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Biomedical subjects

Thomas A Woolsey

Publications and source records attributed to Thomas A Woolsey.

7 recordsLinked to original sources

Computational hyperspectral interferometry for studies of brain function: proof of concept.

Hyperspectral interferometric microscopy uses a unique combination of optics and algorithm design to extract information. Local brain activity rapidly changes local blood flow and red blood cell concentration (absorption) and oxygenation (color). We demonstrate that brain activity evoked during whisker stimulation can be detected with hyperspectral interferometric microscopy to identify the active whisker-barrel cortex in the rat brain. Information about constituent components is extracted across the entire spectral band. Algorithms can be flexibly optimized to discover, detect, quantify, and visualize a wide range of significant biological events, including changes relevant to the diagnosis and treatment of disease.

Animals↗

Albumin-binding MR blood pool agents as MRI contrast agents in an intracranial mouse glioma model.

Intravenous MRI contrast agents are commonly used to improve the detection of intracranial tumors and other central nervous system (CNS) lesions for diagnosis and treatment planning. Two small-molecule, albumin-binding blood pool contrast agents (MP-2269 and MS-325) of potential clinical significance were evaluated at 1.5 Tesla in a mouse glioma model and compared with an extracellular contrast agent (OptiMARK). Tumor image contrast was significantly enhanced and long-lived following administration of 30 micromole/kg of the blood pool agents: specifically, contrast enhancement peaked slowly at 25-30 min following administration, remained constant for >3 hr, and returned to baseline within 20 hr. Comparable but "transient" enhancement was achieved using 100 micromole/kg OptiMARK: specifically, contrast enhancement peaked rapidly at 2-5 min following administration and then declined over 40 min. The blood pool contrast agents demonstrated an approximately threefold increased dose-effectiveness and a lengthened window of tumor contrast enhancement in comparison to commonly available extracellular contrast agents. This demonstrates the potential of alternative contrast-enhanced (CE) MRI examination protocols for tumor detection.

Albumins↗

Glutamate receptor blockade alters the development of intracortical connections in rat barrel cortex.

We tested the hypothesis that glutamate receptor mediated activity is required for the postnatal development of intracortical connections in layers II/III of rodent barrel cortex. To block glutamate receptors, a slow release polymer (elvax) loaded with a glutamate receptor antagonist (D-AP5) was targeted subdurally over the future rat barrel cortex on P0 (day of birth). On P14-16 biotinylated dextran amine (BDA) was injected under the elvax into all layers to label neurons retrogradely. A BDA injection was made stereotactically at the mirror site of the untreated hemisphere of each animal. The animals survived to P22-24. Injection sites and retrogradely labeled cell bodies were identified in tangential sections in relation to the barrel map. D-AP5 treated and untreated hemispheres were matched according to the location of the injection site in the barrel map. Glutamate receptor blockade did not prevent the growth of intrinsic projections, but altered their organization. The normal row-like asymmetry of connections in untreated hemispheres was lacking in the D-AP5 treated cortex (ANOVA, p=0.02). Cortical activity mediated through glutamate receptors contributes to the correct development of connections between barrel columns in layers II/III.

2-Amino-5-phosphonovalerate↗

A method to measure the effective spread of focally injected muscimol into the central nervous system with electrophysiology and light microscopy.

A method was developed to quantitate the volume of brain inactivated by muscimol focally injected. Tritiated muscimol was injected into the cerebellum and closely spaced sequential microelectrode recordings made at different depths by penetrations in an X-Y pattern centered at the injection site to evaluate changes in spontaneous activity in the tissue volume. Animals were euthanized after survivals from 40 min to 6 h, the cerebellum sectioned in the sagittal plane, and the sections dried onto glass slides. The slides were dipped in photographic emulsion, exposed in the dark and developed. Silver grain densities were quantitated by light microscopy from measured standards. The extent and concentration of bound, labeled muscimol co-varied with the observed reduction in recorded spontaneous activity. For future studies, the distribution and density of silver grains alone can serve as an accurate spatial indicator of the area of muscimol inactivation at high spatial resolution.

Animals↗

Spatial integration of vascular changes with neural activity in mouse cortex.

The authors evaluated representations of discretely activated, neighboring brain regions using real-time optical intrinsic signals by transcranial imaging with 540-nm and 610-nm broadband illumination of the mouse barrel cortex. Iron filings were glued to two neighboring whiskers (C2 + D2) that were stimulated magnetically, singly and together. Real-time images were collected, averaged, and analyzed statistically. Postmortem filling of arteries with fluorescent beads was shown in relation to histochemical staining of barrels to accurately relate surface changes to functional cortical columns. Significant optical intrinsic signal changes are related to overlapping distributions of arterioles that feed the two separate areas. Activation of adjacent and interacting cortical columns leads not only to increased magnitude of vascular responses in those columns, but also to wider spatial extent of absorption changes occurring principally in areas of cortex fed by vessels upstream of the active cortex. The localization of changing hemoglobin absorption around upstream blood vessels and their vascular domains suggests that propagated vasodilation of upstream parent vessels is greater when vasodilatory signals from separate areas of active cortex converge on common arterioles that feed them.

Animals↗