Simultaneous Measurements of Blood Oxygenation/Flow

At the Optical Imaging Laboratory we have integrated multi-wavelength optical imaging of blood oxygenation with laser speckle imaging of blood flow into a single instrument, originally developed by Andrew Dunn (Dunn, Optics Letters 2003; Dunn, Neuroimage 2005). Anna Devor and colleagues perform simultaneous recordings of oxyhemoglobin, deoxyhemoglobin, total hemoglobin, blood flow and electrophysiological measurements of multiple unit activity (MUA) and local field potentials (LFP). Using this technology They have demonstrated that a point hemodynamic measure is influenced by neuronal activity across multiple cortical columns (Devor, PNAS 2005). This finding provides a possible explanation for their previous finding that local vascular response increases beyond saturation of local neuronal activity (Devor, Neuron 2003).

CCD Camera-based Voltage- and Calcium-sensitive Dye Imaging

These techniques are complementary to electrophysiological recordings and allow spatial mapping of neuronal activity. While voltage-sensitive measurements are currently limited to CCD camera-based detection, calcium signals can be detected either in a full-field mode using a CCD or in a single-cell mode using two-photon microscopy. Anna Devor and colleagues use voltage- and calcium-sensitive dyes in combination with laminar MUA/LFP recordings to reconstruct the neuronal response aiming to bridge the hemodynamic signals to the underlying single-cell neuronal activity.

Two-photon Imaging of Vascular Activity

At the Optical Imaging Laboratory we have a home-built two-photon system, originally constructed by Matt Bouchard and Elizabeth Hillman. Anna Devor and colleagues use two-photon microscopy to measure changes in blood flow velocity and vessel diameter in individual vessels during functional stimulus. In addition, they have an established collaboration with David Kleinfeld’s group at UCSD, and in particular with Nozomi Nishimura, to image functional changes on the level of a single vessel using two-photon microscopy. The major benefit of using two-photon microscopy is the ability to image non-destructively to depths of up to 500 um.

Two-photon Imaging of Calcium Activity

Laminar Recordings of Spiking and Synaptic Neuronal Activity and Neuronal Modeling

Anna Devor and colleagues employ multi-electrode recording in the cortex and thalamus in combination with voltage- and calcium-sensitive dyes imaging for addressing questions of laminar and columnar signal propagation, and cortical response properties as a function of “on-going” cortical activity (Haslinger 2006). The electrode arrays are designed and manufactured by their collaborator Istvan Ulbert. We have an established collaboration with Anders Dale at UCSD and Gaute Einevoll’s group in Oslo , including Klas Pettersen and Patrick Blomquist, to model neuronal network behavior using their experimental data (Pettersen, J Neurosci Methods 2006). They view this modeling effort as an essential step towards the overall goal of making a connection between fMRI signals and single neuron activity.

Vascular Modeling

The hemodynamic changes measured by fMRI are the macroscopic effects of a complex series of microscopic events. In response to changes in neuronal activity, arteriole blood vessels actively dilate, giving rise to increases in blood flow along individual vascular segments. These eventually result in the net signal changes measured by fMRI. David Boas, director of the optical imaging effort at the Martinos Center, also leads the vascular modeling project. Through modeling he and colleagues integrate experimental data of different modalities (fMRI, CCD-based imaging and two-photon microscopy) and generate experimentally-testable predictions.

Optical Imaging in MRI Environment

In collaboration with Alex De Crespigny Anna Devor and colleagues have introduced optical microscopy to the MRI environment. An MR-compatible optical imager built by Elizabeth Hillman measures oxy- and deoxyhemoglobin simultaneously with (functional) fMRI. They use these data for quantization of BOLD signals in terms of hemoglobin oxygenation (Ted Huppert at Photon Migration Laboratory performs similar simultaneous optical and fMRI measurements in human using non-invasive NIRS technology). Currently they are working towards direct optical measurements of neuronal activity in MRI environment.

3D Imaging of the Hemodynamic Response

Elizabeth Hillman implemented a theoretical concept developed by Andrew Dunn and David Boas in building a laminar optical coherence tomography (LOT) system (Hillman Optics Letters 2004). Using this system in combination with vascular corrosion casts we demonstrated vascular compartments-specific hemodynamic responses. Venous functional responses showed a smaller volume change and significantly later onset times with respect to arteries and capillaries. Arterial components showed larger volume changes, and much earlier returns to baseline than capillary and venous compartments. These results have significant implications for fMRI.

Neurovascular Coupling in Stroke

In collaboration with Bruce Rosen Anna Devor and colleagues study alterations in neurovascular communication following an ischemic injury in a rat stroke model. The stroke team includes Young Kim, who performs MRI to assess the extent and location of the damaged tissue, and John Moore, an expert in surgical procedures.