Lowerison Matthew R, Wang Yike, Lin Bing-Ze, Huang Zhe, Yan Dongliang, Shin YiRang, Song Pengfei
Department of Electrical and Computer Engineering, University of Illinois Urbana-Champaign, Urbana, IL, United States.
Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, United States.
Imaging Neurosci (Camb). 2025 Sep 15;3. doi: 10.1162/IMAG.a.151. eCollection 2025.
Ultrasound localization microscopy is a super-resolution vascular imaging technique which has garnered substantial interest as a tool for small animal neuroimaging, neuroscience research, and the characterization of vascular pathologies. In the context of small animal neurovascular imaging, we posit that increasing the ultrasound imaging frequency is a straightforward approach to enable higher concentrations of microbubble contrast agents, thus increasing the likelihood of microvascular mapping and decreasing the imaging duration. To test this hypothesis, we compared ULM imaging resolution of mouse brain vasculature for three transducers with different center transmit frequencies (15 MHz, 23 MHz, and 31 MHz) under conditions of low and high MB concentration. We demonstrate that higher frequency imaging resulted in more efficient microbubble localization due to a smaller microbubble point-spread function that is easier to localize, and which can achieve a higher localizable concentration within the same unit volume of tissue. We found that increasing the imaging frequency had a minor impact on ULM spatial resolution, as measured by Fourier ring correlation, under the low MB concentration case, but a substantial impact in the high MB concentration case. High-frequency ULM yielded a spatial resolution of 6.9 μm, as measured by Fourier ring correlation, throughout the entire depth of the brain. This highlights the potential of this technology as a highly relevant tool for neuroimaging research, which has substantial implications for neuroscientists investigating microvascular function in disease states, regulation, and brain development.
超声定位显微镜是一种超分辨率血管成像技术，作为一种用于小动物神经成像、神经科学研究和血管病变特征分析的工具，它已引起了广泛关注。在小动物神经血管成像的背景下，我们认为提高超声成像频率是一种直接的方法，可以使微泡造影剂浓度更高，从而增加微血管成像的可能性并缩短成像时间。为了验证这一假设，我们在低浓度和高浓度微泡条件下，比较了三种具有不同中心发射频率（15兆赫、23兆赫和31兆赫）的换能器对小鼠脑血管的超声定位显微镜成像分辨率。我们证明，由于微泡点扩散函数较小，高频成像更容易定位，从而导致更有效的微泡定位，并且在相同单位体积的组织内可以实现更高的可定位浓度。我们发现，在低浓度微泡情况下，通过傅里叶环相关测量，提高成像频率对超声定位显微镜的空间分辨率影响较小，但在高浓度微泡情况下影响较大。通过傅里叶环相关测量，高频超声定位显微镜在整个脑深度范围内的空间分辨率为6.9微米。这突出了这项技术作为神经成像研究高度相关工具的潜力，这对研究疾病状态、调节和脑发育中微血管功能的神经科学家具有重要意义。
