Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma.

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Predicting Microvascular Invasion in Hepatocellular Carcinoma Using CT-based Radiomics Model.

Background Prediction of microvascular invasion (MVI) may help determine treatment strategies for hepatocellular carcinoma (HCC). Purpose To develop a radiomics approach for predicting MVI status based on preoperative multiphase CT images and to identify MVI-associated differentially expressed genes. Materials and Methods Patients with pathologically proven HCC from May 2012 to September 2020 were retrospectively included from four medical centers. Radiomics features were extracted from tumors and peritumor regions on preoperative registration or subtraction CT images. In the training set, these features were used to build five radiomics models via logistic regression after feature reduction. The models were tested using internal and external test sets against a pathologic reference standard to calculate area under the receiver operating characteristic curve (AUC). The optimal AUC radiomics model and clinical-radiologic characteristics were combined to build the hybrid model. The log-rank test was used in the outcome cohort (Kunming center) to analyze early recurrence-free survival and overall survival based on high versus low model-derived score. RNA sequencing data from The Cancer Image Archive were used for gene expression analysis. Results A total of 773 patients (median age, 59 years; IQR, 49-64 years; 633 men) were divided into the training set (n = 334), internal test set (n = 142), external test set (n = 141), outcome cohort (n = 121), and RNA sequencing analysis set (n = 35). The AUCs from the radiomics and hybrid models, respectively, were 0.76 and 0.86 for the internal test set and 0.72 and 0.84 for the external test set. Early recurrence-free survival (P < .01) and overall survival (P < .007) can be categorized using the hybrid model. Differentially expressed genes in patients with findings positive for MVI were involved in glucose metabolism. Conclusion The hybrid model showed the best performance in prediction of MVI. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Summers in this issue.

A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family.

PURPOSE: In order to clarify which variants of the MMR gene could provide current "healthy" members in affected families a more accurate risk assessment or predictive testing. PATIENTS AND METHODS: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing. RESULTS: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro. CONCLUSION: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study.

Simultaneous silencing of XIAP and survivin causes partial mesenchymal-epithelial transition of human pancreatic cancer cells via the PTEN/PI3K/Akt pathway.

Pancreatic cancer has one of the highest mortality rates among malignant tumors and is characterized by rapid invasion, early metastasis and chemoresistance. X-linked inhibitor of apoptosis (XIAP) and survivin are two of the most important members of the IAP family. Previous studies have shown that XIAP and survivin were overexpressed in pancreatic cancer and were closely associated with cell proliferation and chemoresistance to gemcitabine. In the present study, stable inhibition of XIAP and survivin in Panc-1 cells was performed using lentivirus-carried short hairpin RNAs. The expression of XIAP, survivin, E-cadherin, Slug, phosphatase and tensin homolog (PTEN) and phosphorylated Akt was then measured. In addition, cell proliferation, apoptosis, invasion and migration were assessed. The results showed that stable inhibition of XIAP and survivin expression in Panc-1 cells significantly reduced cell proliferation, increased apoptosis and partially reversed the epithelial-mesenchymal transition (EMT). Furthermore, the results of the present study demonstrated that the partial reversal of the EMT was accompanied by inhibited cell invasion and migration as well as increased chemosensitivity to gemcitabine in pancreatic cancer cells; this was indicated to be mediated via the PTEN/phosphatidylinositol 3-kinase/Akt signaling pathway. In conclusion, these results suggested that simultaneous inhibition of XIAP and survivin may be a promising strategy for the treatment of pancreatic cancer.

[CT manifestations of liver involvement in children with Langerhans cell histiocytosis].

OBJECTIVE: To investigate the computed tomography (CT) manifestations of liver involvement in children with Langerhans cell histiocytosis (LCH). METHODS: Retrospective analysis was performed on 9 LCH children with liver involvement confirmed by clinical, laboratory and pathological examinations to investigate the CT manifestations of this condition. These children, including 6 males and 3 females, had undergone both plain CT scan and dual-phase (the arterial and portal venous phases) contrast-enhanced CT scan. RESULTS: The main CT manifestations included hepatomegaly (8 cases); periportal dendritic hypodense lesions or "periportal halo sign" (7 cases) which were mildly or moderately enhanced in the arterial phase; intrahepatic bile duct dilatation (5 cases); lymphadenopathy in the hepatic hilar or retroperitoneal region (4 cases); and diffuse small hypodense nodules (3 cases), which showed annular enhancement on the contrast-enhanced CT scan. CONCLUSIONS: CT findings may be helpful in the early diagnosis and treatment of LCH in children.

[Clinical and imaging features of adult anoxic-ischemic encephalopathy after cardiopulmonary resuscitation].

OBJECTIVE: To explore the clinical and imaging features of anoxic-ischemic encephalopathy (AIE) patients after cardiopulmonary resuscitation. METHODS: A total of 28 qualified AIE patients during the last decade from Xiangya Hospital, Central South University were recruited and analyzed retrospectively. RESULTS: The symptoms of status epilepticus, acute posthypoxic myoclonus, Lance-Adams syndrome, subarachnoid hemorrhage and cognitive deficits were observed. The abnormal findings of magnetic resonance imaging (MRI) or computed tomography (CT), involving neocortex, basal ganglia and para-ventricular white matter, were also recorded. During the early phase of disease, swollen cortex was present on MRI/CT. However, encephalatrophy appeared during the late phase. The more severe symptoms were observed, the more foci were present on MRI/CT. CONCLUSION: The etiologies of AIE patients are heterogeneous after cardiopulmonary resuscitation. The clinical symptoms and imaging studies are of prognostic significance.

Diagnosis of bile duct hepatocellular carcinoma thrombus without obvious intrahepatic mass.

AIM: To study the diagnosis of hepatocellular carcinoma (HCC) presenting as bile duct tumor thrombus with no detectable intrahepatic mass. METHODS: Six patients with pathologically proven bile duct HCC thrombi but no intrahepatic mass demonstrated on the preoperative imaging or palpated intrahepatic mass during operative exploration, were collected. Their clinical and imaging data were retrospectively analyzed. The major findings or signs on comprehensive imaging were correlated with the surgical and pathologic findings. RESULTS: Jaundice was the major clinical symptom of the patients. The elevated serum total bilirubin, direct bilirubin and alanine aminotransferase levels were in concordance with obstructive jaundice and the underlying liver disease. Of the 6 patients showing evidence of viral hepatitis, 5 were positive for serum alpha fetoprotein and carbohydrate antigen 19-9, and 1 was positive for serum carcinoembryonic antigen. No patient was correctly diagnosed by ultrasound. The main features of patients on comprehensive imaging were filling defects with cup-shaped ends of the bile duct, with large filling defects presenting as casting moulds in the expanded bile duct, hypervascular intraluminal nodules, debris or blood clots in the bile duct. No obvious circular thickening of the bile duct walls was observed. CONCLUSION: Even with no detectable intrahepatic tumor, bile duct HCC thrombus should be considered in patients predisposed to HCC, and some imaging signs are indicative of its diagnosis.

[CT hepatic volume measurement combined with CT perfusion imaging in evaluating the hepatic functional reserve].

OBJECTIVE: To investigate the application of CT hepatic volume measurement combined with CT perfusion imaging (CTPI) by Spiral CT in evaluating the hepatic functional reserve in cirrhosis. METHODS: CT volume measurement of livers was performed in 32 patients with cirrhosis and 20 patients with normal livers. CTPI had been taken in 25 patients with cirrhosis and 20 patients with normal livers. The hepatic volume, parameter of blood flow perfusion, and liver volume-perfusion index were observed and analyzed. Correlations between graded fractions of hepatic function and liver volume, parameter of perfusion, and liver volume-perfusion index were also analyzed. RESULTS: The values of liver volumes (LV, LVs) reduced gradually (P<0.01) among the groups of hepatic function Grade A, B, and C. The values of the hepatic portal perfusion (HPP), total liver perfusion (TLP), hepatic arterial perfusion index (HAI), and portal perfusion index (PPI) of the cirrhosis group were significantly lower than those of the normal ones (P<0.01). The values of the HPP reduced gradually among Grade A, B, and C (P<0.05 or P<0.01). The values of PPI reduced significantly between Grade C and Grade A, B (P<0.05 or P<0.01). The liver volume-perfusion indexes (VPI, VPIs, VPPI, VPPIs) reduced gradually among Grade A, B, and C (P<0.05 or P<0.01). The correlation between liver volume-perfusion indexes and graded fractions of hepatic function was higher than other indexes, among which the correlation of VPPIs was the highest. CONCLUSION: Changes of volume and blood flow perfusion of the liver are related to the clinical grade of hepatic function. The CT volume measurement combined with CTPI will be a more comprehensive way in evaluating hepatic functional reserve.

[Population characteristics and individual variations of enhancement of pancreas and aorta: a contrastive analysis of 2 injection rates].

OBJECTIVE: To contrastive analyze the population characteristics and individual variations of enhancement modes of normal pancreas and aorta at intravenous injection rates of 3 mL/s and 2 mL/s. METHODS: Sixty-seven patients with normal pancreas were selected, and were divided randomly into 2 groups with different intravenous injection rates (3 mL/s for 35 patients in Group A and 2 mL/s for 32 patients in Group B). Single-level serial dynamic CT scan was performed at the level where the pancreas was best demonstrated. The enhancement values of pancreas and aorta for each time point of each patient were calculated, and the time-density curves of enhancement of pancreas and aorta of each patient were obtained. The peak enhancement and the time to reach the peak enhancement of pancreas and aorta of each individual patient were evaluated, and the 2 groups were compared. The individual variations of the enhancement modes of pancreas and aorta in each group were analyzed. RESULTS: The peak enhancement of pancreas was (75.7+/-17.0) Hu at (43.9+/-6.6) s for Group A, and (66.5+/-16.0) Hu at (55.2+/-5.0) s for Group B; the peak enhancement of aorta was (226.2+/-35.2) Hu at (35.4+/-4.5) s for Group A, (182.8+/-32.8) Hu at (48.0+/-3.7) s for Group B. There were significant differences in both the peak enhancement and the time to reach the peak enhancement of pancreas and aorta between the 2 groups. The coefficients of variation of time to reach the peak enhancement for pancreas and aorta were 15.0% and 12.7% in Group A, and 9.2% and 7.7% in Group B, respectively. The temporal windows of the optimal enhancement of pancreas were (9.7+/-4.5)s and (13.7+/-3.6)s in Group A and B, respectively. CONCLUSION: Better enhancement of pancreas and aorta is obtained at 3 mL/s than 2 mL/s, the time to reach the peak enhancement of pancreas and aorta is comparatively earlier at 3 mL/s than 2 mL/s, and the temporal windows of optimal enhancement of pancreas and aorta are comparatively shorter at 3 mL/s than 2 mL/s.