led to more reproducible images and improved chest film comparisons. In the 1980s, digital imaging came into being with the introduction of laser-stimulated luminescence of photostimulable phosphors. Other digital imaging technology followed shortly and has continued to evolve. All-digital radiology departments and picture archive and communications systems (PACS) have become more and more common, allowing rapid communication of radiology results and transmission of chest images from physician to physician everywhere in the world. Consultations between centers of excellence in lung cancer have been facilitated significantly because of these advancements.

Some achievements in imaging have gone beyond the simple radiograph, digital or otherwise. These generally were the result of significant technologic innovations, and they have revolutionized lung cancer assessment. Those of us who were active in chest imaging even as late as the middle 1970s recall the walls of chest tomograms (prior to the computed tomography [CT] type) occupying multiple view boxes as we assessed the presence of tracheal lesions, hilar lymph nodes, or lung nodules. Tomography was the invention of numerous scientists and was devised first in the 1920s. By moving the x-ray tube and x-ray detector in opposite directions, a plane of interest could be radiographed, and the other planes were blurred. Then, greater detail of intrathoracic anatomy and pathology could be attained. Much credit for the development of tomography probably should go to Bocage, who patented a tomographic technique in 1921. Clinical use of tomography (in the skull) was suggested first by Vallebon in 1930 and Ziedses des Plantes in 1931. Not long after this, Grossmann developed the first commercial body tomogram machine, and his coworker, Chaoul published tomograms of the lungs, including bronchogenic carcinoma, in 1935 and 1936.15 From then, through 1948, and until the advent of CT imaging in the 1970s, conventional tomography was the advanced radiographic technique used to determine whether or not calcium was present in a nodule, whether satellite nodules existed, whether metastases were responding to treatment, whether an airway was compressed by hilar or mediastinal lymph nodes, and other findings that would help in assessing the presence or effects of bronchogenic carcinoma.

Percutaneous lung biopsy in the lung had been carried out early in the 1900s for the diagnosis of pneumonia and cancer and, by the 1930s, was the topic of several published articles.16 Fluoroscopy was used to assist in lung biopsies, but fluoroscopic methodology was cumbersome. The technique, however, was advanced significantly with the first practical commercial image-intensifying fluoroscopic unit introduced in 1953. Brighter demonstration of the area being studied allowed better visualization of lung lesions, reduced the radiation dose to physicians and patients, allowed cine studies to be made, and permitted projection of the images on television monitors.8, 11 With this innovation, dark adaptation and red goggles became obsolete, although it was not until the early 1960s that these image-intensifying fluoroscopic machines were improved again with larger fields of view and even brighter images. At about that same time, Bjorn Nordenstrom and then Dahlgren and Nordenstrom, using a thin biopsy needle, published their results of transthoracic percutaneous lung biopsies on 375 patients.17, 18 The nearly 90% diagnostic rate and the small number of benign complications led to a worldwide acceptance of this procedure and a significant increase in the number of such interventions for lung nodules. The diagnosis and classification of patients' bronchogenic carcinomas became less invasive and easier.

The names of those involved with discoveries in the realm of nuclear physics comprise a Who's Who list of scientists. Among these are Becquerel, Pierre and Marie Curie, Geiger, Rutherford, and Bohr. The latter 2 influenced George Hevesy, who, in a most inglorious way, demonstrated the principle and application of nuclear tracers. He believed that some food in his boarding house near Owens College in Manchester, England may have been reused, so he devised a tracer study circa 1923. He deposited a small amount of a naturally occurring radioisotope on a bit of meat, which he left on his plate for disposal. The next day, with an electroscope, he was able to detect radioactivity in the freshly served hash.19 Hevesy lost his accommodations that day, but he had laid the groundwork for subsequent isotope tracer investigations applicable to humans. The natural radioactive substances available at that time were not suitable for human use. However, the development of the cyclotron by Lawrence in 1930 and the breakthrough creation of various artificial radionuclides by Irene and Frederic Joliot-Curie in 1934 led ultimately to a wide array of isotopes for use in human imaging.20 For example, with regard to lung cancer, bone scanning—initially with strontium in the 1960s and then with technesium in the 1970s—became a favored way of investigating the possibility of bone metastases. Other uses of nuclear medicine for investigating bronchogenic carcinoma were limited. However, at the same time that Irene and Frederic and Joliot-Curie first produced isotopes in the 1930s, they also demonstrated and confirmed the presence of positron emission in some of their newly formed radioactive material. In the early 1950s, Brownell conducted an experiment that culminated in modern 3-dimensional positron emission tomography (PET) scanning. He used 2 detectors positioned opposite to each other to detect where a positron emitting isotope was located in the brain of a patient.21 In the late 1960s, Brownell and others produced the first noncomputer-analyzed PET studies. With larger arrays of detectors, the information collected was immense and required computer speed and capacity for analysis. Ter-Pogossian et al, in 1974, were the first to use computers successfully to produce improved PET images of the brain.20, 22 They initially used carbon-11, which was linked chemically to glucose, for the assessment of regional brain glucose use. Since then, other positron emitters have been discovered and used in broader imaging applications. Currently, fluorine-18 in the form of fluorodeoxyglucose is being used for patients with bronchogenic carcinoma to distinguish between benign and malignant lung nodules and to aid in staging of disease.

Perhaps the most significant development in imaging of the lungs, and especially the mediastinum (as well as other parts of the body), is CT. The advantages in contrast and spatial resolution derived with this modality have led to profound changes in the way that lung cancer is detected and staged. Soft tissues, bones, pleural space, mediastinum, lungs, and upper abdomen (to include the adrenal glands) all are obtained in a single study. The initial principle behind the possibility of CT was demonstrated in 1917 by Radon, who demonstrated that the image of a 3-dimensional object could be reconstructed from multiple 2-dimensional projections of that object. In the 1950s, Allen Cormack in South Africa, studying the therapeutic radiation dose distributions in various parts of the body, understood that, if the attenuation coefficients across the region were known, then a representation of the body part could be displayed in a gray-scale image.23 Working independently in England, Geoffrey Hounsfield, a computer engineer at the Central Research Laboratory for Electric and Musical Industry, Limited (yes, EMI: the Beatles' label), produced the first radiographic clinical CT scanner in 1971. Working in secret with a physician at the Atkinson Morley's Hospital, 70 head scans were performed within 6 months, and the results were presented at major medical meetings in 1972.24 (Incidentally, and not surprisingly, many other scientists, mathematicians, and physicists have some contributions and claims to the discovery of CT.24) Since 1972, with the development of CT machines capable of faster scan times and thinner image sections, CT of the lungs has become a common procedure. Thousands of articles regarding the various uses of CT in the diagnosis, follow-up, and treatment of bronchogenic carcinoma have been published; its utility is immeasurable.

Since 1948, when the first volume of Cancer, including several articles about bronchogenic carcinoma, was published, there have been numerous improvements in radiologic technology. We also have learned how radiology can offer us assistance when dealing with this disease. Many of the methods we use have remained unchanged in principle over the last 60 years and continue to serve us well. Conversely, some of the newer devices are simply phenomenal. CT, PET, PACS, and interventional devices have altered the way we think about bronchogenic carcinoma. Other advances, such as molecular diagnostic and therapeutic techniques and radioablation, are on the threshold of great success yet are still in their infancy. It remains to be proven how these newer innovations will impact the care of patients with bronchogenic carcinoma. Fortunately, we will not have to wait 60 years to find out.

REFERENCES

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