In this review we have assessed a range of imaging techniques in systems biology spanning from microscopy to clinical imaging. In addition to the techniques reviewed, there are multiple other technologies that have lead to significant contributions to a systems level understanding of biological processes. Two such techniques are optical coherence tomography [97
] and hyperspectral imaging [99
]. With the refinement of current technologies and the development of new techniques, additional information will be available to help dissect biological systems.
As seen in Figure , there is a resolution gap between microscopy and anatomical imaging. This gap also represents the divide between experimental and clinical imaging applications. In contrast, acquiring anatomical and metabolic information with clinical scanners has been achieved by coupling imaging technologies. For example, it is now commonplace for usage of combination PET/CT scanners. This allows for metabolic information acquired in PET to be readily registered with higher resolution anatomical CT images. Also, with fMRI a slower MRI scan is also conducted to form a detailed brain atlas, to which functional images are later registered. As a result there is a resolution continuum between anatomical and metabolic imaging. To reach the same end for microscopy and anatomical imaging, molecular probes such as quantum dots and nanoshells may find more clinical applications and thus improve the resolution that can be achieved with clinical scanners.
Figure 11 Resolution spectrum of imaging techniques. The schematic shows the resolution gap between microscopy and anatomical imaging. Metabolic imaging has successfully been linked to anatomical imaging despite having lower resolution. The schematic axis is linear. (more ...)
Beyond improvements in resolution, a grand challenge remains for the imaging technology development community: to enable dynamic imaging of both biological system components and of their respective connections. For example, the ability to resolve and monitor an entire mammalian cortical circuit in vivo has yet to be realized. Electrophysiology has been increasing complemented by fMRI over the last 15 years, but with fMRI information on neural activity is provided as an indirect measure and on the scale of hundreds of thousands or millions of neurons. Two-photon imaging has provided for single cell resolution, but functionally visualizing hundreds of synapses performing computations is limited by axonal labeling of neuronal populations and also by overall temporal acquisition frequency. As a result, innovations in methods for visualizing neural circuitry and for deciphering spike times will be necessary to further advance systems neuroscience with imaging. In a broader set of application areas, using imaging to simultaneously monitor components of a molecular network will be useful in further understanding cellular processes, such as apoptosis which is critical for the development of new cancer treatments.
The further development of imaging technologies will continue to be important in the advancement of systems biology. Imaging can provide a wide array of data that can be used to build and validate models. The information acquired with imaging can be readily incorporated into models as biochemical concentrations, functional activity, and anatomical coordinates. In addition, imaging provides data for new discoveries and diagnostic information. Oncology and other areas in the biomedical sciences will benefit greatly from imaging and systems biology approaches.