Relationship between hippocampal atrophy and neuropathology markers: a 7T MRI validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol.

OBJECTIVE: The pathologic validation of European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP). METHODS: Temporal lobes of nine Alzheimer's disease (AD) and seven cognitively normal subjects were scanned post-mortem at 7 Tesla. Hippocampal volumes were obtained with HarP. Six-micrometer-thick hippocampal slices were stained for amyloid beta (Aß), tau, and cresyl violet. Hippocampal subfields were manually traced. Neuronal counts, Aß, and tau burden for each hippocampal subfield were obtained. RESULTS: We found significant correlations between hippocampal volume and Braak and Braak staging (ρ = -0.75, P = .001), tau (ρ = -0.53, P = .034), Aß burden (ρ = -0.61, P = .012), and neuronal count (ρ = 0.77, P < .001). Exploratory subfield-wise significant associations were found for Aß in Cornu Ammonis (CA)1 (ρ = -0.58, P = .019) and subiculum (ρ = -0.75, P = .001), tau in CA2 (ρ = -0.59, P = .016), and CA3 (ρ = -0.5, P = .047), and neuronal count in CA1 (ρ = 0.55, P = .028), CA3 (ρ = 0.65, P = .006), and CA4 (ρ = 0.76, P = .001). CONCLUSIONS: The observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD and pathologic validation of HarP.

Delphi definition of the EADC-ADNI Harmonized Protocol for hippocampal segmentation on magnetic resonance.

BACKGROUND: This study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating procedures for magnetic resonance (MR)-based manual hippocampal segmentation. METHODS: The panel received a questionnaire regarding whole hippocampus boundaries and segmentation procedures. Quantitative information was supplied to allow evidence-based answers. A recursive and anonymous Delphi procedure was used to achieve convergence. Significance of agreement among panelists was assessed by exact probability on Fisher's and binomial tests. RESULTS: Agreement was significant on the inclusion of alveus/fimbria (P = .021), whole hippocampal tail (P = .013), medial border of the body according to visible morphology (P = .0006), and on this combined set of features (P = .001). This definition captures 100% of hippocampal tissue, 100% of Alzheimer's disease-related atrophy, and demonstrated good reliability on preliminary intrarater (0.98) and inter-rater (0.94) estimates. DISCUSSION: Consensus was achieved among international experts with respect to hippocampal segmentation using MR resulting in a harmonized segmentation protocol.

Scaling laws for branching vessels of human cerebral cortex.

OBJECTIVE: Vascular architecture, particularly of cerebral microvessels, has profound implications for both health and disease in a variety of areas, such as neuroimaging, angiogenesis and development, Alzheimer's disease, and vascular tumors. We analyzed the architecture of tree-like vessels of the human cerebral cortex. METHODS: Digital three-dimensional images of the microvascular network were obtained from thick sections of India ink-injected human brain by confocal laser microscopy covering a large zone of secondary cortex. A novel segmentation method was used to extract the skeleton and measure the diameter at every vertex. RESULTS: In this paper, we focus on the topology of the cortical tree-like vessels. Using stem-crown decomposition, power-scaling laws were shown to govern the relationships between integrated parameters, such as the distal cumulative length, volume, or normalized flow. This led us toward an experimental confirmation of the allometric equation between mass and metabolic rate. Inversely, the power-law model did not match the relationships between local parameters, such as diameter, and integrated ones. As a consequence, Murray's law did not appropriately model the architecture of cerebrovascular bifurcations. CONCLUSIONS: This study provides a unique, large database and mathematical characterization that may prove valuable for modeling the cerebral.

Practical contouring guidelines with an MR-based atlas of brainstem structures involved in radiation-induced nausea and vomiting.

BACKGROUND AND PURPOSE: The objective of this project was to define consensus guidelines for delineating brainstem substructures (dorsal vagal complex, including the area postrema) involved in radiation-induced nausea and vomiting (RINV). The three parts of the brainstem are rarely delineated, so this study was also an opportunity to find a consensus on this subject. MATERIALS AND METHODS: The dorsal vagal complex (DVC) was identified on autopsy sections and endoscopic descriptions. Anatomic landmarks and boundaries were used to establish radio-anatomic correlations on CT and Magnetic Resonance Imaging (MRI). Additionally, delineation of RINV structures was performed on MRI images and reported on CT scans. Next, guidelines were provided to eight radiation oncologists for delineation guidance of these RINV-related structures on DICOM-RT images of two patients being treated for a nasopharyngeal carcinoma. Interobserver variability was computed. RESULTS: The DVC and the three parts of the brainstem were defined with a concise description of their main anatomic boundaries. The interobserver analysis showed that the DVC, the midbrain, the pons, and the medulla oblongata delineations were reproducible with KI = 0.72, 0.84, 0.94 and 0.89, respectively. The Supplemental Material section provides an atlas of the consensus guidelines projected on 1-mm MR axial slices. CONCLUSIONS: This RINV-atlas was feasible and reproducible for the delineation of RINV structures on planning CT using fused MRI. It may be used to prospectively assess dose-volume relationship for RINV structures and occurrence of nausea vomiting during intracranial or head and neck irradiation.

The circumventricular organs: an atlas of comparative anatomy and vascularization.

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.

A practical guide for the identification of major sulcogyral structures of the human cortex.

The precise sulcogyral localization of cortical lesions is mandatory to improve communication between practitioners and to predict and prevent post-operative deficits. This process, which assumes a good knowledge of the cortex anatomy and a systematic analysis of images, is, nevertheless, sometimes neglected in the neurological and neurosurgical training. This didactic paper proposes a brief overview of the sulcogyral anatomy, using conventional MR-slices, and also reconstructions of the cortical surface after a more or less extended inflation process. This method simplifies the cortical anatomy by removing part of the cortical complexity induced by the folding process, and makes it more understandable. We then reviewed several methods for localizing cortical structures, and proposed a three-step identification: after localizing the lateral, medial or ventro-basal aspect of the hemisphere (step 1), the main interlobar sulci were located to limit the lobes (step 2). Finally, intralobar sulci and gyri were identified (step 3) thanks to the same set of rules. This paper does not propose any new identification method but should be regarded as a set of practical guidelines, useful in daily clinical practice, for detecting the main sulci and gyri of the human cortex.

Branching patterns for arterioles and venules of the human cerebral cortex.

Branching patterns of microvascular networks influence vascular resistance and allow control of peripheral flow distribution. The aim of this paper was to analyze these branching patterns in human cerebral cortex. Digital three-dimensional images of the microvascular network were obtained from thick sections of India ink-injected human brain by confocal laser microscopy covering a large zone of secondary cortex. A novel segmentation method was used to extract the skeletons of 228 vascular trees (152 arterioles and 76 venules) and measure the diameter at every vertex. The branching patterns (area ratios and angles of bifurcations) of nearly 10,000 bifurcations of cortical vascular trees were analyzed, establishing their statistical properties and structural variations as a function of the vessel nature (arterioles versus venules), the parent vessel topological order or the bifurcation type. We also describe their connectivity and discuss the relevance of the assumed optimal design of vascular branching to account for the complex nature of microvascular architecture. The functional implications of some of these structural variations are considered. The branching patterns established from a large database of a human organ contributes to a better understanding of the bifurcation design and provides an essential reference both for diagnosis and for a future large reconstruction of cerebral microvascular network.

Morphometry of the human cerebral cortex microcirculation: general characteristics and space-related profiles.

Studies on human brain microcirculation have thus far yielded few quantitative data, preventing the closest possible interpretation of functional imaging methods such as fMRI and PET that necessarily rely on robustly delineated morphology of haemodynamic systems. Inadequate data in this area can lead to severe underestimation of the spatial specificity of the BOLD response. We took thick sections of Indian ink injected human brain and, using confocal laser microscopy and a novel three-dimensional computer-assisted method we extracted and analyzed hundreds of thousands of vascular segments within a large area of cortex. From this database the global densities, the statistical distributions of diameters and lengths were analysed, separating the tree-like and the net-like parts of the microcirculation. Furthermore, our analysis included variations in volume density along the cortical depth and along vectors parallel to the cortical surface. These morphometric parameters are all key requirements for a sound model of cerebral microcirculation.