Characterizing the properties and orientations of sub-voxel fiber populations, although essential to study white-matter architecture, microstructure and connectivity, remains one of the main challenges faced by the MRI microstructure community. While some progress has been made in overcoming this challenge using models, signal representations and tractography algorithms, these approaches are ultimately limited by their key assumptions or by the lack of specificity of the diffusion signal alone. In order to alleviate these limitations, we combine diffusion-relaxation MR acquisitions incorporating tensor-valued diffusion encoding, Monte-Carlo signal inversions that extract non-parametric intra-voxel distributions of diffusion tensors and relaxation rates, and density-based clustering techniques. This new approach, called "Monte-Carlo density-peak clustering" (MC-DPC), first delineates clusters in the diffusion-orientation subspace of the fiber-like diffusion-relaxation components output by Monte-Carlo signal inversions and then draws from the statistical aspect of these inversion algorithms to compute the median and interquartile range of orientation-resolved means of diffusivities and relaxation rates. Evaluating MC-DPC on tensor-valued diffusion-encoded and T2-weighted correlated datasets in silico and in vivo, we demonstrate its ability to simultaneously capture sub-voxel fiber orientations and cones of uncertainty, and measure fiber-specific diffusion-relaxation properties that are consistent with the known anatomy and existing literature. Straightforwardly translatable to other diffusion-relaxation correlation experiments probing $T_1$ and $T_2^*$, MC-DPC shows potential in tracking bundle-specific patient-control group differences and longitudinal microstructural changes, enabling new tools for microstructure-informed tractography, and mapping tract-specific myelination states.
The study of the interaction between laser and brain tissue has important theoretical and practical significance for brain imaging. A two-dimensional simulation model that studies the propagation of light and heat transfer in brain tissue based on finite element has been developed by using the commercial finite element simulation software COMSOL Multiphysics. In this study, the model consists of three parts of 1) a layer of water on the surface of the brain, 2) brain tissue and 3) short pulsed laser source (the wavelength is 840nm). The laser point source is located in the middle of the layer …
Heat generated from plasmonic nanoparticles can be utilized in plasmonic photothermal therapy. A combination of near-infrared laser and metallic nanoparticles are compelling for the treatment of brain cancer, due to their efficient light-to-heat conversion and bio-compatibility. However, one of the challenges of plasmonic photothermal therapy is to minimize the damage of the surrounding brain tissue. The adjacent tissue can be damaged as the results of either absorption of laser light, thermal conductivity, nanoparticles diffusing from the tumor, or a combination hereof. Hence, we still lack t…
Unconfined compression tests are more convenient to perform on cylindrical samples of brain tissue than tensile tests in order to estimate mechanical properties of the brain tissue because they allow for homogeneous deformations. The reliability of these tests depends significantly on the amount of friction generated at the specimen/platen interface. Thus, there is a crucial need to find an approximate value of the friction coefficient in order to predict a possible overestimation of stresses during unconfined compression tests. In this study, a combined experimental-computational approach was…
3D-Polarized Light Imaging (3D-PLI) reconstructs nerve fibers in histological brain sections by measuring their birefringence. This study investigates another effect caused by the optical anisotropy of brain tissue - diattenuation. Based on numerical and experimental studies and a complete analytical description of the optical system, the diattenuation was determined to be below 4 % in rat brain tissue. It was demonstrated that the diattenuation effect has negligible impact on the fiber orientations derived by 3D-PLI. The diattenuation signal, however, was found to highlight different anatomic…
We studied the transmission of photons in mouse brain in both with and without intact skull states using Monte Carlo method. Photon track, optical absorption density and fluence rate were used as indicators for analysis. We found that, the photon distribution without intact skull goes farther in both longitudinal and transverse directions compared with that of with intact skull. The distribution of optical absorption density and fluence rate was fusiform and rounder on the whole with intact skull. This study will provide reference and theoretical guidance for the optical imaging of mouse brain…
Mechanical characterization of brain tissue has been investigated extensively by various research groups over the past fifty years. These properties are particularly important for modelling Traumatic Brain Injury (TBI). In this research, we present the design and calibration of a High Rate Tension Device (HRTD) capable of performing tests up to a maximum strain rate of 90/s. We use experimental and numerical methods to investigate the effects of inhomogeneous deformation of porcine brain tissue during tension at different specimen thicknesses (4.0-14.0 mm), by performing tension tests at a str…
In this paper we present a methodology to address the problem of brain tissue deformation referred to as 'brain-shift'. This deformation occurs throughout a neurosurgery intervention and strongly alters the accuracy of the neuronavigation systems used to date in clinical routine which rely solely on pre-operative patient imaging to locate the surgical target, such as a tumour or a functional area. After a general description of the framework of our intra-operative image-guided system, we describe a procedure to generate patient specific finite element meshes of the brain and propose a biomecha…
In this paper we present a methodology to address the problem of brain tissue deformation referred to as 'brain-shift'. This deformation occurs throughout a neurosurgery intervention and strongly alters the accuracy of the neuronavigation systems used to date in clinical routine which rely solely on pre-operative patient imaging to locate the surgical target, such as a tumour or a functional area. After a general description of the framework of our intra-operative image-guided system, we describe a procedure to generate patient specific finite element meshes of the brain and propose a biomecha…
The head down tilt (HDT) position is commonly used to simulate vascular and tissue fluid dynamics during spaceflights. In HDT position, the cerebral autoregulation faces difficulties to adjust the vascular tone while the cephalad fluid shifts may yield increased intracranial pressures and altered mechanical properties. Recent MRI T2 mapping in HDT position have shown fluid overpressure in the brain and resulting loss of water contents in the CSF and orbital compartments. Brain MRE was performed here in similar HDT conditions. It was sensitive enough to provide new insights on the overall mecha…
Mesoscopic physics-based dual spectroscopic imaging techniques, partial wave spectroscopy (PWS) and inverse participation ratio (IPR), are used to quantify the nano to submicron scales structural alterations in postnatal pups brain cells and tissues due to fetal alcoholism. Chronic alcoholism during pregnancy, being teratogenic, results in fetal alcohol syndrome and neurological disorder. Results of PWS studies of brain tissues show a higher degree of structural alterations. Furthermore, the IPR analyses of cell nuclei show that spatial molecular mass density structural disorder increases in D…
Extensive research has been carried out for at least 50 years to understand the mechanical properties of brain tissue in order to understand the mechanisms of traumatic brain injury (TBI). The observed large variability in experimental results may be due to the inhomogeneous nature of brain tissue and to the broad range of test conditions. However, test temperature is also considered as one of the factors influencing the properties of brain tissue. In this research, the mechanical properties of porcine brain have been investigated at 22C (room temperature) and at 37C (body temperature) while m…
Identification of white matter fiber tracts of the brain is crucial for delineating the tumor border during neurosurgery. A custom-built Mueller polarimeter was used in reflection configuration for the wide-field imaging of thick section of fixed human brain and fresh calf brain. The experimental images of azimuth of the fast optical axis of linear birefringent medium showed a strong correlation with the silver-stained sample histology image, which is the gold standard for ex-vivo brain fiber tract visualization. The polarimetric images of fresh calf brain tissue demonstrated the same trends i…
We present a quantitative label-free imaging of mouse whole brain tissue slices with sub-micrometre resolution, employing holographic microscopy and an automated scanning platform. From the measured light field images, scattering coefficients and anisotropies are quantitatively retrieved, which enables access to structural information about brain tissues. As a proof of principle, we demonstrate that these scattering parameters enable us to quantitatively address structural alteration in the brain tissues of mice with Alzheimer's disease.
Recommended Implementation of Quantitative Susceptibility Mapping for Clinical Research in The Brain: A Consensus of the ISMRM Electro-Magnetic Tissue Properties Study Group
When transmitting polarised light through histological brain sections, different types of diattenuation (polarisation-dependent attenuation of light) can be observed: In some brain regions, the light is minimally attenuated when it is polarised parallel to the nerve fibres (referred to as D+), in others, it is maximally attenuated (referred to as D-). The underlying mechanisms of these effects and their relationship to tissue properties were so far unknown. Here, we demonstrate in experimental studies that diattenuation of both types D+ and D- can be observed in brain tissue samples from diffe…
In this paper we present a methodology to adress the problem of brain tissue deformation referred to as "brainshift". This deformation occurs throughout a neurosurgery intervention and strongly alters the accuracy of the neuronavigation systems used to date in clinical routine which rely solely on preoperative patient imaging to locate the surgical target, such as a tumour or a functional area. After a general description of the framework of our intraoperative image-guided system, we propose a biomechanical model of the brain which can take into account interactively such deformations as well …
The large variability in experimentally measured mechanical properties of brain tissue is due to many factors including heterogeneity, anisotropy, age dependence and post-mortem time. Moreover, differences in test protocols also influence these measured properties. This paper shows that the temperature at which porcine brain tissue is stored or preserved prior to testing has a significant effect on the mechanical properties of brain tissue, even when tests are conducted at the same temperatures. Three groups of brain tissue were stored separately for at least one hour at three different preser…
We study the effect of lesions on our four-electrode measurements of the ionic conductivity of (1 cm3) samples of human brain excised from patients undergoing pediatric epilepsy surgery. For most (about 94 %) samples the low-frequency ionic conductivity rises upon increasing the applied frequency. We attributed this behavior to the long-range (0.4 mm) diffusion of solvated sodium cations before encountering impenetrable blockages such as cell membranes, blood vessels and cell walls. By contrast, the low-frequency ionic conductivity of some (6 %) brain tissue samples falls with increasing appli…
The mechanical characterization of brain tissue at high loading velocities is vital for understanding and modeling Traumatic Brain Injury (TBI). The most severe form of TBI is diffuse axonal injury (DAI) which involves damage to individual nerve cells (neurons). DAI in animals and humans occurs at strains > 10% and strain rates > 10/s. The mechanical properties of brain tissues at these strains and strain rates are of particular significance, as they can be used in finite element human head models to accurately predict brain injuries under different impact conditions. Existing conventional ten…
Phase contrast X-ray imaging (PCXI) is an emerging imaging modality that has the potential to greatly improve radiography for medical imaging and materials analysis. PCXI makes it possible to visualise soft-tissue structures that are otherwise unresolved with conventional CT by rendering phase gradients in the X-ray wavefield visible. This can improve the contrast resolution of soft tissues structures, like the lungs and brain, by orders of magnitude. Phase retrieval suppresses noise, revealing weakly-attenuating soft tissue structures, however it does not remove the artefacts from the highly …
Invasive intracranial electroencephalography (iEEG) or electrocorticography (ECoG) measures electric potential directly on the surface of the brain and can be used to inform treatment planning for epilepsy surgery. Combined with numerical modeling they can further improve accuracy of epilepsy surgery planning. Accurate solution of the iEEG or ECoG forward problem, which is a crucial prerequisite for solving the inverse problem in epilepsy seizure onset zone localization, requires accurate representation of the patient's brain geometry and tissue electrical conductivity after implantation of el…
More children and adults under the age of 40 die of brain tumor than from any other cancer. Brain surgery constitutes the first and decisive step for the treatment of such tumors. It is extremely crucial to achieve complete tumor resection during surgery, however, this is a highly challenging task, as it is very difficult to visually differentiate tumorous cells from the surrounding healthy white matter. The nerve fiber bundles constitutive of the white matter are organized in such a way that they exhibit a certain degree of structural anisotropy and birefringence. The birefringence exhibited …
Evaluation and optimization of deep learning models for enhanced detection of brain cancer using transmission optical microscopy of thin brain tissue samples
Neurosurgery interventions involve complex tracking systems because a tissue deformation takesplace. The neuronavigation system relies only on preoperative images. In order to overcome the soft tissue deformations and guarantee the accuracy of the navigation a biomechanical model can be used during surgery to simulate the deformation of the brain. Therefore, a mesh generation for an optimal real-time Finite Element Model (FEM) becomes crucial. In this work we present different alternatives from a meshgeneration point of view that were evaluated to optimize the process in terms of elements quan…
During the first years of life, the human brain undergoes dynamic spatially-heterogeneous changes, involving differentiation of neuronal types, dendritic arborization, axonal ingrowth, outgrowth and retraction, synaptogenesis, and myelination. To better quantify these changes, this article presents a method for probing tissue microarchitecture by characterizing water diffusion in a spectrum of length scales, factoring out the effects of intra-voxel orientation heterogeneity. Our method is based on the spherical means of the diffusion signal, computed over gradient directions for a fixed set of…
Neurons transmit active potentials through axons, which are essential for the brain to function. In this study, the axonal networks of the murine brain were visualized with X-ray tomographic microscopy, also known as X-ray microtomography or micro-CT. Murine brain samples were freeze-dried to reconstitute the intrinsic contrast of tissue constituents and subjected to X-ray visualization. A whole brain hemisphere visualized by absorption contrast illustrated three-dimensional structures including those of the striatum, corpus callosum, and anterior commissure. Axonal tracts observed in the stri…
TUM, Munich, Germany（慕尼黑工业大学）；Munich Center for Machine Learning (MCML), Munich, Germany（慕尼黑机器学习中心）；University of Zurich, Switzerland（苏黎世大学）；Chair for AI in Healthcare and Medicine, TUM, Munich, Germany（慕尼黑工业大学医疗保健与医学人工智能讲席）；Institute of Continuum Mechanics and Biomechanics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany（埃尔朗根-纽伦堡大学连续力学与生物力学研究所）
A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of Full-Field Optical Coherence Tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1\mum resolution in 3D with a typical 200\mum imaging depth. A 1cm2 specimen is scanned at a single depth and processed in about 5 minutes. This rapid imaging process is non-invasive and 30 requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and bra…
We review, systematize and discuss models of diffusion in neuronal tissue, by putting them into an overarching physical context of coarse-graining over an increasing diffusion length scale. From this perspective, we view research on quantifying brain microstructure as occurring along the three major avenues. The first avenue focusses on the transient, or time-dependent, effects in diffusion. These effects signify the gradual coarse-graining of tissue structure, which occurs qualitatively differently in different brain tissue compartments. We show that studying the transient effects has the pot…
Dual Photonics Probing of Nano- to Submicron-Scale Structural Alterations in Human Brain Tissues or Cells and Chromatin or DNA with the Progression of Alzheimers Disease
Alterations of brain tissue structural complexity and disorder in Alzheimer's disease (AD): Fractal, multifractal, fractal transformation, and disorder strength analyses
Traumatic brain injury (TBI) occurs when local mechanical load exceeds certain tolerance levels for brain tissue. Extensive research has been done previously for brain matter experiencing compression at quasistatic loading; however, limited data is available to model TBI under dynamic impact conditions. In this research, an experimental setup was developed to perform unconfined compression tests and stress relaxation tests at strain rates < 90/s. The brain tissue showed a stiffer response with increasing strain rates, showing that hyperelastic models are not adequate. Specifically, the compres…
As bone and air produce weak signals with conventional MR sequences, segmentation of these tissues particularly difficult in MRI. We propose to integrate patch-based anatomical signatures and an auto-context model into a machine learning framework to iteratively segment MRI into air, bone and soft tissue. The proposed semantic classification random forest (SCRF) method consists of a training stage and a segmentation stage. During training stage, patch-based anatomical features were extracted from registered MRI-CT training images, and the most informative features were identified to train a se…
Alterations of brain tissue structural complexity and disorder in Parkinson disease (PD): Fractal, multifractal, fractal transformation, and disorder strength analyses
Previous simulation studies by Menzel et al. [Phys. Rev. X 10, 021002 (2020)] have shown that scattering patterns of light transmitted through artificial nerve fiber constellations contain valuable information about the tissue substructure such as the individual fiber orientations in regions with crossing nerve fibers. Here, we present a method that measures these scattering patterns in monkey and human brain tissue using coherent Fourier scatterometry with normally incident light. By transmitting a non-focused laser beam (wavelength of 633 nm) through unstained histological brain sections, we…
Diffusion-weighted magnetic resonance imaging (DW-MRI) is used to characterize brain tissue microstructure employing tissue-specific biophysical models. A current limitation, however, is that most of the proposed models are based on the assumption of negligible water exchange between the intra- and extracellular compartments, which might not be valid in various brain tissues, including unmyelinated axons, gray matter, and tumors. The purpose of this work is to quantify the effect of membrane permeability on the estimates of two popular models neglecting exchange, and compare their performance …
The method 3D polarised light imaging (3D-PLI) measures the birefringence of histological brain sections to determine the spatial course of nerve fibres (myelinated axons). While the in-plane fibre directions can be determined with high accuracy, the computation of the out-of-plane fibre inclinations is more challenging because they are derived from the strength of the birefringence signals (retardation), which depends e.g. on the amount of nerve fibres. One possibility to improve the accuracy is to consider the average transmitted light intensity (transmittance weighting). The current procedu…
The neuroimaging technique three-dimensional polarized light imaging (3D-PLI) provides a high-resolution reconstruction of nerve fibres in human post-mortem brains. The orientations of the fibres are derived from birefringence measurements of histological brain sections assuming that the nerve fibres - consisting of an axon and a surrounding myelin sheath - are uniaxial birefringent and that the measured optic axis is oriented in direction of the nerve fibres (macroscopic model). Although experimental studies support this assumption, the molecular structure of the myelin sheath suggests that t…
For developing a detailed network model of the brain based on image reconstructions, it is necessary to spatially resolve crossing nerve fibers. The accuracy hereby depends on many factors, including the spatial resolution of the imaging technique. 3D Polarized Light Imaging (3D-PLI) allows the three-dimensional reconstruction of nerve fiber tracts in whole brain sections with micrometer in-plane resolution, but leaves uncertainties in pixels containing crossing fibers. Here we introduce Scattered Light Imaging (SLI) to resolve the substructure of nerve fiber crossings. The measurement is perf…
In many laboratories, conventional bright-field transmission microscopes are available to study the structure and organization principles of fibrous tissue samples, but they usually provide only 2D information. To access the third (out-of-plane) dimension, more advanced techniques are employed. An example is 3D Polarized Light Imaging (3D-PLI), which measures the birefringence of histological brain sections to derive the spatial nerve fiber orientations. Here, we show how light scattering in transmission microscopy measurements can be leveraged to gain 3D structural information about fibrous t…
SQUID-based MRI (magnetic resonance imaging) at microtesla fields has developed significantly over the past few years. Here we describe application of this method for magnetic relaxation measurements in the living human brain. We report values of the longitudinal relaxation time T1 for brain tissues, measured in vivo for the first time at microtesla fields. The experiments were performed at 46 microtesla field using a seven-channel SQUID system designed for microtesla MRI and MEG. Values of T1, measured for different tissues at this field, are found to be close (within 5%) to the corresponding…
Concordia University（康考迪亚大学）；Université Grenoble Alpes（格勒诺布尔阿尔卑斯大学）；CNRS（法国国家科学研究中心）；Grenoble INP（格勒诺布尔理工学院）；Western University（韦仕敦大学）；St. Olavs Hospital（圣奥拉夫医院）；Trondheim University Hospital（特隆赫姆大学医院）；Norwegian University of Science and Technology (NTNU)（挪威科技大学）；SINTEF Digital（SINTEF数字研究所）
Purpose: Registration and segmentation of magnetic resonance (MR) and ultrasound (US) images play an essential role in surgical planning and resection of brain tumors. However, validating these techniques is challenging due to the scarcity of publicly accessible sources with high-quality ground truth information. To this end, we propose a unique annotation dataset of tumor tissues and resection cavities from the previously published RESECT dataset (Xiao et al. 2017) to encourage a more rigorous assessments of image processing techniques. Acquisition and validation methods: The RESECT database …
Mesoscale tissue properties and electric fields in brain stimulation: Bridging the macroscopic and microscopic scales using layer-specific cortical conductivity
Duke University（杜克大学）；Technical University of Denmark（丹麦技术大学）；Copenhagen University Hospital Amager and Hvidovre（哥本哈根大学医院阿马格和哈弗尔校区）；Dartmouth College（达特茅斯学院）
The cerebral arteries are difficult to reproduce from first principles, featuring interwoven territories, and intricate layers of grey and white matter with differing metabolic demand. The aim of this study was to identify the ideal configuration of arteries required to sustain an entire brain hemisphere based on minimisation of the energy required to supply the tissue. The 3D distribution of grey and white matter within a healthy human brain was first segmented from Magnetic Resonance Images. A novel simulated annealing algorithm was then applied to determine the optimal configuration of arte…
The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: The individual fiber orientations are determined by illuminating unstained histological brain sections from different directions, measuring the transmitted scattered light under normal incidence, and studying the light intensity profiles of each pixel in the resulting image serie…
