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• Artificial magnetic shield for clinical MRI of a human head at 7 T • Extended birdcage coil for human head MRI • Enhanced transmit efficiency of the extended birdcage coil In magnetic resonance imaging, a birdcage coil is the most commonly used volumetric resonator creating a highly homogeneous radiofrequency magnetic field in a conductive sample. An artificial magnetic radiofrequency shield was recently shown to improve the magnetic field amplitude per unit power (transmit efficiency) of a preclinical birdcage coil by reducing the intrinsic losses in the coil and increasing power absorbed by the sample. In this paper, we propose a new application of an artificial shield in clinical MRI. Thanks to the proposed artificial shield a birdcage coil for human brain imaging operating at 300 MHz (Larmor frequency of protons at static fields of 7 T) can be expanded to increase free space. As a result, the coil becomes more comfortable for the patient and keeping comparable transmit efficiency. The same extended coil with a conventional copper shield would have at least 10% lower efficiency. The proposed artificial shield is implemented as an annular-ring cavity-backed slot in a copper cylinder that tightly surrounds the birdcage. To demonstrate the effect, radiofrequency magnetic field and specific absorption rate distributions were compared numerically and experimentally for the initial and extended coils with different shields. [ABSTRACT FROM AUTHOR]

High sensitivity at ultra-high field (UHF) and sufficient potential to penetrate the brain are the most desirable characteristics in the development of contrast agents (CAs) for magnetic resonance imaging (MRI). However, incorporating such qualities into a single nanocarrier is challenging. Herein, we report a new strategy for a highly brain-permeable MR CA with high sensitivity at UHF by loading dysprosium chelates (DyL) in apoferritin cavities (Apo-DyL). We also design the chelate ligand structure to increase DyL loading capacity within the apoferritin cavity. Using the intracerebroventricular (ICV) injection approach as a new delivery route for Apo-DyL, we demonstrate that apoferritin loaded with DyL can penetrate the brain–ventricular barrier and diffuse into the brain. This brain-permeable capability is unique to Apo-DyL, compared with other types of nanoparticles used in MRI. Apo-DyL also shows significant increase in MR sensitivity of DyL at UHF. Furthermore, based on brain tumor imaging at UHF, Apo-DyL can significantly enhance the tumor for a lower dose of the CA than the previously reported Gd- or Mn-loaded apoferritin nanoplatform. Therefore, Apo-DyL can be a novel nanoplatform that is a highly sensitive and versatile MR CA for UHF brain imaging. [ABSTRACT FROM AUTHOR]

• A parametric quantitative study of dipole 7 Tesla array coil was performed. • The transmit, SAR efficiency and mutual coupling due to coil structure were studied. • The study was performed on a homogeneous phantom as well as on a human body model. • SAR efficiency depends on whether the study being done on a phantom or a human model. In this contribution we present numerical and experimental results of a parametric quantitative study of radiative dipole antennas in a phased array configuration for efficient body magnetic resonance imaging at 7 T via parallel transmission. For magnetic resonance imaging (MRI) at ultrahigh fields (7 T and higher) dipole antennas are commonly used in phased arrays, particularly for body imaging targets. This study reveals the effects of dipole positioning in the array (elevation of dipoles above the subject and inter-dipole spacing) on their mutual coupling, B 1 + per P acc and B 1 + per maximum local SAR efficiencies as well as the RF-shimming capability. The numerical and experimental results are obtained and compared for a homogeneous phantom as well as for a real human models confirmed by in vivo experiments. [ABSTRACT FROM AUTHOR]

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for Parkinson's disease motor symptoms. The ideal site for implantation within STN, however, remains controversial. While many argue that placement of a DBS lead within the sensorimotor territory of the STN yields better motor outcomes, others report similar effects with leads placed in the associative or motor territory of the STN, while still others assert that placing a DBS lead "anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) produces similar clinical efficacy." These discrepancies likely result from methodological differences including targeting preferences, imaging acquisition and the use of brain atlases that do not account for patient-specific anatomic variability. We present a first-in-kind within-patient demonstration of severe mood side effects and minimal motor improvement in a Parkinson's disease patient following placement of a DBS lead in the limbic/associative territory of the STN who experienced marked improvement in motor benefit and resolution of mood side effects following repositioning the lead within the STN sensorimotor territory. 7 Tesla (7 T) magnetic resonance imaging (MRI) data were used to generate a patient-specific anatomical model of the STN with parcellation into distinct functional territories and computational modeling to assess the relative degree of activation of motor, associative and limbic territories., Competing Interests: LES has served as a consultant for Medtronic and Boston Scientific. RP is a consultant for Surgical Information Sciences, Inc. NH is a co-founder and shareholder in Surgical Information Sciences, Inc. JLV serves as a consultant for Medtronic, Boston Scientific, and Abbott, and serves on the scientific advisory board for Surgical Information Sciences, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schrock, Patriat, Goftari, Kim, Johnson, Harel and Vitek.)

Introduction: Multi-component T 2 mapping using a gradient- and spin-echo (GraSE) acquisition has become standard for myelin water imaging at 3 T. Higher magnetic field strengths promise signal-to-noise ratio benefits but face specific absorption rate limits and shortened T 2 times. This study investigates compartmental T 2 times in vivo and addresses advantages and challenges of multi-component T 2 mapping at 7 T., Methods: We acquired 3D multi-echo GraSE data in seven healthy adults at 7 T, with three subjects also scanned at 3 T. Stimulated echoes arising from B 1 + inhomogeneities were accounted for by the extended phase graph (EPG) algorithm. We used the computed T 2 distributions to determine T 2 times that identify different water pools and assessed signal-to-noise and fit-to-noise characteristics of the signal estimation. We compared short T 2 fractions and T 2 properties of the intermediate water pool at 3 T and 7 T., Results: Flip angle mapping confirmed that EPG accurately determined the larger B 1 + inhomogeneity at 7 T. Multi-component T 2 analysis demonstrated shortened T 2 times at 7 T compared with 3 T. Fit-to-noise and signal-to-noise ratios were improved at 7 T but depended on B 1 + homogeneity. Adjusting the shortest T 2 to 8 ms and the T 2 threshold that separates different water compartments to 20 ms yielded short T 2 fractions at 7 T that conformed to 3 T data. Short T 2 fractions in myelin-rich white matter regions were lower at 7 T than at 3 T, and higher in iron-rich structures., Discussion: Adjusting the T 2 compartment boundaries was required due to the shorter T 2 relaxation times at 7 T. Shorter echo spacing would better sample the fast decaying signal but would increase peripheral nerve stimulation. Multi-channel transmission will improve T 2 measurements at 7 T., Conclusion: We used a multi-echo 3D GraSE sequence to characterize the multi-exponential T 2 decay at 7 T. We adapted T 2 parameters for evaluation of the short T 2 fraction. Obtained 7 T multi-component T 2 maps were in good agreement with 3 T data., (© 2020 John Wiley & Sons, Ltd.)

Purpose: Moving to ultra-high fields (≥7 T), the inhomogeneity of both RF (B 1 ) and static (B 0 ) magnetic fields increases, which further motivates us to design a realistic head-shaped phantom, especially for spectroscopic imaging. Such phantoms provide images similar to the human brain and serve as a reliable tool for developing and examining methods in MRI. This study aims to develop and characterize a realistic head-shaped phantom filled with brain-mimicking metabolites for MRS and magnetic resonance spectroscopic imaging in a 7 T MRI scanner., Methods: A 3D head-shaped container with three sections-mimicking brain, muscle and precranial lipid-was constructed. The phantom was designed to provide robustness to heating, mechanical damage and leakage, with easy refilling. The head's shape and the agarose mixture were optimized to provide B 0 and B 1 distributions and T 1 /T 2 relaxation values similar to those of human brain. Eight brain-tissue-mimicking metabolites were included for spectroscopy. The phantom was evaluated for localized spectroscopy, fast spectroscopic imaging and fat suppression., Results: The B 0 and B 1 maps showed distribution similar to that of human brain, with increased B 0 inhomogeneity near the nasal and ear areas and reduced B 1 in the temporal lobe and brain stem regions, as expected in vivo. The metabolites' concentrations were verified by single-voxel spectroscopy, showing an average deviation of 11%. Fast spectroscopic imaging and imaging with fat suppression were demonstrated., Conclusion: A 3D head-shaped phantom for human brain imaging and spectroscopic imaging in 7 T MRI was demonstrated, making it a realistic phantom for methodology development at 7 T., (© 2020 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Background: Cortical lesions are abundant in multiple sclerosis (MS), yet difficult to visualize in vivo. Ultra-high field (UHF) MRI at 7 T and above provides technological advances suited to optimize the detection of cortical lesions in MS., Purpose: To provide a narrative and quantitative systematic review of the literature on UHF MRI of cortical lesions in MS., Methods: A systematic search of all literature on UHF MRI of cortical lesions in MS published before September 2020. Quantitative outcome measures included cortical lesion numbers reported using 3 T and 7 T MRI and between 7 T MRI sequences, along with sensitivity of UHF MRI towards cortical lesions verified by histopathology., Results: 7 T MRI detected on average 52 ± 26% (mean ± 95% confidence interval) more cortical lesions than the best performing image contrast at 3 T, with the largest increase in type II-IV intracortical lesion detection. Across all studies, the mean cortical lesion number was 17 ± 6 per patient. In progressive MS cohorts, approximately four times more cortical lesions were reported than in CIS/early RRMS, and RRMS. Yet, there was no difference in lesion type ratio between these MS subtypes. Furthermore, superiority of one MRI sequence over another could not be established from available data. Post-mortem lesion detection with UHF MRI agreed only modestly with pathological examinations. Mean pro- and retrospective sensitivity was 33 ± 6% and 71 ± 10%, respectively, with the highest sensitivity towards type I and type IV lesions., Conclusion: UHF MRI improves cortical lesion detection in MS considerably compared to 3 T MRI, particularly for type II-IV lesions. Despite modest sensitivity, 7 T MRI is still capable of visualizing all aspects of cortical lesion pathology and could potentially aid clinicians in diagnosing and monitoring MS, and progressive MS in particular. However, standardization of acquisition and segmentation protocols is needed., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Ultra-high field magnetic resonance imaging (MR) may be used to improve intracranial blood flow measurements. However, standard cardiac synchronization methods tend to fail at ultra-high field MR. Therefore, this study aims to investigate an alternative synchronization technique using Doppler ultrasound., Methods: Healthy subjects (n = 9) were examined with 7T MR. Flow was measured in the M1-branch of the middle cerebral artery (MCA) and in the cerebral aqueduct (CA) using through-plane phase contrast (2D flow). Flow in the circle of Willis was measured with three-dimensional, three-directional phase contrast (4D flow). Scans were gated with Doppler ultrasound (DUS) and electrocardiogram (ECG), and pulse oximetry data (POX) was collected simultaneously. False negative and false positive trigger events were counted for ECG, DUS and POX, and quantitative flow measures were compared., Results: There were fewer false positive triggers for DUS compared to ECG (5.3 ± 11 vs. 25 ± 31, p = 0.031), while no other measured parameters differed significantly. Net blood flow in M1 was similar between DUS and ECG for 2D flow (1.5 ± 0.39 vs. 1.6 ± 0.41, bias ± 1.96SD: - 0.021 ± 0.36) and 4D flow (1.8 ± 0.48 vs. 9 ± 0.59, bias ± 1.96SD: - 0.086 ± 0.57 ml). Net CSF flow per heart beat in the CA was also similar for DUS and ECG (3.6 ± 2.1 vs. 3.0 ± 5.8, bias ± 1.96SD: 0.61 ± 13.6 μl)., Conclusion: Gating with DUS produced fewer false trigger events than using ECG, with similar quantitative flow values. DUS gating is a promising technique for cardiac synchronization at 7T.

Purpose: This study investigates the implications of all degrees of freedom of within-scan patient head motion on patient safety., Methods: Electromagnetic simulations were performed by displacing and/or rotating a virtual body model inside an 8-channel transmit array to simulate 6 degrees of freedom of motion. Rotations of up to 20° and displacements of up to 20 mm including off-axis axial/coronal translations were investigated, yielding 104 head positions. Quadrature excitation, RF shimming, and multi-spoke parallel-transmit excitation pulses were designed for axial slice-selection at 7T, for seven slices across the head. Variation of whole-head specific absorption rate (SAR) and 10-g averaged local SAR of the designed pulses, as well as the change in the maximum eigenvalue (worst-case pulse) were investigated by comparing off-center positions to the central position., Results: In their respective worst-cases, patient motion increased the eigenvalue-based local SAR by 42%, whole-head SAR by 60%, and the 10-g averaged local SAR by 210%. Local SAR was observed to be more sensitive to displacements along right-left and anterior-posterior directions than displacement in the superior-inferior direction and rotation., Conclusion: This is the first study to investigate the effect of all 6 degrees of freedom of motion on safety of practical pulses. Although the results agree with the literature for overlapping cases, the results demonstrate higher increases (up to 3.1-fold) in local SAR for off-axis displacement in the axial plane, which had received less attention in the literature. This increase in local SAR could potentially affect the local SAR compliance of subjects, unless realistic within-scan patient motion is taken into account during pulse design., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background and Purpose: Aneurysm size and neck measurements are important for treatment decisions. The introduction of 7T magnetic resonance angiography (MRA) led to new possibilities assessing aneurysm morphology and flow due to the higher signal-to-noise ratio. However, it is unknown if the size measurements on 7T MRA are similar to those on the standard 3T MRA. This study aimed to compare aneurysm size measurements between 7T and 3T MRA., Methods: We included 18 patients with 22 aneurysms who underwent both 3T and 7T MRA. Three acquisition protocols were compared: 3T time of flight (TOF), 7T TOF, and 7T contrast-enhanced MRA. Each aneurysm on each protocol was measured by at least two experienced neuroradiologists. Subsequently, the differences were evaluated using scatterplots and the intraclass correlation coefficients (ICC) of agreement., Results: There was a good agreement among the neuroradiologists for the height and width measurements (mean ICC: .78-.93); the neck measurements showed a moderate agreement with a mean ICC of .57-.72. Between the MR acquisition protocols, there was a high agreement for all measurements with a mean ICC of .81-.96. Measurement differences between acquisition protocols (0-2.9 mm) were in the range of the differences between the neuroradiologists (0-3.6 mm)., Conclusion: Our study showed that 7T MRA, both nonenhanced and contrast-enhanced, has a high agreement in aneurysm size measurements compared to 3T. This suggests that 7T is useful for reliable aneurysm size assessment., (© 2020 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Purpose: To perform a pilot study to quantitatively assess cognitive, vestibular, and physiological function during and after exposure to a magnetic resonance imaging (MRI) system with a static field strength of 10.5 Tesla at multiple time scales., Methods: A total of 29 subjects were exposed to a 10.5 T MRI field and underwent vestibular, cognitive, and physiological testing before, during, and after exposure; for 26 subjects, testing and exposure were repeated within 2-4 weeks of the first visit. Subjects also reported sensory perceptions after each exposure. Comparisons were made between short and long term time points in the study with respect to the parameters measured in the study; short term comparison included pre-vs-isocenter and pre-vs-post (1-24 h), while long term compared pre-exposures 2-4 weeks apart., Results: Of the 79 comparisons, 73 parameters were unchanged or had small improvements after magnet exposure. The exceptions to this included lower scores on short term (i.e. same day) executive function testing, greater isocenter spontaneous eye movement during visit 1 (relative to pre-exposure), increased number of abnormalities on videonystagmography visit 2 versus visit 1 and a mix of small increases (short term visit 2) and decreases (short term visit 1) in blood pressure. In addition, more subjects reported metallic taste at 10.5 T in comparison to similar data obtained in previous studies at 7 T and 9.4 T., Conclusion: Initial results of 10.5 T static field exposure indicate that 1) cognitive performance is not compromised at isocenter, 2) subjects experience increased eye movement at isocenter, and 3) subjects experience small changes in vital signs but no field-induced increase in blood pressure. While small but significant differences were found in some comparisons, none were identified as compromising subject safety. A modified testing protocol informed by these results was devised with the goal of permitting increased enrollment while providing continued monitoring to evaluate field effects., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To date, little is known about the presence and extent of cerebellar cortical pathology in early stages of MS., Objective: The aims of this study were to (i) investigate microstructural changes in the normal-appearing cerebellar cortex of early MS patients by using 7 T MRI and (ii) evaluate the influence of those changes on clinical performance., Methods: Eighteen RRMS patients and nine healthy controls underwent quantitative T 1 and T 2 * measurement at 7 T MRI using high-resolution MP2RAGE and multi-echo gradient-echo imaging. After subtracting lesion masks, average T 1 and T 2 * maps were computed for three layers in the cerebellar cortex and compared between groups using mixed effects models., Results: The volume of the cerebellar cortex and its layers did not differ between patients and controls. In MS patients, significantly longer T 1 values were observed in all vermis cortical layers and in the middle and external cortical layer of the cerebellar hemispheres. No between-group differences in T 2 * values were found. T 1 values correlated with EDSS, SDMT and PASAT., Conclusions: We found MRI evidence of damage in the normal-appearing cerebellar cortex at early MS stages and before volumetric changes. This microstructural alteration appears to be related to EDSS and cognitive performance., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Riccardo Galbusera reports no disclosures in relationship to this work Katrin Parmar reports no disclosures in relationship to this work Yohan Boillat reports no disclosures in relationship to this work Mario Joao Fartaria works for Siemens Switzerland Alexandra-Ramona Todea reports no disclosures in relationship to this work Kieran O’Brien works for Siemens Australia Anna Smolinski reports no disclosures in relationship to this work Ludwig Kappos reports no disclosures in relationship to this work Wietske van der Zwaag reports no disclosures in relationship to this work Cristina Granziera reports no disclosures in relationship to this work., (© The Author(s) 2020.)

Post mortem magnetic resonance imaging (MRI) studies on the human brain are of great interest for the validation of in vivo MRI. It facilitates a link between functional and anatomical information available from MRI in vivo and neuroanatomical knowledge available from histology/immunocytochemistry. However, linking in vivo and post mortem MRI to microscopy techniques poses substantial challenges. Fixation artifacts and tissue deformation of extracted brains, as well as co registration of 2D histology to 3D MRI volumes complicate direct comparison between modalities. Moreover, post mortem brain tissue does not have the same physical properties as in vivo tissue, and therefore MRI approaches need to be adjusted accordingly. Here, we present a pipeline in which whole-brain human post mortem in situ MRI is combined with subsequent tissue processing of the whole human brain, providing a 3-dimensional reconstruction via blockface imaging. To this end, we adapted tissue processing procedures to allow both post mortem MRI and subsequent histological and immunocytochemical processing. For MRI, tissue was packed in a susceptibility matched solution, tailored to fit the dimensions of the MRI coil. Additionally, MRI sequence parameters were adjusted to accommodate T1 and T2 ∗ shortening, and scan time was extended, thereby benefiting the signal-to-noise-ratio that can be achieved using extensive averaging without motion artifacts. After MRI, the brain was extracted from the skull and subsequently cut while performing optimized blockface imaging, thereby allowing three-dimensional reconstructions. Tissues were processed for Nissl and silver staining, and co-registered with the blockface images. The combination of these techniques allows direct comparisons across modalities., (Copyright © 2020 Alkemade, Pine, Kirilina, Keuken, Mulder, Balesar, Groot, Bleys, Trampel, Weiskopf, Herrler, Möller, Bazin and Forstmann.)

Background: The diagnosis of Parkinson's Disease (PD) remains a challenge and is currently based on the assessment of clinical symptoms. PD is also a heterogeneous disease with great variability in symptoms, disease course, and response to therapy. There is a general need for a better understanding of this heterogeneity and the interlinked long-term changes in brain function and structure in PD. Over the past years there is increasing interest in the value of new paradigms in Magnetic Resonance Imaging (MRI) and the potential of ultra-high field strength imaging in the diagnostic work-up of PD. With this multimodal 7 T MRI study, our objectives are: 1) To identify distinctive MRI characteristics in PD patients and to create a diagnostic tool based on these differences. 2) To correlate MRI characteristics to clinical phenotype, genetics and progression of symptoms. 3) To detect future imaging biomarkers for disease progression that could be valuable for the evaluation of new therapies., Methods: The TRACK-PD study is a longitudinal observational study in a cohort of 130 recently diagnosed (≤ 3 years after diagnosis) PD patients and 60 age-matched healthy controls (HC). A 7 T MRI of the brain will be performed at baseline and repeated after 2 and 4 years. Complete assessment of motor, cognitive, neuropsychiatric and autonomic symptoms will be performed at baseline and follow-up visits with wearable sensors, validated questionnaires and rating scales. At baseline a blood DNA sample will also be collected., Discussion: This is the first longitudinal, observational, 7 T MRI study in PD patients. With this study, an important contribution can be made to the improvement of the current diagnostic process in PD. Moreover, this study will be able to provide valuable information related to the different clinical phenotypes of PD and their correlating MRI characteristics. The long-term aim of this study is to better understand PD and develop new biomarkers for disease progression which may help new therapy development. Eventually, this may lead to predictive models for individual PD patients and towards personalized medicine in the future., Trial Registration: Dutch Trial Register, NL7558 . Registered March 11, 2019.

Purpose: To develop a robust design of a human head double-tuned 31 P/ 1 H array, which provides good performance at both 31 P and 1 H frequencies for MR spectroscopic imaging at 9.4T., Methods: Increasing the number of surface loops in a human head array improves the peripheral signal-to-noise ratio (SNR), while the central SNR doesn't substantially change. High peripheral SNR can contaminate MR spectroscopic imaging data at both 1 H and 31 P frequency. To minimize this effect, we limited the number of elements in the 31 P array to 10, i.e., 8 transceiver surface loops circumscribing the head and 2 receive "vertical" loops placed at the superior location. The 1 H-portion of the array also consists of 10 elements, i.e., 8 transceiver surface loops circumscribing the head and 2 transceiver "vertical" loops at the superior location of the head. Both the 31 P array and 1 H array are placed in a single layer at the same distance to the head, which provides high loading and, thus, a good performance for both arrays., Results: Transmit efficiency of the 1 H-portion of the double-tuned array was very similar to that of the single-tuned arrays of similar size. Also, addition of the cross-loops substantially improved the brain coverage., Conclusion: We developed a novel 31 P/ 1 H double-tuned array for MR spectroscopic imaging of a human brain at 9.4T. Placing both 31 P and 1 H loops in a single layer provides for high transmit efficiency at both frequencies without compromising SNR near the brain center at the 31 P-frequency. Addition of the cross-loops at the superior location improves the brain coverage., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Cushing's disease manifests as symptoms of glucocorticoid excess secondary to the increased secretion of corticotropin by a corticotroph adenoma in the pituitary gland. Unfortunately, magnetic resonance imaging (MRI) performed at conventional clinical field strengths of 1.5 or 3 Tesla has limited sensitivity for the detection of these pituitary tumors, and radiologic uncertainty often necessitates more invasive workup to confirm diagnosis and guide resection. It has been postulated that higher static magnetic field strengths may increase the adenoma detection rate and thus the utility of MRI for this clinical application. In this report, we describe our initial experience using ultra-high field 7 Tesla (7 T) MRI in patients with suspected Cushing's disease and negative or equivocal imaging at conventional field strengths. We performed contrast-enhanced 7 T pituitary MRI in 10 patients with up to three different T1-weighted sequences and correlated the imaging abnormalities identified with results of histologic evaluation in patients who subsequently underwent resection. We found that 7 T MRI enabled the identification of previously undetected areas of focal pituitary hypoenhancement in 9 patients (90%), of which 7 corresponded histologically to corticotroph adenomas. These early findings suggest an important adjunctive role for ultra-high field MR imaging in the noninvasive clinical workup of suspected Cushing's disease.

Objective: Cell structural changes are one of the main features observed during the development of amyotrophic lateral sclerosis (ALS). In this work, we propose the use of diffusion tensor imaging (DTI) metrics to assess specific ultrastructural changes in the central nervous system during the early neurodegenerative stages of ALS., Methods: Ultra-high field MRI and DTI data at 17.6T were obtained from fixed, excised mouse brains, and spinal cords from ALS (G93A-SOD1) mice., Results: Changes in fractional anisotropy (FA) and linear, planar, and spherical anisotropy ratios (C L , C P , and C S , respectively) of the diffusion eigenvalues were measured in white matter (WM) and gray matter (GM) areas associated with early axonal degenerative processes (in both the brain and the spinal cord). Specifically, in WM structures (corpus callosum, corticospinal tract, and spinal cord funiculi) as the disease progressed, FA, C L , and C P values decreased, whereas C S values increased. In GM structures (prefrontal cortex, hippocampus, and central spinal cord) FA and C P decreased, whereas the C L and C S values were unchanged or slightly smaller. Histological studies of a fluorescent mice model (YFP, G93A-SOD1 mouse) corroborated the early alterations in neuronal morphology and axonal connectivity measured by DTI., Conclusions: Changes in diffusion tensor shape were observed in this animal model at the early, nonsymptomatic stages of ALS. Further studies of C L , C P , and C S as imaging biomarkers should be undertaken to refine this neuroimaging tool for future clinical use in the detection of the early stages of ALS., Competing Interests: None., (© 2020 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Background: Seven T ultra-high field MRI systems have recently been approved for clinical use by the U.S. and European regulatory agencies. These systems are now being used clinically and will likely be more widely available in the near future. One of the applications of 7 T systems is musculoskeletal disease and particularly peripheral arthritis imaging. Since the introduction of potent anti-rheumatic therapies over the last two decades MRI has gained increasing importance particularly for assessment of disease activity in early stages of several rheumatic disorders. Commonly gadolinium-based contrast agents are used for assessment of synovitis. Due to potential side-effects of gadolinium non-enhanced techniques are desirable that enable visualization of inflammatory disease manifestations. The feasibility of 7 T MRI for evaluation of peripheral arthritis has not been shown up to now. Aim of our study was to evaluate the feasibility of contrast-enhanced (CE) and non-enhanced MRI at 7 T for the assessment of knee joint synovitis., Method: Seven T MRI was acquired for 10 patients with an established diagnosis of psoriatic or rheumatoid arthritis. The study pulse sequence protocol was comprised of a sagittal intermediate-weighted fat-suppressed (FS), axial fluid-attenuated inversion recovery (FLAIR) FS, sagittal 3D T1-weighted dynamic contrast enhanced (DCE) and an axial static 2D T1-weighted FS contrast-enhanced sequence (T1-FS CE). Ordinal scoring on non-enhanced (Hoffa- and effusion-synovitis) and enhanced MRI (11-point synovitis score), and comparison of FLAIR-FS with static T1-FS CE MRI using semiquantitative (SQ) grading and volume assessment was performed. For inter- and intra-reader reliability assessment weighted kappa statistics for ordinal scores and intraclass correlation coefficients (ICC) for continuous variables were used., Results: The total length of study protocol was 15 min 38 s. Different amounts of synovitis were observed in all patients (mild: n = 3; moderate: n = 5; severe: n = 2). Consistently, SQ assessment yielded significantly lower peripatellar summed synovitis scores for the FLAIR-FS sequence compared to the CE T1-FS sequence (p < 0.01). FLAIR-FS showed significantly lower peripatellar synovial volumes (p < 0.01) compared to CE T1-FS imaging with an average percentage difference of 18.6 ± 9.5%. Inter- and intra-reader reliability for ordinal SQ scoring ranged from 0.21 (inter-reader Hoffa-synovitis) to 1.00 (inter-reader effusion-synovitis). Inter- and intra-observer reliability of SQ 3D-DCE parameters ranged from 0.86 to 0.99., Conclusions: Seven T FLAIR-FS ultra-high field MRI is a potential non-enhanced imaging method able to visualize synovial inflammation with high conspicuity and holds promise for further application in research endeavors and clinical routine by trained readers.

Non-invasive magnetic resonance imaging (MRI) techniques are increasingly applied in the clinic with a fast growing body of evidence regarding its value for clinical decision making. In contrast to biochemical or histological markers, the key advantages of imaging biomarkers are the non-invasive nature and the spatial and temporal resolution of these approaches. The following chapter focuses on clinical applications of novel MR biomarkers in humans with a strong focus on oncologic diseases. These include both clinically established biomarkers (part 1-4) and novel MRI techniques that recently demonstrated high potential for clinical utility (part 5-7).

Background: In postmortem analysis of late stage Parkinson's disease (PD) neuronal loss in the substantial nigra (SN) correlates with the antemortem severity of bradykinesia and rigidity, but not tremor., Objective: To investigate the relationship between midbrain nuclei volume as an in vivo biomarker for surviving neurons in mild-to-moderate patients using 7.0 Tesla MRI., Methods: We performed ultra-high resolution quantitative susceptibility mapping (QSM) on the midbrain in 32 PD participants with less than 10 years duration and 8 healthy controls. Following blinded manual segmentation, the individual volumes of the SN, subthalamic nucleus, and red nucleus were measured. We then determined the associations between the midbrain nuclei and clinical metrics (age, disease duration, MDS-UPDRS motor score, and subscores for bradykinesia/rigidity, tremor, and postural instability/gait difficulty)., Results: We found that smaller SN correlated with longer disease duration (r = -0.49, p = 0.004), more severe MDS-UPDRS motor score (r = -0.42, p = 0.016), and more severe bradykinesia-rigidity subscore (r = -0.47, p = 0.007), but not tremor or postural instability/gait difficulty subscores. In a hemi-body analysis, bradykinesia-rigidity severity only correlated with SN contralateral to the less-affected hemi-body, and not contralateral to the more-affected hemi-body, possibly reflecting the greatest change in dopamine neuron loss early in disease. Multivariate generalized estimating equation model confirmed that bradykinesia-rigidity severity, age, and disease duration, but not tremor severity, predicted SN volume., Conclusions: In mild-to-moderate PD, SN volume relates to motor manifestations in a motor domain-specific and laterality-dependent manner. Non-invasive in vivo 7.0 Tesla QSM may serve as a biomarker in longitudinal studies of SN atrophy and in studies of people at risk for developing PD.

Modern high field and ultra high field magnetic resonance imaging (MRI) experiments routinely collect multi-dimensional data with high spatial resolution, whether multi-parametric structural, diffusion or functional MRI. While diffusion and functional imaging have benefited from recent advances in multi-dimensional signal analysis and denoising, structural MRI has remained untouched. In this work, we propose a denoising technique for multi-parametric quantitative MRI, combining a highly popular denoising method from diffusion imaging, over-complete local PCA, with a reconstruction of the complex-valued MR signal in order to define stable estimates of the noise in the decomposition. With this approach, we show signal to noise ratio (SNR) improvements in high resolution MRI without compromising the spatial accuracy or generating spurious perceptual boundaries., (Copyright © 2019 Bazin, Alkemade, van der Zwaag, Caan, Mulder and Forstmann.)

Quantitative Susceptibility Mapping (QSM) provides a way of measuring iron concentration and myelination non-invasively and has the potential of becoming a tool of paramount importance in the study of a host of different pathologies. However, several experimental factors and the physical properties of magnetic susceptibility (χ) can impair the reliability of QSM, and it is therefore essential to assess QSM reproducibility for repeated acquisitions and different field strength. In particular, it has recently been demonstrated that QSM measurements strongly depend on echo time (TE): the same tissue, measured on the same scanner, exhibits different apparent frequency shifts depending on the TE used. This study aims to assess the influence of TE on intra-scanner and inter-scanner reproducibility of QSM, by using MRI systems operating at 3T and 7T. To maximize intra-scanner reproducibility it is necessary to match the TEs of the acquisition protocol, but the application of this rule leads to inconsistent QSM values across scanners operating at different static magnetic field. This study however demonstrates that, provided a careful choice of acquisition parameters, and in particular by using TEs at 3T that are approximately 2.6 times longer than those at 7T, highly reproducible whole-brain χ maps can be achieved also across different scanners, which renders QSM a suitable technique for longitudinal follow-up in clinical settings and in multi-center studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Studies investigating hippocampal volume changes after treatment with serotonergic antidepressants in patients with major depressive disorder yielded inconsistent results, and effects on hippocampal subfields are unclear., Methods: To detail treatment effects on total hippocampal and subfield volumes, we conducted an open-label study with escitalopram followed by venlafaxine upon nonresponse in 20 unmedicated patients with major depressive disorder. Before and after 12 weeks treatment, we measured total hippocampal formation volumes and subfield volumes with ultra-high field (7 Tesla), T1-weighted, structural magnetic resonance imaging, and FreeSurfer. Twenty-eight remitted patients and 22 healthy subjects were included as controls. We hypothesized to detect increased volumes after treatment in major depressive disorder., Results: We did not detect treatment-related changes of total hippocampal or subfield volumes in patients with major depressive disorder. Secondary results indicated that the control group of untreated, stable remitted patients, compared with healthy controls, had larger volumes of the right hippocampal-amygdaloid transition area and right fissure at both measurement time points. Depressed patients exhibited larger volumes of the right subiculum compared with healthy controls at MRI-2. Exploratory data analyses indicated lower baseline volumes in the subgroup of remitting (n = 10) vs nonremitting (n = 10) acute patients., Conclusions: The results demonstrate that monoaminergic antidepressant treatment in major depressive disorder patients was not associated with volume changes in hippocampal subfields. Studies with larger sample sizes to detect smaller effects as well as other imaging modalities are needed to further assess the impact of antidepressant treatment on hippocampal subfields., (© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.)

Purpose: To improve the transmit (Tx) and receive (Rx) performance of a human head array and provide whole-brain coverage at 9.4T, a novel 32-element array design was developed, constructed, and tested., Methods: The array consists of 18 transceiver (TxRx) surface loops and 14 Rx-only vertical loops all placed in a single layer. The new design combines benefits of both TxRx and transmit-only-receive-only (ToRo) designs. The general idea of the design is that the total number of array elements (both TxRx and Rx) should not exceed the number of required Rx elements. First, the necessary number of TxRx loops is placed around the object tightly to optimize the Tx performance. The rest of the elements are loops, which are used only for reception. We also compared the performance of the new array with that of a state-of-the-art ToRo array consisting of 16 Tx-only loops and 31 Rx-only loops., Results: The new array provides whole-brain coverage, ~1.5 times greater Tx efficiency and 1.3 times higher SNR near the brain center as compared to the ToRo array, while the latter delivers higher (up to 1.5 times) peripheral SNR., Conclusion: In general, the new approach of constructing a single-layer array consisting of both TxRx- and Rx-only elements simplifies the array construction by minimizing the total number of elements and makes the entire design more robust and, therefore, safe. Overall, our work provides a recipe for a Tx- and Rx-efficient head array coil suitable for parallel transmission and reception as well as whole-brain imaging at UHF., (© 2018 International Society for Magnetic Resonance in Medicine.)

Perfusion magnetic resonance imaging (MRI) is a promising non-invasive technique providing insights regarding the brain's microvascular architecture in vivo. The scalar perfusion metrics can be used for quantitative diagnostics of various brain abnormalities, in particular, in the stroke cases and tumours. However, conventional MRI-based perfusion approaches such as dynamic contrast-enhanced perfusion imaging or arterial spin labelling have a few weaknesses, for instance, contrast agent deposition, low signal-to-noise ratio, limited temporal and spatial resolution, and specific absorption rate constraints. As an alternative, the intravoxel incoherent motion (IVIM) approach exploits an extension of diffusion MRI in order to estimate perfusion parameters in the human brain. Application of IVIM imaging at ultra-high field MRI might employ the advantage of a higher signal-to-noise ratio, and thereby the use of higher spatial and temporal resolutions. In the present work, we demonstrate an application of recently developed isotropic diffusion weighted sequences to the evaluation of IVIM parameters at an ultra-high 7T field. The used sequence exhibits high immunity to image degrading factors and allows one to acquire the data in a fast and efficient way. Utilising the bi-exponential fitting model of the signal attenuation, we performed an extensive analysis of the IVIM scalar metrics obtained by a isotropic diffusion weighted sequence in vivo and compared results with a conventional pulsed gradient sequence at 7T. In order to evaluate a possible metric bias originating from blood flows, we additionally used a truncated b-value protocol (b-values from 100 to 200 s/mm 2 with the step 20 s/mm 2 ) accompanied to the full range (b-values from 0 to 200 s/mm 2 ). The IVIM scalar metrics have been assessed and analysed together with a large and middle vessel density atlas of the human brain. We found that the diffusion coefficients and perfusion fractions of the voxels consisting of large and middle vessels have higher values in contrast to other tissues. Additionally, we did not find a strong dependence of the IVIM metrics on the density values of the vessel atlas. Perspectives and limitations of the developed isotropic diffusion weighted perfusion are presented and discussed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The recent introduction of advanced magnetic resonance (MR) imaging techniques to characterize focal and global degeneration in multiple sclerosis (MS), like the Composite Hindered and Restricted Model of Diffusion, or CHARMED, diffusional kurtosis imaging (DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI) made available new tools to image axonal pathology non-invasively in vivo. These methods already showed greater sensitivity and specificity compared to conventional diffusion tensor-based metrics (e.g., fractional anisotropy), overcoming some of its limitations. While previous studies uncovered global and focal axonal degeneration in MS patients compared to healthy controls, here our aim is to investigate and compare different diffusion MRI acquisition protocols in their ability to highlight microstructural differences between MS and control tissue over several much used models. For comparison, we contrasted the ability of fractional anisotropy measurements to uncover differences between lesion, normal-appearing white matter (WM), gray matter and healthy tissue under the same imaging protocols. We show that: (1) focal and diffuse differences in several microstructural parameters are observed under clinical settings; (2) advanced models (CHARMED, DKI and NODDI) have increased specificity and sensitivity to neurodegeneration when compared to fractional anisotropy measurements; and (3) both high (3 T) and ultra-high fields (7 T) are viable options for imaging tissue change in MS lesions and normal appearing WM, while higher b-values are less beneficial under the tested short-time (10 min acquisition) conditions., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The quality and precision of post-mortem MRI microscopy may vary depending on the embedding medium used. To investigate this, our study evaluated the impact of 5 widely used media on: (1) image quality, (2) contrast of high spatial resolution gradient-echo (T 1 and T 2 * -weighted) MR images, (3) effective transverse relaxation rate (R 2 * ), and (4) quantitative susceptibility measurements (QSM) of post-mortem brain specimens., Methods: Five formaldehyde-fixed brain slices were scanned using 7.0T MRI in: (1) formaldehyde solution (formalin), (2) phosphate-buffered saline (PBS), (3) deuterium oxide (D 2 O), (4) perfluoropolyether (Galden), and (5) agarose gel. SNR and contrast-to-noise ratii (SNR/CNR) were calculated for cortex/white matter (WM) and basal ganglia/WM regions. In addition, median R 2 * and QSM values were extracted from caudate nucleus, putamen, globus pallidus, WM, and cortical regions., Results: PBS, Galden, and agarose returned higher SNR/CNR compared to formalin and D 2 O. Formalin fixation, and its use as embedding medium for scanning, increased tissue R 2 * . Imaging with agarose, D 2 O, and Galden returned lower R 2 * values than PBS (and formalin). No major QSM offsets were observed, although spatial variance was increased (with respect to R 2 * behaviors) for formalin and agarose., Conclusions: Embedding media affect gradient-echo image quality, R 2 * , and QSM in differing ways. In this study, PBS embedding was identified as the most stable experimental setup, although by a small margin. Agarose and Galden were preferred to formalin or D 2 O embedding. Formalin significantly increased R 2 * causing noisier data and increased QSM variance., (© 2018 International Society for Magnetic Resonance in Medicine.)

Comparison studies between 7T and 1.5 or 3T magnetic resonance imaging (MRI) have demonstrated the added value of ultra-high field (UHF) MRI to better identify, delineate and characterize malformations of cortical development (MCD), and to disambiguate doubtful findings observed at lower field strengths. High resolution structural sequences such as magnetization prepared two rapid acquisition gradient echoes (MP2RAGE), fluid and white matter suppression MP2RAGE (FLAWS), and susceptibility-weighted imaging (SWI) appear to be key to the improvement of MCD diagnosis in clinical practice. 7T MRI offers not only images of high resolution and contrast but also provides many quantitative approaches capable of acting as more efficient probes of microstructure and ameliorating the categorization of MCDs. Post-processing of multiparametric ultra-high resolution and quantitative data may also be used to improve automated detection of MCD via machine learning. Therefore, 7T MRI can be considered as a useful tool in the presurgical evaluation of drug-resistant partial epilepsies, particularly, but not exclusively, in cases of normal appearing conventional MRI. It also opens many perspectives in the fields of in vivo histology and computational anatomy., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

RF coil design for human ultra‐high field (7 T and higher) magnetic resonance (MR) imaging is an area of intense development, to overcome difficult challenges such as RF excitation spatial heterogeneity and low RF transfer efficiency into the spin system. This article proposes a novel category of multi‐channel RF volume coil structures at both 7 T and 10.5 T based on a subject‐loaded multifilar helical‐antenna RF coil that aims at addressing these problems. In some prior applications of helix antennas as MR RF coils at 7 T, the imaged sample was positioned outside the helix. Here, we introduce a radically different approach, with the inner volume of a helix antenna being utilized to image a sample. The new coil uniquely combines traveling‐wave behavior through the overall antenna wire structure and near‐field RF interaction between the conducting elements and the imaged tissues. It thus benefits from the congruence of far‐ and near‐field regimes. Design and analysis of the novel inner‐volume coils are performed by numerical simulations using multiple computational electromagnetics techniques. The fabricated coil prototypes are tested, validated, and evaluated experimentally in 7‐T and 10.5‐T MR human wide bore (90‐cm) MR scanners. Phantom data at 7 T show good consistency between numerical simulations and experimental results. Simulated B1+ transmit efficiencies, in T/√W, are comparable to those of some of the conventional and state‐of‐the‐art RF coil designs at 7 T. Experimental results at 10.5 T show the scalability of the helix coil design. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a disease characterized by a progressive degeneration of motor neurons leading to paralysis. Our previous MRI diffusion tensor imaging studies detected early white matter changes in the spinal cords of mice carrying the G93A-SOD1 mutation. Here, we extend those studies using ultra-high field MRI (17.6 T) and fluorescent microscopy to investigate the appearance of early structural and connectivity changes in the spinal cords of ALS mice. Methods: The spinal cords from presymptomatic and symptomatic mice (80 to 120 days of age) were scanned (ex-vivo) using diffusion-weighted MRI. The fractional anisotropy (FA), axial (AD) and radial (RD) diffusivities were calculated for axial slices from the thoracic, cervical and lumbar regions of the spinal cords. The diffusion parameters were compared with fluorescence microscopy and membrane cellular markers from the same tissue regions. Results: At early stages of the disease (day 80) in the lumbar region, we found, a 19% decrease in FA, a 9% decrease in AD and a 35% increase in RD. Similar changes were observed in cervical and thoracic spinal cord regions. Differences between control and ALS mice groups at the symptomatic stages (day 120) were larger. Quantitative fluorescence microscopy at 80 days, demonstrated a 22% reduction in axonal area and a 22% increase in axonal density. Tractography and quantitative connectome analyses measured by edge weights showed a 52% decrease in the lumbar regions of the spinal cords of this ALS mice group. A significant increase in ADC (23.3%) in the ALS mice group was related to an increase in aquaporin markers. Conclusions: These findings suggest that the combination of ultra-high field diffusion MRI with fluorescent ALS mice reporters is a useful approach to detect and characterize presymptomatic white matter micro-ultrastructural changes and axonal connectivity anomalies in ALS. [ABSTRACT FROM AUTHOR]

With recent improvements in human magnetic resonance imaging (MRI) at ultra-high fields, the amount of data collected per subject in a given MRI experiment has increased considerably. Standard image processing packages are often challenged by the size of these data. Dedicated methods are needed to leverage their extraordinary spatial resolution. Here, we introduce a flexible Python toolbox that implements a set of advanced techniques for high-resolution neuroimaging. With these tools, segmentation and laminar analysis of cortical MRI data can be performed at resolutions up to 500 μm in reasonable times. Comprehensive online documentation makes the toolbox easy to use and install. An extensive developer’s guide encourages contributions from other researchers that will help to accelerate progress in the promising field of high-resolution neuroimaging. [ABSTRACT FROM AUTHOR]

Introduction: The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures. Methods: A human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed. Results: Most of the commonly established projections of the subthalamic nucleus, substantia nigra and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus. Discussion: This study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projection of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation of the subthalamic nucleus (STN) is a widely performed surgical treatment for patients with Parkinson's disease. The goal of the surgery is to place an electrode in the motor region of the STN while avoiding non-motor regions. However, distinguishing the motor region from the neighboring associative and limbic areas in individual patients using imaging modalities was until recently not possible. Here, we have performed a patient-specific dissection of the subdivisions of the STN using ultra-high field MR imaging to allow for individualized surgical planning. Methods: We have acquired 7T diffusion-weighted images of seventeen patients with Parkinson's disease scheduled for deep brain stimulation surgery. Using a previously established protocol, the STN's connections to the motor, limbic, and associative cortical areas were used to map the individual subdivisions of the nucleus. Findings: A reproducible patient-specific parcellation of the STN into a posterolateral motor and gradually overlapping central associative area in all STNs, taking up on average 55·3% and 55·6% of the total nucleus volume. The limbic area was found in the anteromedial part of the nucleus. Interpretation: Our results demonstrate that ultra-high field MR imaging can be used to perform an individualized and highly specific planning of deep brain stimulation surgery of the STN. [ABSTRACT FROM AUTHOR]