BrainPrint: A discriminative characterization of brain morphology

We introduce BrainPrint, a compact and discriminative representation of brain morphology. BrainPrint captures shape information of an ensemble of cortical and subcortical structures by solving the eigenvalue problem of the 2D and 3D Laplace–Beltrami operator on triangular (boundary) and tetrahedral (volumetric) meshes. This discriminative characterization enables new ways to study the similarity between brains; the focus can either be on a specific brain structure of interest or on the overall brain similarity. We highlight four applications for BrainPrint in this article: (i) subject identification, (ii) age and sex prediction, (iii) brain asymmetry analysis, and (iv) potential genetic influences on brain morphology. The properties of BrainPrint require the derivation of new algorithms to account for the heterogeneous mix of brain structures with varying discriminative power. We conduct experiments on three datasets, including over 3000 MRI scans from the ADNI database, 436 MRI scans from the OASIS dataset, and 236 MRI scans from the VETSA twin study. All processing steps for obtaining the compact representation are fully automated, making this processing framework particularly attractive for handling large datasets.National Cancer Institute (U.S.) (1K25-CA181632-01)Athinoula A. Martinos Center for Biomedical Imaging (P41-RR014075)Athinoula A. Martinos Center for Biomedical Imaging (P41-EB015896)National Alliance for Medical Image Computing (U.S.) (U54-EB005149)Neuroimaging Analysis Center (U.S.) (P41-EB015902)National Center for Research Resources (U.S.) (U24 RR021382)National Institute of Biomedical Imaging and Bioengineering (U.S.) (5P41EB015896-15)National Institute of Biomedical Imaging and Bioengineering (U.S.) (R01EB006758)National Institute on Aging (AG022381)National Institute on Aging (5R01AG008122-22)National Institute on Aging (AG018344)National Institute on Aging (AG018386)National Center for Complementary and Alternative Medicine (U.S.) (RC1 AT005728-01)National Institute of Neurological Diseases and Stroke (U.S.) (R01 NS052585-01)National Institute of Neurological Diseases and Stroke (U.S.) (1R21NS072652-01)National Institute of Neurological Diseases and Stroke (U.S.) (1R01NS070963)National Institute of Neurological Diseases and Stroke (U.S.) (R01NS083534)National Institutes of Health (U.S.) ((5U01-MH093765

BrainPrint: A discriminative characterization of brain morphology

We introduce BrainPrint, a compact and discriminative representation of brain morphology. BrainPrint captures shape information of an ensemble of cortical and subcortical structures by solving the eigenvalue problem of the 2D and 3D Laplace–Beltrami operator on triangular (boundary) and tetrahedral (volumetric) meshes. This discriminative characterization enables new ways to study the similarity between brains; the focus can either be on a specific brain structure of interest or on the overall brain similarity. We highlight four applications for BrainPrint in this article: (i) subject identification, (ii) age and sex prediction, (iii) brain asymmetry analysis, and (iv) potential genetic influences on brain morphology. The properties of BrainPrint require the derivation of new algorithms to account for the heterogeneous mix of brain structures with varying discriminative power. We conduct experiments on three datasets, including over 3000 MRI scans from the ADNI database, 436 MRI scans from the OASIS dataset, and 236 MRI scans from the VETSA twin study. All processing steps for obtaining the compact representation are fully automated, making this processing framework particularly attractive for handling large datasets.National Cancer Institute (U.S.) (1K25-CA181632-01)Athinoula A. Martinos Center for Biomedical Imaging (P41-RR014075)Athinoula A. Martinos Center for Biomedical Imaging (P41-EB015896)National Alliance for Medical Image Computing (U.S.) (U54-EB005149)Neuroimaging Analysis Center (U.S.) (P41-EB015902)National Center for Research Resources (U.S.) (U24 RR021382)National Institute of Biomedical Imaging and Bioengineering (U.S.) (5P41EB015896-15)National Institute of Biomedical Imaging and Bioengineering (U.S.) (R01EB006758)National Institute on Aging (AG022381)National Institute on Aging (5R01AG008122-22)National Institute on Aging (AG018344)National Institute on Aging (AG018386)National Center for Complementary and Alternative Medicine (U.S.) (RC1 AT005728-01)National Institute of Neurological Diseases and Stroke (U.S.) (R01 NS052585-01)National Institute of Neurological Diseases and Stroke (U.S.) (1R21NS072652-01)National Institute of Neurological Diseases and Stroke (U.S.) (1R01NS070963)National Institute of Neurological Diseases and Stroke (U.S.) (R01NS083534)National Institutes of Health (U.S.) ((5U01-MH093765

Proceedings of the First International Workshop on Mathematical Foundations of Computational Anatomy (MFCA'06) - Geometrical and Statistical Methods for Modelling Biological Shape Variability

International audienceNon-linear registration and shape analysis are well developed research topic in the medical image analysis community. There is nowadays a growing number of methods that can faithfully deal with the underlying biomechanical behaviour of intra-subject shape deformations. However, it is more difficult to relate the anatomical shape of different subjects. The goal of computational anatomy is to analyse and to statistically model this specific type of geometrical information. In the absence of any justified physical model, a natural attitude is to explore very general mathematical methods, for instance diffeomorphisms. However, working with such infinite dimensional space raises some deep computational and mathematical problems. In particular, one of the key problem is to do statistics. Likewise, modelling the variability of surfaces leads to rely on shape spaces that are much more complex than for curves. To cope with these, different methodological and computational frameworks have been proposed. The goal of the workshop was to foster interactions between researchers investigating the combination of geometry and statistics for modelling biological shape variability from image and surfaces. A special emphasis was put on theoretical developments, applications and results being welcomed as illustrations. Contributions were solicited in the following areas: * Riemannian and group theoretical methods on non-linear transformation spaces * Advanced statistics on deformations and shapes * Metrics for computational anatomy * Geometry and statistics of surfaces 26 submissions of very high quality were recieved and were reviewed by two members of the programm committee. 12 papers were finally selected for oral presentations and 8 for poster presentations. 16 of these papers are published in these proceedings, and 4 papers are published in the proceedings of MICCAI'06 (for copyright reasons, only extended abstracts are provided here)

Alterazioni della corteccia cerebrale e correlati clinici nella Corea di Huntington

Presupposti dello studio La malattia di Huntington è una patologia neurodegenerativa monogenetica autosomica dominante causata da una mutazione del gene HTT. L’età media di insorgenza è di 35-50 anni di età a cui seguiranno il manifestarsi dei sintomi motori, tra cui le ipercinesie coreiche, sintomi cognitivi e psichiatrici il cui andamento progressivo porterà all’exitus in 15-20 anni. La diagnosi si basa sulla clinica suggestiva della patologia associata al test genetico, mentre il trattamento farmacologico palliativo varia in dipendenza di quali sono i sintomi presenti nel paziente, i quali variano a loro volta in base al numero di triplette CAG e l'age of onset. Diversi studi hanno dimostrato che è possibile evidenziare, a livello del singolo paziente, un caratteristico fenotipo di alterazione cerebrale, il cui pattern è progressivamente ingravescente nella HD; però data l’eterogeneità esistente tra gli studi a livello di pazienti inclusi e delle metriche atte a misurare le alterazioni mediante RM, non è possibile definire tra quest’ultime la più efficace ai fini dei trial clinici. Scopo dello studio Lo scopo dello studio è quello di 1)esplorare le alterazioni sottocorticali e corticali nel gruppo HD rispetto al gruppo HC composto da sani di pari età via VBM 2) caratterizzare la natura dell’alterazioni corticali mediante un approccio multimodale indagando se quest’ultime riflettano un progressivo danno corticale, un’alterata plasticità corticale o se invece siano il riflesso di un danno da neurosviluppo 3)identificare quali aree riscontrate significativamente alterate spiegano maggiormente i sintomi descritti e le variabili cliniche analizzate. Materiali e metodi Per questo studio trasversale sono stati inclusi 19 pazienti HD valutati da un punto di vista genetico, clinico, comportamentale, cognitivo e confrontati con un gruppo di 34 soggetti sani di pari range di età per il pattern di alterazioni cerebrali mediante PET/RM 3T Siemens Biograph. Il pattern di alterazione corticale e sottocorticale del singolo paziente è stato calcolato tramite Voxel Based Morphometry a partire dalle immagini anatomiche pesate in MPRAGE T1w3d, poi corrette per i possibili danni vascolari con immagini 3d FLAIR mediante un confronto non-parametrico con soggetti sani di pari età e sesso amiloide-free del dataset ADNI. La natura dell’alterazione in corteccia è stata poi esplorata con Freesufer per le componenti di atrofia(Ctf), plasticità locale e di alterazione da neurosviluppo(LGI). Tramite step-wise regression si è rilevato il ruolo prevalente delle alterazioni in VBM e corticali ai sintomi motori, cognitivi e disautonomie funzionali. Risultati Il nostro studio è riuscito a distinguere il contributo specifico delle aree corticali rispetto ai sintomi motori ed il declino cognitivo, associando invece alla degenerazione striatale e alle alterazioni WM i deficit nelle abilità funzionali. Inoltre, si è comprovato che l’alterazione corticale deriva dalla combinazione in aree distinte dalla riduzione di spessore corticale e delle connessioni cortico-corticali, mentre il misfolding da neurosviluppo è rilevante solo nei joung onset. Clinicamente si riporta un progressivo peggioramento della porzione motoria e funzionale, associata ad un declino cognitivo progressivo compresa la cognitività sociale, finora inesplorata in letteratura, fin dall’esordio della HD. Conclusioni Le alterazioni corticali e sottocorticali sono in linea con la letteratura, a cui si aggiungono nuove evidenze di rilievo: alterazioni della via dorsale e ventrale del linguaggio e l’alterazione come fascio e corticale della componente uditiva. Il contributo differente e parallelo del sottocorticale e corticale in relazione con il fenotipo clinico, sintomi motori e clinici suggerisce possibili target farmacologici, marker di inclusione e di progressione per futuri trial clinici atti a migliorare la gestione clinica del pazienteBackground Huntington's disease is a monogenetic autosomal dominant neurodegenerative disorder due to a mutation in the HTT gene. The average age of onset is 35-50 years of age followed by the onset of motor symptoms, including choreic hyperkinesias, cognitive and psychiatric symptoms whose progressive course will lead to exitus in 15-20 years. The diagnosis is based on the clinic suggestive of the pathology associated with the genetic test, while the palliative pharmacological treatment varies according to which symptoms are present in the patient, which in turn vary according to the number of CAG triplets and the age of onset. Several studies have shown that it is possible to highlight, at the level of the individual patient, a characteristic phenotype of brain alteration, the pattern of which is progressively worsening in HD. However, given the heterogeneity between studies in terms of the patients included and the metrics used to measure alterations by MRI, it is not possible to define the most effective among the latter for the purposes of clinical trials. Aim The aim of the study is to 1) explore the subcortical and cortical alterations in the HD group in comparison to the HC group of age-matched healthy people via VBM 2) characterize the nature of the cortical alterations through a multimodal approach by investigating whether they reflect progressive cortical damage, altered cortical plasticity or if instead they are reflection of a neurodevelopmental damage; 3) Finally, identify which significantly altered areas better explain the described symptoms and the clinical variables investigated. Materials and methods For this cross-sectional study, 19 HD patients were included and evaluated from a genetic, clinical, behavioral, cognitive point of view and compared with a group of 34 healthy subjects of the same age range for the pattern of brain alterations by means of PET/MRI 3T Siemens Biograph. The pattern of cortical and subcortical alteration of the individual patient was calculated by Voxel Based Morphometry from MPRAGE T1w3d-weighted anatomical images, then corrected for possible vascular damage with 3d FLAIR images through a non-parametric comparison with amyloid-free healthy subjects of the same age and sex from the ADNI dataset. The nature of the alteration in cortex was then explored with Freesufer for the components of atrophy (Ctf), local plasticity, and neurodevelopmental alteration (LGI). The prevalent contribution of VBM and cortical alterations to motor symptoms, cognitive symptoms, and functional dysautonomias was found through step-wise regression. Results Our study was able to distinguish the specific contribution of cortical areas regards motor symptoms and cognitive decline, associating instead deficits in functional abilities to striatal degeneration and WM alterations. Furthermore, it has been shown that cortical alteration derives from the combination in distinct areas of reduced cortical thickness and cortical-cortical connections, whereas neurodevelopmental misfolding is relevant only in joung onset. Clinically, a progressive deterioration of the motor and functional portion is reported, associated with progressive cognitive decline including social cognition, hitherto unexplored in the literature, since the onset of HD. Conclusions the cortical and subcortical alterations are in line with the literature, to which new relevant findings are added: alterations in the dorsal and ventral pathway of language and the alteration both as bundle and cortical of the auditory component. The different and parallel contribution observed in the subcortical and cortical in relation to the clinical phenotype, motor symptoms and clinical symptoms suggests possible pharmacological targets, inclusion and progression markers for future clinical trials aimed at improving the clinical management of the patient

Quantifying gyrification using Laplace Beltrami eigenfunction level-sets

Cortical surface is folded into gyri and sulci in the brains of higher mammals. Gyrification indices (GI) are widely used to characterise cortical folding complexity, and are important metrics employed in the quantitative assessment of normal brain development and neurodevelopmental disorders. A new GI metric is proposed that endeavours to combine the advantages of surface-based methods with curvature-based methods. The proposed metric employs a measurement of curvature; however, the use of Laplace-Beltrami eigenfunction level-sets introduces the advantage of focusing on folds, a characteristic previously attributed only to surface-based methods. Applying Laplace-Beltrami eigenfunction level-sets also avoids the need to define an outer surface and correspondence function required by surface-based methods. We demonstrate the utility of the proposed GI with an application to fetal ovine MRI data across key developmental time points

Atlas Construction for Measuring the Variability of Complex Anatomical Structures

RÉSUMÉ La recherche sur l'anatomie humaine, en particulier sur le cœur et le cerveau, est d'un intérêt particulier car leurs anomalies entraînent des pathologies qui sont parmi les principales causes de décès dans le monde et engendrent des coûts substantiels. Heureusement, les progrès en imagerie médicale permettent des diagnostics et des traitements autrefois impossibles. En contrepartie, la quantité phénoménale de données produites par ces technologies nécessite le développement d'outils efficaces pour leur traitement. L'objectif de cette thèse est de proposer un ensemble d'outils permettant de normaliser des mesures prélevées sur différents individus, essentiels à l'étude des caractéristiques de structures anatomiques complexes. La normalisation de mesures consiste à rassembler une collection d'images dans une référence commune, aussi appelée construction d'atlas numériques, afin de combiner des mesures provenant de différents patients. Le processus de construction inclut deux étapes principales; la segmentation d'images pour trouver des régions d'intérêts et le recalage d'images afin de déterminer les correspondances entres régions d'intérêts. Les méthodes actuelles de constructions d'atlas peuvent nécessiter des interventions manuelles, souvent fastidieuses, variables, et sont en outre limitées par leurs mécanismes internes. Principalement, le recalage d'images dépend d'une déformation incrémentales d'images sujettes a des minimums locaux. Le recalage n'est ainsi pas optimal lors de grandes déformations et ces limitations requièrent la nécessite de proposer de nouvelles approches pour la construction d'atlas. Les questions de recherche de cette thèse se concentrent donc sur l'automatisation des méthodes actuelles ainsi que sur la capture de déformations complexes de structures anatomiques, en particulier sur le cœur et le cerveau. La méthodologie adoptée a conduit à trois objectifs de recherche spécifiques. Le premier prévoit un nouveau cadre de construction automatise d'atlas afin de créer le premier atlas humain de l'architecture de fibres cardiaques. Le deuxième vise à explorer une nouvelle approche basée sur la correspondance spectrale, nommée FOCUSR, afin de capturer une grande variabilité de formes sur des maillages. Le troisième aboutit finalement à développer une approche fondamentalement différente pour le recalage d'images à fortes déformations, nommée les démons spectraux. Le premier objectif vise plus particulièrement à construire un atlas statistique de l'architecture des fibres cardiaques a partir de 10 cœurs ex vivo humains. Le système développé a mené à deux contributions techniques et une médicale, soit l'amélioration de la segmentation de structures cardiaques et l'automatisation du calcul de forme moyenne, ainsi que notamment la première étude chez l'homme de la variabilité de l'architecture des fibres cardiaques. Pour résumer les principales conclusions, les fibres du cœur humain moyen varient de +- 12 degrés, l'angle d'helix s'étend entre -41 degrés (+- 26 degrés) sur l'épicarde à +66 degrés (+- 15 degrés) sur l'endocarde, tandis que l'angle transverse varie entre +9 degrés (+- 12 degrés) et +34 degrés (+- 29 degrés) à travers le myocarde. Ces résultats sont importants car ces fibres jouent un rôle clef dans diverses fonctions mécaniques et électrophysiologiques du cœur. Le deuxième objectif cherche à capturer une grande variabilité de formes entre structures anatomiques complexes, plus particulièrement entre cortex cérébraux à cause de l'extrême variabilité de ces surfaces et de leur intérêt pour l'étude de fonctions cognitives. La nouvelle méthode de correspondance surfacique, nommée FOCUSR, exploite des représentations spectrales car l'appariement devient plus facile et rapide dans le domaine spectral plutôt que dans l'espace Euclidien classique. Dans sa forme la plus simple, FOCUSR améliore les méthodes spectrales actuelles par un recalage non rigide des représentations spectrales, toutefois, son plein potentiel est atteint en exploitant des données supplémentaires lors de la mise en correspondance. Par exemple, les résultats ont montré que la profondeur des sillons et de la courbure du cortex cérébral améliore significativement la correspondance de surfaces de cerveaux. Enfin, le troisième objectif vise à améliorer le recalage d'images d'organes ayant des fortes variabilités entre individus ou subis de fortes déformations, telles que celles créées par le mouvement cardiaque. La méthodologie amenée par la correspondance spectrale permet d'améliorer les approches conventionnelles de recalage d'images. En effet, les représentations spectrales, capturant des similitudes géométriques globales entre différentes formes, permettent de surmonter les limitations actuelles des méthodes de recalage qui restent guidées par des forces locales. Le nouvel algorithme, nommé démons spectraux, peut ainsi supporter de très grandes déformations locales et complexes entre images, et peut être tout autant adapté a d'autres approches, telle que dans un cadre de recalage conjoint d'images. Il en résulte un cadre complet de construction d'atlas, nommé démons spectraux multijoints, où la forme moyenne est calculée directement lors du processus de recalage plutôt qu'avec une approche séquentielle de recalage et de moyennage. La réalisation de ces trois objectifs spécifiques a permis des avancées dans l'état de l'art au niveau des méthodes de correspondance spectrales et de construction d'atlas, en permettant l'utilisation d'organes présentant une forte variabilité de formes. Dans l'ensemble, les différentes stratégies fournissent de nouvelles contributions sur la façon de trouver et d'exploiter des descripteurs globaux d'images et de surfaces. D'un point de vue global, le développement des objectifs spécifiques établit un lien entre : a) la première série d'outils, mettant en évidence les défis à recaler des images à fortes déformations, b) la deuxième série d'outils, servant à capturer de fortes déformations entre surfaces mais qui ne reste pas directement applicable a des images, et c) la troisième série d'outils, faisant un retour sur le traitement d'images en permettant la construction d'atlas a partir d'images ayant subies de fortes déformations. Il y a cependant plusieurs limitations générales qui méritent d'être investiguées, par exemple, les données partielles (tronquées ou occluses) ne sont pas actuellement prises en charge les nouveaux outils, ou encore, les stratégies algorithmiques utilisées laissent toujours place à l'amélioration. Cette thèse donne de nouvelles perspectives dans les domaines de l'imagerie cardiaque et de la neuroimagerie, toutefois, les nouveaux outils développés sont assez génériques pour être appliqués a tout recalage d'images ou de surfaces. Les recommandations portent sur des recherches supplémentaires qui établissent des liens avec la segmentation à base de graphes, pouvant conduire à un cadre complet de construction d'atlas où la segmentation, le recalage, et le moyennage de formes seraient tous interdépendants. Il est également recommandé de poursuivre la recherche sur la construction de meilleurs modèles électromécaniques cardiaques à partir des résultats de cette thèse. En somme, les nouveaux outils offrent de nouvelles bases de recherche et développement pour la normalisation de formes, ce qui peut potentiellement avoir un impact sur le diagnostic, ainsi que la planification et la pratique d'interventions médicales.----------ABSTRACT Research on human anatomy, in particular on the heart and the brain, is a primary concern for society since their related diseases are among top killers across the globe and have exploding associated costs. Fortunately, recent advances in medical imaging offer new possibilities for diagnostics and treatments. On the other hand, the growth in data produced by these relatively new technologies necessitates the development of efficient tools for processing data. The focus of this thesis is to provide a set of tools for normalizing measurements across individuals in order to study complex anatomical characteristics. The normalization of measurements consists of bringing a collection of images into a common reference, also known as atlas construction, in order to combine measurements made on different individuals. The process of constructing an atlas involves the topics of segmentation, which finds regions of interest in the data (e.g., an organ, a structure), and registration, which finds correspondences between regions of interest. Current frameworks may require tedious and hardly reproducible user interactions, and are additionally limited by their computational schemes, which rely on slow iterative deformations of images, prone to local minima. Image registration is, therefore, not optimal with large deformations. Such limitations indicate the need to research new approaches for atlas construction. The research questions are consequently addressing the problems of automating current frameworks and capturing global and complex deformations between anatomical structures, in particular between human hearts and brains. More precisely, the methodology adopted in the thesis led to three specific research objectives. Briefly, the first step aims at developing a new automated framework for atlas construction in order to build the first human atlas of the cardiac fiber architecture. The second step intends to explore a new approach based on spectral correspondence, named FOCUSR, in order to precisely capture large shape variability. The third step leads, finally, to a fundamentally new approach for image registration with large deformations, named the Spectral Demons algorithm. The first objective aims more specifically at constructing a statistical atlas of the cardiac fiber architecture from a unique human dataset of 10 ex vivo hearts. The developed framework made two technical, and one medical, contributions, that are the improvement of the segmentation of cardiac structures, the automation of the shape averaging process, and more importantly, the first human study on the variability of the cardiac fiber architecture. To summarize the main finding, the fiber orientations in human hearts has been found to vary with about +- 12 degrees, the range of the helix angle spans from -41 degrees (+- 26 degrees) on the epicardium to +66 degrees (+- 15 degrees) on the endocardium, while, the range of the transverse angle spans from +9 degrees (+- 12 degrees) to +34 degrees (+- 29 degrees) across the myocardial wall. These findings are significant in cardiology since the fiber architecture plays a key role in cardiac mechanical functions and in electrophysiology. The second objective intends to capture large shape variability between complex anatomical structures, in particular between cerebral cortices due to their highly convoluted surfaces and their high anatomical and functional variability across individuals. The new method for surface correspondence, named FOCUSR, exploits spectral representations since matching is easier in the spectral domain rather than in the conventional Euclidean space. In its simplest form, FOCUSR improves current spectral approaches by refining spectral representations with a nonrigid alignment; however, its full power is demonstrated when using additional features during matching. For instance, the results showed that sulcal depth and cortical curvature improve significantly the accuracy of cortical surface matching. Finally, the third objective is to improve image registration for organs with a high inter-subject variability or undergoing very large deformations, such as the heart. The new approach brought by the spectral matching technique allows the improvement of conventional image registration methods. Indeed, spectral representations, which capture global geometric similarities and large deformations between different shapes, may be used to overcome a major limitation of current registration methods, which are in fact guided by local forces and restrained to small deformations. The new algorithm, named Spectral Demons, can capture very large and complex deformations between images, and can additionally be adapted to other approaches, such as in a groupwise configuration. This results in a complete framework for atlas construction, named Groupwise Spectral Demons, where the average shape is computed during the registration process rather than in sequential steps. The achievements of these three specific objectives permitted advances in the state-of-the-art of spectral matching methods and of atlas construction, enabling the registration of organs with significant shape variability. Overall, the investigation of these different strategies provides new contributions on how to find and exploit global descriptions of images and surfaces. From a global perspective, these objectives establish a link between: a) the first set of tools, that highlights the challenges in registering images with very large deformations, b) the second set of tools, that captures very large deformations between surfaces but are not applicable to images, and c) the third set of tools, that comes back on processing images and allows a natural construction of atlases from images with very large deformations. There are, however, several general remaining limitations, for instance, partial data (truncated or occluded) is currently not supported by the new tools, or also, the strategy for computing and using spectral representations still leaves room for improvement. This thesis gives new perspectives in cardiac and neuroimaging, yet at the same time, the new tools remain general enough for virtually any application that uses surface or image registration. It is recommended to research additional links with graph-based segmentation methods, which may lead to a complete framework for atlas construction where segmentation, registration and shape averaging are all interlinked. It is also recommended to pursue research on building better cardiac electromechanical models from the findings of this thesis. Nevertheless, the new tools provide new grounds for research and application of shape normalization, which may potentially impact diagnostic, as well as planning and performance of medical interventions

A gyrification analysis approach based on Laplace Beltrami eigenfunction level sets

An accurate measure of the complexity of patterns of cortical folding or gyrification is necessary for understanding normal brain development and neurodevelopmental disorders. Conventional gyrification indices (GIs) are calculated based on surface curvature (curvature-based GI) or an outer hull surface of the cortex (outer surface-based GI). The latter is dependent on the definition of the outer hull surface and a corresponding function between surfaces. In the present study, we propose the Laplace Beltrami-based gyrification index (LB-GI). This is a new curvature-based local GI computed using the first three Laplace Beltrami eigenfunction level sets. As with outer surface-based GI methods, this method is based on the hypothesis that gyrification stems from a flat surface during development. However, instead of quantifying gyrification with reference to corresponding points on an outer hull surface, LB-GI quantifies the gyrification at each point on the cortical surface with reference to their surrounding gyral points, overcoming several shortcomings of existing methods. The LB-GI was applied to investigate the cortical maturation profile of the human brain from preschool to early adulthood using the PING database. The results revealed more detail in patterns of cortical folding than conventional curvature-based methods, especially on frontal and posterior tips of the brain, such as the frontal pole, lateral occipital, lateral cuneus, and lingual. Negative associations of cortical folding with age were observed at cortical regions, including bilateral lingual, lateral occipital, precentral gyrus, postcentral gyrus, and superior frontal gyrus. The results also indicated positive significant associations between age and the LB-GI of bilateral insula, the medial orbitofrontal, frontal pole and rostral anterior cingulate regions. It is anticipated that the LB-GI will be advantageous in providing further insights in the understanding of brain development and degeneration in large clinical neuroimaging studies