A. In Vivo Imaging: Limitations and Advances Initially, the toxicity of radiopaque substances limited in vivo imaging. Earl Osborne, a syphilologist working at Mayo Clinic, accidentally discovered radiocontrast when he noted that the urinary tracts of syphilis patients treated with oral sodium iodide agents were radiopaque.⁴ In 1919, Argentine Carlos Heuser performed the first vascular study in a living human by injecting dilute potassium iodide into a vein on the dorsum of a patient’s hand and following the bolus to the heart fluoroscopically.⁵ In Munich, Berberich and Hirsch obtained the first femoral venogram in 1923 by infusing a solution of aqueous 20% strontium bromide. Soon after, in 1924, Brooks pioneered intraarterial injection of sodium iodide to obtain the first clinical femoral arteriogram.⁶ Egas Moniz, a French neurologist, initiated carotid and intracranial angiograpy in 1927 as a means to localized intracranial tumors by their characteristic vasculature.⁷ For his contributions, he was awarded the 1949 Nobel Prize in Physiology or Medicine.

Early inorganic contrast agents were highly toxic and principally used experimentally. However, in the late 1920s, with the advent of new, organic, iodine-containing radiocontrast media, clinical angiography began to develop rapidly. While searching for new syphilis remedies in Berlin, Binz and Rath developed the first water-soluble iodinated pyridine contrast called Selectran Neutral.⁸ In 1933, Swick and Wallingford synthesized para-aminoiodohippuric acid with three iodine atoms per molecule, Hippuran, heralding the dawn of the modern era of polyiodinated contrast agents.⁹ Ionic contrast media with higher iodine content and improved water solubility proliferated over the ensuing decades; however, the quest for less toxic media continued. Swedish radiologist Torsten Almén pioneered nonionic contrast media in 1969 with monomeric metrizamide (Amipaque); he remained at the forefront of the field with
the 1982 release of the low-osmolar monomer iohexol (Omnipaque) and the 1993 introduction of the iso-osmolar dimer iodixanol (Visipaque).¹⁰

Concomitant to these advances in contrast media, procedural advances permitted expanded use of angiography. In 1929, a Berlin surgical resident named Werner Forssmann inserted a urinary catheter through his own basilic vein to visualize his right ventricle.¹¹ Although he lost his job for the stunt, he was awarded the Nobel Prize in 1956 for his contribution. In 1953, Swedish radiologist Ivar Seldinger described guidewire technique that allowed reliable access to any major artery or vein.¹² Selective angiography was soon performed in every vascular territory. Notably, however, the first selective coronary angiogram obtained by Sones at the Cleveland Clinic on October 30, 1958 was performed inadvertently during aortography when the catheter landed in the right coronary artery.¹³

B. Transcatheter Vascular Intervention Transcatheter vascular intervention began in 1964 when Dotter and Judkins used rigid, Teflon-coated catheters to dilate 11 femoral and popliteal stenoses.¹⁴ Soon after, Fogarty described catheter aspiration of arterial thrombus.¹⁵ Using homemade equipment, Andreas Grüntzig performed the first iliac double-lumen balloon angioplasty on January 23, 1975 at University Hospital in Zurich¹⁶ and reported the first coronary angioplasty on September 16, 1977.¹⁷ Ten years later in Toulouse, Jacques Puel reported the first clinical use of a self-expanding coronary stent on March 28, 1986.¹⁸ Puel and Ulrich Sigwart of Lausanne reported the first ileofemoral self-expanding stents in 1987.¹⁹ Later that year, Julio Palmaz and Richard Schatz implanted the first balloon-expandable peripheral and coronary stents.²⁰ Adjunctive endovascular tools soon followed including intravascular ultrasound (IVUS) in 1988²¹ and coronary rotational atherectomy in 1989.²² The last 25 years have seen a proliferation of devices too numerous to recount including drug-eluting stents, drug-coated balloons, lesion crossing devices, luminal reentry devices, and additional atherectomy modalities.

A. Patients Patients undergoing fluoroscopically guided procedures may be acutely exposed to significant doses of radiation. In the days to weeks following exposure, DNA damage may cause dose-dependent deterministic effects including skin erythema, epilation, and cataracts²³ at doses as low as 2-5 Gy. Exposure of 10-50 Gy may cause life-threatening hematopoetic, gastrointestinal, and cerebrovascular syndromes.²⁴

B. Operators Procedural operators are chronically exposed to scatter radiation. Both patients and operators are at stochastic risk for malignancy. The risk of malignancy is not precisely dose-dependent but follows a linear nonthreshold model. Similarly, DNA damage to reproductive tissues may result in fetal malformations and childhood malignancies. The United States Nuclear Regulatory Commission limits the annual whole-body doses of radiation users to 50 millisieverts (mSv) with specific limits of 150 mSv to the lens of the eye and 500 mSv to the skin of the extremities. Pregnant individuals must keep their exposure below 5 mSv during the duration of pregnancy.

C. Procedural X-ray Dosage Several modifiable factors affect the procedural X-ray dosage. Operators may reduce radiation exposure to patients and themselves by minimizing fluoroscopy time, frame rate, magnification, source-to-image distance, DSA imaging, and steep angulation, while maximizing beam filtration and collimation, shielding of radiation-sensitive tissues, and personal distance from the X-ray source.