Subject-Specific Calculation of Left Atrial Appendage Blood-Borne Particle Residence Time Distribution in Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, mostly in the left atrial appendage (LAA). The current standard of stratifying stroke risk, based on the CHA2DS2-VASc score, does not consider LAA morphology, and the clinically accepted LAA morphology-based classification is highly subjective. The aim of this study was to determine whether LAA blood-borne particle residence time distribution and the proposed quantitative index of LAA 3D geometry can add independent information to the CHA2DS2-VASc score. Data were collected from 16 AF subjects. Subject-specific measurements included left atrial (LA) and LAA 3D geometry obtained by cardiac computed tomography, cardiac output, and heart rate.We quantified 3D LAA appearance in terms of a novel LAA appearance complexity index (LAA-ACI). We employed computational fluid dynamics analysis and a systems-based approach to quantify residence time distribution and associated calculated variable (LAA mean residence time, tm) in each subject. The LAA-ACI captured the subject-specific LAA 3D geometry in terms of a single number. LAA tm varied significantly within a given LAA morphology as defined by the current subjectivemethod and it was not simply a reflection of LAA geometry/appearance. In addition, LAA-ACI and LAA tm varied significantly for a given CHA2DS2-VASc score, indicating that these two indices of stasis are not simply a reflection of the subjects’ clinical status. We conclude that LAA-ACI and LAA tm add independent information to the CHA2DS2-VASc score about stasis risk and thereby can potentially enhance its ability to stratify stroke risk in AF patients

Hemodynamic Indices and Shape-Based Models of Left Atrial Appendage to Enhance Stroke Prediction in Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, mostly in the left atrial appendage (LAA). The current standard of stratifying stroke risk, based on the CHA2DS2-VASc score, does not consider LAA morphology/hemodynamics. The aim of this study was to determine whether LAA morphology and hemodynamics-based indices can stratify stroke risk independent of CHA2DS2-VASc score, left atrium size, and AF type. In a retrospective matched case-control study, patient-specific measurements in 128 AF patients included left atrial (LA) and LAA 3D geometry obtained by cardiac computed tomography, heart rate, cardiac output, and hematocrit. We quantified patient-specific 3D LAA morphology in terms of a novel LAA appearance complexity index (LAA-ACI) and employed computational fluid dynamics (CFD) analysis to quantify LAA mean residence time, tm and asymptotic concentration, C∞ of blood-borne particles. Effects of confounding variables were examined to optimize the CFD analysis. cardiac output, but not by the temporal pattern of pulmonary vein inlet flow, significantly affected LAA tm. Both the hematocrit level and the blood rheology model (Newtonian vs. non-Newtonian) also significantly affected LAA tm. Finally, 10,000 s was found to be a sufficient length of CFD simulation to calculate LAA tm in a consistent and reliable manner. LAA tm varied significantly within a given LAA morphology as defined by the current subjective method, and it was not simply a reflection of LAA geometry/appearance. In addition, LAA-ACI and tm varied significantly for a given CHA2DS2-VASc score, indicating that these two indices of stasis are not simply a reflection of the subjects’ clinical status. Using multiple logistic regression, we observed that ACI, tm, and C∞ had a modest, but statistically insignificant performance in predicting stroke (area under the ROC curve = 0.56–0.61). The temporal dissociation between adverse changes in LAA shape and hemodynamics-based indices and the actual stroke event can contribute to the negative result; a longitudinal study is necessary to address this issue. In addition, it is possible that a multiscale model that combines CFD-based hemodynamics simulation and biology-based thrombus formation can yield indices that can better stratify stroke risk in AF patients

Subject-Specific Calculation of Left Atrial Appendage Blood-Borne Particle Residence Time Distribution in Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, mostly in the left atrial appendage (LAA). The current standard of stratifying stroke risk, based on the CHA2DS2-VASc score, does not consider LAA morphology, and the clinically accepted LAA morphology-based classification is highly subjective. The aim of this study was to determine whether LAA blood-borne particle residence time distribution and the proposed quantitative index of LAA 3D geometry can add independent information to the CHA2DS2-VASc score. Data were collected from 16 AF subjects. Subject-specific measurements included left atrial (LA) and LAA 3D geometry obtained by cardiac computed tomography, cardiac output, and heart rate.We quantified 3D LAA appearance in terms of a novel LAA appearance complexity index (LAA-ACI). We employed computational fluid dynamics analysis and a systems-based approach to quantify residence time distribution and associated calculated variable (LAA mean residence time, tm) in each subject. The LAA-ACI captured the subject-specific LAA 3D geometry in terms of a single number. LAA tm varied significantly within a given LAA morphology as defined by the current subjectivemethod and it was not simply a reflection of LAA geometry/appearance. In addition, LAA-ACI and LAA tm varied significantly for a given CHA2DS2-VASc score, indicating that these two indices of stasis are not simply a reflection of the subjects’ clinical status. We conclude that LAA-ACI and LAA tm add independent information to the CHA2DS2-VASc score about stasis risk and thereby can potentially enhance its ability to stratify stroke risk in AF patients

Subject-Specific Calculation of Left Atrial Appendage Blood-Borne Particle Residence Time Distribution in Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, mostly in the left atrial appendage (LAA). The current standard of stratifying stroke risk, based on the CHA2DS2-VASc score, does not consider LAA morphology, and the clinically accepted LAA morphology-based classification is highly subjective. The aim of this study was to determine whether LAA blood-borne particle residence time distribution and the proposed quantitative index of LAA 3D geometry can add independent information to the CHA2DS2-VASc score. Data were collected from 16 AF subjects. Subject-specific measurements included left atrial (LA) and LAA 3D geometry obtained by cardiac computed tomography, cardiac output, and heart rate.We quantified 3D LAA appearance in terms of a novel LAA appearance complexity index (LAA-ACI). We employed computational fluid dynamics analysis and a systems-based approach to quantify residence time distribution and associated calculated variable (LAA mean residence time, tm) in each subject. The LAA-ACI captured the subject-specific LAA 3D geometry in terms of a single number. LAA tm varied significantly within a given LAA morphology as defined by the current subjectivemethod and it was not simply a reflection of LAA geometry/appearance. In addition, LAA-ACI and LAA tm varied significantly for a given CHA2DS2-VASc score, indicating that these two indices of stasis are not simply a reflection of the subjects’ clinical status. We conclude that LAA-ACI and LAA tm add independent information to the CHA2DS2-VASc score about stasis risk and thereby can potentially enhance its ability to stratify stroke risk in AF patients

Alteration of functional connectivity in the cortex and major brain networks of non-human primates following focused ultrasound exposure in the dorsal striatum

Background: Focused ultrasound (FUS) is a non-invasive neuromodulation technology that is being investigated for potential treatment of neurological and psychiatric disorders. FUS combined with microbubbles can temporarily open the intact blood-brain barrier (BBB) of animals and humans, and facilitate drug delivery. FUS exposure, either with or without microbubbles, has been demonstrated to alter the behavior of non-human primates (NHP), and previous studies have demonstrated the transient and long-term effects of FUS neuromodulation on functional connectivity using resting state functional MRI. The behavioral effects of FUS vary depending on whether or not it is applied in conjunction with microbubbles to open the BBB, but it is unknown whether opening the BBB affects functional connectivity differently than FUS alone. Objective: To compare the effects of applying FUS alone (FUS neuromodulation) and FUS with microbubbles (FUS-BBB opening) on changes of resting state functional connectivity in NHP. Methods: We applied 2 min FUS exposure without (neuromodulation) and with microbubbles (BBB opening) in the dorsal striatum of lightly anesthetized non-human primates, and acquired resting state functional MRI 40 min respectively after FUS exposure. The functional connectivity (FC) in the cortex and major brain networks between the two approaches were measured and compared. Results: When applying FUS exposure to the caudate nucleus of NHP, we found that both FUS neuromodulation can activate FC between caudate and insular cortex, while inhibiting the FC between caudate and motor cortex. FUS-BBB opening can activate FC between the caudate and medial prefrontal cortex, and within the frontotemporal network (FTN). We also found both FUS and FUS-BBB opening can significantly activate FC within the default mode network (DMN). Conclusion: The results suggest applying FUS to a deep brain structure can alter functional connectivity in the DMN and FTN, and that FUS neuromodulation and FUS-mediated BBB opening can have different effects on patterns of functional connectivity

Association of low-voltage areas with the regional wall deformation and the left atrial shape in patients with atrial fibrillation:A proof of concept study

Background: Left atrium (LA) remodeling is associated with atrial fibrillation (AF) and reduced success after AF ablation, but its relation with low-voltage areas (LVA) is not known. This study aimed to evaluate the relation between regional LA changes and LVAs in AF patients. Methods: Pre-interventional CT data of patients (n = 24) with LA-LVA ( \u3c 0.5 mV) in voltage mapping after AF ablation were analyzed (Surgery Explorer, QuantMD LLC). To quantify asymmetry (ASI = LA-A/LAV) a cutting plane parallel to the rear wall and along the pulmonary veins divided the LA-volume (LAV) into anterior (LA-A) and posterior parts. To quantify sphericity (LAS = 1-R/S), a patient-specific best-fit LA sphere was created. The average radius (R) and the mean deviation (S) from this sphere were calculated. The average local deviation (D) was measured for the roof, posterior, septum, inferior septum, inferior-posterior and lateral walls. Results: The roof, posterior and septal regions had negative local deviations. There was a correlation between roof and septum (r = 0.42, p = 0.04), lateral and inferior-posterior (r = 0.48, p = 0.02) as well as posterior and inferior-septal deviations (r = -0.41, p = 0.046). ASI correlated with septum deformation (r = -0.43, p = 0.04). LAS correlated with dilatation (LAV, r = 0.49, p = 0.02), roof (r = 0.52, p = 0.009) and posterior deformation (r = -0.56, p = 0.005). Extended LVA correlated with local deformation of all LA walls, except the roof and the septum. LVA association with LAV, ASI and LAS did not reach statistical significance. Conclusion: Extended LVA correlates with local wall deformations better than other remodeling surrogates. Therefore, their calculation could help predict LVA presence and deserve further evaluation in clinical studies