Diagnosis of liver fibrosis and liver function reserve through non-invasive multispectral photoacoustic imaging.

Liver function reserve (LFR) is the sum of remnant functional hepatic cells after liver injury. In the pathologic process of liver fibrosis (LF), LFR is impaired. LFR assessment can help determine the safe scope of liver resection or drug regimen and predict prognosis of patients with liver disease. Here, we used a photoacoustic imaging (PAI) system to assess LF and LFR in rabbit models. We performed PAI, ultrasound elastography and biopsy for 21 rabbits developing none (n = 6) and LF (n = 15). In vivo indocyanine green (ICG) measurements by PAI showed that LF group presented a significantly attenuated ICG clearance compared to control group, indicating LFR impairment of LF. Another finding was a significantly higher collagen photoacoustic signal intensity value was observed in LF both in vivo and in vitro. Our findings demonstrated that PAI was potentially effective to evaluate LFR and collagen accumulation of LF.

ICG clearance test based on photoacoustic imaging for assessment of human liver function reserve: An initial clinical study.

Liver function reserve (LFR) plays an extensive and important role in patients with liver disease. Indocyanine green (ICG) clearance test is the standard diagnostic approach for LFR evaluation which was performed by spectrophotometry or pulse dye densitometry (PDD). Spectrophotometry is the gold standard, it's invasive and not real-time. PDD is non-invasive, but accuracy of PDD is controversial. Taken spectrophotometry as the reference standard, this study investigated the accuracy of photoacoustic imaging (PAI) method for LFR assessment and compared to PDD in healthy volunteers. The results demonstrated a strong correlation between PAI method and spectrophotometry (r = 0.9649, p < 0.0001). No significant difference was shown in ICG clearance between PAI and spectrophotometry method (rate constant k1 vs. k2, 0.001158 +-0.00042 vs. 0.001491 +- 0.00045, p = 0.0727; half-life t1 vs. t2, 601.2 s vs. 474.4 s, p = 0.1450). These results indicated that PAI may be valuable as a noninvasive, accurate diagnostic tool for LFR assessment in human.

Staging liver fibrosis in patients with chronic hepatitis B using two-dimensional shear wave elastography based on histopathological findings: a prospective multicenter study.

Background: With the rapid development of shear wave elastography technology, the clinical application prospect of two-dimensional shear wave elastography (2D SWE) for non-invasive monitoring of liver fibrosis is extremely promising. This study aimed to evaluate the diagnostic performance of ElastQ, a noval 2D SWE method, in the staging of liver fibrosis in patients with chronic hepatitis B with histopathological results as the reference standard. Methods: Between August 2020 and December 2021, a prospective multicenter study of 602 consecutive patients with chronic hepatitis B was conducted in 14 hospitals. All patients underwent liver biopsy and 2D SWE examination. The patients were divided into a training cohort and a validation cohort. The area under the receiver operating characteristic curve (AUROC) was calculated, and the optimal cut-off values for ElastQ were obtained. Results: Overall, 2D SWE values showed a strong correlation with fibrosis stage (r=0.71, P<0.001). In the training cohort, the AUROCs of ElastQ for diagnosing fibrosis stages ≥S1, ≥S2, ≥S3, and S4 were 0.817 [95% confidence interval (CI): 0.777-0.853), 0.887 (95% CI: 0.852-0.915), 0.912 (95% CI: 0.881-0.937), and 0.832 (95% CI: 0.793-0.866)], respectively. In the validation cohort, the AUROCs of ElastQ for diagnosing fibrosis stages ≥S1, ≥S2, ≥S3, and S4 were 0.807 (95% CI: 0.742-0.861), 0.868 (95% CI: 0.810-0.914), 0.855 (95% CI: 0.796-0.903), and 0.851 (95% CI: 0.791-0.900), respectively. The optimal liver stiffness cut-off values for the identification of fibrosis stages ≥S1, ≥S2, ≥S3, and S4 were 5.72 kPa (sensitivity: 78%, specificity: 70%), 6.85 kPa (sensitivity: 77%, specificity: 86%), 7.43 kPa (sensitivity: 80%, specificity: 86%), and 8.03 kPa (sensitivity: 81%, specificity: 73%), respectively. Conclusions: Two-dimensional SWE can accurately stage liver fibrosis in patients with chronic hepatitis B.

Role of Surface Charge of Nanoscale Ultrasound Contrast Agents in Complement Activation and Phagocytosis.

Purpose: To prepare nanoscale ultrasound contrast agents (Nano-UCAs) and examine the role of their surface charge in complement activation and phagocytosis. Materials and Methods: We analyzed serum proteins present in the corona formed on Nano-UCAs and evaluated two important protein markers of complement activation (C3 and SC5b-9). The effect of surface charge on phagocytosis was further assessed using THP-1 macrophages. Results: When Nano-UCAs were incubated with human serum, they were opsonized by various blood proteins, especially C3. Highly charged Nano-UCAs, whether positive or negative, were favorably opsonized by complement proteins and phagocytized by macrophages. Conclusion: Charged Nano-UCAs show a higher tendency to activated complement system, and are efficiently engulfed by macrophages. The present results provide meaningful insights into the role of the surface charge of nanoparticles in the activation of the innate immune system, which is important not only for the design of targeted Nano-UCAs, but also for the effectiveness and safety of other theranostic agents.

Shear wave elastography using sound touch elastography and supersonic shear imaging for liver measurements: a comparative study.

Background: Measurements of liver stiffness obtained with 2-dimensional shear wave elastography (2D-SWE) have been widely used to clinically assess liver fibrosis. However, differences between different 2D-SWE systems can lead to confusion when interpreting measurements. This study investigated the variability between a recently released sound touch elastography (STE) system and a supersonic shear imaging (SSI) system and assessed the degree of intersystem discrepancy using the different liver stiffness value (LSV) thresholds recommended by the Society of Radiologists in Ultrasound (SRU) for assessing liver fibrosis. Methods: A total of 4,152 patients who had undergone STE and SSI on the same day were enrolled in this retrospective study. First, intrasystem agreement for STE and SSI was assessed. Then, intraclass correlation coefficients (ICCs) and the Bland-Altman method were used to assess intersystem variability for all cases, classified according to the thresholds recommended by the SRU. The effects of age, gender, and body-mass index (BMI) were evaluated using multivariate linear regression analysis and attributive intervals were computed for STE and SSI at each of the different thresholds. Results: The ICCs for STE and SSI intrasystem agreement were 0.94 [95% confidence interval (CI): 0.937-0.943; P<0.001] and 0.984 (95% CI: 0.984-0.985; P<0.001), respectively. The 95% limit of agreement (LOA) for all cases ranged from -6.96 to 7.44 kPa. The 95% LOA increased as the threshold values rose, and intersystem variability was obvious, even at the smallest threshold (the 95% LOA at values ≤5 kPa was -0.85 to 2.08 kPa, while that at values >17 kPa was -20.81 to 14.71 kPa). The adjusted R2 for age, gender, and BMI was only 0.018 (all P value <0.05). Conclusions: There was clear variability between STE and SSI, in contrast with some previous studies with small sample sizes, and consistent with others. Intersystem variability increased with the elevation of the LSV thresholds recommended by the SRU. Gender and BMI had little effect on intersystem variability. Future research could compare STE and SSI in different liver diseases, assessing the feasibility of the SRU-recommended thresholds in proven pathologies and evaluating the test-retest repeatability.

In vivo liver thermoacoustic imaging and demonstration based on localization wire.

PURPOSE: Liver disease causes significant morbidity and mortality worldwide. Liver imaging plays an essential role in the noninvasive liver disease evaluation because of the limitation of liver biopsy. This paper aims to image in vivo liver with thermoacoustic imaging (TAI) and demonstrate this liver imaging technique with a cross-validation method. METHODS: The imaging system composed of a large aperture antenna and a flexible transducer array was used, and we performed the position calibration using the delay and sum algorithm. The localization wire was utilized in the cross-validation of in vivo liver TAI. RESULTS: We successfully validated in vivo liver TAI. In vivo images of different liver lobes without labels were observed. The imaging depth reached about 4 cm. CONCLUSIONS: TAI has the potential to image the liver and provide useful dielectric properties of the liver tissue. This study realized the first in vivo liver TAI, suggesting its prospect in detecting liver disease noninvasively.

Noninvasive assessment of liver fibrosis in chronic hepatitis B carriers with sound touch elastography: study of surgical pathology specimens.

PURPOSE: To evaluate the diagnostic performance of sound touch elastography (STE) for staging liver fibrosis in chronic hepatitis B (CHB) patients using pathological stage of surgical specimens as the reference standard. METHOD: 239 CHB patients were included. Liver stiffness measurements (LSMs) on STE and Supersonic shear imaging (SSI), gamma glutamyl transferase-to-platelet ratio (GPR), aspartate aminotransferase-to-platelet ratio index (APRI) and four-factor Fibrosis-4 (FIB-4) index were obtained. Areas under the receiver operating characteristic (ROC) curves (AUCs) for the diagnosis of fibrosis stage were calculated and compared. RESULTS: The LSMs obtained by STE and SSI significantly correlated with the fibrosis stages (r = 0.757; r = 0.758, respectively, both p < 0.001). No significant differences in AUCs were observed between STE and SSI in identifying fibrosis ≥stage 1 (0.92 vs. 0.94), ≥stage 2 (0.89 vs. 0.91), ≥stage 3 (0.90 vs. 0.91) or stage 4 (0.92 vs. 0.91). Both STE and SSI had significantly higher AUCs in identifying each fibrosis stage than the GPR (0.68, 0.77, 0.76 and 0.79), APRI (0.53, 0.66, 0.74 and 0.69) and FIB-4 (0.61, 0.77, 0.79 and 0.74). CONCLUSIONS: STE is an efficient tool for assessing liver fibrosis in CHB patients, with performance comparable to that of SSI and superior to that of biomarkers.

The combination of the preoperative albumin-bilirubin grade and the fibrosis-4 index predicts the prognosis of patients with hepatocellular carcinoma after liver resection.

There is little information regarding the use of a combination of the albumin-bilirubin (ALBI) grade and the fibrosis-4 index (FIB-4) in predicting hepatocellular carcinoma (HCC) patient outcomes after liver resection. In this study, we aimed to analyze the predictive ability of a combination of the ALBI grade and the FIB-4 score (ALBI-FIB-4) for HCC patients within the Milan criteria after liver resection. The data of HCC patients within the Milan criteria who underwent liver resection between 2011 and 2019 at our center were reviewed (n = 544). Patients with an FIB-4 index > 3.25 were considered to have a high FIB-4 index and were given a score of 1, whereas patients with an FIB-4 index ≤ 3.25 were considered to have a low FIB-4 index and were given a score of 0. The ALBI-FIB-4 score was a summary score that combined the ALBI grade and the score based on the FIB-4 index. During the follow-up period, 279 patients experienced recurrence, and 175 patients died. Multivariate analysis showed that tumor size, the presence of multiple tumors, the presence of microvascular invasion and the ALBI-FIB-4 score were four independent risk factors for both postoperative recurrence-free survival (RFS) and overall survival (OS). The 5-year RFS of patients with high ALBI-FIB-4 scores of 1, 2, and 3 were 55.0%, 44.2% and 35.3%, respectively (p = 0.004). The 5-year OS rates of patients with high ALBI-FIB-4 scores of 1, 2, and 3 were 72.9%, 66.4% and 54.8%, respectively (p = 0.011). The ALBI-FIB-4 score may be a surrogate marker for predicting the prognosis of patients with HCC after liver resection. A high ALBI-FIB-4 score was associated with a high incidence of postoperative recurrence and mortality.

Barriers and facilitators in providing oral care to nursing home residents, from the perspective of care aides: A systematic review and meta-analysis.

BACKGROUND: Oral health of nursing home residents is generally poor, with severe consequences for residents' general health and quality of life and for the health care system. Care aides in nursing homes provide up to 80% of direct care (including oral care) to residents, but providing oral care is often challenging. Interventions to improve oral care must tailor to identified barriers and facilitators to be effective. This review identifies and synthesizes the evidence on barriers and facilitators care aides perceive in providing oral care to nursing home residents. METHODS: We systematically searched the databases MEDLINE, Embase, Evidence Based Reviews-Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science. We also searched by hand the contents of key journals, publications of key authors, and reference lists of all studies included. We included qualitative and quantitative research studies that assess barriers and facilitators, as perceived by care aides, to providing oral care to nursing home residents. We conducted a thematic analysis of barriers and facilitators, extracted prevalence of care aides reporting certain barriers and facilitators from studies reporting quantitative data, and conducted random-effects meta-analyses of prevalence. RESULTS: We included 45 references that represent 41 unique studies: 15 cross-sectional studies, 13 qualitative studies, 7 mixed methods studies, 3 one-group pre-post studies, and 3 randomized controlled trials. Methodological quality was generally weak. We identified barriers and facilitators related to residents, their family members, care providers, organization of care services, and social interactions. Pooled estimates (95% confidence intervals) of barriers were: residents resisting care=45% (15%-77%); care providers' lack of knowledge, education or training in providing oral care=24% (7%-47%); general difficulties in providing oral care=26% (19%-33%); lack of time=31% (17%-47%); general dislike of oral care=19% (8%-33%); and lack of staff=22% (13%-31%). CONCLUSIONS: We found a lack of robust evidence on barriers and facilitators that care aides perceive in providing oral care to nursing home residents, suggesting a need for robust research studies in this area. Effective strategies to overcome barriers and to increase facilitators in providing oral care are one of the most critical research gaps in the area of improving oral care for nursing home residents. Strategies to prevent or manage residents' responsive behaviors and to improve care aides' oral care knowledge are especially needed.