Karin A. Herrmann

IL-22 is produced by activated T cells and signals through a receptor complex consisting of IL-22R1 and IL-10R2. The aim of this study was to analyze IL-22 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal epithelial cells (IEC). Expression studies were performed by RT-PCR. Signal transduction was analyzed by Western blot experiments, cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and Fas-induced apoptosis by flow cytometry. IEC migration was studied in wounding assays. The IEC lines Caco-2, DLD-1, SW480, HCT116, and HT-29 express both IL-22 receptor subunits IL-22R1 and IL-10R2. Stimulation with TNF-α, IL-1β, and LPS significantly upregulated IL-22R1 without affecting IL-10R2 mRNA expression. IL-22 binding to its receptor complex activates STAT1/3, Akt, ERK1/2, and SAPK/JNK MAP kinases. IL-22 significantly increased cell proliferation ( P = 0.002) and phosphatidylinsitol 3-kinase-dependent IEC cell migration ( P < 0.00001) as well as mRNA expression of TNF-α, IL-8, and human β-defensin-2. IL-22 had no effect on Fas-induced apoptosis. IL-22 mRNA expression was increased in inflamed colonic lesions of patients with Crohn’s disease and correlated highly with the IL-8 expression in these lesions ( r = 0.840). Moreover, IL-22 expression was increased in murine dextran sulfate sodium-induced colitis. IEC express functional receptors for IL-22, which increases the expression of proinflammatory cytokines and promotes the innate immune response by increased defensin expression. Moreover, our data indicate intestinal barrier functions for this cytokine-promoting IEC migration, which suggests an important function in intestinal inflammation and wound healing. IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and IEC migration.

Dynamic susceptibility contrast MRI (DSC-MRI) is the current standard for the measurement of Cerebral Blood Flow (CBF) and Cerebral Blood Volume (CBV), but it is not suitable for the measurement of Extraction Flow (EF) and may not allow for absolute quantification. The objective of this study was to develop and evaluate a methodology to measure CBF, CBV, and EF from T1-weighted dynamic contrast-enhanced MRI (DCE-MRI). A two-compartment modeling approach was developed, which applies both to tissues with an intact and with a broken Blood-Brain-Barrier (BBB). The approach was evaluated using measurements in normal grey matter (GM) and white matter (WM) and in tumors of 15 patients. Accuracy and precision were estimated with simulations of normal brain tissue. All tumor and normal tissue curves were accurately fitted by the model. CBF (mL/100 mL/min) was 82 +/- 21 in GM and 23 +/- 14 in WM, CBV (mL/100 mL) was 2.6 +/- 0.8 in GM and 1.3 +/- 0.4 in WM. EF (mL/100 mL/min) was close to zero in GM (-0.009 +/- 0.05) and WM (-0.03 +/- 0.08). Simulations show an overlap between CBF values of WM and GM, which is eliminated when Contrast-to-Noise (CNR) is improved. The model provides a consistent description of tracer kinetics in all brain tissues, and an accurate assessment of perfusion and permeability in reference tissues. The measurement sequence requires optimization to improve CNR and the precision in the perfusion parameters. With this approach, DCE-MRI presents a promising alternative to DSC-MRI for quantitative bolus-tracking in the brain.

The appropriate staging of malignant tumors is increasingly important as new therapeutic strategies develop. Because metastatic involvement of the liver in extrahepatic malignant disease may significantly change therapeutic approach, it is important to rule out such involvement with high confidence. Moreover, the differentiation between incidental benign lesions, such as hemangioma, focal nodular hyperplasia (FNH), or adenoma, is of high interest. Magnetic resonance (MR) imaging has proved reliable for diagnostic work-up of the liver. Liver-specific contrast agents have been especially helpful in detecting and precisely characterizing focal liver lesions, but the use of these agents has been limited because it has not been possible to perform both proper vascular phase and liver-specific phase within a reasonable time frame and in a single examination after a single injection of contrast agent. However, the hepatobiliary contrast agent gadolinium-ethoxybenzyl (Gd-EOB)-DTPA now allows combined dynamic imaging and hepatocyte-specific imaging in one examination. Gd-EOB-DTPA can be injected as a bolus and shows the enhancement characteristics and vascularity of liver lesions. In the delayed phase, which is acquired most appropriately 20 min after injection, Gd-EOB-DTPA is taken up selectively by functioning hepatocytes. Thus, malignant liver lesions, e.g. metastases, are spared from contrast uptake of the surrounding liver parenchyma. These lesions are hypointense in contrast to the surrounding bright liver. We review the current literature and present a practical approach to Gd-EOB-enhanced MR imaging using imaging examples of patients with liver metastases.

PURPOSE: To prospectively compare findings of magnetic resonance (MR) lymphangiography with those of lymphoscintigraphy, evaluate the pattern and delay of lymphatic drainage, compare typical findings, and investigate discrepancies between the techniques. MATERIALS AND METHODS: This prospective study was performed according to the Declaration of Helsinki and was approved by the local ethics committee. Thirty consecutive patients with uni- or bilateral lymphedema and lymph vessel transplants of the lower extremities were examined with 3.0-T fat-saturated three-dimensional gradient-echo MR after gadopentetate dimeglumine injection. Results of all examinations were correlated with corresponding results of lymphoscintigraphy examinations. Results of both techniques were separately reviewed in consensus by a radiologist and a nuclear physician, who rated delay and pattern of drainage, number of enhancing levels, and quality of conspicuity of the depiction of lymph nodes and lymph vessels. Sensitivity and specificity were calculated by using combined results of both techniques and clinical presentation findings as reference standard. Correlation was calculated with weighted k coefficients. RESULTS: Weak lymphatic drainage at lymphoscintigraphy correlated with lymphangiectasia at MR lymphangiography (13 of 33 affected extremities). Lymph vessels were clearly visualized with MR lymphangiography (five of 24 affected extremities), while they were not detectable with lymphoscintigraphy. Depiction of inguinal lymph nodes was clearer with lymphoscintigraphy (five of 60 extremities). Correlation of both techniques was excellent for delay (κ=0.93) and pattern (κ=0.84) of drainage, good for depiction of lymph nodes (κ=0.67) and number of enhancing levels (κ=0.77), and moderate for depiction of lymph vessels (κ=0.50). Sensitivity and specificity for delay and pattern of drainage were concordant, whereas MR lymphangiography showed a higher sensitivity for lymph vessel abnormalities (100% vs 79%) and lower specificity for lymph node abnormalities (78% vs 100%). CONCLUSION: Imaging findings of MR lymphangiography and lymphoscintigraphy show a clear concordance. With lymphoscintigraphy, better visualization of inguinal lymph nodes was achieved, whereas with MR lymphangiography, better depiction of lymph vessels and morphologic features of lymph vessel abnormalities were achieved.