Magnetic Susceptibility Source Separation Solely from Gradient Echo Data: Histological Validation

Quantitative susceptibility mapping (QSM) facilitates mapping of the bulk magnetic susceptibility of tissue from the phase of complex gradient echo (GRE) MRI data. QSM phase processing combined with an <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi mathvariant="bold-italic">R</mi><mn mathvariant="bold">2</mn><mo>*</mo></msubsup></mrow></semantics></math></inline-formula> model of magnitude of multiecho gradient echo data (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi mathvariant="bold-italic">R</mi><mn mathvariant="bold">2</mn><mo>*</mo></msubsup><mi mathvariant="bold-italic">Q</mi><mi mathvariant="bold-italic">S</mi><mi mathvariant="bold-italic">M</mi></mrow></semantics></math></inline-formula>) allows separation of dia- and para-magnetic components (e.g., myelin and iron) that contribute constructively to<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo> </mo><msubsup><mi mathvariant="bold-italic">R</mi><mn mathvariant="bold">2</mn><mo>*</mo></msubsup></mrow></semantics></math></inline-formula> value but destructively to the QSM value of a voxel. This <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi mathvariant="bold-italic">R</mi><mn mathvariant="bold">2</mn><mo>*</mo></msubsup><mi mathvariant="bold-italic">Q</mi><mi mathvariant="bold-italic">S</mi><mi mathvariant="bold-italic">M</mi></mrow></semantics></math></inline-formula> technique is validated against quantitative histology—optical density of myelin basic protein and Perls’ iron histological stains of rim and core of 10 ex vivo multiple sclerosis lesions, as well as neighboring normal appearing white matter. We found that <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi mathvariant="bold-italic">R</mi><mn mathvariant="bold">2</mn><mo>*</mo></msubsup><mi mathvariant="bold-italic">Q</mi><mi mathvariant="bold-italic">S</mi><mi mathvariant="bold-italic">M</mi></mrow></semantics></math></inline-formula> source maps are in good qualitative agreement with histology, e.g., showing increased iron concentration at the edge of the rim+ lesions and myelin loss in the lesions’ core. Furthermore, our results indicate statistically significant correlation between paramagnetic and diamagnetic tissue components estimated with <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi mathvariant="bold-italic">R</mi><mn mathvariant="bold">2</mn><mo>*</mo></msubsup><mi mathvariant="bold-italic">Q</mi><mi mathvariant="bold-italic">S</mi><mi mathvariant="bold-italic">M</mi></mrow></semantics></math></inline-formula> and optical densities of Perls’ and MPB stains. These findings provide direct support for the use of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi mathvariant="bold-italic">R</mi><mn mathvariant="bold">2</mn><mo>*</mo></msubsup><mi mathvariant="bold-italic">Q</mi><mi mathvariant="bold-italic">S</mi><mi mathvariant="bold-italic">M</mi></mrow></semantics></math></inline-formula> magnetic source separation based solely on GRE complex data to characterize MS lesion composition.