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.

Testicular torsion diagnosis and injury assessment using photoacoustic oxygenation imaging.

Testicular torsion (TT) is a medical emergency that requires immediate diagnostic evaluation. Photoacoustic imaging (PAI) has the potential to provide spatially resolved oxygen saturation (sO2), which can serve as a valuable marker in TT diagnosis. We investigated the potential of PAI as an alternative method for TT diagnosis and testicular injury assessment. We measured sO2 levels in different degrees of TT models using PAI at various time points. Based on histopathological results, we found that the averaged sO2 per pixel (sO2®) and reduction of sO2® (rsO2) in twisted testicles had significant correlations with hypoxic conditions. Both sO2® and rsO2 exhibited excellent diagnostic abilities in detecting TT and identifying ischemia/hypoxia injury following TT. Furthermore, PAI-measured sO2 demonstrated favorable diagnostic capabilities in discriminating if the testicle had suffered irreversible injury. In summary, PAI presents a potentially promising novel approach in evaluating TT and warrants further clinical investigation.

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.

Microwave-induced thermoacoustic imaging for the early detection of canine intracerebral hemorrhage.

Purpose: This study aimed to investigate the feasibility and validation of microwave-induced thermoacoustic imaging (TAI) for the early detection of canine intracerebral hemorrhage. Methods: A TAI system was used to record the thermoacoustic signal (TAS) of canine intracerebral hemorrhage in the study. First, the difference in TAS between deionized water, fresh ex vivo porcine blood and brain tissue was explored. Second, the canine hemorrhagic stroke model was established, and canine brain ultrasound examination and TAI examination were performed before modeling and at 0.5 h, 1 h, 2 h, 3 h, 4 h, 4.5 h, 5 h and 6 h after modeling. Finally, pathology and ultrasound were used as the reference diagnoses to verify the accuracy of the thermoacoustic imaging data. Results: The results showed that significant differences were observed in TASs among deionized water, fresh ex vivo porcine blood and brain tissue. The intensity of the thermoacoustic signal of blood was significantly higher than that of ex vivo porcine brain tissue and deionized water. The intracerebral hemorrhage model of five beagles was successfully established. Hematomas presented hyperintensity in TAI. Considering ultrasound and pathology as reference diagnoses, TAI can be used to visualize canine intracerebral hemorrhage at 0.5 h, 1 h, 2 h, 3 h, 4 h, 4.5 h, 5 h and 6 h after modeling. Conclusion: This is the first experimental study to explore the use of TAI in the detection of intracerebral hemorrhage in large live animals (canine). The results indicated that TAI could detect canine intracerebral hemorrhage in the early stage and has the potential to be a rapid and noninvasive method for the detection of intracerebral hemorrhage in humans.

Assessment of liver function reserve by photoacoustic tomography: a feasibility study.

Assessment of liver function reserve (LFR) is essential to determine liver resection scope and predict prognosis for patients with liver disease. Indocyanine green (ICG) concentration change is a classic marker to reflect liver function reserve as ICG is selectively taken up and eliminated by liver. Here we proposed a noninvasive approach for LFR assessment based on a real-time photoacoustic tomography (PAT) system. This feasibility study was to detect ICG concentration change by PAT in phantom and in vivo using both normal and partial hepatectomy (PH) rabbits. A linear relationship between photoacoustic signal intensity of ICG and ICG concentration was found in vitro. In vivo ICG concentration change over time after ICG injection was observed by PAT in normal rabbits, which was consistent with the findings measured by invasive spectrophotometry. Finally, clear difference in ICG clearance between the control and PH models was identified by PAT. Taken together, our study indicated the clinical potential of PAT to in vivo evaluate LFR noninvasively.

Loss of FoxA2 accelerates neoplastic changes in the intrahepatic bile duct partly via the MAPK signaling pathway.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is characterized by a highly aggressive nature and a dismal outcome. FOXA2 is an archetypal transcription factor involved in cholangiocyte proliferation. RESULTS: FOXA2 expression was negatively correlated with tumor stage (p = 0.024). Univariate and multivariate analyses showed that low FoxA2 expression was associated with tumor relapse and survival. At 20 weeks after TAA administration, FoxA2-/- mice displayed significant manifestations of neoplasia, while WT mice did not.RNA sequencing analysis showed that the expression of genes in the MAPK signaling pathway was significantly higher in FoxA2-/- mice. IHC and Western blot results showed that p-ERK1/2, CREB1 and RAS were highly expressed in FoxA2-/- mice. Furthermore, using in vitro experiments with siRNA, we found that low expression of FoxA2 could exacerbate the metastatic potential of ICC. The expression of p-ERK1/2 and RAS, which are key mediators of the MAPK signaling pathway, was significantly increased. CONCLUSION: Low FOXA2 expression negatively affected the prognosis of patients with ICC. Loss of FoxA2 expression could promote intrahepatic bile duct neoplasia partly via activation of the MAPK signaling pathway. MATERIALS AND METHODS: In all, the data of 85 patients with ICC were retrospectively collected and analyzed. TAA was used to induce ICC in FoxA2-/- mice and WT mice. RNA-sequencing analysis was used to identify the expression of different genes.

The outcome of the HCC patients underwent ALPPS: Retrospective study.

The complete resection offers the best long-term survival for advanced hepatocellular carcinoma patients. ALPPS as a choice of resection, how is its outcome compared to one-stage resection, liver transplantation and TACE? This retrospective study included 20 ALPPS patients. To minimize the effect of confounding influences of measured covariates, PSM was performed. The overall survival (OS), morbidity, mortality and the increasing rate, KGR were analyzed. The OS in ALPPS group is 27.4 (±3.8 months) moths and the TACE group is 13.5(±1.2 months) (P < .001), LT group is 41.3 (±3.2 months) (P = .048), Resection group is 31.8 (±2.6 months) (P = .368). And the medium increasing volume is 209.5 cm (±61.5 cm) with the increasing ratio 52.4% (+26.9%). The ALPPS is a feasible treatment for HCC patients and it provides a better long-term survival than TACE and it is similar to Resection, less than LT.

Left hepatectomy combined with hepatic artery resection for hilar cholangiocarcinoma: A retrospective cohort study.

AIMS: To investigate the efficacy of our technique and policy on left hepatectomy (LH) with hepatic artery resection but without arterial reconstruction (HAR) in selected patients with hilar cholangiocarcinoma. METHODS: From May 2005 to May 2012, 61 patients with hilar cholangiocarcinoma underwent left hepatectomy. These patients were divided into two groups: the LH with HAR group (n = 26) and the LH alone group (n = 35), based on whether hepatic artery resection was performed. We evaluated the serum total and direct bilirubin on postoperative day 7, length of hospital stay after surgery, postoperative complications, long-term postoperative survival and disease-free survival. RESULTS: The improvement in jaundice after surgery was comparable between the two groups (P = 0.837). There were no significant differences in the rates of postoperative complications or mortality between the LH with HAR group and the LH group (P = 0.654 and no assessment, respectively). The cumulative 1-, 2-, 3- and 5-year survival rates were 61.5%, 49%, 40.8% and 30.6% and 71.4%, 58.7%, 51.3% and 38.5%, respectively, in the LH with HAR group and the LH group (P = 0.383, including perioperative deaths). The cumulative 1-, 2-, 3- and 5-year disease-free survival rates were 61.9%, 41.6%, 29.7% and 14.8% and 58.2%, 50.7%, 44.3% and 23.6% in the LH with HAR group and the LH group, respectively (P = 0.695, including perioperative deaths). The postoperative complication rate was higher in patients with severe jaundice than those with non-severe jaundice, but no significant difference was detected (56.3% (9/16) vs. 46.7% (46.7%), P = 0.804). Similarly, 18.8% (3/16) postoperative mortality was found in patients with severe jaundice, compared to 4.4% (2/45) in those with non-severe jaundice. The difference was not significant (P = 0.139). For the cumulative 1-, 2-, 3- and 5-year survival and cumulative 1-, 2-, 3- and 5-year disease-free survival rates, patients with severe jaundice had poorer outcomes than those with non-severe jaundice (56.3%, 43.8%, 35% and 26.3% vs. 66.7%, 58.8%, 52.2% and 41.8%, P = 0.317; 50%, 42.9%, 35.7% and 13.4% vs. 63.8%, 54%, 35.6% and 21.3%, P = 0.753). CONCLUSION: Left hepatectomy combined with hepatic artery resection and no reconstruction for hilar cholangiocarcinoma is recommended when the following conditions are satisfied: 1) Bismuth-Corlette I, II, or IIIb hilar cholangiocarcinoma; 2) the tumor has infiltrated the hepatic artery with disappearance or markedly reduced arterial flow as detected by intraoperative ultrasound; 3) the color of the liver by visual observation does not change when the hepatic artery has been blocked for 5 min; and 4) removal of the tumor-infiltrated hepatic artery increases the probability of R0 resection for hilar cholangiocarcinoma. For obstructive jaundice from hilar cholangiocarcinoma, we recommend bile duct drainage before resection in patients with elevated preoperative serum TB.