Please cite this article in press as: Sarkola T, et al. Transcutaneous very-high-resolution ultrasound to quantify arterial wall layers of muscular and elastic arteries: Validation of a method. Atherosclerosis (2010), doi:10.1016/j.atherosclerosis.2010.06.043 ARTICLE IN PRESS G Model ATH-11533; No. of Pages 8 Atherosclerosis xxx (2010) xxx–xxx Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Transcutaneous very-high-resolution ultrasound to quantify arterial wall layers of muscular and elastic arteries: Validation of a method Taisto Sarkola a,1 , Andrew Redington a,b , Fred Keeley b , Timothy Bradley a , Edgar Jaeggi a,b,∗ a Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada b Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Canada article info Article history: Received 18 February 2010 Received in revised form 21 June 2010 Accepted 29 June 2010 Available online xxx Keywords: Intima-media thickness Ultrasound Artery Morphology Noninvasive abstract Background: High-resolution ultrasound (HRU) is used to measure carotid intima-media thickness (IMT). We postulated that very-high-resolution ultrasound (VHRU, 25–55 MHz) provides more detailed infor- mation on arterial morphology. Methods: Rabbit and pig arterial specimens and artificial elastin membranes were studied with HRU and VHRU, and compared to histology. Bilateral carotid, brachial, radial, ulnar, femoral, and tibial arteries were imaged in vivo in 15 humans to determine the precision of VHRU and in 53 teenagers to compare VHRU to HRU. Results: The assessment of IMT, adventitia thickness (AT) and combined intima-media-adventitia thick- ness (IMAT) in muscular arteries was accurate and precise by VHRU with the exception that the AT of the smallest arteries was not delineated with 25 MHz. VHRU was accurate and precise for IMAT in small and for IMT in large elastic arteries and allowed to qualitatively assess elastin fibers of the media. HRU was accurate for IMT of large muscular and elastic arteries only. Intima thickness (IT) was grossly overestimated by both VHRU and HRU. Conclusion: Transcutaneous VHRU provides a noninvasive method of quantifying elastic and muscular arterial AT, IMT and IMAT in children and adults, but neither VHRU nor HRU is able to assess IT in non-diseased vessels. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The noninvasive measurement of the combined intima-media thickness (IMT) by conventional high-resolution B-mode vascular ultrasound imaging (HRU) with transducers in the 5–15 MHz range has become widely used as a surrogate marker for the progression of atherosclerotic disease [1–4]. HRU has been validated for the carotid [5–8] and femoral arteries [9] and applied in a wide range of clinical settings both in adults and adolescents [10,11]. Neverthe- less, the spatial resolution of HRU systems appears insufficient for more detailed imaging of different arterial wall layers and for the examination of the peripheral vasculature and the carotid arteries of the younger child. The recent emergence of commercially available very-high frequency ultrasound systems (VHRU) with transducers in the ∗ Corresponding author at: Labatt Family Heart Centre, The Hospital for Sick Chil- dren, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Tel.: +1 416 813 7466; fax: +1 416 813 7547. E-mail addresses: taisto.sarkola@helsinki.fi (T. Sarkola), edgar.jaeggi@sickkids.ca (E. Jaeggi). 1 Dr Sarkola’s address (after 1.7.2010): Division of Cardiology, Helsinki University Central Hospital for Children and Adolescents, POB 00029, HUS, Finland. 25–55 MHz range allows imaging of more superficial tissues in almost microscopic detail. VHRU is, however, precluded in the imaging of more deep structures due to attenuation of the ultra- sound beam. To date, VHRU has mainly been used to image coronary arteries by intravascular ultrasound (IVUS [12]), for small animal research [13] and, most recently, to evaluate the morphology of peripheral arteries [14,15]. According to these studies it was pos- sible to accurately determine media and total wall thickness in superficial arteries of pigs [14]. Furthermore, the measurement of the intima thickness (IT) separately from the media was validated against silicone phantoms and vascular specimens in the IT range of 0.15–0.40 mm. This method was then applied to study peripheral muscular arteries in healthy volunteers in vivo, but their measure- ments appeared to be out of the physiologic range [15]. To the best of our knowledge, the utility of VHRU has not been exam- ined systematically, in terms of varying transducer frequencies, and their ability to measure the intima, media and adventitia sep- arately and together in muscular and elastic arteries in adults and children. The primary aims of this study were therefore to investigate the accuracy and precision of VHRU in the assessment of the intima, media and adventitia in small and large muscular and elastic arter- ies as well as to compare VHRU with HRU. 0021-9150/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2010.06.043