Biomineralization Synthesis of HoMn Nanoparticles for Ultrahigh-Field-Tailored and T1-T2 Dual-Mode MRI-Guided Cancer Theranostics.

Ultrahigh field magnetic resonance imaging (UHF-MRI) (≥7 T) can dramatically boost image resolution and signal-to-noise ratio, which have distinct advantages in multifunctional imaging. However, their research and application are currently limited by the absence of high-field contrast agents (CAs) and the low sensitivity and accuracy of T1/T2 single-modality CAs. Therefore, the development of T1-T2 dual-mode CAs that respond to UHF-MRI and nanoformulations with therapeutic sensitization can bring ideas for the integrated application of precise and synchronous tumor theranostics. Herein, we present a biomimetic mineralization strategy for synthesizing holmium/manganese oxide-bovine serum albumin-photosensitizer chlorin e6 nanohybrids. The hybrid nanoparticles exhibited better tumor accumulation, a suitable time imaging window, and excellent pH-response T1-T2 dual-mode UHF-MRI performance. The antitumor effect comes from the amelioration of the hypoxic tumor microenvironment to promote the synergistic effect of photodynamic therapy and radiotherapy, along with negligible acute toxicity. Undoubtedly, this work not only provides a different perspective for developing multifunctional nanotherapeutics but also promotes the potential clinical exploitation and translation of UHF CAs.

QRAGE-Simultaneous multiparametric quantitative MRI of water content, T1, T2*, and magnetic susceptibility at ultrahigh field strength.

PURPOSE: To introduce quantitative rapid gradient-echo (QRAGE), a novel approach for the simultaneous mapping of multiple quantitative MRI parameters, including water content, T1, T2*, and magnetic susceptibility at ultrahigh field strength. METHODS: QRAGE leverages a newly developed multi-echo MPnRAGE sequence, facilitating the acquisition of 171 distinct contrast images across a range of inversion and TE points. To maintain a short acquisition time, we introduce MIRAGE2, a novel model-based reconstruction method that exploits prior knowledge of temporal signal evolution, represented as damped complex exponentials. MIRAGE2 minimizes local Block-Hankel and Casorati matrices. Parameter maps are derived from the reconstructed contrast images through postprocessing steps. We validate QRAGE through extensive simulations, phantom studies, and in vivo experiments, demonstrating its capability for high-precision imaging. RESULTS: In vivo brain measurements show the promising performance of QRAGE, with test-retest SDs and deviations from reference methods of < 0.8% for water content, < 17 ms for T1, and < 0.7 ms for T2*. QRAGE achieves whole-brain coverage at a 1-mm isotropic resolution in just 7 min and 15 s, comparable to the acquisition time of an MP2RAGE scan. In addition, QRAGE generates a contrast image akin to the UNI image produced by MP2RAGE. CONCLUSION: QRAGE is a new, successful approach for simultaneously mapping multiple MR parameters at ultrahigh field.

A Quantitative Comparison of 31P Magnetic Resonance Spectroscopy RF Coil Sensitivity and SNR between 7T and 10.5T Human MRI Scanners Using a Loop-Dipole 31P-1H Probe.

In vivo phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) imaging (MRSI) is an important non-invasive imaging tool for studying cerebral energy metabolism, intracellular nicotinamide adenine dinucleotide (NAD) and redox ratio, and mitochondrial function. However, it is challenging to achieve high signal-to-noise ratio (SNR) 31P MRS/MRSI results owing to low phosphorus metabolites concentration and low phosphorous gyromagnetic ratio (γ). Many works have demonstrated that ultrahigh field (UHF) could significantly improve the 31P-MRS SNR. However, there is a lack of studies of the 31P MRSI SNR in the 10.5 Tesla (T) human scanner. In this study, we designed and constructed a novel 31P-1H dual-frequency loop-dipole probe that can operate at both 7T and 10.5T for a quantitative comparison of 31P MRSI SNR between the two magnetic fields, taking into account the RF coil B1 fields (RF coil receive and transmit fields) and relaxation times. We found that the SNR of the 31P MRS signal is 1.5 times higher at 10.5T as compared to 7T, and the power dependence of SNR on magnetic field strength (B0) is 1.9.

Assessing Cerebral Microvascular Volumetric Pulsatility with High-Resolution 4D CBV MRI at 7T.

Arterial pulsation is crucial for promoting fluid circulation and for influencing neuronal activity. Previous studies assessed the pulsatility index based on blood flow velocity pulsatility in relatively large cerebral arteries of human. Here, we introduce a novel method to quantify the volumetric pulsatility of cerebral microvasculature across cortical layers and in white matter (WM), using high-resolution 4D vascular space occupancy (VASO) MRI with simultaneous recording of pulse signals at 7T. Microvascular volumetric pulsatility index (mvPI) and cerebral blood volume (CBV) changes across cardiac cycles are assessed through retrospective sorting of VASO signals into cardiac phases and estimating mean CBV in resting state (CBV0) by arterial spin labeling (ASL) MRI at 7T. Using data from 11 young (28.4±5.8 years) and 7 older (61.3±6.2 years) healthy participants, we investigated the aging effect on mvPI and compared microvascular pulsatility with large arterial pulsatility assessed by 4D-flow MRI. We observed the highest mvPI in the cerebrospinal fluid (CSF) on the cortical surface (0.19±0.06), which decreased towards the cortical layers as well as in larger arteries. In the deep WM, a significantly increased mvPI (p = 0.029) was observed in the older participants compared to younger ones. Additionally, mvPI in deep WM is significantly associated with the velocity pulsatility index (vePI) of large arteries (r = 0.5997, p = 0.0181). We further performed test-retest scans, non-parametric reliability test and simulations to demonstrate the reproducibility and accuracy of our method. To the best of our knowledge, our method offers the first in vivo measurement of microvascular volumetric pulsatility in human brain which has implications for cerebral microvascular health and its relationship research with glymphatic system, aging and neurodegenerative diseases.

Shaping the RF Transmit Field in 7T MRI Using a Nonuniform Metasurface Constructed of Short Conducting Strips.

The ability of metamaterial structures to offer unique properties and new solutions has opened new avenues in a wide range of applications, including super-resolution in optics and efficient antennas in radiofrequency (RF) engineering. In magnetic resonance imaging (MRI), metamaterials hold the promise of increasing the RF magnetic field intensity while minimizing power deposition. Here, we propose a metasurface based on a two-dimensional (2D) array of short conducting strips combined with a high dielectric substrate, which was tuned to operate at ultrahigh field 7T human MRI. While studied in optics and electromagnetics in the GHz-to-THz range, this study is the first to design such a metasurface for proton imaging at 7T MRI. We performed electromagnetic (EM) simulation of the brain MRI setup with the new metasurface placed in the proximity to the temporal lobe, which showed 2.2-fold local increase in the RF transmit efficiency, with superior performance than an array of electric dipoles. In this study, we also investigate the effect of the spatial distribution of the subunits to control the target RF field's distribution. While the common design is based on a uniform distribution of the subunits, nonuniform distribution, such as a denser center (convex) or more condensed edges (concave), provides an extra dimension to tailor both the magnetic and electric fields. The concave distribution achieved 1.5-1.8-fold reduction in the power deposition compared to the uniform distribution in the brain MRI setups examined.

B1-MRF: Large dynamic range MRF-based absolute B 1 + mapping in the human body at 7T.

PURPOSE: This study aims to map the transmit magnetic field ( B 1 + $$ {B}_1^{+} $$ ) in the human body at 7T using MR fingerprinting (MRF), with a focus on achieving high accuracy and precision across a large dynamic range, particularly at low flip angles (FAs). METHODS: A FLASH-based MRF sequence (B1-MRF) with high B 1 + $$ {B}_1^{+} $$ sensitivity was developed. Phantom and in vivo abdominal imaging were performed at 7T, and the results were compared with established reference methods, including a slow but precise preparation-based method (PEX), saturated TurboFLASH (satTFL), actual flip angle imaging (AFI) and Bloch-Siegert shift (BSS). RESULTS: The MRF signal curve was highly sensitive to B 1 + $$ {B}_1^{+} $$ , while T1 sensitivity was comparatively low. The phantom experiment showed good agreement of B 1 + $$ {B}_1^{+} $$ to PEX for a T1 range of 204-1691 ms evaluated at FAs from 0° to 70°. Compared to the references, a dynamic range increase larger than a factor of two was determined experimentally. In vivo liver scans showed a strong correlation between B1-MRF, satTFL, and RPE-AFI in a low body mass index (BMI) subject (18.1 kg/m2). However, in larger BMI subjects (≥25.5 kg/m2), inconsistencies were observed in low B 1 + $$ {B}_1^{+} $$ regions for satTFL and RPE-AFI, while B1-MRF still provided consistent results in these regions. CONCLUSION: B1-MRF provides accurate and precise B 1 + $$ {B}_1^{+} $$ maps over a wide range of FAs, surpassing the capabilities of existing methods in the FA range < 60°. Its enhanced sensitivity at low FAs is advantageous for various applications requiring precise B 1 + $$ {B}_1^{+} $$ estimates, potentially advancing the frontiers of ultra-high field (UHF) body imaging at 7T and beyond.

Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla.

Introduction: Nicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging. Methods: In this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method. Results: The processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age. Discussion: These results illustrate favorable outcomes of our first attempt to use ultrahigh field 31P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.

Sequence-agnostic motion-correction leveraging efficiently calibrated Pilot Tone signals.

PURPOSE: This study leverages externally generated Pilot Tone (PT) signals to perform motion-corrected brain MRI for sequences with arbitrary k-space sampling and image contrast. THEORY AND METHODS: PT signals are promising external motion sensors due to their cost-effectiveness, easy workflow, and consistent performance across contrasts and sampling patterns. However, they lack robust calibration pipelines. This work calibrates PT signal to rigid motion parameters acquired during short blocks (˜4 s) of motion calibration (MC) acquisitions, which are short enough to unobstructively fit between acquisitions. MC acquisitions leverage self-navigated trajectories that enable state-of-the-art motion estimation methods for efficient calibration. To capture the range of patient motion occurring throughout the examination, distributed motion calibration (DMC) uses data acquired from MC scans distributed across the entire examination. After calibration, PT is used to retrospectively motion-correct sequences with arbitrary k-space sampling and image contrast. Additionally, a data-driven calibration refinement is proposed to tailor calibration models to individual acquisitions. In vivo experiments involving 12 healthy volunteers tested the DMC protocol's ability to robustly correct subject motion. RESULTS: The proposed calibration pipeline produces pose parameters consistent with reference values, even when distributing only six of these approximately 4-s MC blocks, resulting in a total acquisition time of 22 s. In vivo motion experiments reveal significant ( p < 0.05 $$ p<0.05 $$ ) improved motion correction with increased signal to residual ratio for both MPRAGE and SPACE sequences with standard k-space acquisition, especially when motion is large. Additionally, results highlight the benefits of using a distributed calibration approach. CONCLUSIONS: This study presents a framework for performing motion-corrected brain MRI in sequences with arbitrary k-space encoding and contrast, using externally generated PT signals. The DMC protocol is introduced, promoting observation of patient motion occurring throughout the examination and providing a calibration pipeline suitable for clinical deployment. The method's application is demonstrated in standard volumetric MPRAGE and SPACE sequences.

Accelerated 3D multi-channel B 1 + mapping at 7 T for the brain and heart.

PURPOSE: To acquire accurate volumetric multi-channel B 1 + $$ {\mathrm{B}}_1^{+} $$ maps in under 14 s whole-brain or 23 heartbeats whole-heart for parallel transmit (pTx) applications at 7 T. THEORY AND METHODS: We evaluate the combination of three recently proposed techniques. The acquisition of multi-channel transmit array B 1 + $$ {\mathrm{B}}_1^{+} $$ maps is accelerated using transmit low rank (TxLR) with absolute B 1 + $$ {\mathrm{B}}_1^{+} $$ mapping (Sandwich) acquired in a B 1 + $$ {\mathrm{B}}_1^{+} $$ time-interleaved acquisition of modes (B1TIAMO) fashion. Simulations using synthetic body images derived from Sim4Life were used to test the achievable acceleration for small scan matrices of 24 × 24. Next, we evaluated the method by retrospectively undersampling a fully sampled B 1 + $$ {\mathrm{B}}_1^{+} $$ library of nine subjects in the brain. Finally, Cartesian undersampled phantom and in vivo images were acquired in both the brain of three subjects (8Tx/32 receive [Rx]) and the heart of another three subjects (8Tx/8Rx) at 7 T. RESULTS: Simulation and in vivo results show that volumetric multi-channel B 1 + $$ {\mathrm{B}}_1^{+} $$ maps can be acquired using acceleration factors of 4 in the body, reducing the acquisition time to within 23 heartbeats, which was previously not possible. In silico heart simulations demonstrated a RMS error to the fully sampled native resolution ground truth of 4.2° when combined in first-order circularly polarized mode (mean flip angle 66°) at an acceleration factor of 4. The 14 s 3D B 1 + $$ {\mathrm{B}}_1^{+} $$ maps acquired in the brain have a RMS error of 1.9° to the fully sampled (mean flip angle 86°). CONCLUSION: The proposed method is demonstrated as a fast pTx calibration technique in the brain and a promising method for pTx calibration in the body.

Active shimming for a 25 T NMR superconducting magnet by spectrum convergence method.

In the design of ultrahigh field nuclear magnetic resonance (NMR) superconducting magnets, it typically requires a high homogeneous magnetic field in the diameter of spherical volume (DSV) to obtain high spectrum resolution. However, shimming technique presents challenges due to the magnet bore space limitations, as accurate measurement of magnetic field distribution is very difficult, especially for customized micro-bore magnets. In this study, we introduced an active shimming method that utilized iterative adjustment of shim coil currents to improve the magnetic field homogeneity based on the full width at half maximum (FWHM) of the spectrum. The proposed method can determine the optimal set of currents for shim coils, effectively enhancing spatial field homogeneity by converging the FWHM. Experimental validation on a 25 T NMR superconducting magnet demonstrated the efficacy of the proposed method. Specifically, the active shimming method improved the field homogeneity of a 10 mm DSV from 7.09 ppm to 2.27 ppm with only four shim coils, providing a superior magnetic field environment for solid NMR and further magnetic resonance imaging (MRI) experiment. Furthermore, the proposed method can be promoted to more customized micro-bore magnets that require high magnetic field homogeneity.

Free-breathing high-resolution respiratory-gated radial stack-of-stars magnetic resonance imaging of the upper abdomen at 7 T.

Ultrahigh field magnetic resonance imaging (MRI) (≥ 7 T) has the potential to provide superior spatial resolution and unique image contrast. Apart from radiofrequency transmit inhomogeneities in the body at this field strength, imaging of the upper abdomen faces additional challenges associated with motion-induced ghosting artifacts. To address these challenges, the goal of this work was to develop a technique for high-resolution free-breathing upper abdominal MRI at 7 T with a large field of view. Free-breathing 3D gradient-recalled echo (GRE) water-excited radial stack-of-stars data were acquired in seven healthy volunteers (five males/two females, body mass index: 19.6-24.8 kg/m2) at 7 T using an eight-channel transceive array coil. Two volunteers were also examined at 3 T. In each volunteer, the liver and kidney regions were scanned in two separate acquisitions. To homogenize signal excitation, the time-interleaved acquisition of modes (TIAMO) method was used with personalized pairs of B1 shims, based on a 23-s Cartesian fast low angle shot (FLASH) acquisition. Utilizing free-induction decay navigator signals, respiratory-gated images were reconstructed at a spatial resolution of 0.8 × 0.8 × 1.0 mm3. Two experienced radiologists rated the image quality and the impact of B1 inhomogeneity and motion-related artifacts on multipoint scales. The images of all volunteers showcased effective water excitation and were accurately corrected for respiratory motion. The impact of B1 inhomogeneity on image quality was minimal, underscoring the efficacy of the multitransmit TIAMO shim. The high spatial resolution allowed excellent depiction of small structures such as the adrenal glands, the proximal ureter, the diaphragm, and small blood vessels, although some streaking artifacts persisted in liver image data. In direct comparisons with 3 T performed for two volunteers, 7-T acquisitions demonstrated increases in signal-to-noise ratio of 77% and 58%. Overall, this work demonstrates the feasibility of free-breathing MRI in the upper abdomen at submillimeter spatial resolution at a magnetic field strength of 7 T.

High-resolution 1H-MRSI at 9.4 T by integrating relaxation enhancement and subspace imaging.

Achieving high-resolution and high signal-to-noise ratio (SNR) in vivo metabolic imaging via fast magnetic resonance spectroscopic imaging (MRSI) has been a longstanding challenge. This study combines the methods of relaxation enhancement (RE) and subspace imaging for the first time, enabling high-resolution and high-SNR in vivo MRSI of rodent brains at 9.4 T. Specifically, an RE-based chemical shift imaging sequence, which combines a frequency-selective pulse to excite only the metabolite frequencies with minimum perturbation of the water spins and a pair of adiabatic pulses to spatially localize the slice of interest, is designed and evaluated in vivo. This strategy effectively shortens the apparent T1 of metabolites, thereby increasing the SNR during relatively short repetition time ((TR) compared with acquisitions with only spatially selective wideband excitations, and does not require water suppression. The SNR was further enhanced via a state-of-the-art subspace reconstruction method. A novel subspace learning strategy tailored for 9.4 T and RE acquisitions is developed. In vivo, high-resolution (e.g., voxel size of 0.6 × 0.6 × 1.5 mm3) MRSI of both healthy mouse brains and a glioma-bearing mouse brain in 12.5 min has been demonstrated.

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.

Ultrahigh field diffusion magnetic resonance imaging uncovers intriguing microstructural changes in the adult zebrafish brain caused by Toll-like receptor 2 genomic deletion.

Toll-like receptor 2 (TLR2) belongs to the TLR protein family that plays an important role in the immune and inflammation response system. While TLR2 is predominantly expressed in immune cells, its expression has also been detected in the brain, specifically in microglia and astrocytes. Recent studies indicate that genomic deletion of TLR2 can result in impaired neurobehavioural function. It is currently not clear if the genomic deletion of TLR2 leads to any alterations in the microstructural features of the brain. In the current study, we noninvasively assess microstructural changes in the brain of TLR2-deficient (tlr2-/-) zebrafish using state-of-the art magnetic resonance imaging (MRI) methods at ultrahigh magnetic field strength (17.6 T). A significant increase in cortical thickness and an overall trend towards increased brain volumes were observed in young tlr2-/- zebrafish. An elevated T2 relaxation time and significantly reduced apparent diffusion coefficient (ADC) unveil brain-wide microstructural alterations, potentially indicative of cytotoxic oedema and astrogliosis in the tlr2-/- zebrafish. Multicomponent analysis of the ADC diffusivity signal by the phasor approach shows an increase in the slow ADC component associated with restricted diffusion. Diffusion tensor imaging and diffusion kurtosis imaging analysis revealed diminished diffusivity and enhanced kurtosis in various white matter tracks in tlr2-/- compared with control zebrafish, identifying the microstructural underpinnings associated with compromised white matter integrity and axonal degeneration. Taken together, our findings demonstrate that the genomic deletion of TLR2 results in severe alterations to the microstructural features of the zebrafish brain. This study also highlights the potential of ultrahigh field diffusion MRI techniques in discerning exceptionally fine microstructural details within the small zebrafish brain, offering potential for investigating microstructural changes in zebrafish models of various brain diseases.

Performance of receive head arrays versus ultimate intrinsic SNR at 7 T and 10.5 T.

PURPOSE: We examined magnetic field dependent SNR gains and ability to capture them with multichannel receive arrays for human head imaging in going from 7 T, the most commonly used ultrahigh magnetic field (UHF) platform at the present, to 10.5 T, which represents the emerging new frontier of >10 T in UHFs. METHODS: Electromagnetic (EM) models of 31-channel and 63-channel multichannel arrays built for 10.5 T were developed for 10.5 T and 7 T simulations. A 7 T version of the 63-channel array with an identical coil layout was also built. Array performance was evaluated in the EM model using a phantom mimicking the size and electrical properties of the human head and a digital human head model. Experimental data was obtained at 7 T and 10.5 T with the 63-channel array. Ultimate intrinsic SNR (uiSNR) was calculated for the two field strengths using a voxelized cloud of dipoles enclosing the phantom or the digital human head model as a reference to assess the performance of the two arrays and field depended SNR gains. RESULTS: uiSNR calculations in both the phantom and the digital human head model demonstrated SNR gains at 10.5 T relative to 7 T of 2.6 centrally, ˜2 at the location corresponding to the edge of the brain, ˜1.4 at the periphery. The EM models demonstrated that, centrally, both arrays captured ˜90% of the uiSNR at 7 T, but only ˜65% at 10.5 T, leading only to ˜2-fold gain in array SNR in going from 7 to 10.5 T. This trend was also observed experimentally with the 63-channel array capturing a larger fraction of the uiSNR at 7 T compared to 10.5 T, although the percentage of uiSNR captured were slightly lower at both field strengths compared to EM simulation results. CONCLUSIONS: Major uiSNR gains are predicted for human head imaging in going from 7 T to 10.5 T, ranging from ˜2-fold at locations corresponding to the edge of the brain to 2.6-fold at the center, corresponding to approximately quadratic increase with the magnetic field. Realistic 31- and 63-channel receive arrays, however, approach the central uiSNR at 7 T, but fail to do so at 10.5 T, suggesting that more coils and/or different type of coils will be needed at 10.5 T and higher magnetic fields.

Hippocampal subfields and thalamic nuclei associations with clinical outcomes in multiple sclerosis: An ultrahigh field MRI study.

BACKGROUND: Previous studies have shown that thalamic and hippocampal neurodegeneration is associated with clinical decline in Multiple Sclerosis (MS). However, contributions of the specific thalamic nuclei and hippocampal subfields require further examination. OBJECTIVE: Using 7 Tesla (7T) magnetic resonance imaging (MRI), we investigated the cross-sectional associations between functionally grouped thalamic nuclei and hippocampal subfields volumes and T1 relaxation times (T1-RT) and subsequent clinical outcomes in MS. METHODS: High-resolution T1-weighted and T2-weighted images were acquired at 7T (n=31), preprocessed, and segmented using the Thalamus Optimized Multi Atlas Segmentation (THOMAS, for thalamic nuclei) and the Automatic Segmentation of Hippocampal Subfields (ASHS, for hippocampal subfields) packages. We calculated Pearson correlations between hippocampal subfields and thalamic nuclei volumes and T1-RT and subsequent multi-modal rater-determined and patient-reported clinical outcomes (∼2.5 years after imaging acquisition), correcting for confounders and multiple tests. RESULTS: Smaller volume bilaterally in the anterior thalamus region correlated with worse performance in gait function, as measured by the Patient Determined Disease Steps (PDDS). Additionally, larger volume in most functional groups of thalamic nuclei correlated with better visual information processing and cognitive function, as measured by the Symbol Digit Modalities Test (SDMT). In bilateral medial and left posterior thalamic regions, there was an inverse association between volumes and T1-RT, potentially indicating higher tissue degeneration in these regions. We also observed marginal associations between the right hippocampal subfields (both volumes and T1-RT) and subsequent clinical outcomes, though they did not survive correction for multiple testing. CONCLUSION: Ultrahigh field MRI identified markers of structural damage in the thalamic nuclei associated with subsequently worse clinical outcomes in individuals with MS. Longitudinal studies will enable better understanding of the role of microstructural integrity in these brain regions in influencing MS outcomes.

The feasibility of half-dose contrast-enhanced scanning of brain tumours at 5.0 T: a preliminary study.

PURPOSE: This study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T. METHODS: Twelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC). RESULTS: A total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p < 0.001). The CNR was also significantly greater at 5.0 T than at 3.0 T for grey matter/tumour lesions, white matter/tumour lesions, and grey matter/white matter (p < 0.001). Subjective evaluation revealed that the internal structure and outline of the tumour lesions were more clearly displayed with a half-dose at 5.0 T (Likert scale 8.1 ± 0.3 at 3.0 T, 8.9 ± 0.3 at 5.0 T, p < 0.001), and the effects of enhancement in the lesions were comparable to those with a full dose at 3.0 T (7.8 ± 0.3 at 3.0 T, 8.7 ± 0.4 at 5.0 T, p < 0.001). All subjective scores were good to excellent at both 5.0 T and 3.0 T. CONCLUSION: Both quantitative and subjective evaluation parameters suggested that half-dose enhanced scanning via 5.0 T MRI might be feasible for meeting clinical diagnostic requirements, as the image quality remains optimal. Enhanced scanning at 5.0 T with a half-dose of contrast agents might benefit patients with conditions that require less intravenous contrast agent, such as renal dysfunction.

High-field downfield MR spectroscopic imaging in the human brain.

PURPOSE: To investigate the feasibility of downfield MR spectroscopic imaging (DF-MRSI) in the human brain at 7T. METHODS: A 7T DF-MRSI pulse sequence was implemented based on the previously described methodology at 3T, with 3D phase-encoding, 1 3 ‾ 3 1 ‾ $$ 1\overline{3}3\overline{1} $$ spectral-spatial excitation, and frequency selective refocusing. Data were pre-processed followed by analysis using the "LCModel" software package, and metabolite maps created from the LCModel results. Total scan time, including brain MRI and a water-reference MRSI, was 24 min. The sequence was tested in 10 normal volunteers. Estimated metabolite levels and uncertainty values (Cramer Rao lower bounds, CRLBs) for nine downfield peaks were compared between seven different brain regions, anterior cingulate cortex (ACC), centrum semiovale (CSO), corpus callosum (CC), cerebellar vermis (CV), dorsolateral prefrontal cortex (DLPFC), posterior cingulate cortex (PCC), and thalamus (Thal). RESULTS: DF peaks were relatively uniformly distributed throughout the brain, with only a small number of peaks showing any significant regional variations. Most DF peaks had average CRLB<25% in most brain regions. Average SNR values were higher for the brain regions ACC and DLPFC (˜7 ± 0.95, mean ± SD) while in a range of 3.4-6.0 for other brain regions. Average linewidth (FWHM) values were greater than 35 Hz in the ACC, CV, and Thal, and 22 Hz in CC, CSO, DLPFC, and PCC. CONCLUSION: High-field DF-MRSI is able to spatially map exchangeable protons in the human brain at high resolution and with near whole-brain coverage in acceptable scan times, and in the future may be used to study metabolism of brain tumors or other neuropathological disorders.

Submillimeter balanced SSFP BOLD-functional MRI accelerated with 3D stack-of-spirals at 9.4 T.

PURPOSE: This work aims to improve the speed of balanced SSFP (bSSFP) acquisition with segmented 3D stack-of-spirals for functional brain studies at ultrahigh field. METHODS: Functional experiments were performed with an accelerated 3D stack-of-spirals sequence with water excitation for fat suppression. The resulting data were reconstructed using an iterative algorithm with corrections for system imperfections such as trajectory deviations and B0 inhomogeneity. In the first set of experiments, we evaluated the signal change and stability with respect to echo and TR for a full-field checkerboard stimulus. To demonstrate the high spatio-temporal resolution of the developed method, the results of three optimized protocols at submillimeter resolution (0.6-mm isotropic and 0.8-mm isotropic) and at 1.2 mm isotropic resolution for whole-brain coverage were shown. RESULTS: Water excitation and the model-based iterative reconstruction improved image quality. The BOLD-related signal changes increased with longer TE and longer TR. We observed an increase in thermal noise performance at lower TE and higher TR. However, signal stability deteriorates at higher TE and TR. Therefore, optimized protocols used shorter TE and moderately long TR to maximize the sensitivity and speed. Reproducible activations were detected along the gray-matter gyri in the submillimeter protocols with a median signal change of approximately 4% across subjects. CONCLUSIONS: Three-dimensional stack-of-spirals enables passband balanced SSFP functional imaging at a much higher spatial and temporal scale, compared with conventional spoiled gradient-echo train sequences.

Magnetic Resonance Spectroscopy (MRS) in Alzheimer's Disease.

MRS is a noninvasive technique to measure different metabolites in the brain. Changes in the levels of certain metabolites can be used as surrogate markers for Alzheimer's disease. They can potentially be used for diagnosis, prediction of prognosis, or even assessing response to treatment.There are different techniques for MRS acquisitions including STimulated Echo Acquisition Mode (STEAM) and Point Resolved Spectroscopy (PRESS). In terms of localization, single or multi-voxel methods can be used. Based on current data: 1. NAA, marker of neuronal integrity and viability, reduces in AD with longitudinal changes over the time as the disease progresses. There are data claiming that reduction of NAA is associated with tau accumulation, early neurodegenerative processes, and cognitive decline. Therefore, it can be used as a stage biomarker for AD to assess the severity of the disease. With advancement of disease modifying therapies, there is a potential role for NAA in the future to be used as a marker of response to treatment. 2. mI, marker of glial cell proliferation and activation, is associated with AB pathology and has early changes in the course of the disease. The NAA/mI ratio can be predictive of AD development with high specificity and can be utilized in the clinical setting to stratify cases for further evaluation with PET for potential treatments. 3. The changes in the level of other metabolites such as Chol, Glu, Gln, and GABA are controversial because of the lack of standardization of MRS techniques, current technical limitations, and possible region specific changes. 4. Ultrahigh field MRS and more advanced techniques can overcome many of these limitations and enable us to measure more metabolites with higher accuracy. 5. Standardization of MRS techniques, validation of metabolites' changes against PET using PET-guided technique, and longitudinal follow-ups to investigate the temporal changes of the metabolites in relation to other biomarkers and cognition will be crucial to confirm the utility of MRS as a potential noninvasive biomarker for AD.