Dennis L. Parker

Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation.

Background— Atrial fibrillation (AF) is associated with diffuse left atrial fibrosis and a reduction in endocardial voltage. These changes are indicators of AF severity and appear to be predictors of treatment outcome. In this study, we report the utility of delayed-enhancement magnetic resonance imaging (DE-MRI) in detecting abnormal atrial tissue before radiofrequency ablation and in predicting procedural outcome. Methods and Results— Eighty-one patients presenting for pulmonary vein antrum isolation for treatment of AF underwent 3-dimensional DE-MRI of the left atrium before the ablation. Six healthy volunteers also were scanned. DE-MRI images were manually segmented to isolate the left atrium, and custom software was implemented to quantify the spatial extent of delayed enhancement, which was then compared with the regions of low voltage from electroanatomic maps from the pulmonary vein antrum isolation procedure. Patients were assessed for AF recurrence at least 6 months after pulmonary vein antrum isolation, with an average follow-up of 9.6±3.7 months (range, 6 to 19 months). On the basis of the extent of preablation enhancement, 43 patients were classified as having minimal enhancement (average enhancement, 8.0±4.2%), 30 as having moderate enhancement (21.3±5.8%), and 8 as having extensive enhancement (50.1±15.4%). The rate of AF recurrence was 6 patients (14.0%) with minimal enhancement, 13 (43.3%) with moderate enhancement, and 6 (75%) with extensive enhancement (P<0.001). Conclusions— DE-MRI provides a noninvasive means of assessing left atrial myocardial tissue in patients suffering from AF and might provide insight into the progress of the disease. Preablation DE-MRI holds promise for predicting responders to AF ablation and may provide a metric of overall disease progression.

Analysis of partial volume effects in diffusion-tensor MRI.

The diffusion tensor is currently the accepted model of diffusion in biological tissues. The measured diffusion behavior may be more complex when two or more distinct tissues with different diffusion tensors occupy the same voxel. In this study, a partial volume model of MRI signal behavior for two diffusion‐tensor compartments is presented. Simulations using this model demonstrate that the conventional single diffusion tensor model could lead to highly variable and inaccurate measurements of diffusion behavior. The differences between the single and two‐tensor models depend on the orientations, fractions, and exchange between the two diffusion tensor compartments, as well as the diffusion‐tensor encoding technique and diffusion‐weighting that is used in the measurements. The current single compartment models inaccuracies could cause diffusion‐based characterization of cerebral ischemia and white matter connectivity to be incorrect. A diffusion‐tensor MRI imaging experiment on a normal human brain revealed significant partial volume effects between oblique white matter regions when using very large voxels and large diffusion‐weighting (b ∼ 2.69 × 103 sec/mm2). However, the apparent partial volume effects in white matter decreased significantly when smaller voxel dimensions were used. For diffusion tensor studies obtained using typical diffusion‐weighting values (b ∼ 1 × 103 sec/mm2) partial volume effects are much more difficult to detect and resolve. More accurate measurements of multiple diffusion compartments may lead to improved confidence in diffusion measurements for clinical applications. Magn Reson Med 45:770–780, 2001.

New magnetic resonance imaging-based method for defining the extent of left atrial wall injury after the ablation of atrial fibrillation.

OBJECTIVES We describe a noninvasive method of detecting and quantifying left atrial (LA) wall injury after pulmonary vein antrum isolation (PVAI) in patients with atrial fibrillation (AF). Using a 3-dimensional (3D) delayed-enhancement magnetic resonance imaging (MRI) sequence and novel processing methods, LA wall scarring is visualized at high resolution after radiofrequency ablation (RFA). BACKGROUND Radiofrequency ablation to achieve PVAI is a promising approach to curing AF. Controlled lesion delivery and scar formation within the LA are indicators of procedural success, but the assessment of these factors is limited to invasive methods. Noninvasive evaluation of LA wall injury to assess permanent tissue injury may be an important step in improving procedural success. METHODS Imaging of the LA wall with a 3D delayed-enhanced cardiac MRI sequence was performed before and 3 months after ablation in 46 patients undergoing PVAI for AF. Our 3D respiratory-navigated MRI sequence using parallel imaging resulted in 1.25 x 1.25 x 2.5 mm (reconstructed to 0.6 x 0.6 x 1.25 mm) spatial resolution with imaging times ranging 8 to 12 min. RESULTS Radiofrequency ablation resulted in hyperenhancement of the LA wall in all patients post-PVAI and may represent tissue scarring. New methods of reconstructing the LA in 3D allowed quantification of LA scarring using automated methods. Arrhythmia recurrence at 3 months correlated with the degree of wall enhancement with >13% injury predicting freedom from AF (odds ratio: 18.5, 95% confidence interval: 1.27 to 268, p = 0.032). CONCLUSIONS We define noninvasive MRI methods that allow for the detection and quantification of LA wall scarring after RF ablation in patients with AF. Moreover, there seems to be a correlation between the extent of LA wall injury and short-term procedural outcome.

Comparison of gradient encoding schemes for diffusion-tensor MRI

The accuracy of single diffusion tensor MRI (DT‐MRI) measurements depends upon the encoding scheme used. In this study, the diffusion tensor accuracy of several strategies for DT‐MRI encoding are compared. The encoding strategies are based upon heuristic, numerically optimized, and regular polyhedra schemes. The criteria for numerical optimization include the minimum tensor variance (MV), minimum force (MF), minimum potential energy (ME), and minimum condition number. The regular polyhedra scheme includes variations of the icosahedron. Analytical comparisons and Monte Carlo simulations show that the icosahedron scheme is optimum for six encoding directions. The MV, MF, and ME solutions for six directions are functionally equivalent to the icosahedron scheme. Two commonly used heuristic DT‐MRI encoding schemes with six directions, which are based upon the geometric landmarks of a cube (vertices, edge centers, and face centers), are found to be suboptimal. For more than six encoding directions, many methods are able to generate a set of equivalent optimum encoding directions including the regular polyhedra, and the ME, MF and MV numerical optimization solutions. For seven directions, a previously described heuristic encoding scheme (tetrahedral plus x, y, z) was also found to be optimum. This study indicates that there is no significant advantage to using more than six encoding directions as long as an optimum encoding is used for six directions. Future DT‐MRI studies are necessary to validate these observations. J. Magn. Reson. Imaging 2001;13:769–780.

Ultrasound-Mediated Tumor Imaging and Nanotherapy using Drug Loaded, Block Copolymer Stabilized Perfluorocarbon Nanoemulsions

Perfluorocarbon nanoemulsions can deliver lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or (19)F MRI. In the first generation of block copolymer stabilized perfluorocarbon nanoemulsions, perfluoropentane (PFP) was used as the droplet forming compound. Although manifesting excellent therapeutic and ultrasound imaging properties, PFP nanoemulsions were unstable at storage, difficult to handle, and underwent hard to control phenomenon of irreversible droplet-to-bubble transition upon injection. To solve the above problems, perfluoro-15-crown-5-ether (PFCE) was used as a core forming compound in the second generation of block copolymer stabilized perfluorocarbon nanoemulsions. PFCE nanodroplets manifest both ultrasound and fluorine ((19)F) MR contrast properties, which allows using multimodal imaging and (19)F MR spectroscopy for monitoring nanodroplet pharmacokinetics and biodistribution. In the present paper, acoustic, imaging, and therapeutic properties of unloaded and paclitaxel (PTX) loaded PFCE nanoemulsions are reported. As manifested by the (19)F MR spectroscopy, PFCE nanodroplets are long circulating, with about 50% of the injected dose remaining in circulation 2h after the systemic injection. Sonication with 1-MHz therapeutic ultrasound triggered reversible droplet-to-bubble transition in PFCE nanoemulsions. Microbubbles formed by acoustic vaporization of nanodroplets underwent stable cavitation. The nanodroplet size (200nm to 350nm depending on a type of the shell and conditions of emulsification) as well as long residence in circulation favored their passive accumulation in tumor tissue that was confirmed by ultrasonography. In the breast and pancreatic cancer animal models, ultrasound-mediated therapy with paclitaxel-loaded PFCE nanoemulsions showed excellent therapeutic properties characterized by tumor regression and suppression of metastasis. Anticipated mechanisms of the observed effects are discussed.

Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: a high-resolution magnetic resonance imaging trial.

BACKGROUND Magnetic resonance imaging (MRI) can noninvasively assess changes in atherosclerotic plaque morphology and composition. The ORION trial assessed the effects of rosuvastatin on carotid plaque volume and composition. METHODS The randomized, double-blind ORION trial used 1.5-T MRI to image carotid atherosclerotic plaques at baseline and after 24 months of treatment. Forty-three patients with fasting low-density lipoprotein cholesterol > or = 100 and < 250 mg/dL and 16% to 79% carotid stenosis by duplex ultrasound were randomized to receive either a low (5 mg) or high (40/80 mg) dose of rosuvastatin. RESULTS After 24 months, 33 patients had matched serial MRI scans to compare by reviewers blinded to clinical data, dosage, and temporal sequence of scans. Low-density lipoprotein cholesterol was significantly reduced from baseline in both the low- and high-dose groups (38.2% and 59.9%, respectively, both P < .001). At 24 months, there were no significant changes in carotid plaque volume for either dosage group. In all patients with a lipid-rich necrotic core (LRNC) at baseline, the mean proportion of the vessel wall composed of LRNC (%LRNC) decreased by 41.4% (P = .005). CONCLUSIONS In patients with moderate hypercholesterolemia, both low- and high-dose rosuvastatin were effective in reducing low-density lipoprotein cholesterol. Furthermore, rosuvastatin was associated with a reduction in %LRNC, whereas the overall plaque burden remained unchanged over the course of 2 years of treatment. These findings provide evidence that statin therapy may have a beneficial effect on plaque volume and composition, as assessed by noninvasive MRI.

Association of Left Atrial Fibrosis Detected by Delayed-Enhancement Magnetic Resonance Imaging and the Risk of Stroke in Patients With Atrial Fibrillation

OBJECTIVES This study tried to determine the association between left atrial (LA) fibrosis, detected using delayed-enhanced magnetic resonance imaging (DE-MRI), and the CHADS(2) score (point system based on individual clinical risk factors including congestive heart failure, hypertension, age, diabetes, and prior stroke) variables, specifically stroke. BACKGROUND In patients with atrial fibrillation (AF), conventional markers for the risk of stroke base their higher predictive effect on clinical features, particularly previous stroke history, and not individual LA pathophysiological properties. We aimed to determine the association between LA fibrosis, detected using DE-MRI, and the CHADS(2) score variables, specifically stroke. METHODS Patients with AF who presented to the AF clinic and received a DE-MRI of the LA were evaluated. Their risk factor profiles, including a CHADS(2) score, were catalogued. The degree of LA fibrosis was determined as a percentage of the LA area. Any history of previous strokes, warfarin use, or cerebrovascular disease was recorded. RESULTS A total of 387 patients, having a mean age of 65 ± 12 years, 36.8% female, were included in this study. A history of previous stroke was present in 36 (9.3%) patients. Those patients with previous strokes had a significantly higher percentage of LA fibrosis (24.4 ± 12.4% vs. 16.2 ± 9.9%, p < 0.01). A larger amount of LA fibrosis was also seen in those patients with a higher CHADS(2) score (≥ 2: 18.7 ± 11.4 vs. <2: 14.7 ± 9.2, p < 0.01). A logistic regression analysis of all variables except strokes (CHAD score) demonstrated that LA fibrosis independently predicted cerebrovascular events (p = 0.002) and significantly increased the predictive performance of the score (area under the curve = 0.77). CONCLUSIONS Our preliminary, multicenter results suggest DE-MRI-based detection of LA fibrosis is independently associated with prior history of strokes. We propose that the amount of DE-MRI-determined LA fibrosis could represent a marker for stroke and a possible therapeutic target with potential applicability for clinical treatment for patients with AF.

On the dark rim artifact in dynamic contrast-enhanced MRI myocardial perfusion studies

A dark band or rim along parts of the subendocardial border of the left ventricle (LV) and the myocardium has been noticed in some dynamic contrast‐enhanced MR perfusion studies. The artifact is thought to be due to susceptibility effects from the gadolinium bolus, motion, or resolution, or a combination of these. Here motionless ex vivo hearts in which the cavity was filled with gadolinium are used to show that dark rim artifacts can be consistent with resolution effects alone. Magn Reson Med, 2005.

A geometric analysis of diffusion tensor measurements of the human brain

The degree of diffusion tensor anisotropy is often associated with the organization of structural tissues such as white matter. Numerous measures of diffusion anisotropy have been proposed, which could lead to confusion in interpreting and comparing results from different studies. In this study, a new method for representing the diffusion tensor shape, called the three‐phase (3P) plot, is described. This is a graphical technique based upon a barycentric coordinate system, which weights the tensor shape by a combination of linear, cylindrical, and spherical shape factors. This coordinate system can be used to map and potentially segment different tissues based upon the tensor shape. In addition, the 3P plot can be used to examine the shape properties of existing measures of diffusion anisotropy. In this paper, the 3P plot is used to compare four well‐known anisotropy measures: the anisotropy index, the fractional anisotropy, the relative anisotropy, and the volume fraction. Computer simulations and diffusion tensor images of normal brains were obtained to study the properties of this new mapping technique. Magn Reson Med 44:283–291, 2000.

Uncertainty and bias in contrast concentration measurements using spoiled gradient echo pulse sequences

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a widely used technique for assessing tissue physiology. Spoiled gradient echo (SPGR) pulse sequences are one of the most common methods for acquisition of DCE-MRI data, providing high temporal and spatial resolution with strong T(1)-weighting. Conversion of SPGR signal to concentration is briefly reviewed, and a new closed-form expression for concentration measurement uncertainty for finite signal-to-noise ratio (SNR) and baseline scan time is derived. This result is applicable to arbitrary concentration-dependent relaxation rate and is valid over the same domain as the theoretical SPGR signal equation. Expressions for the lower and upper bounds on measurable concentration are also derived. The existence of a concentration- and tissue-dependent optimal flip angle that minimizes concentration uncertainty is demonstrated and it is shown that, for clinically relevant pulse sequence parameters, this optimal flip angle is significantly larger than the corresponding Ernst angle. Analysis of three pulse sequences from the DCE-MRI literature shows that optimization of flip angle using the methods discussed here leads to potential improvements of 10-1166% in effective SNR over the 0.5-5.0 mM concentration range with minimal or no loss of measurement accuracy down to 0.1 mM. In vivo data from three study patients provide further support for our theoretical expression for concentration measurement uncertainty, with predicted and experimental estimates agreeing to within +/- 30%. Equations for concentration bias resulting from biases in flip angle and from pre-contrast relaxation time and contrast relaxivity (both longitudinal and transverse) are also derived in closed-form. The resulting equations show the potential for significant contributions to bias in concentration measurement arising from even relatively small mis-specification of flip angle and/or pre-contrast longitudinal relaxation time, particularly at high contrast concentrations.