AbstractObjectiveThis study evaluates the performance of the novel MRI sequence stimulus‐induced rotary saturation (SIRS) to map responses to interictal epileptic activity in the human cortex. Spin‐lock pulses have been applied to indirectly detect neuronal activity through magnetic field perturbations. Following initial reports about the feasibility of the method in humans and animals with epilepsy, we aimed to investigate the diagnostic yield of spin‐lock MR pulses in comparison with scalp‐EEG in first seizure patients.MethodsWe employed a novel method for measurements of neuronal activity through the detection of a resonant oscillating field, stimulus‐induced rotary saturation contrast (SIRS) at spin‐lock frequencies of 120 and 240 Hz acquired at a single 3T MRI system. Within a prospective observational study, we conducted SIRS experiments in 55 patients within 7 days after a suspected first unprovoked epileptic seizure and 61 healthy control subjects. In this study, we report on the analysis of data from a single 3T MRI system, encompassing 35 first seizure patients and 31 controls.ResultsThe SIRS method was applicable in all patients and healthy controls at frequencies of 120 and 240 Hz. We did not observe any significant age‐ or sex‐related differences. Specificity of SIRS at 120 Hz was 90.3% and 93.5% at 240 Hz. Sensitivity was 17.1% at 120 Hz and 40.0% at 240 Hz.SignificanceSIRS targets neuronal oscillating magnetic fields in patients with epilepsy. The coupling of presaturated spins to epilepsy‐related magnetic field perturbations may serve as a—at this stage experimental—diagnostic test in first seizure patients to complement EEG findings as a standard screening test.Plain Language SummaryRoutine diagnostic tests carry several limitations when applied after a suspected first seizure. SIRS is a noninvasive MRI method to enable time‐sensitive diagnosis of image correlates of epileptic activity with increased sensitivity compared to routine EEG.

Background: Phenylketonuria (PKU) represents a congenital metabolic defect that disrupts the process of converting phenylalanine (Phe) into tyrosine. Earlier investigations have revealed diminished cognitive performance and changes in brain structure and function (including the presence of white matter lesions) among individuals affected by PKU. However, there exists limited understanding regarding cerebral blood flow (CBF) and its potential associations with cognition, white matter lesions, and metabolic parameters in patients with PKU, which we therefore aimed to investigate in this study. Method: Arterial spin labeling perfusion MRI was performed to measure CBF in 30 adults with early-treated classical PKU (median age 35.5 years) and 59 healthy controls (median age 30.0 years). For all participants, brain Phe levels were measured with 1H spectroscopy, and white matter lesions were rated by two neuroradiologists on T2 weighted images. White matter integrity was examined with diffusion tensor imaging (DTI). For patients only, concurrent plasma Phe levels were assessed after an overnight fasting period. Furthermore, past Phe levels were collected to estimate historical metabolic control. On the day of the MRI, each participant underwent a cognitive assessment measuring IQ and performance in executive functions, attention, and processing speed. Results: No significant group difference was observed in global CBF between patients and controls (F (1, 87) = 3.81, p = 0.054). Investigating CBF on the level of cerebral arterial territories, reduced CBF was observed in the left middle and posterior cerebral artery (MCA and PCA), with the most prominent reduction of CBF in the anterior subdivision of the MCA (F (1, 87) = 6.15, p = 0.015, surviving FDR correction). White matter lesions in patients were associated with cerebral blood flow reduction in the affected structure. Particularly, patients with lesions in the occipital lobe showed significant CBF reductions in the left PCA (U = 352, p = 0.013, surviving FDR correction). Additionally, axial diffusivity measured with DTI was positively associated with CBF in the ACA and PCA (surviving FDR correction). Cerebral blood flow did not correlate with cognitive performance or metabolic parameters. Conclusion: The relationship between cerebral blood flow and white matter indicates a complex interplay between vascular health and white matter alterations in patients with PKU. It highlights the importance of considering a multifactorial model when investigating the impact of PKU on the brain.

Spin-lock (SL) pulses have been proposed to directly detect neuronal activity otherwise inaccessible through standard functional magnetic resonance imaging. However, the practical limits of this technique remain unexplored. Key challenges in SL-based detection include ultra-weak signal variations, sensitivity to magnetic field inhomogeneities, and potential contamination from blood oxygen level-dependent effects, all of which hinder the reliable isolation of neuronal signals. This pilot study evaluates the performance of the stimulus-induced rotary saturation (SIRS) technique to map visual stimulation response in the human cortex. A rotary echo spin-lock (RESL) preparation followed by a 2D echo planar imaging readout was used to investigate 12 healthy subjects at rest and during continuous exposure to 8 Hz flickering light. The SL amplitude was fixed to the target neuroelectric oscillations at that frequency. The signal variance was used as contrast metric, and two alternative post-processing pipelines (regression-filtering-rectification and normalized subtraction) were statistically evaluated. Higher variance in the SL signal was detected in four of the 12 subjects. Although group-level analysis indicated activation in the occipital pole, analysis of variance revealed that this difference was not statistically significant, highlighting the need for comparable control measures and more robust preparations. Further optimization in sensitivity and robustness is required to noninvasively detect physiological neuroelectric activity in the human brain.

Paediatric cancer survivors often suffer from cognitive long-term difficulties. Consequently, strengthening cognition is of major clinical relevance. This study investigated cerebral changes in relation to cognition in non-brain tumour paediatric cancer survivors after working memory or physical training compared to a control group. Thirty-four children (>= one-year post-treatment) either underwent eight weeks of working memory training (n = 10), physical training (n = 11), or a waiting period (n = 13). Cognition and MRI, including arterial spin labelling and diffusion tensor imaging, were assessed at three time points (baseline, post-training, and three-month follow-up). Results show lower cerebral blood flow immediately after working memory training (z = -2.073, p = .038) and higher structural connectivity at the three-month follow-up (z = -2.240, p = .025). No cerebral changes occurred after physical training. Short-term changes in cerebral blood flow correlated with short-term changes in cognitive flexibility (r = -.667, p = .049), while long-term changes in structural connectivity correlated with long-term changes in working memory (r = .786, p = .021). Despite the caution given when interpreting data from small samples, this study suggests a link between working memory training and neurophysiological changes. Further research is needed to validate these findings.

Pediatric cancer survivors (PCS) experience functional difficulties and brain alterations. However, little is known about cerebral perfusion and its relationship to functional outcome (cognitive and motor performance) in PCS. We examined cerebral blood flow (CBF) in non-brain tumor PCS and the associations between CBF and age, as well as functional outcome. Forty PCS and 40 age-comparable controls were included. CBF did not differ between PCS and controls. CBF decreased with age only in controls. In PCS, CBF was associated with functional outcome. Our data indicate an altered relationship between age and CBF in survivors, with stronger brain-behavior mechanisms after cancer.

PURPOSE:The use of magnetic resonance imaging (MRI) is often limited in patients with auditory implants because of the presence of metallic components and magnets. The aim of this study was to evaluate the clinical usefulness of a customized MRI sequence for metal artifact suppression in patients with BONEBRIDGETM BCI 602 implants (MED-EL, Innsbruck, Austria), the successor of the BCI 601 model.METHODS:Using our in-house developed and customized metal artifact reduction sequence (SEMAC-VAT WARP), MRI artifacts were evaluated qualitatively and quantitatively. MRI sequences were performed with and without artifact reduction on two whole head specimens with and without the BCI 602 implant. In addition, the influence of two different implantation sites (mastoid versus retrosigmoid) and head orientation on artifact presence was investigated.RESULTS:Artifact volume was reduced by more than the 50%. Results were comparable with those obtained with the BCI 601, showing no significant differences in the dimensions of artifacts caused by the implant.CONCLUSION:SEMAC-VAT WARP was once more proved to be efficient at reducing metal artifacts on MR images. The dimensions of artifacts associated with the BCI 602 are not smaller than those caused by the BCI 601.

Extracting quantitative information of neuronal signals by non-invasive imaging is an outstanding challenge for understanding brain function and pathology. However, state-of-the-art techniques offer low sensitivity to deep electrical sources. Stimulus induced rotary saturation is a recently proposed magnetic resonance imaging sequence that detects oscillatory magnetic fields using a spin-lock preparation. Phantom experiments and simulations proved its efficiency and sensitivity, but the susceptibility of the method to field inhomogeneities is still not well understood. In this study, we simulated and analyzed the dynamic of three spin-lock preparations and their response to field inhomogeneities in the presence of a resonant oscillating field. We show that the composite spin-lock preparation is more robust against field variations within the double resonance effect. In addition, we tested the capability of the chosen composite spin-lock preparation to recover information about the spectral components of a composite signal. This study sets the bases to move one step further towards the clinical application of MR-based neuronal current imaging.

Purpose At ultra-high field (UHF), B-1(+)-inhomogeneities and high specific absorption rate (SAR) of adiabatic slice-selective RF-pulses make spatial resolved spectral-editing extremely challenging with the conventional MEGA-approach. The purpose of the study was to develop a whole-brain resolved spectral-editing MRSI at UHF (UHF, B-0 >= 7T) within clinical acceptable measurement-time and minimal chemical-shift-displacement-artifacts (CSDA) allowing for simultaneous GABA/Glx-, 2HG-, and PE-editing on a clinical approved 7T-scanner. Methods Slice-selective adiabatic refocusing RF-pulses (2 pi-SSAP) dominate the SAR to the patient in (semi)LASER based MEGA-editing sequences, causing large CSDA and long measurement times to fulfill SAR requirements, even using SAR-minimized GOIA-pulses. Therefore, a novel type of spectral-editing, called SLOW-editing, using two different pairs of phase-compensated chemical-shift selective adiabatic refocusing-pulses (2 pi-CSAP) with different refocusing bandwidths were investigated to overcome these problems. Results Compared to conventional echo-planar spectroscopic imaging (EPSI) and MEGA-editing, SLOW-editing shows robust refocusing and editing performance despite to B-1(+)-inhomogeneity, and robustness to B-0-inhomogeneities (0.2 ppm >= Delta B-0 >= -0.2 ppm). The narrow bandwidth (similar to 0.6-0.8 kHz) CSAP reduces the SAR by 92%, RF peak power by 84%, in-excitation slab CSDA by 77%, and has no in-plane CSDA. Furthermore, the CSAP implicitly dephases water, lipid and all the other signals outside of range (>= 4.6 ppm and <= 1.4 ppm), resulting in additional water and lipid suppression (factors >= 1000s) at zero SAR-cost, and no spectral aliasing artifacts. Conclusion A new spectral-editing has been developed that is especially suitable for UHF, and was successfully applied for 2HG, GABA+, PE, and Glx-editing within 10 min clinical acceptable measurement time.

Abstract Introduction Non‐central nervous system cancer in childhood (non‐CNS CC) and its treatments pose a major threat to brain development, with implications for functional networks. Structural and functional alterations might underlie the cognitive late‐effects identified in survivors of non‐CNS CC. The present study evaluated resting‐state functional networks and their associations with cognition in a mixed sample of non‐CNS CC survivors (i.e., leukemia, lymphoma, and other non‐CNS solid tumors). Methods Forty‐three patients (off‐therapy for at least 1 year and aged 7–16 years) were compared with 43 healthy controls matched for age and sex. High‐resolution T1‐weighted structural magnetic resonance and resting‐state functional magnetic resonance imaging were acquired. Executive functions, attention, processing speed, and memory were assessed outside the scanner. Results Cognitive performance was within the normal range for both groups; however, patients after CNS‐directed therapy showed lower executive functions than controls. Seed‐based connectivity analyses revealed that patients exhibited stronger functional connectivity between fronto‐ and temporo‐parietal pathways and weaker connectivity between parietal‐cerebellar and temporal‐occipital pathways in the right hemisphere than controls. Functional hyperconnectivity was related to weaker memory performance in the patients' group. Conclusion These data suggest that even in the absence of brain tumors, non‐CNS CC and its treatment can lead to persistent cerebral alterations in resting‐state network connectivity.

Abstract Background The diagnosis of idiopathic epilepsy (IE) in dogs is based on exclusion of other potential causes of seizures. Recently, a novel magnetic resonance imaging (MRI) sequence that utilizes a variant of the rotary saturation approach has been suggested to detect weak transient magnetic field oscillations generated by neuronal currents in humans with epilepsy. Hypothesis/Objectives Effects on the magnetic field evoked by intrinsic epileptic activity can be detected by MRI in the canine brain. As proof‐of‐concept, the novel MRI sequence to detect neuronal currents was applied in dogs. Animals Twelve dogs with IE and 5 control dogs without a history of epileptic seizures were examined. Methods Prospective case‐control study as proof‐of‐concept. All dogs underwent a clinical neurological examination, scalp electroencephalography, cerebrospinal fluid analysis, and MRI. The MRI examination included a spin‐locking (SL) experiment applying a low‐power on‐resonance radiofrequency pulse in a predefined frequency domain in the range of oscillations generated by the epileptogenic tissue. Results In 11 of 12 dogs with IE, rotary saturation effects were detected by the MRI sequence. Four of 5 control dogs did not show rotary saturation effects. One control dog with a diagnosis of neuronal ceroid lipofuscinosis had SL‐related effects, but did not have epileptic seizures clinically. Conclusions and Clinical Importance The proposed MRI method detected neuronal currents in dogs with epileptic seizures and represents a potential new line of research to investigate neuronal currents possibly related to IE in dogs.

Background: Childhood cancer survivors (Ccs) are at risk for cognitive late-effects, which might result from cortical alterations, even if cancer does not affect the brain. The study aimed to examine gray and white matter volume and its relationship to cognition. Methods: Forty-three Ccs of non-central nervous system cancers and 43 healthy controls, aged 7-16 years, were examined. Cognitive functions and fine motor coordination were assessed and T1-weighted images were collected for voxel-based morphometry. Results: Executive functions (p = .024, d = .31) were poorer in Ccs than controls, however still within the normal range. The volume of the amygdala (p = .011, LATIN SMALL LETTER ENG(2) = .117) and the striatum (p = .03, LATIN SMALL LETTER ENG(2) = .102) was reduced in Ccs. No significant structure-function correlations were found, neither in patients nor controls. Conclusion: Non-CNS childhood cancer and its treatment impacts on brain structures relevant to emotion processing.

Abstract Introduction: Clinical data support that the dentatorubrothalamic tract (DRTT) is an effective target for deep brain stimulation (DBS) in medically refractory tremor. Nevertheless, the achievement of a realistically detailed depiction of DRTT for preoperative direct targeting remains a challenge.Methods: Ten patients with Parkinson’s disease from the Inselspital Bern database were selected. We used diffusion spectrum imaging (DSI) scans for deterministic fiber tracking of the DRTT with the Track Vis software. Thereafter we compared our DSI-characterized DRTT with the existing anatomical data.Results: In 6 out of 10 individuals the full course of DRTT has been in high affiliation/consistency/association/adherence with the anatomical course of DRTT as described in literature.Conclusions: In this study DSI fiber tracking was used to characterize successfully the DRTT anatomical course in its complexity in a quest of the optimal DBS target for parkinsonian tremor. To our knowledge such attempt has not occurred before. Further studies are required to standardize the protocol of DRTT fiber Tracking and to implement it as a valid DBS preoperative planning technique.

Childhood cancer and its treatment puts survivors at risk of low working memory capacity. Working memory represents a core cognitive function, which is crucial in daily life and academic tasks. The aim of this functional MRI (fMRI) study was to examine the working memory network of survivors of childhood cancer without central nervous system (CNS) involvement and its relation to cognitive performance. Thirty survivors (aged 7-16 years, >= 1 year after cancer treatment) and 30 healthy controls performed a visuospatial working memory task during MRI, including a low- and a high-demand condition. Working memory performance was assessed using standardized tests outside the scanner. When cognitive demands increased, survivors performed worse than controls and showed evidence for slightly atypical working memory-related activation. The survivor group exhibited hyperactivation in the right-hemispheric superior parietal lobe (SPL) in the high- compared to the low-demand working memory condition, while maintaining their performance levels. Hyperactivation in the right SPL coincided with poorer working memory performance outside the scanner in survivors. Even in survivors of childhood cancer without CNS involvement, we find neural markers pointing toward late effects in the cerebral working memory network.

Background Several fMRI studies found hyperactivity in the hippocampus during pattern separation tasks in patients with Mild Cognitive Impairment (MCI; a prodromal stage of Alzheimer’s disease). This was associated with memory deficits, subsequent cognitive decline, and faster clinical progression. A reduction of hippocampal hyperactivity with an antiepileptic drug improved memory performance. Pharmacological interventions, however, entail the risk of side effects. An alternative approach may be real-time fMRI neurofeedback, during which individuals learn to control region-specific brain activity. In the current project we aim to test the potential of neurofeedback to reduce hippocampal hyperactivity and thereby improve memory performance. Methods In a single-blind parallel-group study, we will randomize n = 84 individuals ( n = 42 patients with MCI, n = 42 healthy elderly volunteers) to one of two groups receiving feedback from either the hippocampus or a functionally independent region. Percent signal change of the hemodynamic response within the respective target region will be displayed to the participant with a thermometer icon. We hypothesize that only feedback from the hippocampus will decrease hippocampal hyperactivity during pattern separation and thereby improve memory performance. Discussion Results of this study will reveal whether real-time fMRI neurofeedback is able to reduce hippocampal hyperactivity and thereby improve memory performance. In addition, the results of this study may identify predictors of successful neurofeedback as well as the most successful regulation strategies. Trial registration The study has been registered with clinicaltrials.gov on the 16th of July 2019 (trial identifier: NCT04020744 ).

Predicting outcome in comatose patients after successful cardiopulmonary resuscitation is challenging. Our primary aim was to assess the potential contribution of resting-state-functional magnetic resonance imaging (RS-fMRI) in predicting neurological outcome. RS-fMRI was used to evaluate functional and effective connectivity within the default mode network in a cohort of 90 comatose patients and their impact on functional neurological outcome after 3 months. The RS-fMRI processing protocol comprises the evaluation of functional and effective connectivity within the default mode network. Seed-to-voxel and ROI-to-ROI feature analysis was performed as starting point for a supervised machine-learning approach. Classification of the Cerebral Performance Category (CPC) 1–3 (good to acceptable outcome) versus CPC 4–5 (adverse outcome) achieved a positive predictive value of 91.7%, sensitivity of 90.2%, and accuracy of 87.8%. A direct link to the level of consciousness and outcome after 3 months was identified for measures of segregation in the precuneus, in medial and right frontal regions. Thalamic connectivity appeared significantly reduced in patients without conscious response. Decreased within-network connectivity in the default mode network and within cortico-thalamic circuits correlated with clinical outcome after 3 months. Our results indicate a potential role of these markers for decision-making in comatose patients early after cardiac arrest.

Sustained anxiety is a key symptom of anxiety disorders and may be associated with neural activation in the right inferior parietal lobe (rIPL), particularly under unpredictable threat. This finding suggests a moderating role of the rIPL in sustained anxiety, which we tested in the current study. We applied cathodal or sham transcranial direct current stimulation (tDCS) to the rIPL as a symptom provocation method in 22 healthy participants in a randomized, double-blind, crossover study, prior to two recordings of cerebral blood flow (CBF). In between, we applied a threat-of-shock paradigm with three conditions: unpredictable (U), predictable (P), or no electric shocks (N). We hypothesized increased anxiety under U, but not under P or N. Furthermore, we expected reduced CBF in the rIPL after tDCS compared to sham. As predicted, anxiety was higher in the U than the P and N conditions, and active tDCS augmented this effect. While tDCS did not alter CBF in the rIPL, it did attenuate the observed increase in brain regions that typically increase activation as a response to anxiety. These findings suggest that the rIPL moderates sustained anxiety as a gateway to brain regions crucial in anxiety. Alternatively, anodal tDCS over the left orbitofrontal cortex (lOFC) may have increased anxiety through disruption of OFC-amygdala interactions.

Diagnosis of epilepsy after a first unprovoked seizure is possible according to the guidelines by the International League Against Epilepsy, if the risk recurrence of a second unprovoked seizure is exceeding 60%. However, this cutoff constitutes only a proxy depending on the patients’ history, magnetic resonance imaging (MRI), and electroencephalography (EEG) findings but nevertheless also from the treating neurologists’ individual experience. In a Switzerland-wide observational study, we aim to recruit patients that were admitted to the emergency department with the referral diagnosis of a first and unprovoked seizure. We make use of optimized MRI protocols to identify potential structural epileptogenic lesions, introduce new imaging-based markers of epileptogenecity, and use most recent postprocessing methods as automatic morphometry, spike map analysis, and functional connectivity. With these diagnostic tools, we aim to segregate patients that present with epileptic seizures versus mimicks and non-epileptic seizures and stratify for every finding in MRI and EEG its predictive value for a second unprovoked seizure. These findings shall support neurologists to calculate and not only estimate the seizure recurrence rate in future.