Indocyanine Green Clearance Research Articles

Utility of Quantitative Assessment of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl Human Serum Albumin SPECT/CT in the Identification of Severe Liver Fibrosis: Its Complementary Diagnostic Value with Other Liver Function Indices.

To evaluate the value of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (99mTc-GSA) single photon emission computed tomography (SPECT) for assessing liver fibrosis, and to assess its complementary value to other liver function indices such as fibrosis-4 (FIB-4) index and indocyanine green (ICG) clearance test parameters (ICG-R15 and ICG-K). Seventy-eight patients with chronic liver disease and hepatocellular carcinoma who underwent 99mTc-GSA scintigraphy and other liver function tests including ICG test and FIB-4 index prior to hepatectomy were studied. 99mTc-GSA imaging was performed with SPECT/CT scanner (Discovery NM/CT 670). Immediately after injection of 99mTc-GSA, dynamic imaging was performed for 20min, followed by SPECT data acquisition for 6min. LHL15 which is a conventional index by 99mTc-GSA planar images, and liver uptake ration (LUR) was measured from 99mTc-GSA SPECT images. From the liver resection specimens, the degree of liver fibrosis was graded according to the Ludwig scale (F0-4). Significant differences in LUR, LHL15, ICG-R15, ICG-K, platelet count and FIB-4 index were found between the F0-3 and F4 liver fibrosis patient groups (P < 0.05). Multivariate logistic regression analysis revealed that LUR and ICG-K were independent factors for identifying severe liver fibrosis (F4). Area under the curve of receiver operating curve analysis for the logistic regression model using LUR and ICG-K was 0.83. In the patient group with higher FIB-4 (≥ 3.16), the diagnostic performance of LUR for detecting severe liver fibrosis was significantly better than LHL15 (AUC: 0.83 vs. 0.75, P = 0.048). In the high FIB-4 index group, the sensitivity and specificity for identifying F4 was 88% and 85%, respectively, with LUR cutoff value of 41.2%. LUR, measured by 99mTc-GSA SPECT, is a useful indicator for identifying sever liver fibrosis. Particularly in patients with high FIB-4 index (≥ 3.16), LUR can be a valuable indicator to identify severe liver fibrosis with high diagnostic accuracy.

Susceptibility of hepato-splanchnic perfusion to intra-abdominal pressure in peritoneal dialysis patients.

The impact of peritoneal filling on hepato-splanchnic perfusion during peritoneal dialysis has not been fully elucidated yet. Measurements were done in 20 prevalent peritoneal dialysis patients during a peritoneal equilibration test (PET) with 2L of standard dialysate. Data were obtained in the drained state at baseline (T0), after instillation (T1), and after 2 h of dwell time (T2). Intra-abdominal pressure (IAP) was measured by Durand's approach. The hepatic clearance index (KI) of indocyanine-green (ICG) was determined as an indirect measure of hepato-splanchnic blood flow. Cardiac index (CI), heart rate (HR), and total peripheral resistance index (TPRI) were derived from continuous arterial pulse analysis. Fluid volume overload (VO) was evaluated by multifrequency bioimpedance analysis. Ejection fraction (EF) was obtained from echocardiographic examination. IAP was 5.8 ± 3.5 mmHg at baseline (T0), rose to 9.4 ± 2.8 mmHg after instillation of dialysate (T1), and further to 9.7 ± 2.8 mmHg after 2 h of dwell time (p < 0.001). KI slightly declined from 0.60 ± 0.22 L/min/m2 at T0 to 0.53 ± 0.15 L/min/m2 at T1 (p = 0.075), and returned to 0.59 ± 0.22 L/min/m2 at T2 (p = 0.052). CI, HR, and TPRI did not change significantly. In five patients with an EF < 40% KI was significantly lower at T1 (0.42 ± 0.12 L/min/m2; p = 0.039), and further decreased at T2 (0.40 ± 0.04 L/min/m2; p = 0.016) compared to patients with normal EF (T1: 0.58 ± 0.15 L/min/m2 and T2: 0.67 ± 0.22 L/min/m2). Overall, hepatic clearance of ICG as a marker of hepato-splanchnic blood flow is not affected by the filling of the peritoneal cavity.

Predictability of combining Technetium-99m-galactosyl human serum albumin single-photon emission computed tomography/computed tomography and indocyanine green clearance test for posthepatectomy liver failure.

To evaluate the predictive ability of combining Technetium-99m-galactosyl human serum albumin (99mTc‑GSA) single-photon emission computed tomography (SPECT)/computed tomography (CT) volume and plasma clearance rate of indocyanine green (ICGK) for posthepatectomy liver failure (PHLF). Fifty patients who underwent 99mTc-GSA scintigraphy as a preoperative examination for segmentectomy or more from July 2021 to June 2023 were evaluated prospectively. Patients were divided into two groups according to the presence or absence of posthepatectomy liver failure (PHLF). Total functional liver volume (t-FLV) and remnant FLV (r-FLV) were measured from 99mTc-GSA SPECT/CT image. Future liver remnant ICGK (ICGK-F) was calculated by ICGK and remnant liver volume from CT. Area under the curve (AUC) of ICGK-F, r-FLV, r-FLV/t-FLV, ICGK × r-FLV, ICGK × r-FLV/t-FLV was calculated to evaluate predictive ability of each parameter for PHLF. PHLF was occurred in 7 patients. AUC of ICGK × r-FLV was significantly higher than that of ICGK-F (0.99; 95% confidence interval [CI]: 0.96-1 vs 0.82; 95%CI: 0.64-0.96; p = 0.036). There was no significant difference between the AUC of r-FLV, r-FLV/t-FLV, ICGK × r-FLV/t-FLV and that of ICGK-F, respectively. The combination of 99mTc‑GSA SPECT/CT volume and ICGK can predict PHLF more accurately than ICGK-F.

Von Willebrand Factor Antigen Improves Risk Stratification for Patients with a Diagnosis of Resectable Hepatocellular Carcinoma.

Posthepatectomy liver failure (PHLF), complications of portal hypertension, and disease recurrence determine the outcome for hepatocellular carcinoma (HCC) patients undergoing liver resection. This study aimed to evaluate the von Willebrand factor antigen (vWF-Ag) as a non-invasive test for clinically significant portal hypertension (CSPH) and a predictive biomarker for time to recurrence (TTR) and overall survival (OS). The study recruited 72 HCC patients with detailed preoperative workup from a prospective trial (NCT02118545) and followed for complications, TTR, and OS. Additionally, 163 compensated patients with resectable HCC were recruited to evaluate vWF-Ag cutoffs for ruling out or ruling in CSPH. Finally, vWF-Ag cutoffs were prospectively evaluated in an external validation cohort of 34 HCC patients undergoing liver resection. In receiver operating characteristic (ROC) analyses, vWF-Ag (area under the curve [AUC], 0.828) was similarly predictive of PHLF as indocyanine green clearance (disappearance rate: AUC, 0.880; retention rate: AUC, 0.894), whereas computation of future liver remnant was inferior (AUC, 0.756). Cox-regression showed an association of vWF-Ag with TTR (per 10%: hazard ratio [HR], 1.056; 95% confidence interval [CI] 1.017-1.097) and OS (per 10%: HR, 1.067; 95% CI 1.022-1.113). In the analyses, VWF-Ag yielded an AUC of 0.824 for diagnosing CSPH, with a vWF-Ag of 182% or lower ruling out and higher than 291% ruling in CSPH. Therefore, a highest-risk group (> 291%, 9.7% of patients) with a 57.1% incidence of PHLF was identified, whereas no patient with a vWF-Ag of 182% or lower (52.7%) experienced PHLF. The predictive value of vWF-Ag for PHLF and OS was externally validated. For patients with resectable HCC, VWF-Ag allows for simplified preoperative risk stratification. Patients with vWF-Ag levels higher than 291% might be considered for alternative treatments, whereas vWF-Ag levels of 182% or lower identify patients best suited for surgery.

Indocyanine green fluorescence quantification during normothermic ex situ perfusion for the assessment of porcine liver grafts after circulatory death.

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.

Utility of gadoxetate disodium-enhanced magnetic resonance imaging in evaluating liver failure risk after major hepatic resection.

Post-hepatectomy liver failure (PHLF) is still a predominant cause of hepatectomy-related mortality. However, it is difficult to evaluate the remnant liver functional reserve accurately before surgery to prevent PHLF. In this study, we aimed to explore the role of gadoxetate disodium-enhanced magnetic resonance imaging (MRI) in evaluating remnant liver functional reserve. For this cross-sectional study, the sample retrospectively included 56 patients undergoing liver resections of at least three segments between June 2019 and September 2022 at The General Hospital of the Western Theater Command. Pre-surgery assessments involved liver computer tomography (CT), an indocyanine green (ICG) clearance test, the Child-Pugh scoring system, and liver function serum biochemical indicators. Each patient underwent a gadoxetate disodium-enhanced MRI before the hepatectomy, and we measured the remnant hepatocellular uptake index (rHUI) as well as the standard remnant hepatocellular uptake index (SrHUI). We examined the diagnostic utility of rHUI, SrHUI, indocyanine green retention rate of 15 minutes (ICG R15), and Albumin for PHLF. Receiver operating characteristics (ROC) analyses were used to measure the preoperative liver function parameters (namely, rHUI, SrHUI, ICG R15, and Albumin) for predicting PHLF. The areas under the curve (AUCs) were calculated and compared between different preoperative liver function parameters using the Wilson/Brown method. The Pearson or Spearman correlation coefficient was used for correlation analysis between ICG R15, Albumin, and rHUI and between ICG R15, Albumin, and SrHUI, respectively. Twelve patients (21.43%) had complications of PHLF. We found significant differences in rHUI, SrHUI, ICG R15, and Albumin between the non-PHLF and PHLF groups. The pooled r between ICG R15 and rHUI was -0.591 [95% confidence interval (CI): -0.740 to -0.389, P<0.001], and between ICG R15 and SrHUI was -0.534 (95% CI: -0.703 to -0.308, P<0.001). The area under the curve (AUC) values of rHUI, SrHUI, ICG R15, and Ablumin were 0.871 (sensitivity 81.82%; specificity 91.67%), 0.878 (sensitivity 79.55%; specificity 83.33%), 0.835 (sensitivity 99.73%; specificity 66.67%), and 0.782 (sensitivity 88.64%; specificity 58.33%), respectively. We found that the rHUI and SrHUI calculated using the gadoxetate disodium-enhanced MRI reflected a combination of remnant hepatocyte function and liver volume, and these were useful as a quantitative assessment indicator of remnant liver functional reserve and can be a better predictor of PHLF after major hepatic resection.

Change of indocyanine green clearance ability and liver function after transcatheter intra-arterial therapies and its impact on outcomes of resectable hepatocellular carcinoma: a retrospective cohort study.

Indocyanine green (ICG) clearance test is a classical measurement of hepatic reserve, which involves surgical safety and patient recovery of hepatocellular carcinoma (HCC). The authors aim to compare effects of hepatic arterial infusion chemotherapy (HAIC) and transcatheter arterial chemoembolization (TACE) on liver function and outcomes of subsequent hepatectomy. HCC patients receiving HAIC/TACE in SYSUCC with repeated ICG clearance tests were retrospectively enrolled. ICG eliminating rate (ICG-K), ICG retention rate at 15 min (ICG-R15) and ordinary laboratory tests were collected. Peri-therapeutic changes of values were compared between the groups. Propensity score matching (PSM) and inverse probability of treatment weighing (IPTW) were employed to validate findings. Post-hepatectomy liver failure (PHLF), overall survival (OS) and recurrence-free survival (RFS) were analyzed in patients with subsequent curative hepatectomy. Two hundred and four patients treated with HAIC ( n =130) and TACE ( n =74) were included. ΔICG-R15 was greater in the HAIC arm before matching (mean, 3.8% vs. 0.7%, P <0.001), after PSM (mean, 4.7% vs. 1.1%, P =0.014) and IPTW (mean, 2.0% vs. -3.6%, P <0.001). No difference was found for ΔALB, ΔALBI, ΔTBIL, ΔALT, ΔAST and ΔPT-INR. Multivariable analyses revealed elder age, cirrhosis, HAIC, greater ΔTBIL and ΔALBI were associated with deteriorating ICG-R15. Among those (105 for HAIC and 48 for TACE) receiving hepatectomy, occurrence of grade B/C PHLF (4.8% vs. 8.3%, P =0.616), OS (median, unreached vs. unreached, P =0.94) and RFS (median, 26.7 vs. 17.1months, P =0.096) were comparable between the two arms. In subgroup analyses, preoperative HAIC yield superior RFS (median, 26.7 vs. 16.2months, P =0.042) in patients with baseline ICG-R15 less than or equal to 10%. Preoperative FOLFOX-HAIC caused apparent impairment of ICG clearance ability than TACE yet comparable impact on liver function and post-hepatectomy outcomes.

Indocyanine green clearance test as a predictor of chemotherapy liver toxicity and post-operative complications in patients with colorectal liver metastases

Indocyanine green clearance test as a predictor of chemotherapy liver toxicity and post-operative complications in patients with colorectal liver metastases

Indocyanine green: A novel marker for assessment of graft quality during ex situ normothermic machine perfusion ofhuman livers.

Ex situ machine perfusion facilitates the assessment of livers prior to transplantation. However, currently available markers of liver function poorly predict long-term graft function. Indocyanine green (ICG) is a liver-specific dye which, although common invivo, has never been comprehensively evaluated for the assessment of graft quality during ex situ machine perfusion. This study aimed to assess the utility of ICG in the ex situ setting. Using a customized long-term perfusion system, human livers that were not suitable for transplantation were perfused using a red cell-based perfusate. ICG was delivered into the perfusate on days 0, 1, and 4 to assess ICG clearance (spectrophotometric absorbance at 805 nm) and ICG fluorescence (near-infrared camera). Sixteen partial livers were perfused for a median duration of 172 h (7.2 days). On day 0, the median ICG perfusate disappearance rate (PDR) was 7.5%/min and the median ICG retention at 15 min was 9.9%. Grafts that survived ≥7 days had a significantly higher median ICG PDR on day 0 (14.5%/min vs. 6.5%/min, p = 0.005) but not on days 1 or 4. ICG perfusion demonstrated that long-surviving grafts had a significantly lower median red-value (89.8 vs. 118.6, p = 0.011) and a significantly lower median blue-value (12.9 vs. 22.6, p = 0.045) than short-surviving grafts. ICG is a novel marker for the assessment of liver function during ex situ normothermic machine perfusion. ICG PDR and quantitative ICG perfusion can distinguish between long- and short-surviving grafts and demonstrate the utility of ICG in the assessment of graft quality prior to transplant.

Clearance tests as a diagnosis method of hepatobiliary system pathologies in animals

In present-day conditions of industrial agriculture, the animal's body works at the limit of its capabilities, which leads to degenerative diseases of various organs and systems. The development of ergonomic ways of modern diagnosis of these pathologies at the early stages contributes to the maintenance of quantitative and qualitative indices of productivity of animals and to the extension of the time of their economic use. The liver with a great number of functions performed is subjected to the highest load. The aim of the article is to review the available clearance tests in order to diagnose the pathology of the hepatobiliary system of animals at the early stage, considering advantages and disadvantages of the tests. As the result of the search of themed issues in various bibliographic databases there have been selected 45 mostly cited scientific articles. The article reviews such clearance tests as indocyanine green clearance test, aminopyrine breath test, sorbitol elimination test, galactose elimination test, phenylalanine breath test, and hepatobiliary scintigraphy method. Functional tests allow not only diagnosing and differentiating hepatopathologies, but also visualizing their course and liver recovery. Unlike laboratory tests, clearance tests make it possible to evaluate the work of the liver in dynamics. The disadvantages of clearance tests are lack of information for their wide use and frequency of particular differences in elimination of specific substances. To reduce the proportion of existing shortcomings, it is possible to combine clearance tests with other laboratory methods for diagnosing hepatopathy in animals.

Near-Infrared Fluorescence Tomography and Imaging of Ventricular Cerebrospinal Fluid Flow and Extracranial Outflow in Non-Human Primates.

The role of the lymphatics in the clearance of cerebrospinal fluid (CSF) from the brain has been implicated in multiple neurodegenerative conditions. In premature infants, intraventricular hemorrhage causes increased CSF production and, if clearance is impeded, hydrocephalus and severe developmental disabilities can result. In this work, we developed and deployed near-infrared fluorescence (NIRF) tomography and imaging to assess CSF ventricular dynamics and extracranial outflow in similarly sized, intact non-human primates (NHP) following microdose of indocyanine green (ICG) administered to the right lateral ventricle. Fluorescence optical tomography measurements were made by delivering ~10 mW of 785 nm light to the scalp by sequential illumination of 8 fiber optics and imaging the 830 nm emission light collected from 22 fibers using a gallium arsenide intensified, charge coupled device. Acquisition times were 16 seconds. Image reconstruction used the diffusion approximation and hard-priors obtained from MRI to enable dynamic mapping of ICG-laden CSF ventricular dynamics and drainage into the subarachnoid space (SAS) of NHPs. Subsequent, planar NIRF imaging of the scalp confirmed extracranial efflux into SAS and abdominal imaging showed ICG clearance through the hepatobiliary system. Necropsy confirmed imaging results and showed that deep cervical lymph nodes were the routes of extracranial CSF egress. The results confirm the ability to use trace doses of ICG to monitor ventricular CSF dynamics and extracranial outflow in NHP. The techniques may also be feasible for similarly-sized infants and children who may suffer impairment of CSF outflow due to intraventricular hemorrhage.

Liver remnant volume to body weight ratio of 0.65% as a lower limit in right hepatic trisectionectomy with bile duct resection

BackgroundPrevious studies have suggested the utility of an indocyanine green plasma clearance rate of the future liver remnant (FLR) (ICGK-F) ≥0.05 in hepatobiliary resection to reduce the surgical risk. The present study aimed to verify whether future liver remnant size rather than ICGK-F matters in extended hepatobiliary resection. MethodsBetween 2004 and 2021, patients who underwent right hepatic trisectionectomy with bile duct resection were included. The effect of the FLR volume-to-body weight ratio (FLR/BW) and ICGK-F on posthepatectomy liver failure was evaluated along with other parameters. ResultsAmong 91 study patients, the median ICGK-F, FLR, and FLR/BW were 0.057 (range, 0.027–0.099), 392 mL (145–705), and 0.78% (0.40–1.37), respectively. Posthepatectomy liver failure occurred in 23 patients. The incidence was 10 (40%) in 25 patients with an ICGK-F <0.05 and 12 (18%) in 65 patients with an ICGK-F ≥0.05 (P = .053); 13 (52%) in 25 patients with a FLR/BW <0.65% and 10 (15%) in 66 patients with a FLR/BW ≥0.65% (P = .001). Multivariate analysis showed that a FLR/BW <0.65% (odds ratio, 11.7; P = .005), age ≥65 years (odds ratio, 31.7; P < .001), and blood loss ≥25 mL/kg (odds ratio, 22.1; P = .004) were independent predictors of posthepatectomy liver failure, but ICGK-F <0.05 was not (P = .499). According to the meeting number of 3 factors, posthepatectomy liver failure incidence was 0 of 22 (0%) in patients with 0 factors, 6 of 43 (14%) in patients with 1, and 17 of 26 (65%) in patients with 2 or 3 (P < .001). ConclusionA FLR/BW ≥0.65% may serve as a volumetric basis to reduce posthepatectomy liver failure after extended hepatobiliary resection.

An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.

Indocyanine green clearance test as a predictor of linezolid overexposure in septic patients

Hepatic impairment increases the risk of drug overexposure in septic patients. However, there is a lack of effective indicators to predict overexposure risk. The indocyanine green (ICG) clearance test is a helpful method for dynamically assessing hepatic function and perfusion. This study aimed to investigate whether the ICG test could serve as a potential predictor of linezolid trough concentration (Cmin) and to compare its efficacy with that of conventional liver function markers. A total of 35 consecutive septic patients treated with linezolid were grouped into either linezolid Cmin of ≤7 µg/mL or >7 µg/mL. Correlations between linezolid Cmin and ICG-PDR (plasma disappearance rate), ICG-R15 (retention ratio after 15 min) and other traditional indicators were analysed by Spearman's rank test. A multivariable regression model was employed to discern factors contributing independently to overexposure. Statistical differences were observed between groups for APACHE II score (P=0.031), SOFA score (P=0.018), creatinine clearance (CLCr) (P=0.003), thrombocytes (P=0.039), lactate (P=0.003), ICG-PDR (P < 0.001) and ICG-R15 (P < 0.001). Moreover, linezolid Cmin was correlated with ICG-PDR (ρ=-0.628, P < 0.001), ICG-R15 (ρ=0.676, P < 0.001) and CLCr (ρ=-0.503, P=0.002). ICG-PDR was identified as an independent predictor of linezolid overexposure, with an optimal cut-off value of 17.70%/min (93.3% sensitivity, 85.0% specificity; P < 0.001). This pilot clinical trial represents the first investigation of potential of the ICG test to predict linezolid overexposure in septic patients.

In vivo evaluation of liver function by multimodal imaging in an alcohol-induced liver injury model.

Visually evaluating liver function is a hot topic in hepatology research. There are few reliable and practical visualization methods for evaluating the liver function in vivo in experimental studies. In this study, we established a multimodal imaging approach for in vivo liver function evaluation and compared healthy mice with chronic alcoholic liver injury (cALI) model mice to explore its potential applicability in experimental research. In vivo fluorescence imaging (IVFI) technology was utilized to visually represent the clearance of indocyanine green from the liver of both healthy mice and mice with cALI. The reserve liver function was evaluated via IVFI using the Cy5.5-galactosylated polylysine probe, which targets the asialoglycoprotein receptor of hepatocytes. Hepatic microcirculation was assessed through laser speckle perfusion imaging of hepatic blood perfusion. The liver microstructure was then investigated by in vivo confocal laser endomicroscopy imaging. Finally, hepatic asialoglycoprotein receptor expression, histology, and the levels of serum alanine aminotransferase and aspartate aminotransferase were measured. In vivo multimodal imaging results intuitively and dynamically showed that indocyanine green clearance [mean ± standard deviation (SD): 30.83±14.71, 95% confidence interval (CI): 20.3 to 41.35], the fluorescence signal intensity (mean ± SD: 1,217.92±117.63; 95% CI: 1,148.38 to 1,290.84) and fluorescence aggregation area (mean ± SD: 5,855.80±1,271.81; 95% CI: 5,051.57 to 6,653.88) of Cy5.5-galactosylated polylysine targeting the asialoglycoprotein receptor, and hepatic blood perfusion (mean ± SD: 1,494.86±299.33; 95% CI: 1,316.98 to 1,690.16) in model mice were significantly lower than those in healthy mice (all P<0.001). Compared to healthy mice, the model mice exhibited a significant decline in liver asialoglycoprotein receptor expression (mean ± SD: 219.03±16.34; 95% CI: 208.97 to 230.69; P<0.001), increased serum alanine aminotransferase (mean ± SD: 149.70±47.89 U/L; 95% CI: 81.75 to 128.89; P=0.01) and aspartate aminotransferase levels (mean ± SD: 106.30±36.13 U/L; 95% CI: 122.01 to 180.17; P=0.021), hepatocyte swelling and deformation, disappearance of the hepatic cord structure, partial necrosis, and disintegration of hepatocytes. The imaging features of fluorescence signals in liver regions, hepatic blood perfusion and microstructure were biologically related to hepatic asialoglycoprotein receptor expression, serum indices of liver function, and histopathology in model mice. Utilizing in vivo multimodal imaging technology to assess liver function is a viable approach for experimental research, providing dynamic and intuitive visual evaluations in a rapid manner.

Enhanced stability and photothermal efficiency of Indocyanine Green J-aggregates by nanoformulation with Calix[4]arene for photothermal therapy of cancers.

Photothermal therapy (PTT) is a method of growing attention, owing to its controllable process, high efficiency and minimal side effect. Indocyanine Green (ICG) is as Food and Drug Administration (FDA) approved agent that stands on the frontline of further developments of PTT toward clinics. However, the applicability of ICG-mediated PTT is limited by the rapid in vivo clearance and photo-degradation of ICG. To improve those parameters, nanosized ICG-loaded nanoparticles (ICG-J/CX) were fabricated in this study by co-assembly of anionic ICG J-aggregates (ICG-J) with cationic tetraguanidinium calix[4]arene (CX). This very simple approach produces ICG-J/CX with a well-defined nanometer range size and a close to neutral charge. The nanoparticles demonstrate high photothermal conversion efficiency (PCE) and dramatically improved photostability, as compared with ICG. The in vitro cellular uptake and cytotoxicity studies further demonstrated that the ICG-J/CX nanoparticles enhance uptake and photothermal efficiency in comparison with ICG or non-formulated ICG-J, overall demonstrating that ICG-J/CX mediated photothermal therapy have significant potential for attaining cancer treatment.

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.

Albumin-indocyanine green evaluation of future liver remnant predicts liver failure after anatomical hepatectomy for hepatocellular carcinoma: A dual-center retrospective study.

The albumin-indocyanine green evaluation (ALICE) score is a useful predictor of post-hepatectomy liver failure (PHLF); however, its usefulness in combination with future liver remnant (FLR), measured by 3-D volumetry, has not been investigated. This study aimed to investigate the relationship between the ALICE of the FLR (ALICE-FLR) score and severe PHLF. The clinical data of 215 patients who underwent anatomical hepatectomy for hepatocellular carcinoma without portal vein embolization at two institutes between January 2010 and December 2021 were analyzed retrospectively. PHLF occurrence and severity were determined according to the International Study Group of Liver Surgery's definition. Grades B and C PHLF were defined as severe PHLF. The ALICE-FLR, ALICE scores, and indocyanine green clearance of FLR (ICGK-FLR) were evaluated for severe PHLF prediction. Severe PHLF was observed in 40 patients (18.6%). The areas under the curve (AUCs) for the ALICE-FLR, ALICE scores, ICGK-FLR, and FLR were 0.76, 0.64, 0.73, and 0.69, respectively. The AUC of the ALICE-FLR score was significantly higher than that of the ALICE score. The ALICE-FLR score was identified as an independent predictor of severe PHLF (the odds ratio for every 0.01 increment in the ALICE-FLR score was 1.24; 95% confidence interval, 1.070-1.453; p = 0.004). Among patients with severe PHLF, the ALICE-FLR score was significantly higher in the grade C than in the grade B PHLF group. The combination of liver function models, including indocyanine green, albumin, and FLR is considered compatible for predicting severe PHLF.

Volume-Assisted Estimation of Remnant Liver Function Based on Gd-EOB-DTPA Enhanced MR Relaxometry: A Prospective Observational Trial.

In the context of liver surgery, predicting postoperative liver dysfunction is essential. This study explored the potential of preoperative liver function assessment by MRI for predicting postoperative liver dysfunction and compared these results with the established indocyanine green (ICG) clearance test. This prospective study included patients undergoing liver resection with preoperative MRI planning. Liver function was quantified using T1 relaxometry and correlated with established liver function scores. The analysis revealed an improved model for predicting postoperative liver dysfunction, exhibiting an accuracy (ACC) of 0.79, surpassing the 0.70 of the preoperative ICG test, alongside a higher area under the curve (0.75). Notably, the proposed model also successfully predicted all cases of liver failure and showed potential in predicting liver synthesis dysfunction (ACC 0.78). This model showed promise in patient survival rates with a Hazard ratio of 0.87, underscoring its potential as a valuable tool for preoperative evaluation. The findings imply that MRI-based assessment of liver function can provide significant benefits in the early identification and management of patients at risk for postoperative liver dysfunction.

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy.

Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.