This application evaluates the Epidermal Growth Factor Receptor splice variant III (EGFRvIII) status in primary glioblastoma, by quantitative pattern analysis of the spatial heterogeneity of peritumoral perfusion dynamics from Dynamic Susceptibility Contrast (DSC) MRI scans, through the Peritumoral Heterogeneity Index (PHI / φ-index) [1-3].

REQUIREMENTS:

T1-Gd: To annotate the immediate peritumoral ROI.
T2-FLAIR: To annotate the distant peritumoral ROI.
DSC-MRI: To perform the analysis and extract the PHI.
(Command-line only) ROI Label file consisting of near-region (Label=1) and far-region (Label=2)

USAGE:

Annotate 2 ROIs: one near (Label:1) the enhancing tumor and another far (Label:2) from it (but still within the peritumoral region). Rules for ROI annotation are provided below [3].
Once the 2 ROIs are annotated, the application can be launched by using the menu option: 'Applications -> EGFRvIII Surrogate Index'.
A pop-up window appears displaying the results (within <1 minute).

This application is also available as with a stand-alone CLI for data analysts to build pipelines around, using the following example command:
```
${CaPTk_InstallDir}/bin/EGFRvIIISurrogateIndex.exe -i C:/inputDSCImage.nii.gz -m C:/maskWithNearAndFarLabels.nii.gz
```
Additionally, you can process a batch directory (subdirectories are subjects, and each must have a perfusion and mask image). Pass "--help" to the CLI application for more details.
```
${CaPTk_InstallDir}/bin/EGFRvIIISurrogateIndex.exe -b C:/inputDirectory/ -o C:/output.csv
```

RULES FOR ROI ANNOTATION:

These two ROIs are used to sample tissue located on the two boundaries of the peritumoaral edema/invasion area: near to and far from the tumor, respectively, and hence to evaluate the heterogeneity or spatial gradient of perfusion signals [1-3].
The "near" ROI is initially defined in the T1-Gd volume, adjacent to the enhancing part of the tumor, described by hyperintense signal on T1-Gd. The T2-FLAIR volume is then used to revise this ROI in terms of all its voxels being within the peritumoral edematous tissue, described by hyperintense signal on the T2-FLAIR volume.
The T2-FLAIR volume is also used to define the ROI at the farthest from the tumor but still within the edematous tissue, i.e., the enhancing FLAIR abnormality signal.
These ROIs are described by lines drawn in multiple slices of each image (T1-Gd and T2-FLAIR) for each subject.
Please note that during annotation:
- Both ROIs are always within the peritumoral edema/invasion area,
- None of the ROIs are in proximity to the ventricles,
- Both ROIs are representative of infiltration into white matter and not into gray matter,
- The distant ROI is at the farthest possible distance from the enhancing part of the tumor while still within edema, and
- No vessels are involved within any of the defined ROIs, as denoted in the T1-Gd volume.

References:

S.Bakas, H.Akbari, J.Pisapia, M.Rozycki, D.M.O'Rourke, C.Davatzikos. "Identification of Imaging Signatures of the Epidermal Growth Factor Receptor Variant III (EGFRvIII) in Glioblastoma", Neuro Oncol. 17(Suppl 5):v154, 2015, DOI:10.1093/neuonc/nov225.05
S.Bakas, Z.A.Binder, H.Akbari, M.Martinez-Lage, M.Rozycki, J.J.D.Morrissette, N.Dahmane, D.M.O'Rourke, C.Davatzikos, "Highly-expressed wild-type EGFR and EGFRvIII mutant glioblastomas have similar MRI signature, consistent with deep peritumoral infiltration", Neuro Oncol. 18(Suppl 6):vi125-vi126, 2016, DOI:10.1093/neuonc/now212.523
S.Bakas, H.Akbari, J.Pisapia, M.Martinez-Lage, M.Rozycki, S.Rathore, N.Dahmane, D.M.O'Rourke, C.Davatzikos, "In vivo detection of EGFRvIII in glioblastoma via perfusion magnetic resonance imaging signature consistent with deep peritumoral infiltration: the phi-index", Clin Cancer Res. 23(16):4724-4734, 2017, DOI:10.1158/1078-0432.CCR-16-1871