Dilated Dense U-Net for Infant Hippocampus Subfield Segmentation

Accurate and automatic segmentation of infant hippocampal subfields from magnetic resonance (MR) images is an important step for studying memory related infant neurological diseases. However, existing hippocampal subfield segmentation methods were generally designed based on adult subjects, and would compromise performance when applied to infant subjects due to insufficient tissue contrast and fast changing structural patterns of early hippocampal development. In this paper, we propose a new fully convolutional network (FCN) for infant hippocampal subfield segmentation by embedding the dilated dense network in the U-net, namely DUnet. The embedded dilated dense network can generate multi-scale features while keeping high spatial resolution, which is useful in fusing the low-level features in the contracting path with the high-level features in the expanding path. To further improve the performance, we group every pair of convolutional layers with one residual connection in the DUnet, and obtain the Residual DUnet (ResDUnet). Experimental results show that our proposed DUnet and ResDUnet improve the average Dice coefficient by 2.1 and 2.5% for infant hippocampal subfield segmentation, respectively, when compared with the classic 3D U-net. The results also demonstrate that our methods outperform other state-of-the-art methods

Multimodal Hippocampal Subfield Grading For Alzheimer’s Disease Classification

Numerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer’s disease (AD). Most of these methods have focused on the hippocampus, which is known to be one of the earliest structures impacted by the disease. To date, patch-based grading approaches provide among the best biomarkers based on the hippocampus. However, this structure is complex and is divided into different subfields, not equally impacted by AD. Former in-vivo imaging studies mainly investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity measurements. The aim of our work is to improve the current classification performances based on the hippocampus with a new multimodal patch-based framework combining structural and diffusivity MRI. The combination of these two MRI modalities enables the capture of subtle structural and microstructural alterations. Moreover, we propose to study the efficiency of this new framework applied to the hippocampal subfields. To this end, we compare the classification accuracy provided by the different hippocampal subfields using volume, mean diffusivity, and our novel multimodal patch-based grading framework combining structural and diffusion MRI. The experiments conducted in this work show that our new multimodal patch-based method applied to the whole hippocampus provides the most discriminating biomarker for advanced AD detection while our new framework applied into subiculum obtains the best results for AD prediction, improving by two percentage points the accuracy compared to the whole hippocampus

Data mining MR image features of select structures for lateralization of mesial temporal lobe epilepsy

PURPOSE: This study systematically investigates the predictive power of volumetric imaging feature sets extracted from select neuroanatomical sites in lateralizing the epileptogenic focus in mesial temporal lobe epilepsy (mTLE) patients. METHODS: A cohort of 68 unilateral mTLE patients who had achieved an Engel class I outcome postsurgically was studied retrospectively. The volumes of multiple brain structures were extracted from preoperative magnetic resonance (MR) images in each. The MR image data set consisted of 54 patients with imaging evidence for hippocampal sclerosis (HS-P) and 14 patients without (HS-N). Data mining techniques (i.e., feature extraction, feature selection, machine learning classifiers) were applied to provide measures of the relative contributions of structures and their correlations with one another. After removing redundant correlated structures, a minimum set of structures was determined as a marker for mTLE lateralization. RESULTS: Using a logistic regression classifier, the volumes of both hippocampus and amygdala showed correct lateralization rates of 94.1%. This reflected about 11.7% improvement in accuracy relative to using hippocampal volume alone. The addition of thalamic volume increased the lateralization rate to 98.5%. This ternary-structural marker provided a 100% and 92.9% mTLE lateralization accuracy, respectively, for the HS-P and HS-N groups. CONCLUSIONS: The proposed tristructural MR imaging biomarker provides greater lateralization accuracy relative to single- and double-structural biomarkers and thus, may play a more effective role in the surgical decision-making process. Also, lateralization of the patients with insignificant atrophy of hippocampus by the proposed method supports the notion of associated structural changes involving the amygdala and thalamus

Quantitative MRI correlates of hippocampal and neocortical pathology in intractable temporal lobe epilepsy

Intractable or drug-resistant epilepsy occurs in over 30% of epilepsy patients, with many of these patients undergoing surgical excision of the affected brain region to achieve seizure control. Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to investigate histopathological correlates of quantitative relaxometry and DTI from hippocampal and neocortical specimens of intractable TLE patients. To achieve this goal I developed and evaluated a pipeline for histology to in-vivo MRI image registration, which finds dense spatial correspondence between both modalities. This protocol was divided in two steps whereby sparsely sectioned histology from temporal lobe specimens was first registered to the intermediate ex-vivo MRI which is then registered to the in-vivo MRI, completing a pipeline for histology to in-vivo MRI registration. When correlating relaxometry and DTI with neuronal density and morphology in the temporal lobe neocortex, I found T1 to be a predictor of neuronal density in the neocortical GM and demonstrated that employing multi-parametric MRI (combining T1 and FA together) provided a significantly better fit than each parameter alone in predicting density of neurons. This work was the first to relate in-vivo T1 and FA values to the proportion of neurons in GM. When investigating these quantitative multimodal parameters with histological features within the hippocampal subfields, I demonstrated that MD correlates with neuronal density and size, and can act as a marker for neuron integrity within the hippocampus. More importantly, this work was the first to highlight the potential of subfield relaxometry and diffusion parameters (mainly T2 and MD) as well as volumetry in predicting the extent of cell loss per subfield pre-operatively, with a precision so far unachievable. These results suggest that high-resolution quantitative MRI sequences could impact clinical practice for pre-operative evaluation and prediction of surgical outcomes of intractable epilepsy

Diagnostic Performance of MRI Volumetry in Epilepsy Patients With Hippocampal Sclerosis Supported Through a Random Forest Automatic Classification Algorithm

Introduction: Several methods offer free volumetry services for MR data that adequately quantify volume differences in the hippocampus and its subregions. These methods are frequently used to assist in clinical diagnosis of suspected hippocampal sclerosis in temporal lobe epilepsy. A strong association between severity of histopathological anomalies and hippocampal volumes was reported using MR volumetry with a higher diagnostic yield than visual examination alone. Interpretation of volumetry results is challenging due to inherent methodological differences and to the reported variability of hippocampal volume. Furthermore, normal morphometric differences are recognized in diverse populations that may need consideration. To address this concern, we highlighted procedural discrepancies including atlas definition and computation of total intracranial volume that may impact volumetry results. We aimed to quantify diagnostic performance and to propose reference values for hippocampal volume from two well-established techniques: FreeSurfer v.06 and volBrain-HIPS. Methods: Volumetry measures were calculated using clinical T1 MRI from a local population of 61 healthy controls and 57 epilepsy patients with confirmed unilateral hippocampal sclerosis. We further validated the results by a state-of-the-art machine learning classification algorithm (Random Forest) computing accuracy and feature relevance to distinguish between patients and controls. This validation process was performed using the FreeSurfer dataset alone, considering morphometric values not only from the hippocampus but also from additional non-hippocampal brain regions that could be potentially relevant for group classification. Mean reference values and 95% confidence intervals were calculated for left and right hippocampi along with hippocampal asymmetry degree to test diagnostic accuracy. Results: Both methods showed excellent classification performance (AUC:> 0.914) with noticeable differences in absolute (cm3) and normalized volumes. Hippocampal asymmetry was the most accurate discriminator from all estimates (AUC:1~0.97). Similar results were achieved in the validation test with an automatic classifier (AUC:>0.960), disclosing hippocampal structures as the most relevant features for group differentiation among other brain regions. Conclusion: We calculated reference volumetry values from two commonly used methods to accurately identify patients with temporal epilepsy and hippocampal sclerosis. Validation with an automatic classifier confirmed the principal role of the hippocampus and its subregions for diagnosis.Fil: Princich, Juan Pablo. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital de Pediatria Juan Pedro Garrahan. Direccion Asociada de Docencia E Investigacion; ArgentinaFil: Donnelly Kehoe, Patricio Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; ArgentinaFil: Deleglise, Álvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Vallejo Azar, Mariana Nahir. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Pascariello, Guido Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; ArgentinaFil: Seoane, Pablo. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Verón Do Santos, José Gabriel. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Collavini, Santiago. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; Argentina. Universidad Nacional Arturo Jauretche. Instituto de Ingeniería y Agronomía; ArgentinaFil: Nasimbera, Alejandro Hugo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentin

Anatomical and microstructural determinants of hippocampal subfield functional connectome embedding

The hippocampus plays key roles in cognition and affect and serves as a model system for structure/function studies in animals. So far, its complex anatomy has challenged investigations targeting its substructural organization in humans. State-of-the-art MRI offers the resolution and versatility to identify hippocampal subfields, assess its microstructure, and study topographical principles of its connectivity in vivo. We developed an approach to unfold the human hippocampus and examine spatial variations of intrinsic functional connectivity in a large cohort of healthy adults. In addition to mapping common and unique connections across subfields, we identified two main axes of subregional connectivity transitions. An anterior/posterior gradient followed long-axis landmarks and metaanalytical findings from task-based functional MRI, while a medial/lateral gradient followed hippocampal infolding and correlated with proxies of cortical myelin. Findings were consistent in an independent sample and highly stable across resting-state scans. Our results provide robust evidence for long-axis specialization in the resting human hippocampus and suggest an intriguing interplay between connectivity and microstructure

Multi-modal characterization of rapid anterior hippocampal volume increase associated with aerobic exercise.

The hippocampus has been shown to demonstrate a remarkable degree of plasticity in response to a variety of tasks and experiences. For example, the size of the human hippocampus has been shown to increase in response to aerobic exercise. However, it is currently unknown what underlies these changes. Here we scanned sedentary, young to middle-aged human adults before and after a six-week exercise intervention using nine different neuroimaging measures of brain structure, vasculature, and diffusion. We then tested two different hypotheses regarding the nature of the underlying changes in the tissue. Surprisingly, we found no evidence of a vascular change as has been previously reported. Rather, the pattern of changes is better explained by an increase in myelination. Finally, we show hippocampal volume increase is temporary, returning to baseline after an additional six weeks without aerobic exercise. This is the first demonstration of a change in hippocampal volume in early to middle adulthood suggesting that hippocampal volume is modulated by aerobic exercise throughout the lifespan rather than only in the presence of age related atrophy. It is also the first demonstration of hippocampal volume change over a period of only six weeks, suggesting gross morphometric hippocampal plasticity occurs faster than previously thought

Globally Optimal Coupled Surfaces for Semi-automatic Segmentation of Medical Images

Manual delineations are of paramount importance in medical imaging, for instance to train supervised methods and evaluate automatic segmentation algorithms. In volumetric images, manually tracing regions of interest is an excruciating process in which much time is wasted labeling neighboring 2D slices that are similar to each other. Here we present a method to compute a set of discrete minimal surfaces whose boundaries are specified by user-provided segmentations on one or more planes. Using this method, the user can for example manually delineate one slice every n and let the algorithm complete the segmentation for the slices in between. Using a discrete framework, this method globally minimizes a cost function that combines a regularizer with a data term based on image intensities, while ensuring that the surfaces do not intersect each other or leave holes in between. While the resulting optimization problem is an integer program and thus NP-hard, we show that the equality constraint matrix is totally unimodular, which enables us to solve the linear program (LP) relaxation instead. We can then capitalize on the existence of efficient LP solvers to compute a globally optimal solution in practical times. Experiments on two different datasets illustrate the superiority of the proposed method over the use of independent, label-wise optimal surfaces (∼ 5% mean increase in Dice when one every six slices is labeled, with some structures improving up to ∼ 10% in Dice)