According to Zamora and Castillo (2017), X-rays were first discovered in November 1875 when Wilhelm Conrad Roentgen obtained the first human body images. One of the most famous initial images was a human hand with a ring in place belonging to Roentgen's wife (Zamora & Castillo, 2017). Zamora and Castillo (2017) note that X-rays could effectively distinguish between soft tissues and bones. However, it became very clear that there was very little contrast between soft tissues on standard X-rays, necessitating a product to provide adequate contrast (Zamora & Castillo, 2017). Initially, Roentgen focused on using high atomic number elements, given that they cast dark shadows on imaging. Specifically, he used elements such as Iodine, Bismuth, and Barium. Note that Iodine and barium are still being used today as contrast agents.
The first accounts of an external contrast medium used in radiology were in Vienna by Lindenthal and Haschek. They injected an amputated hand with a mixture of petroleum, lime, and cinnabar. Meanwhile, at Johns Hopkins Hospital, Hemmeter asked patients to ingest rubber bags filled with lead or mercury acetate into their gastrointestinal system as a form of contrast media. He subsequently used bismuth sulfate and eventually stopped using the bags, given that bismuth subnitrate was a commonly used salt to treat peptic ulcers and other disorders. Bismuth subnitrate was subsequently replaced by barium sulfate partially due to the toxic effects of bismuth salts and the lack of bismuth during the First World War. From that point forward, barium has remained the agent of choice for gastrointestinal studies with a limited role in bronchography for a few decades.
By 1917, Cameron began using iodides, including sodium and potassium iodides, as contrast media. Iodine had become popular for use as an antibacterial before penicillin was even discovered in 1928. Iodine was first injected intravenously as a contrast agent at the Mayo Clinic in 1923 by Osborne and his colleagues. It was used in a patient undergoing intravenous excretory urography since it was officially recognized that urine containing Iodine was radiopaque. The initial iodinated contrast media were not water-soluble, making them relatively toxic in patients. In the 1920s, the first water-soluble agents were developed, setting the stage for developing new contrast agents. Today, water-soluble contrast agents are used for intravenous urography, angiography, and myelography. Note that hyperosmolar agents can cause excruciating pain for patients when injected. As such, it became a focus for scientists to develop agents with decreased osmolality.
Computed Tomography (CT)--based contrast agents are similar to radiography iodine-based contrast agents given that the physics is similar, relying on the attenuation of different materials (Zamora & Castillo, 2017).