The P387 thrombospondin-4 variant promotes accumulation of macrophages in atherosclerotic lesions.

Thrombospondin-4 (TSP4) is a pro-angiogenic protein that has been implicated in tissue remodeling and local vascular inflammation. TSP4 and, in particular, its SNP variant, P387 TSP4, have been associated with cardiovascular disease. Macrophages are central to initiation and resolution of inflammation and development of atherosclerotic lesions, but the effects of the P387 TSP4 on macrophages remain essentially unknown. We examined the effects of the P387 TSP4 variant on macrophages in cell culture and in vivo in a murine model of atherosclerosis. Furthermore, the levels and distributions of the two TSP4 variants were assessed in human atherosclerotic arteries. In ApoE-/- /P387-TSP4 knock-in mice, lesions size measured by Oil Red O did not change, but the lesions accumulated more macrophages than lesions bearing A387 TSP4. The levels of inflammatory markers were increased in lesions of ApoE-/- /P387-TSP4 knock-in mice compared to ApoE-/- mice. Lesions in human arteries from individuals carrying the P387 variant had higher levels of TSP4 and higher macrophage accumulation. P387 TSP4 was more active in supporting adhesion of cultured human and mouse macrophages in experiments using recombinant TSP4 variants and in cells derived from P387-TSP4 knock-in mice. TSP4 supports the adhesion of macrophages and their accumulation in atherosclerotic lesions without changing the size of lesions. P387 TSP4 is more active in supporting these pro-inflammatory events in the vascular wall, which may contribute to the increased association of P387 TSP4 with cardiovascular disease.

Cyclic Variation of Spectral Parameters for the Differentiation of Atrial Myocardium Before and Immediately Following Radiofrequency Ablation.

Radiofrequency ablation (RFA) is a common treatment of atrial fibrillation. However, current treatment is associated with a greater than 20% recurrence rate, in part due to inadequate monitoring of tissue viability during ablation. Spectral parameters, in particular cyclic variation of integrated backscatter (CVIB), have shown promise as early indicators of myocardial recovery from ischemia. Our aim was to demonstrate the use of spectral parameters to differentiate atrial myocardium before and after radiofrequency ablation. An AcuNav 10 F catheter was used to collect radiofrequency signals from the posterior wall of the left atrium of patients before and immediately after RFA for AF. The normalized power spectrum was obtained and three spectral parameters (integrated backscatter [IB], slope, and intercept) were extracted across two continuous heart cycles. Parameters were gated for ventricular end-diastole and compared before and after ablation. Additionally, the cyclic variation of each of these three parameters was generated as an average of the variation across the two recorded heart cycles. Data from 14 patients before and after ablation demonstrated a significant difference in the magnitude of the cyclic variation of integrated backscatter (9.0 vs. 6.0 dB, p < .001) and cyclic variation of the intercept (14.0 vs. 11.5 dB, p = .04). No significant difference was noted in the magnitude of the cyclic variation of the slope. Among spectral parameters gated for end-diastole, significant differences were noted in the slope (-4.39 vs. -3.73 dB/MHz, p = .002) and intercept (16.8 vs. 11.9 dB, p = .002). No significant difference was noted in the integrated backscatter. Spectral parameters are able to differentiate atrial myocardium before and immediately following ablation and may be useful in monitoring atrial ablations.

Artificial Intelligence in Intracoronary Imaging.

PURPOSE OF REVIEW: This paper investigates present uses and future potential of artificial intelligence (AI) applied to intracoronary imaging technologies. RECENT FINDINGS: Advances in data analytics and digitized medical imaging have enabled clinical application of AI to improve patient outcomes and reduce costs through better diagnosis and enhanced workflow. Applications of AI to IVUS and IVOCT have produced improvements in image segmentation, plaque analysis, and stent evaluation. Machine learning algorithms are able to predict future coronary events through the use of imaging results, clinical evaluations, laboratory tests, and demographics. The application of AI to intracoronary imaging holds significant promise for improved understanding and treatment of coronary heart disease. Even in these early stages, AI has demonstrated the ability to improve the prediction of cardiac events. Large curated data sets and databases are needed to speed the development of AI and enable testing and comparison among algorithms.

New programs for translating research to patient care: Lessons learned at the NIH Center for Accelerated Innovations at Cleveland Clinic.

The NIH Center for Accelerated Innovations at Cleveland Clinic (NCAI-CC) was funded by the National Heart Lung and Blood Institute (NHLBI) to support academic investigators in technology development and commercialization. NCAI-CC was one of three multi-institutional Centers established in the fall of 2013. The goal of each Center was to catalyze the growth of an ecosystem of commercialization within their affiliated institutions and regions by managing a program of funding and guiding translational project development and by delivering commercialization education programs to participating investigators. NCAI-CC created and managed such a funding program, ultimately supporting 75 different projects across seven separate academic institutions and developed tailored educational content following the National Science Foundation I-Corps™ curriculum and delivered the program to 79 teams from 12 institutions. We determined early on that in establishment and implementation of projects, it is important to support the teams and principal investigators throughout the program. The support includes a change in principal investigator mindset from specific aims orientation to goals and deliverables on projects. Our skills development efforts emphasized commercialization and a deep understanding of customer needs for new technology adoption. Here, we review our experiences, outcomes, and insights, including the challenges identified in program implementation.

Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque.

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is expressed abundantly in the necrotic core of coronary lesions, and products of its enzymatic activity may contribute to inflammation and cell death, rendering plaque vulnerable to rupture. METHODS AND RESULTS: This study compared the effects of 12 months of treatment with darapladib (an oral Lp-PLA(2) inhibitor, 160 mg daily) or placebo on coronary atheroma deformability (intravascular ultrasound palpography) and plasma high-sensitivity C-reactive protein in 330 patients with angiographically documented coronary disease. Secondary end points included changes in necrotic core size (intravascular ultrasound radiofrequency), atheroma size (intravascular ultrasound gray scale), and blood biomarkers. BACKGROUND: =0.37). In contrast, Lp-PLA(2) activity was inhibited by 59% with darapladib (P<0.001 versus placebo). After 12 months, there were no significant differences between groups in plaque deformability (P=0.22) or plasma high-sensitivity C-reactive protein (P=0.35). In the placebo-treated group, however, necrotic core volume increased significantly (4.5+/-17.9 mm(3); P=0.009), whereas darapladib halted this increase (-0.5+/-13.9 mm(3); P=0.71), resulting in a significant treatment difference of -5.2 mm(3) (P=0.012). These intraplaque compositional changes occurred without a significant treatment difference in total atheroma volume (P=0.95). CONCLUSIONS: Despite adherence to a high level of standard-of-care treatment, the necrotic core continued to expand among patients receiving placebo. In contrast, Lp-PLA(2) inhibition with darapladib prevented necrotic core expansion, a key determinant of plaque vulnerability. These findings suggest that Lp-PLA(2) inhibition may represent a novel therapeutic approach.

Impact of intramural thrombus in coronary arteries on the accuracy of tissue characterization by in vivo intravascular ultrasound radiofrequency data analysis.

Virtual Histology (VH) intravascular ultrasound (IVUS) allows differentiation between 4 different tissue phenotypes. However, the current classification tree for analysis cannot differentiate the presence of intramural thrombus. The aim of this study was to evaluate the impact of intramural thrombus for correlative accuracy between in vitro histopathology of coronary atherosclerotic plaque obtained by directional coronary atherectomy and corresponding in vivo tissue characterization obtained by VH IVUS. Coronary IVUS imaging of 30 coronary artery lesions was obtained using a 20-MHz phased-array IVUS catheter with a motorized pull-back system at set 0.5 mm/s. The debulking region of the in vivo histologic image was predicted from comparison between pre- and post-first debulking VH IVUS images. Cross-sectional histologic slices were cut every 0.5 mm starting from the most proximal part of the formalin-fixed debulking tissue. Histologic slices were divided into 2 groups by the presence or absence of pathologic thrombus. A total of 259 in vitro histologic slices were obtained, and pathologic thrombus was detected in 81 slices. Correlation was favorable, with high sensitivity for all plaque components, but specificities for fibrous (thrombus slices vs nonthrombus slices 36% vs 94%) and fibrofatty (9% vs 60%) tissue were lower in thrombus slices. Therefore, predictive accuracies for the 2 plaque components were lower in thrombus slices (fibrous tissue 78% vs 99%, fibrofatty tissue 68% vs 83%, respectively). In conclusion, intramural thrombus was colored as fibrous or fibrofatty by VH IVUS, reducing VH accuracy in these kinds of lesions.

Spectral Analysis of Ultrasound Radiofrequency Backscatter for the Detection of Intercostal Blood Vessels.

Spectral analysis of ultrasound radiofrequency backscatter has the potential to identify intercostal blood vessels during ultrasound-guided placement of paravertebral nerve blocks and intercostal nerve blocks. Autoregressive models were used for spectral estimation, and bandwidth, autoregressive order and region-of-interest size were evaluated. Eight spectral parameters were calculated and used to create random forests. An autoregressive order of 10, bandwidth of 6 dB and region-of-interest size of 1.0 mm resulted in the minimum out-of-bag error. An additional random forest, using these chosen values, was created from 70% of the data and evaluated independently from the remaining 30% of data. The random forest achieved a predictive accuracy of 92% and Youden's index of 0.85. These results suggest that spectral analysis of ultrasound radiofrequency backscatter has the potential to identify intercostal blood vessels. (jokling@siue.edu) © 2018 World Federation for Ultrasound in Medicine and Biology.

Coronary plaque classification with intravascular ultrasound radiofrequency data analysis.

BACKGROUND: Atherosclerotic plaque stability is related to histological composition. However, current diagnostic tools do not allow adequate in vivo identification and characterization of plaques. Spectral analysis of backscattered intravascular ultrasound (IVUS) data has potential for real-time in vivo plaque classification. METHODS AND RESULTS: Eighty-eight plaques from 51 left anterior descending coronary arteries were imaged ex vivo at physiological pressure with the use of 30-MHz IVUS transducers. After IVUS imaging, the arteries were pressure-fixed and corresponding histology was collected in matched images. Regions of interest, selected from histology, were 101 fibrous, 56 fibrolipidic, 50 calcified, and 70 calcified-necrotic regions. Classification schemes for model building were computed for autoregressive and classic Fourier spectra by using 75% of the data. The remaining data were used for validation. Autoregressive classification schemes performed better than those from classic Fourier spectra with accuracies of 90.4% for fibrous, 92.8% for fibrolipidic, 90.9% for calcified, and 89.5% for calcified-necrotic regions in the training data set and 79.7%, 81.2%, 92.8%, and 85.5% in the test data, respectively. Tissue maps were reconstructed with the use of accurate predictions of plaque composition from the autoregressive classification scheme. CONCLUSIONS: Coronary plaque composition can be predicted through the use of IVUS radiofrequency data analysis. Autoregressive classification schemes performed better than classic Fourier methods. These techniques allow real-time analysis of IVUS data, enabling in vivo plaque characterization.

Myocardial ischemic injury after heart transplantation is associated with upregulation of vitronectin receptor (alpha(v)beta3), activation of the matrix metalloproteinase induction system, and subsequent development of coronary vasculopathy.

BACKGROUND: Myocardial ischemic injury after heart transplantation is associated with subsequent development of graft vasculopathy. Both vitronectin receptor (integrin alpha(v)beta3) and tissue factor play key roles in vascular endothelial cell injury. Matrix metalloproteinases (MMPs) are activated in ischemic injury models. METHODS AND RESULTS: Thirteen patients developed myocardial ischemic injury within 2 weeks of cardiac transplantation (ischemia group). These were compared with 10 transplantation patients who had no evidence of ischemia (control group). Endomyocardial biopsies were evaluated within 2 weeks of transplantation for alpha(v)beta3, tissue factor, and extracellular MMP inducer (EMMPRIN). At 1 year, MMPs were evaluated, and interstitial myocardial fibrosis was quantified. All patients underwent intravascular ultrasound at 1 month and 1 year after transplantation. Compared with control, the ischemia group demonstrated evidence of significant increased expression of alpha(v)beta3 (3.2-fold, P<0.001), tissue factor (2.5-fold, P<0.001), and EMMPRIN (1.9-fold, P=0.01). At 1 year, the ischemia group had a significant increase in myocardial fibrosis (24+/-1.8% versus 14+/-1.1%, P<0.001) and zymographic activity of MMP-2 (1.4-fold, P<0.001), MMP-3 (1.2-fold, P<0.001), and MMP-9 (1.3-fold, P=0.01). Coronary vasculopathy progression was also more advanced in the ischemia group (change in coronary maximal intimal thickness over 1 year 0.54+/-0.1 versus 0.26+/-0.06 mm; P=0.031). CONCLUSIONS: Myocardial ischemic injury after cardiac transplantation is associated with upregulation of alpha(v)beta3, tissue factor, and activation of the MMP induction system, which may contribute to the subsequent development of allograft remodeling and vasculopathy.

Coronary plaque morphology and frequency of ulceration distant from culprit lesions in patients with unstable and stable presentation.

OBJECTIVE: Intravascular ultrasound studies describe ruptured coronary plaques at sites remote from the culprit lesion in patients with acute myocardial infarction (MI), suggesting multifocal plaque vulnerability. However, the role of intravascular ultrasound in the diagnosis of lesion vulnerability before rupture is unclear. METHODS AND RESULTS: We compared morphology and frequency of ulceration of additional plaques proximal to the culprit lesion in 105 patients treated with emergent stenting during an evolving, acute MI in the CADILLAC study and 92 patients with stable/subacute presentation who underwent elective stenting. Additional plaques proximal to the culprit lesion were found in 52 (50%) and 54 (59%) patients in the acute MI and stable/subacute group, respectively. The prevalence of ulceration was significantly higher in the acute MI than in the stable/subacute group (19% versus 4%; P=0.014). However, there was no significant difference in other morphological lesion characteristics. CONCLUSIONS: Additional plaques are frequently found adjacent to the culprit lesions in patients undergoing percutaneous coronary intervention independent of clinical presentation. The increased prevalence of plaque ulceration but otherwise similar morphology of additional lesions in patients with acute MI versus stable/subacute presentation demonstrates the limitations of imaging in the assessment of plaque vulnerability.

Real-time plaque characterization and visualization with spectral analysis of intravascular ultrasound data.

Coronary artery disease is the number one cause of death in the United States and the Western world, and approximately 250,000 affected people die per year without ever being admitted to a hospital. One of the main reasons of such a high death-rate without any diagnosis is that more than 50 or heart-attacks) occur in patients with no prior history of known heart disease or symptoms. Coronary artery disease leads to the occlusion of arteries that are vital in providing nutrients to the heart muscles. The disease develops by progressive accumulation or formation of "plaque" within an artery. Certain types of plaques could occlude blood flow and yet might be "stable". These plaques usually have a high fibrous content, and are known as hard plaques. On the other hand, "unstable" or "soft" plaques might not cause much occlusion but could be vulnerable to rupture. Rupture of such plaques could lead to total or partial occlusion in arteries resulting in sudden cardiac death or heart-attack. In fact, 68 coronary arteries are less than 50.Intravascular ultrasound (IVUS) is a minimally invasive imaging modality that provides cross-section images of arteries in real-time, allowing visualization of atherosclerotic plaques in vivo. In standard IVUS gray-scale images, calcified regions of plaque and dense fibrous components generally reflect ultrasound energy well and thus appear bright and homogeneous on IVUS images. Conversely, regions of low echo reflectance in IVUS images are usually labeled "soft" or "mixed" plaque. However, this visual interpretation has been demonstrated to be very inconsistent in accurately determining plaque composition and does not allow real-time assessment of quantitative plaque constituents.Spectral analysis of the backscattered radiofrequency (RF) ultrasound signals allows detailed assessment of plaque composition. Advanced mathematical techniques can be employed to extract spectral information from these RF data to determine composition. The spectral content or signature of RF data reflected from tissue depends on density, compressibility, concentration, size, etc. A combination of spectral parameters were used to develop statistical classification schemes for analysis of in vivo IVUS data in real-time. The clinical data acquisition system is ECG gated and the analysis software developed by our group reconstructs IVUS gray-scale images from the acquired RF data. A combination of spectral parameters and active contour models is used for real-time 3D plaque segmentation followed by computation of color-coded tissue maps for each image cross-section and longitudinal views of the entire vessel. The "fly-through" mode allows one to visualize the complete length of the artery internally with the histology components at the lumen surface. In addition, vessel and plaque metrics such as areas and volumes of individual plaque components (collagen, fibro-lipid, calcium, lipid-core) are also available.

Ex vivo validation of 45 MHz intravascular ultrasound backscatter tissue characterization.

AIMS: The objectives of the present study are to describe the algorithm for VH(®) IVUS using the 45-MHz rotational IVUS catheter and the associated ex vivo validation in comparison to the gold standard histology. METHODS AND RESULTS: The first phase of the present study was to construct the 45 MHz VH IVUS algorithm by using a total of 55 human coronary artery specimens [111 independent coronary lesions and 510 homogenous regions of interest (ROIs)], obtained at autopsy. Regions were selected from histology and matched with their corresponding IVUS data to build the plaque classification system using spectral analysis and statistical random forests. In the second phase, the ex vivo validation of the VH IVUS algorithm assessed a total of 1060 ROIs (120 lesions from 60 coronary arteries) in comparison with histology. In an independent manner, two interventional cardiologists also classified a randomly selected subset of the ROIs for assessment of inter- and intra-observer reproducibility of VH IVUS image interpretation.When including all ROIs, the predictive accuracies were 90.8% for fibrous tissue, 85.8% for fibro fatty tissue, 88.3% for necrotic core, and 88.0% for dense calcium. The exclusion of ROIs in the acoustically attenuated areas improved the predictive accuracies, ranging from 91.9 to 96.8%. The independent analysis of randomly selected 253 ROIs showed substantial agreement for inter-observer (k = 0.66) and intra-observer (k = 0.88) reproducibility. CONCLUSION: Tissue classification by 45 MHz VH IVUS technology, when not influenced by calcium-induced acoustic attenuation, provided combined tissue accuracy >88% to identify tissue types compared with the gold standard histologic assessment, with high inter- and intra-observer reproducibility.

Automated three-dimensional assessment of coronary artery anatomy with intravascular ultrasound scanning.

BACKGROUND: Angiography allows the definition of advanced, severe stages of coronary artery disease, but early atherosclerotic lesions, which do not lead to luminal stenosis, are not identified reliably. In contrast, intravascular ultrasound scanning allows the precise characterization and quantification of a wide range of atherosclerotic lesions, independent of the severity of luminal stenosis. METHODS: Three-dimensional (3-D) reconstruction of entire coronary segments is possible with the integration of sequential 2-dimensional tomographic images and allows volumetric analysis of coronary arteries. RESULTS: Automated systems able to recognize lumen and vessel borders and to display 3-D images are becoming available. CONCLUSION: These systems have the potential for on-line 3-D image reconstruction for clinical decision-making and fast routine volumetric analysis in research studies. This review describes 3-D intravascular ultrasound scanning acquisition, analysis, and processing, and the associated technical challenges.

Relation of matrix-metalloproteinase 3 found in coronary lesion samples retrieved by directional coronary atherectomy to intravascular ultrasound observations on coronary remodeling.

We investigated the relation between the presence of matrix-metalloproteinases (MMPs) and direction of remodeling in the coronary lesions of 35 patients. Positive arterial remodeling describes a compensatory expansion of the external elastic membrane (EEM) area of atherosclerotic lesions. An association between positive remodeling and unstable clinical presentation has been previously described. However, the pathophysiology of the remodeling process is not completely understood. Preinterventional intravascular ultrasound images and directional atherectomy (DCA) samples were analyzed. The remodeling ratio was calculated as the EEM area at the lesion site divided by the EEM area at the proximal reference. Positive, intermediate, and negative remodeling were defined as ratios of >1.05, 0.95 to 1.05, and <0.95, respectively. The histologic samples were immunostained for MMP-1, -2, -3, and -9. Positive, intermediate, and negative remodeling was present in 15, 7, and 13 lesions, respectively. Mild and intense cell-associated staining for MMP-1 was found in 21 (68%) and 10 (32%) patients, respectively. Staining for MMP-3 was mild in 20 patients (67%) and intense in 10 patients (33%). Immunostaining for MMP-2 and -9 was mild in all samples. Intense staining for MMP-3 was significantly more common in lesions with positive than negative and/or intermediate remodeling (58% vs 17%; p = 0.04; p = 0.053 after adjustment for gender). Thus, in this in vivo intravascular ultrasound and histologic study, increased cell-associated MMP-3 staining was associated with positive arterial remodeling.

Acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system.

BACKGROUND: A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. METHODS: Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for alphavbeta3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). RESULTS: Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of alphavbeta3 (1.9-fold, p < 0.001), tissue factor (1.8-fold, p < 0.001), and EMMPRIN (1.5-fold, p < 0.001). All patients in the AVR group received plasmapheresis; 11 of 14 patients had evidence of ischemic necrosis on biopsy specimens, and 3 of 14 patients experienced hemodynamic compromise and graft dysfunction and died within 3 weeks of transplant. Another patient died at 10 months after transplant. CONCLUSIONS: Acute vascular rejection is associated with up-regulation of alphavbeta3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.

Early constriction or expansion of the external elastic membrane area determines the late remodeling response and cumulative lumen loss in transplant vasculopathy: an intravascular ultrasound study with 4-year follow-up.

BACKGROUND: Early constriction of the external elastic membrane (EEM) area has been observed after cardiac transplantation. The aim of this study was to compare the late disease process of transplant vasculopathy between coronary segments with early constrictive and expansive remodeling. METHODS: Serial intravascular ultrasound data obtained annually for 4 years after transplantation in 38 transplant recipients was available. In 135 matched segments from 59 coronary arteries ultrasound images were digitized at 1-mm intervals. Mean values of the external elastic membrane (EEM), lumen and intimal areas were calculated. On the basis of a decrease or increase in EEM area within the first year after transplantation, we defined segments with early constrictive remodeling (CR, n = 71) or early expansive remodeling (ER, n = 64). RESULTS: Annual changes in intimal area were similar between segments with early CR and ER throughout the follow-up period. However, during the second and third year, annual increases in EEM area were greater in segments with early CR than in segments with early ER (second year: 1.5 +/- 2.7 vs 0.6 +/- 2.8 mm(2), p = 0.052; third year: 1.3 +/- 2.5 vs -0.03 +/- 2.6 mm(2), p = 0.003). Despite this late expansion, segments with early CR showed a cumulative decrease in the EEM area and a greater lumen loss than segments with early ER (-2.5 +/- 3.4 vs -0.6 +/- 2.6 mm(2), p < 0.001). CONCLUSIONS: In transplant vasculopathy, the late remodeling response was different between segments with early constrictive and expansive remodeling, despite similar intimal thickening. Early constriction caused an overall decrease in EEM area and greater loss of lumen during follow-up.

Variability of area measurements obtained with different intravascular ultrasound catheter systems: Impact on clinical trials and a method for accurate calibration.

BACKGROUND: Atherosclerotic plaque burden is the major end point in ongoing progression trials. Intravascular ultrasound allows precise measurements of coronary artery dimensions. However, the variability of measurements among different catheter systems is incompletely characterized. METHODS: Intravascular ultrasound imaging was performed in a cylindric phantom with 5 sections of different, known, cross-sectional area ranging from 3.24 to 27.99 mm(2). A total of 3637 measurements with different catheter systems (Atlantis SR and Ultracross, Scimed/Boston Scientific; and Invision and Avanar, Jomed) were performed. Measurements were divided into model building and validation datasets. For each catheter, calibration models were developed. RESULTS: Overestimation and underestimation of the true cross-sectional area of up to 18% was observed with different catheter systems. Calibration equations for the different systems could be developed that predicted the true diameter and area with high statistical precision (adjusted R(2) > 0.99). CONCLUSIONS: Area measurements vary among different intravascular ultrasound catheter systems. Calibration equations can correct for these differences and allow the comparison of measurements among catheters.

N-acetyl-cysteine in the prevention of vascular restenosis after percutaneous balloon angioplasty.

BACKGROUND: Vascular inflammation generating oxidized metabolites at the site of balloon angioplasty is believed to play a major role in the process of vessel restenosis. Glutathione, the most potent endogenous antioxidant, may have protective effects after angioplasty by suppressing local inflammatory response. The aim of the study was to test the hypothesis that oral administration of N-acetyl-cysteine (NAC, a precursor of glutathione) reduces restenosis in an animal model of vascular injury. METHODS: In New Zealand white rabbits, an atherosclerotic lesion was introduced to both iliac arteries by air denudation of the endothelium while feeding the animals a high-cholesterol diet. After 4 weeks, all animals underwent balloon angioplasty of the endothelial injury site and half of the group was started on 150 mg/kg NAC per day. Quantitative angiography was performed prior to the angioplasty and at the final procedure 3 weeks later. Glutathione levels were determined in all animals at the beginning and the end of the study. RESULTS: Although not statistically significant, plasma glutathione level increased in the NAC group from 32.4+/-4.4 to 39.7+/-11.6 micromol/l, while it decreased from 30.6+/-13.4 to 28.3+/-11.5 micromol/l in the control group. During the study period, 6 vessels occluded leaving 14 vessels for analysis. Quantitative angiographic analyses prior to angioplasty and at follow-up showed no significant difference with respect to stenosis progression between the groups. Measurement of neointima formation by histology showed also no significant difference between the groups (0.175+/-0.040 mm(2) vs. 0.123+/-0.075 mm(2)), neither did intimal macrophage count as a marker for local inflammatory response. CONCLUSIONS: Despite an increase in plasma glutathione level in the NAC-treated group, there was no reduction in lesion progression after balloon angioplasty. Therefore, NAC does not seem to prevent restenosis after vascular intervention in this animal model.

Peripheral application of intravascular ultrasound virtual histology.

Intravascular ultrasound (IVUS) provides direct depiction of coronary artery anatomy. Traditional use of this tomographic imaging modality has been in determination of geometric measurements of an artery, such as lumen or plaque size. However, by analyzing the backscattered or radiofrequency (RF) data it is possible to glean information on the composition of plaques. This chapter describes the theory of spectral analysis and its application clinical practice.

Moderately nonlinear ultrasound propagation in blood-mimicking fluid.

In medical diagnostic ultrasound (US), higher than-in-water nonlinearity of body fluids and tissue usually does not produce strong nonlinearly distorted waves because of the high absorption. The relative influence of absorption and nonlinearity can be characterized by the Gol'dberg number Gamma. There are two limiting cases in nonlinear acoustics: weak waves (Gamma < 1) or strong waves (Gamma >> 1). However, at diagnostic frequencies in tissue and body fluids, the nonlinear effects and effects of absorption more likely are comparable (Gol'dberg number Gamma approximately 1). The aim of this work was to study the nonlinear propagation of a moderately nonlinear US second harmonic signal in a blood-mimicking fluid. Quasilinear solutions to the KZK equation are presented, assuming radiation from a flat and geometrically focused circular Gaussian source. The solutions are expressed in a new simplified closed form and are in very good agreement with those of previous studies measuring and modeling Gaussian beams. The solutions also show good agreement with the measurements of the beams produced by commercially available transducers, even without special Gaussian shading.