The key elements for fear extinction learning are unexpected omissions of expected aversive events, which are considered to be rewarding. Given its reception of reward information, we tested the hypothesis that the cerebellum contributes to reward-like prediction error processing driving extinction learning via its connections with the ventral tegmental area (VTA). Forty-three young and healthy participants performed a three-day fear conditioning paradigm in a 7T MR scanner. The cerebellum and VTA were active during unexpected omissions of aversive unconditioned stimuli in the initial extinction trials and in other learning phases, in line with the proposed role of prediction-error processing. Increased functional connectivity was observed between the cerebellum and VTA, indicating that they are functionally coupled during fear extinction learning. These results suggest that an interaction between the cerebellum and VTA should be incorporated into the existing model of the fear extinction network.

Background Susac syndrome (SuS) is a rare autoimmune disease that leads to hearing impairment, visual field deficits, and encephalopathy due to an occlusion of precapillary arterioles in the brain, retina, and inner ear. Given the potentially disastrous outcome and difficulties in distinguishing SuS from its differential diagnoses, such as multiple sclerosis (MS), our exploratory study aimed at identifying potential new SuS-specific neuroimaging markers. Methods Seven patients with a definite diagnosis of SuS underwent magnetic resonance imaging (MRI) at 7 Tesla (7T), including T2* weighted and quantitative susceptibility mapping (QSM) sequences. T2 weighted hyperintense lesions were analyzed with regard to number, volume, localization, central vein sign, T1 hypointensity, and focal iron deposits in the center of SuS lesions (“iron dots”). Seven T MRI datasets from the same institute, comprising 75 patients with, among others, MS, served as controls. Results The “iron dot” sign was present in 71.4% (5/7) of the SuS patients, compared to 0% in our control cohort. Thus, sensitivity was 71.4% and specificity 100%. A central vein sign was only incidentally detected. Conclusion We are the first to demonstrate this type of “iron dot” lesions on highly resolving 7T T2*w and QSM images in vivo as a promising neuroimaging marker of SuS, corroborating previous histopathological ex vivo findings.

Background: Attenuation correction (AC) is an important methodical step in positron emission tomography/magnetic resonance imaging (PET/MRI) to correct for attenuated and scattered PET photons.Purpose: The overall quality of magnetic resonance (MR)-based AC in whole-body PET/MRI was evaluated in direct comparison to computed tomography (CT)-based AC serving as reference. The quantitative impact of isolated tissue classes in the MR-AC was systematically investigated to identify potential optimization needs and strategies.Methods: Data of n = 60 whole-body PET/CT patients with normal lung tissue and without metal implants/prostheses were used to generate six different AC-models based on the CT data for each patient, simulating variations of MR-AC. The original continuous CT-AC (CT-org) is referred to as reference. A pseudo MR-AC (CT-mrac), generated from CT data, with four tissue classes and a bone atlas represents the MR-AC. Relative difference in linear attenuation coefficients (LAC) and standardized uptake values were calculated. From the results two improvements regarding soft tissue AC and lung AC were proposed and evaluated.Results: The overall performance of MR-AC is in good agreement compared to CT-AC. Lungs, heart, and bone tissue were identified as the regions with most deviation to the CT-AC (myocardium -15%, bone tissue -14%, and lungs +/- 20%). Using single-valued LACs for AC in the lung only provides limited accuracy. For improved soft tissue AC, splitting the combined soft tissue class into muscles and organs each with adapted LAC could reduce the deviations to the CT-AC to < +/- 1%. For improved lung AC, applying a gradient LAC in the lungs could remarkably reduce over- or undercorrections in PET signal compared to CT-AC (+/- 5%).Conclusions: The AC is important to ensure best PET image quality and accurate PET quantification for diagnostics and radiotherapy planning. The optimized segment-based AC proposed in this study, which was evaluated on PET/CT data, inherently reduces quantification bias in normal lung tissue and soft tissue compared to the CT-AC reference.

Background124-iodine (124I) is used for positron emission tomography (PET) diagnostics and therapy planning in patients with differentiated thyroid cancer (DTC). Small lesion sizes (<10 mm) and low 124I uptake are challenging conditions for the detection of DTC lymph node lesions. PurposeThe aim of this study was to systematically investigate the lesion detectability and quantification performance under clinically challenging imaging conditions using non-time-of-flight (TOF) PET/magnetic resonance imaging (MRI) in the clinical context of radionuclide therapy planning of DTC patients. MethodsPET/MR measurements were performed on the Siemens Biograph mMR using a small lesion NEMA-like phantom (six glass spheres, diameters 3.7-9.7 mm). 60 min list-mode data were acquired for nine activity concentrations (AC) ranging from 25 kBq/mL to 0.25 kBq/mL using a sphere-to-background ratio of 20:1. PET list-mode data were divided into five timeframes (60, 30, 16, 8, and 4 min) and reconstructed using either ordered-subsets expectation maximization (OSEM) or OSEM+ point spread function (PSF) algorithm. For all reconstructions, the smallest detectable sphere size was investigated in a human observer study. Partial volume effect (PVE) corrected PET images (contour and oversize-based approach) were analyzed considering a +/- 30% deviation range between imaged and true AC as acceptable. Clinical data of eight DTC patients with small lymph node lesions were evaluated to assess agreement between the PVE correction approaches. ResultsLonger PET acquisition times, higher ACs, and PSF reconstructions resulted in improved PET image quality and overall improved lesion detectability. The smallest 3.7 mm sphere was only visible under the best imaging conditions. Using a typical clinical 124I whole-body PET/MRI protocol with an acquisition time of 8 min using OSEM reconstructions, all lesions of >= 6.5 mm in diameter could be detected and the quantification provided reliable results approximately above 5.0 kBq/mL. An accurate quantification of ACs in the 4.8 mm sphere was not feasible in this study. In the clinical evaluation of 10 lesions, a good agreement between oversize- and contour-based PVE corrections was observed (<15% deviation). ConclusionsThe results showed that a reliable quantification of 124I uptake with PET/MRI is feasible and, therefore, could be used to perform radioiodine pre-therapy lesion dosimetry and individualized therapy planning in DTC patients.

Functional brain imaging studies in humans suggest involvement of the cerebellum in fear conditioning but do not allow conclusions about the functional significance. The main aim of the present study was to examine whether patients with cerebellar degeneration show impaired fear conditioning and whether this is accompanied by alterations in cerebellar cortical activations. To this end, a 2 d differential fear conditioning study was conducted in 20 cerebellar patients and 21 control subjects using a 7 tesla (7 T) MRI system. Fear acquisition and extinction training were performed on day 1, followed by recall on day 2. Cerebellar patients learned to differentiate between the CS+ and CS-. Acquisition and consolidation of learned fear, however, was slowed. Additionally, extinction learning appeared to be delayed. The fMRI signal was reduced in relation to the prediction of the aversive stimulus and altered in relation to its unexpected omission. Similarly, mice with cerebellar cortical degeneration (spinocerebellar ataxia type 6, SCA6) were able to learn the fear association, but retrieval of fear memory was reduced. In sum, cerebellar cortical degeneration led to mild abnormalities in the acquisition of learned fear responses in both humans and mice, particularly manifesting postacquisition training. Future research is warranted to investigate the basis of altered fMRI signals related to fear learning.

Abstract The highest magnetic field strength for human-sized magnetic resonance imaging (MRI) currently lies at 11.7 tesla. Given the opportunities for enhanced sensitivity and improved data quality at higher static magnetic fields, several initiatives around the world are pursuing the implementation of further human MRI systems at or above 11.7 tesla. In general, members of the magnetic resonance (MR) research community are not experts on magnet technology. However, the magnet is the technological heart of any MR system, and the MRI community is challenging the magnet research and design community to fulfill the current engineering gap in implementing large-bore, highly homogeneous and stabile magnets at field strengths that go beyond the performance capability of niobium–titanium. In this article, we present an overview of magnet design for such systems from the perspective of MR scientists. The underlying motivation and need for higher magnetic fields are briefly introduced, and system design considerations for the magnet as well as for the MRI subsystems such as the gradients, the shimming arrangement, and the radiofrequency hardware are presented. Finally, important limitations to higher magnetic fields from physiological considerations are described, operating under the assumption that any engineering or economic barriers to realizing such systems will be overcome.

Background Interindividual variation in fear learning is partly attributable to the genetic make-up in each individual. Genetic variants may impact the structural and functional connectivity of the human fear extinction network such that genetically driven alterations of network properties give in part rise to the observed individual rates of learning. Our aim was to identify genetic risk indices that predict physiological measures of fear learning mediated by connectivity patterns in key regions within the human fear network. Methods We computed polygenic risk scores (PRS) for several psychiatric disorders and related traits (major depressive disorder, post-traumatic stress disorder, cross-disorder risk, anxiety disorders, neuroticism) and cognitive abilities (short-term memory and verbal learning), structural and functional connectivity measures for all possible pairs out of five key brain regions within the human fear network (amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), and the cerebellar nuclei), as well as learning measures derived from modeled non-linear slopes of skin conductance responses to either conditioned stimuli (CS+) that predict the occurrence of an aversive unconditioned stimulus or stimuli that do not (CS-) during acquisition and extinction training in one hundred and seventy-two individuals. Results Structural connectivity among all ROIs examined arised as the dominant MRI marker that mediates the association between PRS and learning. Amygdala connectivity featured prominently. All tested predictors were associated with learning for various experimental phases and stimulus-type combinations. All traits except for our control (prostate cancer) showed a high degree of genetic correlation with many others, indicating pleiotropic confound present in our PRS. After correcting for pleiotropy, only cross-disorder risk PRS and short-term memory PGS remained as meaningful genetic predictors, when testing for each stimuli separately. In the case of a combined learning measure, all but PTSD-PGS were found to be predictive of learning even after pleiotropy control. Discussion Our results show for the first time that the additive genetic load for a variety of mental disorders and cognitive capabilities can explain heterogeneity in conditioned fear responses. Genetic risk indices draw their predictive power probably from cross-trait signals picked up in conventional univariate GWAS. Structural connectivity proved to be a useful endophenotype. However, the amount of the total effect that is attributable to the mediation varies greatly across traits, implying that for some traits other MRI markers may be more suitable to explain the path between genetic variation and physiology/behavior. A task to be undertaken in future research.

To investigate the influence of Gadolinium-based contrast agents (CA) on MR-based attenuation correction (MRAC) in evaluating target lesions in [68Ga]Ga-DOTA-TOC. Twenty-four patients with detectable metastases from neuroendocrine tumors underwent whole-body [68Ga]-DOTATOC PET/MRI for staging purposes. According to a consensus reading, 72 target lesions (primaries and metastases) were selected for measurement of standardized uptake values (SUVmax, SUVpeak, SUVmean). High-resolution CAIPI-accelerated Dixon 3D VIBE sequences with bone atlas and truncation correction were acquired before and after contrast agent application. PET data were subsequently reconstructed using both resulting μmaps (MRACnative and MRACpostCA). Each target lesion was assessed in both versions of MRAC-PET utilizing a volume of interest (VOI). Measured values were compared using the Pearson Correlation Coefficient. In addition, a Bland–Altman analysis was performed to determine the limits of agreement (LOA). A strong correlation was achieved for the SUV values before and after contrast medium administration (SUVmax. 0.99; SUVpeak. 0.997; SUVmean. 0.993; p < 0.001). Bland–Altman-analysis, however, showed wider LOA between both PET datasets for SUVmax (4.5 and − 4.7) when compared to SUVpeak (1.7 and − 2.1), and SUVmean (1.8 and − 2.2). No major deviations between the measured values in pre- and post-contrast attenuation-corrected PET images have been observed. Minor alterations may occur due to the application of a contrast medium. This has to be accounted for in patients undergoing repeated PET/MR imaging, especially in the context of therapy monitoring. Our lesion-based analysis examines the impact of gadolinium-based contrast agents on attenuation correction of PET/MRI and the subsequent influence on tracer quantification. Our lesion based approach did not found any major differences between both assessments, indicating that any influence on lesion analysis is negligible.

Multiple sites within Germany operate human MRI systems with magnetic fields either at 7 Tesla or 9.4 Tesla. In 2013, these sites formed a network to facilitate and harmonize the research being conducted at the different sites and make this technology available to a larger community of researchers and clinicians not only within Germany, but also worldwide. The German Ultrahigh Field Imaging (GUFI) network has defined a strategic goal to establish a 14 Tesla whole-body human MRI system as a national research resource in Germany as the next progression in magnetic field strength. This paper summarizes the history of this initiative, the current status, the motivation for pursuing MR imaging and spectroscopy at such a high magnetic field strength, and the technical and funding challenges involved. It focuses on the scientific and science policy process from the perspective in Germany, and is not intended to be a comprehensive systematic review of the benefits and technical challenges of higher field strengths.

Deep learning approaches are capable of learning the mapping function from MR to CT images and thus allow synthesizing pseudo-CTs. However, due to the lack of visual information in the source MRI domain, they often fail to generate bone regions accurately. To address this issue, we propose a double Grad-CAM guidance for U-Net (DGCG U-Net), which indirectly forces the network to focus more on bone structures. More specifically, we first train a Grad-CAM guided classification model in such a way that it distinguishes MR and CT images based solely on bone regions. After that, we utilize this pre-trained classifier and again use Grad-CAM technique to guide our U-Net model by forcing it to focus on bone regions. The performance of the proposed approach is evaluated on the publicly available RIRE data set. The results demonstrate that our model, compared to the baseline GCG U-Net, generates more accurate pseudo-CTs, resulting in approximately 2.5

Background: Accurate detection of lymph node (LN) metastases in prostate cancer (PCa) is a challenging but crucial step for disease staging. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) enables distinction between healthy LNs and nodes suspicious for harboring metastases. When combined with MRI at an ultra-high magnetic field, an unprecedented spatial resolution can be exploited to visualize these LNs. Purpose: The aim of this study was to explore USPIO-enhanced MRI at 7 T in comparison to 3 T for the detection of small suspicious LNs in the same cohort of patients with PCa. Materials and Methods: Twenty PCa patients with high-risk primary or recurrent disease were referred to our hospital for an investigational USPIO-enhanced 3 T MRI examination with ferumoxtran-10. With consent, they underwent a 7 T MRI on the same day. Three-dimensional anatomical and T2*-weighted images of both examinations were evaluated blinded, with an interval, by 2 readers who annotated LNs suspicious for metastases. Number, size, and level of suspicion (LoS) of LNs were paired within patients and compared between field strengths. Results: At 7 T, both readers annotated significantly more LNs compared with 3 T (474 and 284 vs 344 and 162), with 116 suspicious LNs on 7 T (range, 1-34 per patient) and 79 suspicious LNs on 3 T (range, 1-14 per patient) in 17 patients. For suspicious LNs, the median short axis diameter was 2.6 mm on 7 T (1.3-9.5 mm) and 2.8 mm for 3 T (1.7-10.4 mm, P = 0.05), with large overlap in short axis of annotated LNs between LoS groups. At 7 T, significantly more suspicious LNs had a short axis <2.5 mm compared with 3 T (44% vs 27%). Magnetic resonance imaging at 7 T provided better image quality and structure delineation and a higher LoS score for suspicious nodes. Conclusions: In the same cohort of patients with PCa, more and more small LNs were detected on 7 T USPIO-enhanced MRI compared with 3 T MRI. Suspicious LNs are generally very small, and increased nodal size was not a good indication of suspicion for the presence of metastases. The high spatial resolution of USPIO-enhanced MRI at 7 T improves structure delineation and the visibility of very small suspicious LNs, potentially expanding the in vivo detection limits of pelvic LN metastases in PCa patients.

Inhomogeneities across large FOVs are problematic at ultra-high field. We propose a software-based TIAMO implementation to enable similar flip angles across the body without hardware interference on the 7T MR scanner. Using an interleaved and complementary CP+/CP2+ excitation scheme, we acquired water-selective and lipid-selective 3D GRE data at high resolution demonstrating homogeneous signal distribution across the pelvis and lower abdomen.

To investigate the diagnostic feasibility of a shortened breast PET/MRI protocol in breast cancer patients.Altogether 90 women with newly diagnosed T1tumor-staged (T1ts) and T2tumor-staged (T2ts) breast cancer were included in this retrospective study. All underwent a dedicated comprehensive breast [18F]FDG-PET/MRI. List-mode PET data were retrospectively reconstructed with 20, 15, 10, and 5 min for each patient to simulate the effect of reduced PET acquisition times. The SUVmax/mean of all malign breast lesions was measured. Furthermore, breast PET data reconstructions were analyzed regarding image quality, lesion detectability, signal-to-noise ratio (SNR), and image noise (IN). The simultaneously acquired comprehensive MRI protocol was then shortened by retrospectively removing sequences from the protocol. Differences in malignant breast lesion detectability between the original and the fast breast MRI protocol were evaluated lesion-based. The 20-min PET reconstructions and the original MRI protocol served as reference.In all PET reconstructions, 127 congruent breast lesions could be detected. Group comparison and T1ts vs. T2ts subgroup comparison revealed no significant difference of subjective image quality between 20, 15, 10, and 5 min acquisition times. SNR of qualitative image evaluation revealed no significant difference between different PET acquisition times. A slight but significant increase of IN with decreasing PET acquisition times could be detected. Lesion SUVmax group comparison between all PET acquisition times revealed no significant differences. Lesion-based evaluation revealed no significant difference in breast lesion detectability between original and fast breast MRI protocols.Breast [18F]FDG-PET/MRI protocols can be shortened from 20 to below 10 min without losing essential diagnostic information.• A highly accurate breast cancer evaluation is possible by the shortened breast [18F]FDG-PET/MRI examination protocol. • Significant time saving at breast [18F]FDG-PET/MRI protocol could increase patient satisfaction and patient throughput for breast cancer patients at PET/MRI.

This study evaluates a numerical approach to simulate artifacts due to presence of orthopedic metallic implants in the MR environment. Further to previously published studies, the numerical approach is validated by comparing simulations and measurements of orthopedic implants at three different field strengths (1.5T, 3T, and 7T). Artifact simulations and measurements of the implants show high correlation at all field strengths. The method potentially can be applied to improve the artifacts testing procedure for medical implants according to ASTM F2119. Additionally, the influence of different imaging parameters (echo time and bandwidth) on the artifact size is quantified via numerical simulations.

American football players were examined before and after a season of the German Football League. High resolution quantitative MRI at 7T for evaluations of volumetric changes and alterations in T1 relaxation times of various brain regions was performed. Age- and gender-matched subjects with no history of contact and collision sports served as a control group. In addition, structural susceptibility weighted imaging was compared between 3T and 7T. Loss of gray matter volume and an overall increase in T1 relaxation times were observed in players between both scans. SWI was superior in detecting cerebral microbleeds at 7T compared to 3T.