Kon-Tiki revisited

Atherosclerosis, Vulnerable plaque, Vasa vasorum, Intravascular ultrasound, Ultrasound contrast agents, Harmonic imaging, Easter Island

On Easter Sunday 1722 three Dutch sailing vessels under command of Admiral Jacob Roggeveen slipped into the shelter of an Island not yet plotted on any map, roughly 4000km west of South America. ¹ This was the very day that mankind was challenged with several mysteries. The inlanders referred to the Island as Te-Pito-o-te-Henua (navel of the world), it also goes by the name of Rapa Nui, but Roggeveen baptized it Easter Island. It is a small island in the shape of a triangle, with the longest side being 25km. The Dutch had only been there for less than a day, but their record of this visit turned out to be of considerable value, since it was very detailed and it would take another 50 years for the Island to be visited again by foreigners. ^2,3 They described three different ethnic groups living on this Island, one with dark skin, darker than Spaniards, one white, with long ears and one with a reddish skin, as if they had been tanning for too long. The Dutch described the people to be peaceful and non-violent, however, thieves. In the ten hours spent on the Island, which were described as mutually friendly, less than 15 inhabitants were recorded to be killed, apparently a low number by Dutch West Indies standards. On the coastline there were around 50 sites with intriguing statues, all but one facing land inwards. There are many mysteries surrounding these statues, but probably the most intriguing one is the following: the statues themselves (Moai) are carved out of the volcano Rano Raraku ( Fig. 1 ). Their appearance is very Polynesian like. In the part of the world north of Easter Island anything that comes overseas, like language, comes from the West. This is driven by gulf streams and winds, and mostly by the fact that Polynesians were considered to be much better ship builders than South Americans. So far no mystery: the people building the statues probably moved in from the West. These Moai however are placed on platforms (Ahu's) which show striking resemblance with the Inca building style, e.g. seen in Machu Pichu. This indicates that the culture would have come from the East, and this was believed to be impossible.

Figure 1

Van der Steen at Rano Raraku, Easter Island.

This enigma was solved by Thor Heyerdahl. ⁴ In 1947 he build a balsa raft in the Inca pattern, that he named Kon-Tiki after the legendary pre-Incan sun-king Kon-Tiki Viracocha, who had reigned in Tiahuanaco before leading his long eared followers in sailing from mainland South America across the Pacific ( Fig. 2 ). On this raft Heyerdahl set sail from Callao in Peru with a crew of six men, and reached within 101 days the Polynesian atoll Raroia, over 5000 miles West. ⁵ This proved that these primitive ships were good enough to reach Easter Island from South America. It is now commonly accepted that Easter Island culture has influences from both the East and the West.

Figure 2

Kon-Tiki Veracocha, the legendary pre Incan sun king.

Currently, cardiology is facing a similar problem: the pathogenesis of atherosclerosis. Two apparently conflicting theories are:

1. (1)

   Atherosclerotic plaque results from monocytes which migrate through dysfunctional endothelium and transform into macrophages which then become foam cells.

2. (2)

   Atherosclerotic plaque growth is driven by the development of neovascular vasa vasorum, which provide a conduit for inflammatory cells to enter plaques.

The latter is not a new theory ^6,7 but evidence of the significance of vasa vasorum in plaque development which is now accumulating rapidly. It has been shown that vasa vasorum play an important role in the inflammatory process ⁸ and are associated with intraplaque hemorrhage. ⁹ Hypercholesterolemic animal models show elevated levels of vasa vasorum, and this coincides with the presence of plaque. ^10,11 Furthermore, there is evidence to suggest that the location of vasa vasorum may be predictive for the nature of the atherosclerosis, in particular plaque vulnerability. ^12,13 It should be emphasized that the studies just mentioned were either conducted on animal models or rely on pathology. The problem with pathology is that we are looking at a status quo and not necessarily at causal relationships. After all: do the vasa vasorum cause plaque growth, or does the presence of plaque initiate the genesis of vasa vasorum? A strong case can be made for both and, in fact, it seems likely that each may play a role at different stages of plaque development. ¹⁴ From a clinical perspective, unravelling the complexities of the role of vasa vasorum in plaque development may have implications for plaque risk assessment (conceivably providing an independent marker of plaque vulnerability) as well as for therapeutics. It is clear that methods to measure vasa vasorum in vivo in humans would give insight into many aspects of this paradigm, and could become valuable clinical tools.

The use of carotid ultrasound in combination with ultrasound contrast agents for the detection of vasa vasorum has recently been reported. ¹⁵ For coronary arteries the detection method of choice would arguably be intravascular ultrasound (IVUS) in combination with contrast agents. ¹⁶ In this issue a report by Gulel et al. shows an example of how this could be applied. ¹⁷ However, to optimize intracoronary vasa vasorum detection, there are however several technological challenges in play. The first is that most contrast agents are optimized for frequencies used in clinical radiology or echocardiography. IVUS employs significantly higher frequencies and most contrast agents in native form are less effective at those frequencies. Another factor is that current IVUS equipment, including the probes, are rather primitive as compared to high-end echocardiography machines and transducers. Consequently contrast detection techniques like pulse-inversion or harmonic imaging have yet to be implemented in commercial systems. As a result, the use of ‘off the shelf’ contrast agents and current IVUS machines result in a very limited contrast to tissue ratio, which in turn severely limits sensitivity and measurement robustness. So, while the results of Gulel et al. ¹⁷ and Carlier et al. ¹⁶ are encouraging, it should be recognized that until these issues are addressed, the potential of contrast IVUS vasa vasorum imaging will not be fully realized. Recently, IVUS harmonic imaging has shown to be feasible by building new IVUS elements ¹⁸ and using more advanced imaging schemes. ^19–22 Furthermore, it has been shown that there are contrast agents that can be used for high frequency applications. ^21,22 These developments open the way to high sensitive and high contrast in vivo vasa vasorum detection ^23,24 ( Fig. 3 ).

Figure 3

IVUS Vasa vasorum imaging in an atherosclerotic rabbit Aorta in fundamental mode (left) and harmonic mode (right).

Vasa vasorum detection using harmonic IVUS and ultrasound contrast agents has the potential to be a modern day Kon-Tiki for the clinical assessment of atherosclerosis. It may reveal a good mechanistic insight in the pathogenesis of plaque and will likely play a role in therapy guidance, or even therapy itself.

We are only at the beginning though and there is still a lot of work to be done. Those of us that have met him would agree that it is a pity that Thor Heyerdahl is not among us any more to lead the effort.