Systematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases

Abstract

Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration.

Keywords: Alzheimer's disease; Parkinson's disease; brain; iron; neurodegenerative diseases; quantitative susceptibility mapping.

Figure 1

PRISMA flow diagram for inclusion of records (Moher et al., 2009).

Figure 2

Parkinson's disease: Effect sizes for the intergroup differences of magnetic susceptibility in the SN, SNr, and SNc between PD and healthy groups. Red bars indicate significantly higher susceptibility in the patient group, while green color shows a non-significant difference.

Figure 3

Parkinson's disease: Effect sizes for the intergroup differences of magnetic susceptibility in the RN between PD and healthy groups. Red bars indicate significantly higher susceptibility in the patient group, while green color shows a non-significant difference.

Figure 4

Amyotrophic lateral sclerosis: Effect sizes for the intergroup differences of magnetic susceptibility in the motor cortex between ALS and control groups. Red bars indicate significantly higher susceptibility in the patient group, while green color shows a non-significant difference.

Figure 5

Wilson's disease: Effect sizes for the intergroup differences of magnetic susceptibility in the basal ganglia between WD and healthy groups. Red bars indicate significantly higher susceptibility in the patient group, while green color shows a non-significant difference.

Figure 6

Huntington's disease: Effect sizes for the intergroup differences of magnetic susceptibility in the basal ganglia between HD and control groups. Red bars indicate significantly higher susceptibility in the patient group.