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3/4/2014 OHBM Developmental brain ADC atlas creation from clinical images Submission Number: 3973 Authors: Yangming Ou1, Nathaniel Reynolds1, Randy Gollub2, Rudolph Pienaar3, Yanbing Wang4, Taowei Wang4, Darren Sack4, Katherine Andriole5, Steven Pieper6, Christopher Herrick4, Shawn Murphy4, Patricia Grant 3, Lilla Zollei4 Institutions: 1Massachusetts General Hospital, Boston, United States, 2Massachusetts General Hospital, Charlestown, United States, 3Children's Hospital Boston, Boston, United States, 4MGH, Boston, United States, 5BWH, Boston, United States, 6Isomics, Boston, United States First Author: Yangming Ou - Lecture Information | Contact Me Massachusetts General Hospital Boston, United States Introduction: Development of age-specific brain atlases for diffusion-weighted images would significantly enhance clinicians' ability to consistently detect subtle abnormalities. However, the utility of such an atlas depends on the ability to accurately characterize the range of normal development and therefore necessitates large number of datasets. Here we test the ability to leverage large number of MRIs within the clinical PACS to create age-specific normative brain atlases. The Apparent Diffusion Coefficient (ADC) provides a measure of water content in the brain, and thus a surrogate marker for myelin development [1]. Myelination undergoes dramatic changes from birth to 6 yrs of age and thus ADC can track brain development over time within and potentially across subjects [2]. Prior developmental brain atlases have focused primarily on T1 or T2 showing volumetric changes with age [7,8,10], with only one including an FA atlases and ADC values [9]. Also, most cover narrow age ranges (29-44 gestational weeks [10], 0-1-2 year old [7], 37-53 post-conceptional weeks, or >4 years old [8]). Our proposed atlases densely cover 0-6 years. Methods: At Partners HealthCare institutions, the Research Patient Data Registry (RPDR) and the Medical Imaging Informatics Bench to Bedside (mi2b2) workbench enable the repurposing of electronic medical records (EMRs) and medical images for clinical research. The RPDR allows users to perform IRB-approved queries to query and obtain patient cohorts that match demographic, clinical, and medical history facts. The mi2b2 workbench allows the retrieval of clinical images from PACS in an institutionally approved manner. We submitted a detailed data request to RPDR for all pediatric patients who had a head MRI after 2000. By identifying an exclusionary set of diagnoses from the ICD9 records, extracting gestational age from inpatient billing records, determining the desired brain MRI from the Radiology records, and regular expression searching of the Radiology reports for indications of normal brain morphometry, we identified "potentially normative" brain MRI studies acquired after 2006 for patients who were under the age of 6 at the time of scan. An expert medical history review of these patients is currently under way. All DICOM images were converted into NIfTI format. Non-brain structures were removed by a multi-atlas skull-stripping framework [3], reimplemented specifically for neonatal and pediatric brain ADC images: 6 representative ADC images with ages spanning 0-6 years were manually skull stripped to serve as references to skull strip all other ADC images using DRAMMS deformable registration [4] and STAPLE label fusion [5]. The skull stripping succeeded in more than 95% of the subjects and the few failed cases were manually corrected. The skull-stripped ADC images were divided into 12 age bins (see Fig 3), and for each age bin, an unbiased, age-specific atlas was constructed by averaging the geometry and intensity of all subjects within this age bin [6]. Results: The detailed data request submitted to RPDR returned the EMRs of 4745 pediatric patients with a head MRI. From them 1600 patients were <6yr at the time of scan, with potentially normative brain MRI acquired after 2006. In this preliminary study we included 152 pre-computed ADC maps with visually good image quality and visually free of major pathologies. Fig 1 shows representative results of automated skull stripping on ADC images of 06 yr subjects, which visually highly agree with expert knowledge. Fig 2 shows how multiple subjects in an age range were averaged into an unbiased atlas. Figure 3 shows the constructed ADC atlases from weeks old neonates to 6 yr old pediatrics. Conclusions: Mi2b2 workbench can query and access large number of PACS data. In this pilot study, we established a pipeline to construct atlases densely sampling 0-6 yr age range. The atlases display ADC values. Our future work will be to study ADC trends for whole brain, various tissue types and structures. Informatics: Atlases https://ww4.aievolution.com/hbm1401/index.cfm?do=abs.viewAbs&subView=1&abs=4329 1/5 3/4/2014 OHBM https://ww4.aievolution.com/hbm1401/index.cfm?do=abs.viewAbs&subView=1&abs=4329 2/5 3/4/2014 OHBM https://ww4.aievolution.com/hbm1401/index.cfm?do=abs.viewAbs&subView=1&abs=4329 3/5 3/4/2014 OHBM Abstract Information Would you accept an oral presentation if your abstract is selected for an oral session? Yes Please indicate below if your study was a "resting state" or "task-activation” study. Other Healthy subjects only or patients (note that patient studies may also involve healthy subjects): Healthy subjects Internal Review Board (IRB) or Animal Use and Care Committee (AUCC) Approval. Please indicate approval below. Please note: Failure to have IRB or AUCC approval, if applicable will lead to automatic rejection of abstract. Yes, I have IRB or AUCC approval Please indicate which method was used in your research: Diffusion MRI For human MRI, what field strength scanner do you use? 3.0T What post processing software packages do you use? Other, Please list - DRAMMS https://ww4.aievolution.com/hbm1401/index.cfm?do=abs.viewAbs&subView=1&abs=4329 4/5 3/4/2014 OHBM References Reference 1) Hagmann, P., Sporns, O., Madan, N., Cammoun, L., Pienaar, R., Wedeen, V. J., ... & Grant, P. E. (2010). White matter maturation reshapes structural connectivity in the late developing human brain. Proceedings of the National Academy of Sciences, 107(44), 19067-19072. 2) Hermoye L. (2006) 'Pediatric diffusion tensor imaging: normal database and observation of the white matter maturation in early childhood' Neuroimage 29: pp. 493-504. 3) Doshi, J., Erus, G., Ou, Y., Gaonkar, B., & Davatzikos, C. (2013). Multi-Atlas Skull-Stripping. Academic radiology, 20(12), 1566-1576. 4) Ou, Y., Sotiras, A., Paragios, N., & Davatzikos, C. (2011). DRAMMS: Deformable registration via attribute matching and mutual-saliency weighting.Medical image analysis, 15(4), 622-639. 5) Warfield, S. K., Zou, K. H., & Wells, W. M. (2004). Simultaneous truth and performance level estimation (STAPLE): an algorithm for the validation of image segmentation. Medical Imaging, IEEE Transactions on, 23(7), 903-921. 6) Guimond, A., Meunier, J., & Thirion, J. P. (2000). Average brain models: A convergence study. Computer vision and image understanding, 77(2), 192-210. 7) Shi, F., Yap, P. T., Wu, G., Jia, H., Gilmore, J. H., Lin, W., & Shen, D. (2011). Infant brain atlases from neonates to 1-and 2-year-olds. PLoS One, 6(4), e18746. 8) Fonov, V., Evans, A. C., Botteron, K., Almli, C. R., McKinstry, R. C., & Collins, D. L. (2011). Unbiased average age-appropriate atlases for pediatric studies.NeuroImage, 54(1), 313-327. 9) Oishi, K., Mori, S., Donohue, P. K., Ernst, T., Anderson, L., Buchthal, S., ... & Chang, L. (2011). Multi-contrast human neonatal brain atlas: application to normal neonate development analysis. NeuroImage, 56(1), 8-20. 10) Kuklisova-Murgasova, M., Aljabar, P., Srinivasan, L., Counsell, S. J., Doria, V., Serag, A., ... & Rueckert, D. (2011). A dynamic 4D probabilistic atlas of the developing brain. NeuroImage, 54(4), 2750-2763. https://ww4.aievolution.com/hbm1401/index.cfm?do=abs.viewAbs&subView=1&abs=4329 5/5