Transcranial Ultrasound Localization Microscopy in Moya Moya patients using a clinical ultrasound system

BackgroundDeep brain structures are supplied by perforating arteries, these arteries are too thin to be observed with non-invasive and widely available clinical imaging methods. In Moya Moya disease, main arteries in the base of the brain progressively narrowed, and perforating arteries grow densely and tortuously to compensate the lack of blood supply in deep brain structures. PurposeThe aim of this study is to evaluate the efficacy of transcranial ultrasound localization microscopy (ULM) in visualizing perforating arteries, utilizing a standard low-frame-rate ultrasound clinical scanner and contrast sequences commonly employed in hospital settings. MethodsThis prospective single-center study included ischemic stroke patients not related to perforating arteries, i.e. control patients, and Moya Moya disease patients (n{degrees} 2022-A02486-37). Contrast-enhanced ultrasound sequences (CEUS) were performed by an experienced neurologist and the images acquired were used to perform post-processing ULM. ULM density maps, i.e. number of microbubbles tracked per pixel, were compared with conventional 3T TOF MRI and color Doppler imaging (one-way ANOVA test). We also compared ULM density maps between the control and Moya Moya groups (two-sided parametric Students t-tests, or Mann-Whitney test). ResultsWe included a group of 15 control patients and another group of 9 Moya Moya patients between March 2023 and March 2024. The patients had an average age of 45 years with 65% of them being male. Perforating arteries were captured on all subjects, with a mean diameter of 0.8 {+/-} 0.3 mm in control patients, while it was not so far possible with TOF MRI or color Doppler (P < 0.05). Moreover, ULM enabled the differentiation between healthy subjects and those with Moya Moya disease through track mean distance (P = 0.05). ConclusionsUsing a low-frame-rate ultrasound scanner, CEUS and accessible post-processing tools, we have demonstrated that transcranial ULM can facilitate the visualization and characterization of perforating arteries, even in cases where they were previously undetectable using standard non-invasive imaging techniques. We speculate that with the advent of high-frame-rate 3D ULM, this technique may find widespread utility in hospitals. Key Results- 2D low-frame rate Ultrasound Localization Microscopy (ULM) allows visualization of perforating arteries, i.e. diameter of 0.8 {+/-} 0.3 mm. - ULM described vessels that were not visible in conventional imaging techniques, i.e. TOF MRI and color Doppler. - ULM reconstruction and quantification of the perforating arteries enabled the pathological group (Moya Moya) to be distinguished from control subjects. Summary statementTranscranial 2D ULM performed with a standard low frame-rate clinical ultrasound scanner enabled visualization and morphological description of perforating arteries. The study involved 24 subjects, including 9 Moya Moya patients.