Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS 46 rue d'Ulm, Paris 75005 [corrected] France.
J Biomed Opt. 2011 Nov;16(11):116012. doi: 10.1117/1.3650770.
Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.
髓鞘破坏是中枢和周围神经系统多种神经病变的原因。髓鞘成像因此成为一种重要的诊断工具。然而，体内成像一直受到限制，要么是无法分辨单个纤维的低分辨率技术，要么是对单个纤维的低穿透成像，而这些技术无法提供用于诊断目的的大量组织的定量信息。在这里，我们在活体啮齿动物上进行了无需标记且具有微米级分辨率和 >300-μm 穿透深度的髓鞘成像。这是通过一种高数值孔径红外全场相干显微镜的原型（称为深度光学相干显微镜 (deep-OCM)）实现的，该原型包括用于补偿折射率失配和高速率干涉测量的像差校正。我们能够在大鼠大脑皮层的大体积灰质中测量单个有髓纤维的密度。在周围神经系统中，深度 OCM 允许在进行少量手术之后，原位成像坐骨神经的大分数中单根有髓纤维。这允许对正常和 Krox20 突变小鼠进行定量比较，在这些小鼠中，周围神经系统的髓鞘形成受损。这为脱髓鞘疾病的髓鞘慢性成像和微创医学诊断开辟了有前景的前景。
