Ultrasound - Crohn's Disease
Can Ultrasound using microbubbles as contrast detect and monitor changes in areas of inflammed bowel in patients with Crohn's disease?
Overview:
Crohn’s disease is a chronic inflammatory condition of the bowel, predominately affecting the young and requiring lifelong medical and often surgical therapy. The natural history of the disease is one of intermittent acute exacerbations characterised by an acute inflammatory response, separated by periods of relative quiescence. Medical therapy is based largely on immunosuppressive medication. Although relatively effective, these drugs are not without significant side effects, some of them life threatening, notably sepsis secondary to immunosuppression. Newer immuno-modulating agents such as anti-TNF medication have been shown to be effective in patients with severe disease refractory to first line therapy. However two weeks after initial treatment only around 50-60% of recipients respond to anti TNF therapy, a figure dropping to below 50% after 30 weeks, despite repeated dose. Furthermore such agents are expensive, require intravenous or subcutaneous administration and are not without additional significant side effects including anaphylaxis, and fatal infections, and have been linked to future malignancies, particularly lymphoma.
Rational use of such immunosuppressive therapies in Crohn’s disease therefore relies on accurate identification of those patients who will benefit most from treatment. In routine clinical practice, anti-TNF therapy is often administered initially over 3 doses, each separated by two to four weeks, with patients usually undergoing a full 6 weeks course before a final judgement is made regarding treatment efficacy. At the present time this judgement is usually made by assessing the clinical response of patients using symptom based questionnaires such as the Crohn’s disease activity index. Such clinical assessments based on patient symtomatology are relatively subjective, and patients with inactive disease (such as those with chronic fibrotic strictures) often attract high scores. Biochemical markers such as ESR and CRP are useful adjuncts but again do not in themselves always correlate with disease activity.
Ideally it would be possible to predict which patients with luminal Crohns disease will respond to anti-TNF therapy before the medication is given. However even if an accurate judgement of efficacy could be made after the first dose of medication, this would be a significant advantage, potentially sparing non-responders a further two doses from which they are destined to receive no benefit. In the absence of an external marker such as active entero-cutaneous fistula, neither clinical assessment nor biochemical markers are sufficiently accurate to make this early assessment, but radiological techniques notably MRI and ultrasound hold considerable promise as alternatives.
It is known that active Crohn’s disease is associated with changes in mural vascularity and assessment of mural blood flow using Doppler ultrasound has been shown to correlate with disease activity. However, although subjective assessment of mural vascularity using Doppler is simple, the technique is somewhat limited due to relatively low blood flow within bowel wall, which may be undetectable using conventional Doppler ultrasound settings, even if pathologically increased.
Intravenously administered ultrasound contrast agents are widely used in routine radiological practice to improve the detection and characterisation of vascular phenomena within various organs, including the small bowel. Such agents consist of tiny “microbubbles” which augment the Doppler signal of flowing blood and increase the sensitivity of Doppler ultrasound in low flow states. The agents, which have a proven safety record, enter the vascular pool after intravenous administration before being excreted via the lungs after a few minutes. New analysis software also now also allows quantification of mural blood flow within a defined region of interest.
The purpose of this study will be to measure and quantify changes in bowel wall blood flow using contrast enhanced ultrasound in patients with active Crohn’s disease undergoing Infliximab therapy, and assess whether measured changes can predict ultimate response to treatment.
Primary Study Aims:
- Using anatomical and contrast-enhanced ultrasound, document and quantify the effect of anti-TNF medication on mural morphology and blood flow.
- Correlate anatomical and contrast-enhanced ultrasound derived changes in mural morphology and blood flow with clinical and biochemical markers of response to anti-TNF medication.
- Investigate whether contrast-enhanced ultrasound derived changes in mural blood flow can predict ultimate clinical response to medication.
Secondary Study Aims:
- Re-affirm the correlation between anatomical and contrast-enhanced ultrasound derived changes in mural morphology and blood flow with clinical and biochemical markers of disease activity.
- Investigate whether anatomical and contrast-enhanced ultrasound derived mural morphology and blood flow before commencement of anti-TNF therapy can predict ultimate clinical response.