Mathilde Wagner

Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging

Tumour heterogeneity poses a significant challenge for treatment stratification. The goals of this study were to quantify heterogeneity in hepatocellular carcinoma (HCC) using multiparametric magnetic resonance imaging (mpMRI), and to report preliminary data correlating quantitative MRI parameters with advanced histopathology and gene expression in a patient subset. Thirty-two HCC patients with 39 HCC lesions underwent mpMRI including diffusion-weighted imaging (DWI), blood-oxygenation-level-dependent (BOLD), tissue-oxygenation-level-dependent (TOLD) and dynamic contrast-enhanced (DCE)-MRI. Histogram characteristics [central tendency (mean, median) and heterogeneity (standard deviation, kurtosis, skewness) MRI parameters] in HCC and liver parenchyma were compared using Wilcoxon signed-rank tests. Histogram data was correlated between MRI methods in all patients and with histopathology and gene expression in 14 patients. HCCs exhibited significantly higher intra-tissue heterogeneity vs. liver with all MRI methods (P < 0.030). Although central tendency parameters showed significant correlations between MRI methods and with each of histopathology and gene expression, heterogeneity parameters exhibited additional complementary correlations between BOLD and DCE-MRI and with histopathologic hypoxia marker HIF1α and gene expression of Wnt target GLUL, pharmacological target FGFR4, stemness markers EPCAM and KRT19 and immune checkpoint PDCD1. Histogram analysis combining central tendency and heterogeneity mpMRI features is promising for non-invasive HCC characterization on the imaging, histologic and genomics levels.

Magnetic Resonance Imaging Predicts Histopathological Composition of Ileal Crohn’s Disease

Background and Aims Recently, smooth muscle hypertrophy has been suggested to be a contributor to small bowel lesions secondary to Crohns disease [CD], in addition to inflammation and fibrosis. Here, we assess the value of magnetic resonance imaging [MRI] for the characterisation of histopathological tissue composition of small bowel CD, including inflammation, fibrosis, and smooth muscle hypertrophy. Methods A total of 35 consecutive patients [male/female 17/18, mean age 33 years] with ileal CD, who underwent small bowel resection and a preoperative contrast-enhanced MRI examination within 1 month before surgery, were retrospectively included. Image assessment included qualitative [pattern/degree of enhancement, presence of ulcerations/fistulas/abscesses] and quantitative parameters [wall thickness on T2/T1-weighted images [WI], enhancement ratios, apparent diffusion coefficient [ADC], Clermont and Magnetic Resonance Index of Activity [MaRIA] scores). MRI parameters were compared with histopathological findings including active inflammation, collagen deposition, and muscle hypertrophy using chi square/Fisher or Mann-Whitney tests and univariate/multivariate logistic/linear regression analyses. Results Forty ileal segments were analysed in 35 patients. Layered pattern at early-post-contrast phase was more prevalent (odds ratio [OR] = 8; p = 0.008), ADC was significantly lower [OR = 0.005; p = 0.022], and MaRIA score was significantly higher [OR = 1.125; p = 0.022] in inflammation grades 2-3 compared with grade 1. Wall thickness on T2WI was significantly increased [OR = 1.688; p = 0.043], and fistulas [OR = 14.5; p = 0.017] were more prevalent in segments with disproportionately increased muscle hypertrophy versus those with disproportionately increased fibrosis. MaRIA/Clermont scores, wall thickness on T1WI and T2WI, and ADC were all significantly correlated with degree of muscular hypertrophy. Conclusions MRI predicts the degree of inflammation, and can distinguish prominent muscle hypertrophy from prominent fibrosis in ileal CD with reasonable accuracy (area under receiver operating characteristic curve [AUROC] > 0.7).

Detection of liver micrometastases from colorectal origin by perfusion CT in a rat model

BACKGROUND Some patients with colorectal carcinoma have liver metastases (LMs) which cannot be detected by conventional imaging. This study aimed to assess whether hepatic perfusion changes induced by micrometastases can be detected by perfusion computed tomography (CT). METHODS LMs were produced in rats by injecting carcinoma cells into the portal vein. Perfusion CT was performed at microscopic (day 10), interval (day 17), and macroscopic stage (day 34). Perfusion parameters were computed using a dual-input one-compartmental model. RESULTS Micro and macro LMs presented a mean diameter of 0.5 and 2.6 mm, respectively. Compared to controls, LMs at interval (1.1 mm) and macroscopic stage induced significant perfusion changes: a decrease of 42% (P=0.004) and 41% (P=0.029) in hepatic transit time and an increase of 292% (P=0.073) and 240% (P=0.001) in portal delay, respectively. CONCLUSIONS LMs with a mean diameter between 1.1 and 2.6 mm induced significant hepatic perfusion changes, detected by CT. Such detection may help to select patients and propose chemotherapy at the time of primary tumor resection.

Hepatic adenomatosis in liver cirrhosis

Hepatocellular adenoma (HCA) is a benign liver tumor most frequently occurring in women using oral contraception. HCA develops in normal or nearly normal livers and is extremely rare in cirrhosis. The authors present magnetic resonance imaging and histopathologic findings in a 57-year-old man with liver cirrhosis and hepatic adenomatosis. As the differentiation between HCA and hepatocellular carcinoma (HCC) can be difficult with imaging, we would like to highlight the importance of ancillary findings such as the presence of iron on MRI, which can be observed in HCA.

Unusual Hepatic Lesion in a Patient With a Lung Tumor

Radiology Department, Hôpital Pitié-salpêtrière, Paris, France 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 Question: A 48-year-old man with no medical history was admitted for hemoptysis. Thoracic-abdominal-pelvic computed tomography (CT) was performed and showed a suspicious, 25 40-mmmass in the lower anterobasal segment of the left lung and a well-circumscribed, 22 18-mm hepatic lesion in segment V, with a slight heterogeneous enhancement at the portal phases (Figure A). Fiberoptic bronchoscopy found a bleeding mass and transbronchial biopsy revealed a pulmonary adenocarcinoma. A 18F-fludeoxyglucose (FDG) positron emission tomography-CT was performed for accurate staging of lung cancer and showed an intense uptake of the lower left lung mass (standardized uptake value 1⁄4 12) and no other significant uptake. The absence of 18F-FDG uptake in the hepatic lesion was considered as unusual and magnetic resonance imaging (MRI) of the liver was performed to characterize the segment V lesion. Liver showed normal appearance, with no sign of hepatic steatosis on dual gradient-echo in-phase and opposed-phase sequences. The lesion was slightly hyperintense to liver parenchyma and heterogeneous on T2-weighted sequence (Figure B) and hypointense on T1-weighted sequence, with no restriction in diffusion-weighted imaging. Slight heterogeneous enhancement was observable on the dynamic T1-weighted fat saturation after contrast material injection at the arterial and the portal phases with homogeneous enhancement on late phase (Figure C). Contrast-enhanced ultrasonography was also performed. The lesion appeared on B-mode as a well-defined, heterogeneous, slightly hyperechoic nodule. Share wave elastography revealed comparable stiffness versus the surrounding hepatic parenchyma. The enhancement was comparable to the surrounding liver at arterial portal (Figure D) and late phases, without washout at the late phase. What is the most likely diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. 111 112 113 114 115 116 Conflicts of interest The authors disclose no conflicts.

Noninvasive prediction of portal pressure with MR elastography and DCE-MRI of the liver and spleen: Preliminary results: MRI Diagnosis of Portal Hypertension

Portal hypertension (PH), defined by hepatic venous pressure gradient (HVPG) ≥5 mmHg and clinically significant PH, defined by HVPG ≥10 mmHg, are complications of chronic liver disease.

Luminally-polarized mural and vascular remodeling in ileal strictures of Crohn's Disease

Intestinal stricture, a major complication of Crohns disease (CD), results from fibromuscular remodeling and expansion of the intestinal wall. The corresponding microanatomical alterations have not been fully described, hindering progress toward understanding their pathogenesis and devising appropriate treatments. We used tissue-specific staining and quantitative digital histomorphometry for this purpose. Serial histologic sections from 37 surgically resected ileal strictures and adjacent nonstrictured controls from patients with CD were evaluated after staining for smooth muscle actin, collagen (Sirius red), and collagen types I, III, and V. Overall mural thickening in strictures was increased 2.2 ± 0.2-fold compared with nonstrictured regions of the same specimens. The muscular layer most altered was the muscularis mucosae (MM). Compared with the internal and external layers of the muscularis propria, (MP) which were expanded 1.9 ± 0.2- and 1.3 ± 0.1-fold, respectively, the MM was expanded 17.7 ± 2.6-fold, reflecting the combined effects of architectural disarray, an 11.6 ± 1.4-fold increase smooth muscle content, and elaboration of pericellular type V collagen. In contrast, the architecture of the MP was preserved and pericellular collagen was virtually absent; rather, fibrosis in this layer was limited to expansion of the intramuscular septa by collagen types I and III. The muscular arteries and veins within the strictured submucosa frequently exhibited eccentric, luminally oriented adventitial mantles comprising hyperplastic myocytes and extracellular type V collagen. We conclude that the fibromuscular remodeling which results in CD-associated ileal strictures predominantly involves the MM and submucosal vasculature in a luminally polarized fashion and suggests that mucosal-based factors may contribute to stricture pathogenesis.

Prediction of the histopathologic findings of intrahepatic cholangiocarcinoma: qualitative and quantitative assessment of diffusion-weighted imaging

ObjectiveTo correlate qualitative and quantitative diffusion weighted imaging (DWI) characteristics of intrahepatic cholangiocarcinoma (ICC) with histopathologic tumour grade and fibrosis content.MethodsFifty-one patients (21M/30F; mean age 61y) with ICC and MRI including DWI were included in this IRB-approved multicentre retrospective study. Qualitative tumour features were assessed. Tumour apparent diffusion coefficient (ADC) mean, minimum, and normalized (nADCliver) values were computed. Tumour grade [well(G1), moderately(G2), or poorly differentiated(G3)] and tumour fibrosis content [minimal(1), moderate(2), or abundant(3)] were categorized pathologically. Imaging findings and ADC values were compared with pathologic measures. Utility of ADC values for predicting tumour grade was assessed using ROC analysis.Results51 ICCs (mean size 6.5±1.1 cm) were assessed. 33/51(64%) of ICCs demonstrated diffuse hyperintensity and 15/51(29%) demonstrated target appearance on DWI. Infiltrative morphology (p=0.02) and tumour size (p=0.04) were associated with G3. ADCmean and nADCmean of G3 (1.32±0.47x10-3 mm2/sec and 0.97±0.95) were lower than G1+G2 (1.57±0.39x10-3 mm2/sec and 1.24±0.49; p=0.03 and p=0.04). ADCmean and nADCmean were inversely correlated with tumour grade (p<0.025). No correlation was found between ADC and tumour fibrosis content. AUROC, sensitivity and specificity of nADCmean for G3 versus G1+G2 were 0.71, 89.5% and 55.5%.ConclusionADC quantification has reasonable accuracy for predicting ICC grade.Key Points• ADC quantification was useful for predicting ICC tumour grade.• Infiltrative tumour morphology and size were associated with poorly differentiated ICCs.• ADC values depended more on ICC tumour grade than fibrosis content.• Ability to predict ICC tumour grade non-invasively could impact patient management.

Multiparametric FDG-PET/MRI of Hepatocellular Carcinoma: Initial Experience

Purpose To compare multiparametric (mp)FDG-PET/MRI metrics between hepatocellular carcinoma (HCC) and liver parenchyma and to assess the correlation between mpMRI and FDG-PET standard uptake values (SUVs) in liver parenchyma and HCC. Methods This prospective, institutional review board-approved study enrolled 15 patients (M/F 12/3; mean age 61 y) with HCC. mpMRI including blood-oxygen-level-dependent (BOLD) MRI, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and dynamic contrast-enhanced-(DCE-) MRI was performed simultaneously with 18F-FDG-PET on a 3T PET/MRI hybrid system. Quantitative BOLD, IVIM and DCE-MRI parameters (Tofts model (TM) and shutter-speed model (SSM)), and PET parameters (SUVmean and SUVmax) were quantified and compared between HCC lesions and liver parenchyma using Wilcoxon signed-rank tests. SUV ratios between HCCs and liver were also calculated (SUVmean T/L and SUVmax T/L). Diagnostic performance of (combined) mp-PET/MRI parameters for characterization of HCC was assessed using ROC analysis. Spearman correlations between PET and mpMRI parameters in HCC tumors and liver parenchyma were evaluated. Results 21 HCC lesions (mean size 4.0 ± 2.4 cm; range 2–13 cm) were analyzed. HCCs exhibited significantly higher arterial fraction (from DCE-MRI) and lower R2∗ pre-O2 and post-O2 (from BOLD-MRI) versus liver parenchyma (P < 0.032). The highest diagnostic performance for differentiation between HCC and liver parenchyma was achieved for combined ART SSM and R2∗ post-O2 (AUC = 0.91). SUVmax showed reasonable performance for differentiation of HCC versus liver (AUC = 0.75). In HCC, DCE-MRI parameters Ktrans (TM and SSM) and ve TM exhibited significant negative correlations with SUVmax T/L (r ranges from −0.624 to −0.566; FDR-adjusted P < 0.050). Conclusions Despite the observed reasonable diagnostic performance of FDG-PET SUVmax for HCC detection and several significant correlations between FDG-PET SUV and DCE-MRI parameters, FDG-PET did not provide clear additional value for HCC characterization compared to mpMRI in this pilot study.

Adénocarcinomes du pancréas borderline et localement avancés réséqués après chimiothérapie néo-adjuvante par Folfirinox : résultats d’une étude multicentrique AGEO/FRENCH

Objectif Evaluer les resultats de la resection chirurgicale d’adenocarcinome pancreatique (ADCP), borderline (BR) ou localement avance (LA) apres Folfirinox (FLX) en neo-adjuvant. Methodes Les patients (pts) operes apres FLX ont ete retrospectivement inclus dans cette etude multicentrique. Les tumeurs ont ete classees BR/LA selon la classification du MD Anderson. Resultats De novembre 2010 a decembre 2013, 77 pts (âge median 59 ans) ont ete inclus : 43 ADCP (56 %) classes BR et 34 (44 %) LA au diagnostic. La chirurgie etait realisee apres une mediane de 6 cycles (1–30) de FLX. 53 pts (69 %) ont recu une radiochimiotherapie (RCT) preoperatoire. 63 tumeurs (82 %) etaient cephaliques (taille moyenne 33mm [16–110]) et 26 (34 %) ont requis une resection vasculaire. 22 % des pts ont presente une complication classee Clavien III/IV. La mortalite post-operatoire a 2 mois etait de 2,6 % (2 deces). Le taux de resection R0 etait de 82 % (63/77), avec 16 % (12/77) de reponse histologique complete (RHC). Apres une duree mediane de suivi de 19 mois, 23 pts (30 %) ont presente une recidive tumorale, don’t 12 deces (16 %). La survie sans recidive et la survie globale etaient de 22,8 mois [IC 95 % : 18,5–27,1] et 39,5 mois [IC 95 % : 35,3–43,7]. Conclusion La resection chirurgicale pour ADCP BR/LA apres FLX semble sure, meme apres RCT. Le taux de resection R0 et de RHC suggere une evaluation prospective de cette strategie. Des donnees de suivi actualisees seront presentees durant l’AFC.