Evaluation of iron content in human cerebral cavernous malformation using quantitative susceptibility mapping

Abstract

Objectives: The aims of this study were to investigate and validate quantitative susceptibility mapping (QSM) for lesional iron quantification in cerebral cavernous malformations (CCMs).

Materials and methods: Magnetic resonance imaging studies were performed in phantoms and 16 patients on a 3-T scanner. Susceptibility weighted imaging, QSM, and R2* maps were reconstructed from in vivo data acquired with a 3-dimensional, multi-echo, and T2*-weighted gradient echo sequence. Magnetic susceptibility measurements were correlated to susceptibility weighted imaging and R2* results. In addition, iron concentrations from surgically excised CCM lesion specimens were determined using inductively coupled plasma mass spectrometry and correlated with QSM measurements.

Results: The QSM images demonstrated excellent image quality for depicting CCM lesions in both sporadic and familial cases. Susceptibility measurements revealed a positive linear correlation with R2* values (R(2) = 0.99 for total, R(2) = 0.69 for mean; P < 0.01). Quantitative susceptibility mapping values of known iron-rich brain regions matched closely with those of previous studies and in interobserver consistency. A strong correlation was found between QSM and the concentration of iron phantoms (0.925; P < 0.01), as well as between QSM and mass spectroscopy estimation of iron deposition (0.999 for total iron, 0.86 for iron concentration; P < 0.01) in 18 fragments of 4 excised human CCM lesion specimens.

Conclusions: The ability of QSM to evaluate iron deposition in CCM lesions was illustrated via phantom, in vivo, and ex vivo validation studies. Quantitative susceptibility mapping may be a potential biomarker for monitoring CCM disease activity and response to treatments.

Figure 1

Iron phantom results. A representative slice of the QSM results for the Ferumoxytol phantom is shown. A positive linear correlation is observed for all phantoms between the iron concentration and the mean susceptibility values measured by QSM, demonstrating QSM's ability to identify and distinguish paramagnetic materials with different susceptibility levels. The absolute iron concentrations estimated from the QSM measurements (see Discussion for conversion method) closely matched the actual iron concentration in the Ferumoxytol phantom (slope = 1.05, R² = 0.99). The iron quantification was not performed for the remaining sets of phantoms due to unknown conversion factors.

Figure 2

Preventative slices of QSM and validation with previous studies. a) Iron-rich regions including red nucleus, putamen, caudate nucleus, substantia nigra, and globus pallidus are outlined in the magnitude images. b) Corresponding QSM images. c) Mean susceptibility measurements in those regions with various echo times. Comparisons were made to similar studies in the literature (Liu et al. (11) and Bilgic et al. (25)). Note: Sample populations were divided into young and old groups in the Bilgic study. The numbers quoted here are the average for the whole sample population.

Figure 3

Examples of sporadic and familial CCM cases. CCM lesions appear hypointense on SWI and hyperintense on QSM. The hypointensity on the SWI is only a qualitative measurement and cannot be used to assess lesional iron content. In contrast, QSM is a quantitative measurement and the total susceptibility is directly propositional to the lesional iron content. The susceptibility distribution within a single CCM lesion is displayed on the top right.

Figure 4

Lesional susceptibility measurements comparison with lesion volume and R2* values. Top row: total and mean lesion susceptibility versus lesion ROI volume. Bottom row: total and mean lesion susceptibility versus total and mean lesion R2* value, respectively.

Figure 5

Ex vivo lesion sample validation results. The total and the mean susceptibility values of the surgically excised lesion samples were plotted against the iron concentration (mg/g wet tissue) and the total iron content (mg) determined by mass spectroscopy. A sample QSM slice of the human lesion specimen is also shown. The cause for the high iron concentration in lesion sample 1 is unknown, likely a consequence of instrumentation errors.