Sina Straub1, Till Schneider2,3, Christian H. Ziener3, Heinz-Peter Schlemmer3, Mark E. Ladd1, Frederik B. Laun1, and Martin T. Freitag3
1Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany, 3Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Synopsis
The benefit of susceptibility weighted imaging
(SWI) and quantitative susceptibility mapping (QSM) for the detection and quantification
of bleeding of brain metastases of malignant melanoma is assessed. QSM shows
paramagnetic values for hemorrhagic metastases (0.355±0.097 ppm)
and less paramagnetic values (0.239±0.123 ppm) for
hemorrhagic metastases that have T1w-native hyperintense signal. Moreover, our
findings suggest that T1w-native hyperintense melanoma metastases have
relatively diamagnetic susceptibility compared to other structures of the
brain.Target audience
Researchers interested in
susceptibility-weighted imaging (SWI), quantitative susceptibility mapping
(QSM) and the benefits of these imaging techniques to classify melanoma
metastasis.
Purpose
T1-weighted contrast-enhanced and T2-weighted
images are core sequences in the detection of metastatic melanoma in the brain (1).
It was reported that some malignant melanoma metastases appear hyperintense in
native T1w images (2). This pattern may be either resulting from the presence
of melanin (3) or hemorrhage (2). Furthermore, intra-metastatic bleeding might
not be visible on T1w-native images since the T1 signal depends on the age of
hemorrhage. We investigate the feasibility of QSM for the detection and
quantification of bleeding of brain metastases of malignant melanoma.
Methods
The study was approved by the local ethics
committee, every patient gave written informed consent. Thirty-two patients
with melanoma stage IV diagnosed with brain metastases (32‑77 years; mean age
56.7 years) were measured 83 times in total on a 1.5 T whole-body MR system
(Magnetom Symphony, Siemens Healthcare) with a 12-channel head-matrix coil
during routine clinical workup. The clinical protocol included a T1-weighted SE
(pre- and post-contrast), a T2-weighted TSE, a diffusion-weighted EPI, a
T2-weighted FLAIR and a fully flow-compensated 3D gradient-echo sequence.
Imaging parameters for the 3D-GRE were: flip angle=15°, TR/TE=49/40ms,
matrix=320x250x72, voxel size=0.75x0.88x1.9 mm³, bandwidth=80 Hz/pixel,
partial parallel imaging (GRAPPA) with acceleration factor R=2 and 24 reference
lines. T2w-FLAIR: flip angle=150°, TI/TR/TE=2340/8000/98 ms, matrix=320x256x30,
voxel size=0.72x0.9x5 mm3, slice gap=0.5 mm, bandwidth=130 Hz/pixel,
averages=2. After non-contrast enhanced sequences were acquired, a T1-weighted SE
sequence was acquired (flip angle=90°, TR/TE=500/17 ms, matrix=320x260x39,
voxel size=0.72x0.79x4 mm3, slice gap=0.4 mm, bandwidth=130 Hz/pixel)
after application of Gadobenate Dimeglumine (MultiHance, Bracco Imaging, Italy)
for contrast enhancement. Phase images were combined using the vendor-provided adaptive
combine method. Brain masks were generated from magnitude images using FSL-BET
(4). Phase images were unwrapped using a Laplacian-based phase unwrapping (5,6,7).
The background field was removed with V-SHARP (6,7) (with kernel size up to 25
mm). Susceptibility maps were calculated using iLSQR (4,8) and iLSQR-parameters
recommended for effective removal of streaking artifacts and accurate
quantification of susceptibility were used (8). Susceptibility maps of patients
with bleedings were calculated using superposition (9) to minimize artifacts.
Susceptibility maps were referenced to cerebrospinal fluid from the atrium of
the lateral ventricles. Regions of interest for different appearing metastases
were drawn on QSM using MITK Software (10,11).
Results
25 of the 32 patients showed hypointensities in
SWI and hyperintensities in QSM in at least one measurement (Fig.1, Fig.2a,b). Twenty-two
patients showed T1w-native hyperintense brain metastases (Fig.1, Fig.2c,f). Using
SWI/QSM, in 17 patients, T1w-native hyperintensities could be related to
hemorrhagic events (Fig.1f-o, Fig.2a-c), whereas in 5 patients, they could be
related to melanoma metastases with no detectable bleedings (Fig.1a-e). 10
patients with T1w-native hyperintensities related to bleedings showed variable
contrast in T1w native and QSM related to bleeding age (Fig.3). Mean
susceptibility of 20 hemorrhagic metastases which were not T1w-native
hyperintense was 0.355±0.097 ppm and of 11 hemorrhagic metastases which
were T1w-native hyperintense 0.239±0.123 ppm. 11 patients revealed new
bleedings as determined by SWI/QSM while undergoing therapy. In 6 patients,
SWI-hypointensites/QSM-hyperintensities showed only partial signal alteration
of the lesion indicating incomplete bleeding (Fig.2a-c). One patient showed a
metastasis in putamen (Fig.2d-f), that was T1w-native hyperintense (Fig.2f). We
found that the mean susceptibility of the metastasis (-0.005 ppm) is less
paramagnetic than the mean susceptibility of the same region of putamen in the
other hemisphere (0.111 ppm).
Discussion
Metastases of melanoma show a very high
propensity to bleed in the present cohort in accordance with the literature
(12,13). Hyperintensity on QSM images easily identifies bleedings which may
both be T1 hyper- or hypointense (Fig.1) thus representing different age of
hemorrhage. The ROI-based assessment of QSM allows for quantitative assessment
of intra-metastatic bleeding where SWI only provides qualitative results. Therefore,
QSM could be discussed as treatment monitoring tool to indicate response to
therapy of brain metastases, since many patients developed new intra-metastatic
bleedings while undergoing therapy. Surgery is only indicated in patients with
single lesions, thus histopathological ground truth could not be obtained in
the majority of patients, mostly presenting with multiple metastases. However,
SWI was reported with histopathology to reliably visualize paramagnetic blood in
the brain (14) and these reports are used as reference for the present study. Our
results also suggest that the susceptibility of non-bleeding melanoma metastases
is diamagnetic especially compared to structures known for paramagnetism like
putamen (15).
Conclusion
QSM maps should be discussed as part of the
regular clinical protocol for metastases of melanoma since they allow rapid
detection and quantification of intra-metastatic bleeding.
Acknowledgements
No acknowledgement found.References
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