Christiane Girlich

Quantitative assessment of bowel wall vascularisation in Crohn's disease with contrast-enhanced ultrasound and perfusion analysis

Patients with inflammatory bowel disease (IBD) often undergo several radiologic imaging studies, which - with the exception of magnetic resonance imaging (MRI) and B-scan ultrasound (US) - subject patients to ionizing radiation. With contrast enhanced ultrasound microvascular imaging of the bowel is possible. Hence, the aim of our study was to assess the perfusion pattern of inflamed bowel walls in Crohns disease compared with healthy volunteers quantitatively using a specific quantification software. We evaluated 4 volunteers and 20 patients with proven Crohns disease, who went through an active episode based on clinical symptoms and complementary imaging by MRI (19 patients) and computed tomography (1 patient), respectively, with dynamic contrast-enhanced ultrasound (CEUS) using a second generation contrast agent (SonoVue, Bracco, Germany). Retrospectively, we applied the quantification software Qontrast (Bracco, Italy) to obtain contrast-enhanced sonographic perfusion maps for each lesion. Patients had significant higher peak values (median 46.86, lower quartile 37.91, upper quartile 53.20) and significant higher regional blood volume (median 2133.65, lower quartile 1202.90, upper quartile 2820.44) than volunteers. Considering the very low peak value of the healthy, it is easy to understand that the time-to-peak was significantly shorter in the volunteers (median 4.45, lower quartile 1.82, upper quartile 6.88) than in the patients (median 12.15, lower quartile 9.18, upper quartile 15.74). Our study showed clear differences between inflamed and normal bowel wall vascularity regarding all perfusion parameters. These results show that a quantitative assessment of the bowel wall vascularisation and inflammation, respectively, is possible. The software used here enables us to collect data, not only in a semi-quantitative but also in a reproducible, quantitative manner which is comparable with the evaluation of CT or MRI generated data.

Image fusion with volume navigation of contrast enhanced ultrasound (CEUS) with computed tomography (CT) or magnetic resonance imaging (MRI) for post-interventional follow-up after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinomas (HCC): Preliminary results

AIM The assessment of the immediate post-interventional microcirculation and perfusion following transcatheter arterial chemoembolization (TACE) with new real time imaging fusion technique (VNav) of computed tomography (CT) or magnetic resonance imaging (MRI) with contrast enhanced ultrasound (CEUS) compared to follow-up. MATERIAL Following TACE an image fusion of CEUS with CT or MRI of the liver was performed in 20 patients (18 men, 2 women; age 29-75 years) with confirmed hepatocelluar carcinoma (HCC) to evaluate the post-interventional tumor vascularization and perfusion of HCC tumor lesions. Image fusion with CEUS performed immediately was compared with the result at the end of TACE (DSA), with post TACE CT (non-enhanced CT within 24 hours) and with follow up CT (enhanced CT after 6 weeks) after embolization. Ultrasound was performed using a 1-5 MHz multifrequency SonoVue transducer (LOGIQ 9/GE) after a bolus injection of 2-4ml SonoVue® with contrast harmonic imaging (CHI). Thirteen examinations were fused with a contrast enhanced CT, 7 with a MRI performed before TACE. RESULTS The post-interventional volume navigation image fusion of CT or MRI with CEUS showed differences regarding the residual tumor perfusion compared to other modalities. The correlation (Spearman-test) between the perfusion result at the end of TACE, non-enhanced CT after TACE and image fusion with CEUS was 0.42 and 0.50. The difference between the result at the end of TACE and the fusion with CEUS was significant (p < 0.05, Wilcoxon-test). The correlation between fusion of CEUS with CT/MRI and follow-up CT (after 6 weeks) was 0.64, the difference was not significant (p > 0.05). The differences between native CT within 24 hours after TACE and follow up CT after 6 weeks or fusion of CEUS and CT/MRI were significant (p < 0.05). The inter-observer variability was 0.61 at the end of TACE, 0.58 at non-enhanced CT (within 24 hours), 0.87 at fusion CEUS with CT/MRI and 0.74 at follow up CT after 6 weeks (Cohens Kappa test). CONCLUSION Image fusion with volume navigation (VNav) of CEUS with CT or MRI allows an accurate localisation of foci in patients with HCC. This exact mapping permits an easier control and evaluation of the results after TACE. The fusion of CEUS and CT or MRI allows a better evaluation of the microcirculation and the residual tumor perfusion at an earlier point of time than usual modalities of therapy control like non-enhanced CT. This might lead to a more differentiated monitoring of therapy.

Comparison between a clinical activity index (Harvey–Bradshaw-Index), laboratory inflammation markers and quantitative assessment of bowel wall vascularization by contrast-enhanced ultrasound in Crohn's disease

PURPOSE Due to its character as a remitting inflammatory disease, patients suffering from Crohns disease (CD) often undergo several imaging studies subjecting the mostly young patients to ionizing. Contrast enhanced ultrasound for capillary microvascular assessment might be a new diagnostic tool for identifying the activity of inflammation by ultrasound techniques. MATERIALS AND METHODS We prospectively evaluated 45 patients with proven Crohns disease performing contrast enhanced ultrasound (CEUS) and laboratory assessment including C-reactive protein (CRP), leucocytes and hematocrit as well as calculating the Harvey-Bradshaw Index (HBI). Thereafter, we applied the quantification software Qontrast(®) to obtain contrast-enhanced sonographic perfusion maps. RESULTS Analysis of the 41 finally included patients revealed a correlation of CRP to HBI and TTP[s], respectively. Moreover, an association was found for HBI and TTP[s] and for HBI and TTP[s]/Peak [%]. Analysis of 34 patients with a Peak [%] ≥ 25 showed a close association of HBI and CRP. Besides, in these patients CRP correlated to TTP[s] and to TTP[s]/Peak [%]. We found a strong negative correlation between HBI and TTP[s] (r = -0.645, p<0.01), thus, the higher the clinical activity the shorter the time-to-peak. CONCLUSION Quantitative evaluation with CEUS, particularly the calculation of TTP[s] in patients with a Peak [%] ≥ 25, provides a simple method to assess the inflammatory activity in CD.

Comparison between quantitative assessment of bowel wall vascularization by contrast-enhanced ultrasound and results of histopathological scoring in ulcerative colitis.

PurposeIn ulcerative colitis (UC), endoscopic methods are preferred for assessment of extent and activity of disease. Due to the invasive nature of endoscopical examinations, replacement by other, reliable imaging procedures would be helpful. Contrast-enhanced ultrasound (CEUS) in combination with perfusion assessment using a specific quantification software might be such a new diagnostic tool. Thus, we compared the findings of CEUS with the results of endoscopically taken specimens applying a histopathological scoring system.MethodsWe prospectively evaluated 15 patients with proven UC undergoing endoscopy. CEUS was performed and the quantification software Qontrast® applied to obtain contrast-enhanced sonographic perfusion maps. Moreover, in each patient C-reactive protein (CRP) was measured and taken biopsies were assessed using an advanced scoring system. Four patients had to be excluded from final analysis.ResultsThere was a trend to higher Peak (%) values with increasing histological inflammation. Furthermore, a strong negative correlation between the ratio TTP (s)/Peak (%) (Spearman’s correlation r = −0.761, p < 0.01) was found. There was no significant relationship between CRP and histopathological scoring or CEUS parameters, respectively.ConclusionQuantitative evaluation with CEUS, particularly the calculation of the ratio TTP (s)/Peak (%), provides a simple method for assessment of inflammatory activity in UC.

Innovations in contrast enhanced high resolution ultrasound improve sonographic imaging of the intestine

The aim was to describe the perfusion pattern of the inflamed bowel wall and the surrounding tissue in inflammatory bowel disease and diverticulitis of the sigmoid colon applying a high resolution matrix transducer and the new hybrid technique. We performed contrast enhanced ultrasound (CEUS) using an updated version of the 1-5 MHz (C1-5-D convex probe) and the 6-9 MHz probe (9L-D linear probe) as well as a matrix 6-15 MHz transducer (ML 6-15-D Matrix Array Linear Probe) and updated post-processing procedures to examine microvascularization of inflamed bowel wall in Crohns disease (11 patients), ulcerative colitis (1 patient) and diverticulitis of the sigmoid colon (2 patients). Assessment of mural microvascularization was successful as well as identification of fistulas (2 patients) and covered perforation (1 patient). Moreover analysis of time intensity curves revealed increase of signal intensity up to 20 dB. Summarizing, application of high resolution linear probes and use of updated post-processing methods substantially improve detection of inflammation-caused increased microcirculation of the bowel wall and the surrounding tissue as well as identification of complications as fistulas or covered perforations.

Semiquantitative characterization of hepatocellular carcinoma (HCC) – perfusion with contrast-enhanced ultrasound and perfusion analysis

BACKGROUND At the moment, there is only poor specificity of HCC-detection in tumors smaller than 2 cm in a cirrhotic liver. Thus, efforts have to be made to optimize the distinction between regenerative nodules and HCC. AIMS The aim of our study was to describe the particular perfusion pattern of hepatocellular carcinoma using a specific quantification software. METHODS We evaluated 25 patients with proven hepatocellular carcinoma, who underwent dynamic contrast-enhanced ultrasound (CEUS) using a second generation contrast agent (SonoVue, Bracco, Germany). Retrospectively, we applied the quantification software Qontrast (Bracco, Milan, Italy) to obtain contrast-enhanced sonographic perfusion maps for each lesion. RESULTS We found a close positive correlation of the perfusion parameters peak, time-to-peak and regional blood volume between the entire tumors, the center (center/total) and the periphery of the tumors (periphery/total), respectively. Moreover, we found significant higher peak values, a significant higher regional blood volume and a trend to lower time-to-peak in the center of the tumors compared to the tumor periphery. CONCLUSION These results suggest a better established vascular bed in the center of the tumors. This could be a sonographic marker of HCC in contrast to regenerative nodules.

Tumor-Induced Osteomalacia: Increased Level of FGF-23 in a Patient with a Phosphaturic Mesenchymal Tumor at the Tibia Expressing Periostin.

In our case, a 45-year-old male patient had multiple fractures accompanied by hypophosphatemia. FGF-23 levels were significantly increased, and total body magnetic resonance imaging (MRI) revealed a tumor mass located at the distal tibia leading to the diagnosis of tumor-induced osteomalacia (TIO). After resection of the tumor, hypophosphatemia and the increased levels of FGF-23 normalized within a few days. Subsequent microscopic examination and immunohistochemical analysis revealed a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) showing a positive expression of somatostatin receptor 2A (SSTR2A), CD68, and Periostin. Electron microscopy demonstrated a poorly differentiated mesenchymal tumor with a multifocal giant cell component and evidence of neurosecretory-granules. However, the resected margins showed no tumor-free tissue, and therefore a subsequent postoperative radiotherapy was performed. The patient is still in complete remission after 34 months. Tumor resection of PMTMCTs is the therapy of choice. Subsequent radiotherapy in case of incompletely resected tumors can be an important option to avoid recurrence or metastasis even though this occurs rarely. The prognostic value of expression of Periostin has to be evaluated more precisely in a larger series of patients with TIO.

Low Risk of Clostridium difficile Infections in Hospitalized Patients with Inflammatory Bowel Disease in a German Tertiary Referral Center

Introduction: Many reports, mainly from the US and Canada but also a recent report from a center in Europe, have documented the increasing impact of Clostridium difficile infections in patients with inflammatory bowel disease (IBD) during the last years. To determine the prevalence of C. difficile infections in hospitalized IBD patients in a tertiary referral center in Germany, we conducted this retrospective analysis. Methods: Data of all IBD in-patients treated due to an acute flare of their IBD at the Department of Internal Medicine I of the University of Regensburg between January 1, 2001, and June 30, 2008, were analyzed. In patients with a concomitant diagnosis of C. difficile infection, further variables such as IBD-related treatment at the time of infection or outcome were examined. Results: In total, 995 in-patients with IBD were treated in this hospital [638 patients with Crohn’s disease (CD), 357 with ulcerative colitis (UC)] during the study period. Of these, 279 patients with CD and 242 patients with UC were admitted with an acute flare and suffering from diarrhea and abdominal pain. Only 10 of those were diagnosed as having a concomitant infection with C. difficile. Six patients were female and the median age was 49 years (range: 15–80). Six patients with C. difficile infections suffered from UC and 4 patients from CD, all with previous colonic involvement. Eight patients used immunosuppressive therapies; only 2 patients were treated with antibiotics before infection. Conclusion: In contrast to recent reports from other countries, only a low percentage of hospitalized patients with acute flares of their IBD were identified as having an underlying C. difficile infection in this German tertiary referral center. However, in IBD patients with an acute flare, a concomitant C. difficile infection should be excluded, especially in patients with immunosuppressive treatment and colonic involvement of their disease. Further research is needed to evaluate if regions with different risks of C. difficile infections exist and to find out more about potential reasons for this observation.

Clinical Feature and Bowel Ultrasound in Crohn’s Disease – Does Additional Information from Magnetic Resonance Imaging Affect Therapeutic Approach and When Does Extended Diagnostic Investigation Make Sense?

Background/Aims: Some suggest MRI to be superior to ultrasound in Crohn’s disease. We analyzed how often MR enterography (MRE) following a routine ultrasound leads to a change in therapeutic decision. Material and Methods: We retrospectively evaluated 47 patients with Crohn’s disease undergoing routine ultrasound examination. Actual medical history, complete blood count, C-reactive protein (CRP), and sonographic findings were assessed independently by two specialists who retrospectively provided a therapeutic proposal. Additionally, all patients received MRE. Thereafter, the specialists had to provide a new therapeutic concept regarding all the available information. Results: Evaluation of the rectum was not successful by ultrasound, but MRE gave good results. Only 1 of 7 abscesses was identified sonographically. Three of the abscesses missed at sonography were localized in the perirectal/perianal region. MRE detected more inflamed bowel segments, but ultrasound assessment of anatomically fixed bowel parts showed good recognition by MRE. With increasing CRP values, we found more positive results of ultrasound and MRE. Therapeutic change was suggested in only 18 patients. Conclusions: Ultrasound should be performed by an experienced examiner, and a proctological examination should be added. MRE is justified in cases of discrepancy between clinical findings and the results of diagnostic ultrasound and, moreover, if Crohn’s lesions are suspected at sites proximal to the terminal or neoterminal ileum.

Transabdominal Ultrasound with Echoenhancement by Contrast Media in the Diagnosis of Hepatocellular Carcinoma

According to the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), ultrasound (US) is the recommended tool for surveillance of patients at risk of developing hepatocellular carcinoma (HCC). Larger HCCs can be diagnosed with a high accuracy by conventional US. However, the differentiation of smaller malignant lesions in cirrhotic livers can be improved by contrast-enhanced ultrasound (CEUS). Second-generation contrast agents consisting of microbubbles enable us to visualize specific tumor vascularization patterns. With CEUS, it is not only possible to detect and characterize HCC nodules, but to control the effects of ablation techniques of HCC as well, evaluating the former lesion with respect to complete necrosis or residual viable tumor. Limitations of CEUS are its inability to characterize lesions distant to the applicator. Moreover, so far the use of contrast agents in US did not result in increased sensitivity in the detection of small HCCs (<1 cm). Thus, there is currently no indication to use contrast agents to increase the detection rate of HCC in patients undergoing US surveillance.