Integrated Laplacian‐based phase unwrapping and background phase removal for quantitative susceptibility mapping

Quantitative susceptibility mapping (QSM) is a recently developed MRI technique that provides a quantitative measure of tissue magnetic susceptibility. To compute tissue magnetic susceptibilities based on gradient echoes, QSM requires reliable unwrapping of the measured phase images and removal of contributions caused by background susceptibilities. Typically, the two steps are performed separately. Here, we present a method that simultaneously performs phase unwrapping and HARmonic (background) PhasE REmovaL using the LAplacian operator (HARPERELLA). Both numerical simulations and in vivo human brain images show that HARPERELLA effectively removes both phase wraps and background phase, whilst preserving all low spatial frequency components originating from brain tissues. When compared with other QSM phase preprocessing techniques, such as path‐based phase unwrapping followed by background phase removal, HARPERELLA preserves the tissue phase signal in gray matter, white matter and cerebrospinal fluid with excellent robustness, providing a convenient and accurate solution for QSM. The proposed algorithm is provided, together with QSM and susceptibility tensor imaging (STI) tools, in a shared software package named ‘STI Suite’. Copyright © 2013 John Wiley & Sons, Ltd.     

Measurements of cerebral blood volume using quantitative susceptibility mapping,R2* relaxometry,and ferumoxytol‐enhanced MRI

Ferumoxytol‐enhanced MRI holds potential for the non‐invasive assessment of vascular architecture using estimates of cerebral blood volume (CBV). Ferumoxytol specifically enables steady‐state imaging with extended acquisition times, for substantial improvements in resolution and contrast‐to‐noise ratio. With such data, quantitative susceptibility mapping (QSM) can be used to obtain images of local tissue magnetic susceptibility and hence estimate the increase in blood susceptibility after administration of a contrast agent, which in turn can be correlated to tissue CBV. Here, we explore the use of QSM for CBV estimation and compare it with R₂* (1/T₂*)‐based results. Institutional review board approval was obtained, and all subjects provided written informed consent. For this prospective study, MR images were acquired on a 3.0 T scanner in 19 healthy subjects using a multiple‐echo T₂*‐weighted sequence. Scanning was performed before and after the administration of two doses of ferumoxytol (1 mg FE/kg and 4 mg FE/kg). Different QSM approaches were tested on numerical phantom simulations. Results showed that the accuracy of magnetic susceptibility measurements improved with increasing image resolution and decreasing vascular density. In vivo changes in magnetic susceptibility were measured after the administration of ferumoxytol utilizing QSM, and significantly higher QSM‐based CBV was measured in gray matter compared with white matter. QSM‐ and R₂*‐based CBV estimates correlated well, with similar average values, but a larger variance was found in QSM‐based estimates.     

Simultaneous voxel‐based magnetic susceptibility and morphometry analysis using magnetization‐prepared spoiled turbo multiple gradient echo

This study aimed to develop and test a simultaneous acquisition and analysis pipeline for voxel‐based magnetic susceptibility and morphometry (VBMSM) on a single dataset using young volunteers, elderly healthy volunteers, and an Alzheimer's disease (AD) group. 3D T₁‐weighted and multi‐echo phase images for VBM and quantitative susceptibility mapping (QSM) were simultaneously acquired using a magnetization‐prepared spoiled turbo multiple gradient echo sequence with inversion pulse for QSM (MP‐QSM). The magnitude image was split into gray matter (GM) and white matter (WM) and was spatially normalized. The susceptibility map was reconstructed from the phase images. The segmented image and susceptibility map were compared with those obtained from conventional multiple spoiled gradient echo (mGRE) and MP‐spoiled gradient echo (MP‐GRE) in healthy volunteers to validate the availability of MP‐QSM by numerical measurements. To assess the feasibility of the VBMSM analysis pipeline, voxel‐based comparisons of susceptibility and morphometry in MP‐QSM were conducted in volunteers with a bimodal age distribution, and in elderly volunteers and the AD group, using spatially normalized GM and WM volume images and a susceptibility map. GM/WM contrasts in MP‐QSM, MP‐GRE, and mGRE were 0.14 ± 0.011, 0.17 ± 0.015, and 0.045 ± 0.010, respectively. Segmented GM and WM volumes in the MP‐QSM closely coincided with those in the MP‐GRE. Region of interest analyses indicated that the mean susceptibility values in MP‐QSM were completely in agreement with those in mGRE. In an evaluation of the aging effect, a significant increase and decrease in susceptibility and volume were found by VBMSM in deep GM and WM, respectively. Between the elderly volunteers and the AD group, the characteristic susceptibility and volume changes in GM and WM were observed. The proposed MP‐QSM sequence makes it possible to acquire acceptable‐quality images for simultaneous analysis and determine brain atrophy and susceptibility distribution without image registration by using voxel‐based analyses.     

The impact of white matter fiber orientation in single‐acquisition quantitative susceptibility mapping

The aim of this work was to assess the impact of tissue structural orientation on quantitative susceptibility mapping (QSM) reliability, and to provide a criterion to identify voxels in which measures of magnetic susceptibility (χ) are most affected by spatial orientation effects. Four healthy volunteers underwent 7‐T magnetic resonance imaging (MRI). Multi‐echo, gradient‐echo sequences were used to obtain quantitative maps of frequency shift (FS) and χ. Information from diffusion tensor imaging (DTI) was used to investigate the relationship between tissue orientation and FS measures and QSM. After sorting voxels on the basis of their fractional anisotropy (FA), the variations in FS and χ values over tissue orientation were measured. Using a K‐means clustering algorithm, voxels were separated into two groups depending on the variability of measures within each FA interval. The consistency of FS and QSM values, observed at low FA, was disrupted for FA > 0.6. The standard deviation of χ measured at high FA (0.0103 ppm) was nearly five times that at low FA (0.0022 ppm). This result was consistent through data across different head positions and for different brain regions considered separately, which confirmed that such behavior does not depend on structures with different bulk susceptibility oriented along particular angles. The reliability of single‐orientation QSM anticorrelates with local FA. QSM provides replicable values with little variability in brain regions with FA < 0.6, but QSM should be interpreted cautiously in major and coherent fiber bundles, which are strongly affected by structural anisotropy and magnetic susceptibility anisotropy.     

Fast quantitative susceptibility reconstruction via total field inversion with improved weighted L0 norm approximation

Quantitative susceptibility mapping (QSM) is a meaningful MRI technique owing to its unique relation to actual physical tissue magnetic properties. The reconstruction of QSM is usually decomposed into three sub‐problems, which are solved independently. However, this decomposition does not conform to the causes of the problems, and may cause discontinuity of parameters and error accumulation. In this paper, a fast reconstruction method named fast TFI based on total field inversion was proposed. It can accelerate the total field inversion by using a specially selected preconditioner and advanced solution of the weighted L₀ regularization. Due to the employment of an effective model, the proposed method can efficiently reconstruct the QSM of brains with lesions, where other methods may encounter problems. Experimental results from simulation and in vivo data verified that the new method has better reconstruction accuracy, faster convergence ability and excellent robustness, which may promote clinical application of QSM.     

Developmental trajectory of magnetic susceptibility in the healthy rhesus macaque brain

Quantitative susceptibility mapping (QSM) is used to quantify iron deposition in non-human primates in our study. Although QSM has many applications in detecting iron deposits in the human brain, including the distribution of iron deposits in specific brain regions, the change of iron deposition with aging, and the comparison of iron deposits between diseased groups and healthy controls, few studies have applied QSM to non-human primates, while most animal brain experiments focus on biochemical and anatomical results instead of non-invasive experiments. Additionally, brain imaging in children's research is difficult, but can be substituted using young rhesus monkeys, which are very similar to humans, as research animals. Therefore, understanding the relationship between iron deposition and age in rhesus macaques' brains can offer insights into both the developmental trajectory of magnetic susceptibility in the animal model and the correlated evidence in children's research. Twenty-three healthy rhesus macaque monkeys (23 ± 7.85 years, range 2–29 years) were included in this research. Seven regions of interest (ROIs—globus pallidus, substantia nigra, dentate nucleus, caudate nucleus, putamen, thalamus, red nucleus) have been analyzed in terms of QSM and R₂* (apparent relaxation rate). Susceptibility in most ROIs correlated significantly with the growth of age, similarly to the results for R₂*, but showed different trends in the thalamus and red nucleus, which may be caused by the different sensitivities of myelination and iron deposition in R₂* and QSM analysis. By assessing the correlation between iron content and age in healthy rhesus macaques' brains using QSM, we provide a piece of pilot information on normality for advanced animal disease models. Meanwhile, this study also could serve as the normative basis for further clinical studies using QSM for iron content quantification. Due to the comparison of the susceptibility on the same experimental objects, this research can also provide practical support for future research on characteristics for QSM and R₂*.     

Effect of respiratory hyperoxic challenge on magnetic susceptibility in human brain assessed by quantitative susceptibility mapping (QSM)

The purpose of this study was to measure the regional change of magnetic susceptibility in human brain upon inhalation of 100% oxygen by MRI quantitative susceptibility mapping (QSM). Fourteen healthy volunteers were scanned in a 3 T MR scanner with a 3D multi‐gradient‐echo sequence while breathing medical air (normoxia) and pure oxygen (hyperoxia). QSM images and R₂* maps were calculated. Mean susceptibility differences versus white matter were measured in regions of interest covering veins, gray matter (GM), and cerebrospinal fluid (CSF) under both conditions. Hyperoxia resulted in a strong susceptibility decrease in large veins (?154.4 ± 65.9 ppb, p < 10^?6), in a smaller reduction in GM (?1.3 ± 1 ppb, p < 0.001), and in a susceptibility increase in ventricular CSF (3.8 ± 1.8 ppb, p < 10^?5). The susceptibility decrease in veins implied an increase of venous oxygen saturation (SvO₂) by 10.1 ± 4.0%. Compared with QSM, R₂* was more seriously affected by long‐distance effects not related to local tissue oxygenation and increased in cerebral frontal regions (3 ± 2 s^?1, p < 0.0004) due to paramagnetic molecular oxygen in cavities. The results highlight the potential of QSM to yield region‐specific quantitative oxygenation information, and, thus, for applications such as oxygen‐therapy monitoring or identification of hypoxic tumor tissue during radiotherapy planning. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor‐deficient mice

Disruption of the regulatory role of the kidneys leads to diverse renal pathologies; one major hallmark is inflammation and fibrosis. Conventional magnitude MRI has been used to study renal pathologies; however, the quantification or even detection of focal lesions caused by inflammation and fibrosis is challenging. We propose that quantitative susceptibility mapping (QSM) may be particularly sensitive for the identification of inflammation and fibrosis. In this study, we applied QSM in a mouse model deficient for angiotensin receptor type 1 (AT₁). This model is known for graded pathologies, including focal interstitial fibrosis, cortical inflammation, glomerulocysts and inner medullary hypoplasia. We acquired high‐resolution MRI on kidneys from AT₁‐deficient mice that were perfusion fixed with contrast agent. Two MR sequences were used (three‐dimensional spin echo and gradient echo) to produce three image contrasts: T₁, T₂* (magnitude) and QSM. T₁ and T₂* (magnitude) images were acquired to segment major renal structures and to provide landmarks for the focal lesions of inflammation and fibrosis in the three‐dimensional space. The volumes of major renal structures were measured to determine the relationship of the volumes to the degree of renal abnormalities and magnetic susceptibility values. Focal lesions were segmented from QSM images and were found to be closely associated with the major vessels. Susceptibilities were relatively more paramagnetic in wild‐type mice: 1.46 ± 0.36 in the cortex, 2.14 ± 0.94 in the outer medulla and 2.10 ± 2.80 in the inner medulla (10^–2 ppm). Susceptibilities were more diamagnetic in knockout mice: –7.68 ± 4.22 in the cortex, –11.46 ± 2.13 in the outer medulla and –7.57 ± 5.58 in the inner medulla (10^–2 ppm). This result was consistent with the increase in diamagnetic content, e.g. proteins and lipids, associated with inflammation and fibrosis. Focal lesions were validated with conventional histology. QSM was very sensitive in detecting pathology caused by small focal inflammation and fibrosis. QSM offers a new MR contrast mechanism to study this common disease marker in the kidney. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparison of quantitative susceptibility mapping methods on evaluating radiation-induced cerebral microbleeds and basal ganglia at 3T and 7T

Quantitative susceptibility mapping (QSM) has the potential for being a biomarker for various diseases because of its ability to measure tissue susceptibility related to iron deposition, myelin, and hemorrhage from the phase signal of a T₂*-weighted MRI. Despite its promise as a quantitative marker, QSM is faced with many challenges, including its dependence on preprocessing of the raw phase data, the relatively weak tissue signal, and the inherently ill posed relationship between the magnetic dipole and measured phase. The goal of this study was to evaluate the effects of background field removal and dipole inversion algorithms on noise characteristics, image uniformity, and structural contrast for cerebral microbleed (CMB) quantification at both 3T and 7T. We selected four widely used background phase removal and five dipole field inversion algorithms for QSM and applied them to volunteers and patients with CMBs, who were scanned at two different field strengths, with ground truth QSM reference calculated using multiple orientation scans. 7T MRI provided QSM images with lower noise than did 3T MRI. QSIP and VSHARP + iLSQR achieved the highest white matter homogeneity and vein contrast, with QSIP also providing the highest CMB contrast. Compared with ground truth COSMOS QSM images, overall good correlations between susceptibility values of dipole inversion algorithms and the COSMOS reference were observed in basal ganglia regions, with VSHARP + iLSQR achieving the susceptibility values most similar to COSMOS across all regions. This study can provide guidance for selecting the most appropriate QSM processing pipeline based on the application of interest and scanner field strength.     

Quantitative susceptibility mapping and R1 measurement: Determination of the myelin volume fraction in the aging ex vivo rat corpus callosum

In studies of the white matter (WM) in aging brains, both quantitative susceptibility mapping (QSM) and direct R₁ measurement offer potentially useful ex vivo MRI tools that allow volumetric characterization of myelin content changes. Despite the technical importance of such MRI methods in numerous age-related diseases, the supposed linear relationship between the estimates of either the QSM or R₁ method and age-affected myelin contents has not been validated. In this study, the absolute myelin volume fraction (MVF) was determined by transmission electron microscopy (TEM) as a gold standard measure for comparison with the values obtained by the aforementioned MR methods. To theoretically evaluate and understand the MR signal characteristics, QSM simulations were performed using the finite perturber method (FPM). Specifically, the simulation geometry modeling was based on TEM-derived structures aligned orthogonally to the main magnetic field, the construct of which was used to estimate the magnetic field shift (ΔB) changes arising from the conjectured myelin structures. Experimentally, ex vivo corpus callosum (CC) samples from rat brains obtained at 6 weeks (n = 3), 4 months (n = 3), and 20 months (n = 3) after birth were used to establish the relationship between changes quantified by either QSM or R₁ with the absolute MVF by TEM. From the ex vivo brain samples, the scatterplot of mean MVF versus R₁ was fitted to a linear equation, where R_1mean = 0.7948 × MVF_mean + 0.8118 (Pearson's correlation coefficient r = 0.9138; p < 0.01), while the scatterplot of mean MVF versus MRI-derived magnetic susceptibility (χ) was also fitted to a line where χ_{measured,mean} = −0.1218 × MVF_mean − 0.006345 (r = −0.8435; p < 0.01). As a result of the FPM-based QSM simulations, a linearly proportional relationship between the simulated magnetic susceptibility, χ_{simulated,mean}, and MVF (r = −0.9648; p < 0.01) was established. Such a statistically significant linear correlation between MRI-derived values by the QSM (or R₁) method and MVF demonstrated that variable myelin contents in the WM (i.e., CC) can be quantified across multiple stages of aging. These findings further support that both techniques based on QSM and R₁ provide an efficient means of studying the brain-aging process with accurate volumetric quantification of the myelin content in WM.     

High‐resolution diffusion MRI studies of development in pregnant mice visualized by novel spatiotemporal encoding schemes

This study introduces an MRI approach to map diffusion of water in vivo with high resolution under challenging conditions; the approach's potential is then used in diffusivity characterizations of embryos and fetoplacental units in pregnant mice, as well as of newborn mice in their initial postnatal period. The method relies on performing self‐referenced spatiotemporal encoded MRI acquisitions, which can achieve the motional and susceptibility immunities needed to target challenging regions such as a mouse's abdominal cavity in a single shot. When suitably combined with zooming‐in and novel interleaving procedures, these scans can overcome the inhomogeneity and sensitivity challenges arising upon targeting ≈100 μm in‐plane resolutions, and thereby enable longitudinal development studies of abdominal organs that have hitherto eluded in vivo diffusion‐weighted imaging. This is employed here to follow processes related to embryonic implantation and placentation, including the final stages of mouse gastrulation, the development of white matter in fetal brains, the maturation of fetal spines, and the evolution of the different layers making up mouse hemochorial placentas. The protocol's ability to extract diffusivity information in challenging regions as a function of embryonic mouse development is thus demonstrated, and its usefulness as a tool for visualizing pregnancy‐related developmental changes in rodents is discussed.     

Mapping the human brainstem: Brain nuclei and fiber tracts at 3 T and 7 T

Structural high‐resolution imaging of the brainstem can be of high importance in clinical practice. However, ultra‐high field magnetic resonance imaging (MRI) is still restricted in use due to limited availability. Therefore, quantitative MRI techniques (quantitative susceptibility mapping [QSM], relaxation measurements [ , R₁ ], diffusion tensor imaging [DTI]) and T₂ ‐ and proton density (PD)‐weighted imaging in the human brainstem at 3 T and 7 T are compared. Five healthy volunteers (mean age: 21.5 ± 1.9 years) were measured at 3 T and 7 T using multi‐echo gradient echo sequences for susceptibility mapping and relaxometry, magnetization‐prepared 2 rapid acquisition gradient echo sequences for R₁ relaxometry, turbo‐spin echo sequences for PD‐ and T₂ ‐weighted imaging and readout‐segmented echo planar sequences for DTI. Susceptibility maps were computed using Laplacian‐based phase unwrapping, V‐SHARP for background field removal and the streaking artifact reduction for QSM algorithm for dipole inversion. Contrast‐to‐noise ratios (CNRs) were determined at 3 T and 7 T in ten volumes of interest (VOIs). Data acquired at 7 T showed higher CNR. However, in four VOIs, lower CNR was observed for at 7 T. QSM was shown to be the contrast with which the highest number of structures could be identified. The depiction of very fine tracts such as the medial longitudinal fasciculus throughout the brainstem was only possible in susceptibility maps acquired at 7 T. DTI effectively showed the main tracts (crus cerebri, transverse pontine fibers, corticospinal tract, middle and superior cerebellar peduncle, pontocerebellar tract, and pyramid) at both field strengths. Assessing the brainstem with quantitative MRI methods such as QSM, , as well as PD‐ and T₂ ‐weighted imaging with great detail, is also possible at 3 T, especially when using susceptibility mapping calculated from a gradient echo sequence with a wide range of echo times from 10.5 to 52.5 ms. However, tracing smallest structures strongly benefits from imaging at ultra‐high field.     

Arterial spin labeling‐fast imaging with steady‐state free precession (ASL‐FISP): a rapid and quantitative perfusion technique for high‐field MRI

Arterial spin labeling (ASL) is a valuable non‐contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either echo‐planar imaging (EPI) or true fast imaging with steady‐state free precession (true FISP) readouts, which are prone to off‐resonance artifacts on high‐field MRI scanners. We have developed a rapid ASL‐FISP MRI acquisition for high‐field preclinical MRI scanners providing perfusion‐weighted images with little or no artifacts in less than 2 s. In this initial implementation, a flow‐sensitive alternating inversion recovery (FAIR) ASL preparation was combined with a rapid, centrically encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 and 9.4 T (249 ± 38 and 241 ± 17 mL/min/100 g, respectively). The utility of this method was further demonstrated in the detection of significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL‐FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high‐field MRI scanners with minimal image artifacts. Copyright © 2014 John Wiley & Sons, Ltd.     

Oscillating gradient diffusion kurtosis imaging of normal and injured mouse brains

Recent advances in diffusion MRI employ multiple diffusion encoding schemes with varying diffusion direction, weighting, and diffusion time to investigate specific microstructural properties in biological tissues. In this study, we examined time‐dependent diffusion kurtosis contrast in adult mouse brains and in neonatal mouse brains after hypoxic–ischemic (HI) injury. In vivo diffusion kurtosis maps were acquired with a short diffusion time using an oscillating gradient spin echo (OGSE) sequence at 100 Hz and with a relatively long diffusion time (20 ms) using a pulsed gradient spin echo (PGSE) sequence. In the adult mouse brain, we found that the cortex and hippocampus showed larger differences between OGSE kurtosis and PGSE kurtosis than major white matter tracts. In neonatal mouse brains with unilateral HI injury, the OGSE kurtosis map overall provided stronger edema contrast than the PGSE kurtosis map, and the differences between OGSE and PGSE kurtosis measurements in the edema region reflected heterogeneity of injury. This is the first in vivo study that has demonstrated multi‐direction OGSE kurtosis contrasts in the mouse brain. Comparing PGSE and OGSE kurtosis measures may provide additional information on microstructural changes after ischemic stroke.     

Quantitative susceptibility mapping and 23Na imaging‐based in vitro characterization of blood clotting kinetics

Blood clotting is a fundamental biochemical process in post‐hemorrhagic hemostasis. Although the varying appearance of coagulating blood in T₁‐ and T₂‐weighted images is widely used to qualitatively determine bleeding age, the technique permits only a rough discrimination of coagulation stages, and it remains difficult to distinguish acute and chronic hemorrhagic stages because of low T₁‐ and T₂‐weighted signal intensities in both instances. To investigate new biomedical parameters for magnetic resonance imaging‐based characterization of blood clotting kinetics, sodium imaging and quantitative susceptibility mapping (QSM) were compared with conventional T₁‐ and T₂‐weighted imaging, as well as with biochemical hemolysis parameters. For this purpose, a blood‐filled spherical agar phantom was investigated daily for 14 days, as well as after 24 days at 7 T after initial preparation with fresh blood. T₁‐ and T₂‐weighted sequences, a three‐dimensional (3D) gradient echo sequence and a density‐adapted 3D radial projection reconstruction pulse sequence for ²³Na imaging were applied. For hemolysis estimations, free hemoglobin and free potassium concentrations were measured photometrically and with the direct ion‐selective electrode method, respectively, in separate heparinized whole‐blood samples along the same timeline. Initial mean susceptibility was low (0.154 ± 0.020 ppm) and increased steadily during the course of coagulation to reach up to 0.570 ± 0.165 ppm. The highest total sodium (NaT) values (1.02 ± 0.06 arbitrary units) in the clot were observed initially, dropped to 0.69 ± 0.13 arbitrary units after one day and increased again to initial values. Compartmentalized sodium (NaS) showed a similar signal evolution, and the NaS/NaT ratio steadily increased over clot evolution. QSM depicts clot evolution in vitro as a process associated with hemoglobin accumulation and transformation, and enables the differentiation of the acute and chronic coagulation stages. Sodium imaging visualizes clotting independent of susceptibility and seems to correspond to clot integrity. A combination of QSM and sodium imaging may enhance the characterization of hemorrhage.     

Feasibility of neurochemically profiling mouse embryonic brain and its development in utero using 1H MRS at 14.1 T

We aimed to evaluate the feasibility of neurochemical profiling of embryonic mouse brain developments in utero and to seek potential in vivo evidence of an energy shift in a mitochondrial pyruvate carrier 1 (MPC1) deficient mouse model. C57BL/6 embryonic mouse brains were studied in utero by anatomical MRI and short echo localized proton (¹H) MRS at 14.1 T. Two embryonic stages were studied, the energy shift (e.g., embryonic day 12.5–13, E12.5–13) and close to the birth (E17.5–18). In addition, embryonic brains devoid of MPC1 were studied at E12.5–13. The MRI provided sufficient anatomical contrasts for visualization of embryonic brain. Localized ¹H MRS offered abundant metabolites through the embryonic development from E12.5 and close to the birth, e.g., E17.5 and beyond. The abundant neurochemical information at E12.5 provided metabolic status and processes relating to cellular development at this stage, i.e., the energy shift from glycolysis to oxidative phosphorylation, evidenced by accumulation of lactate in E12.5–13 embryonic brain devoid of MPC1. The further evolution of the neurochemical profile of embryonic brains at E17.5–18 is consistent with cellular and metabolic processes towards the birth. Localized ¹H MRS study of embryonic brain development in utero is feasible, and longitudinal neurochemical profiling of embryonic brains offers valuable insight into early brain development.     

Preservation of neural tissue with a formaldehyde‐free phenol‐based embalming protocol

The adverse effects formaldehyde fixation has on tissues both gross anatomically and histologically are well documented. Consequently, researchers are seeking alternative embalming techniques that better preserve in vivo characteristics of tissues. Phenol‐based embalming is one method that has shown promise in its ability to adequately preserve the in vivo qualities of tissues through preliminary explorations at the gross anatomical level. The literature on phenol‐based embalming is currently scarce, especially with regard to its effects on tissues at the microscopic level. For the current study we aimed to document the histologic effects of a formaldehyde‐free phenol‐based embalming solution on neural tissue, with the hope of providing novel insight into the effects of soft‐embalming on tissues at the microscopic level. Cerebral and cerebellar tissue obtained from porcine brains was fixed in phenol‐ and formaldehyde‐based fixatives; the latter served as a control. Fixed samples were processed for histological analysis. The phenol‐based embalming solution provided excellent preservation of the cerebral and cerebellar tissue morphology. Of note was the decrease in separation artifact seen in both tissue types relative to the control tissue, as well as anomalous circular artifacts in the white matter. The results of this study indicate that the phenol‐based embalming solution preserves neural tissue at the histological level, perhaps superiorly in many aspects when compared to the formaldehyde‐fixed samples. Further investigations of both gross anatomy and histology are recommended on the basis of these promising new findings to determine its potential utilities within research and education. Clin. Anat. 32:224–230, 2019. © 2018 Wiley Periodicals, Inc.     

Magnetic resonance imaging and micro-computed tomography combined atlas of developing and adult mouse brains for stereotaxic surgery

Stereotaxic atlases of the mouse brain are important in neuroscience research for targeting of specific internal brain structures during surgical operations. The effectiveness of stereotaxic surgery depends on accurate mapping of the brain structures relative to landmarks on the skull. During postnatal development in the mouse, rapid growth-related changes in the brain occur concurrently with growth of bony plates at the cranial sutures, therefore adult mouse brain atlases cannot be used to precisely guide stereotaxis in developing brains. In this study, three-dimensional stereotaxic atlases of C57BL/6J mouse brains at six postnatal developmental stages: postnatal day (P) 7, P14, P21, P28, P63 and in adults (P140–P160) were developed, using diffusion tensor imaging (DTI) and micro-computed tomography (CT). At present, most widely-used stereotaxic atlases of the mouse brain are based on histology, but the anatomical fidelity of ex vivo atlases to in vivo mouse brains has not been evaluated previously. To account for ex vivo tissue distortion due to fixation as well as individual variability in the brain, we developed a population-averaged in vivo magnetic resonance imaging adult mouse brain stereotaxic atlas, and a distortion-corrected DTI atlas was generated by nonlinearly warping ex vivo data to the population-averaged in vivo atlas. These atlas resources were developed and made available through a new software user-interface with the objective of improving the accuracy of targeting brain structures during stereotaxic surgery in developing and adult C57BL/6J mouse brains.     

Trading off SNR and resolution in MR images

With a fixed time to acquire a magnetic resonance (MR) image, time can be spent to acquire better spatial resolution with decrease in signal‐to‐noise ratio (SNR) or decreased resolution with increase in SNR. This resolution/SNR tradeoff at fixed time has been investigated by a visual rater study using images of ex vivo mouse brains. Simulated images with a tradeoff between SNR and resolution were produced from high‐quality, 3D isotropic mouse brain images to emulate shorter constant acquisition times. The tradeoff images spanned a range of SNRs (63–6) and isotropic resolutions (32–81 µm). Fourteen readers identified the image which best displayed neuroanatomy. Additional experiments tested for (i) intra‐observer consistency, (ii) the effect of emulated scan time, and (iii) specifically biased questions pertaining to the perception of neuroanatomy. Optimal anatomical viewing depended primarily on the SNR of the images. Specifically, for fixed imaging time, preference lay in the SNR range of ～30–35 with strong consistency and there was minimal effect from overall imaging time. Copyright © 2008 John Wiley & Sons, Ltd.     

A model‐based reconstruction for undersampled radial spin‐echo DTI with variational penalties on the diffusion tensor

Radial spin‐echo diffusion imaging allows motion‐robust imaging of tissues with very low T₂ values like articular cartilage with high spatial resolution and signal‐to‐noise ratio (SNR). However, in vivo measurements are challenging, due to the significantly slower data acquisition speed of spin‐echo sequences and the less efficient k‐space coverage of radial sampling, which raises the demand for accelerated protocols by means of undersampling. This work introduces a new reconstruction approach for undersampled diffusion‐tensor imaging (DTI). A model‐based reconstruction implicitly exploits redundancies in the diffusion‐weighted images by reducing the number of unknowns in the optimization problem and compressed sensing is performed directly in the target quantitative domain by imposing a total variation (TV) constraint on the elements of the diffusion tensor. Experiments were performed for an anisotropic phantom and the knee and brain of healthy volunteers (three and two volunteers, respectively). Evaluation of the new approach was conducted by comparing the results with reconstructions performed with gridding, combined parallel imaging and compressed sensing and a recently proposed model‐based approach. The experiments demonstrated improvements in terms of reduction of noise and streaking artifacts in the quantitative parameter maps, as well as a reduction of angular dispersion of the primary eigenvector when using the proposed method, without introducing systematic errors into the maps. This may enable an essential reduction of the acquisition time in radial spin‐echo diffusion‐tensor imaging without degrading parameter quantification and/or SNR. Copyright © 2015 John Wiley & Sons, Ltd.