INTRODUCTION

Brain volume loss (atrophy) has been proven to be an important characteristic of neurological diseases such as Alzheimer’s disease (AD). However, scanner-induced systematic differences in atrophy measures have been reported using different methods 1-4. Therefore, to increase statistical power in clinical trials and to establish atrophy measures as reliable clinical biomarkers, such scanner-induced effects should be minimized. In this study we developed and performed initial validation tests of an MR-compatible phantom and analysis software for robust and reliable evaluation of the brain volume loss.

METHODS

The MRI phantom contains inflatable structures equipped with a precise volume change system (FIG. 1). The phantom contains three brain structures: a cerebral hemisphere, putamen, and caudate nucleus. The hemisphere model was created by scanning a post-mortem healthy brain using a surface 3D scanner (Artec Spider, Arc 3D). The models of putamen and caudate nucleus were generated from MR images of healthy control subjects using FSL-FIRST. Using these models, molds of all three structures were 3D-printed using ZP151 powder (3D systems). Then, the molds were repeatedly dipped into pre-vulcanized latex rubber (pvs-elastica, FromX), to reach a homogenize thickness. Finally, the molds were dissolved in water and phantoms remained. Syringes (Hamilton®, Switzerland) of 100mL and 100µL were incorporated with a custom-made stainless steel plunger with a finely bored syringe barrel to change the volume in the hemisphere and the small structures, respectively. To validate the method, the phantom was imaged at three different clinical 3T MR scanners (GE, Toshiba and Philips) using a standard clinical 3D gradient echo sequence available at each scanner with voxel volumes 1-1.2 µL (FIG. 2). In each scanning session, 5 volume changes were applied as indicated in FIG. 3a, ranging between about 1-5% of the baseline volume. Next, we developed software to measure volume change from MR images, using existing methods and pipelines (FIG. 4). Then, the measured volume change was compared with the known (applied) volume change using intra-class correlation coefficient (ICC, absolute agreement) and mean absolute difference (MAD). SPSS version 22 (IBM) was used.

RESULTS

FIG. 2 shows example phantom MR images. The volume change calculated by our software versus the applied volume change is presented in FIG. 5. ICC ranged from 0.999-1 for hemisphere, 0.976-0.998 for putamen, and 0.985-0.999 for caudate nucleus (FIG. 3b). The MAD were 109-332µL for hemisphere, 2.9-11.9µL for putamen, and 2.2-10.1µL for caudate nucleus (FIG. 3b).

DISCUSSION and CONCLUSIONS

Although other anthropomorphic brain phantoms have been described 5-7, to our knowledge this is the first structural MR-compatible phantom aiming to standardize volume change measurements within and between scanners. Our device can accurately and robustly provide a selected volume change to mimic e.g. the change typically observed in a certain disease. The developed software can measure the volume changes from the images with high precision. Next step is to validate this in patient studies, targeting a method to standardize volume change measurements obtained on different scanners.

Acknowledgements

We would like to thank kind technical supports by the 3D Innovation Lab at the VU University Medical Center, specially D. Koops, F. Verver and S. te Slaa.

References

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