Angiography: How did we start seeing our vessels

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This year, the technique of angiography will turn 99. The first successful angiography was performed on 28th June 1927. This feat by an Portuguese neurologist Egas Moniz led to a new modality to study our vessels. In the past blood vessels could be seen either during a surgical procedure, or after death. However now blood vessels could now be seen with intact human body. Moniz had no clue that decades later, this technique of angiography would change the practice of medicine.

A Prelude to Angiography

While we knew for a long time, that blood travels inside conduits or vessels, we did not have much of clarity, till the middle of 16th century. It was only in 1540s, when Andreas Vesalius, a Belgian surgeon, anatomist and a medical illustrator drew it all. He first dissected actual human cadavers, and produced illustrations of our muscles, bones, nerves and blood vessels. He wrote a seven volume book “De Humani Corporis Fabrica Libri Septem“. Third volume of this book is on blood vessels – arteries and veins. He listed all the vessels human eye could see.

From Vesalius to Harvey

Vesalius died in 1564, celebrated through his life as an eminent surgeon, as well as an imperial physician. Fourteen years later, William Harvey was born in England. Harvey was an accomplished medical student in 1602, when he completed his initial medical education. In 1638, he wrote his 72-page work “Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus“. He for the first time correctly described flow of blood, from heart to the organs, and back to the heart. His work challenged prevalent views about circulation of blood, and hence was met with scepticism, and denial. While we call Vesalius as “Father of Modern Anatomy”, Harvey was first to describe our circulatory system.

Visualising our vessels

William Harvey died in 1657 and for more than subsequent two centuries we could see vessels only in the opened up human bodies. Next advance came only after 1895, when Wilhelm Roengten discovered X-rays. Initial radiographs could show bones. Only a month later, two Austrians, E. von Haschek and O. T. Lindenthal attempted an X-ray of an amputated arm. They pushed a chalk like substance into the artery, and could see it as a faint line. This probably was a first angiography, but in a dead limb.

In early 1920’s Earl D Osborne could show that some dyes, when injected in human body are excreted through urine. In this process, urinary tract and bladder could be seen through an X-ray. This was the first pyelography. It is interesting to note, that Osborne was a dermatologist, who died of a vascular occlusion in 1960. However, this demonstration was a foundation in our understanding of blood vessels.

First angiography in a live person

By 1926, despite X-rays, it was hard to see inside the skull. American Surgeon Dandy had discovered that obtaining X-rays after injection of air in the ventricles of brain (pneumo-encephalography) could help see some brain tumors. Between 1926-27, Moniz and his team tried injecting a variety of substances in carotid artery, to see if these could be seen through an X-ray. He tried strontium and Lithium Bromide in his initial studies. These were used in cadavers, animals (i.e., rabbits and, particularly, dogs) and humans. Sadly, these did not work.

Thereafter Moniz zeroed in on Sodium Iodide, which when injected through blood vessels was not painful, did not lead to immediate reactions, and was opaque to X-rays. This became first useful dye to see an artery. He and his team refined the technique, and standardized the vessel to be used, and amount of dye to be injected. After getting a sense of normal anatomy, on 28th June 1927, he could see a pituitary tumor using angiography.

Visualization of blood vessels of the brain, through an X-ray was a landmark discovery. Moniz was aided in his research by Pedro Almeida Lima, the founder of Portuguese neurosurgery. They received three nominations for the Nobel Prize in 1928, 1932 and 1937 for the discovery of cerebral angiography. Sadly, he did not get the award for this feat.

Blood vessels, Moniz, Forsmann and Nobel Prize

In 1933 Moniz made another discovery. If connection of pre-frontal lobe of brain was severed from rest of the brain, many violent patients with psychosis became more calm and dull. This led to perfection of technique of “pre-frontal leucotomy”, for which Moniz got his 1949 Nobel. Interestingly pre-frontal leucotomy faded away with advent of anti-psychotic medication in 1950s. Angiography however lived on and flourished as a diagnostic technique.

In 1929, a German Physician Werner Forssmann performed the first human cardiac catheterization. He inserted a ureteral catheter into his own arm vein pushed it to his right heart. He rushed to an X-ray machine and could see the radio-opaque catheter on the film. Thus, he was able to see the catheterized vessel on the X-ray. While he published his work in 1929, he was not allowed to work in the field of thoracic surgery.

During second world war, he served in German army, and in 1945 was captured by US army as a Prisoner of War. On his release, he was not allowed to work as a physician due to his Nazi past, and instead worked as a lumbar-jack. In 1950s, his old papers on catherization of a vessel to reach right side of heart were rediscovered. He was awarded Nobel Prize in 1956, and recognized thereafter.

More vessels got visualized

Two years later, in 1929, Reynaldo dos Santos performed the first aortogram in Lisbon, Portugal. Reynaldo was a surgeon, urologist and an academician. Moniz and Reynaldo performed these early angiographies through directly puncturing the concerned arteries.

In fact, many current angiography techniques were developed by the Portuguese. In 1932, a Pulmonologist Lopo de Carvalho performed the first pulmonary angiogram, and in 1948 the first portal vein imaging was performed by a Portuguese surgeon Sousa Pereira. All these early procedures were tedious. The vessel had to be exposed, so as to puncture it and inject a dye. Further, X-ray techniques were also not well developed in these early days.

João Cid dos Santos was a Portuguese vascular surgeon, and a collegue to Moniz and Reynaldo. He was a vascular surgeon, and used angiography to plan vascular surgeries. He pioneered some of the surgeries we do today, to remove clots from vessels (such as endartectomies).

Angiography paves way for more developments

In 1950’s we developed techniques, through which we could reach deeper vessels. In 1953, Sven Seldinger introduced the Seldinger technique to obtain safe access inside blood vessels, using wires. Seldinger was a radiologist from Sweden. We use the same technique to enter all blood vessels today.

In 1958, Mason Sones Jr. at the Cleveland Clinic inadvertently injected contrast dye into the right coronary artery of a patient. Sones recorded the first clear visualization of the coronary arteries in a living patient. By 1960s with development of better catheters and dyes, we were doing more coronary angiographies. Sones’s discovery of technique also informed us about lesions and blocks in these vessels.

In 1970s, we had CT scans, who could now obtain a better image, as compared to the previous X-rays. Now we could see vessels in all dimensions, and from different angles. Contrast agents also became more safe and could better visualize our vessels. A further progress was initiated in 1977 by Gruentzig who invented balloon angioplasty. Twenty years later in 1980s, we entered a digital age in imaging as well as Digital subtraction angiography – a technique to see our vessels, without interference of other tissues.

Angiography is about to turn 100. Today it is a widely available technique, enabling us to see even tiny vessels in heart, brain, and virtually all organs of our body. The technique has progressed from one of diagnosis, to that of treatment, as we can now open up blocked vessels as well as close the unwanted ones.