MRI molecular imaging of (inflammatory) macrophages as a predictor of abdominal aortic aneurysm progression

A prominent histological feature of abdominal aortic aneurysm (AAA) is the
transmural infiltration of macrophages and lymphocytes. Inflammation of the
aortic wall and the progression of AAA are closely related. Early
identification of inflammation could aid in the identification of a subset of
AAA patients in need of close monitoring and medical therapy. Conversely,
patients with little inflammation (stable AAA) could be spared from either
medical or surgical treatment, till later date.
Based on our experience with USPIO enhanced MR, AAA wall stress analysis and
the knowledge of AAA wall components we hypothesize that: I. The degree and
distribution of the inflammation of the abdominal aortic wall in patients with
AAA is - as visualized with USPIO-enhanced MR - related to AAA progression. II.
The degree of the inflammation of the abdominal aortic wall of patients with
AAA is related to systemic inflammatory markers in peripheral blood. III Based
on the USPIO enhanced MR and or systemic inflammatory markers we will be able
to differentiate patients with stable or slowly growing AAA from patients with
rapidly progressive AAA. IV. The distribution of the inflammation is related to
the distribution of the wall stress.

I. The main objective of our study is to differentiate between patients with
stable or slowly growing AAA from patients with rapidly growing AAA. We believe
that inflammation is a major player in the process of growth. In order to
achieve our main objective we need to relate the individual degree and
distribution of the inflammation of the AAA wall to specific growth rate and
patterns. Inflammation will be visualized by means of USPIO-enhanced MR. II.
Secondary objectives are to associate the degree and distribution of the
inflammation of the abdominal aortic wall of patients with AAA with (i)
systemic markers of inflammation, and (ii) the distribution of the wall stress.

Observational follow-up study

The timescale of our protocol is identical to the normal follow up regimen of
patients with small AAA. The exposure of these patients to bi-annual CTA
imaging is considered safe with regards to the exposure to radiation. The
contrast medium (Iodine) used is routinely used and has been shown to rarely
generate anaphylactic response and/or shock. Mild symptoms are seen in less
than 1% of all cases and severe symptoms are rare. The use of a 64-slice
machine ensures minimal contrast dosage. Patients with severe renal dysfunction
will be excluded (eGFR < 30). With regards to the USPIO, we are fortunate to
have the experience of the team members of the department of Radiology with the
USPIO (Sinerem®, Guerbet, Paris). No adverse events were observed in the
carotid artery plaque study. Sinerem is well-tolerated in human subjects and
has minimal side-effects. The preclinical pharmacokinetic and safety profile of
ferumoxtran-10 appears to be satisfactory in view of its proposed use as a
single-dose diagnostic agent in human for MR imaging of lymph nodes. (Bourrinet
et al. Invest Radiol. 2006 Mar;41(3):313-24.)