• New QSM acquisition methods are being developed that are less prone to motion artifacts often observed in pediatric population.

• QSM are being used in studying iron loading, and white matter myelination.

• Emerging applications of QSM include the evaluation of pediatric patients with brain tumors, sickle cell disease, and thalassemia diseases among others.

MRI physicist and radiologists interested in applying QSM in pediatric population.To learn motion problems associated with pediatrics population, and techniques to mitigate these problems, to learn current applications of QSM in clinical population.

Quantitative susceptibility mapping (QSM) is a recently developed MR technique that can estimate the magnetic susceptibility distribution [1-4]. The magnetic field is measured from the phase image of a gradient echo sequence, and a series of image processing steps was performed including multiple coil combination, phase unwrapping and dipole field deconvolution. Technical advances in all the steps involved have enabled to enable clinical translation of this method.

In additional to common technical challenges associated with QSM, its application in pediatric patients has to cope with more severe motion artifacts often found in this population. Since QSM builds on the same MRI sequences used for susceptibility-weighted-imaging (SWI), previous novel MRI sequences developed for SWI can be similarly applied to QSM. Holdsworth SJ et al. [5] showed that short-axis propeller echo planar imaging (SAP-EPI) can be used to reduce the scan time and the sensitivity to patient movement. However, the SAP-EPI sequence suffers from geometric distortion associated with every EPI based sequence, and this drawback should be weighted when considering the choice of protocol, particularly for patients who recently undergo surgeries and have surgical cavities.

The major sources of magnetic susceptibility contrast in the brain originate from the deposition of different forms of iron deposition and the myelin of white matter. Iron contents are para- or ferromagnetic and have positive magnetic susceptibility value, whereas myelin is diamagnetic and has negative magnetic susceptibility value. QSM is therefore sensitive to pathological processes that alters the iron contents or white matter myelination, such as when there are microbleeds or demyelination. The evaluation and interpretation of QSM should be done in the context of normal development, particularly for pediatric populations. In the early years of age, there are rapid changes of brain microstructures, including the myelination of white matter and gradual deposition of iron in the cortex and deep brain nuclei. A study of susceptibility change across the lifespan showed that the susceptibility value of white matter decreased exponentially while the susceptibility value of many cortex and deep brain nuclei increased exponentially with age with many structures reaching their stabled values between the mid twenties and mid-thirties [6]. Although deep nuclei, such as the globus pallidus, the putamen and the caudate nuclei, are commonly found to have high susceptibility values in adults suggesting high iron content, it is shown that there is little contrast between these nuclei and white matter at the first year age of life. At fifth year of age, the visual contrast of deep brain nuclei approaches that of adults showing high iron deposition in these regions, however the internal and external parts of the globus pallidus can be easily differentiated in contrast to those of adults. These unique features of pediatric brain should be recognized and not be misinterpreted as pathological. More studies with larger sample size in the early ages are warranted to depict a more comprehensive picture of the developmental processes.

Clinical applications of QSM in pediatric population are being explored. QSM has been used to study brain iron loading in a group of patients with sickle cell disease as compared to normal controls [7]. Pediatric sickle cell disease patients with high cerebral blood flow receive chronic blood transfusion to reduce the risk of stroke. As a result they suffer from systematic iron overload that affects multiple organs. The quantification of iron loading in their brain can help shed lights on the cognitive problems associated with these patients. The study found a significant correlation of susceptibility value of many deep brain structures with age. After controlling for the effect of age, significantly higher susceptibility values were found in the patient group in choroid plexus, red nucleus and dentate nucleus, suggesting high iron loading in these regions. Similarly, another study in patients with thalassemia patients who need blood transfusion showed significantly higher iron concentration in the choroid plexus [8]. QSM has also been used to study the complex structure of microbleeds and calcification in the tumor bed in pediatric patients [2]. A positive association between iron concentration in the basal ganglia as measured by QSM and spatial IQ has been established by a recent study [9].

In conclusion, QSM provides a unique image contrast that adds insights to the study of normal brain development and provides another sensitive tool for studying much pathology in pediatric population.