Effects of prospective motion correction on perivascular spaces at 7T MRI evaluated using motion artifact simulation.

PURPOSE: The effectiveness of prospective motion correction (PMC) is often evaluated by comparing artifacts in images acquired with and without PMC (NoPMC). However, such an approach is not applicable in clinical setting due to unavailability of NoPMC images. We aim to develop a simulation approach for demonstrating the ability of fat-navigator-based PMC in improving perivascular space (PVS) visibility in T2-weighted MRI. METHODS: MRI datasets from two earlier studies were used for motion artifact simulation and evaluating PMC, including T2-weighted NoPMC and PMC images. To simulate motion artifacts, k-space data at motion-perturbed positions were calculated from artifact-free images using nonuniform Fourier transform and misplaced onto the Cartesian grid before inverse Fourier transform. The simulation's ability to reproduce motion-induced blurring, ringing, and ghosting artifacts was evaluated using sharpness at lateral ventricle/white matter boundary, ringing artifact magnitude in the Fourier spectrum, and background noise, respectively. PVS volume fraction in white matter was employed to reflect its visibility. RESULTS: In simulation, sharpness, PVS volume fraction, and background noise exhibited significant negative correlations with motion score. Significant correlations were found in sharpness, ringing artifact magnitude, and PVS volume fraction between simulated and real NoPMC images (p ≤ 0.006). In contrast, such correlations were reduced and nonsignificant between simulated and real PMC images (p ≥ 0.48), suggesting reduction of motion effects with PMC. CONCLUSIONS: The proposed simulation approach is an effective tool to study the effects of motion and PMC on PVS visibility. PMC may reduce the systematic bias of PVS volume fraction caused by motion artifacts.

Improving motion robustness of 3D MR fingerprinting with a fat navigator.

PURPOSE: To develop a 3D MR fingerprinting (MRF) method in combination with fat navigators to improve its motion robustness for neuroimaging. METHODS: A rapid fat navigator was developed using the stack-of-spirals acquisition and non-Cartesian spiral GRAPPA. The fat navigator module was implemented in the 3D MRF sequence with high scan efficiency. The developed method was first validated in phantoms and five healthy subjects with intentional head motion. The method was further applied to infants with neonatal opioid withdrawal symptoms. The 3D MRF scans with fat navigators acquired with and without acceleration along the partition-encoding direction were both examined in the study. RESULTS: Both phantom and in vivo results demonstrated that the added fat navigator modules did not influence the quantification accuracy in MRF. In combination with non-Cartesian spiral GRAPPA, a rapid fat navigator sampling with whole-brain coverage was achieved in ˜0.5 s at 3T, reducing its sensitivity to potential motion. Based on the motion waveforms extracted from fat navigators, the motion robustness of the 3D MRF was largely improved. With the proposed method, the motion-corrupted MRF datasets yielded T1 and T2 maps with significantly reduced artifacts and high correlations with measurements from the reference motion-free MRF scans. CONCLUSION: We developed a 3D MRF method coupled with rapid fat navigators to improve its motion robustness for quantitative neuroimaging. Our results demonstrate that (1) accurate tissue quantification was preserved with the fat navigator modules and (2) the motion robustness for quantitative tissue mapping was largely improved with the developed method.

Prospective motion correction and automatic segmentation of penetrating arteries in phase contrast MRI at 7 T.

PURPOSE: To develop a prospective motion correction (MC) method for phase contrast (PC) MRI of penetrating arteries (PAs) in centrum semiovale at 7 T and to evaluate its performance using automatic PA segmentation. METHODS: Head motion was monitored and corrected during the scan based on fat navigator images. Two convolutional neural networks (CNN) were developed to automatically segment PAs and exclude surface vessels. Real-life scans with MC and without MC (NoMC) were performed to evaluate the MC performance. Motion score was calculated from the ranges of translational and rotational motion parameters. MC versus NoMC pairs with similar motion scores during MC and NoMC scans were compared. Data corrupted by motion were reacquired to further improve PA visualization. RESULTS: PA counts (NPA ) and PC and magnitude contrasts (MgC) relative to neighboring tissue were significantly correlated with motion score and were higher in MC than NoMC images at motion scores above 0.5-0.8 mm. Data reacquisition further increased PC but had no significant effect on NPA and MgC. CNNs had higher sensitivity and Dice similarity coefficient for detecting PAs than a threshold-based method. CONCLUSIONS: Prospective MC can improve the count and contrast of segmented PAs in the presence of severe motion. CNN-based PA segmentation has improved performance in delineating PAs than the threshold-based method.

Effects of motion and retrospective motion correction on the visualization and quantification of perivascular spaces in ultrahigh resolution T2-weighted images at 7T.

PURPOSE: Motion can strongly affect MRI image quality and derived imaging measures. We studied the effects of motion and retrospective motion correction (MC) on the visualization and quantitative measures of the perivascular space and penetrating vessel (PVSV) complex, an essential part of the glymphatic system, on high-resolution T2 -weighted MRI images at 7T. METHODS: MC was achieved by adjusting k-space data based on head positions measured using fat navigator images. PVSV visibility and quantitative measures including diameter, volume fraction (VF), count, and contrast were compared between images with and without MC. RESULTS: Without MC, VF, and count decreased significantly with increasing head rotation. MC improved PVSV visualization in all cases with severe motion artifacts. MC decreased diameter in white matter (WM) and increased VF, count, and contrast in basal ganglia and WM. The changes of VF, count, and contrast after MC strongly correlated with motion severity. MC eliminated the significant dependences of VF and count on rotation and reduced the inter-subject variations of VF and count. The effect sizes of age and breathing gas effects on VF and count, and contrast increased in most cases after MC, while those on diameter exhibited inconsistent behavior. CONCLUSIONS: Motion affects PVSV quantification without MC. MC improves PVSV visibility and increases the statistical power of detecting physiological PVSV VF, count, and contrast changes but may have limited benefits for increasing the power for detecting diameter changes.

Morphology of perivascular spaces and enclosed blood vessels in young to middle-aged healthy adults at 7T: Dependences on age, brain region, and breathing gas.

Perivascular spaces (PVSs) are fluid-filled spaces surrounding penetrating blood vessels in the brain and are an integral pathway of the glymphatic system. A PVS and the enclosed blood vessel are commonly visualized as a single vessel-like complex (denoted as PVSV) in high-resolution MRI images. Quantitative characterization of the PVSV morphology in MRI images in healthy subjects may serve as a reference for detecting disease related PVS and/or blood vessel alterations in patients with brain diseases. To this end, we evaluated the age dependences, spatial heterogeneities, and dynamic properties of PVSV morphological features in 45 healthy subjects (21-55 years old), using an ultra-high-resolution three-dimensional transverse relaxation time weighted MRI sequence (0.41 â€‹× â€‹0.41 â€‹× â€‹0.4 â€‹mm3) at 7T. Quantitative PVSV parameters, including apparent diameter, count, volume fraction (VF), and relative contrast to noise ratio (rCNR) were calculated in the white matter and subcortical structures. Dynamic changes were induced by carbogen breathing which are known to induce vasodilation and increase the blood oxygenation level in the brain. PVSV count and VF significantly increased with age in basal ganglia (BG), so did rCNR in BG, midbrain, and white matter (WM). Apparent PVSV diameter also showed a positive association with age in the three brain regions, although it did not reach statistical significance. The PVSV VF and count showed large inter-subject variations, with coefficients of variation ranging from 0.17 to 0.74 after regressing out age and gender effects. Both apparent diameter and VF exhibited significant spatial heterogeneity, which cannot be explained solely by radio-frequency field inhomogeneities. Carbogen breathing significantly increased VF in BG and WM, and rCNR in thalamus, BG, and WM compared to air breathing. Our results are consistent with gradual dilation of PVSs with age in healthy adults. The PVSV morphology exhibited spatial heterogeneity and large inter-subject variations and changed during carbogen breathing compared to air breathing.

Hippocampal Sulcus Remnant: Common Finding in Nonelderly Adults on Ultra-High-Resolution 7T Magnetic Resonance Imaging.

OBJECTIVE: The objective of this study was to investigate the frequency of hippocampal sulcus remnants (HSRs) in nonelderly adults using ultra-high-resolution 7T magnetic resonance (MR) images and their imaging features. METHODS: A total of 33 healthy adults underwent 7T MR, and multiplanar images of 66 temporal lobes were reviewed independently by 2 neuroradiologists. The detectability of the HSR was calculated. In addition, the interobserver agreement on the rating scale was evaluated using the κ statistic. RESULTS: Both observers identified HSRs with 7T MR images in all subjects. Excellent interobserver agreement was shown (κ = 1.0). The shape of HSRs was variable (spot-like, curvilinear, ovoid, or beaded appearance). Volumes of the HSRs were not correlated with age. CONCLUSIONS: Hippocampal sulcus remnants are commonly seen in healthy nonelderly adults using 7T MR imaging. Accurate diagnosis of HSR based on the microanatomy of hippocampus makes it easier to differentiate them from lesions, and it may help prevent unnecessary treatment.

Quantitative phase contrast MRI of penetrating arteries in centrum semiovale at 7T.

Pathological changes of penetrating arteries (PA) within the centrum semiovale is an important contributing factor of cerebral small vessel disease (SVD). However, quantitative characterization of the PAs remains challenging due to their sub-voxel sizes. Here, we proposed a Model-based Analysis of Complex Difference images (MACD) of phase contrast MRI capable of measuring the mean velocities (vmean), diameters (D), and volume flow rates (VFR) of PAs without contamination from neighboring static tissues at 7 T. Simulation, phantom and in vivo studies were performed to evaluate the reproducibility and errors of the proposed method. For comparison, a Model-based Analysis of Phase difference images (MAP) was also carried out in the simulation. The proposed MACD analysis approach was applied in vivo to study the age dependence of PA properties in healthy subjects between 21 and 55 years old. Simulation showed that our proposed MACD approach yielded smaller errors than MAP, with errors increasing at lower velocities and diameters for both methods. In the phantom study, errors of the MACD-derived vmean, D, and VFR were ≤20% of their true values when vmean≥1cm/s and similar at different spatial resolutions. On the other hand, errors of the uncorrected apparent velocities were 24-60% and depended strongly on voxel size. The MACD errors linearly increased with the angle (α) between the vessel and slice normal direction at α ≤ 2° but remained almost constant at larger α. Results of the in vivo studies showed that the coefficients of repeatability for vmean, D, and VFR for PAs with α = 0° were 0.67 cm/s, 0.060 mm, and 0.067 mm3/s, respectively. No significant age dependence was found for the number, vmean, D, and VFR of PAs. The mean vmean, D, and VFR over all PAs with α = 0° were 1.79 ±â€¯0.62 cm/s, 0.17 ±â€¯0.05 mm, and 0.36 ±â€¯0.18 mm3/s, respectively. Quantitative measurements of PAs with the MACD method may serve as a useful tool for illuminating the vascular pathology in cerebral SVD.

Investigating magnetic susceptibility of human knee joint at 7 Tesla.

PURPOSE: To evaluate the magnetic susceptibility properties of different anatomical structures within the knee joint using quantitative susceptibility mapping (QSM). METHODS: A collagen tissue model was simulated and ex vivo animal cartilage experiments were conducted at 9.4 Tesla (T) to evaluate the B0 orientation-dependent magnetic susceptibility contrast observed in cartilage. Furthermore, nine volunteers (six healthy subjects without knee pain history and three patients with known knee injury, between 29 and 58 years old) were scanned using gradient-echo acquisitions on a high-field 7T MR scanner. Susceptibility values of different tissues were quantified and diseased cartilage and meniscus were compared against that of healthy volunteers. RESULTS: Simulation and ex vivo animal cartilage experiments demonstrated that collagen fibrils exhibit an anisotropic susceptibility. A gradual change of magnetic susceptibility was observed in the articular cartilage from the superficial zone to the deep zone, forming a multilayer ultrastructure consistent with anisotropy of collagen fibrils. Meniscal tears caused a clear reduction of susceptibility contrast between the injured meniscus and surrounding cartilage illustrated by a loss of the sharp boundaries between the two. Moreover, QSM showed more dramatic contrast in the focal degenerated articular cartilage than R2* mapping. CONCLUSION: The arrangement of the collagen fibrils is significant, and likely the most dominant source of magnetic susceptibility anisotropy. Quantitative susceptibility mapping offers a means to characterize magnetic susceptibility properties of tissues in the knee joint. It is sensitive to collagen damage or degeneration and may be useful for evaluating the status of knee diseases, such as meniscal tears and cartilage disease. Magn Reson Med 78:1933-1943, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Visualization of perivascular spaces in the human brain at 7T: sequence optimization and morphology characterization.

Noninvasive imaging of perivascular spaces (PVSs) may provide useful insights into their role in normal brain physiology and diseases. Fast MRI sequences with sub-millimeter spatial resolutions and high contrast-to-noise ratio (CNR) are required for accurate delineation of PVS in human. To achieve the optimal condition for PVS imaging at 7T, we carried out detailed simulation and experimental studies to characterize the dependence of CNR on imaging sequences (T1 versus T2-weighted) and sequence parameters. In addition, PVSs were segmented semi-automatically, which revealed much larger numbers of PVSs in young healthy subjects (age 21-37years) than previously reported. To the best of our knowledge, our study provides, for the first time, detailed length, volume, and diameter distributions of PVS in the white matter and subcortical nuclei, which can serve as a reference for future studies of PVS abnormalities under diseased conditions.

Segmentation of perivascular spaces in 7T MR image using auto-context model with orientation-normalized features.

Quantitative study of perivascular spaces (PVSs) in brain magnetic resonance (MR) images is important for understanding the brain lymphatic system and its relationship with neurological diseases. One of the major challenges is the accurate extraction of PVSs that have very thin tubular structures with various directions in three-dimensional (3D) MR images. In this paper, we propose a learning-based PVS segmentation method to address this challenge. Specifically, we first determine a region of interest (ROI) by using the anatomical brain structure and the vesselness information derived from eigenvalues of image derivatives. Then, in the ROI, we extract a number of randomized Haar features which are normalized with respect to the principal directions of the underlying image derivatives. The classifier is trained by the random forest model that can effectively learn both discriminative features and classifier parameters to maximize the information gain. Finally, a sequential learning strategy is used to further enforce various contextual patterns around the thin tubular structures into the classifier. For evaluation, we apply our proposed method to the 7T brain MR images scanned from 17 healthy subjects aged from 25 to 37. The performance is measured by voxel-wise segmentation accuracy, cluster-wise classification accuracy, and similarity of geometric properties, such as volume, length, and diameter distributions between the predicted and the true PVSs. Moreover, the accuracies are also evaluated on the simulation images with motion artifacts and lacunes to demonstrate the potential of our method in segmenting PVSs from elderly and patient populations. The experimental results show that our proposed method outperforms all existing PVS segmentation methods.

Compressed sensing fMRI using gradient-recalled echo and EPI sequences.

Compressed sensing (CS) may be useful for accelerating data acquisitions in high-resolution fMRI. However, due to the inherent slow temporal dynamics of the hemodynamic signals and concerns of potential statistical power loss, the CS approach for fMRI (CS-fMRI) has not been extensively investigated. To evaluate the utility of CS in fMRI application, we systematically investigated the properties of CS-fMRI using computer simulations and in vivo experiments of rat forepaw sensory and odor stimulations with gradient-recalled echo (GRE) and echo planar imaging (EPI) sequences. Various undersampling patterns along the phase-encoding direction were studied and k-t FOCUSS was used as the CS reconstruction algorithm, which exploits the temporal redundancy of images. Functional sensitivity, specificity, and time courses were compared between fully-sampled and CS-fMRI with reduction factors of 2 and 4. CS-fMRI with GRE, but not with EPI, improves the statistical sensitivity for activation detection over the fully sampled data when the ratio of the fMRI signal change to noise is low. CS improves the temporal resolution and reduces temporal noise correlations. While CS reduces the functional response amplitudes, the noise variance is also reduced to make the overall activation detection more sensitive. Consequently, CS is a valuable fMRI acceleration approach, especially for GRE fMRI studies.

Sensitivity and source of amine-proton exchange and amide-proton transfer magnetic resonance imaging in cerebral ischemia.

PURPOSE: Amide-proton transfer (APT) and amine-water proton exchange (APEX) MRI can be viable to map pH-decreasing ischemic regions. However, their exact contributions are unclear. METHODS: We measured APEX- and APT-weighted magnetization transfer ratio asymmetry (denoted as APEXw and APTw), apparent diffusion coefficient, T2 , and T1 images and localized proton spectra in rats with permanent middle cerebral artery occlusion at 9.4 T. Phantoms and theoretical studies were also performed. RESULTS: Within 1-h postocclusion, APEXw and APTw maps showed hyperintensity (3.1% of M0 ) and hypointensity (-1.8%), respectively, in regions with decreased apparent diffusion coefficient. Ischemia increased lactate and gamma aminobutyric acid concentrations, but decreased glutamate and taurine concentrations. Over time, the APEXw contrast decreased with glutamate, taurine, and creatine, whereas the APTw contrast and lactate level were similar. Phantom and theoretical studies suggest that the source of APEXw signal is mainly from proteins at normal pH, whereas at decreased pH, gamma aminobutyric acid and glutamate contributions increase, inducing the positive APEXw contrast in ischemic regions. The APTw contrast is sensitive to lactate concentration and pH, but contaminated from contributions of the faster APEX processes. CONCLUSION: Positive APEXw contrast is more sensitive to ischemia than negative APTw contrast. They may provide complementary tissue metabolic information.

Mild Traumatic Brain Injury and Career Stage Associate with Visible Perivascular Spaces in Special Operations Forces Soldiers.

Mild traumatic brain injury (mTBI) and occupational blast exposure in military Service Members may lead to impaired brain waste clearance which increases neurological disease risk. Perivascular spaces (PVS) are a key part of the glymphatic system which supports brain waste clearance, preferentially during sleep. Visible PVS on clinical magnetic resonance imaging have been previously observed in patients with neurodegenerative diseases and animal neurotrauma models. The purpose of this study was to determine associations between PVS morphological characteristics, military career stage, and mTBI history in Special Operations Forces (SOF) Soldiers. Participants underwent T2-weighed neuroimaging to capture three-dimensional whole brain volumes. Segmentation was performed using a previously validated, multi-scale deep convolutional encoder-decoder neural network. Only PVS clusters within the white matter mask were quantified for analyses. Due to non-normal PVS metric distribution, non-parametric Mann-Whitney U tests were used to determine group differences in PVS outcomes. In total, 223 healthy SOF combat Soldiers (age = 33.1 ± 4.3yrs) were included, 217 reported career stage. Soldiers with mTBI history had greater PVS number (z = 2.51, P = 0.013) and PVS volume (z = 2.42, P = 0.016). In-career SOF combat Soldiers had greater PVS number (z = 2.56, P = 0.01) and PVS volume (z = 2.28, P = 0.02) compared to a baseline cohort. Mild TBI history is associated with increased PVS burden in SOF combat Soldiers that are clinically recovered from mTBI. This may indicate ongoing physiological changes that could lead to impaired waste clearance via the glymphatic system. Future studies should determine if PVS number and volume are meaningful neurobiological outcomes for neurodegenerative disease risk and if clinical interventions such as improving sleep can reduce PVS burden.

Diet-Stimulated Marrow Adiposity Fails to Worsen Early, Age-Related Bone Loss.

INTRODUCTION: Longitudinal effect of diet-induced obesity on bone is uncertain. Prior work showed both no effect and a decrement in bone density or quality when obesity begins prior to skeletal maturity. We aimed to quantify long-term effects of obesity on bone and bone marrow adipose tissue (BMAT) in adulthood. METHODS: Skeletally mature, female C57BL/6 mice (n = 70) aged 12 weeks were randomly allocated to low-fat diet (LFD; 10% kcal fat; n = 30) or high-fat diet (HFD; 60% kcal fat; n = 30), with analyses at 12, 15, 18, and 24 weeks (n = 10/group). Tibial microarchitecture was analyzed by µCT, and volumetric BMAT was quantified via 9.4T MRI/advanced image analysis. Histomorphometry of adipocytes and osteoclasts, and qPCR were performed. RESULTS: Body weight and visceral white adipose tissue accumulated in response to HFD started in adulthood. Trabecular bone parameters declined with advancing experimental age. BV/TV declined 22% in LFD (p = 0.0001) and 17% in HFD (p = 0.0022) by 24 weeks. HFD failed to appreciably alter BV/TV and had negligible impact on other microarchitecture parameters. Both dietary intervention and age accounted for variance in BMAT, with regional differences: distal femoral BMAT was more responsive to diet, while proximal femoral BMAT was more attenuated by age. BMAT increased 60% in the distal metaphysis in HFD at 18 and 24 weeks (p = 0.0011). BMAT in the proximal femoral diaphysis, unchanged by diet, decreased 45% due to age (p = 0.0002). Marrow adipocyte size via histomorphometry supported MRI quantification. Osteoclast number did not differ between groups. Tibial qPCR showed attenuation of some adipose, metabolism, and bone genes. A regulator of fatty acid ß-oxidation, cytochrome C (CYCS), was 500% more abundant in HFD bone (p < 0.0001; diet effect). CYCS also increased due to age, but to a lesser extent. HFD mildly increased OCN, TRAP, and SOST. CONCLUSIONS: Long-term high fat feeding after skeletal maturity, despite upregulation of visceral adiposity, body weight, and BMAT, failed to attenuate bone microarchitecture. In adulthood, we found aging to be a more potent regulator of microarchitecture than diet-induced obesity.

Effects of the α2-adrenergic receptor agonist dexmedetomidine on neural, vascular and BOLD fMRI responses in the somatosensory cortex.

This article describes the effects of dexmedetomidine (DEX) - the active ingredient of medetomidine, which is the latest popular sedative for functional magnetic resonance imaging (fMRI) in rodents - on multiple unit activity, local field potential (LFP), cerebral blood flow (CBF), pial vessel diameter [indicative of cerebral blood volume (CBV)], and blood oxygenation level-dependent (BOLD) fMRI. These measurements were obtained from the rat somatosensory cortex during 10 s of forepaw stimulation. We found that the continuous intravascular systemic infusion of DEX (50 µg/kg/h, doses typically used in fMRI studies) caused epileptic activities, and that supplemental isoflurane (ISO) administration of ~0.3% helped to suppress the development of epileptic activities and maintained robust neuronal and hemodynamic responses for up to 3 h. Supplemental administration of N(2)O in addition to DEX nearly abolished hemodynamic responses even if neuronal activity remained. Under DEX + ISO anesthesia, spike firing rate and the delta power of LFP increased, whereas beta and gamma power decreased, as compared with ISO-only anesthesia. DEX administration caused pial arteries and veins to constrict nearly equally, resulting in decreases in baseline CBF and CBV. Evoked LFP and CBF responses to forepaw stimulation were largest at a frequency of 8-10 Hz, and a non-linear relationship was observed. Similarly, BOLD fMRI responses measured at 9.4 T were largest at a frequency of 10 Hz. Both pial arteries and veins dilated rapidly (artery, 32.2%; vein, 5.8%), and venous diameter returned to baseline slower than arterial diameter. These results will be useful for designing, conducting and interpreting fMRI experiments under DEX sedation.

MR imaging of the amide-proton transfer effect and the pH-insensitive nuclear overhauser effect at 9.4 T.

The amide proton transfer (APT) effect has emerged as a unique endogenous molecular imaging contrast mechanism with great clinical potentials. However, in vivo quantitative mapping of APT using the conventional asymmetry analysis is difficult due to the confounding nuclear Overhauser effect (NOE) and the asymmetry of the magnetization transfer effect. Here, we showed that the asymmetry of magnetization transfer contrast from immobile macromolecules is highly significant, and the wide spectral separation associated with a high magnetic field of 9.4 T delineates APT and NOE peaks in a Z-spectrum. Therefore, high-resolution apparent APT and NOE maps can be obtained from measurements at three offsets. The apparent APT value was greater in gray matter compared to white matter in normal rat brain and was sensitive to tissue acidosis and correlated well with apparent diffusion coefficient in the rat focal ischemic brain. In contrast, no ischemia-induced contrast was observed in the apparent NOE map. The concentration dependence and the pH insensitivity of NOE were confirmed in phantom experiments. Our results demonstrate that in vivo apparent APT and NOE maps can be easily obtained at high magnetic fields and the pH-insensitive NOE may be a useful indicator of mobile macromolecular contents.

In vivo detection of penetrating arteriole alterations in cerebral white matter in patients with diabetes with 7 T MRI.

Cerebral small vessel disease (SVD) is responsible for primary intracerebral hemorrhages, lacunar infarcts and white matter hyperintensity in T2 weighted images. While the brain lesions attributed to small vessel disease can be characterized by conventional MRI, it remains challenging to noninvasively measure the early pathological changes of the small underlying vessels. We evaluated the feasibility of detecting alterations in white matter penetrating arterioles (PA) in patients with diabetes with ultra-high field 7 T MRI. 19 participants with diabetes mellitus (DM) and 19 age- and sex-matched healthy controls were scanned with whole brain T2 and susceptibility weighted MRI and a single slice phase contrast MRI 15 mm above the corpus callosum. The PC-MRI scans were repeated three times. PA masks were manually drawn on the first images after anonymization or automatically segmented on all three images. For each PA, lumen diameter, flow velocity and volume flow rate were derived by model-based analyses of complex difference images. Quasi-Poisson regression was performed for PA count using disease condition, age, and sex as independent variables. Linear mixed effect model analyses were performed for the other measurements using disease condition and age as fixed effect and participant pair specific disease condition as random effect. No severe radiological features of SVD were observed in T2 and susceptibility weighted images in any of the participants except for white matter hyperintensities with Fazekas score of 1 or 2 in 68% and 26% of patients and controls, respectively. The minimum diameter of visible PA was 78 µm and the majority had diameters <250 µm. Among the manually segmented PA with tilt angle less than 30o from the slice normal direction, flow velocities were lower in the DM group (1.9 ± 0.6 vs. 2.2 ± 0.6; p = 0.022), while no significant difference was observed in count, diameter, or volume flow rate. Similar results were observed in the automatically segmented PA. We also observed significantly increased diameter or decreased velocity with age in some of the scans. This study suggests that early PA alterations that are discriminative of disease state and age might be detectable in human cerebral white matter with 7 T MRI in vivo.

Contributions of dynamic venous blood volume versus oxygenation level changes to BOLD fMRI.

Blood-oxygenation-level-dependent (BOLD) fMRI has contributions from venous oxygenation and venous cerebral blood volume (CBV) changes. To examine the relative contribution of venous CBV change (ΔCBV(v)) to BOLD fMRI, BOLD and arterial CBV changes (ΔCBV(a)) to a 40-s forepaw stimulation in six α-chloralose anesthetized rats were measured using a magnetization transfer-varied fMRI technique, while total CBV change (ΔCBV(t)) was measured with injection of iron oxide nanoparticles. ΔCBV(v) was obtained by subtracting ΔCBV(a) from ΔCBV(t). We observed a fast ΔCBV(a) response with a time constant of 2.9 ± 2.3s and a slower ΔCBV(v) response with a time constant of 13.5 ± 5.7s and an onset delay of 6.1 ± 3.3s. These results are consistent with earlier studies under different anesthesia and stimulus, supporting that fast CBV(a) and slow CBV(v) responses are generalizable. Assuming the observed post-stimulus BOLD undershoot is at least partly explained by the ΔCBV(v) contribution, the relative contribution of the ΔCBV(v)- and oxygenation-change-related components to the BOLD response was estimated. The relative ΔCBV(v) contribution increases with time during stimulation; whereby it is <0.14 during initial 10s and reaches a maximum possible value of ~0.45 relative to the oxygenation contribution during the 30-40s period after stimulus onset. Our data indicates that the contribution of venous oxygenation change to BOLD fMRI is dominant for short stimulations.

Magnetic resonance imaging of the Amine-Proton EXchange (APEX) dependent contrast.

Chemical exchange between water and labile protons from amino-acids, proteins and other molecules can be exploited to provide tissue contrast with magnetic resonance imaging (MRI) techniques. Using an off-resonance Spin-Locking (SL) scheme for signal preparation is advantageous because the image contrast can be tuned to specific exchange rates by adjusting SL pulse parameters. While the amide-proton transfer (APT) contrast is obtained optimally with steady-state preparation, using a low power and long irradiation pulse, image contrast from the faster amine-water proton exchange (APEX) is optimized in the transient state with a higher power and a shorter SL pulse. Our phantom experiments show that the APEX contrast is sensitive to protein and amino acid concentration, as well as pH. In vivo 9.4-T SL MRI data of rat brains with irradiation parameters optimized to slow exchange rates have a sharp peak at 3.5 ppm and also broad peak at -2 to -5 ppm, inducing negative contrast in APT-weighted images, while the APEX image has large positive signal resulting from a weighted summation of many different amine-groups. Brain ischemia induced by cardiac arrest decreases pure APT signal from ~1.7% to ~0%, and increases the APEX signal from ~8% to ~16%. In the middle cerebral artery occlusion (MCAO) model, the APEX signal shows different spatial and temporal patterns with large inter-animal variations compared to APT and water diffusion maps. Because of the similarity between the chemical exchange saturation transfer (CEST) and SL techniques, APEX contrast can also be obtained by a CEST approach using similar irradiation parameters. APEX may provide useful information for many diseases involving a change in levels of proteins, peptides, amino-acids, or pH, and may serve as a sensitive neuroimaging biomarker.

Visual Motion Coherence Responses in Human Visual Cortex.

Random dot kinematograms (RDKs) have recently been used to train subjects with cortical scotomas to perform direction of motion discrimination, partially restoring visual motion perception. To study the recovery of visual perception, it is important to understand how visual areas in normal subjects and subjects with cortical scotomas respond to RDK stimuli. Studies in normal subjects have shown that blood oxygen level-dependent (BOLD) responses in human area hV5/MT+ increase monotonically with coherence, in general agreement with electrophysiology studies in primates. However, RDK responses in prior studies were obtained while the subject was performing fixation, not a motion discrimination condition. Furthermore, BOLD responses were gauged against a baseline condition of uniform illumination or static dots, potentially decreasing the specificity of responses for the spatial integration of local motion signals (motion coherence). Here, we revisit this question starting from a baseline RDK condition of no coherence, thereby isolating the component of BOLD response due specifically to the spatial integration of local motion signals. In agreement with prior studies, we found that responses in the area hV5/MT+ of healthy subjects were monotonically increasing when subjects fixated without performing a motion discrimination task. In contrast, when subjects were performing an RDK direction of motion discrimination task, responses in the area hV5/MT+ remained flat, changing minimally, if at all, as a function of motion coherence. A similar pattern of responses was seen in the area hV5/MT+ of subjects with dense cortical scotomas performing direction of motion discrimination for RDKs presented inside the scotoma. Passive RDK presentation within the scotoma elicited no significant hV5/MT+ responses. These observations shed further light on how visual cortex responses behave as a function of motion coherence, helping to prepare the ground for future studies using these methods to study visual system recovery after injury.