Super-resolution Ultrasound Microvascular Angiography for Spinal Cord Penumbra Imaging

Objective: After spinal cord injury (SCI) or ischemia, timely intervention in the penumbra, such as recanalization and tissue reperfusion, is essential for preservation of its function. However, limited by imaging resolution and micro-blood flow sensitivity, golden standard angiography modalities, including magnetic resonance angiography (MRA) and digital subtraction angiography (DSA), are still not applicable for spinal cord microvascular imaging. Regarding spinal cord penumbra, to the best of authors' knowledge, currently, there is no efficient in vivo imaging modality for its evaluation. With tens-of-micrometer resolution and deep penetration, advanced ultrasound locali-zation microscopy (ULM) could potentially meet the needs of emergent diagnosis and long-term monitoring of spinal cord penumbra.Methods: ULM microvasculature imaging was performed on rats with all laminae removed to obtain the blood sup-ply in major spinal cord segments (C5-L5). For adult rats with spinal cord penumbra induced by compression injury (1 s, 10 s and 15 s), ULM imaging was conducted. The corresponding angiography results are investigated in terms of microvessel saturation, morphology, and flow velocity. The Basso/Beattie/Bresnahan (BBB) locomotor rating scale and hematoxylin and eosin staining were utilized for model validation and comparison.Results: The feasibility of ULM enabling spinal cord penumbra imaging and development monitoring was demon-strated. The focal injury core and penumbra can be clearly identified using the proposed method. Significant dif-ference of perfusion can be observed after 1 s, 10 s and 15 s compression. Quantitative results show a high correlation between in vivo ultrasonic angiography, BBB functional evaluation and ex vivo histology assessment under different compression duration.Conclusion: It is demonstrated that the super-resolution ULM micro-vasculature imaging can be used to evaluate the penumbra in spinal cord at acute and early stage of chronic phase, providing an efficient modality for micro-hemodynamics monitoring of the spinal cord.