Background Atrial fibrillation (AF) is associated with diffuse left atrial (LA) 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 MRI (DE-MRI) in detecting abnormal atrial tissue prior to radiofrequency ablation and in predicting procedural outcome. Methods and Results Eighty-one patients presenting for pulmonary vein antrum isolation (PVAI) for treatment of AF underwent 3D DE-MRI of the LA prior to the ablation. Six healthy volunteers were also scanned. DE-MRI images were manually segmented to isolate the LA and custom software was implemented to quantify the spatial extent of delayed enhancement, which was then compared to the regions of low voltage from electroanatomical maps from the PVAI procedure. Patients were assessed for AF recurrence at least six months following PVAI with average follow-up of 9.6 ± 3.7 months (range = 6 to 19 months). Based on the extent of pre-ablation enhancement, 43 patients were classified as having minimal enhancement (average enhancement = 8.0% ± 4.2%), 30 as moderate (enhancement = 21.3% ± 5.8%), and 8 as extensive (enhancement = 50.1% ± 15.4%). The rate of AF recurrence was 6 patients (14.0%) with minimal enhancement, 13 (43.3%) with moderate and 6 (75%) patients with extensive enhancement (p <0.001). Conclusion DE-MRI provides a non-invasive means of assessing LA myocardial tissue in patients suffering from AF and might provide insight into the progress of the disease. Pre-ablation DE-MRI holds promise to predict responders to AF ablation and may provide a metric of overall disease progression.

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 twotensor models depend on the orientations, fractions, and exchange between the two diffusion tensor compartments, as well as the diffusion-tensor encoding technique and diffusionweighting that is used in the measurements. The current single compartment model's inaccuracies could cause diffusionbased 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 ϳ 2.69 ؋ 10 3 sec/mm 2 ). However, the apparent partial volume effects in white matter decreased significantly when smaller voxel dimensions were used. The diffusion-tensor is a mathematically elegant description of diffusion as a function of direction. Basser and Pierpaoli (1) applied the tensor formalism to diffusion measurements of biological tissues obtained by MRI and NMR spectroscopy. One of the most important observations is that organized fibrous tissues, such as muscle and cerebral white matter, demonstrate anisotropic diffusion. The direction of greatest diffusivity corresponds to the fiber axis direction. The diffusion tensor describes the magnitude of the water diffusion, the degree of diffusion anisotropy, and the orientation of the anisotropy.Measurements of the diffusion tensor and its components (i.e., the trace) have been found to have several applications in the human brain (2,3). The trace of the diffusion tensor has been found to be valuable for detecting and evaluating brain ischemia and stroke (4,5). Measures of diffusion tensor anisotropy have been used to study white matter in terms of morphology (6), disease and trauma (8,9), brain development (10,11), and neurosurgical planning (12). Several investigators have recently proposed using the principal eigenvectors of the diffusion tensor to estimate white matter connectivity (13)(14)(15). Each of these applications will be influenced by the accuracy of the measurements of the diffusion tensor. Recent studies have investigated the effects of measurement noise (16,17) and the tensor encoding strategy (18) on the accuracy of the diffusion tensor and its derived parameters.Partial volume effects can also significantly influence the accuracy of diffusion tensor measurements. This is particularly true for most DT-MRI studies that use EPI techniques with relatively large voxels (ϳ1.5-5.0 mm on a side). Previous stud...

Perfluorocarbon nanoemulsions can deliver lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or 19F 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 (19F) MR contrast properties, which allows using multimodal imaging and 19F 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 19F MR spectroscopy, PFCE nanodroplets are long circulating, with about 50% of the injected dose remaining in circulation two hours 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 (200 nm to 350 nm 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.

Background While catheter ablation therapy for atrial fibrillation (AF) is becoming more common, results vary widely and patient selection criteria remain poorly defined. We hypothesized that late gadolinium enhancement magnetic resonance imaging (LGE-MRI) can identify left atrial (LA) wall structural remodeling (SRM) and stratify patients who are likely or not to benefit from ablation therapy. Methods and Results LGE-MRI was performed on 426 consecutive AF patients without contraindications to MRI and before undergoing their first ablation procedure and on 21 non-AF control subjects. Patients were categorized by SRM stage (I–IV) based on percentage of LA wall enhancement for correlation with procedure outcomes. Histological validation of SRM was performed comparing LGE-MRI to surgical biopsy. A total of 386 patients (91%) with adequate LGE-MRI scans were included in the study. Post-ablation, 123 (31.9%) experienced recurrent atrial arrhythmias over one-year follow-up. Recurrent arrhythmias (failed ablations) occurred at higher SRM stages with 28/133 (21.0%) stage I, 40/140 (29.3%) stage II, 24/71 (33.8%) stage III, and 30/42 (71.4%) stage IV. In multi-variate analysis, ablation outcome was best predicted by advanced SRM stage (hazard ratio (HR) 4.89; p<0.0001) and diabetes (HR 1.64; p=0.036) while increased LA volume and persistent AF were not significant predictors. LA wall enhancement was significantly greater in AF patients vs. non-AF controls (16.6±11.2% vs. 3.1±1.9%, p<0.0001). Histological evidence of remodeling from surgical biopsy specimens correlated with SRM on LGE-MRI. Conclusions Atrial SRM is identified on LGE-MRI and extensive LGE (≥30% LA wall enhancement) predicts poor response to catheter ablation therapy for AF.

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 concentrationdependent 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.

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.

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.

The accuracy of volume flow rate measurements obtained with phase-contrast methods was assessed by means of computer simulation and in vitro experiments. Factors studied include (a) the partial-volume effect due to voxel dimensions relative to vessel dimensions and orientation and (b) intravoxel phase dispersion. It is shown that limited resolution (partial-volume effect) is the major obstacle to accurate flow measurement for both laminar and plug flow. The results show that at least 16 voxels must cover the cross section of the vessel lumen to obtain a measurement accuracy to within 10%. Measurement accuracy also greatly depends on the relative signal intensity of stationary tissue and is better for laminar flow than plug flow.