Rationale for multi-dimensional microscopy

Revision as of 15:32, 30 April 2009

Many complex and dynamic tissue microenvironments play critical roles in health and disease – examples include stem-cell niches, brain tissue surrounding neuroprosthetic devices, retinal tissue, tumors, cancer stem-cell niches, and immune system components. Progress in these areas is much too slow compared to the need. Much of the biology remains unknown Therapeutic potential remains unrealized. Grand Challenges wait to be tackled. There is a compelling need to accelerate progress.

Why Imaging? Many high-throughput investigational technologies have been developed (and continue to be developed) to address this need. For example, many types of gene and protein microarrays have been developed that allow a large number of genes and proteins to be studied at once. This is powerful, but suffers from an important limitation. Obtaining this information requires one to 'grind up' all the cells. This process disrupts cellular structure, and loses all location information. We no longer know where a protein of interest is located within a cell. Obtaining spatial information requires imaging

Another high-throughput method is flow cytometry, that allows scientists to observe large numbers of cells in a short period. Tissues are broken up to the point that the cells of interest are suspended in a liquid medium. These suspended cells are then made to flow past optical sensors that record fluorescent signals. More advanced instruments even permit sorting of cells based on the recorded signals. Finally, some of the newer instruments, known as imaging flow cytometers can also record images of individual cells as they flow past the sensor. This method can preserve some amount of intra-cellular location information. However, flow-based methods inevitably disrupt tissue structure. We lose all information about the spatial arrangement and juxtaposition of cells in tissue. For many studies, this type of tissue context information is important.

In summary, methods that disrupt cell & tissue structure miss vital information on sub-cellular localization, location of cells in the tissue & relative to implanted devices (if any), structure of the cellular microenvironment, spatial relationships among cell & tissue entities, spatial dynamics of entities, and interactions. Only imaging of intact cells & tissue can provide these types of information.

Why Multi-dimensional Imaging? In a nutshell, multi-dimensional images offer a lot more information about living systems.