Fabrication of Customizable Intraplaque Hemorrhage Phantoms for Magnetic Resonance Imaging

Abstract

Purpose: Magnetic resonance (MR) imaging detection of methemoglobin, a molecular marker of intraplaque hemorrhage (IPH), in atherosclerotic plaque is a promising method of assessing stroke risk. However, the multicenter imaging studies required to further validate this technique necessitate the development of IPH phantoms to standardize images acquired across different scanners. This study developed a set of phantoms that modeled methemoglobin-laden IPH for use in MR image standardization.

Procedures: A time-stable material mimicking the MR properties of methemoglobin in IPH was created by doping agarose hydrogel with gadolinium and sodium alginate. This material was used to create a phantom that consisted of 9 cylindrical IPH sites (with sizes from 1 to 8 mm). Anatomical replicas of IPH-positive atherosclerosis were also created using 3D printed molds. These plaque replicas also modeled other common plaque components including a lipid core and atheroma cap. T1 mapping and a magnetization-prepared rapid acquisition gradient echo (MPRAGE) carotid imaging protocol were used to assess phantom realism and long-term stability.

Results: Cylindrical phantom IPH sites possessed a T1 time of 335 ± 51 ms and exhibited little change in size or MPRAGE signal intensity over 31 days; the mean (SD) magnitude of changes in size and signal were 6.4 % (2.7 %) and 7.3 % (6.7 %), respectively. IPH sites incorporated into complex anatomical plaque phantoms exhibited contrast comparable to clinical images.

Conclusions: The cylindrical IPH phantom accurately modeled the short T1 time characteristic of methemoglobin-laden IPH, with the IPH sites exhibiting little variation in imaging properties over 31 days. Furthermore, MPRAGE images of the anatomical atherosclerosis replicas closely matched those of clinical plaques. In combination, these phantoms will allow for IPH imaging protocol standardization and thus facilitate future multicenter IPH imaging.

Keywords: Carotid plaque; Intraplaque hemorrhage; MR imaging; MRI phantoms; Magnetic resonance angiography; Methemoglobin.

Fig. 1.

Mean T1 relaxation times for methemoglobin-mimicking hydrogels (containing sodium alginate) over the 42-day assessment period. Error bars indicate standard deviation.

Fig. 2.

T1 maps of methemoglobin-mimicking hydrogels (20.7 mm diameter) with sodium alginate (a–c) and without (d–f), after an assessment period of 42 days. The circular sites shown in each image are surrounded by agar gel. MPRAGE contrast (g–i) (between the methemoglobin hydrogel and background agar) as a function of radial position for the methemoglobin hydrogels shown in (a–f). Shaded regions represent the maximum and minimum contrast values observed at a given radial position. GdCl₃·6H₂O concentrations in the methemoglobin gels were 0.0027 wt % for the top row (a, d, g), 0.005 wt % for the middle row (b, e, h), and 0.015 wt % for the bottom row (c, f, i).

Fig. 3.

Characterization of the IPH size standard phantom: a Representative image of the phantom scanned using the high-resolution MPRAGE sequence. b Mean cross-sectional areas of the IPH sites, before and after a 31-day storage period.

Fig. 4.

High-resolution MPRAGE images of the moderate IPH (a) and severe IPH (b) anatomical atherosclerosis models. The presented slices show plaque cross sections at different axial positions along the length of the mock vessel.