CAREER: Hybrid adaptive optics: a new paradigm for faster, deeper, volumetric microscopy in scattering media

光学显微镜在疾病临床管理的生物医学发现中发挥了关键作用，但对于需要在大体积上进行快速、无创成像的应用，特别是在光学致密生物介质深处成像时，仍然存在重大挑战。该建议通过开发新的分割方法来解决这些限制，并在最先进的计算和硬件方法之间共享图像形成的工作。这些方法将通过对现有方法无法研究的生物现象进行成像来证明。伴随的教育和推广活动将培养对生物医学光学和成像的更广泛的认识，并培训科学家和工程师有效地与公众互动，并吸引公众。该提案的推广方面将为初高中学生创建体验式和互动式探究式研讨会，为伊萨卡科学中心开发互动式演示，并培训研究生有效地与公众交流他们的科学。深入生物介质的高通量体积显微镜对于动态生物过程的研究非常重要，例如与集体细胞迁移相关的生物物理相互作用，或小鼠大脑中的神经网络活动。光学相干显微镜（OCM）和三光子显微镜（3PM）是目前能够在散射生物样品中进行最深显微镜成像的模式。然而，它们的体积成像速度和穿透深度目前受到深度相关光子收集或由于像差和多重散射引起的波前畸变的限制。该方案将硬件自适应光学（AO）和计算自适应光学（CAO）协同结合，显著提高体积OCM和3PM的成像速度和成像深度范围。这种混合AO方法将用于开辟新的研究途径，包括研究三维迁移过程中细胞间牵引力的协调，以及研究小鼠大脑深处神经网络活动的行为和时空模式之间的联系。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Optical microscopy has played a key role in biomedical discoveries for clinical management of disease, but significant challenges remain for applications that require rapid, non-invasive imaging over large volumes, particularly when imaging deep into optically dense biological media. This proposal addresses these limitations by developing new ways of splitting up, and sharing the work of image formation between state-of-the-art computational and hardware approaches. These methods will be demonstrated by imaging biological phenomena that cannot be studied with existing methods. The accompanying education and outreach activities will foster a broader appreciation for biomedical optics and imaging, and train scientists and engineers to effectively interact with, and engage the public. Outreach aspects of this proposal will create experiential and interactive inquiry-based workshops for middle and high school students, develop interactive demonstrations for the Ithaca Sciencenter and train graduate students to effectively communicate their science with the public. High-throughput volumetric microscopy deep in biological media is important for the study of dynamic biological processes, such as the biophysical interactions associated with collective cell migration, or neural network activity in the mouse brain. Optical coherence microscopy (OCM) and three-photon microscopy (3PM) are currently the modalities that enable the deepest microscopic imaging in scattering biological samples. However, their volumetric imaging speed and penetration depth is currently limited by depth-dependent photon collection, or by wavefront distortions due to aberrations and multiple scattering. This proposal will synergistically combine hardware adaptive optics (AO) and computational adaptive optics (CAO), to dramatically improve the speed and imaging depth range of volumetric OCM and 3PM.This hybrid AO approach will be used to launch new avenues of investigation, including studies on inter-cell coordination of cell traction forces during 3D migration, and investigations on the connection between behavior and spatiotemporal patterns of neural network activity deep in the mouse brain.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.