Intra- and inter-operator reproducibility of automated cloud-based carotid lumen diameter ultrasound measurement.

BACKGROUND: Common carotid artery lumen diameter (LD) ultrasound measurement systems are either manual or semi-automated and lack reproducibility and variability studies. This pilot study presents an automated and cloud-based LD measurements software system (AtheroCloud) and evaluates its: (i) intra/inter-operator reproducibility and (ii) intra/inter-observer variability. METHODS: 100 patients (83M, mean age: 68±11years), IRB approved, consisted of L/R CCA artery (200 ultrasound images), acquired using a 7.5-MHz linear transducer. The intra/inter-operator reproducibility was verified using three operator's readings. Near-wall and far carotid wall borders were manually traced by two observers for intra/inter-observer variability analysis. RESULTS: The mean coefficient of correlation (CC) for intra- and inter-operator reproducibility between all the three automated reading pairs were: 0.99 (P<0.0001) and 0.97 (P<0.0001), respectively. The mean CC for intra- and inter-observer variability between both the manual reading pairs were 0.98 (P<0.0001) and 0.98 (P<0.0001), respectively. The Figure-of-Merit between the mean of the three automated readings against the four manuals were 98.32%, 99.50%, 98.94% and 98.49%, respectively. CONCLUSIONS: The AtheroCloud LD measurement system showed high intra/inter-operator reproducibility hence can be adapted for vascular screening mode or pharmaceutical clinical trial mode.

Morphologic TPA (mTPA) and composite risk score for moderate carotid atherosclerotic plaque is strongly associated with HbA1c in diabetes cohort.

BACKGROUND: This study examines the association between six types of carotid artery disease image-based phenotypes and HbA1c in diabetes patients. Six phenotypes (intima-media thickness measurements (cIMT (ave.), cIMT (max.), cIMT (min.)), bidirectional wall variability (cIMTV), morphology-based total plaque area (mTPA), and composite risk score (CRS)) were measured in an automated setting using AtheroEdge™ (AtheroPoint, CA, USA). METHOD: Consecutive 199 patients (157 M, age: 68.96 ±â€¯10.98 years), L/R common carotid artery (CCA; 398 US scans) who underwent a carotid ultrasound (L/R) were retrospectively analyzed using AtheroEdge™ system. Two operators (novice and experienced) manually calibrated all the US scans using AtheroEdge™. Logistic regression (LR) and Odds ratio (OR) was computed and phenotypes were ranked. RESULTS: The baseline results showed 150 low-risk patients (HbA1c < 6.50 mg/dl) and 49 high-risk patients (HbA1c ≥ 6.50 mg/dl). The fasting blood sugar (FBS) was highly associated with HbA1c (P < 0.001). Except for cIMTV, all phenotypes showed an OR > 1.0 (P < 0.001) for left common carotid artery (LCCA), right carotid artery (RCCA), and mean of left and right common carotid artery (MCCA). After adjusting the FBS, the OR for mTPA showed a higher risk for LCCA, RCCA, and MCCA. The coefficient of correlation (CC) between phenotypes and HbA1c were strong and inter-CC between cIMT and mTPA/CRS was above 0.9 (P < 0.001). The statistical tests showed that phenotypes were significantly associated with diabetes (P-value<0.0001). CONCLUSIONS: All phenotypes using AtheroEdge™, except cIMTV, showed a strong association with HbA1c. mTPA and CRS were equally strong phenotypes as cIMT. The CRS phenotype showed the strongest relationship to HbA1c.

Calcium detection, its quantification, and grayscale morphology-based risk stratification using machine learning in multimodality big data coronary and carotid scans: A review.

PURPOSE OF REVIEW: Atherosclerosis is the leading cause of cardiovascular disease (CVD) and stroke. Typically, atherosclerotic calcium is found during the mature stage of the atherosclerosis disease. It is therefore often a challenge to identify and quantify the calcium. This is due to the presence of multiple components of plaque buildup in the arterial walls. The American College of Cardiology/American Heart Association guidelines point to the importance of calcium in the coronary and carotid arteries and further recommend its quantification for the prevention of heart disease. It is therefore essential to stratify the CVD risk of the patient into low- and high-risk bins. RECENT FINDING: Calcium formation in the artery walls is multifocal in nature with sizes at the micrometer level. Thus, its detection requires high-resolution imaging. Clinical experience has shown that even though optical coherence tomography offers better resolution, intravascular ultrasound still remains an important imaging modality for coronary wall imaging. For a computer-based analysis system to be complete, it must be scientifically and clinically validated. This study presents a state-of-the-art review (condensation of 152 publications after examining 200 articles) covering the methods for calcium detection and its quantification for coronary and carotid arteries, the pros and cons of these methods, and the risk stratification strategies. The review also presents different kinds of statistical models and gold standard solutions for the evaluation of software systems useful for calcium detection and quantification. Finally, the review concludes with a possible vision for designing the next-generation system for better clinical outcomes.

Web-based accurate measurements of carotid lumen diameter and stenosis severity: An ultrasound-based clinical tool for stroke risk assessment during multicenter clinical trials.

BACKGROUND: This pilot study presents a completely automated, novel, smart, cloud-based, point-of-care system for (a) carotid lumen diameter (LD); (b) stenosis severity index (SSI) and (c) total lumen area (TLA) measurement using B-mode ultrasound. The proposed system was (i) validated against manual reading taken by the Neurologist and (ii) benchmarked against the commercially available system. METHOD: One hundred patients (73 M/27 F, mean age: 68 ± 11 years), institutional review board approved, written informed consent, consisted of left/right common carotid artery (200 ultrasound scans) were acquired using a 7.5-MHz linear transducer. RESULTS: The measured mean LD for left and right carotids were (in mm): (i) for proposed system (6.49 ± 1.77, 6.66 ± 1.70); and (ii) for manual (6.29 ± 1.79, 6.45 ± 1.63), respectively and coefficient of correlation between cloud-based automated against manual were 0.98 (P < 0.0001) and 0.99 (P < 0.0001), respectively. The corresponding TLA error, Precision-of-Merit, and Figure-of-Merit when measured against the manual were: 4.56 ± 3.54%, 96.18 ± 3.21%, and 96.85%, respectively. The AUC for the receiving operating characteristics for the cloud-based system was: 1.0. Four statistical tests such as: Two-tailed z-test, Mann-Whitney test, Kolmogorov-Smirnov (KS) and one-way ANOVA were performed to demonstrate consistency and reliability. CONCLUSIONS: The proposed system is reliable, accurate, fast, completely automated, anytime-anywhere solution for multi-center clinical trials and routine vascular screening.

Wall-based measurement features provides an improved IVUS coronary artery risk assessment when fused with plaque texture-based features during machine learning paradigm.

BACKGROUND: Planning of percutaneous interventional procedures involves a pre-screening and risk stratification of the coronary artery disease. Current screening tools use stand-alone plaque texture-based features and therefore lack the ability to stratify the risk. METHOD: This IRB approved study presents a novel strategy for coronary artery disease risk stratification using an amalgamation of IVUS plaque texture-based and wall-based measurement features. Due to common genetic plaque makeup, carotid plaque burden was chosen as a gold standard for risk labels during training-phase of machine learning (ML) paradigm. Cross-validation protocol was adopted to compute the accuracy of the ML framework. A set of 59 plaque texture-based features was padded with six wall-based measurement features to show the improvement in stratification accuracy. The ML system was executed using principle component analysis-based framework for dimensionality reduction and uses support vector machine classifier for training and testing-phases. RESULTS: The ML system produced a stratification accuracy of 91.28%, demonstrating an improvement of 5.69% when wall-based measurement features were combined with plaque texture-based features. The fused system showed an improvement in mean sensitivity, specificity, positive predictive value, and area under the curve by: 6.39%, 4.59%, 3.31% and 5.48%, respectively when compared to the stand-alone system. While meeting the stability criteria of 5%, the ML system also showed a high average feature retaining power and mean reliability of 89.32% and 98.24%, respectively. CONCLUSIONS: The ML system showed an improvement in risk stratification accuracy when the wall-based measurement features were fused with the plaque texture-based features.

Relationship between Automated Coronary Calcium Volumes and a Set of Manual Coronary Lumen Volume, Vessel Volume and Atheroma Volume in Japanese Diabetic Cohort.

INTRODUCTION: A high degree of correlation exists between Coronary Artery Diseases (CAD) and calcification of the vessel wall. For Percutaneous Coronary Interventional (PCI) planning, it is essential to have an exact understanding of the extent to which calcium volume is correlated to the lumen, vessel, and atheroma volume regions in the coronary artery, which is unclear in recent studies. AIM: Four automated Coronary Calcium Volume (aCCV) measurement methods {threshold, Fuzzy c-Means (FCM), K-means, and Hidden Markov Random Field (HMRF)} and its correlation with three manual (experts) coronary parameters namely: Coronary Vessel Volume (mCVV), Coronary Lumen Volume (mCLV), and Coronary Atheroma Volume (mCAV), was determined in a Japanese diabetic cohort. MATERIALS AND METHODS: Intravascular Ultrasound (IVUS) image dataset from 19 patients (around 40,090 frames) was collected using 40 MHz IVUS catheter (Atlantis® SR Pro, Boston Scientific®, pullback speed of 0.5 mm/sec). The methodology consisted of automatically computing the calcium volume in the entire IVUS coronary videos using FCM, K-means, and HMRF based pixel classification and comparing it against the previously published threshold-based method. The Coefficient of Correlation (CC) was then established between the four aCCV and three manually (experts) coronary parameters: mCVV, mCLV, and mCAV computed using iMAP software Boston Scientific®. Statistical tests (Two-tailed paired Student t-test, Wilcoxon signed rank test, Mann-Whitney test, Chi-square test, and Kolmogorov-Smirnov KS-test) were performed to demonstrate consistency, reliability, and accuracy of the proposed work. RESULTS: Correlation coefficient of: (a) automated threshold-based volume; (b) automated FCM based volume; (c) automated K-means based volume; and (d) automated HMRF based volume and corresponding three manually (expert's) coronary parameters (mCLV, mCVV, mCAV) were: (0.51, 0.40, 0.48), (0.52, 0.38, 0.49), (0.56, 0.45, 0.52), and (0.57, 0.42, 0.56), respectively. The CC between age and haemoglobin was 0.50. CONCLUSION: Automated coronary volume measurement using HMRF method is more accurate compared to threshold, FCM, and K-means-based method, since it is more strongly correlated with three expert's readings.

Well-balanced system for coronary calcium detection and volume measurement in a low resolution intravascular ultrasound videos.

BACKGROUND: Accurate and fast quantitative assessment of calcium volume is required during the planning of percutaneous coronary interventions procedures. Low resolution in intravascular ultrasound (IVUS) coronary videos poses a threat to calcium detection causing over-estimation in volume measurement. We introduce a correction block that counter-balances the bias introduced during the calcium detection process. METHOD: Nineteen patients image dataset (around 40,090 frames), IRB approved, were collected using 40MHz IVUS catheter (Atlantis® SR Pro, Boston Scientific®, pullback speed of 0.5mm/sec). A new set of 20 generalized and well-balanced systems each consisting of three stages: (i) calcium detection, (ii) calibration and (iii) measurement, while ensuring accuracy of four soft classifiers (Threshold, FCM, K-means and HMRF) and workflow speed using five multiresolution techniques (bilinear, bicubic, wavelet, Lanczos, Gaussian Pyramid) were designed. Results of the three calcium detection methods were benchmarked against the Threshold-based method. RESULTS: All 20 well-balanced systems with calibration block show superior performance. Using calibration block, FCM versus Threshold-based method shows the highest cross-correlation 0.99 (P<0.0001), Jaccard index 0.984±0.013 (P<0.0001), and Dice similarity 0.992±0.007 (P<0.0001). The corresponding area under the curve for four calcium detection techniques is: 1.0, 1.0, 0.97 and 0.93, respectively. The mean overall performance improvement is 38.54% and when adapting calibration block. The mean workflow speed improvement is 62.14% when adapting multiresolution paradigm. Three clinical tests shows consistency, reliability, and stability of our well-balanced system. CONCLUSIONS: A well-balanced system with a combination of Threshold embedded with Lanczos multiresolution was optimal and can be useable in clinical settings.

Five multiresolution-based calcium volume measurement techniques from coronary IVUS videos: A comparative approach.

BACKGROUND AND OBJECTIVE: Fast intravascular ultrasound (IVUS) video processing is required for calcium volume computation during the planning phase of percutaneous coronary interventional (PCI) procedures. Nonlinear multiresolution techniques are generally applied to improve the processing time by down-sampling the video frames. METHODS: This paper presents four different segmentation methods for calcium volume measurement, namely Threshold-based, Fuzzy c-Means (FCM), K-means, and Hidden Markov Random Field (HMRF) embedded with five different kinds of multiresolution techniques (bilinear, bicubic, wavelet, Lanczos, and Gaussian pyramid). This leads to 20 different kinds of combinations. IVUS image data sets consisting of 38,760 IVUS frames taken from 19 patients were collected using 40 MHz IVUS catheter (Atlantis® SR Pro, Boston Scientific®, pullback speed of 0.5 mm/sec.). The performance of these 20 systems is compared with and without multiresolution using the following metrics: (a) computational time; (b) calcium volume; (c) image quality degradation ratio; and (d) quality assessment ratio. RESULTS: Among the four segmentation methods embedded with five kinds of multiresolution techniques, FCM segmentation combined with wavelet-based multiresolution gave the best performance. FCM and wavelet experienced the highest percentage mean improvement in computational time of 77.15% and 74.07%, respectively. Wavelet interpolation experiences the highest mean precision-of-merit (PoM) of 94.06 ± 3.64% and 81.34 ± 16.29% as compared to other multiresolution techniques for volume level and frame level respectively. Wavelet multiresolution technique also experiences the highest Jaccard Index and Dice Similarity of 0.7 and 0.8, respectively. Multiresolution is a nonlinear operation which introduces bias and thus degrades the image. The proposed system also provides a bias correction approach to enrich the system, giving a better mean calcium volume similarity for all the multiresolution-based segmentation methods. After including the bias correction, bicubic interpolation gives the largest increase in mean calcium volume similarity of 4.13% compared to the rest of the multiresolution techniques. The system is automated and can be adapted in clinical settings. CONCLUSIONS: We demonstrated the time improvement in calcium volume computation without compromising the quality of IVUS image. Among the 20 different combinations of multiresolution with calcium volume segmentation methods, the FCM embedded with wavelet-based multiresolution gave the best performance.

Accurate cloud-based smart IMT measurement, its validation and stroke risk stratification in carotid ultrasound: A web-based point-of-care tool for multicenter clinical trial.

This study presents AtheroCloud™ - a novel cloud-based smart carotid intima-media thickness (cIMT) measurement tool using B-mode ultrasound for stroke/cardiovascular risk assessment and its stratification. This is an anytime-anywhere clinical tool for routine screening and multi-center clinical trials. In this pilot study, the physician can upload ultrasound scans in one of the following formats (DICOM, JPEG, BMP, PNG, GIF or TIFF) directly into the proprietary cloud of AtheroPoint from the local server of the physician's office. They can then run the intelligent and automated AtheroCloud™ cIMT measurements in point-of-care settings in less than five seconds per image, while saving the vascular reports in the cloud. We statistically benchmark AtheroCloud™ cIMT readings against sonographer (a registered vascular technologist) readings and manual measurements derived from the tracings of the radiologist. One hundred patients (75 M/25 F, mean age: 68±11 years), IRB approved, Toho University, Japan, consisted of Left/Right common carotid artery (CCA) artery (200 ultrasound scans), (Toshiba, Tokyo, Japan) were collected using a 7.5MHz transducer. The measured cIMTs for L/R carotid were as follows (in mm): (i) AtheroCloud™ (0.87±0.20, 0.77±0.20); (ii) sonographer (0.97±0.26, 0.89±0.29) and (iii) manual (0.90±0.20, 0.79±0.20), respectively. The coefficient of correlation (CC) between sonographer and manual for L/R cIMT was 0.74 (P<0.0001) and 0.65 (P<0.0001), while, between AtheroCloud™ and manual was 0.96 (P<0.0001) and 0.97 (P<0.0001), respectively. We observed that 91.15% of the population in AtheroCloud™ had a mean cIMT error less than 0.11mm compared to sonographer's 68.31%. The area under curve for receiving operating characteristics was 0.99 for AtheroCloud™ against 0.81 for sonographer. Our Framingham Risk Score stratified the population into three bins as follows: 39% in low-risk, 70.66% in medium-risk and 10.66% in high-risk bins. Statistical tests were performed to demonstrate consistency, reliability and accuracy of the results. The proposed AtheroCloud™ system is completely reliable, automated, fast (3-5 seconds depending upon the image size having an internet speed of 180Mbps), accurate, and an intelligent, web-based clinical tool for multi-center clinical trials and routine telemedicine clinical care.

PCA-based polling strategy in machine learning framework for coronary artery disease risk assessment in intravascular ultrasound: A link between carotid and coronary grayscale plaque morphology.

BACKGROUND AND OBJECTIVE: Percutaneous coronary interventional procedures need advance planning prior to stenting or an endarterectomy. Cardiologists use intravascular ultrasound (IVUS) for screening, risk assessment and stratification of coronary artery disease (CAD). We hypothesize that plaque components are vulnerable to rupture due to plaque progression. Currently, there are no standard grayscale IVUS tools for risk assessment of plaque rupture. This paper presents a novel strategy for risk stratification based on plaque morphology embedded with principal component analysis (PCA) for plaque feature dimensionality reduction and dominant feature selection technique. The risk assessment utilizes 56 grayscale coronary features in a machine learning framework while linking information from carotid and coronary plaque burdens due to their common genetic makeup. METHOD: This system consists of a machine learning paradigm which uses a support vector machine (SVM) combined with PCA for optimal and dominant coronary artery morphological feature extraction. Carotid artery proven intima-media thickness (cIMT) biomarker is adapted as a gold standard during the training phase of the machine learning system. For the performance evaluation, K-fold cross validation protocol is adapted with 20 trials per fold. For choosing the dominant features out of the 56 grayscale features, a polling strategy of PCA is adapted where the original value of the features is unaltered. Different protocols are designed for establishing the stability and reliability criteria of the coronary risk assessment system (cRAS). RESULTS: Using the PCA-based machine learning paradigm and cross-validation protocol, a classification accuracy of 98.43% (AUC 0.98) with K=10 folds using an SVM radial basis function (RBF) kernel was achieved. A reliability index of 97.32% and machine learning stability criteria of 5% were met for the cRAS. CONCLUSIONS: This is the first Computer aided design (CADx) system of its kind that is able to demonstrate the ability of coronary risk assessment and stratification while demonstrating a successful design of the machine learning system based on our assumptions.

Reliable and Accurate Calcium Volume Measurement in Coronary Artery Using Intravascular Ultrasound Videos.

Quantitative assessment of calcified atherosclerotic volume within the coronary artery wall is vital for cardiac interventional procedures. The goal of this study is to automatically measure the calcium volume, given the borders of coronary vessel wall for all the frames of the intravascular ultrasound (IVUS) video. Three soft computing fuzzy classification techniques were adapted namely Fuzzy c-Means (FCM), K-means, and Hidden Markov Random Field (HMRF) for automated segmentation of calcium regions and volume computation. These methods were benchmarked against previously developed threshold-based method. IVUS image data sets (around 30,600 IVUS frames) from 15 patients were collected using 40 MHz IVUS catheter (Atlantis® SR Pro, Boston Scientific®, pullback speed of 0.5 mm/s). Calcium mean volume for FCM, K-means, HMRF and threshold-based method were 37.84 ± 17.38 mm(3), 27.79 ± 10.94 mm(3), 46.44 ± 19.13 mm(3) and 35.92 ± 16.44 mm(3) respectively. Cross-correlation, Jaccard Index and Dice Similarity were highest between FCM and threshold-based method: 0.99, 0.92 ± 0.02 and 0.95 + 0.02 respectively. Student's t-test, z-test and Wilcoxon-test are also performed to demonstrate consistency, reliability and accuracy of the results. Given the vessel wall region, the system reliably and automatically measures the calcium volume in IVUS videos. Further, we validated our system against a trained expert using scoring: K-means showed the best performance with an accuracy of 92.80%. Out procedure and protocol is along the line with method previously published clinically.

A new method for IVUS-based coronary artery disease risk stratification: A link between coronary & carotid ultrasound plaque burdens.

Interventional cardiologists have a deep interest in risk stratification prior to stenting and percutaneous coronary intervention (PCI) procedures. Intravascular ultrasound (IVUS) is most commonly adapted for screening, but current tools lack the ability for risk stratification based on grayscale plaque morphology. Our hypothesis is based on the genetic makeup of the atherosclerosis disease, that there is evidence of a link between coronary atherosclerosis disease and carotid plaque built up. This novel idea is explored in this study for coronary risk assessment and its classification of patients between high risk and low risk. This paper presents a strategy for coronary risk assessment by combining the IVUS grayscale plaque morphology and carotid B-mode ultrasound carotid intima-media thickness (cIMT) - a marker of subclinical atherosclerosis. Support vector machine (SVM) learning paradigm is adapted for risk stratification, where both the learning and testing phases use tissue characteristics derived from six feature combinational spaces, which are then used by the SVM classifier with five different kernels sets. These six feature combinational spaces are designed using 56 novel feature sets. K-fold cross validation protocol with 10 trials per fold is used for optimization of best SVM-kernel and best feature combination set. IRB approved coronary IVUS and carotid B-mode ultrasound were jointly collected on 15 patients (2 days apart) via: (a) 40MHz catheter utilizing iMap (Boston Scientific, Marlborough, MA, USA) with 2865 frames per patient (42,975 frames) and (b) linear probe B-mode carotid ultrasound (Toshiba scanner, Japan). Using the above protocol, the system shows the classification accuracy of 94.95% and AUC of 0.95 using optimized feature combination. This is the first system of its kind for risk stratification as a screening tool to prevent excessive cost burden and better patients' cardiovascular disease management, while validating our two hypotheses.