Correction: Indocyanine-green-loaded microbubbles for localization of sentinel lymph node using near-infrared fluorescence/ultrasound imaging: a feasibility study.

[This corrects the article DOI: 10.1039/C5RA26814A.].

Towards precision medicine based on a continuous deep learning optimization and ensemble approach.

We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We extracted 629 breast masses and 2235 images from 561 cases in the institution to train the model in six stages to diagnose benign and malignant tumors, pathological types, and diseases. We randomly selected 180 out of 3098 cases from two external institutions. The CLS was tested with seven independent datasets and compared with 21 physicians, and the system's diagnostic ability exceeded 20 physicians by training stage six. The optimal integrated method we developed is expected accurately diagnose breast masses. This method can also be extended to the intelligent diagnosis of masses in other organs. Overall, our findings have potential value in further promoting the application of AI diagnosis in precision medicine.

Value of Contrast-Enhanced Ultrasound in Differentiating Clinically Atypical Subacute Thyroiditis from Papillary Thyroid Carcinomas.

Our objective was to provide the various sonographic characteristics of clinically atypical subacute thyroiditis (CAST) in distinguishing CAST from papillary thyroid carcinomas (PTCs) by using conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). Forty-six CAST patients and 50 PTC patients were enrolled in this study. We evaluated the size, shape, margin, echogenicity, calcification, vascularity and CEUS parameters for each nodule. The final diagnosis of CAST was confirmed via fine-needle aspiration (FNA) or surgery. Of the 46 CASTs, 13 (28.3%) were confirmed by surgery to be benign, and 33 (71.7%) were proven by FNA to be benign. Univariate analysis indicated that compared with PTCs, CAST lesions more frequently had wider-than-taller shapes, blurred margins, the absence of microcalcifications, peripheral high echogenicity, the absence of internal vascularity, hypo-enhancement, centrifugal perfusion and a peak intensity index <1 and area under the curve index <1 on pre-operative US and CEUS. A multivariate analysis revealed that clear margins, microcalcifications and centripetal perfusion were independent characteristics related to PTCs for their differentiation from CAST (all p values <0.05). Our study indicated that the pre-operative multiparameter US characteristics may serve as a useful tool for distinguishing CAST from malignant thyroid nodules to avoid surgical excisions or unnecessary FNAs.

Sonographic Characteristics of Papillary Thyroid Carcinoma With Coexistent Hashimoto's Thyroiditis in the Preoperative Prediction of Central Lymph Node Metastasis.

The purpose of this study was to evaluate the usefulness of the sonographic characteristics of papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (HT) for predicting central lymph node metastasis (CLNM). One hundred thirty-three patients who underwent thyroidectomy and central cervical lymph node dissection for PTC with coexistent HT were retrospectively analyzed. All PTCs with HT were preoperatively evaluated by ultrasound (US) regarding their nodular number, size, component, shape, margin, echogenicity, calcification, capsule contact with protrusion, vascularity and contrast enhanced ultrasound (CEUS) parameters. Univariate analysis demonstrated that patients with PTCs with HT and CLNM more frequently had age ≤ 45 years, size > 10 mm, a wider than tall shape, microcalcification, hypo-enhancement and peak intensity index < 1 than those without CLNM (all p<0.05). Binary logistic regression analysis demonstrated that size > 10 mm and CEUS hypo-enhancement were independent characteristics for the presence of CLNM. Our study indicated that preoperative US characteristics could offer help in predicting CLNM in PTCs with coexistent HT.

Evaluating the Sensitivity and Specificity of Promising Circulating Biomarkers to Diagnose Liver Injury in Humans.

Early diagnosis of drug-induced liver injury (DILI) continues to be a major hurdle during drug development and postmarketing. The objective of this study was to evaluate the diagnostic performance of promising biomarkers of liver injury-glutamate dehydrogenase (GLDH), cytokeratin-18 (K18), caspase-cleaved K18 (ccK18), osteopontin (OPN), macrophage colony-stimulating factor (MCSF), MCSF receptor (MCSFR), and microRNA-122 (miR-122) in comparison to the traditional biomarker alanine aminotransferase (ALT). Biomarkers were evaluated individually and as a multivariate model in a cohort of acetaminophen overdose (n = 175) subjects and were further tested in cohorts of healthy adults (n = 135), patients with liver damage from various causes (n = 104), and patients with damage to the muscle (n = 74), kidney (n = 40), gastrointestinal tract (n = 37), and pancreas (n = 34). In the acetaminophen cohort, a multivariate model with GLDH, K18, and miR-122 was able to detect DILI more accurately than individual biomarkers alone. Furthermore, the three-biomarker model could accurately predict patients with liver injury compared with healthy volunteers or patients with damage to muscle, pancreas, gastrointestinal tract, and kidney. Expression of K18, GLDH, and miR-122 was evaluated using a database of transcriptomic profiles across multiple tissues/organs in humans and rats. K18 mRNA (Krt18) and MiR-122 were highly expressed in liver whereas GLDH mRNA (Glud1) was widely expressed. We performed a comprehensive, comparative performance assessment of 7 promising biomarkers and demonstrated that a 3-biomarker multivariate model can accurately detect liver injury.

Behavioral, Histopathologic, and Molecular Biological Responses of Nanoparticle- and Solution-Based Formulations of Vincristine in Mice.

Clinical use of the chemotherapeutic agent vincristine (VCR) is limited by chemotherapy-induced peripheral neuropathy (CiPN). A new formulation of VCR encapsulated by nanoparticles has been proposed and developed to alleviate CiPN. We hypothesized in nonclinical animals that the nanoparticle drug would be less neurotoxic due to different absorption and distribution properties to the peripheral nerve from the unencapsulated free drug. Here, we assessed whether VCR encapsulation in nanoparticles alleviates CiPN using behavioral gait analysis (CatWalk), histopathologic and molecular biological (RT-qPCR) approaches. Adult male C57BL/6 mice were assigned to 3 groups (empty nanoparticle, nano-VCR, solution-based VCR, each n = 8). After 15 days of dosing, animals were euthanized for tissue collection. It was shown that intraperitoneal administration of nano-VCR (0.15 mg/kg, every other day) and the empty nanoparticle resulted in no changes in gait parameters; whereas, injection of solution-based VCR resulted in decreased run speed and increased step cycle and stance (P < 0.05). There were no differences in incidence and severity of degeneration in the sciatic nerves between the nano-VCR-dosed and solution-based VCR-dosed animals. Likewise, decreased levels of a nervous tissue-enriched microRNA-183 in circulating blood did not show a significant difference between the nano- and solution-based VCR groups (P > 0.05). Empty nanoparticle administration did not cause any behavioral, microRNA, or structural changes. In conclusion, this study suggests that the nano-VCR formulation may alleviate behavioral changes in CiPN, but it does not improve the structural changes of CiPN in peripheral nerve. Nanoparticle properties may need to be optimized to improve biological observations.

Chinese Expert Consensus on Protection for Ultrasound Healthcare Workers against COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a worldwide pandemic and poses a serious public health risk. It has been proven that lung ultrasound can be extremely valuable in the diagnosis and treatment of the disease, which could also minimize the number of exposed healthcare workers and equipment. Because healthcare workers in ultrasound departments are in close contact with patients who might be infected or virus carriers, it is extremely important that they be provided sufficient protection. Extremely aggressive protection should be avoided because it might lead to a lack of protection equipment for the hospital. Guidance on proper protection management should be provided in detail, for example, how to choose personal protective equipment, how to disinfect the environment. To address these problems, on behalf of the Chinese Ultrasound Doctors Association, Chinese PLA Professional Committee of Ultrasound in Medicine, Beijing Institute of Ultrasound in Medicine and Chinese Research Hospital Association Ultrasound Professional Committee, the authors have summarized the recommendations for effective protection according to existing hygienic standards, their experience and available literature. After the recommendations were completed, two online conferences were held on January 31, 2020 and February 7, 2020, at which the recommendations were discussed in detail. A modified version of the work was circulated and finally approved by all authors, and is the present Chinese Expert Consensus on Protection for Ultrasound Healthcare Workers against COVID-19.

Contrast-Enhanced Ultrasound of Primary Squamous Cell Carcinoma of the Thyroid: A Case Report.

Introduction: Primary squamous cell carcinoma of the thyroid (ThyPSCC) is an extremely rare aggressive malignancy with a poor prognosis. However, almost no report thus far has investigated the microvasculature of ThyPSCC imaged using contrast-enhanced ultrasound. Case Report: A 59-year-old male patient presented to our hospital with progressively worsening hoarse voice symptoms for 20 days and was diagnosed with left unilateral vocal fold palsy. Ultrasonography revealed a solitary marked hypoechoic thyroid nodule with an unclear boundary in the inferior part of the left lobe. Color Doppler flow imaging showed a poor blood flow signal inside this nodule. Contrast-enhanced ultrasound images showed a persistent low peak enhancement of the nodule from its periphery to its center. The time-intensity curve displayed a wash-in time of 10 s, a time to peak of 37 s, a peak signal intensity of 24.5%, and a wash-out time of 70 s for the thyroid tumor. Finally, left hemithyroidectomy of the thyroid tumor was performed, and histopathologic and immunohistochemical evaluations confirmed the diagnosis of ThyPSCC. Postoperatively, the patient received a combination therapy of chemotherapy, radiotherapy, and targeted therapy, but the patient died 4 months after surgery. Conclusion: Primary squamous cell carcinoma of the thyroid is a rare but aggressive malignancy of the thyroid. Herein, we reported a case of ThyPSCC and its ultrasonography and pathologic findings.

Cerebral hemodynamic response to short-term maternal hyperoxygenation in fetuses with borderline small left hearts.

BACKGROUND: Hypoxia delays brain maturation and contributes to neurodevelopmental morbidity in fetuses with congenital heart defects (CHDs). Maternal hyperoxygenation (MH) can, in theory, promote oxygen/nutrient delivery to the fetal brain, owing to an improved heart structure/function and increased fetal oxygen content. We aimed to determine whether MH alters fetal cerebral hemodynamics in fetuses with CHD. METHODS: Twenty-eight fetuses with borderline small left hearts and 28 age-matched normal fetuses were enrolled and subdivided by gestational age (GA): 23+ 0 ~ 27+ 6 weeks and 28+ 0 ~ 36+ 6 weeks. The middle cerebral artery pulsatility index (MCA-PI), vascular index (VI), flow index (FI) and vascular/flow index (VFI) were measured with baseline room air, after 10 min of MH and after 10 min of recovery for all subjects. RESULTS: MCA-PI, VI, FI and VFI did not differ with MH in the normal fetuses. In fetuses with borderline small left hearts, MCA-PI increased and VI, FI and VFI significantly decreased during the 3rd trimester (from 1.44 ± 0.27, 3.19 ± 0.87, 56.91 ± 9.19, and 1.30 ± 0.33 at baseline to 1.62 ± 0.15, 2.37 ± 0.37, 45.73 ± 4.59, and 0.94 ± 0.15 during MH, respectively, P < 0.05), but this response was not apparent during mid-gestation (p > 0.05). These parameters returned to the baseline levels during the recovery phase. The change in cerebral perfusion depended on the baseline MCA-PI and increased the combined cardiac index (CCOi). CONCLUSIONS: MH alters the cerebral hemodynamics of fetuses with borderline small left hearts during the third trimester. Further investigation is needed to determine whether MH may benefit brain growth and neurodevelopment in this high-risk population.

Petal-Like Calcifications in Thyroid Nodules on Ultrasonography: A Rare Morphologic Characteristic of Calcification Associated With Aggressive Biological Behavior.

This study investigated a rare ultrasonographically detected thyroid petal-like calcification and its relationship with thyroid carcinoma and biological behavior. We described the clinical and ultrasonographical features of thyroid nodules with petal-like calcifications in 18 patients undergoing thyroid surgery and cervical lymph node dissection. All of the thyroid nodules with petal-like calcifications were papillary thyroid carcinomas (PTCs). Of the 18 patients, 13 (72.2%) had cervical central lymph node metastasis, and five (27.8%) had cervical lateral lymph node metastasis. Petal-like calcifications occurred in malignant thyroid nodules with a high incidence of lymph node metastasis, which may be a specific ultrasonographic feature associated with the aggressive biological behavior of PTC.

Fetal pulmonary atresia with ventricular septal defect: Features, associations, and outcome in fetuses with different pulmonary circulation supply types.

OBJECTIVES: To assess features and outcome in fetuses with pulmonary atresia with ventricular septal defect (PA-VSD). METHODS: Fetuses with PA-VSD were prospectively enrolled and grouped on the basis of the pulmonary blood supply, including type A (only arterial duct [DA]), type B (both DA and major aortopulmonary collateral arteries [MAPCAs] present), and type C (MAPCAs only). The echocardiography features, associated chromosomal/genetic malformations, and postnatal outcome were compared among the three groups. RESULTS: Fifty-five fetuses with PA-VSD were enrolled. The presence of confluent PAs varied, with the highest displaying rate in type A and lowest rate in type C (100% vs 41.1%). The intrapericardial pulmonary arteries in all groups were hypoplastic but smaller in types B and C than in type A (P < .05). Deletion of 22q11.2 and right aortic arch were more frequently observed in types B and C than in type A. At the end of the study, overall survival rates in type C were lower than those in type A (22.1% vs 77.3%). CONCLUSION: There are great differences in the size of pulmonary arteries, associated genetic malformations, and perinatal outcomes among fetuses with PA-VSD. These results could be used for family counseling and surgical planning.

Velocity vector imaging echocardiography and NT-proBNP study of fetal cardiac function in pregnancy-induced maternal hypertension.

PURPOSE: To investigate whether acute and transient pressure overload in patients with pregnancy-induced hypertension affects cardiac function in fetuses. METHODS: We enrolled 104 singleton pregnant women with gestational ages ranging 30 to 33 weeks, visiting for prenatal care. Among them, 34 had gestational hypertension (GH), 32 had preeclampsia (PE), and 38 were healthy and formed the control group. Conventional echocardiographic and velocity vector imaging (VVI) variables were prospectively collected. Blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from cord blood drawn at birth. RESULTS: The fetuses of mothers with preeclampsia had significantly lower left (LV) and right ventricle (RV) diastolic strain rate (SRd) and RV strain (S) and systolic strain rate (SRs) than controls. LV and RV S, SRd, and SRS were not different in fetuses of mothers with GH and controls. The NT-proBNP levels were higher in fetuses of patients with PE than in GH and controls. CONCLUSIONS: In the third trimester of pregnancy, fetal biventricular function and NT-proBNP levels are not significantly influenced by GH. Fetuses of mothers with PE present signs of LV and RV diastolic dysfunction, right ventricular systolic dysfunction, and elevated NT-pro-BNP levels. VVI echocardiography appears more sensitive than conventional echocardiography to evaluate fetal cardiac function.

Circulating microRNA and automated motion analysis as novel methods of assessing chemotherapy-induced peripheral neuropathy in mice.

Chemotherapy-induced peripheral neuropathy (CiPN) is a serious adverse effect in the clinic, but nonclinical assessment methods in animal studies are limited to labor intensive behavioral tests or semi-quantitative microscopic evaluation. Hence, microRNA (miRNA) biomarkers and automated in-life behavioral tracking were assessed for their utility as non-invasive methods. To address the lack of diagnostic biomarkers, we explored miR-124, miR-183 and miR-338 in a CiPN model induced by paclitaxel, a well-known neurotoxic agent. In addition, conventional and Vium's innovative Digital Vivarium technology-based in-life behavioral tests and postmortem microscopic examination of the dorsal root ganglion (DRG) and the sciatic nerve were performed. Terminal blood was collected on days 8 or 16, after 20 mg/kg paclitaxel was administered every other day for total of 4 or 7 doses, respectively, for plasma miRNA quantification by RT-qPCR. DRG and sciatic nerve samples were collected from mice sacrificed on day 16 for miRNA quantification. Among the three miRNAs analyzed, only miR-124 was statistically significantly increased (5 fold and 10 fold on day 8 and day 16, respectively). The increase in circulating miR-124 correlated with cold allodynia and axonal degeneration in both DRG and sciatic nerve. Automated home cage motion analysis revealed for the first time that nighttime motion was significantly decreased (P < 0.05) in paclitaxel-dosed animals. Although both increase in circulating miR-124 and decrease in nighttime motion are compelling, our results provide positive evidence warranting further testing using additional peripheral nerve toxicants and diverse experimental CiPN models.

Sonographic Characteristics of Papillary Thyroid Carcinoma with Coexistent Hashimoto's Thyroiditis: Conventional Ultrasound, Acoustic Radiation Force Impulse Imaging and Contrast-Enhanced Ultrasound.

Our objective was to provide the various sonographic characteristics of papillary thyroid carcinomas for Hashimoto's thyroiditis (HT) patients, including conventional ultrasound (US), acoustic radiation force impulse Virtual Touch imaging and quantification (ARFI-VTIQ) and contrast-enhanced ultrasound (CEUS). Sixty-nine HT patients with 85 thyroid nodules (TNs) (49 malignant and 36 benign) were enrolled in this study. We evaluated the size, shape, margin, echogenicity, presence of halo, calcification, vascularity and ARFI-VTIQ and CEUS parameters for each nodule and compared the findings with the reference standards of histopathological and/or cytologic results. Univariate analysis indicated that compared with benign TNs with HT, papillary thyroid carcinomas with HT more often had taller-than-wider shapes, ill-defined margins, microcalcifications, peripheral vascularity, relatively harder stiffness with a higher shear wave speed, hypo-enhancement, peak intensity index <1 and area under the curve index <1 at pre-operative US, ARFI-VTIQ and CEUS. Multivariate analysis revealed that ill-defined margins, microcalcifications and peak intensity index <1 are independent characteristics related to malignant TNs for their differentiation from benign TNs (all p < 0.05). Our study indicated that pre-operative multiparameter US characteristics may serve as a useful tool to identify malignant TNs in HT patients.

Mummified Thyroid Nodules: Conventional and Contrast-Enhanced Ultrasound Features.

OBJECTIVES: The purpose of our study was to highlight the conventional and contrast-enhanced ultrasound (US) features of mummified thyroid nodules, which should help differentiate them from histologically proven papillary thyroid carcinomas (PTCs). METHODS: Thirty-one patients with 33 mummified thyroid nodules, which showed suspicious US findings that were suggestive of malignancy, as well as 33 patients with 38 surgically confirmed PTCs were enrolled in this study. We evaluated the size, shape, margin, echogenicity, presence of shadowing and halo, presence of punctate echogenic foci, vascularity, and contrast enhancement parameters for each nodule. The final diagnosis of mummified thyroid nodules was confirmed via fine-needle aspiration (FNA) or surgery. RESULTS: Of the 33 mummified thyroid nodules, 9 (27.3%) were confirmed by surgery to be benign, and 24 (72.7%) were proven by FNA to be benign. A univariate analysis indicated that the mummified thyroid nodules more frequently showed wider-than-tall shapes, marked hypoechogenicity, the presence of posterior shadowing, the absence of nodular vascularity, hypoenhancement or no enhancement, and peak index and area under the curve indices of less than 1 in the findings of preoperative US and contrast-enhanced US compared to PTCs. A multivariate analysis showed that marked hypoechogenicity and an area under the curve index of less than 1 were independent characteristics related to mummified nodules for discriminating from PTCs (all P < .05). CONCLUSIONS: Benign thyroid nodules may display shrinkage over time and may reveal malignant US features. Awareness of these findings and their connection with initial and follow-up US examinations should help identify mummified thyroid nodules and to avoid surgical excision or unnecessary FNA.

Different vasodilatation characteristics among the main cerebral arteries in fetuses with congenital heart defects.

To observe Doppler changes in the three main cerebral arteries in fetuses with congenital heart defects (CHDs). The pulsatility index (PI) values of the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) were prospectively compared in 78 CHD fetuses and 78 normal control fetuses. Correlations between the cerebral artery PIs and the neurodevelopment scores (psychomotor development index [PDI] and mental development index [MDI]) were assessed. The MCA-PI was decreased significantly in fetuses with hypoplastic left heart syndrome (HLHS). The ACA-PI was reduced significantly in fetuses with HLHS, fetuses with left-sided obstructive lesions (LSOLs) and fetuses with transposition of the great arteries. The PCA-PI was significantly smaller in fetuses with HLHS and fetuses with LSOLs. More fetuses presented signs of cerebral vasodilatation of the ACA than the MCA for certain types of CHD (P < 0.05). The ACA-PI was positively correlated with the PDI and MDI scores in fetuses with CHDs (r2 = 0.26, 0.20, P < 0.01). The MCA-PI was only positively correlated with the PDI scores (r2 = 0.15, P < 0.01). The ACA exhibited signs of vasodilatation more frequently and severely than the MCA. The ACA-PI appears to be more sensitive for predicting abnormal neurodevelopmental outcomes than the MCA-PI.

Left ventricular function of patients with pregnancy-induced hypertension evaluated using velocity vector imaging echocardiography and N-terminal pro-brain natriuretic peptide.

PURPOSE: To investigate whether acute and transient pressure overload in patients with pregnancy-induced hypertension (PIH) affects left ventricular (LV) systolic function. METHODS: From pregnancy to 3 months after delivery, 82 patients were analyzed: 27, 25, and 30 with gestational hypertension, preeclampsia, and the healthy control group, respectively. Conventional echocardiography and velocity vector imaging (VVI) were performed, and blood levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) were analyzed. RESULTS: Compared with the control group, patients with gestational hypertension had significantly lower mean LV peak global longitudinal strain. Importantly, during both pregnancy and after delivery, patients with preeclampsia had significantly lower global longitudinal, circumferential, and radial strain compared with the control group. The NT-pro-BNP levels were significantly higher in patients with PIH compared with normotensive pregnancies, and this situation continued for 3 months after delivery in women with preeclampsia. CONCLUSIONS: In pregnancies complicated by pregnancy-induced hypertension, especially preeclampsia, the systolic function is impaired and NT-pro-BNP levels are elevated compared with normal pregnancy. Velocity vector imaging (VVI) is more sensitive than left ventricular ejection fraction to evaluate heart function in patients with PIH.

Analysis of left ventricular fluid dynamics in dilated cardiomyopathy by echocardiographic particle image velocimetry.

OBJECTIVE: The aim was to analyze left ventricular (LV) fluid dynamics in dilated cardiomyopathy (DCM) by using echocardiographic particle image velocimetry (E-PIV). METHODS: Twenty patients with DCM and twenty healthy volunteers were examined. LV ultrasound contrast was administered by intravenous bolus injection. At least three dynamic contrast-enhanced echocardiographic images of cardiac cycles from apical three-chamber view and four-chamber view were obtained. The acquired echocardiographic image loops were processed off line by HyperFlow. RESULTS: In healthy hearts, the filling flow in the left ventricle finally comes to be a single large clockwise vortex, which smoothly redirects the blood to the outflow tract. Meanwhile, aberrant flow patterns are observed in the patients with DCM. In the DCM group, the vortex area (0.237 ± 0.063 vs 0.196 ± 0.129, P = .029), vortex depth (0.396 ± 0.134 vs 0.293 ± 0.143, P = .025), and vortex length (0.534 ± 0.089 vs 0.435 ± 0.176, P = .004) are significantly higher. The flow force angle (29.979 ± 8.208 vs 35.896 ± 6.044, P = .013) is significantly lower, and energy dissipation (0.975 ± 0.552 vs 0.578 ± 0.295, P = .006) is significantly higher. A negative linear relation is indicated between the following pairs of parameters: vortex depth and LV ejection fraction (EF) (r = -.350, P = .027); vortex length and LV EF (r = -.321, P = .044); energy dissipation and LV EF (r = -.523, P = .001). A positive linear relation is indicated between flow force angle and LV EF (r = .365, P = .021). CONCLUSION: E-PIV can effectively and quantitatively evaluate LV fluid dynamics in patients with DCM. LV fluid dynamics and LV systolic function interact with and affect each other.