Development of hybrid aptamers-engineered PROTACs for degrading VEGF165 in both tumor- and vascular endothelial cells.

Tumors and angiogenesis are connected through a complex interplay. VEGF165, generated from both tumor and vascular endothelial cells, serves as a mutual benefit for both cell types. Therapeutic approaches modulating VEGF165 have been proposed as promising antitumor therapies. PROTACs are bifunctional molecules that exploit the intracellular ubiquitin-proteasome system to degrade specific proteins. To date, there are no targeted PROTACs designed to degrade VEGF165 in both tumor and vascular endothelial cells. The aptamer AS1411 is notable for its ability to selectively recognize and enter both tumor and vascular endothelial cells by targeting the cell surface nucleolin (NCL). Moreover, AS1411 has also been repurposed as an intracellular recruiter of E3 ligase MDM2 via leveraging NCL as a molecular bridge. In this study, we conjugated AS1411 with a VEGF165-specific aptamer V7t1, creating hybrid aptamers-engineered PROTACs. The PROTACs demonstrate remarkable selectivity for both tumor and vascular endothelial cells and facilitate the ubiquitination and proteasomal degradation of VEGF165. The PROTACs inhibit the growth of tumor cells and also impede angiogenesis, without causing toxicity to normal tissues. The hybrid aptamers-engineered PROTACs provide an avenue for disrupting the tumor-angiogenesis interplay through modulation of VEGF165 in both tumor and vascular endothelial cells.

Induction of Extremely Severe Nausea via Vestibular Activation on a 7 Tesla MRI Scanner.

Extremely severe nausea was experienced by four subjects positioned prone on a 7T scanner table with their arm extended overhead for a wrist examination and their head positioned approximately 10-20 cm above the magnet's central axis. Movement through the large static and spatial field gradients of current 7T MRI scanner magnets typically causes mild vestibular activation which is well tolerated by most individuals. However, when positioned off-axis, the head moves through regions of even larger and more rapidly changing magnetic fields which in the current study were sufficient to induce the extremely severe nausea. Ensuring the head remains on-axis mitigates this effect.

Myelin water imaging of in vivo and ex vivo human brains using multi-echo gradient echo at 3 T and 7 T.

PURPOSE: To compare the myelin water fraction (MWF) measurements between 3 T and 7 T and between in vivo and ex vivo human brains, and to investigate the relationship between multi-echo gradient-echo (mGRE)-based 3D MWF and myelin content using histological staining, which has not been validated in the human brain. METHODS: In this study, we performed 3D mGRE-based MWF measurements on five ex vivo human brain hemispheres and five healthy volunteers at 3 T and 7 T with 1 mm isotropic resolution. The data were fitted with the T 2 * $$ {\mathrm{T}}_2^{\ast } $$ based on a three compartment complex-valued model to estimate MWF. We obtained myelin basic protein (MBP) staining from two tissue blocks and co-registered the MWF map and histology image for voxel-wise correlation between the two. RESULTS: The MWF values measured from 7 T were overall higher than 7 T, but data between the two field strength demonstrated high correlations both in vivo (r = 0.88) and ex vivo (r = 0.83) across 19 white matter regions. Moreover, the MWF measurements showed a good agreement between in vivo and ex vivo assessments at 3 T (r = 0.61) and 7 T (r = 0.54). Based on MBP staining, the MWF values exhibited strong positive correlations with myelin content on both 3 T (r = 0.68 and r = 0.78 for the two tissue blocks) and 7 T (r = 0.64 and r = 0.82 for the two tissue blocks). CONCLUSION: The findings demonstrated that the mGRE-based MWF mapping can be used to quantify myelin content in the human brain, despite the field-strength dependency of the measurements.

Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations.

Post-mortem studies have shown that patients dying from severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. We therefore used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. We used 7 T QSM data from 30 patients, scanned 93-548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients' QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. This study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.

T1234: A distortion-matched structural scan solution to misregistration of high resolution fMRI data.

Purpose: High-resolution fMRI at 7T is challenged by suboptimal alignment quality between functional data and structural scans. This study aims to develop a rapid acquisition method that provides distortion-matched, artifact-mitigated structural reference data. Methods: We introduce an efficient sequence protocol termed T1234, which offers adjustable distortions. This approach involves a T1-weighted 2-inversion 3D-EPI sequence with four spatial encoding directions optimized for high-resolution fMRI. A forward Bloch model was used for T1 quantification and protocol optimization. Twenty participants were scanned at 7T using both structural and functional protocols to evaluate the utility of T1234. Results: Results from two protocols are presented. A fast distortion-free protocol reliably produced whole-brain segmentations at 0.8mm isotropic resolution within 3:00-3:40 minutes. It demonstrates robustness across sessions, participants, and three different 7T SIEMENS scanners. For a protocol with geometric distortions that matched functional data, T1234 facilitates layer-specific fMRI signal analysis with enhanced laminar precision. Conclusion: This structural mapping approach enables precise registration with fMRI data. T1234 has been successfully implemented, validated, and tested, and is now available to users at our center and at over 50 centers worldwide.

Phenotyping in vivo chronic inflammation in multiple sclerosis by combined 11C-PBR28 MR-PET and 7T susceptibility-weighted imaging.

BACKGROUND: 11C-PBR28 positron emission tomography (PET), targeting the translocator protein, and paramagnetic rim lesions (PRL) have emerged as promising imaging markers of MS chronic inflammation. No consensus on which is the optimal marker exists. OBJECTIVES: To investigate the ability of 11C-PBR28 PET and PRL assessment to identify chronic inflammation in white matter (WM) MS lesions and their relation to neurological impairment. METHODS: Based on 11C-PBR28 uptake, brain WM lesions from 30 MS patients were classified as PET active or inactive. The PRL presence was assessed on 7T phase reconstructions, T1/T2 ratio was calculated to measure WM microstructural integrity. RESULTS: Less than half (44%) of non-PRL WM lesions were active on 11C-PBR28 imaging either throughout the lesion (whole active) or at its periphery. PET peripherally active lesions and PRL did not differ in T1/T2 ratio and 11C-PBR28 uptake. A positive correlation was observed between PRL and active PET lesion count. Whole active PET lesion volume was the strongest predictor (ß = 0.97, p < 0.001) of increased Expanded Disability Status Scale scores. CONCLUSION: 11C-PBR28 imaging reveals more active WM lesions than 7T PRL assessment. Although PRL and PET active lesion counts are related, neurological disability is better explained by PET whole active lesion volume.

Novel Bioreactor Design for Non-invasive Longitudinal Monitoring of Tissue-Engineered Heart Valves in 7T MRI and Ultrasound.

The development of cardiovascular implants is abundant, yet their clinical adoption remains a significant challenge in the treatment of valvular diseases. Tissue-engineered heart valves (TEHV) have emerged as a promising solution due to their remodeling capabilities, which have been extensively studied in recent years. However, ensuring reproducible production and clinical translation of TEHV requires robust longitudinal monitoring methods.Cardiovascular magnetic resonance imaging (MRI) is a non-invasive, radiation-free technique providing detailed valvular imaging and functional assessment. To facilitate this, we designed a state-of-the-art metal-free bioreactor enabling dynamic MRI and ultrasound imaging. Our compact bioreactor, tailored to fit a 72 mm bore 7 T MRI coil, features an integrated backflow design ensuring MRI compatibility. A pneumatic drive system operates the bioreactor, minimizing potential MRI interference. The bioreactor was digitally designed and constructed using polymethyl methacrylate, utilizing only polyether ether ketone screws for secure fastening. Our biohybrid TEHV incorporates a non-degradable polyethylene terephthalate textile scaffold with fibrin matrix hydrogel and human arterial smooth muscle cells.As a result, the bioreactor was successfully proven to be MRI compatible, with no blooming artifacts detected. The dynamic movement of the TEHVs was observed using gated MRI motion artifact compensation and ultrasound imaging techniques. In addition, the conditioning of TEHVs in the bioreactor enhanced ECM production. Immunohistology demonstrated abundant collagen, α-smooth muscle actin, and a monolayer of endothelial cells throughout the valve cusp. Our innovative methodology provides a physiologically relevant environment for TEHV conditioning and development, enabling accurate monitoring and assessment of functionality, thus accelerating clinical acceptance.

Prospective 3D Fat Navigator (FatNav) motion correction for 7T Terra MRI.

Ultra-high field (7T) MRI allows scans at sub-millimetre resolution with exquisite signal-to-noise ratio (SNR). As 7T MRI becomes more widely used clinically, the challenge of patient motion must be overcome. Retrospective motion correction is used successfully for some protocols, but for acquisitions such as slice-by-slice scans only prospective motion correction can deliver the full potential of 7T MRI. We report the first implementation of prospective 3D Fat Navigator ("FatNav") motion correction for the Siemens 7T Terra MRI. We implemented a modular Sequence Building Block for FatNav and embedded it into the vendor's gradient-recalled echo (GRE) sequence. We modified the reconstruction pipeline to reconstruct FatNav images online, coregistering them and sending motion updates to the host sequence online. We tested five registration algorithms for performance and accuracy on synthetic FatNav data. We implemented the best three of these in our sequence and tested them online. We acquired T1 and T2* weighted brain images of healthy volunteers correcting every other image for motion to visualise the effectiveness of online motion correction. Data were acquired with and without head immobilisation. We also tested performance while correcting every measurement for motion. Our implementation uses a 1.23 s 3D FatNav acquisition module and delivers motion updates in less than 3 s, which is sufficient for motion updates every few k-space lines in typical scans. Corrected images are crisper with fewer visible motion artefacts. This improved sharpness is reflected quantitatively by an increase in the variance of the image Laplacian which is 1.59 x better for corrected vs uncorrected images. Profiles across the cerebral falx are 33% steeper for corrected vs uncorrected images. Prospective FatNav improves GRE image quality in the brain. Our modular Sequence Building Block provides a simple method to integrate motion correction in 7T MRI pulse sequences.

Regional response to light illuminance across the human hypothalamus.

Light exerts multiple non-image-forming biological effects on physiology including the stimulation of alertness and cognition. However, the subcortical circuitry underlying the stimulating impact of light is not established in humans. We used 7 Tesla functional magnetic resonance imaging to assess the impact of variations in light illuminance on the regional activity of the hypothalamus while healthy young adults (N=26; 16 women; 24.3±2.9 y) were completing two auditory cognitive tasks. We find that, during both the executive and emotional tasks, higher illuminance triggered an activity increase over the posterior part of the hypothalamus, which includes part of the tuberomamillary nucleus and the posterior part of the lateral hypothalamus. In contrast, increasing illuminance evoked a decrease in activity over the anterior and ventral parts of the hypothalamus, encompassing notably the suprachiasmatic nucleus and another part of the tuberomammillary nucleus. Critically, the performance of the executive task was improved under higher illuminance and was negatively correlated with the activity of the posterior hypothalamus area. These findings reveal the distinct local dynamics of different hypothalamus regions that underlie the impact of light on cognition.

Resting-state functional connectivity abnormalities in subjective cognitive decline: A 7T MRI study.

Resting-state functional connectivity (FC) MRI is sensitive to brain changes in Alzheimer's disease in preclinical stages, however studies in persons with subjective cognitive decline (SCD) have reported conflicting findings, and no study is available at 7T MRI. In this study, we investigated FC alterations in sixty-six participants recruited at the Geneva Memory Center (24 controls, 14 SCD, 28 cognitively impaired [CI]). Participants were classified as SCD if they reported cognitive complaints without objective cognitive deficits, and underwent 7T fMRI to assess FC in canonical brain networks and their association with cognitive/clinical features. SCD showed normal cognition, a trend for higher depressive symptoms, and normal AD biomarkers. Compared to the other two groups, SCD showed higher FC in frontal default mode network (DMN) and insular and superior temporal nodes of ventral attention network (VAN). Higher FC in the DMN and VAN was associated with worse cognition but not depression, suggesting that hyper-connectivity in these networks may be a signature of age-related cognitive decline in SCD at low risk of developing AD.

Fuzzy ripple artifact in high resolution fMRI: identification, cause, and mitigation.

Purpose: High resolution fMRI is a rapidly growing research field focused on capturing functional signal changes across cortical layers. However, the data acquisition is limited by low spatial frequency EPI artifacts; termed here as Fuzzy Ripples. These artifacts limit the practical applicability of acquisition protocols with higher spatial resolution, faster acquisition speed, and they challenge imaging in lower brain areas. Methods: We characterize Fuzzy Ripple artifacts across commonly used sequences and distinguish them from conventional EPI Nyquist ghosts, off-resonance effects, and GRAPPA artifacts. To investigate their origin, we employ dual polarity readouts. Results: Our findings indicate that Fuzzy Ripples are primarily caused by readout-specific imperfections in k-space trajectories, which can be exacerbated by inductive coupling between third-order shims and readout gradients. We also find that these artifacts can be mitigated through complex-valued averaging of dual polarity EPI or by disconnecting the third-order shim coils. Conclusion: The proposed mitigation strategies allow overcoming current limitations in layer-fMRI protocols: (1)Achieving resolutions beyond 0.8mm is feasible, and even at 3T, we achieved 0.53mm voxel functional connectivity mapping.(2)Sub-millimeter sampling acceleration can be increased to allow sub-second TRs and laminar whole brain protocols with up to GRAPPA 8.(3)Sub-millimeter fMRI is achievable in lower brain areas, including the cerebellum.

The role of 7 T MRI to assess atrophy of the subcortical deep gray matter in relapsing-remitting multiple sclerosis.

BACKGROUND: Deep gray matter (DGM) atrophy and lesions are found in multiple sclerosis (MS). OBJECTIVE: To optimize automated segmentation for 7 T DGM volumetrics and assess sensitivity to atrophy and relationship to DGM lesions and disability in relapsing-remitting (RR) MS. METHODS: 30 RRMS subjects [mean age 44.0 years, median Expanded Disability Status Scale (EDSS) score 2] and 14 healthy controls underwent 7 T MRI with 3D magnetization-prepared 2 rapid gradient-echoes (MP2RAGE) and fluid-attenuated inversion recovery. Customizing an automated pipeline to assess DGM structure volumes required pre-processing combining two MP2RAGE inversion times and uniform T1 images, and noise-suppressed reconstruction. DGM volumes were normalized. Brain DGM lesions and white matter T2 lesion volume (T2LV) were expert-quantified. Spearman correlations and Wilcoxon rank-sum tests were assessed. RESULTS: DGM lesions were found in 77% (n = 23) of MS subjects and no controls, with thalamic lesions most prevalent (73%). An average of 3.6 DGM lesions was found per person with MS. Total DGM volumes were lower in MS vs. controls (p = 0.034), varying by region, most pronounced in the caudate (p = 0.008). DGM volumes inversely correlated with EDSS (total DGM: r = - 0.45, p = 0.014; globus pallidus: r =  - 0.42, p = 0.023; putamen: r = - 0.44, p = 0.016; caudate: r = - 0.37, p = 0.047) and T2LV (total DGM: r = - 0.53, p = 0.003; putamen: r = - 0.40, p = 0.030; thalamus: r = - 0.63, p < 0.001). DGM atrophy was most closely linked to disability among all MRI measures. Thalamic lesion volume correlated inversely with thalamic volume (r = - 0.38, p = 0.045). CONCLUSION: 7 T MRI shows a link between DGM atrophy and both white matter lesions and physical disability in RRMS. Thalamic lesions are associated with thalamic atrophy.

Reduced physiology-induced temporal instability achieved with variable-flip-angle fast low-angle excitation echo-planar technique with multishot echo planar time-resolved imaging.

PURPOSE: Echo planar time-resolved imaging (EPTI) is a new imaging approach that addresses the limitations of EPI by providing high-resolution, distortion- and T2/ T 2 * $$ {\mathrm{T}}_2^{\ast } $$  blurring-free imaging for functional MRI (fMRI). However, as in all multishot sequences, intershot phase variations induced by physiological processes can introduce temporal instabilities to the reconstructed time-series data. This study aims to reduce these instabilities in multishot EPTI. THEORY AND METHODS: In conventional multishot EPTI, the time intervals between the shots comprising each slice can introduce intershot phase variations. Here, the fast low-angle excitation echo-planar technique (FLEET), in which all shots of each slice are acquired consecutively with minimal time delays, was combined with a variable flip angle (VFA) technique to improve intershot consistency and maximize signal. A recursive Shinnar-Le Roux RF pulse design algorithm was used to generate pulses for different shots to produce consistent slice profiles and signal intensities across shots. Blipped controlled aliasing in parallel imaging simultaneous multislice was also combined with the proposed VFA-FLEET EPTI to improve temporal resolution and increase spatial coverage. RESULTS: The temporal stability of VFA-FLEET EPTI was compared with conventional EPTI at 7 T. The results demonstrated that VFA-FLEET can provide spatial-specific increase of temporal stability. We performed high-resolution task-fMRI experiments at 7 T using VFA-FLEET EPTI, and reliable BOLD responses to a visual stimulus were detected. CONCLUSION: The intershot phase variations induced by physiological processes in multishot EPTI can manifest as specific spatial patterns of physiological noise enhancement and lead to reduced temporal stability. The VFA-FLEET technique can substantially reduce these physiology-induced instabilities in multishot EPTI acquisitions. The proposed method provides sufficient stability and sensitivity for high-resolution fMRI studies.

Prefrontal Metabolite Alterations in Individuals with Posttraumatic Stress Disorder: A 7T Magnetic Resonance Spectroscopy Study.

Background: Evidence from animal and human studies suggests glutamatergic dysfunction in posttraumatic stress disorder (PTSD). The purpose of this study was to investigate glutamate abnormalities in the dorsolateral prefrontal cortex (DLFPC) of individuals with PTSD using 7T MRS, which has better spectral resolution and signal-to-noise ratio than lower field strengths, thus allowing for better spectral quality and higher sensitivity. We hypothesized that individuals with PTSD would have lower glutamate levels compared to trauma-exposed individuals without PTSD and individuals without trauma exposure. Additionally, we explored potential alterations in other neurometabolites and the relationship between glutamate and psychiatric symptoms. Methods: Individuals with PTSD (n = 27), trauma-exposed individuals without PTSD (n = 27), and individuals without trauma exposure (n = 26) underwent 7T MRS to measure glutamate and other neurometabolites in the left DLPFC. The severities of PTSD, depression, anxiety, and dissociation symptoms were assessed. Results: We found that glutamate was lower in the PTSD and trauma-exposed groups compared to the group without trauma exposure. Furthermore, N-acetylaspartate (NAA) was lower and lactate was higher in the PTSD group compared to the group without trauma exposure. Glutamate was negatively correlated with depression symptom severity in the PTSD group. Glutamate was not correlated with PTSD symptom severity. Conclusion: In this first 7T MRS study of PTSD, we observed altered concentrations of glutamate, NAA, and lactate. Our findings provide evidence for multiple possible pathological processes in individuals with PTSD. High-field MRS offers insight into the neurometabolic alterations associated with PTSD and is a powerful tool to probe trauma- and stress-related neurotransmission and metabolism in vivo.

Automated deep learning segmentation of high-resolution 7 Tesla postmortem MRI for quantitative analysis of structure-pathology correlations in neurodegenerative diseases.

Postmortem MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high-resolution dataset of 135 postmortem human brain tissue specimens imaged at 0.3 mm3 isotropic using a T2w sequence on a 7T whole-body MRI scanner. We developed a deep learning pipeline to segment the cortical mantle by benchmarking the performance of nine deep neural architectures, followed by post-hoc topological correction. We evaluate the reliability of this pipeline via overlap metrics with manual segmentation in 6 specimens, and intra-class correlation between cortical thickness measures extracted from the automatic segmentation and expert-generated reference measures in 36 specimens. We also segment four subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities, and the normal appearing white matter, providing a limited evaluation of accuracy. We show generalizing capabilities across whole-brain hemispheres in different specimens, and also on unseen images acquired at 0.28 mm3 and 0.16 mm3 isotropic T2*w fast low angle shot (FLASH) sequence at 7T. We report associations between localized cortical thickness and volumetric measurements across key regions, and semi-quantitative neuropathological ratings in a subset of 82 individuals with Alzheimer's disease (AD) continuum diagnoses. Our code, Jupyter notebooks, and the containerized executables are publicly available at the project webpage (https://pulkit-khandelwal.github.io/exvivo-brain-upenn/).

Morphology of the popliteomeniscal fascicles around the popliteal hiatus on three-dimensional images reconstructed from 7 T magnetic resonance imaging: A cadaveric study.

BACKGROUND: This study aimed to clarify the characteristic features of the anteroinferior and posterosuperior popliteomeniscal fascicles (aiPMF and psPMF, respectively) and popliteal hiatus using three-dimensional (3D) reconstructions of 7 T magnetic resonance imaging (MRI) arthrography. METHODS: Six knees from human cadavers fixed using the Thiel embalming method were examined using 7 T MRI arthrography. 3D Images of the structures around the popliteal hiatus were reconstructed. Morphologies of the psPMF, aiPMF, and popliteal hiatus were investigated and their positional relationships analyzed. RESULTS: The PMFs attached to the periphery of the lateral meniscus (LM) to form the popliteal hiatus. Each coursed in an oblique direction. The mean length of the psPMF and aiPMF attachments to the LM were 6.8 and 21.6 mm, respectively; mean popliteal hiatus length was 12.8 mm. These lengths corresponded to 7.5%, 24.3%, and 14.5% of the total length of the LM, respectively. The aiPMF was thick near the lateral aspect of the articular capsule and became thinner towards the posteromedial aspect of the LM. The psPMF was thick near the posterior aspect of the articular capsule and became thinner towards the posterolateral aspect of the LM. CONCLUSION: Morphological properties of the aiPMF, psPMF, their attachments to the LM, and the popliteal hiatus were consistent across the cadaver specimens examined. Each PMF was thin near the popliteal hiatus and became thicker towards its attachment to the articular capsule. These findings may be useful for anatomical repair for the LM hypermobility.

Examination of methods to separate overlapping metabolites at 7T.

PURPOSE: Neurochemicals of interest quantified by MRS are often composites of overlapping signals. At higher field strengths (i.e., 7T), there is better separation of these signals. As the availability of higher field strengths is increasing, it is important to re-evaluate the separability of overlapping metabolite signals. METHODS: This study compares the ability of stimulated echo acquisition mode (STEAM-8; TE = 8 ms), short-TE semi-LASER (sLASER-34; TE = 34 ms), and long-TE semi-LASER (sLASER-105; TE = 105 ms) acquisitions to separate the commonly acquired neurochemicals at 7T (Glx, consisting of glutamate and glutamine; total N-acetyl aspartate, consisting of N-acetyl aspartate and N-acetylaspartylglutamate; total creatine, consisting of creatine and phosphocreatine; and total choline, consisting of choline, phosphocholine, and glycerophosphocholine). RESULTS: sLASER-34 produced the lowest fit errors for most neurochemicals; however, STEAM-8 had better within-subject reproducibility and required fewer subjects to detect a change between groups. However, this is dependent on the neurochemical of interest. CONCLUSION: We recommend short-TE STEAM for separation of most standard neurochemicals at 7T over short-TE or long-TE sLASER.

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.

Glutamate dynamics and BOLD response during OCD symptom provocation in the lateral occipital cortex: A 7 Tesla fMRI-fMRS study.

Obsessive-compulsive disorder (OCD) is linked with dysfunction in frontal-striatal, fronto-limbic, and visual brain regions. Research using proton magnetic resonance spectroscopy (1H-MRS) suggests that altered neurometabolite levels, like glutamate, may contribute to this dysfunction. However, static neurometabolite levels in OCD patients have shown inconsistent results, likely due to previous studies' limited focus on neurometabolite dynamics. We employ functional MRS (fMRS) and functional magnetic resonance imaging (fMRI) to explore these dynamics and brain activation during OCD symptom provocation. We utilized a combined 7-tesla fMRI-fMRS setup to examine task-related BOLD response and glutamate changes in the lateral occipital cortex (LOC) of 30 OCD participants and 34 matched controls during an OCD-specific symptom provocation task. The study examined main effects and between-group differences in brain activation and glutamate levels during the task. A whole sample task-effects analysis on data meeting predefined quality criteria showed significant glutamate increases (n = 41 (22 OCD, 19 controls), mean change: 3.2 %, z = 3.75, p < .001) and task activation (n = 54 (26 OCD, 28 controls), p < .001) in the LOC during OCD blocks compared to neutral blocks. However, no differences in task-induced glutamate dynamics or activation between groups were found, nor a correlation between glutamate levels and task activation. We were able to measure task-induced increases in glutamate and BOLD levels, emphasizing its feasibility for OCD research. The absence of group differences highlights the need for further exploration to discern to what extent neurometabolite dynamics differ between OCD patients and controls. Once established, future studies can use pre-post intervention fMRS-fMRI to probe the effects of therapies modulating glutamate pathways in OCD.

RF shimming in the cervical spinal cord at 7 T.

PURPOSE: Advancing the development of 7 T MRI for spinal cord imaging is crucial for the enhanced diagnosis and monitoring of various neurodegenerative diseases and traumas. However, a significant challenge at this field strength is the transmit field inhomogeneity. Such inhomogeneity is particularly problematic for imaging the small, deep anatomical structures of the cervical spinal cord, as it can cause uneven signal intensity and elevate the local specific absorption ratio, compromising image quality. This multisite study explores several RF shimming techniques in the cervical spinal cord. METHODS: Data were collected from 5 participants between two 7 T sites with a custom 8Tx/20Rx parallel transmission coil. We explored two radiofrequency (RF) shimming approaches from an MRI vendor and four from an open-source toolbox, showcasing their ability to enhance transmit field and signal homogeneity along the cervical spinal cord. RESULTS: The circularly polarized (CP), coefficient of variation (CoV), and specific absorption rate (SAR) efficiency shim modes showed the highest B1 + efficiency, and the vendor-based "patient" and "volume" modes showed the lowest B1 + efficiency. The coefficient of variation method produced the highest CSF/spinal cord contrast on T2*-weighted scans (ratio of 1.27 ± 0.03), and the lowest variation of that contrast along the superior-inferior axis. CONCLUSION: The study's findings highlight the potential of RF shimming to advance 7 T MRI's clinical utility for central nervous system imaging by enabling more homogenous and efficient spinal cord imaging. Additionally, the research incorporates a reproducible Jupyter Notebook, enhancing the study's transparency and facilitating peer verification.