Gerald R. Moran

A randomized trial of coenzyme Q10 in mitochondrial disorders

Case reports and open‐label studies suggest that coenzyme Q10 (CoQ10) treatment may have beneficial effects in mitochondrial disease patients; however, controlled trials are warranted to clinically prove its effectiveness. Thirty patients with mitochondrial cytopathy received 1200 mg/day CoQ10 for 60 days in a randomized, double‐blind, cross‐over trial. Blood lactate, urinary markers of oxidative stress, body composition, activities of daily living, quality of life, forearm handgrip strength and oxygen desaturation, cycle exercise cardiorespiratory variables, and brain metabolites were measured. CoQ10 treatment attenuated the rise in lactate after cycle ergometry, increased (∽1.93 ml) VO2/kg lean mass after 5 minutes of cycling (P < 0.005), and decreased gray matter choline‐containing compounds (P < 0.05). Sixty days of moderate‐ to high‐dose CoQ10 treatment had minor effects on cycle exercise aerobic capacity and post‐exercise lactate but did not affect other clinically relevant variables such as strength or resting lactate. Muscle Nerve, 2010

A trust region subproblem for 3D electrical impedance tomography inverse problem using experimental data

Image reconstruction in electrical impedance tomography (EIT) is an ill-posed nonlinear inverse problem. Regularization methods are needed to solve this problem. The results of the ill- posed EIT problem strongly depends on noise level in measured data as well as regularization parameter. In this paper, we present trust region subproblem (TRS), with the use of L-curve maximum curvature criteria to flnd a regularization parameter. Currently Krylov subspace methods especially conjugate gradient least squares (CGLS) are used for large scale 3D problem. CGLS is an e-cient technique when the norm of measured noise is exactly known. This paper demonstrates that CGLS and TRS converge to the same point on the L-curve with the same noise level. TRS can be implemented e-ciently for large scale inverse EIT problem as CGLS with no need a priori knowledge of the noise level.

Myocardial viability imaging using Gd-DTPA: physiological modeling of infarcted myocardium, and impact on injection strategy and imaging time.

Results of simulations are shown which illustrate how the concentration‐time curves of an extravascular extracellular (EVEC) contrast agent, such as Gd‐DTPA, vary in myocardial tissue. The simulations show that the variable permeability of dead myocytes within a recent myocardial infarction will significantly alter delayed enhancement patterns following a bolus injection, invariably reducing the sensitivity of this technique for the detection of permanently damaged tissue. It is further predicted that if the bolus injection is followed by a suitably selected constant infusion, the infarct size and infarct volume of distribution may be more accurately determined, even though the degree of enhancement of an infarcted region (with normal flow) above normal tissue is slightly higher for the bolus technique within the first 30 min following the injection. The degree of enhancement of an infarcted region (with normal flow) above normal tissue was comparable between the two techniques at the point in the constant infusion at which the volume of contrast injected was the same as in the bolus case, i.e., at approximately 30 min after the bolus injection. The constant infusion approach became superior thereafter as overall tissue concentrations became greater in both normal and infarcted tissue, and these concentrations remained more stable with the constant infusion approach. Preliminary experimental results in a canine model of infarction/reperfusion illustrated a delayed wash‐in of contrast agent in infarcted tissue, which may be explained by a physiological model in which dead myocytes in infarcted myocardium have non‐infinite permeability. Magn Reson Med 48:791–800, 2002.

Determining the extent to which delayed-enhancement images reflect the partition-coefficient of Gd-DTPA in canine studies of reperfused and unreperfused myocardial infarction

MRI after a constant infusion (CI) of Gd‐DTPA has been used to identify the extent of myocardial infarction (MI). However, Gd‐DTPA‐enhanced “viability” imaging is more commonly performed with a bolus (for “delayed‐enhancement” (DE) imaging). This study sought to determine how image delay time and time postinfarction influence the assessment of necrosis by DE. Both infusion and DE imaging was performed in dogs with reperfused (N = 6) or unreperfused (N = 4) MI. Estimates of the partition‐coefficient of Gd‐DTPA (λ) with DE were compared with those calculated after 60 min of infusion, and the comparisons were repeated until 4 (reperfused) or 8 (unreperfused) weeks postinfarction. In reperfused animals, the concordance (Rc) between DE and infusion estimates of λ was > 0.90 for most image delays > 8 min postinjection, for day 0 through week 3, with Rc at day 0 greater than at week 4 (P = 0.022). In unreperfused animals, there was an interaction between image delay time and time postinfarction (P < 0.001): Rc > 0.90 corresponded to longer image delays at week 1 than at weeks 4–8. Therefore, when image delays are selected appropriately, DE images can strongly reflect λ and identify irreversibly injured myocardium. Magn Reson Med 52:1069–1079, 2004.

Modeling (1H) exchange: an estimate of the error introduced in MRI by assuming the fast exchange limit in bolus tracking.

A simulation is presented which calculates the MRI signal expected from a model tissue for a given pulse sequence after a bolus injection of a contrast agent. The calculation assumes two physiologic compartments only, the intravascular and extravascular spaces. The determination of the concentration of contrast in each compartment as a function of time and position has been outlined in a previous publication (Moran and Prato, Magn Reson Med 2001;45:42–45). These contrast agent concentrations are used here to determine the NMR relaxation times as a function of time and position within the tissue. Knowledge of this simulated tissue ‘map’ of relaxation times as a function of time provides the information required to determine whether the proton exchange rate is fast or slow on the NMR timescale. Since with a bolus injection the concentration of contrast and hence the relaxation time may vary with position along the capillary, some segments of the capillary are allowed to be in fast exchange with the extravascular space, while others may be in slow exchange. Using this information, and parameters specific to a given tissue, the MRI signal for a given pulse sequence is constructed which correctly accounts for differences in proton exchange across the length of the capillary. It is shown that extravascular contrast agents show less signal dependence on water exchange, and thus may be more appropriate for quantitative imaging when using fast exchange assumptions. It is also shown that nondistributed compartment models can incorrectly estimate the water exchange that is occurring at the capillary level if exchange‐minimizing pulse sequences are not used. Magn Reson Med 51:816–827, 2004.

A novel approach for EIT regularization via spatial and spectral principal component analysis.

Electrical impedance tomography, EIT, is an imaging modality in which the internal conductivity distribution of an object is reconstructed based on voltage measurements on the boundary. This reconstruction problem is a nonlinear and ill-posed inverse problem, which requires regularization to ensure a stable solution. Most popular regularization approaches enforce smoothness in the inverse solution. In this paper, we propose a novel approach to build a subspace for regularization using a spectral and spatial multi-frequency analysis approach. The approach is based on the construction of a subspace for the expected conductivity distributions using principal component analysis. It is shown via simulations that the reconstructed images obtained with the proposed method are better than with the standard regularization approach. Using this approach, the percentage of misclassified finite elements was reduced up to twelve fold from the initial percentages after five iterations. The advantage of this technique is that prior information is extracted from the characteristic response of an object at different frequencies and spatially across the finite elements.

Dogleg trust-region application in electrical impedance tomography

This paper presents a trust-region implementation for image reconstruction of conductivity changes in electrical impedance tomography. A dogleg trust-region algorithm is applied in different cases to detect abnormalities. The dogleg algorithm approximates a Levenberg-Marquardt step within the trust region of the model function with a quadratic model. The comparison of Levenberg-Marquardt and dogleg algorithms is presented using the reconstructed images. This comparison of two techniques suggests the implementation of the dogleg method could result in the reduction of the execution time to less than 50% of that of the Levenberg-Marquardt algorithm without any quantifiable loss of quality of reconstructed images.

Increasing the Detection Rate of Normal Fetal Cardiac Structures: A Real-Time Approach

The purpose of this study was to determine if acquiring real-time sweeps of the fetal heart would be a more effective method of identifying normal cardiac structures compared with using static images during routine second-trimester obstetric sonograms. Subjects were scanned using three different techniques. The static image acquisition (protocol A) included three images of the fetal heart. Protocol B used two gray-scale sweeps through the fetal heart. Protocol C acquired three color loops of the fetal heart. The sweeps demonstrated a complete normal cardiac assessment in 71% of studies, compared with the static image and color Doppler techniques that completed a normal cardiac assessment in only 39% of studies, respectively. The real-time technique detected four chambers, the left ventricular outflow tract (LVOT), the right ventricular outflow tract (RVOT), the LVOT/RVOT crossover, and size and axis of the heart with a greater frequency than the static images and color loops in all cases. In addition, the real-time technique was able to demonstrate the pulmonary veins in 56% of cases compared with 3.6% for static images. The color Doppler acquisition demonstrated blood flow through the atrial-ventricular and semilunar valves in 86% of cases.

Regularization of EIT problem using trust region subproblem method

The electrical impedance tomography (EIT) problem is to image electrical properties, such as conductivity and permittivity, in the interior of a body given measurements of voltages at the boundary of the object. In this paper we present a new approach for regularization of the ill-posed EIT problem. This approach is based on the trust region subprob- lem (TRS), which uses L-curve maximum curvature criteria to find a regularization parameter. A comparison of the TRS method with conjugate gradient least squares (CGLS) for an experimental phantom study is presented. CGLS is an efficient technique when the norm of measured noise is exactly known. Our results show that both methods converge to the same point on the L-curve when the noise level is known. The TRS algorithm has the advantage that it does not require any knowledge of the norm of the noise.