Precise in Vivo Inflammation Imaging in the NIR-II Window Using 1065 nm Photoacoustic Probe for in Situ Visual Monitoring of Pathological Processes Related to Hepatitis.

The interaction between light and biological tissues in the second near-infrared (NIR-II) window is weak, which can effectively reduce the scattering and absorption of incoming light by biological tissues and enhance the resolution and sensing ability of in vivo photoacoustic (PA) imaging. In particular, tissues that carry blood and water produce the lowest PA background in the wavelength range of 1050 to 1150 nm. However, the development of the NIR-II PA probe for the above window faces great challenges. To tackle this challenge, the reduction-reoxidation of an organic dye was used to develop a PA imaging probe (Hydro-1048) as the first NIR-II PA probe of a hydroxy radical (·OH) for molecular imaging in deep tissue. The ·OH oxidized the C-N single bond in Hydro-1048 to double bonds, which formed Et-1065. This conversion extended the conjugate system of the molecule and shifted the absorption peak from 520 to 1065 nm, which resulted in a strong PA signal after irradiation with a 1065 nm laser. At a detection limit of 0.6 nM, a good linear relationship within the range of 5-1000 nM was obtained for the PA signal intensity versus the concentration of ·OH. The developed NIR-II PA probe can be used for the noninvasive high-resolution imaging of ·OH in deep tissue, and the PA imaging of ·OH can also be used to visually monitor in situ pathological processes related to hepatitis.

An Activatable Afterglow/MRI Bimodal Nanoprobe with Fast Response to H2 S for In Vivo Imaging of Acute Hepatitis.

Accurate detection of hepatic hydrogen sulfide (H2 S) to monitor H2 S-related enzymes' activity is critical for acute hepatitis diagnosis, but remains a challenge due to the dynamic and transient nature of H2 S. Here, we report a H2 S-activatable near-infrared afterglow/MRI bimodal probe F1-GdNP, which shows an "always-on" MRI signal and "off-on" afterglow signal toward H2 S. F1-GdNP shows fast response, high sensitivity and specificity toward H2 S, permitting afterglow imaging of H2 S and evaluation of cystathionine γ-lyase (CSE)'s activity in living mice. We further employ the high spatial-resolution MRI signal of F1-GdNP to track its delivery and accumulation in liver. Importantly, F1-GdNP offers a high signal-to-background ratio (SBR=86.2±12.0) to sensitively report on the increased hepatic H2 S level in the acute hepatitis mice via afterglow imaging, which correlated well with the upregulated CSE activity in the liver, showcasing the good potential of F1-GdNP for monitoring of acute hepatitis process in vivo.

Hemodynamic Alteration in the Liver in Acute Hepatitis: A Quantitative Evaluation Using Computed Tomographic Perfusion.

BACKGROUND/AIM: We aimed to elucidate the hemodynamic alterations in the liver of patients with acute hepatitis (AH) using computed tomography perfusion imaging. PATIENTS AND METHODS: For 14 patients with AH and nine patients with no disease (ND group), we compared the mean arterial blood flow (AF), portal blood flow (PF) and perfusion index (%) [PI=AF/(AF+PF) ×100] of the right and left liver lobes and investigated their relationship with clinical factors. RESULTS: The mean PI of the right lobe in the AH group (30.5±10.0%) was significantly higher than that in the ND group (20.8±9.7%) (p=0.031). For all patients of the AH and ND groups, the PI of the right lobe was increased as the prothrombin time decreased (R=-0.56, p=0.006) and as the prothrombin time-international normalized ratio increased (R=0.48, p=0.02). CONCLUSION: The PI of the right liver lobe may increase in AH and may be a predictive parameter for the severity of hepatic failure.

Comparison of clinical features between immune-related sclerosing cholangitis and hepatitis.

Background Immune-related hepatotoxicity is often regarded as immune-related hepatitis (irHepatitis) despite including immune-related sclerosing cholangitis (irSC). This study examined the clinical differences between irSC and irHepatitis. Methods A single-center retrospective study of 530 consecutive patients who received immunotherapy between August 2014 and April 2020 was performed. IrSC and irHepatitis were respectively defined as the radiological presence and absence of bile duct dilation and wall thickness. Results Forty-one patients (7.7%) developed immune-related hepatotoxicity. A CT scan was performed on 12 patients, including 11 of 12 with ≥ grade 3 aminotransferase elevations. IrSC and irHepatitis were diagnosed in 4 (0.8%) and 8 (1.5%) patients, respectively. All the irSC patients had been treated with anti-PD-1. IrHepatitis was more common among patients receiving anti-CTLA-4 than among those receiving anti-PD-1/PD-L1 inhibitors (14%, 7/50 vs. 0.2%, 1/480, P < 0.001). A ≥ grade 2 alkaline phosphatase (ALP) elevation resulting in a cholestatic pattern was seen in all 4 irSC patients. Among the irSC patients, 3 (3/4, 75%) developed ≥ grade 3 aminotransferases elevation. The median duration from the start of immunotherapy until ≥ grade 2 liver enzymes elevation was 257 and 55.5 days in irSC and irHepatitis patients. The median times for progression from grade 2 to 3 liver enzyme elevation were 17.5 and 0 days, respectively. Conclusions IrSC and irHepatitis have different characteristics in the class of immune checkpoint inhibitor and onset pattern. Radiological examination for the diagnosis of irSC should be considered for patients with ≥ grade 2 ALP elevation resulting in a cholestatic pattern. (Registration number J2020-36, Date of registration June 3, 2020).

[Fitz-Hugh-Curtis syndrome can give pain under the right upper quadrant].

Fitz-Hugh-Curtis syndrome is a complication to pelvic inflammatory disease causing perihepatitis as described in this case report. A 21-year-old woman was admitted to the hospital due to pain under the right upper quadrant and febrility. Gallstones and pyelonephritis were ruled out. The Chlamydia test came back positive, and the patient had an elevated cancer antigen 125-level. She was suspected to have Fitz-Hugh-Curtis syndrome. On a second look on the ultrasound scan of the liver the capsule was seen to have a characteristic three-layered appearance. The patient was treated with doxycycline. On follow-up she was asymptomatic, and the laboratory parameters were normalised.

Quantitative magnetic resonance imaging for chronic liver disease.

Chronic liver disease (CLD) has rapidly increased in prevalence over the past two decades, resulting in significant morbidity and mortality worldwide. Historically, the clinical gold standard for diagnosis, assessment of severity, and longitudinal monitoring of CLD has been liver biopsy with histological analysis, but this approach has limitations that may make it suboptimal for clinical and research settings. Magnetic resonance (MR)-based biomarkers can overcome the limitations by allowing accurate, precise, and quantitative assessment of key components of CLD without the risk of invasive procedures. This review briefly describes the limitations associated with liver biopsy and the need for non-invasive biomarkers. It then discusses the current state-of-the-art for MRI-based biomarkers of liver iron, fat, and fibrosis, and inflammation.

Gas Where It Shouldn't Be! Imaging Spectrum of Emphysematous Infections in the Abdomen and Pelvis.

OBJECTIVE. The purpose of this article is to review the spectrum, etiopathogenesis, clinical presentation, imaging features, differential diagnoses, and management of emphysematous infections of the abdomen and pelvis. CONCLUSION. Emphysematous infections are associated with high morbidity and mortality and thus need urgent medical and surgical interventions. CT is the most sensitive modality to detect gas; CT provides definitive diagnosis in most cases and can depict the extent of involvement.

Bone Marrow of Contention: A Rare Case of Recurrent Acute Hepatitis.

Hepatitis-associated aplastic anemia is a well-recognized clinical syndrome in which marrow failure follows the development of hepatitis. Although aplastic anemia is intimately related to paroxysmal nocturnal hemoglobinuria, until now, no cases of PNH-associated hepatitis have been described. We report a case of recurrent acute hepatitis preceding the clinical onset of PNH. Treatment of PNH with the complement inhibitor eculizumab (Soliris®) prevented both recurrences of episodes of intravascular hemolysis and liver enzyme alteration. This is the first known published case of PNH-associated hepatitis.

Imaging spectrum of adverse events of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs), a form of immunotherapy, are increasingly used for a variety of malignancies and have been linked to numerous treatment-related side effects known as immune-related adverse events (irAEs). IrAEs can affect multiple organ systems and are important to recognise in order to avoid misinterpretation as progressive tumour and to ensure appropriate management. In this pictorial review, we will briefly discuss radiological response criteria of immunotherapy and describe the imaging appearances of the wide spectrum of these ICI-associated toxicities.

MR Imaging of the Perihepatic Space.

The perihepatic space is frequently involved in a spectrum of diseases, including intrahepatic lesions extending to the liver capsule and disease conditions involving adjacent organs extending to the perihepatic space or spreading thanks to the communication from intraperitoneal or extraperitoneal sites through the hepatic ligaments. Lesions resulting from the dissemination of peritoneal processes may also affect the perihepatic space. Here we discuss how to assess the perihepatic origin of a lesion and describe the magnetic resonance imaging (MRI) features of normal structures and fluids that may be abnormally located in the perihepatic space. We then review and illustrate the MRI findings present in cases of perihepatic infectious, tumor-related, and miscellaneous conditions. Finally, we highlight the value of MRI over computed tomography.

Pre-operative Detection of Liver Fibrosis in Hepatocellular Carcinoma Patients Using 2D Shear Wave Elastography: Where to Measure?

The aim of this study was to pre-operatively investigate the diagnostic performance of 2D shear wave elastography (2D-SWE) for staging liver fibrosis and inflammation in patients with hepatocellular carcinoma (HCC) who then undergo surgery and to determine the optimal locations for measurement. In total, 106 patients were enrolled in this prospective study from March 2017 to May 2018. Two-dimensional SWE was used to measure liver stiffness (LS) in each patient 0-1, 1-2 and 2-5 cm from the tumor border (groups 1, 2 and 3, respectively). Spearman's correlation was used to evaluate the relationships between LS and hepatic fibrosis and between LS and inflammation. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracy of 2D-SWE. The technical success rate of SWE in tissue distant from the tumor (group 3) was significantly higher than that in peri-tumoral tissue (groups 1 and 2) (p < 0.001). Moreover, the area under the ROC for diagnosing cirrhosis (F4) and severe inflammation (A3) was higher for group 3 than for groups 1 and 2. Our results suggest that 2D-SWE is a helpful approach to assessment of hepatic fibrosis in HCC patients before hepatic resection. We found that to achieve a superior success rate and preferable diagnosis accuracy for patients with HCC, LS measurement should be performed 2-5 cm from the tumor margin.

Diagnosis efficacy of CEUS for hepatic inflammatory lesions.

PURPOSE: In this study, the efficacy of US/CEUS and clinicopathologic parameters in differential diagnosis of hepatic inflammatory lesions were evaluated. METHODS: This was a retrospective study in which CEUS imaging was performed on 182 patients. Among these patients, 44 patients had hepatic inflammatory lesions and 138 patients had malignant lesions. The ultrasound (US), CEUS, and clinicopathologic parameters with respect to differential diagnosis of hepatic inflammatory lesions were analyzed. RESULTS: Irregular lesion shape and unclear margin were commonly seen in hepatic inflammatory lesions by US/CEUS examination. Hypoenhancement in arterial phase (AP) and portal venous phase (PVP), and isoenhancement in delayed phase (DP) were more commonly found in inflammatory lesions rather than malignant lesions [9% (4/44), 68% (30/44), and 16% (7/44) vs 2% (3/138), 11% (15/138), 1% (1/138), respectively; P < .05]. The enhancement coverage was also a significant indicator for the differentiation of inflammatory lesions and malignant lesions (P < .05). History of hepatitis or cirrhosis, and higher serum alpha-fetoprotein (AFP) level were indicators for malignant lesions, while liver parasites and higher body temperature were indicators for inflammatory lesions. When the US/CEUS findings were combined with clinicopathologic parameters, the diagnostic accuracy of inflammatory lesions could reach 93.3%, with sensitivity, specificity, positive predictive value, and negative predictive value of 63.64%, 96.03%, 84.85%, and 88.32%, respectively. CONCLUSION: The US/CEUS findings combined with clinical characteristics can accurately differentiate hepatic inflammatory lesions and malignant lesions. The results of study will improve the diagnostic confidence for hepatic inflammatory lesions.

qFIBS: An Automated Technique for Quantitative Evaluation of Fibrosis, Inflammation, Ballooning, and Steatosis in Patients With Nonalcoholic Steatohepatitis.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. Clinical trials use the NASH Clinical Research Network (CRN) system for semiquantitative histological assessment of disease severity. Interobserver variability may hamper histological assessment, and diagnostic consensus is not always achieved. We evaluate a second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) imaging-based tool to provide an automated quantitative assessment of histological features pertinent to NASH. APPROACH AND RESULTS: Images were acquired by SHG/TPEF from 219 nonalcoholic fatty liver disease (NAFLD)/NASH liver biopsy samples from seven centers in Asia and Europe. These were used to develop and validate qFIBS, a computational algorithm that quantifies key histological features of NASH. qFIBS was developed based on in silico analysis of selected signature parameters for four cardinal histopathological features, that is, fibrosis (qFibrosis), inflammation (qInflammation), hepatocyte ballooning (qBallooning), and steatosis (qSteatosis), treating each as a continuous rather than categorical variable. Automated qFIBS analysis outputs showed strong correlation with each respective component of the NASH CRN scoring (P < 0.001; qFibrosis [r = 0.776], qInflammation [r = 0.557], qBallooning [r = 0.533], and qSteatosis [r = 0.802]) and high area under the receiver operating characteristic curve values (qFibrosis [0.870-0.951; 95% confidence interval {CI}, 0.787-1.000; P < 0.001], qInflammation [0.820-0.838; 95% CI, 0.726-0.933; P < 0.001), qBallooning [0.813-0.844; 95% CI, 0.708-0.957; P < 0.001], and qSteatosis [0.939-0.986; 95% CI, 0.867-1.000; P < 0.001]) and was able to distinguish differing grades/stages of histological disease. Performance of qFIBS was best when assessing degree of steatosis and fibrosis, but performed less well when distinguishing severe inflammation and higher ballooning grades. CONCLUSIONS: qFIBS is an automated tool that accurately quantifies the critical components of NASH histological assessment. It offers a tool that could potentially aid reproducibility and standardization of liver biopsy assessments required for NASH therapeutic clinical trials.

Does Supersonic Shear Wave Elastography Help Differentiate Biliary Atresia from Other Causes of Cholestatic Hepatitis in Infants Less than 90 Days Old? Compared with Grey-Scale US.

PURPOSE: To investigate the diagnostic performance of shear wave elastography (SWE) for measuring liver stiffness to identify and differentiate biliary atresia (BA) from cholestatic hepatitis in infants younger than 90 days. METHODS: A total of 138 infants younger than 90 days with cholestatic hepatitis were examined by SWE. The infants were subclassified into BA and nonbiliary atresia (non-BA) groups. Receiver operating characteristic (ROC) analysis was used to determine the sensitivity and specificity of hepatic Young's modulus measurements, the ultrasonic findings in the differential diagnosis of suspected BA, and the cut-off value to diagnose BA. RESULTS: In all infants with cholestatic hepatitis, the cut-off value of hepatic Young's modulus to differentiate the BA group from the non-BA group was 12.35 kPa and the area under the ROC curve (AUC) was 0.937, with a sensitivity of 84.3% and a specificity of 89.7%; nevertheless the AUC of the abnormal gallbladder (AbGB) was 0.940, with a sensitivity of 96.1% and a specificity of 92.0%. In the parallel test, triangular cord (TC) sign combined with AbGB had the best diagnostic performance and the AUC was 0.960, with a sensitivity of 100% and a specificity of 92.0%. In the serial test, SWE combined with AbGB achieved the best diagnostic performance; the AUC was 0.902, the sensitivity and specificity were 80.4% and 100%, respectively. CONCLUSIONS: SWE could not only help differentiate BA from cholestatic hepatic diseases but also increase the diagnostic specificity when combined with grey-scale ultrasound in the serial test.