Comments on How to Perform Valid Ultrasound Measurements of Carotid Artery Intima-Media Thickness and Lumen Diameter

The joint experience from many research laboratories around the world shows that high quality 2-D ultrasound images may be recorded from the common carotid artery and the carotid artery bulb. In most cases, the image from the carotid artery shows a typical double-line pattern similar in appearance from the near and far wall of the artery. In spite of the similarity of the near and far wall images the thickness of the intima-media complex can only be measured in a valid way in the far wall position. This is because it is only in the far wall that the intima-media complex is defined by leading edges from echoes of interest. In vitro experiments and measurements of arterial wall segment thicknesses obtained by histology and by vascular ultrasound also confirm that only far wall intima-media thickness, in contrast to near wall thickness, may be accurately measured. The anatomical location of a biological structure is always defined by a leading edge of an echo, and the thickness of a structure as the distance between the leading edges of two different echoes. If lumen diameter is measured in the carotid artery, this measurement should be carried out according to the leading edge principle. If changes in common carotid lumen diameter are observed in prospective studies, analyses of common carotid artery cross-sectional area may help in interpreting the results. In measurements of intima-media thickness it would seem advisable to focus on far wall common carotid artery and carotid artery bulb recordings. Our advice would be to define a composite mean of 10 mm sections from the far wall common carotid and far wall carotid artery bulb intima-media thickness as the primary outcome variable. We conclude that main outcome variables in ultrasound studies of atherosclerosis should be from the far wall. It would seem advisable to focus on far wall common carotid artery and carotid artery bulb intima-media thickness. It is likely that including near wall measurements and measurements from the internal carotid artery will decrease measurement precision and lead to increases in sample size in scientific studies; or even dilute positive results in an otherwise well designed study. John Wikstrand* Wallenberg Laboratory for Cardiovascular Research, Gothenburg University, Sweden John Wikstrand Journal of Heart and Stroke Remedy Publications LLC. 2019 | Volume 4 | Issue 1 | Article 1056 2 in atherosclerotic prone areas is used as an indicator of intimal thickening. The first limitation is thus that we measure a surrogate variable for intimal thickening, that is intima-media thickness. This may underestimate intimal thickening since media thickness may decrease in connection with intimal thickening during atherosclerosis development. In rare cases a primary increase in media thickness may also occur, which can increase intima-media thickness. This may lead to an overestimation of intima thickness when intima-media thickness is used as a surrogate variable for intimal thickening. Figure 2 shows an ultrasound recording from a carotid artery illustrating the typical double-line pattern from both the near and the far wall of a carotid artery. Figure 3 shows the definition of leading and far edge of the near wall intima-lumen interface echo in a section of the common carotid artery. The typical double-line pattern from both the near and far wall is also clearly illustrated in this figure. Theoretical Considerations-Visibility of Below-Resolution Structures Small structures, the dimensions of which are far beyond the resolution limits of the equipment, can be detected and produce a clearly visible ultrasound echo [1,2]. The explanation for this phenomenon is that each tissue interface, no matter what size, produces an echo if there is sufficient difference in structure, i.e. in acoustic impedance between two structures (i.e. the very thin interface between two fluids such as oil and water will produce a clear echo that is much thicker than the interface itself, which is infinitely thin). Thus, the thickness of an echo defining an interface is not related to the thickness of the actual structure of interest (for further comments, see below). The anatomical delineation of a biological structure is always defined by a leading edge, i.e. the upper demarcation line of an echo (Figure 3). In vitro Experiments A B-mode two-dimensional image from the carotid artery may be described as containing seven echo zones: three from the near wall, three from the far wall, and an echo free zone in between (Figure 2 and 3) [1,2]. When inspecting the three echo zones from the near and far walls, respectively, and comparing it with a picture of the anatomy of the arterial wall (Figure 1) one may be deluded into believing that this similarity implies that the three echo zones anatomically correspond to intima, media and adventitia, and that the echo free space in the middle corresponded to lumen of the artery. This was actually also argued to be the case when the technique was new [4]. However, keeping the fundamental principles of the ultrasound method in mind (summarized above), this cannot be the case. Our group decided to perform a couple of in-vitro experiments to prove our case. The in vitro experiments were designed to illustrate two things of fundamental importance when interpreting the ultrasound image of an artery: 1. The thickness of the echo created by the interface between the liquid (blood) in the lumen and the intima of the vessel wall has no anatomical relationship to the thickness of the intima itself; and 2. The transition between the vessel wall and the vessel lumen in the near wall is defined by the leading edge of the echo from the lumen-intima interface, not by the far edge of this echo. Thus the thickness of the echo created by the interface between the intima and the liquid (blood) in the lumen in the near wall has no anatomical relationship to the thickness of the intima. Summary of experiments performed The in vitro experiments were performed on human arteries removed at autopsy [1,2]. Experiment 1: Trepanation experiment. The vessel was cut open longitudinally and mounted, slightly stretched, with pins on a rectangular rubber sheet. Now, with a corneal trepanation instrument intima and part of the media was removed at various depths (Figure 4). The vessel was then placed in a bath with buffer solution. The ultrasound transducer was mounted in a fixture in the bath at a distance of about 10 mm above the vessel specimen. The intimal surface faced the transducer. The results clearly illustrates that a sharp demarcation echo still can be recorded between the buffer solution and the blood vessel even after the trepanation procedure has removed the intima. The echo was there irrespective of the depth of the trepanation into the media (the echo looked the same even if the intima was removed). The conclusion is that we cannot measure the thickness of the intima by measuring the thickness of the echo created by the difference in acoustic impedance between liquid (blood or buffer solution) and the intima. Figure 1: Anatomy of the arterial wall with its three different layers. Figure 2: Ultrasound recording from a carotid artery showing the typical double-line pattern from both the near and far wall of the artery. The arrow indicates the transition from common carotid artery to carotid artery bulb. Figure 3: Definition of leading edge and far edge of the near wall intimalumen interface in a section of the common carotid artery. The typical doubleline pattern from both the near and far wall is also illustrated. John Wikstrand Journal of Heart and Stroke Remedy Publications LLC. 2019 | Volume 4 | Issue 1 | Article 1056 3 Experiment 2: Using an air bubble: In the second experiment, part of an intact carotid artery was mounted in the bath with buffer solution. The transducer was mounted as before at a distance of 10 mm above the near wall of the vessel. The artery was closed at one end, while the other end was connected to a syringe filled with buffer solution and some air. Using the syringe, an air bubble was now slowly created above the buffer solution and in direct contact with the near wall intima. The results showed, as expected, that a sharp, high contrast echo was created by the intima/air interface (Figure 5). The most important observation, of course, was that the leading edge of the near wall intima/air bubble interface echo corresponded to the leading edge of the near wall intima/buffer interface echo. When the air bubble extends along the vessel wall the near wall “intima” echo disappears completely, it is so to say swallowed by the echo from the air bubble. The results of this experiment clearly illustrates that the near wall/ lumen transition is defined by the leading edge of this echo line 2 in (Figure 6), not by the far edge line 3 in (Figure 6) [4]. As a reaction to the in vitro experiments performed by our group [1,2], Gene Bond’s group at Bowman Gray School of Medicine in Winston-Salem decided to re-evaluate in vitro measurements of arterial wall segment thickness obtained by histology and by ultrasound recordings [4]. Wong et al. interpreted the similarity of the echo picture with anatomy to indicate that the thicknesses of the echoes (Figure 3) corresponded to the thicknesses of intima, media and adventitia, respectively (Figure 1). They therefore embarked on trying to correlate the thickness of single echoes by measuring on leading and far edges of the different echoes [4]. They concluded, however, that their experiments showed that it was not possible to accurately measure single layers in the arterial wall with ultrasound, nor was it possible to accurately measure the intima-media thickness in the near wall. Their experiments corroborated our findings that only far wall intima-media thickness could be accurately measured. Near Wall Adventitia-Media Interface and Near Wall Intima-Media Thickness The following important quest