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.

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.

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.

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.

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.

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.

In vivo study of transverse carpal ligament stiffness using acoustic radiation force impulse (ARFI) imaging.

The transverse carpal ligament (TCL) forms the volar boundary of the carpal tunnel and may provide mechanical constraint to the median nerve, leading to carpal tunnel syndrome. Therefore, the mechanical properties of the TCL are essential to better understand the etiology of carpal tunnel syndrome. The purpose of this study was to investigate the in vivo TCL stiffness using acoustic radiation force impulse (ARFI) imaging. The shear wave velocity (SWV) of the TCL was measured using Virtual Touch IQ(TM) software in 15 healthy, male subjects. The skin and the thenar muscles were also examined as reference tissues. In addition, the effects of measurement location and ultrasound transducer compression on the SWV were studied. The SWV of the TCL was dependent on the tissue location, with greater SWV values within the muscle-attached region than those outside of the muscle-attached region. The SWV of the TCL was significantly smaller without compression (5.21 ± 1.08 m/s) than with compression (6.62 ± 1.18 m/s). The SWV measurements of the skin and the thenar muscles were also affected by transducer compression, but to different extents than the SWV of the TCL. Therefore to standardize the ARFI imaging procedure, it is recommended that a layer of ultrasound gel be maintained to minimize the effects of tissue compression. This study demonstrated the feasibility of ARFI imaging for assessing the stiffness characteristics of the TCL in vivo, which has the potential to identify pathomechanical changes of the tissue.

Left atrial appendage occlusion: pilot study of a fourth-generation, minimally invasive device.

OBJECTIVE: Exclusion of the left atrial appendage is proposed to reduce the risk of stroke in patients with atrial fibrillation. The aim of this study was to evaluate the feasibility and efficacy of a fourth-generation atrial exclusion device developed for minimally invasive applications. METHODS: The novel atrial exclusion device consists of two polymer beams and two elastomeric bands that connect the two beams at either end. Fifteen mongrel dogs were implanted with the device at the base of the left atrial appendage through a median sternotomy and were evaluated at 30 (n = 7), 90 (n = 6), and 180 (n = 2) days after implantation by epicardial echocardiography, left atrial and coronary angiography, gross pathology, and histology. RESULTS: Left atrial appendage exclusion was completed without hemodynamic instability. Coronary angiography revealed that the left circumflex artery was patent in all cases. A new endothelial tissue layer developed, as expected, on the occluded orifice of the left atrium. CONCLUSIONS: This novel atrial exclusion device achieved easy, reliable, and safe exclusion of the left atrial appendage, with favorable histological results in a canine model for up to 6 months. Clinical application could provide a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation.

Histologic evaluation of stapled right atrial appendages with fabric buttressing.

OBJECTIVE: The aim of this study was to histologically evaluate the importance of using buttressing materials in stapling the atrial appendages. METHODS: We stapled the right atrial appendage with a commercial apparatus in 11 mongrel dogs. To evaluate the efficiency of using a buttressing material as an adjunct to stapling, we conducted 30-day studies without (group A: n = 2) or with buttressing material (group B: n = 3) and 90-day studies without (group C: n = 3) or with buttressing material (group D: n = 3) and thereafter made assessments using Doppler echocardiography and performed histologic analyses on all stapled appendages. RESULTS: During surgery, blood oozing from the stapling sites was observed in four of five cases of groups A and C; with buttressing, there was no oozing in groups B and D. In groups A and B, we observed the myocardium of the appendage being focally replaced with fibrous tissue. Myocardium in group C was infiltrated diffusely with loose fibrous tissue and in group D had been almost completely replaced with fibrous tissue. CONCLUSIONS: The buttressing material was useful not only in preventing oozing but also likely promoting the growth of fibrous tissue in the right atrial appendage.

Tissue characterisation using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting.

This document suggests standards for the acquisition, measurement, and reporting of radiofrequency data analysis (virtual histology - VH) intravascular ultrasound (IVUS) studies. Readers should view this document as the authors' best attempt in an area of rapidly evolving investigation, an area where rigorous evidence is not yet available or widely accepted. Nevertheless, this document is based on known pathologic data as well as previously reported imaging data; where practical, this data is summarised in the current document, a document which will also include recommendations for future evolution of the technology.

A novel device for left atrial appendage exclusion: the third-generation atrial exclusion device.

OBJECTIVE: Occlusion of the left atrial appendage is proposed to reduce the risk of stroke in patients with atrial fibrillation. The third-generation atrial exclusion device, modified to provide uniform distribution of pressure at appendage exclusion, was assessed for safety and effectiveness in a canine model and compared with a surgical stapler. METHODS: The atrial exclusion device consists of 2 parallel, straight, rigid titanium tubes and 2 nitinol springs with a knit-braided polyester fabric. Fourteen mongrel dogs were implanted with the device at the base of the left atrial appendage via a median sternotomy. In each dog, the right atrial appendage was stapled with a commercial apparatus for comparison. The animals were evaluated at 7 days (n = 3), 30 days (n = 5), and 90 days (n = 6) after implantation by epicardial echocardiography, left atrial and coronary angiography, gross pathology, and histology. RESULTS: Left atrial appendage exclusion was complete and achieved without hemodynamic instability, and coronary angiography revealed that the left circumflex artery was patent in all cases. A new endothelial tissue layer developed on the occluded orifice of the left atrium 90 days after implantation. This endothelial layer was not evident on the stapled right atrial appendage. CONCLUSION: In dogs, the third-generation atrial exclusion device achieved easy, reliable, and safe exclusion of the left atrial appendage with favorable histologic results. Clinical application could provide a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation.

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.

Normalization and backscatter spectral analysis of human carotid arterial data acquired using a clinical linear array ultrasound imaging system.

The risk of plaque rupture in carotid atherosclerotic disease is associated more closely with the composition of plaque rather than the severity of stenosis. The constituents of plaque can be determined from ultrasonic spectral parameters obtained from normalized backscatter tissue data. Calibration of the data is done using echoes off a specular reflector which removes the system response of an ultrasound transducer, Terason (Teratech Corporation), from the backscatter data. A reference spectrum study is used to compare specular reflectors based on time domain (echo) and frequency domain (power spectrum, centroid and parabola test) analysis. Nylon and a tissue-mimicking phantom (velocity = 1560 m/s, slope of attenuation = 0.7 dB/cm MHz) have an intermediate acoustic impedance with respect to water and appear good choices as specular reflectors for clinical ultrasound imaging scanners compared to Plexiglas and other higher reflecting materials. A tissue-mimicking phantom is used to correct for attenuation in plaque, diffraction and saturation of electronics of the ultrasound scanner. Autoregressive power spectrum estimation methods are used to extract spectral parameters (spectral slope, y-intercept, midband fit, maximum and minimum power with corresponding frequencies, and integrated backscatter) from calibrated tissue data and linear and quadratic discriminant rules developed for classification of carotid arterial plaque. Regions of interest (n = 64; 64 samples x 8 scan lines with 30 MHz sampling frequency) consisting of 48 fibrous-fibrofatty (Class 1), 11 thrombus-necrotic core (Class 2), and 5 dense calcium (Class 3) areas selected for analysis show that fibrosis can be differentiated from necrosis and calcification. The quadratic discriminant rule identified necrosis with a lower misclassification rate (9.1%) than the linear discriminant rule (18.2%).

Automated coronary plaque characterisation with intravascular ultrasound backscatter: ex vivo validation.

AIMS: Atherosclerosis is considered both a systemic and focal disease. Current diagnostic tools do not allow adequate in vivo identification and characterisation of lesions. Advanced spectral analysis of IVUS backscatter has displayed the potential for real-time plaque characterisation. The aim of this study is to determine the ex vivo accuracy of automated plaque characterisation by spectral analysis of intravascular ultrasound (IVUS) backscatter. METHODS AND RESULTS: Plaques (n=184) from 51 coronary arteries were imaged by IVUS. The arteries were then pressure fixed and matching histology collected. Regions were selected from histology and corresponding IVUS data were used to build the plaque classification system using spectral analysis and classi-fication trees. Tissue-maps were validated ex vivo by comparison with histology via 899 selected regions (n=94 plaques) that comprised 471 fibrous tissue (FT), 130 fibro-fatty (FF), 132 necrotic-core (NC) and 156 dense-calcium (DC) regions. The overall predictive accuracies were 93.5% for FT, 94.1% for FF, 95.8% for NC, and 96.7% for DC with sensitivities and specificities ranging from 72% to 99%. The Kappa statistic was calculated to be 0.845 indicating very high agreement with histology. CONCLUSIONS: Automated spectral analysis of IVUS backscatter provides accurate ex vivo information on plaque composition, with considerable potential for assessment of plaque vulnerability in real-time.

Evaluation of a novel device for left atrial appendage exclusion: the second-generation atrial exclusion device.

BACKGROUND: The left atrial appendage is a frequent source of thromboemboli in patients with atrial fibrillation. Exclusion of the left atrial appendage may reduce the risk of stroke in patients with atrial fibrillation. The atrial exclusion device, previously developed to perform left atrial appendage exclusion on a beating heart, was modified to accommodate different anatomic patterns of the human left atrial appendage and to ensure uniform pressure and occlusion. The purpose of this study was to evaluate this second-generation atrial exclusion device during a midterm period in a canine model. METHODS: Ten mongrel dogs (mean weight 28.9 +/- 4.6 kg) were used in this study. The atrial exclusion device, constructed from two parallel and rigid titanium tubes and two nitinol springs with a knit-braided polyester fabric, was implanted at the base of the left atrial appendage through a left thoracotomy on a beating heart using a specially designed delivery tool. Dogs were evaluated at 30 days (n = 4) and 90 days (n = 6) by epicardial echocardiography, left atrial and coronary angiography, gross pathology, and histologic inspection. RESULTS: Device implantation was performed without complications in all dogs. Complete left atrial appendage exclusion without device migration or hemodynamic instability was confirmed, and there was no damage to the left circumflex artery or pulmonary artery. Macroscopic and microscopic assessments revealed favorable biocompatibility during midterm follow-up. CONCLUSION: The atrial exclusion device enabled rapid, reliable, and safe exclusion of the left atrial appendage. Clinical application may provide a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation.

Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology.

OBJECTIVES: The goal of the present study was to compare the accuracy of in vivo tissue characterization obtained by intravascular ultrasound (IVUS) radiofrequency (RF) data analysis, known as Virtual Histology (VH), to the in vitro histopathology of coronary atherosclerotic plaques obtained by directional coronary atherectomy. BACKGROUND: Vulnerable plaque leading to acute coronary syndrome (ACS) has been associated with specific plaque composition, and its characterization is an important clinical focus. METHODS: Virtual histology IVUS images were performed before and after a single debulking cut using directional coronary atherectomy. Debulking region of in vivo histology image was predicted by comparing pre- and post-debulking VH images. Analysis of VH images with the corresponding tissue cross section was performed. RESULTS: Fifteen stable angina pectoris (AP) and 15 ACS patients were enrolled. The results of IVUS RF data analysis correlated well with histopathologic examination (predictive accuracy from all patients data: 87.1% for fibrous, 87.1% for fibro-fatty, 88.3% for necrotic core, and 96.5% for dense calcium regions, respectively). In addition, the frequency of necrotic core was significantly higher in the ACS group than in the stable AP group (in vitro histopathology: 22.6% vs. 12.6%, p = 0.02; in vivo virtual histology: 24.5% vs. 10.4%, p = 0.002). CONCLUSIONS: Correlation of in vivo IVUS RF data analysis with histopathology shows a high accuracy. In vivo IVUS RF data analysis is a useful modality for the classification of different types of coronary components, and may play an important role in the detection of vulnerable plaque.

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.