Ultrasound-Derived Fat Fraction for Hepatic Steatosis Assessment: Prospective Study of Agreement With MRI PDFF and Sources of Variability in a Heterogeneous Population.

Background: Metabolic dysfunction-associated steatotic liver disease is a growing global public health concern. Quantitative ultrasound measurements, such as ultrasound-derived fat fraction (UDFF), could provide noninvasive, cost-effective, and portable steatosis evaluation. Objective: To evaluate utility of UDFF for steatosis assessment using PDFF as reference in patients undergoing liver MRI for heterogeneous indications, and to assess UDFF variability. Methods: This prospective study included a primary analysis of 187 patients (mean age, 53.8 years; 112 men, 75 women) who underwent 3-T liver MRI for any clinical indication from December 2020 to July 2021. Patients underwent investigational proton-density fat fraction (PDFF) measurement using MR spectroscopy, and investigational ultrasound with UDFF calculation (mean of 5 intercostal measurements) within 1 hour after MRI. In a subanalysis, 21 of these patients underwent additional UDFF measurements 1, 3, and 5 hours after meal consumption. The study also included repeatability and reproducibility (R&R) analysis of 30 patients (mean age, 26.3 years; 11 men, 20 women) who underwent clinical abdominal ultrasound between November 2022 and January 2023; in these patients, three operators sequentially performed UDFF measurements. Results: In primary analysis, UDFF and PDFF showed intraclass correlation coefficient (ICC) of 0.79. In Bland-Altmananalysis, UDFF and PDFF showed mean difference of 1.5% (95% CI, 0.6-2.4%), with 95% limits of agreement from -11.0% to 14.0%. UDFF exhibited AUC for detecting PDFF at historic thresholds of ≥6.5%, ≥17.4%, and ≥22.1% of 0.90, 0.95, and 0.95, respectively. In subanalysis, mean UDFF was not significantly different across time points with respect to meal consumption (p=.21). In R&R analysis, ICC for intraoperator repeatability ranged from 0.98 to 0.99, and for interoperator reproducibility from 0.90 to 0.96. Visual assessment of patient-level data plots indicated increasing variability of mean UDFF measurements across operators, and of intercostal measurements within individual patients, with increasing steatosis. Conclusion: UDFF showed robust agreement with PDFF, diagnostic performance for steatosis grades, as well as intraoperator repeatability and interoperator reproducibility. Nonetheless, UDFF exhibited bias toward slightly larger values versus PDFF, intraoperator and interoperator variation increased with increasing steatosis. Clinical Impact: UDFF shows promise for steatosis assessment across diverse populations, although continued optimization remains warranted.

4D Volume Intracardiac Echocardiography for Intraprocedural Guidance of Transcatheter Left Atrial Appendage Closure.

BACKGROUND: Fluoroscopy and transesophageal echocardiography (TEE) are used to guide transcatheter left atrial appendage (LAA) closure in patients with atrial fibrillation to prevent thromboembolic events. This study examines whether real-time three-dimensional volume ICE guidance (4D volume ICE) can be used as an alternative to TEE during LAA closure (LAAC). METHODS AND RESULTS: Fifteen patients with atrial fibrillation (AF), who had high risk for stroke and contraindication for long-term warfarin therapy, were enrolled in the study. The WATCHMAN device was used for transcatheter LAAC under fluoroscopy. LAA and device sizing was performed using TEE and volume ICE guidance from the right heart. Intraprocedural ICE measurements were consistent with TEE; LAA maximal width and depth, and maximal diameter of the implanted device were moderately correlated (Pearson's coefficient: 0.63, 0.65, and 0.71 respectively; p<0.05) with good agreement (bias: -0.03 cm, -0.07 cm, and 0.003 cm respectively). The average imaging success rate, defined by the number of patients with all the required intraprocedural measurements, was 67% for ICE and 100% for TEE. The WATCHMAN device was successfully implanted in all patients with a device to patient ratio of 1.33. CONCLUSIONS: 4D volume ICE can be used as an intraprocedural sizing and guidance tool for transcatheter LAAC with measurements comparable to TEE. Challenging patient characteristics significantly degrade the diagnostic image quality when imaging from the right heart. Standardized workflow with proper patient selection and optimal preprocedural planning may improve the diagnostic quality of volume ICE guidance for transcatheter LAAC procedure.

Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry.

Vascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound-based, particle image velocimetry technique (echo PIV) to compute 2-D velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatiotemporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak systole (118 ± 16%) and the smallest during mid-diastole (4.3± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%), whereas WSS was overestimated for end-diastolic measurements (-44 ± 55%). Our data indicate that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatiotemporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV-derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.

Echo Particle Image Velocimetry for Estimation of Carotid Artery Wall Shear Stress: Repeatability, Reproducibility and Comparison with Phase-Contrast Magnetic Resonance Imaging.

Measurement of hemodynamic wall shear stress (WSS) is important in investigating the role of WSS in the initiation and progression of atherosclerosis. Echo particle image velocimetry (echo PIV) is a novel ultrasound-based technique for measuring WSS in vivo that has previously been validated in vitro using the standard optical PIV technique. We evaluated the repeatability and reproducibility of echo PIV for measuring WSS in the human common carotid artery. We measured WSS in 28 healthy participants (18 males and 10 females, mean age: 56 ± 12 y). Echo PIV was highly repeatable, with an intra-observer variability of 1.0 ± 0.1 dyn/cm2 for peak systolic (maximum), 0.9 dyn/cm2 for mean and 0.5 dyn/cm2 for end-diastolic (minimum) WSS measurements. Likewise, echo PIV was reproducible, with a low inter-observer variability (max: 2.0 ± 0.2 dyn/cm2, mean: 1.3 ± 0.1 dyn/cm2, end-diastolic: 0.7 dyn/cm2) and more variable inter-scan (test-retest) variability (max: 7.1 ± 2.3 dyn/cm2, mean: 2.9 ± 0.4 dyn/cm2, min: 1.5 ± 0.1 dyn/cm2). We compared echo PIV with the reference method, phase-contrast magnetic resonance imaging (PC-MRI); echo PIV-based WSS measurements agreed qualitatively with PC-MRI measurements (r = 0.89, p < 0.05). Significant differences were observed in some WSS measurements (echo PIV vs. PC-MRI): WSS at peak systole: 21 ± 7.0 dyn/cm2 vs. 15 ± 5.0 dyn/cm2; time-averaged WSS: 8.9 ± 3.0 dyn/cm2 vs. 7.1 ± 3.0 dyn/cm2 (p < 0.05); WSS at end diastole: 3.8 ± 2.8 dyn/cm2 vs. 3.9 ± 2 dyn/cm2 (p > 0.05). For the first time, we report that echo PIV can measure WSS with good repeatability and reproducibility in adult humans with a broad age range. Echo PIV is feasible in humans and offers an easy-to-use, ultrasound-based, quantitative technique for measuring WSS in vivo in humans with good repeatability and reproducibility.

The early addition of arsenic trioxide versus high-dose arabinoside is more effective and safe as consolidation chemotherapy for risk-tailored patients with acute promyelocytic leukemia: multicenter experience.

The purpose of the study was to evaluate event-free survival (EFS), overall survival (OS) and safety for early addition of arsenic trioxide (As(2)O(3)) as frontline consolidation therapy compared to high-dose arabinoside (HiDAC) in adult patients with de novo acute promyelocytic leukemia (APL). 271 patients (aged 17-65 years) received consolidation therapy containing As(2)O(3) (two 21-day courses) or HiDAC regimen. EFS at 5 years was 75% versus 54% (P < 0.001), and OS at 5 years was 83% versus 71% (P = 0.002) in As(2)O(3) and HiDAC treatment arms. 139 patients treated with As(2)O(3), EFS at 5 years reached 79% versus 56% (P = 0.014), but OS at 5 years was 77% versus 84% (P = 0.32) in low-risk (WBC ≤ 10 × 10(9)/L) and high-risk (WBC > 10 × 10(9)/L) cohorts. Further, patients treated with As(2)O(3) rarely incurred agranulocytosis (1.4%, P < 0.001), or severe infection (0.7%, P < 0.001). It is still very well tolerated compared to HiDAC. We confirmed that As(2)O(3) as a first-line consolidation regimen provided significant benefits of OS to patients with APL. The As(2)O(3) regimen made low-risk patients gain more EFS benefits than high-risk group. The high-risk cohort receiving As(2)O(3) overcame the negative impact, yielding OS similar to that for with the low-risk patients treated with As(2)O(3).

Computerized lung sound analysis as diagnostic aid for the detection of abnormal lung sounds: a systematic review and meta-analysis.

RATIONALE: The standardized use of a stethoscope for chest auscultation in clinical research is limited by its inherent inter-listener variability. Electronic auscultation and automated classification of recorded lung sounds may help prevent some of these shortcomings. OBJECTIVE: We sought to perform a systematic review and meta-analysis of studies implementing computerized lung sound analysis (CLSA) to aid in the detection of abnormal lung sounds for specific respiratory disorders. METHODS: We searched for articles on CLSA in MEDLINE, EMBASE, Cochrane Library and ISI Web of Knowledge through July 31, 2010. Following qualitative review, we conducted a meta-analysis to estimate the sensitivity and specificity of CLSA for the detection of abnormal lung sounds. MEASUREMENTS AND MAIN RESULTS: Of 208 articles identified, we selected eight studies for review. Most studies employed either electret microphones or piezoelectric sensors for auscultation, and Fourier Transform and Neural Network algorithms for analysis and automated classification of lung sounds. Overall sensitivity for the detection of wheezes or crackles using CLSA was 80% (95% CI 72-86%) and specificity was 85% (95% CI 78-91%). CONCLUSIONS: While quality data on CLSA are relatively limited, analysis of existing information suggests that CLSA can provide a relatively high specificity for detecting abnormal lung sounds such as crackles and wheezes. Further research and product development could promote the value of CLSA in research studies or its diagnostic utility in clinical settings.