In vivo microscopy in pre-clinical (rodent) models

Figure 1. Customized multimodal microscope [Yaseen, et al, BOE 2015]

The OMNI Lab strives to develop and apply high-resolution optical technologies to investigate brain function in rodent models of human disease. Specifically, we apply advanced optical microscopy methods to investigate metabolic and immune features during healthy brain function and their disease-related alterations. The overarching goal of these efforts is to characterize the etiologies of debilitating brain pathologies, including stroke and neurodegenerative diseases. Understanding at the cellular level how these pathologies advance within living brains will ultimately help identify precise and robust biomarkers for diagnosis and therapy.

As the OMNI lab starts up at Northeastern University, initial investigations will primarily utilize multiphoton microscopy. Using a commercial Bruker Ultima 2pPlus microscope, we apply lifetime-based microscopy techniques (both fluorescence- and phosphorecence- lifetime imaging) to image the brains of awake mice. Experiments are performed in rodent models of human pathologies such as Alzheimer's disease following surgical exposure of the brain and implantation of a cranial window.

Figure 1 displays a schematic of the OCTOPµS, a custom-designed multi-modal microscope developed by the OMNI Lab's Principal Investigator and colleagues while at the Martinos Center for Biomedical Imaging. The system features multiple imaging technologies for monitoring a diverse array of metrics reflecting cerebral blood flow and energy metabolism. As the OMNI lab advances, projects will involve similar technology developments to capitalize on modalities such as laser speckle contrast imaging, optical coherence tomography, and optical intrinsic signal imaging.

Figure 2. Blood flow and ATP synthesis (drastically simplified)

A simplified diagram of blood flow and energy metabolism is illustrated in figure 2. Our optical microscopy techniques offer a wealth of methods to monitor multiple facets of these processes in a minimally invasive, non-disruptive fashion at the cellular and sub-cellular scale. Using a novel assortment of fluorescent and phosphorescent labels, our studies involve assessment of several features within the living brains of animal models, including:

  • Intravascular oxygen pressure (pO2)
  • Extracellular pO2
  • Microvascular blood flow and morphology
  • Intrinsic NADH as a marker of mitochondrial ATP synthesis
  • Microglial morphology and motion
  • Astrocyte morphology and function

Observing these parameters, and combinations thereof, within the same sample provides a multi-faceted characterization of metabolic and neuroimmune activity. These studies will help us gain a more detailed understanding of the putative connections between metabolism and immunity during disease progression, and the effects of prospective therapies or preventative measures.