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Investigating Diffusion Tensor Imaging as a Non-Invasive
Biomarker of Pediatric Kidney Transplant Health
Jesse Courtier, MD, and Marsha Lee, MD
Background
In children with end-stage renal disease, kidney transplantation
is the preferred choice for therapy, with overall lower
long-term morbidity and mortality compared with dialysis.
Annually, approximately 800 renal transplants are performed
in the United States in children under 18 years of age.
The monitoring of kidney transplant function in pediatric
recipients is critical to optimize the longevity of their
transplants and therefore their overall quality of life. Transplant
rejection, however, cannot be easily determined
using routine renal function laboratory tests such as BUN,
serum creatinine or calculated eGFR, since rejection can
be present even when these values are normal. Thus, renal
transplant biopsies are routinely performed to screen for
subclinical rejection and to evaluate for rejection in cases of
elevated serum creatinine.
Preliminary work has demonstrated the potential of
magnetic resonance diffusion tensor imaging (MR-DTI) with
quantified measurement of fractional anisotropy (FA) as
a non-invasive method of assessing renal allograft function.
Primarily used in neuroimaging, diffusion-weighted
imaging (DWI) takes advantage of the differences between
water molecular motion (Brownian motion) within various
anatomic structures to generate contrast. In general, water
molecules with restricted motion (e.g., within nerve tracts)
appear hyper-intense compared to water molecules that are
in free space (e.g., CSF). Diffusion tensor imaging (DTI) further
assesses the directionality of water molecular motion.
This has been used to tremendous advantage in neuroimaging
where neuro-axonal tracts are longer than they are wide,
which results in anisotropic diffusive properties and thus
allows for mapping of specific axonal tracts (tractography).
Similar to the brain, renal tubular architecture exhibits a
high degree of anisotropy, which lends itself to assessment
by DTI. The “degree of straightness” of the renal architecture
can be quantified by measuring the FA within the kidney
transplant (Figure 1). It is postulated that processes such as
rejection lead to distortion of the normally highly organized
renal architecture, thus leading to measurable decreases
in the FA. This difference can also be seen visually with
tractography imaging (Figures 2A and 2B).
Figure 1 Processed Fractional Anisotropy map of a renal
transplant in a 17-year-old girl with regions of interest
placed in the renal medulla.
Current Research and Preliminary Findings
In a collaborative project of the UCSF Departments of
Radiology and Biomedical Imaging, Pediatrics (division
of Nephrology), Pathology, and GE Healthcare, this novel
application of DTI in pediatric kidney transplants is currently
being tested. Seed grants from the UCSF Department
of Radiology and Biomedical Imaging and the Society for
Pediatric Radiology provided funding. In this study, children
with kidney transplants underwent ultrasound-guided renal
transplant biopsy for either surveillance or “for-cause” (clinically
suspected rejection) indications. These children first
underwent MRI with DTI, followed by ultrasound-guided
biopsy of their renal transplants on the same day. Multiple
FA values were measured in the renal cortex and medulla
and compared to histopathologic results.
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