No abstract

Quantitative susceptibility mapping (QSM) has enabled MRI of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM technology may be regarded to be sufficiently developed and validated to warrant wide dissemination for clinical applications of imaging isotropic susceptibility, which is dominated by metals in tissue, including iron and calcium. These biometals are highly regulated as vital participants in normal cellular biochemistry, and their dysregulations are manifested in a variety of pathologic processes. Therefore, QSM can be used to assess important tissue functions and disease. To facilitate QSM clinical translation, this review aims to organize pertinent information for implementing a robust automated QSM technique in routine MRI practice and to summarize available knowledge on diseases for which QSM can be used to improve patient care. In brief, QSM can be generated with postprocessing whenever gradient echo MRI is performed. QSM can be useful for diseases that involve neurodegeneration, inflammation, hemorrhage, abnormal oxygen consumption, substantial alterations in highly paramagnetic cellular iron, bone mineralization, or pathologic calcification; and for all disorders in which MRI diagnosis or surveillance requires contrast agent injection. Clinicians may consider integrating QSM into their routine imaging practices by including gradient echo sequences in all relevant MRI protocols.

Our objective was to analyze gene expression pattern in muscles from patients with amyotrophic lateral sclerosis (ALS) and multifocal motor neuropathy (MMN) compared to controls. Biopsied skeletal muscles from three ALS, three MMN and three control subjects had total RNA extracted and subjected to genome-wide gene expression analysis using Affymetrix GeneChip Exon 1.0 ST array. The most significant expression pattern differences were confirmed with RT-PCR in four additional ALS patients. Results showed that over 3000 genes were identified across the groups using q < 10%. Among 50 genes that were overexpressed only in the ALS group were: leucine-rich repeat kinase-2, follistatin, collagen type XIX alpha-1, ceramide kinase-like, sestrin-3 and CXorf64. No genes were significantly overexpressed in MMN alone. Underexpressed genes only in ALS included actinin α3, fructose-1,6-bisphosphatase-2 and homeobox C10; whereas only in MMN: hemoglobin A1 and CXorf64. Ankyrin repeat domain-1 was overexpressed in both groups. Underexpressed genes in both groups included myosin light chain kinase-2, enolase-3 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-1. Validation analysis using RT-PCR confirmed the data for leucine-rich repeat kinase-2, follistatin, collagen type XIX alpha-1, ceramide kinase-like, sestrin-3 and CXorf64. In conclusion, there is differential tissue-specific gene expression in patients with ALS relative to MMN and controls. Further studies are necessary to evaluate the identified genes in larger patient groups and different tissues.

Objective Diagnosis of amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) is often difficult due to absence of disease biomarkers. Our aim was to investigate quantitative susceptibility mapping (QSM) of the motor cortex as a potential quantitative biomarker for the diagnosis of ALS and PLS. Materials and Methods Utilizing an institutional review board approved retrospective database, QSM images for 16 patients with upper motor neuron disease (12 with ALS and 4 with PLS; mean age 56.3; 56% male) and 23 control patients (mean age 56.6; 57% male) were reviewed. Two neuroradiologists, blinded to diagnosis, qualitatively assessed QSM, T2, T2*, and T2 FLAIR-weighted images. Relative motor cortex susceptibility (RMCS) was quantitatively calculated by subtracting adjacent white matter/CSF signal intensity from mean motor cortex susceptibility on the axial image most representative of the hand lobule, and receiver operating characteristic (ROC) analysis was performed. The Fisher’s exact and Student’s t tests were used to evaluate for statistical differences between the groups. Results Qualitatively, QSM had higher diagnostic accuracy than T2, T2*, or T2 FLAIR for the diagnosis of ALS/PLS. Quantitatively, RMCS was found to be significantly higher in patients with motor neuron disease than in control patients (46.0 and 35.0, respectively; p<0.001). ROC analysis demonstrated an area-under-the-curve of 0.88 (p<0.0001) and an optimal cutoff value of 40.5 ppb for distinguishing between control and ALS/PLS patients (sensitivity, 87.5%; specificity, 87.0%). Conclusions QSM is a sensitive and specific quantitative biomarker of iron deposition in the motor cortex in ALS and PLS.