Diffusion-weighted MRI in Juvenile Idiopathic Arthritis

JIA is not a single disease, but a term that encompasses all forms of arthritis
that begin before the age of 16 years, persist for more than 6 weeks, and are
of unknown etiology and pathophysiology. Studies in developed countries have
reported a prevalence that varies between 16 and 150 per 100.000. Therefore, it
is the most common chronic disease in childhood and represents one of the
leading causes of pediatric acquired disability. It is characterized by
prolonged synovial inflammation that can lead to destruction of joints, pain
and loss of function. The increasing evidence that early therapeutic
intervention improves long-term outcome and the development of highly effective
treatments highlight the need for objective and accurate measures in the
assessment of disease activity, individual response to therapy, efficacy of
treatment and longer term outcomes in JIA.

Current measures used to assess disease activity in JIA largely rely on
unreliable clinical symptoms, joint examination findings, and laboratory
measures, and are not accurate in the evaluation of inflammatory disease in
JIA. Within the past 10 years, the use of magnetic resonance imaging (MRI) and
advances in MRI techniques have substantially improved the evaluation of joint
pathologies in JIA patients. To date, contrast-enhanced MRI is the most
sensitive imaging modality for the assessment of synovial hypertrophy, the most
critical hallmark of disease activity in JIA, as well as in the detection of
destructive changes of cartilage and bone. Contrast-enhanced MRI is MRI with
the use of an intravenous contrast agent (Gd). Gd facilitates better
differentiation between joint effusion and synovial hypertrophy through better
visualization of the hypervascularity of the inflamed synovial membrane,
reflecting ongoing inflammation. However, the use of Gd markedly prolongs the
examination time and increases costs and patient discomfort, due to longer
examination time and the risk of allergic reactions to the intravenous contrast
agent, which may further reduce the feasibility of MRI in pediatric JIA
patients. Therefore, the development of new non-invasive MRI techniques which
can be used for the evaluation of early inflammatory changes in JIA is
warranted. Diffusion-weighted MR Imaging (DWI) is such a non-invasive
technique.

DWI makes use of the random movement of water molecules. In a totally
unrestricted environment, water movement would be completely random: Brownian
motion or free diffusion. Within tissues, the movement of water is not
completely random, but hampered by interaction with tissue compartments, cell
membranes, and intracellular organelles. The extent of tissue cellularity and
the presence of intact cell membranes help determine the impedance of water
molecule diffusion. Tissue types that have been reported to be associated with
impeded diffusion include tumor, cytotoxic edema, abscess, and fibrosis.
Tissues with low cellularity or that consist of cells with disrupted membranes
permit greater movement of water molecules. DWI is primarily used in neurologic
and oncologic diseases, though it can be used for evaluating musculoskeletal
pathology. In adults it has been demonstrated that DWI preformed as well
contrast-enhanced MRI in the evaluation of synovial hypertrophy. Therefore we
hypothesized that DWI can be used for the evaluation of disease activity in JIA
patients.

Primary objectives are:

To assess the diagnostic accuracy of DWI in the evaluation of disease activity
in JIA as compared to contrast-enhanced MRI as the reference standard.
To assess the accuracy of DWI in detecting joint inflammation as compared to
the physical examination in the evaluation of different stages of disease
activity in JIA patients.

Secondary objectives are:

To evaluate the correlation between DWI and semi-quantitative scores of
synovial hypertrophy using the Juvenile Arthritis MRI Scoring (JAMRIS) system
(at baseline and at two-year follow-up).
To evaluate the degree of association between DWI parameters and scores
obtained from the physical examination (at baseline and at two-year follow-up).
To evaluate the correlation between DWI parameters and laboratory assessments
of inflammatory parameters (at baseline and at two-year follow-up).
To evaluate the value of DWI in predicting the clinical course in 1 year time
in JIA patients.
To evaluate the responsiveness to change of DWI parameters.

Prospective observational

Patients will undergo a complete work-up comprising of clinical history,
physical examination, laboratory assessments, radiographs and an open-bore
MRI-scan with intravenous contrast medium as part of their clinical
investigation:
1. An additional diffusion-weighted MRI (DWI) sequence will be added to the
regular MRI scan (extra scan time 6 minutes)
2. Two tubes of blood will be taken during standard blood sampling.

At two-year follow-up, patients again will undergo a work-up comprising of
clinical history, physical examination, laboratory assessments, and an
open-bore MRI-scan with intravenous contrast medium as part of their clinical
investigation:
1. An additional diffusion-weighted MRI (DWI) sequence will be added to the
regular MRI scan (extra scan time 6 minutes)
2. Two tubes of blood will be taken during standard blood sampling.

No side-effects or risks have been reported on MR imaging, provided
containdications are taken into consideration.