MICCAI2005

Abstract: The explosion of progress in the elds of cell biology, biochemistry, and molecular biology has offered unprecedented knowledge of the components involved embryonic development. The dramatic progress of these reductionistic approaches poses the challenge of integrating this knowledge into an understanding of developmental mechanics that pattern and construct the embryo. The classic publications in the field of experimental embryology illustrate the power of describing cell behavior (cf. lineages, movements) and perturbing the embryo to test hypotheses of the underlying mechanisms. Advanced imaging techniques offer an important stepping-stone between these disparate approaches, permitting questions about cellular and molecular events to be posed in the most relevant setting of the intact embryo.

Both confocal laser scanning microscopy (CLSM) and two-photon laser scanning microscopy (TPLSM) permit cells to be followed as they migrate in the intact embryo. In vivo imaging of multiple labels should otffer the ability to test proposed mechanisms by following different GFP-color variants on multiple molecular species in the same cell. However, there are two major stumbling blocks. First, image acquisition by laser-scanning confocal microscopy is often too slow to capture individual image planes with su cient rapidity. Second, it is dificult to capture 4-D data at suficient temporal resolution especially if there is any motion. When the studied motion is periodic, such as for a beating heart, a way to circumvent this problem is studied motion is periodic, such as for a beating heart, a way to circumvent this problem is to acquire, successively, sets of 2D+time data at increasing depths and later rearrange them to recover a 3D+time sequence. Recently we have utilized a newly-developed fast acquisition confocal microscope (Zeiss LSM 5 LIVE) to acquire very rapid, high-resolution 2D optical sections of uorescently labeled cells in the developing zebrafish heart and have established image registration algorithms allowing for the registration of periodic movements. This method has allowed us to create 4-dimensional working models of the heart and analyze mechanical forces related to wall and valve motions from different stages of heart development. This approach is generalizable to many different setting in developmental biology and neurobiology.

In systems in which light-based imaging is problematic, we are employing microscopic MRI. In MRI, radio frequency energy is used to excite the protons of the water, which generates no toxic by-products. Spatial resolution is created by imposing gradient magnetic fields on the specimen, thereby making it possible to encode the signals from individual volume elements (voxels) by their resonant frequency and phase. By increasing the magnitudes of the static and gradient magnetic fields, and by improving the electronics, it has become possible to increase the resolution of MRI from the 1mm voxels of a clinical instrument to 10µm. This approach has the promise of making imaging analyses possible in the systems with limited access to the embryos (e.g. mouse) or in which light scattering renders deep structures invisible (e.g. frog).

Professor Arthur Toga is the director of LONI ((Laboratory of Neuro Imaging), one of the country's foremost neurological research centers. LONI works towards uncovering new knowledge that will lead to better health for everyone by conducting research and building population-based and disease-specific digital brain atlases, helping in the training of research investigators; and fostering communication of medical information.

Abstract: The ability to statistically and visually compare and contrast brain image data from multiple subjects is essential to understanding normal variability and differentiating normal from diseased populations. This talk describes some of these approaches and their application in basic and clinical neuroscience. There are numerous probabilistic atlases that describe specific subpopulations, measure their variability and characterize the structural differences between them. Utilizing data from structural MRI, we have built atlases with defined coordinate systems creating a framework for mapping data from functional, histological and other studies of the same population in several species. This talk describes the basic approach and some of the constructs that enable the calculation of probabilistic atlases and examples of their results from several different normal and diseased populations. The talk will also illustrate some approaches useful in understanding multidimensional data and the relationships between them over time. Finally, there will be challenges identified for future mapping and modeling between modalities, time, subjects and species.

Research: I am interested in the development of new algorithms and the computer science aspects important to neuroimaging. New visualization techniques and statistical measurement are employed in the study of morphometric variability in humans, subhuman primates and rodents. My laboratory (Laboratory of Neuro Imaging) has been working on the creation of three dimensional digital neuroanatomic and functional neuroanatomic atlases for stereotactic localization and multisubject comparison. Specific programs include the development of local deformation techniques to equate brain data sets from different modalities and different subjects and the development of electronic data bases for the archival, interaction and distribution of brain data.

Keynote Speakers

Scott Fraser: "Imaging the developmental mechanics of the vertebrate embryo", Friday Oct. 28th, 8.30-9:30

Art Toga: "Mapping the Structure and Function of the Brain: Where we are and we want to be", Saturday Oct. 29th, 11.00-12.00