Biophysically motivated efficient estimation of the spatially isotropic R*2 component from a single gradient‐recalled echo measurement

Purpose To propose and validate an efficient method, based on a biophysically motivated signal model, for removing the orientation‐dependent part of R*2 using a single gradient‐recalled echo (GRE) measurement. Methods The proposed method utilized a temporal second‐order approximation of the hollow‐cylinder‐fiber model, in which the parameter describing the linear signal decay corresponded to the orientation‐independent part of R*2. The estimated parameters were compared to the classical, mono‐exponential decay model for R*2 in a sample of an ex vivo human optic chiasm (OC). The OC was measured at 16 distinct orientations relative to the external magnetic field using GRE at 7T. To show that the proposed signal model can remove the orientation dependence of R*2, it was compared to the established phenomenological method for separating R*2 into orientation‐dependent and ‐independent parts. Results Using the phenomenological method on the classical signal model, the well‐known separation of R*2 into orientation‐dependent and ‐independent parts was verified. For the proposed model, no significant orientation dependence in the linear signal decay parameter was observed. Conclusions Since the proposed second‐order model features orientation‐dependent and ‐independent components at distinct temporal orders, it can be used to remove the orientation dependence of R*2 using only a single GRE measurement

Finding the best clearing approach: Towards 3D wide-scale multimodal imaging of aged human brain tissue

The accessibility of new wide-scale multimodal imaging techniques led to numerous clearing techniques emerging over the last decade. However, clearing mesoscopic-sized blocks of aged human brain tissue remains an extremely challenging task. Homogenizing refractive indices and reducing light absorption and scattering are the foundation of tissue clearing. Due to its dense and highly myelinated nature, especially in white matter, the human brain poses particular challenges to clearing techniques. Here, we present a comparative study of seven tissue clearing approaches and their impact on aged human brain tissue blocks (> 5 mm). The goal was to identify the most practical and efficient method in regards to macroscopic transparency, brief clearing time, compatibility with immunohistochemical processing and wide-scale multimodal microscopic imaging. We successfully cleared 26 × 26 × 5 mm3-sized human brain samples with two hydrophilic and two hydrophobic clearing techniques. Optical properties as well as light and antibody penetration depths highly vary between these methods. In addition to finding the best clearing approach, we compared three microscopic imaging setups (the Zeiss Laser Scanning Microscope (LSM) 880 , the Miltenyi Biotec Ultramicroscope ll (UM ll) and the 3i Marianas LightSheet microscope) regarding optimal imaging of large-scale tissue samples. We demonstrate that combining the CLARITY technique (Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging compatible Tissue hYdrogel) with the Zeiss LSM 880 and combining the iDISCO technique (immunolabeling-enabled three-dimensional imaging of solvent-cleared organs) with the Miltenyi Biotec UM ll are the most practical and efficient approaches to sufficiently clear aged human brain tissue and generate 3D microscopic images. Our results point out challenges that arise from seven clearing and three imaging techniques applied to non-standardized tissue samples such as aged human brain tissue

Iron-induced relaxation mechanisms in the human substantia nigra: Towards quantifying iron load in dopaminergic neurons

Pathological iron accumulation in the human brain is a biomarker for neurodegeneration. Several diagnostically promising MR- based methods for in vivo iron quantification were proposed, based on the empirical relationship between R 2 * and iron concentration. However, these do not account for different chemical forms and cellular distribution of iron. We combined post mortem MRI, advanced quantitative histology and biophysical modeling to develop a generative theory linking obtained iron concentrations to quantitative MR parameters. The impact of nanoscale molecular interaction of water with iron and of iron-rich dopaminergic neurons was quantified in substantia nigra

Biophysically motivated efficient estimation of the spatially isotropic R∗2 component from a single gradient-recalled echo measurement

Purpose To propose and validate an efficient method, based on a biophysically motivated signal model, for removing the orientation‐dependent part of R∗2 using a single gradient‐recalled echo (GRE) measurement. Methods The proposed method utilized a temporal second‐order approximation of the hollow‐cylinder‐fiber model, in which the parameter describing the linear signal decay corresponded to the orientation‐independent part of R∗2. The estimated parameters were compared to the classical, mono‐exponential decay model for R∗2 in a sample of an ex vivo human optic chiasm (OC). The OC was measured at 16 distinct orientations relative to the external magnetic field using GRE at 7T. To show that the proposed signal model can remove the orientation dependence of R∗2, it was compared to the established phenomenological method for separating R∗2 into orientation‐dependent and ‐independent parts. Results Using the phenomenological method on the classical signal model, the well‐known separation of R∗2 into orientation‐dependent and ‐independent parts was verified. For the proposed model, no significant orientation dependence in the linear signal decay parameter was observed. Conclusions Since the proposed second‐order model features orientation‐dependent and ‐independent components at distinct temporal orders, it can be used to remove the orientation dependence of R∗2 using only a single GRE measurement

Biophysically motivated efficient estimation of the spatially isotropic R*₂ component from a single gradient‐recalled echo measurement

PURPOSE: To propose and validate an efficient method, based on a biophysically motivated signal model, for removing the orientation‐dependent part of R*₂ using a single gradient‐recalled echo (GRE) measurement. METHODS: The proposed method utilized a temporal second‐order approximation of the hollow‐cylinder‐fiber model, in which the parameter describing the linear signal decay corresponded to the orientation‐independent part of R*₂. The estimated parameters were compared to the classical, mono‐exponential decay model for R*₂ in a sample of an ex vivo human optic chiasm (OC). The OC was measured at 16 distinct orientations relative to the external magnetic field using GRE at 7T. To show that the proposed signal model can remove the orientation dependence of R*₂, it was compared to the established phenomenological method for separating R*₂ into orientation‐dependent and ‐independent parts

Swallow tail sign and nigrosome 1: Close but not quite the same

MRI-based quantification of dopaminergic neurons (DN) and their neuromelanin (NM) in substantia nigra (SN) has great potential to serve as a specific biomarker for neurodegeneration in movement disorders. We used 22-µm-resolution post mortem MR microscopy combined with ion beam microscopy to characterize the magnetic properties of DN. MR microscopy visualized individual DN and provided 3D cellular maps of the entire SN. Static dephasing was determined as main effective transverse relaxation mechanism of DN. We characterized the susceptibility of iron in DN and estimated that the contribution of DN to R2* and QSM may also be detected with in vivo MRI

Field dependence of T2* contrast in human substantia nigra

MRI holds high promise to diagnose Parkinson’s disease (PD) at clinical field strength B0.However, it remains unclear which B0 optimizes T2* contrast in substantia nigra, which provideshigh diagnostic accuracy. We used quantitative MRI at B0=1.5T-9.4T, MR microscopy, andhistochemistry to characterize the field dependence of the major contributors to R2* (1/T2*):dopaminergic neurons, ferritin, and myelin. R2* maps were similar at B0=3T-9.4T, and allcontributions scaled approximately linearly with B0. Hence, the contrast mechanisms are similaracross currently available MRI field strengths in vivo, which informs the design of novel PDbiomarkers