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Joanne Markham

Publications and source records attributed to Joanne Markham.

3 recordsLinked to original sources

Intravenous levodopa administration in humans based on a two-compartment kinetic model.

Levodopa, when combined with a decarboxylase inhibitor, essentially delivers dopamine directly to the brain, with no net effect on brain blood vessels. For future neuroimaging studies of Parkinson disease and Tourette syndrome, we sought to rapidly produce a biologically relevant levodopa concentration in plasma and then maintain that concentration long enough to assess motor, cognitive, emotional, and neuroimaging responses, while minimizing side effects in levodopa-naive individuals. Based on available pharmacokinetic data and a two-compartment model, we designed a decreasing-exponential-rate infusion to meet these goals. This report gives results of double-blind levodopa and placebo infusions in six healthy subjects. Mean plasma levodopa concentrations were within 3% of their 1200 ng/mL target at 20 and 40 min into the infusion, and within 20% between approximately 12 and 90 min. Levodopa significantly reduced serum prolactin and raised serum growth hormone concentrations. Volunteers had no significant side effects.

Administration, Oral↗

Arterial input functions for dynamic susceptibility contrast MRI: requirements and signal options.

Cerebral perfusion imaging using dynamic susceptibility contrast (DSC) has been the subject of considerable research and shows promise for basic science and clinical use. In DSC, the MRI signals in brain tissue and feeding arteries are monitored dynamically in response to a bolus injection of paramagnetic agents, such as gadolinium (Gd) chelates. DSC has the potential to allow quantitative imaging of parameters such as cerebral blood flow (CBF) with a high signal-to-noise ratio (SNR) in a short scan time; however, quantitation depends critically on accurate and precise measurement of the arterial input function (AIF). We discuss many requirements and factors that make it difficult to measure the AIF. The AIF signal should be linear with respect to Gd concentration, convertible to the same concentration scale as the tissue signal, and independent of hematocrit. Complicated relationships between signal and concentration can violate these requirements. The additional requirements of a high SNR and high spatial/temporal resolution are technically challenging. AIF measurements can also be affected by signal saturation and aliasing, as well as dispersion/delay between the AIF sampling site and the tissue. We present new in vivo preliminary results for magnitude-based (DeltaR2*) and phase-based (Deltaphi) AIF measurements that show a linearity advantage of phase, and a disparity in the scaling of Deltaphi AIFs, DeltaR2* AIFs, and DeltaR2* tissue curves. Finally, we discuss issues related to the choice of AIF signal for quantitative perfusion imaging.

Brain↗

Numerical evaluation of Hankel transforms for oscillating functions.

Six methods for the numerical calculation of zero-order Hankel transforms of oscillating functions were evaluated. One method based on Filon quadrature philosophy, two published projection-slice methods, and a third projection-slice method based on a new approach to computation of the Abel transform were implemented; alternative versions of two of the projection-slice methods were derived for more accurate approximations in the projection step. These six algorithms were tested with an oscillating sweep signal and with the calculation of a three-dimensional diffraction-limited point-spread function of a fluorescence microscope. We found that the Filon quadrature method is highly accurate but also computationally demanding. The projection-slice methods, in particular the new one that we derived, offer an excellent compromise between accuracy and computational efficiency.

Algorithms↗