David Muccigrosso

Noncontrast skeletal muscle oximetry

The objective of this study was to develop a new noncontrast method to directly quantify regional skeletal muscle oxygenation.

Human coronary plaque wall thickness correlated positively with flow shear stress and negatively with plaque wall stress: An IVUS-based fluid-structure interaction multi-patient study

BackgroundAtherosclerotic plaque progression and rupture are believed to be associated with mechanical stress conditions. In this paper, patient-specific in vivo intravascular ultrasound (IVUS) coronary plaque image data were used to construct computational models with fluid-structure interaction (FSI) and cyclic bending to investigate correlations between plaque wall thickness and both flow shear stress and plaque wall stress conditions.MethodsIVUS data were acquired from 10 patients after voluntary informed consent. The X-ray angiogram was obtained prior to the pullback of the IVUS catheter to determine the location of the coronary artery stenosis, vessel curvature and cardiac motion. Cyclic bending was specified in the model representing the effect by heart contraction. 3D anisotropic FSI models were constructed and solved to obtain flow shear stress (FSS) and plaque wall stress (PWS) values. FSS and PWS values were obtained for statistical analysis. Correlations with p < 0.05 were deemed significant.ResultsNine out of the 10 patients showed positive correlation between wall thickness and flow shear stress. The mean Pearson correlation r-value was 0.278 ± 0.181. Similarly, 9 out of the 10 patients showed negative correlation between wall thickness and plaque wall stress. The mean Pearson correlation r-value was -0.530 ± 0.210.ConclusionOur results showed that plaque vessel wall thickness correlated positively with FSS and negatively with PWS. The patient-specific IVUS-based modeling approach has the potential to be used to investigate and identify possible mechanisms governing plaque progression and rupture and assist in diagnosis and intervention procedures. This represents a new direction of research. Further investigations using more patient follow-up data are warranted.

Morphological and Stress Vulnerability Indices for Human Coronary Plaques and Their Correlations with Cap Thickness and Lipid Percent: An IVUS-Based Fluid-Structure Interaction Multi-Patient Study

Plaque vulnerability, defined as the likelihood that a plaque would rupture, is difficult to quantify due to lack of in vivo plaque rupture data. Morphological and stress-based plaque vulnerability indices were introduced as alternatives to obtain quantitative vulnerability assessment. Correlations between these indices and key plaque features were investigated. In vivo intravascular ultrasound (IVUS) data were acquired from 14 patients and IVUS-based 3D fluid-structure interaction (FSI) coronary plaque models with cyclic bending were constructed to obtain plaque wall stress/strain and flow shear stress for analysis. For the 617 slices from the 14 patients, lipid percentage, min cap thickness, critical plaque wall stress (CPWS), strain (CPWSn) and flow shear stress (CFSS) were recorded, and cap index, lipid index and morphological index were assigned to each slice using methods consistent with American Heart Association (AHA) plaque classification schemes. A stress index was introduced based on CPWS. Linear Mixed-Effects (LME) models were used to analyze the correlations between the mechanical and morphological indices and key morphological factors associated with plaque rupture. Our results indicated that for all 617 slices, CPWS correlated with min cap thickness, cap index, morphological index with r = -0.6414, 0.7852, and 0.7411 respectively (p<0.0001). The correlation between CPWS and lipid percentage, lipid index were weaker (r = 0.2445, r = 0.2338, p<0.0001). Stress index correlated with cap index, lipid index, morphological index positively with r = 0.8185, 0.3067, and 0.7715, respectively, all with p<0.0001. For all 617 slices, the stress index has 66.77% agreement with morphological index. Morphological and stress indices may serve as quantitative plaque vulnerability assessment supported by their strong correlations with morphological features associated with plaque rupture. Differences between the two indices may lead to better plaque assessment schemes when both indices were jointly used with further validations from clinical studies.

Higher critical plaque wall stress in patients who died of coronary artery disease compared with those who died of other causes: a 3D FSI study based on ex vivo MRI of coronary plaques

Mechanical forces play an important role in the rupture of vulnerable plaques. This process is often associated with cardiovascular syndromes, such as heart attack and stroke. In this study, magnetic resonance imaging (MRI)-based models were used to investigate the association between plaque wall stress (PWS) and coronary artery disease (CAD). Ex vivo MRI data of coronary plaques from 12 patients were used to construct 12 three-dimensional (3D) fluid-structure interaction (FSI) computational models. Six of the patients had died from CAD and six had died from non-CAD causes. PWS was assessed using all nodal points on the lumen surface of each plaque. The maximum PWS from all possible vulnerable sites of each plaque was defined as the 3D critical plaque wall stress (CPWS). Mean 3D CPWS in the CAD group was 94.3% higher than that in the non-CAD group (265.6 vs. 136.7 kPa, P=0.0029). There was no statistically significant difference in global maximum plaque wall stress (GMPWS) between the two groups (P=0.347). There was also no statistically significant difference in plaque burden between the CAD group (84.4±5%) and the non-CAD group (82.0±8%, P=0.552). The results indicate that plaques from patients who died from CAD were associated with higher CPWS compared with those from patients who died from non-CAD causes. With further validation, analysis of CPWS may prove to be an important component in assessment of plaque vulnerability.

3D MRI-based multicomponent thin layer structure only plaque models for atherosclerotic plaques.

MRI-based fluid-structure interactions (FSI) models for atherosclerotic plaques have been developed to perform mechanical analysis to investigate the association of plaque wall stress (PWS) with cardiovascular disease. However, the time consuming 3D FSI model construction process is a great hinder for its clinical implementations. In this study, a 3D thin-layer structure only (TLS) plaque model was proposed as an approximation with much less computational cost to 3D FSI models for better clinical implementation potential. 192 TLS models were constructed based on 192 ex vivo MRI Images of 12 human coronary atherosclerotic plaques. Plaque stresses were extracted from all lumen nodal points. The maximum value of Plaque wall stress (MPWS) and average value of plaque wall stress (APWS) of each slice were used to compare with those from corresponding FSI models. The relative errors for MPWS and APWS were 9.76% and 9.89%, respectively. Both MPWS and APWS values obtained from TLS models showed very good correlation with those from 3D FSI models. Correlation results from TLS models were in consistent with FSI models. Our results indicated that the proposed 3D TLS plaque models may be used as a good approximation to 3D FSI models with much less computational cost. With further validation, 3D TLS models may be possibly used to replace FSI models to save time and perform mechanical analysis for atherosclerotic plaques for clinical implementation.

Oximetric angiosome imaging in diabetic feet

To develop a noncontrast oximetric angiosome imaging approach to assess skeletal muscle oxygenation in diabetic feet.

T2 preparation method for measuring hyperemic myocardial O2 consumption: in vivo validation by positron emission tomography

To validate a new T2‐prepared method for the quantification of regional myocardial O2 consumption during pharmacologic stress with positron emission tomography (PET).

A non-contrast CMR index for assessing myocardial fibrosis

PURPOSE Safe, sensitive, and non-invasive imaging methods to assess the presence, extent, and turnover of myocardial fibrosis are needed for early stratification of risk in patients who might develop heart failure after myocardial infarction. We describe a non-contrast cardiac magnetic resonance (CMR) approach for sensitive detection of myocardial fibrosis using a canine model of myocardial infarction and reperfusion. METHODS Seven dogs had coronary thrombotic occlusion of the left anterior descending coronary arteries followed by fibrinolytic reperfusion. CMR studies were performed at 7days after reperfusion. A CMR spin-locking T1ρ mapping sequence was used to acquire T1ρ dispersion data with spin-lock frequencies of 0 and 511Hz. A fibrosis index map was derived on a pixel-by-pixel basis. CMR native T1 mapping, first-pass myocardial perfusion imaging, and post-contrast late gadolinium enhancement imaging were also performed for assessing myocardial ischemia and fibrosis. Hearts were dissected after CMR for histopathological staining and two myocardial tissue segments from the septal regions of adjacent left ventricular slices were qualitatively assessed to grade the extent of myocardial fibrosis. RESULTS Histopathology of 14 myocardial tissue segments from septal regions was graded as grade 1 (fibrosis area, <20% of a low power field, n=9), grade 2 (fibrosis area, 20-50% of field, n=4), or grade 3 (fibrosis area, >50% of field, n=1). A dramatic difference in fibrosis index (183%, P<0.001) was observed by CMR from grade 1 to 2, whereas differences were much smaller for T1ρ (9%, P=0.14), native T1 (5.5%, P=0.12), and perfusion (-21%, P=0.05). CONCLUSION A non-contrast CMR index based on T1ρ dispersion contrast was shown in preliminary studies to detect and correlate with the extent of myocardial fibrosis identified histopathologically. A non-contrast approach may have important implications for managing cardiac patients with heart failure, particularly in the presence of impaired renal function.

Fluid-structure interaction models based on patient-specific IVUS at baseline and follow-up for prediction of coronary plaque progression by morphological and biomechanical factors: A preliminary study

Plaque morphology and biomechanics are believed to be closely associated with plaque progression. In this paper, we test the hypothesis that integrating morphological and biomechanical risk factors would result in better predictive power for plaque progression prediction. A sample size of 374 intravascular ultrasound (IVUS) slices was obtained from 9 patients with IVUS follow-up data. 3D fluid-structure interaction models were constructed to obtain both structural stress/strain and fluid biomechanical conditions. Data for eight morphological and biomechanical risk factors were extracted for each slice. Plaque area increase (PAI) and wall thickness increase (WTI) were chosen as two measures for plaque progression. Progression measure and risk factors were fed to generalized linear mixed models and linear mixed-effect models to perform prediction and correlation analysis, respectively. All combinations of eight risk factors were exhausted to identify the optimal predictor(s) with highest prediction accuracy defined as sum of sensitivity and specificity. When using a single risk factor, plaque wall stress (PWS) at baseline was the best predictor for plaque progression (PAI and WTI). The optimal predictor among all possible combinations for PAI was PWS + PWSn + Lipid percent + Min cap thickness + Plaque Area (PA) + Plaque Burden (PB) (prediction accuracy = 1.5928) while Wall Thickness (WT) + Plaque Wall Strain (PWSn) + Plaque Area (PA) was the best for WTI (1.2589). This indicated that PAI was a more predictable measure than WTI. The combination including both morphological and biomechanical parameters had improved prediction accuracy, compared to predictions using only morphological features.

Sudden death in coronary artery disease are associated with high 3D critical plaque wall stress: A 3D multi-patient fsi study based on EX vivo MRI of coronary plaques

Conference Name:ASME 2013 Summer Bioengineering Conference, SBC 2013. Conference Address: Sunriver, OR, United states. Time:June 26, 2013 - June 29, 2013.