Imaging Kidney Transplant Rejection Using Ferumoxytol-Enhanced Magnetic Resonance

In children with kidney transplants, immunologically mediated rejection is the major cause of
allograft failure. Thus, the therapeutic success of kidney transplants is highly dependent on
the ability to avoid rejection during both the acute and chronic phase after transplantation.
Children with kidney transplants currently undergo at least three routine (protocol) biopsies
during the first two years after the transplantation in addition to biopsies required to
investigate deterioration of kidney function. These biopsies are invasive and nearly always
require general anesthesia, causing anxiety and distress of the patients and their parents,
as well as significant costs to our health care system. There is currently no non-invasive
diagnostic tool capable of detecting rejection in vivo. Thus, the goal of this study is to
develop a non-invasive imaging test for in vivo detection of kidney transplant rejection. The
investigators propose to accomplish this goal by detecting macrophage infiltration in kidney
transplants with iron oxide nanoparticle-enhanced MR imaging. Macrophages play a major role
in transplant rejection. CD68-positive macrophages comprise approximately 50% of the
infiltrating leukocyte population in renal allograft rejection, they co-localize with areas
of tissue-damage and fibrosis, and are preponderant in more severe forms of rejection. The
investigators hypothesize that iron oxide nanoparticle-enhanced MR imaging can detect
differences in macrophage infiltrations in renal allografts undergoing rejection as opposed
to allografts without significant rejection. This hypothesis is based on the bio-physical
properties of intravenously injected superparamagnetic iron oxide nanoparticles, which are
phagocytosed by tissue macrophages and cause strong signal effects on MR images.

The specific aims of the study are the following:

Aim #1. Technical Development of a Quantitative Susceptibility Mapping (QSM)-Sequence for in
vivo MRI detection and quantification of iron oxide nanoparticle-labeled macrophages.This aim
will focus on the technical development of Quantitative Susceptibility Mapping (QSM), a novel
MR imaging pulse sequence that will be used to accurately quantify the tissue concentration
of free ferumoxytol and ferumoxytol in macrophages in renal allografts. Based on pulse
sequence optimizations of phantoms with known concentrations of free and cell-bound iron, we
expect to generate accurate estimates of tissue iron concentrations and macrophages with the
QSM-MRI method.

Aim #2. Detect rejection in kidney allografts with ferumoxytol-enhanced MRI. The
investigators hypothesize that ferumoxytol can detect and quantify macrophages in kidney
allografts, based upon the observation that iron oxide nanoparticles can be taken up by
macrophages in malignant tumors. The investigators will evaluate the ability of ferumoxytol
to map macrophage quantities in renal allografts, with histopathological correlation. We
expect significantly higher ferumoxytol-MRI enhancement and macrophage quantities in rejected
allografts compared to non-rejected allografts.

Inclusion Criteria:

- Completed solid organ transplant with referral for transplant follow-up

Exclusion Criteria:

- Exclusion criteria comprise MR-incompatible metal implants, need of sedation (since an
anesthesia is not supported by this), claustrophobia or hemosiderosis/hemochromatosis.