Clinical Significance of Contrast-Enhanced Ultrasound Galactography in Pre-operative Diagnosis of Patients With Pathologic Nipple Discharge.

OBJECTIVE: The aim of the work described here was to investigate the feasibility and diagnostic value of using contrast-enhanced ultrasound (CEUS) galactography with SonoVue in patients with pathologic nipple discharge (PND). METHODS: Twenty-eight patients who underwent breast surgery for PND from May 2019 to August 2021 were included. Routine ultrasound, ductoscopy and CEUS galactography were performed successively. Lesions were diagnosed and localized. The sensitivity, specificity and pre-operative localization value of each examination method were evaluated on post-operative pathology. RESULTS: CEUS galactography was successfully conducted in all 28 patients and revealed negative ductal ectasia, filling stop and filling defect. Ductoscopy revealed positive nodules in 21 cases and negative nodules in 7 cases. A total of 18 nodules were found by routine ultrasound, and the relationship between all nodules and the discharge duct was confirmed after CEUS galactography. Compared with the other two methods, CEUS galactography had higher sensitivity, positive predictive value and negative predictive value (100%, 81.82% and 100%, respectively), while it has the same specificity as routine ultrasound (both 60%). The pre-operative location of the nipple duct was consistent with the intra-operative findings in 28 patients after CEUS galactography. CONCLUSION: The ultrasound contrast agent SonoVue can be used for CEUS galactography in patients with PND. CEUS galactography can improve the detection of ductal nodules and locate the nipple discharge duct pre-operatively. As the technique does not emit radiation and SonoVue is easily metabolized and safe, CEUS galactography is better than conventional imaging for PND patients.

Evaluation of Early Diabetic Kidney Disease Using Ultrasound Localization Microscopy: A Feasibility Study.

OBJECTIVE: The purpose of this study is to detect the hemodynamic changes of microvessels in the early stage of diabetic kidney disease (DKD) and to test the feasibility of ultrasound localization microscopy (ULM) in early diagnosis of DKD. METHODS: In this study, streptozotocin (STZ) induced DKD rat model was used. Normal rats served as the control group. Conventional ultrasound, contrast-enhanced ultrasound (CEUS), and ULM data were collected and analyzed. The kidney cortex was divided into four segments, which are 0.25-0.5 mm (Segment 1), 0.5-0.75 mm (Segment 2), 0.75-1 mm (Segment 3), and 1-1.25 mm (Segment 4) away from the renal capsule, respectively. The mean blood flow velocities of arteries and veins in each segment were separately calculated, and also the velocity gradients and overall mean velocities of arteries and veins. Mann-Whitney U test was used for comparison of the data. RESULTS: Quantitative results of microvessel velocity obtained by ULM show that the arterial velocity of Segments 2, 3, and 4, and the overall mean arterial velocity of the four segments in the DKD group are significantly lower than those in the normal group. The venous velocity of Segment 3 and the overall mean venous velocity of the four segments in the DKD group are higher than those in the normal group. The arterial velocity gradient in the DKD group is lower than that in the normal group. CONCLUSION: ULM can visualize and quantify the blood flow and may be used for early diagnosis of DKD.

Evaluation of early arterial wall lesions by elastography parameters in spontaneously hypertensive rats.

BACKGROUND: Arterialsclerosis caused by hypertension can lead to many complications, such as heart attack, stroke and so on. Early diagnosis and treatment of arterialsclerosis can prevent cardiovascular and cerebrovascular diseases and improve the prognosis. The present study aimed to explore the value of ultrasonography in evaluating the early lesion of the local arterial wall in hypertensive rats and identify useful elastography parameters. METHODS: A total of 24 spontaneously hypertensive rats (SHR), 10-, 20-, 30-, and 40-weeks-old, were used in this study, with 6 rats in each group. Blood pressure was recorded using the Animal Noninvasive Blood Pressure Measurement System (Kent company, model CODA, USA), and the local elasticity of the abdominal aorta of rats was measured using a ultrasound diagnostic instrument (VINNO, Suzhou city, China). According to the histopathological results, SHR were divided into two groups: the normal arterial elasticity and the early arterial wall lesions. Mann-Whitney U test was used to compare the differences in elastic parameters and influencing factors between the above two groups, and receiver operating characteristic curve (ROC) was used to analyze and judge the value of each elastic parameter in evaluating early arterial lesions. RESULTS: A total of 22 cases were divided into two groups: 14 in the normal arterial elasticity and 8 in the early arterial wall lesions. The differences in age, blood pressure, pulse wave velocity (PWV), compliance coefficient (CC), distensibility coefficient (DC), and elasticity parameter (EP) between the two groups were compared. The differences in PWV, CC, DC and EP were statistically significant. Subsequently, the ROC curve analysis was performed for the above four evaluation indexes of arterial elasticity; the results were as follows: the area under the curve of PWV, CC, DC, and EP was 0.946, 0.781, 0.946, and 0.911, respectively. CONCLUSIONS: Early arterial wall lesions can be evaluated by ultrasound measurement of local PWV. PWV and DC can accurately evaluate the early arterial wall lesions in SHR, and the combined application of the two can improve the sensitivity and specificity of the approach.

In vivo assessment of hypertensive nephrosclerosis using ultrasound localization microscopy.

PURPOSE: As a typical chronic kidney disease (CKD), hypertensive nephrosclerosis (HN) is a common syndrome of hypertension, characterized by chronic kidney microvascular damage. Early diagnosis of microvascular damage using conventional ultrasound imaging encounters challenges in sensitivity and specificity owing to the inherent diffraction limit. Ultrasound localization microscopy (ULM) has been developed to obtain microvasculature and microvascular hemodynamics within the kidney, and would be a promising tool for the early diagnosis of CKD. METHODS: In this study, the advantage of quantitative indexes obtained by using ULM (mean arterial blood flow speeds of different segments of interlobular arteries) over indexes obtained using conventional clinical serum (ß2-microglobulin, serum urea nitrogen, and creatinine) and urine (24-h urine volume and urine protein) tests and ultrasound Doppler imaging (peak systolic velocity [PSV], end-diastolic velocity [EDV], and resistance index [RI]) and contrast-enhanced ultrasound imaging (CEUS; rise time [RT], peak intensity [IMAX], mean transit time [mTT], and area under the time-intensity curve [AUC]) for early diagnosis of HN were investigated. Examinations were carried out on six spontaneously hypertensive rats (SHR) and five normal Wistar-Kyoto (WKY) rats at the age of 10 weeks. RESULTS: The experimental results show that the indicators derived from conventional clinical inspections (serum and urine tests) and ultrasound imaging (PSV, EDV, RI, RT, IMAX, mTT, and AUC) do not show significant difference between hypertensive and healthy rats (p > 0.05), while the TTP of the SHR group (28.52 ± 5.52 s) derived from CEUS is significantly higher than that of the WKY group (18.68 ± 7.32 s; p < 0.05). The mean blood flow speed in interlobular artery of SHR (12.47 ± 1.06 mm/s) derived from ULM is significantly higher than that of WKY rats (10.13 ± 1.17 mm/s; p < 0.01). CONCLUSION: The advantages of ULM over conventional clinical inspections and ultrasound imaging methods for early diagnosis of HN were validated. The quantitative results show that ULM can effectively diagnose HN at the early stage by detecting the blood flow speed changes of interlobular arteries. ULM may promise a reliable technique for early diagnosis of HN in the future.

Clinical joints manifestations in patients with psoriatic arthritis on musculoskeletal ultrasound.

OBJECTIVE: To investigate the clinical joints manifestations under musculoskeletal ultrasound (MSUS) and hematological findings in patients with psoriatic arthritis (PsA), which may provide a basis for improving the early diagnosis of PsA. METHODS: From September 2016 to February 2021, 328 patients with psoriasis visited the dermatological and rheumatic outpatient of the Beijing Friendship Hospital were enrolled in this retrospective study. Patients were enrolled according to a paired-design method. The PsA group included 164 patients diagnosed with PsA, and the control group included 164 patients diagnosed with psoriasis without PsA. Both groups of patients were evaluated by a rheumatoid immunologist, a dermatologist, and a sonographer. Demographic data, course of disease, severity of skin lesions, combined diseases, and previous treatment were all collected. All patients received MSUS and blood examinations. Lower extremity enthsis diseases were evaluated by Glasgow ultrasound enthesitis scoring system (GUESS). RESULTS: In the comparison of baseline clinical characteristics, the PsA group has longer course of psoriasis (P = 0.005), longer course of joints pain (P = 0.035), higher incidence of peripheral joints pain (P = 0.001), higher GUESS score (P < 0.001), and higher incidence of involved nails or toenails (P = 0.036) The most common joints involved were proximal interphalangeal joint (33.5%), knee (27.4%), and metacarpophalangeal joint (25.0%). Differences in clinical manifestations at different lower limb enthesitis on MSUS have also been proved. The positive incidences of rheumatoid factor (RF) (P = 0.002) and anti-cyclic citrullinated peptide (CCP) antibody (P < 0.001) in the PsA group were significantly higher than those in the control group. Binary Logistic regression showed that patients with anti-CCP antibody positive had a higher risk of active PsA compared to patients with negative antibodies in PsA group (OR: 0.626, 95%CI: 0.361-0.792, P < 0.05). CONCLUSION: In conclusion, the most common joints involved were proximal interphalangeal joint, knee, and metacarpophalangeal joint in patients with PsA, and the common types of diseased joints manifestations on MSUS were synovial thickening, fluid accumulation, bone destruction, increased blood flow signals, and attachment site inflammation. GUESS scoring systems can be used to identify PsA in patients with psoriasis. Psoriasis patients with RF and anti-CCP antibody positive were more likely to develop PsA, and anti-CCP antibody positive was a risk factor for active PsA. KEY POINTS: • GUESS scoring systems can be used to identify PsA in patients with psoriasis. • Psoriasis patients with RF and anti-CCP antibody positive were more likely to develop PsA, and anti-CCP antibody positive was a risk factor for active PsA.

Ocular Image and Haemodynamic Features Associated with Different Gradings of Ipsilateral Internal Carotid Artery Stenosis.

OBJECTIVES: To analyse the changes of ocular haemodynamics and morphology in Chinese patients with internal carotid artery (ICA) stenosis in the current study. METHODS: A retrospective case-control study was conducted with 219 patients. The haemodynamic characteristics, the calibre of retinal vessels, and the subfoveal choroidal thickness (SFChT) were compared. We analysed the correlations with the degree of ipsilateral ICA stenosis. RESULTS: There were no significant differences among the groups in the central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and AVR (p = 0.073, p = 0.188, and p = 0.738, resp.). The peak systolic velocity (PSV) and end diastolic velocity (EDV) in the central retinal artery (CRA) and the posterior ciliary artery (PCA) were significantly lower than normal eyes (p < 0.001). The outer retinal layer thickness and SFChT values of the ICA stenosis groups were significantly lower than normal eyes (p = 0.030 and p < 0.001, resp.). CONCLUSION: The PSV and EDV in CRA and PCA and the SFChT and outer retinal layer thickness of ICA eyes were significantly lower than normal eyes. ICA stenosis may impact choroidal haemodynamics, and decreased choroidal circulation might affect the discordance of the SFChT and the outer retinal layer thickness.

Acoustic Radiation Force Impulse (ARFI) Elastography for non­invasive evaluation of hepatic fibrosis in chronic hepatitis B and C patients: a systematic review and meta-analysis.

AIM: The purpose of the study was to assess the effect of Acoustic Radiation Force Impulse (ARFI) elastography in the diagnosis of liver fibrosis in chronic hepatitis B and C patients through Meta-analysis. MATERIAL AND METHODS: Four databases (PubMed, the Cochrane Library, WanFang data, and CNKI) were searched. The key words were: ("ARFI" or "acoustic radiation force impulse") combined with "liver fibrosis" and ("chronic hepatitis" or "HBV HCV"). Heterogeneity (I2) was assessed, and its source was analyzed through meta-regression. RESULTS: 21 articles with 2,691 patients were included. The compositeSe=0.79 (95% CI: 0.76-0.83) and Sp=0.86 (95% CI: 0.85-0.88). ARFI elastography showed a better ability to evaluate higherstage liver fibrosis and liver cirrhosis (F=3 and F=4, respectively). For F≥3, Se=0.84 (95% CI: 0.80-0.88, I2=61.37), Sp=0.90 (95% CI: 0.86-0.92, I2=65.10), and AUROC=0.94 (95% CI: 0.91-0.95). Se and Sp and AUROC of F=4 were 0.86 (95% CI: 0.80-0.91, I2=70.67), 0.84 (95% CI: 0.80-0.88, I2=78.94) and 0.91 (95% CI: 0.89-0.94), respectively. Besides, the combined RFI values indicate that CHC patients had higher ARFI values especially in the F3 stage (1.87 [95% CI: 1.67-2.06] and 2.31[95% CI: 2.09-2.52] for CHB and CHC, respectively). CONCLUSION: ARFI elastography is accurate and reliable in the diagnosis of CHB- and CHC-induced liver fibrosis and is especially suitable for the evaluation of stages F≥3 and F=4. CHC patients manifest higher ARFI values than CHB patients especially in the F3 stage.

Shear wave elastography results correlate with liver fibrosis histology and liver function reserve.

AIM: To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. METHODS: Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. RESULTS: At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to ½ of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures: significantly lower with F4 (P = 0.037) and F3 (P = 0.032) as compared to F0 and significantly lower with F4 as compared to F2 (P = 0.032). CONCLUSION: SWE LSM shows a good correlation with histologic fibrosis grading and pharmacologic quantitative liver function reserve in experimental severe fibrosis and cirrhosis.

Contrast-Enhanced Ultrasonography Diagnostic Evaluation of Esophageal Varices in Patients With Cirrhosis.

The purpose of this study was to clarify the usefulness of contrast-enhanced ultrasonography (CEUS) for the diagnosis of esophageal varices (EVs) in patients with cirrhosis. A total of 81 cases (56 patients with EVs and 25 control subjects without EV) were examined by CEUS and by esophagogastroduodenoscopy. According to the esophagogastroduodenoscopy results, we divided the subjects into 3 groups: G0, G1, and G2. The G0 group had 25 patients who exhibited no liver abnormality other than liver cyst or hemangioma without EVs, G1 comprised 9 patients with small EVs and 13 with medium EVs. G2 was composed of 34 cases of severe EVs. Under CEUS, the following parameters were measured: the thickness of double-layer mucosa and submucosa in the lower esophagus (Tm), the maximum anteroposterior diameter of the lower esophagus (De), and the ratio of Tm to De (Tm/De). Time-intensity curves of the lower esophagus and aorta were drawn using QLAB software. One-factor analysis of variance was used to compare means between the 3 groups. The diagnostic value of CEUS was assessed by receiver operating characteristic curves. Bayes discriminant analysis was adopted for building discriminant equations. Tm, De, Tm/De, Tep, and Iep/Iap were greater in patients with EVs (G1 and G2) than in those without EVs (G0). The Tms for the G0, G1, and G2 groups were 4.16 ± 0.59 mm, 7.06 ± 0.89 mm, and 10.10 ± 1.77 mm (P < 0.01), respectively, with 7.65 mm being the best cutoff value for diagnosing ≥ G2 (sensitivity 96.9%, specificity 90.0%). The area under the receiver operating characteristic curve was 0.987. Three discriminant equations were obtained by Bayes discriminant analysis: y0 = -6.2 + 2.5Tm, y1 = -15.1 + 4.1Tm and y2 = -31.7 + 6.0Tm, respectively. The equations correctly classified 91.7% of cases in the study, making an error rate of 8.3%. Tm attained from CEUS can be a new, convenient, noninvasive parameter for evaluating esophageal varices in patients with liver cirrhosis.

Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis.

AIM: To explore the feasibility of non-invasive quantitative estimation of portal venous pressure by contrast-enhanced ultrasound (CEUS) in a canine model. METHODS: Liver fibrosis was established in adult canines (Beagles; n = 14) by subcutaneous injection of carbon tetrachloride (CCl4). CEUS parameters, including the area under the time-intensity curve and intensity at portal/arterial phases (Qp/Qa and Ip/Ia, respectively), were used to quantitatively assess the blood flow ratio of the portal vein/hepatic artery at multiple time points. The free portal venous pressures (FPP) were measured by a multi-channel baroreceptor using a percutaneous approach at baseline and 8, 16, and 24 wk after CCl4 injections in each canine. Liver biopsies were obtained at the end of 8, 16, and 24 wk from each animal, and the stage of the fibrosis was assessed according to the Metavir scoring system. A Pearson correlation test was performed to compare the FPP with Qp/Qa and Ip/Ia. RESULTS: Pathologic examination of 42 biopsies from the 14 canines at weeks 8, 16, and 24 revealed that liver fibrosis was induced by CCl4 and represented various stages of liver fibrosis, including F0 (n = 3), F1 (n = 12), F2 (n = 14), F3 (n = 11), and F4 (n = 2). There were significant differences in the measurements of Qp/Qa (19.85 ± 3.30 vs 10.43 ± 1.21, 9.63 ± 1.03, and 8.77 ± 0.96) and Ip/Ia (1.77 ± 0.37 vs 1.03 ± 0.12, 0.83 ± 0.10, and 0.69 ± 0.13) between control and canine fibrosis at 8, 16, and 24 wk, respectively (all P < 0.001). There were statistically significant negative correlations between FPP and Qp/Qa (r = -0.707, P < 0.001), and between FPP and Ip/Ia (r = -0.759, P < 0.001) in the canine fibrosis model. Prediction of elevated FPP based on Qp/Qa and Ip/Ia was highly sensitive, as assessed by the area under the receiver operating curve (0.866 and 0.895, respectively). CONCLUSION: CEUS is a potential method to accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters.

Hepatic perfusion parameters of contrast-enhanced ultrasonography correlate with the severity of chronic liver disease.

In the study described here, we introduced a new ratio acquired with contrast-enhanced ultrasonography (CEUS): a liver parenchyma blood supply ratio that differentiates arterial and portal phases. Our purpose was to determine whether this ratio and other liver parenchyma perfusion parameters acquired with CEUS can be correlated with the severity of chronic liver disease. Twelve patients with non-cirrhotic chronic liver disease, 35 patients with cirrhosis (child class A: n = 10; child class B: n = 13; child class C: n = 12) and 21 healthy volunteers were examined by CEUS. Time-intensity curves were drawn for regions of interest located in liver parenchyma and right kidney cortex using QLAB quantification software. The arterial and portal phases were differentiated by the time to the maximum enhancement of right kidney and liver parenchyma perfusion data acquired from the time-intensity curves: the intensity of liver parenchyma perfused by hepatic arterial flow (I(ap)), the intensity of total perfusion of liver parenchyma (I(peak)), the intensity of liver parenchyma perfused by portal venous flow (I(pp)) and the ratio of portal perfusion to total perfusion of liver parenchyma expressed by the parameters I(pp)/I(peak), I(peak), I(pp) and I(pp)/I(peak) significantly decreased in patients with cirrhosis and in patients with non-cirrhotic chronic liver disease, whereas Iap increased. The parameters I(pp), I(peak), I(pp)/I(peak) and Iap correlated with the severity of chronic liver disease (r = -0.938, p < 0.001; r = -0.790, p < 0.001; r = -0.931 p < 0.001; r = 0.31, p < 0.05). The diagnostic accuracy rates for cirrhosis expressed as areas under receiver operating characteristic curves were 0.93 for I(peak), 0.98 for I(pp), 0.98 for I(pp)/I(peak), and 0.69 for I(ap). Liver parenchyma perfusion parameters obtained by CEUS were correlated with the severity of chronic liver disease and have the potential to assess cirrhosis non-invasively.