Detection of liver metastases in cancer patients with geographic fatty infiltration of the liver: the added value of contrast-enhanced sonography

The aim of this study is to assess the role of contrast-enhanced ultrasonography (CEUS) in the detection of liver metastases in cancer patients with geographic liver fatty deposition on greyscale ultrasonography (US)

Microbubbles in vascular imaging

Ultrasound is integral in diagnostic imaging of vascular disease. It is a common first line imaging modality in the detection of deep vein thrombosis (DVT) and carotid atherosclerosis. The therapeutic use of ultrasound in vascular disease is also clinically established through ultrasound thrombolysis for acute DVT. Contrast agents are widely used in other imaging modalities, however, contrast enhanced ultrasound (CEUS) using microbubbles remains a largely specialist clinical investigation with truly established roles in hepatic imaging only. Aim The aim of this thesis was to investigate diagnostic and therapeutic roles of CEUS in vascular disease. Diagnostically, carotid plaque characteristics were evaluated for stroke risk stratification in patients with carotid atherosclerosis. Therapeutically, microbubble augmented ultrasound thrombolysis was investigated in-vitro as a novel technique for acute thrombus removal in the prevention of post thrombotic syndrome. Methods A validated in-vitro flow model of DVT was adapted and developed for a formal feasibility study of microbubble augmented ultrasound thrombolysis. Two cross sectional studies of patients with 50-99% carotid stenosis were performed assessing firstly, plaque ulceration and secondly plaque perfusion using CEUS. Results Using commercially available microbubbles and ultrasound platform, significantly improved thrombus dissolution was demonstrated using CEUS over ultrasound alone in the in-vitro flow model of acute DVT. In particular, increased destruction of the thrombus fibrin mesh network was observed. CEUS demonstrated greater sensitivity than carotid duplex in the detection of carotid plaque ulceration with a trend toward symptomatic carotid plaques. A reduced plaque perfusion detected by both semi-qualitative and quantitative analysis was associated with a symptomatic status in patients with a 50-99% stenosis. Conclusion CEUS is a viable adjunct to vascular imaging with ultrasound. Microbubble augmented ultrasound thrombolysis is a feasible, non-invasive, non-irradiating intervention which warrants further investigation in-vivo. Carotid plaque CEUS may contribute to future scoring systems in stroke risk stratification but requires prospective validation.Open Acces

Solid benign liver tumours : biological behaviour and management

In this thesis, the diagnosis and treatment of benign solid liver lesions is beiing studied. Among these, focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) may offer the most challenge in management in daily clinical practice. We have investigated that FNHs might grow but that this has no complications and surgery is not indicated. In addition, we have looked at hepatocellular adenoma (HCA)

Ultrasonographic evaluation of disease activity in Crohn’s Disease

Background: Crohn's disease (CD) is a chronic inflammatory disorder in the gastrointestinal (GI) tract, characterized by alternating periods of remission and relapse. Patients’ symptoms do not reliably represent inflammatory activity and management should be based on objective evaluation. Currently, ileocolonoscopy is the established reference standard method for both diagnosis and monitoring disease activity in most cases, but holds several limitations restricting repeated use. Consequently, there is a need for safe, objective and accurate methods to measure the degree of inflammation and treatment response. Gastrointestinal ultrasound (GIUS) is a promising modality in assessing disease activity and may be a useful tool for aiding physicians improving treatment decisions. Aims: The primary objective of the PhD project was to examine the usefulness of ultrasound in evaluating disease activity in patients with Crohn’s disease. Specifically, we aimed to investigate the ability of Dynamic Contrast-Enhanced Ultrasound (DCE-US) to provide information of treatment effects (paper I), to assess the diagnostic accuracy of GIUS in separating endoscopic remission from active disease (paper II), and to construct and validate a simple ultrasonographic activity index to quantify disease activity (paper III). Material and Methods: In paper I, 14 CD patients receiving medical therapy due to an acute exacerbation were examined with conventional- and contrast-enhanced ultrasound at four time points. In paper II, 145 CD patients scheduled for ileocolonoscopy were prospectively examined with GIUS within 2 weeks prior to or after the endoscopic procedure. The Simple Endoscopic Score for Crohn’s disease (SES-CD) was used as a reference standard. In paper III, 164 patients scheduled for ileocolonoscopy were prospectively examined with GIUS, identically performed as in paper II. 40- and 124 CD patients were included in the construction- and validation cohorts, respectively. Results: In paper I, we found significant differences in relative perfusion between responders and non-responders one month after treatment start. As a secondary finding, differences in bowel wall layers were revealed, where the proper muscle- and submucosal layers were significantly thicker in non-responders at one and three months after treatment initiation, respectively. In paper II, we found that bowel wall thickness measurements on GIUS had 92.2% sensitivity, 86% specificity and 90.3% accuracy in separating the disease status. By adding color Doppler in sections with increased wall thickness and fecal calprotectin in sonographic colitis, the diagnostic accuracy improved. In paper III, we developed a simplified ultrasound score consisting of bowel wall thickness and color Doppler. The ultrasound score correlated well with SES-CD in both patient cohorts (Development cohort: r=0.83, p<0.001, Validation cohort: r=0.78, p<0.001), and revealed excellent interobserver agreement (Development cohort: ICC=0.95.Validation cohort: ICC=0.90). Conclusions: We conclude that ultrasound is able to differentiate between patients with endoscopic remission and active disease, and a simple ultrasonographic scoring system is useful to evaluate the degree of endoscopic disease activity in CD. Furthermore, GIUS enables prediction of treatment effect shortly after treatment start, thus improving treatment decisions