Báez-Yáñez Mario Gilberto, Siero Jeroen C W, Curcic Vanja, van Osch Matthias J P, Petridou Natalia
Translational Neuroimaging Group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands.
Spinoza Centre for Neuroimaging Amsterdam, Amsterdam, The Netherlands.
Imaging Neurosci (Camb). 2025 May 9;3. doi: 10.1162/imag_a_00573. eCollection 2025.
Recent advancements in MRI hardware, including ultra-high magnetic field scanners (≥7T) and MR data acquisition methods, have enhanced functional imaging techniques, allowing for the detailed study of brain function, particularly at the mesoscopic level of cortical organization. This has enabled the measurement of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal changes across cortical depth in the human brain, facilitating the study of neuronal activity at laminar level. In order to better understand the generation of cortical depth-dependent BOLD signals, biophysical modeling and computational simulations permit the characterization of the impact of vascular architecture, as well as the biophysical and hemodynamic effects at the mesoscopic level. In this study, we employed four realistic 3D vascular models that mimic the human cortical vascular architecture and simulated various vessel-dependent oxygen saturation and hematocrit states, aiming to characterize the intravascular and extravascular contributions to gradient-echo (GE) and spin-echo (SE) BOLD signal changes across human cortical depth at 7T. We found that differences in the local vascular architecture between the four models, away from the pial surface, do not significantly influence the shape and amplitude of BOLD profiles. This implies that signal profiles within a cortical region of a given angioarchitecture can be averaged within a given layer without introducing substantial errors in the results. The findings futher reveal that in deeper laminae, relative relaxation rates for both GE and SE decrease linearly with increasing oxygen saturation levels, with GE showing a stronger effect. In contrast, the top lamina shows a non-linear behavior due to large vessel contributions, particularly venous, with GE displaying higher relaxation rates (4-8 times larger dependent on oxygen saturation levels) than SE. Relative BOLD signal changes also follow linear trends in deeper layers, with GE peaking at ~8% and SE at ~4%, reflecting the higher microvascular specificity of SE. However, SE does not fully eliminate large vessel contributions at the pial surface, where diffusion effects and vessel architecture play a role. Hematocrit levels linearly change the BOLD signal amplitude and significantly influence laminar contributions across cortical depth and imaging techniques. While GE signals are dominated by extravascular effects, SE retains notable intravascular venous contributions at high oxygen saturation levels, which is particularly relevant in experiments involving controlled vascular oxygenation, that is, gas challenges. These results underscore how vascular features, hematocrit, and biophysical interactions shape cortical depth-dependent BOLD signals and their specificity in ultra-high field imaging.
MRI硬件的最新进展，包括超高磁场扫描仪（≥7T）和MR数据采集方法，增强了功能成像技术，使得对脑功能的详细研究成为可能，尤其是在皮质组织的介观水平上。这使得能够测量人类大脑皮质深度上的血氧水平依赖（BOLD）功能磁共振成像（fMRI）信号变化，有助于在层状水平上研究神经元活动。为了更好地理解皮质深度依赖的BOLD信号的产生，生物物理建模和计算模拟能够表征血管结构的影响，以及介观水平上的生物物理和血液动力学效应。在本研究中，我们采用了四个模拟人类皮质血管结构的逼真3D血管模型，并模拟了各种与血管相关的氧饱和度和血细胞比容状态，旨在表征7T时人类皮质深度上血管内和血管外对梯度回波（GE）和自旋回波（SE）BOLD信号变化的贡献。我们发现，在远离软脑膜表面的四个模型之间，局部血管结构的差异不会显著影响BOLD曲线的形状和幅度。这意味着在给定血管构筑的皮质区域内，信号曲线可以在给定层内进行平均，而不会在结果中引入实质性误差。研究结果进一步表明，在较深的层中，GE和SE的相对弛豫率都随着氧饱和度水平的增加而线性降低，其中GE的影响更强。相比之下，最上层由于大血管（尤其是静脉）的贡献而表现出非线性行为，GE的弛豫率（取决于氧饱和度水平，高出4 - 8倍）高于SE。相对BOLD信号变化在较深的层中也呈现线性趋势，GE在8%时达到峰值，SE在4%时达到峰值，这反映了SE具有更高的微血管特异性。然而，SE并没有完全消除软脑膜表面大血管的贡献，在该表面扩散效应和血管结构发挥着作用。血细胞比容水平线性改变BOLD信号幅度，并显著影响整个皮质深度和成像技术的层状贡献。虽然GE信号主要由血管外效应主导，但在高氧饱和度水平下，SE仍保留显著的血管内静脉贡献，这在涉及可控血管氧合（即气体激发）的实验中尤为重要。这些结果强调了血管特征、血细胞比容和生物物理相互作用如何塑造皮质深度依赖的BOLD信号及其在超高场成像中的特异性。
