I am interested in improving detection of metabolism and neurotransmission in vivo. This primarily involves techniques for enhancing effective resolution by spectral editing, direct enhancement of resolution at high field, and technology development for sorting spin-states (hyperpolarization).
My research revolves around a central goal of improving measurement precision and specificity for the in vivo detection of metabolism and neurotransmission. The solution to this challenge is to improve spectral information content, and this problem can be subdivided into 3 technologies: 1) spectroscopic editing, 2) high-field pulse/sequence development, and 3) spin-sorting by (hyper)polarization. Proton spectra of coupled metabolites such as GABA and glutamine are typically unresolved in the human brain; an ongoing project involves specially preparing (editing) spin-states to reduce this covariance and improve precision in this obscured molecules. A brute force alternative is to detect at high field although the increased resolution and sensitivity is accompanied by distinct challenges. Projects are underway to leverage reduced demands for spectral selectivity while attaining uniform slice-select rotations. Higher fields also improve the feasibility of detecting Boltzman population differences in carbon-labeled compounds and active projects include measuring glucose conversion at 7 Tesla in nonhuman primates. Equilibrium carbon turnover studies reflect metabolic steady-states - to probe shorter time-scales, spin-sorting experiments (hyperpolarization) are being pursued. These projects involve hardware development and spin dynamics, with the endpoint of mapping pathway-specific flux in vivo.
Waddell KW, Coffey AM, Chekmenev EY. In Situ Detection of PHIP polarization at 48 mT: Demonstration using a Centrally Controlled Polarizer. JACS. In press.
Waddell KW, Zanjanipour P, Pradhan S, Xu L, Welch EB, Joers JM, Avison MJ, Gore JC. Anterior Cingulate and Cerebellar GABA and Glu Correlations Measured by 1H J-Difference Spectroscopy. MRI. In Press.
Sadagopal S, Lorey SL, Barnett L, Basham R, Lebo L, Erdem H, Haman K, Avison MJ, Waddell KW, Haas DW, Kalams SA. Enhancement of HIV-specific CD8+ T Cells in Cerebrospinal Fluid Compared to Blood among Anti-retroviral Therapy Naive HIV+ Subjects. J Virol, 2008, 82(21), 10418-28.
Waddell KW, Avison MJ, Joers JM, Gore JC. A Practical Guide to Robust Detection of GABA in Human Brain by J-difference Spectroscopy at 3 Tesla Using a Standard Volume Coil. Magn Res Imag, 2007, 25, 1032-1038. PMCID: PMC2131736