Signal-to-noise ratio versus field strength for small surface coils.

The increasing signal-to-noise ratio (SNR) is the main reason to use ultrahigh field MRI. Here, we investigate the dependence of the SNR on the magnetic field strength, especially for small animal applications, where small surface coils are used and coil noise cannot be ignored. Measurements were performed at five field strengths from 3 to 14.1 T, using 2.2-cm surface coils with an identical coil design for transmit and receive on two water samples with and without salt. SNR was measured in a series of spoiled gradient echo images with varying flip angle and corrected for saturation based on a series of flip angle and T1 measurements. Furthermore, the noise figure of the receive chain was determined and eliminated to remove instrument dependence. Finally, the coil sensitivity was determined based on the principle of reciprocity to obtain a measure for ultimate SNR. Before coil sensitivity correction, the SNR increase in nonconductive samples is highly supralinear with B0 1.6-2.7, depending on distance to the coil, while in the conductive sample, the growth is smaller, being around linear close to the surface coil and increasing up to a B0 2.0 dependence when moving away from the coil. After sensitivity correction, the SNR increase is independent of loading with B0 2.1. This study confirms the supralinear increase of SNR with increasing field strengths. Compared with most human measurements with larger coil sizes, smaller surface coils, as mainly used in animal studies, have a higher contribution of coil noise and thus a different behavior of SNR at high fields.

High Spatiotemporal Resolution Radial Encoding Single-Vessel fMRI.

High-field preclinical functional MRI (fMRI) is enabled the high spatial resolution mapping of vessel-specific hemodynamic responses, that is single-vessel fMRI. In contrast to investigating the neuronal sources of the fMRI signal, single-vessel fMRI focuses on elucidating its vascular origin, which can be readily implemented to identify vascular changes relevant to vascular dementia or cognitive impairment. However, the limited spatial and temporal resolution of fMRI is hindered hemodynamic mapping of intracortical microvessels. Here, the radial encoding MRI scheme is implemented to measure BOLD signals of individual vessels penetrating the rat somatosensory cortex. Radial encoding MRI is employed to map cortical activation with a focal field of view (FOV), allowing vessel-specific functional mapping with 50 × 50 µm2 in-plane resolution at a 1 to 2 Hz sampling rate. Besides detecting refined hemodynamic responses of intracortical micro-venules, the radial encoding-based single-vessel fMRI enables the distinction of fMRI signals from vessel and peri-vessel voxels due to the different contribution of intravascular and extravascular effects.

Evaluation of the contribution of individual arteries to the cerebral blood supply in patients with Moyamoya angiopathy: comparison of vessel-encoded arterial spin labeling and digital subtraction angiography.

PURPOSE: Vessel-encoded arterial spin labeling (VE-ASL) is able to provide noninvasive information about the contribution of individual arteries to the cerebral perfusion. The aim of this study was to compare VE-ASL to the diagnostic standard digital subtraction angiography (DSA) with respect to its ability to visualize vascular territories. METHODS: In total, 20 VE-ASL and DSA data sets of 17 patients with Moyamoya angiopathy with and without revascularization surgery were retrospectively analyzed. Two neuroradiologists independently assessed the agreement between VE-ASL and DSA using a 4-point Likert scale (no- very high agreement). Additionally, grading of the vascular supply of subterritories (A1-A2, M1-M6) on the VE-ASL images and angiograms was performed. The intermodal agreement was calculated for all subterritories in total and for the subdivision into without and after revascularization (direct or indirect bypass). RESULTS: There was a very high agreement between the VE-ASL and the DSA data sets (median = 1, modus = 1) with a substantial inter-rater agreement (kw = 0.762 (95% CI 0.561-0.963)). The inter-modality agreement between VE-ASL and DSA in vascular subterritories was almost perfect for all subterritories (k = 0.899 (0.865-0.945)), in the subgroup of direct revascularized subterritories (k = 0.827 (0.738-0.915)), in the subgroup of indirect revascularized subterritories (k = 0.843 (0.683-1.003)), and in the subgroup of never revascularized subterritories (k = 0.958 (0.899-1.017)). CONCLUSION: Vessel-encoded ASL seems to be a promising non-invasive method to depict the contributions of individual arteries to the cerebral perfusion before and after revascularization surgery.

Alpha-180 spin-echo based line-scanning method for high resolution laminar-specific fMRI.

Laminar-specific functional magnetic resonance imaging (fMRI) has been widely used to study circuit-specific neuronal activity by mapping spatiotemporal fMRI response patterns across cortical layers. Hemodynamic responses reflect indirect neuronal activity given limit of spatial and temporal resolution. Previous gradient-echo based line-scanning fMRI (GELINE) method was proposed with high temporal (50 ms) and spatial (50 µm) resolution to better characterize the fMRI onset time across cortical layers by employing 2 saturation RF pulses. However, the imperfect RF saturation performance led to poor boundary definition of the reduced region of interest (ROI) and aliasing problems outside of the ROI. Here, we propose α (alpha)-180 spin-echo-based line-scanning fMRI (SELINE) method to resolve this issue by employing a refocusing 180° RF pulse perpendicular to the excitation slice. In contrast to GELINE signals peaked at the superficial layer, we detected varied peaks of laminar-specific BOLD signals across deeper cortical layers with the SELINE method, indicating the well-defined exclusion of the large drain-vein effect with the spin-echo sequence. Furthermore, we applied the SELINE method with 200 ms TR to sample the fast hemodynamic changes across cortical layers with a less draining vein effect. In summary, this SELINE method provides a novel acquisition scheme to identify microvascular-sensitive laminar-specific BOLD responses across cortical depth.

Free-breathing Arterial Spin Labeling MRI for the Detection of Pulmonary Embolism.

Background Arterial spin labeling (ASL) MRI can be used to assess organ perfusion but has yet to be implemented for perfusion evaluation of the lung. Purpose To evaluate pseudo-continuous ASL (PCASL) MRI for the detection of acute pulmonary embolism (PE) and its potential as an alternative to CT pulmonary angiography (CTPA). Materials and Methods Between November 2020 and November 2021, 97 patients (median age, 61 years; 48 women) with suspected PE were enrolled in this prospective study. PCASL MRI was performed within a 72-hour period following CTPA under free-breathing conditions and included three orthogonal planes. The pulmonary trunk was labeled during systole, and the image was acquired during diastole of the subsequent cardiac cycle. Additionally, multisection, coronal, balanced, steady-state free-precession imaging was carried out. Two radiologists blindly assessed overall image quality, artifacts, and diagnostic confidence (five-point Likert scale, 5 = best). Patients were categorized as positive or negative for PE, and a lobe-wise assessment in PCASL MRI and CTPA was conducted. Sensitivity and specificity were calculated on a patient level with the final clinical diagnosis serving as the reference standard. Interchangeability between MRI and CTPA was also tested with use of an individual equivalence index (IEI). Results PCASL MRI was performed successfully in all patients with high scores for image quality, artifact, and diagnostic confidence (κ ≥ .74). Of the 97 patients, 38 were positive for PE. PCASL MRI depicted PE correctly in 35 of 38 patients with three false-positive and three false-negative findings, resulting in a sensitivity of 35 of 38 patients (92% [95% CI: 79, 98]) and a specificity of 56 of 59 patients (95% [95% CI: 86, 99]). Interchangeability analysis revealed an IEI of 2.6% (95% CI: 1.2, 3.8). Conclusion Free-breathing pseudo-continuous arterial spin labeling MRI depicted abnormal lung perfusion caused by acute pulmonary embolism and may be useful as a contrast material-free alternative to CT pulmonary angiography for selected patients. German Clinical Trials Register no. DRKS00023599 © RSNA, 2023.

Concurrent intrinsic optical imaging and fMRI at ultra-high field using magnetic field proof optical components.

Intrinsic optical imaging (IOI) is a well established technique to quantify activation-related hemodynamical changes at the surface of the brain, which can be used to investigate the underlying processes of BOLD signal formation. To directly and quantitatively relate IOI and fMRI, simultaneous measurements with the two modalities are necessary. Here, a novel technical solution for a completely in-bore setup is presented, which uses only magnetic field proof components and thus allows concurrent recordings with a quality similar to that obtained in separate experiments. Measurements of the somatosensory cortex of rats with electrical forepaw stimulation were used to verify this approach. The high spatial and temporal resolution of the fMRI data, which is possible due to the high magnetic field of 14.1 T, the use of a point-spread function-based distortion correction and optimized additional anatomical images, allowed accurate colocalization of the images of the two modalities. Accordingly, detailed investigations of the temporal and spatial relationships between the hemodynamic parameters and the fMRI signal, which demonstrate the linear dependence of the BOLD effect on changes in the concentrations of oxygenated and deoxygenated hemoglobin, are possible. Comparisons between the signals emerging from arterial, venous and parenchymal areas are possible and show clearly distinct characteristics. The presented setup allows combining MRI measurements and optical recordings without serious losses in the data quality of either modality. While the proposed combination of fMRI and IOI can help to gain valuable insight into the generation of the BOLD effect, the setup can be easily modified to include different types of optical or MRI measurements.

Correction: Assessment of single-vessel cerebral blood velocity by phase contrast fMRI.

[This corrects the article DOI: 10.1371/journal.pbio.3000923.].

Assessment of single-vessel cerebral blood velocity by phase contrast fMRI.

Current approaches to high-field functional MRI (fMRI) provide 2 means to map hemodynamics at the level of single vessels in the brain. One is through changes in deoxyhemoglobin in venules, i.e., blood oxygenation level-dependent (BOLD) fMRI, while the second is through changes in arteriole diameter, i.e., cerebral blood volume (CBV) fMRI. Here, we introduce cerebral blood flow-related velocity-based fMRI, denoted CBFv-fMRI, which uses high-resolution phase contrast (PC) MRI to form velocity measurements of flow. We use CBFv-fMRI in measure changes in blood velocity in single penetrating microvessels across rat parietal cortex. In contrast to the venule-dominated BOLD and arteriole-dominated CBV fMRI signals, CBFv-fMRI is comparable from both arterioles and venules. A single fMRI platform is used to map changes in blood pO2 (BOLD), volume (CBV), and velocity (CBFv). This combined high-resolution single-vessel fMRI mapping scheme enables vessel-specific hemodynamic mapping in animal models of normal and diseased states and further has translational potential to map vascular dementia in diseased or injured human brains with ultra-high-field fMRI.

Quantitative and simultaneous measurement of oxygen consumption rates in rat brain and skeletal muscle using 17 O MRS imaging at 16.4T.

PURPOSE: Oxygen-17 (17 O) MRS imaging, successfully used in the brain, is extended by imaging the oxygen metabolic rate in the resting skeletal muscle and used to determine the total whole-body oxygen metabolic rate in the rat. METHODS: During and after inhalations of 17 O2 gas, dynamic 17 O MRSI was performed in rats (n = 8) ventilated with N2 O or N2 at 16.4 T. Time courses of the H217 O concentration from regions of interest located in brain and muscle tissue were examined and used to fit an animal-adapted 3-phase metabolic model of oxygen consumption. CBF was determined with an independent washout method. Finally, body oxygen metabolic rate was calculated using a global steady-state approach. RESULTS: Cerebral metabolic rate of oxygen consumption was 1.97 ± 0.19 µmol/g/min on average. The resting metabolic rate of oxygen consumption in skeletal muscle was 0.32 ± 0.12 µmol/g/min and >6 times lower than cerebral metabolic rate of oxygen consumption. Global oxygen consumed by the body was 24.2 ± 3.6 mL O2 /kg body weight/min. CBF was estimated to be 0.28 ± 0.02 mL/g/min and 0.34 ± 0.06 mL/g/min for the N2 and N2 O ventilation condition, respectively. CONCLUSION: We have evaluated the feasibility of 17 O MRSI for imaging and quantifying the oxygen consumption rate in low metabolizing organs such as the skeletal muscle at rest. Additionally, we have shown that CBF is slightly increased in the case of ventilation with N2 O. We expect this study to be beneficial to the application of 17 O MRSI to a wider range of organs, although further validation is advised.

Intravascular BOLD signal characterization of balanced SSFP experiments in human blood at high to ultrahigh fields.

PURPOSE: To investigate the intravascular contribution to the overall balanced SSFP (bSSFP) BOLD effect in human blood at high to ultrahigh field strengths (3 T, 9.4 T, and 14.1 T). METHODS: Venous blood prepared at two different oxygenation levels (deoxygenated: Y ≈ 71%, oxygenated: Y ≈ 94%) was measured with phase-cycled bSSFP for varying TRs/flip angles at 3 T, 9.4 T, and 14.1 T. The oxygen sensitivity was analyzed by intrinsic MIRACLE (motion-insensitive rapid configuration relaxometry)-R2 estimation and passband signal differences. The intravascular BOLD-related signal change was extracted from the measured data for microvasculature and macrovasculature, and compared with the extravascular contribution obtained by Monte Carlo simulations. RESULTS: The MIRACLE-R2 values showed a characteristic increase with longer TRs in deoxygenated blood, corroborating that SE-R2 data cannot be used to assess the intravascular bSSFP BOLD effect. Passband bSSFP signal differences measured at optimal flip angles of 30° at 3 T and 20° at 9.4 T/14.1 T revealed considerable relative intravascular contributions of 95%/70% at 3 T, 74%/43% at 9.4 T, 66%/46% at 14.1 T for TR = 5 ms, and 90%/65% at 3 T, 36%/27% at 9.4 T, 13%/15% at 14.1 T for TR = 10 ms in macrovascular/microvascular regimes. CONCLUSION: The results indicate that intravascular effects have to be considered to better understand the origin of bSSFP BOLD contrast in functional MRI experiments, especially at short TRs. The MIRACLE-R2 method demonstrated the ability to quantify the apparent decrease in R2 due to rapid RF refocusing.

Imaging Pulmonary Blood Flow Using Pseudocontinuous Arterial Spin Labeling (PCASL) With Balanced Steady-State Free-Precession (bSSFP) Readout at 1.5T.

BACKGROUND: Quantitative assessment of pulmonary blood flow and visualization of its temporal and spatial distribution without contrast media is of clinical significance. PURPOSE: To assess the potential of electrocardiogram (ECG)-triggered pseudocontinuous arterial spin labeling (PCASL) imaging with balanced steady-state free-precession (bSSFP) readout to measure lung perfusion under free-breathing (FB) conditions and to study temporal and spatial characteristics of pulmonary blood flow. STUDY TYPE: Prospective, observational. SUBJECTS: Fourteen volunteers; three patients with pulmonary embolism. FIELD STRENGTH/SEQUENCES: 1.5T, PCASL-bSSFP. ASSESSMENT: The pulmonary trunk was labeled during systole. The following examinations were performed: 1) FB and timed breath-hold (TBH) examinations with a postlabeling delay (PLD) of 1000 msec, and 2) TBH examinations with multiple PLDs (100-1500 msec). Scan-rescan measurements were performed in four volunteers and one patient. Images were registered and the perfusion was evaluated in large vessels, small vessels, and parenchyma. Mean structural similarity indices (MSSIM) was computed and time-to-peak (TTP) of parenchymal perfusion in multiple PLDs was evaluated. Image quality reading was performed with three independent blinded readers. STATISTICAL TESTS: Wilcoxon test to compare MSSIM, perfusion, and Likert scores. Spearman's correlation to correlate TTP and cardiac cycle duration. The repeatability coefficient (RC) and within-subject coefficient of variation (wCV) for scan-rescan measurements. Intraclass correlation coefficient (ICC) for interreader agreement. RESULTS: Image registration resulted in a significant (P < 0.05) increase of MSSIM. FB perfusion values were 6% higher than TBH (3.28 ± 1.09 vs. 3.10 ± 0.99 mL/min/mL). TTP was highly correlated with individuals' cardiac cycle duration (Spearman = 0.89, P < 0.001). RC and wCV were better for TBH than FB (0.13-0.19 vs. 0.47-1.54 mL/min/mL; 6-7 vs. 19-60%). Image quality was rated very good, with ICCs 0.71-0.89. DATA CONCLUSION: ECG-triggered PCASL-bSSFP imaging of the lung at 1.5T can provide very good image quality and quantitative perfusion maps even under FB. The course of labeled blood through the lung shows a strong dependence on the individuals' cardiac cycle duration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2 J. MAGN. RESON. IMAGING 2020;52:1767-1782.

A ratiometric 19F MR-based method for the quantification of Ca2+ using responsive paramagnetic probes.

We present a method for assessing the extracellular calcium concentration using 19F chemical shift imaging. Specifically, a custom made calcium-responsive and lanthanide-based 19F MRI probe that undergoes a strong and highly specific modulation of its signal upon coordination with calcium ions was developed and its performance is presented.

Ultra-High Field MRI in Alzheimer's Disease: Effective Transverse Relaxation Rate and Quantitative Susceptibility Mapping of Human Brain In Vivo and Ex Vivo compared to Histology.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. So far, diagnosis of AD is only unequivocally defined through postmortem histology. Amyloid plaques are a classical hallmark of AD and amyloid load is currently quantified by Positron Emission tomography (PET) in vivo. Ultra-high field magnetic resonance imaging (UHF-MRI) can potentially provide a non-invasive biomarker for AD by allowing imaging of pathological processes at a very-high spatial resolution. The first aim of this work was to reproduce the characteristic cortical pattern previously observed in vivo in AD patients using weighted-imaging at 7T. We extended these findings using quantitative susceptibility mapping (QSM) and quantification of the effective transverse relaxation rate (R2*) at 9.4T. The second aim was to investigate the origin of the contrast patterns observed in vivo in the cortex of AD patients at 9.4T by comparing quantitative UHF-MRI (9.4T and 14.1T) of postmortem samples with histology. We observed a distinctive cortical pattern in vivo in patients compared to healthy controls (HC), and these findings were confirmed ex vivo. Specifically, we found a close link between the signal changes detected by QSM in the AD sample at 14.1T and the distribution pattern of amyloid plaques in the histological sections of the same specimen. Our findings showed that QSM and R2* maps can distinguish AD from HC at UHF by detecting cortical alterations directly related to amyloid plaques in AD patients. Furthermore, we provided a method to quantify amyloid plaque load in AD patients at UHF non-invasively.

Impact of prospective motion correction, distortion correction methods and large vein bias on the spatial accuracy of cortical laminar fMRI at 9.4 Tesla.

Functional imaging with sub-millimeter spatial resolution is a basic requirement for assessing functional MRI (fMRI) responses across different cortical depths and is used extensively in the emerging field of laminar fMRI. Such studies seek to investigate the detailed functional organization of the brain and may develop to a new powerful tool for human neuroscience. However, several studies have shown that measurement of laminar fMRI responses can be biased by the image acquisition and data processing strategies. In this work, measurements with three different gradient-echo EPI BOLD fMRI protocols with a voxel size down to 650 â€‹µm isotropic were performed at 9.4 â€‹T. We estimated how prospective motion correction can help to improve spatial accuracy by reducing the number of spatial resampling steps in postprocessing. In addition, we demonstrate key requirements for accurate geometric distortion correction to ensure that distortion correction maps are properly aligned to the functional data and that strong variations of distortions near large veins can lead to signal overlays which cannot be corrected for during postprocessing. Furthermore, this study illustrates the spatial extent of bias induced by pial and other larger veins in laminar BOLD experiments. Since these issues under investigation affect studies performed with more conventional spatial resolutions, the methods applied in this work may also help to improve the understanding of the BOLD signal more broadly.

A CMOS NMR needle for probing brain physiology with high spatial and temporal resolution.

Magnetic resonance imaging and spectroscopy are versatile methods for probing brain physiology, but their intrinsically low sensitivity limits the achievable spatial and temporal resolution. Here, we introduce a monolithically integrated NMR-on-a-chip needle that combines an ultra-sensitive 300 µm NMR coil with a complete NMR transceiver, enabling in vivo measurements of blood oxygenation and flow in nanoliter volumes at a sampling rate of 200 Hz.

Quantification of hydroxyl exchange of D-Glucose at physiological conditions for optimization of glucoCEST MRI at 3, 7 and 9.4 Tesla.

AIMS: To determine individual glucose hydroxyl exchange rates at physiological conditions and use this information for numerical optimization of glucoCEST/CESL preparation. To give guidelines for in vivo glucoCEST/CESL measurement parameters at clinical and ultra-high field strengths. METHODS: Five glucose solution samples at different pH values were measured at 14.1 T at various B1 power levels. Multi-B1 -Z-spectra Bloch-McConnell fits at physiological pH were further improved by the fitting of Z-spectra of five pH values simultaneously. The obtained exchange rates were used in a six-pool Bloch-McConnell simulation including a tissue-like water pool and semi-solid MT pool with different CEST and CESL presaturation pulse trains. In vivo glucose injection experiments were performed in a tumor mouse model at 7 T. RESULTS AND DISCUSSION: Glucose Z-spectra could be fitted with four exchanging pools at 0.66, 1.28, 2.08 and 2.88 ppm. Corresponding hydroxyl exchange rates could be determined at pH = 7.2, T = 37°C and 1X PBS. Simulation of saturation transfer for this glucose system in a gray matter-like and a tumor-like system revealed optimal pulses at different field strengths of 9.4, 7 and 3 T. Different existing sequences and approaches are simulated and discussed. The optima found could be experimentally verified in an animal model at 7 T. CONCLUSION: For the determined fast exchange regime, presaturation pulses in the spin-lock regime (long recover time, short yet strong saturation) were found to be optimal. This study gives an estimation for optimization of the glucoCEST signal in vivo on the basis of glucose exchange rate at physiological conditions.

Spatial-temporal perfusion patterns of the human liver assessed by pseudo-continuous arterial spin labeling MRI.

PURPOSE: To investigate the capabilities of a modern pseudo-continuous arterial spin labeling (PCASL) technique for non-invasive assessment of the temporal and spatial distribution of the liver perfusion in healthy volunteers on a clinical MR system at 3T. MATERIALS AND METHODS: A 2D-PCASL multi-slice echo planar imaging sequence was adapted to the specific conditions in liver: a) labeling by PCASL was optimized to the flow characteristics in the portal vein, b) background suppression was applied for reduction of motion related artifacts, c) post labeling delays (PLDs) were varied over a large range (0.7-3.5s) in order to get better insight in the temporal and spatial distribution of tagged blood in the liver, and d) a special timed-breathing protocol was used allowing for recording of 16 to 18 label-control image pairs and a reference M0 image for each of 4 to 6 slices within approx. 5min for one PLD. RESULTS: Measurements with multiple PLDs showed dominating perfusion signal in macroscopic blood vessels for PLDs up to 1.5 s, whereas pure liver parenchyma revealed maximum perfusion signal for a PLD of approx. 2 s, and detectable signal up to PLDs of 3.5 s. Data fitting to a perfusion model for liver provided a mean global perfusion of 153±15ml/100g/min and a mean transit time of 1938±332ms in liver parenchyma. Measurements with a single PLD of 2 s demonstrated that portal-venous and arterial perfusion components can be measured separately by two measurements with two different positions of the labeling plane (one for labeling of the global hepatopetal blood flow and one for selective labeling of the portal blood flow only). Relative contribution of blood from the hepatic artery to the global liver perfusion, the hepatic perfusion index (HPI), amounted to approx. 23%. CONCLUSION: Modern and adapted protocols for assessment of liver perfusion by PCASL have the potential to provide perfusion and blood transit time maps in reasonable acquisition time.

In-vivo quantitative structural imaging of the human midbrain and the superior colliculus at 9.4T.

We explored anatomical details of the superior colliculus (SC) by in vivo magnetic resonance imaging (MRI) at 9.4T. The high signal-to-noise ratio allowed the acquisition of high resolution, multi-modal images with voxel sizes ranging between 176 × 132 × 600 µm and (800)3µm. Quantitative mapping of the longitudinal relaxation rate R1, the effective transverse relaxation rate R2*, and the magnetic susceptibility QSM was performed in 14 healthy volunteers. The images were analyzed in native space as well as after normalization to a common brain space (MNI). The coefficient-of-variation (CoV) across subjects was evaluated in prominent regions of the midbrain, reaching the best reproducibility (CoV of 5%) in the R2* maps of the SC in MNI space, while the CoV in the QSM maps remained high regardless of brain-space. To investigate whether more complex neurobiological architectural features could be detected, depth profiles through the SC layers towards the red nucleus (RN) were evaluated at different levels of the SC along the rostro-caudal axis. This analysis revealed alterations of the quantitative MRI parameters concordant with previous post mortem histology studies of the cyto- and myeloarchitecture of the SC. In general, the R1 maps were hyperintense in areas characterized by the presence of abundant myelinated fibers, and likely enabled detection of the deep white layer VII of the SC adjacent to the periaqueductal gray. While R1 maps failed to reveal finer details, possibly due to the relatively coarse spatial sampling used for this modality, these could be recovered in R2* maps and in QSM. In the central part of the SC along its rostro-caudal axis, increased R2* values and decreased susceptibility values were observed 2 mm below the SC surface, likely reflecting the myelinated fibers in the superficial optic layer (layer III). Towards the deeper layers, a second increase in R2* was paralleled by a paramagnetic shift in QSM suggesting the presence of an iron-rich layer about 3 mm below the surface of the SC, attributed to the intermediate gray layer (IV) composed of multipolar neurons. These results dovetail observations in histological specimens and animal studies and demonstrate that high-resolution multi-modal MRI at 9.4T can reveal several microstructural features of the SC in vivo.

Ultra-Slow Single-Vessel BOLD and CBV-Based fMRI Spatiotemporal Dynamics and Their Correlation with Neuronal Intracellular Calcium Signals.

Functional MRI has been used to map brain activity and functional connectivity based on the strength and temporal coherence of neurovascular-coupled hemodynamic signals. Here, single-vessel fMRI reveals vessel-specific correlation patterns in both rodents and humans. In anesthetized rats, fluctuations in the vessel-specific fMRI signal are correlated with the intracellular calcium signal measured in neighboring neurons. Further, the blood-oxygen-level-dependent (BOLD) signal from individual venules and the cerebral-blood-volume signal from individual arterioles show correlations at ultra-slow (<0.1 Hz), anesthetic-modulated rhythms. These data support a model that links neuronal activity to intrinsic oscillations in the cerebral vasculature, with a spatial correlation length of ∼2 mm for arterioles. In complementary data from awake human subjects, the BOLD signal is spatially correlated among sulcus veins and specified intracortical veins of the visual cortex at similar ultra-slow rhythms. These data support the use of fMRI to resolve functional connectivity at the level of single vessels.