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Table 1.

MRI protocol between 2006–2014.

For T1w-CE, patients were injected with 0.1mmol/kg of Gadobutrol (Gadovist, Bayer Healthcare, Germany). b-values for DTI were 0, 1000 s/mm2 for 12 diffusion directions.

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Fig 1.

Segmentation of the T2w-hyperintensity zone to derive ADmin/MDmin/RDmin.

Because DTI-maps are intrinsically co-registered the ROI may easily be transferred to each of the employed parameter maps. The colored crosshair in the images indicates the localization of the automatically determined minimum value. In the given example, the patient was diagnosed with anaplastic transformation.

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Fig 2.

Flow-chart of included patients.

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Table 2.

Tumor histology of finally included patients determined after surgical resection according to the WHO 2007 criteria[2].

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Fig 3.

Female patient (43y) with a malignant transformation of a primary gemistocytic Astrocytoma WHO II.

The transformation (red triangle) is visible in the T1w-CE images and at the same timepoint also in the diffusion tensor-derived parameter maps axial (AD), mean (MD) and radial diffusivity (RD). The area of changed brain tissue is most extensive in the T2w-FLAIR. Please note that only in the axial diffusivity map, white matter is depicted hyperintense (yellow arrow) which leads to difference in contrast. The T2 hyperintense region in the T2 FLAIR is matching with the hyperintense region in the DTI-parameter maps.

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Fig 4.

Female patient (24y) with a malignant transformation (anaplastic astrocytoma WHO III) of a primary fibrillary Astrocytoma WHO II.

The transformation according to currently accepted radiologic definition was visible as a new punctual CE at the last column. However, changes in cellularity (red triangles) were preceding CE (white triangle) more than one year. The area of the most focal diffusion restriction corresponds to the focal uptake. Upper row: Axial diffusivity maps; Middle row: T1w-CE; Bottom row: T2w-FLAIR. Dates are given in day/month/year.

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Fig 5.

Female patient (41y) with a malignant transformation (anaplastic astrocytoma WHO III) of a primary resected fibrillary Astrocytoma WHO II in the right occipital lobe.

In the first examination (upper line) a subtle diffusion restriction is observed (red triangles) that predicts the future growth (lower line) of the malignant transformation, indicated by a hypointense cluster in the AD map. The difference between the first examination and the follow-up is 5 ½ months.

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Fig 6.

Male patient (42y) with a malignant transformation (anaplastic astrocytoma WHO III) of a primary resected fibrillary Astrocytoma WHO II in the right occipital lobe (resection cavity is not shown).

Focal, small diffusion restrictions predict the anaplastic transformation before CE appears. The difference between the first examination (upper row) and the follow-up (bottom row) is 20 months.

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Fig 7.

Female patient (44y) with malignant transformation of a primary resected oligoastrocytoma WHO II into anaplastic oligoastrocytoma III in the left frontal lobe demonstrating heterogeneity within the patchy contrast-enhancing region.

Increased diffusion restriction (red triangles) is noted at the same timepoint as new CE. Within the patchy area of CE, the spatial position of hypercellularity is visualized as red cluster (last image). Comparing T2w-FLAIR and axial diffusivity, the hypercellularity is found to be located in a T2w-hypointense region with a punctual CE focus. However, large proportions of patchy CE do not match with the diffusion restriction. Such information is important to consider for guidance of stereotactic biopsy and focal treatment planning.

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Fig 8.

Boxplot analysis of obtained ROI-averaged diffusivity parameters to visualize group differences (stable versus progress).

Plotted values were obtained at the first appearance of CE (progress) or at the last acquired timepoint available (stable). Quantitative results including p-values are given in Table 3.

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Fig 9.

Reciever operating characteristic analysis of minimum diffusion tensor parameters.

Quantitative results are given in Table 4.

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Table 3.

Quantitative analysis of group-wise data distribution regarding ADmin/MDmin/RDmin as visualized in Fig 8, given for 18 patients with MT versus 29 stable patients at the same time point of follow-up.

In 6 patients of the MT group mean ADmin/MDmin/RDmin values were 0.82±0.09/0.73±0.05/0.62±0.07 mm2/s with a signal drop of 64.1%/73.0%/63.9% compared to the stable group in the examination prior to first CE appearance thus indicating early MT.

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Table 4.

Reciever operating characteristic analysis of minimum values (averaged between the two readers).

The test was positive for recurrence if the variable results were less than or equal to the cut-off value. Axial diffusivity was found to have superior diagnostic value (sensitivity, specificity, area under the curve and positive predictive values) to detect the recurrence compared to mean and radial diffusivity. Positive predictive values of ADmin/MDmin/RDmin for the given cut-offs were 81.0%/60.7%/73.9%.

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