Nuevos métodos para el análisis automático del volumen de estructuras cerebrales a partir de imágenes de resonancia magnética nuclear

En la actualidad, la medicina y en especial el área de imagen médica, ha sido uno de los campos de la ciencia que más se ha beneficiado de las tecnologías de la información. En esta tesis nos centramos en las imágenes de resonancia magnética cerebral y los métodos de segmentación automática del volumen cerebral. En el primer capítulo describimos los antecedentes de este trabajo mediante una breve introducción de los principios físicos de la resonancia magnética y una revisión del estado del arte en relación con las técnicas de segmentación y su evolución a lo largo de las últimas décadas. En los capítulos tres, cuatro y cinco presentamos tres métodos de segmentación automática de diferentes partes del cerebro que mejoran el estado del arte en términos de calidad del resultado y velocidad. Finalmente, en el capítulo seis se comentan las conclusiones generales y se proponen líneas de desarrollo futuras.Nowadays, medicine and specially the medical image area, is one of the science fields that has benefited more from the information technologies. In this thesis we focus on cerebral magnetic resonance imaging and automatic segmentation methods of the brain volume. In the first chapter we describe a background for this work by a brief introduction of the physic fundaments of magnetic resonance and a revision of the state-of-the-art regarding to segmentation techniques and its evolution along the last decades. In the chapters three, four and five we present three methods for automatically segment different parts of the brain that leverage the state-of-the-art in terms of result quality and computation time. Finally, in chapter six we comment the general conclusions and propose lines for future works.En l'actualitat, la medicina i en especial l'àrea d'imatge mèdica, ha estat un dels camps de la ciència que més s'ha beneficiat de les tecnologies de la informació. En aquesta tesi ens centrem en les imatges de ressonància magnètica cerebral i el desenvolupament de mètodes de segmentaciò automàtica del volum cerebral. En el primer capítol descrvim els antecedents d'aquest treball mitjançant una breu introducció dels principis físics de la ressonància magnètica i una revisió de l'estat de l'art en relació amb les tècniques de segmentació i la seva evolució al llarg de les últimes dècades. En els capítols tres, quatre, i cinc presentem tres mètodes de segmentació automàtica per a diferents parts del cervell que milloren l'estat de l'art en quant a qualitat dels seus resultats i velocitat. Finalment, en el capitol sis es comenten les conclusions generals i es proposen línies de desenvolupament ions generals i es proposen línies de desenvolupament futures.Romero Gómez, JE. (2018). Nuevos métodos para el análisis automático del volumen de estructuras cerebrales a partir de imágenes de resonancia magnética nuclear [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/10634

Software para el estudio del volumen de estructuras corticales en imágenes de RMN cerebrales

El estudio del volumen intracraneal requiere del uso de herramientas que permitan objetivar el diagnóstico y ofrezcan un rendimiento y precisión elevados. La segmentación automática del volumen cerebral es el primer paso hacia un estudio más completo del cerebro y supondrá una herramienta versátil en el estudio de diversas patologías. Propósito: Mejorar un método ya implementado que segmenta el volumen cerebral con una calidad aceptable pero en un tiempo de ejecución elevado basado en comparación de regiones contra una biblioteca de casos de ejemplo segmentada manualmente. Método: El método recorre uno a uno todos los voxels del cerebro a segmentar extrayendo la región que lo envuelve y comparándola con regiones de los casos de ejemplo de la biblioteca. Esto era ineficiente así que se han introducido mejoras que van desde la carga y preselección de los casos más semejantes para usarlos en la segmentación hasta introducir una estimación pre calculada del etiquetado de los voxels que no suelen variar para evitar tener que procesarlos. Resultados: Se parte de un método que obtiene segmentaciones con una 98% de fiabilidad y en un tiempo de ejecución de 160 segundos y se ha mejorado hasta una fiabilidad del 99% en un tiempo inferior a 40 segundos.Romero Gómez, JE. (2011). Software para el estudio del volumen de estructuras corticales en imágenes de RMN cerebrales. http://hdl.handle.net/10251/14239.Archivo delegad

Wetting of Nematic Liquid Crystals on Crenellated Substrates: A Frank–Oseen Approach

We revisit the wetting of nematic liquid crystals in contact with crenellated substrates, studied previously using the Landau–de Gennes formalism. However, due to computational limitations, the characteristic length scales of the substrate relief considered in that study limited to less than 100 nematic correlation lengths. The current work uses an extended Frank–Oseen formalism, which includes not only the free-energy contribution due to the elastic deformations but also the surface tension contributions and, if disclinations or other orientational field singularities are present, their core contributions. Within this framework, which was successfully applied to the anchoring transitions of a nematic liquid crystal in contact with structured substrates, we extended the study to much larger length scales including the macroscopic scale. In particular, we analyzed the interfacial states and the transitions between them at the nematic–isotropic coexistence

HIPS: A new hippocampus subfield segmentation method

[EN] The importance of the hippocampus in the study of several neurodegenerative diseases such as Alzheimer's disease makes it a structure of great interest in neuroimaging. However, few segmentation methods have been proposed to measure its subfields due to its complex structure and the lack of high resolution magnetic resonance (MR) data. In this work, we present a new pipeline for automatic hippocampus subfield segmentation using two available hippocampus subfield delineation protocols that can work with both high and standard resolution data. The proposed method is based on multi-atlas label fusion technology that benefits from a novel multi-contrast patch match search process (using high resolution T1-weighted and T2-weighted images). The proposed method also includes as post-processing a new neural network-based error correction step to minimize systematic segmentation errors. The method has been evaluated on both high and standard resolution images and compared to other state-of-the-art methods showing better results in terms of accuracy and execution time.This research was supported by Spanish UPV2016-0099 and TIN2013-43457-R grants from UPV and the Ministerio de Economia y Competitividad. This study has been carried out with financial support from the French State, managed by the French National Research Agency (ANR) in the frame of the Investments for the future Program IdEx Bordeaux (ANR-10-IDEX-03-02, HL-MRI Project), Cluster of excellence CPU and TRAIL (HR-DTI ANR-10-LABX-57) and the CNRS multidisciplinary project "Defi imag'In". We also want to thank Javier Juan Albarracin for his valuable contribution to the development of this method.Romero Gómez, JE.; Coupe, P.; Manjón Herrera, JV. (2017). HIPS: A new hippocampus subfield segmentation method. NeuroImage. 163:286-295. https://doi.org/10.1016/j.neuroimage.2017.09.049S28629516

Impact of short-term extreme temperature events on physiological performance of Salicornia ramosissima J. Woods under optimal and sub-optimal saline conditions

Increasing extreme temperature climatic events could exert an important effect on plant photosynthetic performance, which could be modulated by the co-occurrence with other environmental factors, such as salinity, in estuarine ecosystems. Therefore, a mesocosm experiment was designed to assess the impact of temperature events for three days (13/5 °C, 25/13 °C and 40/28 °C) in combination with two NaCl concentrations (171 and 1050 mM NaCl) on the physiological performance of Salicornia ramosissima. Extreme temperature events had a negative impact on S. ramosissima photosynthetic efficiency, this effect being more marked with cold wave at both salinities, compared with heat wave, even in presence of NaCl excess. This differential thermotolerance in the photosynthetic apparatus was ascribed to the greater integrity and functioning of its photosynthetic pathway at high temperature, as indicated by constant gs, Vc,max values at optimal salinity and the higher values of those parameters and gm recorded in combination with NaCl excess. Moreover, S. ramosissima was able to upregulate the energy sink capacity of its photochemical apparatus at elevated temperature and salinity by a greater energy excess dissipation capacity. This could have contributed to reducing the risk of oxidative stress, along with the recorded higher capacity for antioxidant enzyme activity modulation under these conditions.España, MINECO Project CGL2016– 75550-

Comparación de 3 pautas de sedación para pacientes sometidos a anestesia subaracnoidea. Ensayo clínico aleatorizado, simple ciego

ResumenIntroducciónLa sedación es un conjunto de acciones dirigidas a lograr que un paciente se encuentre tranquilo, cómodo, libre de dolor o de malos recuerdos mientras se realiza un procedimiento diagnóstico o terapéutico. Dado que las técnicas anestésicas regionales empleadas en la práctica clínica habitual son procedimientos relativamente traumáticos y dolorosos, se han asociado a sedación, para hacer este tipo de intervenciones más confortables para el paciente y hacer más fácil la colaboración del mismo.ObjetivoDeterminar la eficacia de 3 pautas de sedación en pacientes que van a ser sometidos a anestesia subaracnoidea.MetodologíaEstudio experimental, ensayo clínico, aleatorizado, prospectivo, simple ciego, en el cual se compararon 3 pautas para sedación en pacientes sometidos a anestesia subaracnoidea.ResultadosTodos los pacientes del estudio tuvieron ansiolisis, colaboraron a la punción y refirieron que volverían a recibir una anestesia subaracnoidea sin temor; además, no se reportaron complicaciones tales como depresión respiratoria, náuseas, vómitos u otra, con las pautas de sedación utilizadas, siendo alta la satisfacción por parte de los pacientes. El reflejo de retirada (p=0,0003) y el dolor a la punción (p=0,0069) se presentaron en mayor proporción en el grupo que usó como pauta solo midazolam intravenoso. En este mismo grupo hubo menor satisfacción con la sedación; sin embargo, las 3 pautas mostraron una buena eficacia.ConclusionesLas 3 pautas de sedación propuestas fueron eficaces para su uso en anestesia subaracnoidea, con mejores resultados cuando se usó midazolam más fentanilo o midazolam más ketamina.p-2011-1682 Colciencias. Registro # NCT0213664 (clinicaltrials.gov,prospectivo).AbstractIntroductionSedation is defined as the set of actions aimed at having a quiet, comfortable, pain-free patient during a diagnostic or therapeutic procedure without any bad memories. Since the standard regional anesthesia techniques used in clinical practice are relatively traumatic and painful procedures, sedation has been introduced to make these interventions more comfortable for the patient and to facilitate the patient's cooperation.ObjectiveTo establish the efficacy of three sedation guidelines in patients undergoing subarachnoid anesthesia.MethodologyExperimental, randomized, prospective, single blind clinical trial comparing three guidelines for the sedation of patients undergoing subarachnoid anesthesia.ResultsAll of the patients in the trial received anxiolysis, collaborated with the puncture and said that they would not be afraid to receive subarachnoid anesthesia in the future. There were no complications including respiratory depression, nausea, vomiting or any other complications reported with the use of the sedation guidelines. Patient satisfaction was high. Withdrawal reflex (P=0.0003) and puncture related pain (P=0.0069) were more common in the group using the intravenous midazolam-only guideline and patient satisfaction with sedation was also lower in this group; however, the three guidelines showed good efficacy.ConclusionsThe three sedation guidelines presented were effectively used in subarachnoid anesthesia; the results were more favorable with the use of midazolam + fentanyl or midazolam + ketamine.p-2011-1682 Colciencias. Registro # NCT0213664 (clinicaltrials.gov,prospectivo)

Fingerprint indoor position system based on OpenMAC

This paper presents a work in progress for the developing of a fingerprint indoor position system based on OpenMAC, an IEEE 802.15.4 embedded software implementation from Atmel to be used in different scenarios like e_health, ambient living or smart building. The system is thought to work as another one that we have yet developed but using the BitCloud Stack, a full-featured, second generation embedded software stack from the same supplier, but improving it. The first steps followed up in the system development are shown in this paper.Junta de Andalucía p08-TIC-363

Combined Effects of Non-Conforming Fly Ash and Recycled Masonry Aggregates on Mortar Properties

This work evaluates the effects of using non-conforming fly ash (Nc-FA) generated in a thermoelectric power plant as filler material for mortars made with natural sand (NA) and recycled sand from masonry waste (FRMA). The incorporation of powdered recycled masonry filler (R-MF) is also tested as an alternative to siliceous filler (Si-F). Three families of mortars were designed to study: the effect of replacing Si-F with Nc-FA on mortars made with NA; the effect of replacing Si-F with Nc-FA on mortars made with 50% of NA and 50% of FRMA; and the effect of replacing Si-F with R-MF on mortars made with NA and FRMA. Replacing Si-F with Nc-FA is a viable alternative that increases the mechanical strength, the workability and durability properties and decreases the shrinkage. The use of FRMA and Nc-FA improved the mechanical strength of mortars, and it slightly increased the shrinkage. The replacement of Si-F with R-MF on mortars made with FRMA is not a good alternative, because it has a negative impact on all of the properties tested. This work can help both to reduce cement and natural resources’ consumption and to increase the recycling rate of Nc-FA and FRM

Regional hippocampal vulnerability in early multiple sclerosis: a dynamic pathological spreading from dentate gyrus to CA1

"This is the peer reviewed version of the following article: Planche, V., Koubiyr, I., Romero, J. E., Manjon, J. V., Coupé, P., Deloire, M., ... & Tourdias, T. (2018). Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA 1. Human brain mapping, 39(4), 1814-1824., which has been published in final form at https://doi.org/10.1002/hbm.23970. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Background: Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. Method: We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. Results: At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R-2 = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (beta = 0.87, p < .05). Conclusion: The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance.ARSEP Foundation; Bordeaux University Hospital; TEVA Laboratories; French Agence Nationale de la Recherche, Grant/Award Numbers: ANR-10-LABX-57, ANR-10-LABX-43, ANR-10-IDEX-03-02, ANR-10-COHO-002; UPV, Grant/Award Numbers: UPV2016-0099, TIN2013-43457-R; Ministerio de Economia y competitividadPlanche, V.; Koubiyr, I.; Romero Gómez, JE.; Manjón Herrera, JV.; Coupe, P.; Deloire, M.; Dousset, V.... (2018). Regional hippocampal vulnerability in early multiple sclerosis: a dynamic pathological spreading from dentate gyrus to CA1. Human Brain Mapping. 39(4):1814-1824. https://doi.org/10.1002/hbm.23970S18141824394Avants, B. B., Tustison, N. J., Song, G., Cook, P. A., Klein, A., & Gee, J. C. (2011). A reproducible evaluation of ANTs similarity metric performance in brain image registration. NeuroImage, 54(3), 2033-2044. doi:10.1016/j.neuroimage.2010.09.025Bakker, A., Kirwan, C. B., Miller, M., & Stark, C. E. L. (2008). Pattern Separation in the Human Hippocampal CA3 and Dentate Gyrus. Science, 319(5870), 1640-1642. doi:10.1126/science.1152882Coupé, P., Manjón, J. V., Chamberland, M., Descoteaux, M., & Hiba, B. (2013). Collaborative patch-based super-resolution for diffusion-weighted images. NeuroImage, 83, 245-261. doi:10.1016/j.neuroimage.2013.06.030De Stefano, N., Airas, L., Grigoriadis, N., Mattle, H. P., O’Riordan, J., Oreja-Guevara, C., … Kieseier, B. C. (2014). Clinical Relevance of Brain Volume Measures in Multiple Sclerosis. CNS Drugs, 28(2), 147-156. doi:10.1007/s40263-014-0140-zDu, A. T., Schuff, N., Kramer, J. H., Ganzer, S., Zhu, X. P., Jagust, W. J., … Weiner, M. W. (2004). Higher atrophy rate of entorhinal cortex than hippocampus in AD. Neurology, 62(3), 422-427. doi:10.1212/01.wnl.0000106462.72282.90Dutta, R., Chang, A., Doud, M. K., Kidd, G. J., Ribaudo, M. V., Young, E. A., … Trapp, B. D. (2011). Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients. Annals of Neurology, 69(3), 445-454. doi:10.1002/ana.22337De Flores, R., La Joie, R., & Chételat, G. (2015). Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease. Neuroscience, 309, 29-50. doi:10.1016/j.neuroscience.2015.08.033Fraser, M. A., Shaw, M. E., & Cherbuin, N. (2015). A systematic review and meta-analysis of longitudinal hippocampal atrophy in healthy human ageing. NeuroImage, 112, 364-374. doi:10.1016/j.neuroimage.2015.03.035Frisoni, G. B., Ganzola, R., Canu, E., Rub, U., Pizzini, F. B., Alessandrini, F., … Thompson, P. M. (2008). Mapping local hippocampal changes in Alzheimer’s disease and normal ageing with MRI at 3 Tesla. Brain, 131(12), 3266-3276. doi:10.1093/brain/awn280Gold, S. M., Kern, K. C., O’Connor, M.-F., Montag, M. J., Kim, A., Yoo, Y. S., … Sicotte, N. L. (2010). Smaller Cornu Ammonis 2–3/Dentate Gyrus Volumes and Elevated Cortisol in Multiple Sclerosis Patients with Depressive Symptoms. Biological Psychiatry, 68(6), 553-559. doi:10.1016/j.biopsych.2010.04.025Habbas, S., Santello, M., Becker, D., Stubbe, H., Zappia, G., Liaudet, N., … Volterra, A. (2015). Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling. Cell, 163(7), 1730-1741. doi:10.1016/j.cell.2015.11.023Hulst, H. E., Schoonheim, M. M., Van Geest, Q., Uitdehaag, B. M., Barkhof, F., & Geurts, J. J. (2015). Memory impairment in multiple sclerosis: Relevance of hippocampal activation and hippocampal connectivity. Multiple Sclerosis Journal, 21(13), 1705-1712. doi:10.1177/1352458514567727Jack, C. R., Petersen, R. C., Xu, Y., O’Brien, P. C., Smith, G. E., Ivnik, R. J., … Kokmen, E. (2000). Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology, 55(4), 484-490. doi:10.1212/wnl.55.4.484Jack, C. R., Barkhof, F., Bernstein, M. A., Cantillon, M., Cole, P. E., DeCarli, C., … Foster, N. L. (2011). Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer’s disease. Alzheimer’s & Dementia, 7(4), 474-485.e4. doi:10.1016/j.jalz.2011.04.007Kerchner, G. A., Bernstein, J. D., Fenesy, M. C., Deutsch, G. K., Saranathan, M., Zeineh, M. M., & Rutt, B. K. (2013). Shared Vulnerability of Two Synaptically-Connected Medial Temporal Lobe Areas to Age and Cognitive Decline: A Seven Tesla Magnetic Resonance Imaging Study. Journal of Neuroscience, 33(42), 16666-16672. doi:10.1523/jneurosci.1915-13.2013La Joie, R., Fouquet, M., Mézenge, F., Landeau, B., Villain, N., Mevel, K., … Chételat, G. (2010). Differential effect of age on hippocampal subfields assessed using a new high-resolution 3T MR sequence. NeuroImage, 53(2), 506-514. doi:10.1016/j.neuroimage.2010.06.024Longoni, G., Rocca, M. A., Pagani, E., Riccitelli, G. C., Colombo, B., Rodegher, M., … Filippi, M. (2013). Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS. Brain Structure and Function, 220(1), 435-444. doi:10.1007/s00429-013-0665-9Manjón, J. V., & Coupé, P. (2016). volBrain: An Online MRI Brain Volumetry System. Frontiers in Neuroinformatics, 10. doi:10.3389/fninf.2016.00030Manjón, J. V., Coupé, P., Martí-Bonmatí, L., Collins, D. L., & Robles, M. (2009). Adaptive non-local means denoising of MR images with spatially varying noise levels. Journal of Magnetic Resonance Imaging, 31(1), 192-203. doi:10.1002/jmri.22003Manjón, J. V., Eskildsen, S. F., Coupé, P., Romero, J. E., Collins, D. L., & Robles, M. (2014). Nonlocal Intracranial Cavity Extraction. International Journal of Biomedical Imaging, 2014, 1-11. doi:10.1155/2014/820205Maruszak, A., & Thuret, S. (2014). Why looking at the whole hippocampus is not enough—a critical role for anteroposterior axis, subfield and activation analyses to enhance predictive value of hippocampal changes for Alzheimer’s disease diagnosis. Frontiers in Cellular Neuroscience, 8. doi:10.3389/fncel.2014.00095Miller, D. H., Chard, D. T., & Ciccarelli, O. (2012). Clinically isolated syndromes. The Lancet Neurology, 11(2), 157-169. doi:10.1016/s1474-4422(11)70274-5Morra, J. H., Tu, Z., Apostolova, L. G., Green, A. E., Avedissian, C., … Madsen, S. K. (2009). Automated 3D mapping of hippocampal atrophy and its clinical correlates in 400 subjects with Alzheimer’s disease, mild cognitive impairment, and elderly controls. Human Brain Mapping, 30(9), 2766-2788. doi:10.1002/hbm.20708Ny�l, L. G., & Udupa, J. K. (1999). On standardizing the MR image intensity scale. Magnetic Resonance in Medicine, 42(6), 1072-1081. doi:10.1002/(sici)1522-2594(199912)42:63.0.co;2-mPapadopoulos, D., Dukes, S., Patel, R., Nicholas, R., Vora, A., & Reynolds, R. (2009). Substantial Archaeocortical Atrophy and Neuronal Loss in Multiple Sclerosis. Brain Pathology, 19(2), 238-253. doi:10.1111/j.1750-3639.2008.00177.xPérez-Miralles, F., Sastre-Garriga, J., Tintoré, M., Arrambide, G., Nos, C., Perkal, H., … Montalban, X. (2013). Clinical impact of early brain atrophy in clinically isolated syndromes. Multiple Sclerosis Journal, 19(14), 1878-1886. doi:10.1177/1352458513488231Planche, V., Ruet, A., Coupé, P., Lamargue-Hamel, D., Deloire, M., Pereira, B., … Tourdias, T. (2016). Hippocampal microstructural damage correlates with memory impairment in clinically isolated syndrome suggestive of multiple sclerosis. Multiple Sclerosis Journal, 23(9), 1214-1224. doi:10.1177/1352458516675750Planche, V., Panatier, A., Hiba, B., Ducourneau, E.-G., Raffard, G., Dubourdieu, N., … Tourdias, T. (2017). Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis. Brain, Behavior, and Immunity, 60, 240-254. doi:10.1016/j.bbi.2016.11.010Planche, V., Ruet, A., Charré-Morin, J., Deloire, M., Brochet, B., & Tourdias, T. (2017). Pattern separation performance is decreased in patients with early multiple sclerosis. Brain and Behavior, 7(8), e00739. doi:10.1002/brb3.739Polman, C. H., Reingold, S. C., Banwell, B., Clanet, M., Cohen, J. A., Filippi, M., … Wolinsky, J. S. (2011). Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Annals of Neurology, 69(2), 292-302. doi:10.1002/ana.22366Rocca, M. A., Longoni, G., Pagani, E., Boffa, G., Colombo, B., Rodegher, M., … Filippi, M. (2015). In vivo evidence of hippocampal dentate gyrus expansion in multiple sclerosis. Human Brain Mapping, 36(11), 4702-4713. doi:10.1002/hbm.22946Romero, J. E., Coupe, P., & Manjón, J. V. (2016). High Resolution Hippocampus Subfield Segmentation Using Multispectral Multiatlas Patch-Based Label Fusion. Lecture Notes in Computer Science, 117-124. doi:10.1007/978-3-319-47118-1_15Romero, J. E., Coupé, P., & Manjón, J. V. (2017). HIPS: A new hippocampus subfield segmentation method. NeuroImage, 163, 286-295. doi:10.1016/j.neuroimage.2017.09.049Schmidt, P., Gaser, C., Arsic, M., Buck, D., Förschler, A., Berthele, A., … Mühlau, M. (2012). An automated tool for detection of FLAIR-hyperintense white-matter lesions in Multiple Sclerosis. NeuroImage, 59(4), 3774-3783. doi:10.1016/j.neuroimage.2011.11.032Sicotte, N. L., Kern, K. C., Giesser, B. S., Arshanapalli, A., Schultz, A., Montag, M., … Bookheimer, S. Y. (2008). Regional hippocampal atrophy in multiple sclerosis. Brain, 131(4), 1134-1141. doi:10.1093/brain/awn030Small, S. A. (2014). Isolating Pathogenic Mechanisms Embedded within the Hippocampal Circuit through Regional Vulnerability. Neuron, 84(1), 32-39. doi:10.1016/j.neuron.2014.08.030Stark, S. M., Yassa, M. A., Lacy, J. W., & Stark, C. E. L. (2013). A task to assess behavioral pattern separation (BPS) in humans: Data from healthy aging and mild cognitive impairment. Neuropsychologia, 51(12), 2442-2449. doi:10.1016/j.neuropsychologia.2012.12.014Thompson, P. M., Hayashi, K. M., de Zubicaray, G. I., Janke, A. L., Rose, S. E., Semple, J., … Toga, A. W. (2004). Mapping hippocampal and ventricular change in Alzheimer disease. NeuroImage, 22(4), 1754-1766. doi:10.1016/j.neuroimage.2004.03.040Tustison, N. J., Avants, B. B., Cook, P. A., Yuanjie Zheng, Egan, A., Yushkevich, P. A., & Gee, J. C. (2010). N4ITK: Improved N3 Bias Correction. IEEE Transactions on Medical Imaging, 29(6), 1310-1320. doi:10.1109/tmi.2010.2046908Wang, L., Swank, J. S., Glick, I. E., Gado, M. H., Miller, M. I., Morris, J. C., & Csernansky, J. G. (2003). Changes in hippocampal volume and shape across time distinguish dementia of the Alzheimer type from healthy aging☆. NeuroImage, 20(2), 667-682. doi:10.1016/s1053-8119(03)00361-6West, M. ., Coleman, P. ., Flood, D. ., & Troncoso, J. . (1994). Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. The Lancet, 344(8925), 769-772. doi:10.1016/s0140-6736(94)92338-8Winterburn, J. L., Pruessner, J. C., Chavez, S., Schira, M. M., Lobaugh, N. J., Voineskos, A. N., & Chakravarty, M. M. (2013). A novel in vivo atlas of human hippocampal subfields using high-resolution 3T magnetic resonance imaging. NeuroImage, 74, 254-265. doi:10.1016/j.neuroimage.2013.02.003Wisse, L. E. M., Daugherty, A. M., Olsen, R. K., Berron, D., Carr, V. A., … Stark, C. E. L. (2016). A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals? Hippocampus, 27(1), 3-11. doi:10.1002/hipo.22671Yushkevich, P. A., Amaral, R. S. C., Augustinack, J. C., Bender, A. R., Bernstein, J. D., Boccardi, M., … Zeineh, M. M. (2015). Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: Towards a harmonized segmentation protocol. NeuroImage, 111, 526-541. doi:10.1016/j.neuroimage.2015.01.00