Videomicroscopy, image processing, and analysis of whole histologic sections of the human brain

Serial histologic sections of a whole human brain may have extensions of up to 130 x 130 mm within the coronal plane around the temporal lobe. To date, however, technology has not provided a bright field microscope that is able to shift the object holder continuously in the x- and y-direction over such distances and still possess the same optical capabilities as comparable devices. We developed a new light microscope to continuously quantify such sections. We also developed the computing environment for controlling the device and for analyzing the data produced. In principle, we are now able to quantify each neuron of a human brain. The data ultimately will provide the most detailed structural information about the human brain ascertained thus far. Such detailed information of the spatial distribution of neurons is essential to develop realistic models for simulation of large-scale neuronal networks and to investigate the significance of neuronal arrangements with respect to neuronal signal processing in the CNS. After preprocessing of the data produced by the new microscope, we are able to detect lamination patterns in the spatial distribution of gravity centers of cells. Furthermore, morphological features like size of the projection area and mean staining intensity are visualized as a particle process. The particle process presents the sizes and staining intensity of perikaryons and allows a distinction of gray matter and white matter. These results provide evidence that the system works correctly and can be applied to a systematic analysis of a larger sequence of serial histologic sections. The objective of this study is to introduce the very large section analyzing microscope (VLSAM) and to present the initial data produced by the system. Moreover, we will discuss workload and future developments of the parallel image analysis system that are associated with the microscope.