Investigation of alternative RF power limit control methods for 0.5T, 1.5T, and 3T parallel transmission cardiac imaging: A simulation study.

PURPOSE: To investigate safety and performance aspects of parallel-transmit (pTx) RF control-modes for a body coil at B 0 ≤ 3 T $$ {B}_0\le 3\mathrm{T} $$ . METHODS: Electromagnetic simulations of 11 human voxel models in cardiac imaging position were conducted for B 0 = 0.5 T $$ {B}_0=0.5\mathrm{T} $$ , 1.5 T $$ 1.5\mathrm{T} $$ and 3 T $$ 3\mathrm{T} $$ and a body coil with a configurable number of transmit channels (1, 2, 4, 8, 16). Three safety modes were considered: the 'SAR-controlled mode' (SCM), where specific absorption rate (SAR) is limited directly, a 'phase agnostic SAR-controlled mode' (PASCM), where phase information is neglected, and a 'power-controlled mode' (PCM), where the voltage amplitude for each channel is limited. For either mode, safety limits were established based on a set of 'anchor' simulations and then evaluated in 'target' simulations on previously unseen models. The comparison allowed to derive safety factors accounting for varying patient anatomies. All control modes were compared in terms of the B 1 + $$ {B}_1^{+} $$ amplitude and homogeneity they permit under their respective safety requirements. RESULTS: Large safety factors (approximately five) are needed if only one or two anchor models are investigated but they shrink with increasing number of anchors. The achievable B 1 + $$ {B}_1^{+} $$ is highest for SCM but this advantage is reduced when the safety factor is included. PCM appears to be more robust against variations of subjects. PASCM performance is mostly in between SCM and PCM. Compared to standard circularly polarized (CP) excitation, pTx offers minor B 1 + $$ {B}_1^{+} $$ improvements if local SAR limits are always enforced. CONCLUSION: PTx body coils can safely be used at B 0 ≤ 3 T $$ {B}_0\le 3\mathrm{T} $$ . Uncertainties in patient anatomy must be accounted for, however, by simulating many models.

Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease.

Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.

Multicenter evaluation of left ventricular assist device implantation with or without ECMO bridge in cardiogenic shock.

BACKGROUND: The efficacy of extracorporeal membrane oxygenation (ECMO) as a bridge to left ventricular assist device (LVAD) remains unclear, and recipients of the more contemporary HeartMate 3 (HM3) LVAD are not well represented in previous studies. We therefore undertook a multicenter, retrospective study of this population. METHODS AND RESULTS: INTERMACS 1 LVAD recipients from five U.S. centers were included. In-hospital and one-year outcomes were recorded. The primary outcome was the overall mortality hazard comparing ECMO versus non-ECMO patients by propensity-weighted survival analysis. Secondary outcomes included survival by LVAD type, as well as postoperative and one-year outcomes. One hundred and twenty-seven patients were included; 24 received ECMO as a bridge to LVAD. Mortality was higher in patients bridged with ECMO in the primary analysis (HR 3.22 [95%CI 1.06-9.77], p = 0.039). Right ventricular assist device was more common in the ECMO group (ECMO: 54.2% vs non-ECMO: 11.7%, p < 0.001). Ischemic stroke was higher at one year in the ECMO group (ECMO: 25.0% vs non-ECMO: 4.9%, p = 0.006). Among the study cohort, one-year mortality was lower in HM3 than in HeartMate II (HMII) or HeartWare HVAD (10.5% vs 46.9% vs 31.6%, respectively; p < 0.001) recipients. Pump thrombosis at one year was lower in HM3 than in HMII or HVAD (1.8% vs 16.1% vs 16.2%, respectively; p = 0.026) recipients. CONCLUSIONS: Higher mortality was observed with ECMO as a bridge to LVAD, likely due to higher acuity illness, yet acceptable one-year survival was seen compared with historical rates. The receipt of the HM3 was associated with improved survival compared with older generation devices.

Wirelessly interfacing sensor-equipped implants and MR scanners for improved safety and imaging.

PURPOSE: To investigate a novel reduced RF heating method for imaging in the presence of active implanted medical devices (AIMDs) which employs a sensor-equipped implant that provides wireless feedback. METHODS: The implant, consisting of a generator case and a lead, measures RF-induced E $$ E $$ -fields at the implant tip using a simple sensor in the generator case and transmits these values wirelessly to the MR scanner. Based on the sensor signal alone, parallel transmission (pTx) excitation vectors were calculated to suppress tip heating and maintain image quality. A sensor-based imaging metric was introduced to assess the image quality. The methodology was studied at 7T in testbed experiments, and at a 3T scanner in an ASTM phantom containing AIMDs instrumented with six realistic deep brain stimulation (DBS) lead configurations adapted from patients. RESULTS: The implant successfully measured RF-induced E $$ E $$ -fields (Pearson correlation coefficient squared [R2 ] = 0.93) and temperature rises (R2 = 0.95) at the implant tip. The implant acquired the relevant data needed to calculate the pTx excitation vectors and transmitted them wirelessly to the MR scanner within a single shot RF sequence (<60 ms). Temperature rises for six realistic DBS lead configurations were reduced to 0.03-0.14 K for heating suppression modes compared to 0.52-3.33 K for the worst-case heating, while imaging quality remained comparable (five of six lead imaging scores were ≥0.80/1.00) to conventional circular polarization (CP) images. CONCLUSION: Implants with sensors that can communicate with an MR scanner can substantially improve safety for patients in a fast and automated manner, easing the current burden for MR personnel.

Towards an integrated radiofrequency safety concept for implant carriers in MRI based on sensor-equipped implants and parallel transmission.

To protect implant carriers in MRI from excessive radiofrequency (RF) heating it has previously been suggested to assess that hazard via sensors on the implant. Other work recommended parallel transmission (pTx) to actively mitigate implant-related heating. Here, both ideas are integrated into one comprehensive safety concept where native pTx safety (without implant) is ensured by state-of-the-art field simulations and the implant-specific hazard is quantified in situ using physical sensors. The concept is demonstrated by electromagnetic simulations performed on a human voxel model with a simplified spinal-cord implant in an eight-channel pTx body coil at 3 T . To integrate implant and native safety, the sensor signal must be calibrated in terms of an established safety metric (e.g., specific absorption rate [SAR]). Virtual experiments show that E -field and implant-current sensors are well suited for this purpose, while temperature sensors require some caution, and B 1 probes are inadequate. Based on an implant sensor matrix Q s , constructed in situ from sensor readings, and precomputed native SAR limits, a vector space of safe RF excitations is determined where both global (native) and local (implant-related) safety requirements are satisfied. Within this safe-excitation subspace, the solution with the best image quality in terms of B 1 + magnitude and homogeneity is then found by a straightforward optimization algorithm. In the investigated example, the optimized pTx shim provides a 3-fold higher mean B 1 + magnitude compared with circularly polarized excitation for a maximum implant-related temperature increase ∆ T imp ≤ 1 K . To date, sensor-equipped implants interfaced to a pTx scanner exist as demonstrator items in research labs, but commercial devices are not yet within sight. This paper aims to demonstrate the significant benefits of such an approach and how this could impact implant-related RF safety in MRI. Today, the responsibility for safe implant scanning lies with the implant manufacturer and the MRI operator; within the sensor concept, the MRI manufacturer would assume much of the operator's current responsibility.

The impact of respiratory motion on electromagnetic fields and specific absorption rate in cardiac imaging at 7T.

PURPOSE: To present electromagnetic simulation setups for detailed analyses of respiration's impact on B 1 + $$ {B}_1^{+} $$ and E-fields, local specific absorption rate (SAR) and associated safety-limits for 7T cardiac imaging. METHODS: Finite-difference time-domain electromagnetic field simulations were performed at five respiratory states using a breathing body model and a 16-element 7T body transceiver RF-coil array. B 1 + $$ {B}_1^{+} $$ and SAR are analyzed for fixed and moving coil configurations. SAR variations are investigated using phase/amplitude shimming considering (i) a local SAR-controlled mode (here SAR calculations consider RF amplitudes and phases) and (ii) a channel-wise power-controlled mode (SAR boundary calculation is independent of the channels' phases, only dependent on the channels' maximum amplitude). RESULTS: Respiration-induced variations of both B 1 + $$ {B}_1^{+} $$ amplitude and phase are observed. The flip angle homogeneity depends on the respiratory state used for B 1 + $$ {B}_1^{+} $$ shimming; best results were achieved for shimming on inhale and exhale simultaneously ( | Δ C V | < 35 % $$ \mid \Delta CV\mid <35\% $$ ). The results reflect that respiration impacts position and amplitude of the local SAR maximum. With the local-SAR-control mode, a safety factor of up to 1.4 is needed to accommodate for respiratory variations while the power control mode appears respiration-robust when the coil moves with respiration (SAR peak decrease: 9% exhale→inhale). Instead, a spatially fixed coil setup yields higher SAR variations with respiration. CONCLUSION: Respiratory motion does not only affect the B 1 + $$ {B}_1^{+} $$ distribution and hence the image contrast, but also location and magnitude of the peak spatial SAR. Therefore, respiration effects may need to be included in safety analyses of RF coils applied to the human thorax.

Rapid safety assessment and mitigation of radiofrequency induced implant heating using small root mean square sensors and the sensor matrix Qs.

PURPOSE: Rapid detection and mitigation of radiofrequency (RF)-induced implant heating during MRI based on small and low-cost embedded sensors. THEORY AND METHODS: A diode and a thermistor are embedded at the tip of an elongated mock implant. RF-induced voltages or temperature change measured by these root mean square (RMS) sensors are used to construct the sensor Q-Matrix (QS ). Hazard prediction, monitoring and parallel transmit (pTx)-based mitigation using these sensors is demonstrated in benchtop measurements at 300 MHz and within a 3T MRI. RESULTS: QS acquisition and mitigation can be performed in <20 ms demonstrating real-time capability. The acquisitions can be performed using safe low powers (<3 W) due to the high reading precision of the diode (126 µV) and thermistor (26 µK). The orthogonal projection method used for pTx mitigation was able to reduce the induced signals and temperatures in all 155 investigated locations. Using the QS approach in a pTx capable 3T MRI with either a two-channel body coil or an eight-channel head coil, RF-induced heating was successfully assessed, monitored and mitigated while the image quality outside the implant region was preserved. CONCLUSION: Small (<1.5 mm3 ) and low-cost (<1 €) RMS sensors embedded in an implant can provide all relevant information to predict, monitor and mitigate RF-induced heating in implants, while preserving image quality. The proposed pTx-based QS approach is independent of simulations or in vitro testing and therefore complements these existing safety assessments.

Voxel-wise lesion mapping of restless legs syndrome in multiple sclerosis.

OBJECTIVE: Restless legs syndrome (RLS) is known to be associated with multiple sclerosis (MS) and may be caused by MS lesions in specific cerebral brain regions. Applying a voxel-wise lesion analysis, we tried to identify the contribution of cerebral MS lesions to RLS. METHODS: In this retrospective study, we established a cohort of people with MS with documented RLS and controls of people with MS without RLS matched disease severity. Diagnosis of MS and RLS was based on the current guidelines. The MS lesions were analyzed on T2-weighted magnetic resonance imaging scans (1.5 or 3 T). After manual delineation, lesion maps were converted into stereotaxic space. We generated a lesion overlap and performed a Liebermeister test with 4000 permutations to compare the absence or presence of RLS voxel-wise between patients with and without lesions in a given voxel. RESULTS: Forty of the patients with RLS and MS fulfilled the inclusion criteria. The voxel-wise analysis yielded associations between RLS and MS in the subcortex of the left gyrus precentralis. CONCLUSION: Our voxel-wise analysis shows associations in the subcortex of the left gyrus precentralis. Thus, our data suggests that a dysfunction of the efferent motor system due to cerebral lesions may contribute to the pathophysiology of RLS in MS.

Pilot tone-based motion correction for prospective respiratory compensated cardiac cine MRI.

PURPOSE: To evaluate prospective motion correction using the pilot tone (PT) as a quantitative respiratory motion signal with high temporal resolution for cardiac cine images during free breathing. METHODS: Before cine data acquisition, a short prescan was performed, calibrating the PT to the respiratory-induced heart motion using respiratory-resolved real-time images. The calibrated PT was then applied for nearly real-time prospective motion correction of cine MRI through slice tracking (ie, updating the slice position before every readout). Additionally, in-plane motion correction was performed retrospectively also based on the calibrated PT data. The proposed method was evaluated in a moving phantom and 10 healthy volunteers. RESULTS: The PT showed very good correlation to the phantom motion. In volunteer studies using a long-term scan over 7.96 ± 1.40 min, the mean absolute error between registered and predicted motion from the PT was 1.44 ± 0.46 mm in head-feet and 0.46 ± 0.07 mm in anterior-posterior direction. Irregular breathing could also be corrected well with the PT. The PT motion correction leads to a significant improvement of contrast-to-noise ratio by 68% (P ≤ .01) between blood pool and myocardium and sharpness of endocardium by 24% (P = .04) in comparison to uncorrected data. The image score, which refers to the cine image quality, has improved with the utilization of the proposed PT motion correction. CONCLUSION: The proposed approach provides respiratory motion-corrected cine images of the heart with improved image quality and a high scan efficiency using the PT. The PT is independent of the MR acquisition, making this a very flexible motion-correction approach.

MRI-Related Heating of Implants and Devices: A Review.

During an MRI scan, the radiofrequency field from the scanner's transmit coil, but also the switched gradient fields, induce currents in any conductive object in the bore. This makes any metallic medical implant an additional risk for an MRI patient, because those currents can heat up the surrounding tissues to dangerous levels. This is one of the reasons why implants are, until today, considered a contraindication for MRI; for example, by scanner manufacturers. Due to the increasing prevalence of medical implants in our aging societies, such general exclusion is no longer acceptable. Also, it should be no longer needed, because of a much-improved safety-assessment methodology, in particular in the field of numerical simulations. The present article reviews existing literature on implant-related heating effects in MRI. Concepts for risk assessment and quantification are presented and also some first attempts towards an active safety management and risk mitigation. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 5.

The anesthetic approach for endovascular recanalization therapy depends on the lesion site in acute ischemic stroke.

PURPOSE: Endovascular therapy (EVT) of large-vessel occlusion in acute ischemic stroke (AIS) may be performed in general anesthesia (GA) or conscious sedation (CS). We intended to determine the contribution of ischemic cerebral lesion sites on the physician's decision between GA and CS using voxel-based lesion symptom mapping (VLSM). METHODS: In a prospective local database, we sought patients with documented AIS and EVT. Age, stroke severity, lesion volume, vigilance, and aphasia scores were compared between EVT patients with GA and CS. The ischemic lesions were analyzed on CT or MRI scans and transformed into stereotaxic space. We determined the lesion overlap and assessed whether GA or CS is associated with specific cerebral lesion sites using the voxel-wise Liebermeister test. RESULTS: One hundred seventy-nine patients with AIS and EVT were included in the analysis. The VLSM analysis yielded associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas. Stroke severity and lesion volume were significantly higher in the GA group. The prevalence of aphasia and aphasia severity was significantly higher and parameters of vigilance lower in the GA group. CONCLUSIONS: The VLSM analysis showed associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas including the thalamus that are known to cause neurologic deficits, such as aphasia or compromised vigilance, in AIS-patients with EVT. Our data suggest that higher disability, clinical impairment due to neurological deficits like aphasia, or reduced alertness of affected patients may influence the physician's decision on using GA in EVT.

Comparison of a 100-pF Capacitor With a 12 906-Ω Resistor Using a Digital Impedance Bridge.

We tested a digital impedance bridge in a hybrid structure for comparison of a capacitor with a resistor where the impedance ratio was measured in two separate parts. The modulus of the impedance ratio was matched arbitrarily close to the input-to-output ratio, in magnitude, of a two-stage inductive voltage divider by adjusting the operating frequency of the bridge; the residual deviation between the two together with the phase factor of the impedance ratio was measured using a custom detection system based on a four-channel 24-bit digitizer. The ratio of the inductive voltage divider was calibrated, in situ, using a conventional four-arm bridge with two known capacitors. Fluctuations of the source voltages were largely removed through postprocessing of the digitized data, and the measurement results were limited by the digitizer error. We have achieved an overall bridge resolution and stability of 0.02 µF/F in 2 h for measuring a 100-pF capacitor relative to a 12 906-Ω resistor at 1233 Hz. The relative combined standard uncertainty (k = 1) is 0.13 µF/F, dominated by the digitizer error.

Parallel transmission medical implant safety testbed: Real-time mitigation of RF induced tip heating using time-domain E-field sensors.

PURPOSE: To implement a modular, flexible, open-source hardware configuration for parallel transmission (pTx) experiments on medical implant safety and to demonstrate real-time mitigation strategies for radio frequency (RF) induced implant heating based on sensor measurements. METHODS: The hardware comprises a home-built 8-channel pTx system (scalable to 32-channels), wideband power amplifiers and a positioning system with submillimeter precision. The orthogonal projection (OP) method is used to mitigate RF induced tip heating and to maintain sufficient B1+ for imaging. Experiments are performed at 297MHz and inside a clinical 3T MRI using 8-channel pTx RF coils, a guidewire substitute inside a phantom with attached thermistor and time-domain E-field probes. RESULTS: Repeatability and precision are ~3% for E-field measurements including guidewire repositioning, ~3% for temperature slopes and an ~6% root-mean-square deviation between B1+ measurements and simulations. Real-time pTx mitigation with the OP mode reduces the E-fields everywhere within the investigated area with a maximum reduction factor of 26 compared to the circularly polarized mode. Tip heating was measured with ~100 µK resolution and ~14 Hz sampling frequency and showed substantial reduction for the OP vs CP mode. CONCLUSION: The pTx medical implant safety testbed presents a much-needed flexible and modular hardware configuration for the in-vitro assessment of implant safety, covering all field strengths from 0.5-7 T. Sensor based real-time mitigation strategies utilizing pTx and the OP method allow to substantially reduce RF induced implant heating while maintaining sufficient image quality without the need for a priori knowledge based on simulations or in-vitro testing.

Voxel-wise lesion mapping of self-reported urinary incontinence in multiple sclerosis.

AIMS: Besides spinal lesions, urinary incontinence may be attributed to particular cerebral lesion sites in multiple sclerosis (MS) patients. We intended to determine the contribution of suprapontine lesions to urinary incontinence in MS using a voxel-wise lesion analysis. METHODS: In this retrospective study, we sought MS patients with documented urinary incontinence in a local database. We established a control group of MS-patients without documented urinary incontinence matched for gender, age, and disease severity. Patients with urinary incontinence due to local diseases of the urinary tract were excluded. The MS lesions were analyzed on T2-weighted magnetic resonance imaging scans (1.5 or 3T). After manual delineation and transformation into stereotaxic space, we determined the lesion overlap and compared the presence or absence of urinary incontinence voxel-wise between patients with and without lesions in a given voxel performing the Liebermeister test with 4000 permutations. RESULTS: A total of 56 patients with urinary incontinence and MS fulfilled the criteria and were included. The analysis yielded associations between urinary incontinence and MS in the frontal white matter, temporo-occipital, and parahippocampal regions. CONCLUSIONS: Our voxel-wise analysis indicated associations between self-reported urinary incontinence and lesions in the left frontal white matter and right parahippocampal region. Thus, our data suggest that dysfunction of supraspinal bladder control due to cerebral lesions may contribute to the pathophysiology of urinary incontinence in MS.

Angioedema in Stroke Patients With Thrombolysis.

Background and Purpose- Oral angioedema (OA) is a rare but life-threatening complication in patients with ischemic stroke receiving intravenous thrombolysis with r-tPA (recombinant tissue-type plasminogen activator). This study intended to determine associations between thrombolysis-related OA and ischemic stroke lesion sites using a voxel-wise lesion analysis. Methods- Prospective registry data were used to identify ischemic stroke patients with thrombolysis-related OA between 2002 and 2018. For the study registry, ethics approval was obtained by the Ethics Committee of the Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg (clinical registry registration: 377_17Bc). Ischemic stroke patients with thrombolysis treatment but without OA admitted in the years 2011 and 2012 comprised the control group. Ischemic lesions were manually outlined on magnetic resonance imaging (1.5T or 3T) or computed tomographic scans and transformed into stereotaxic space. We determined the lesion overlap and compared the absence or presence of OA voxel-wise between patients with and without lesions in a given voxel using the Liebermeister test. Stroke severity was rated using the National Institutes of Health Stroke Scale score, and blood pressure, heart rate, blood glucose levels, and body temperature were determined on admission. Results- Fifteen ischemic stroke patients with thrombolysis-related OA were identified. The voxel-wise analysis yielded associations between OA and ischemic lesions in the insulo-opercular region with a right hemispheric dominance. Mean blood pressure was significantly lower in patients with OA than in controls. Age, National Institutes of Health Stroke Scale scores, infarct volumes, heart rate, and blood glucose levels did not differ between patients with and without OA. Conclusions- The voxel-wise analysis linked thrombolysis-related OA to right insulo-opercular lesions. The lower blood pressure in patients with thrombolysis-related OA may reflect bradykinin effects causing vasodilatation and increasing vascular permeability.

Cerebral lesion correlates of sympathetic cardiovascular activation in multiple sclerosis.

Cardiovascular autonomic dysfunction is common in multiple sclerosis (MS) and contributes significantly to disability. We hypothesized that cerebral MS-lesions in specific areas of the central autonomic network might account for imbalance of the sympathetic and parasympathetic cardiovascular modulation. Therefore, we used voxel-based lesion symptom mapping (VLSM) to determine associations between cardiovascular autonomic dysfunction and cerebral MS-related lesion sites. In 74 MS-patients (mean age 37.0 ± 10.5 years), we recorded electrocardiographic RR-intervals and systolic and diastolic blood pressure. Using trigonometric regressive spectral analysis, we assessed low (0.04-0.15 Hz) and high (0.15-0.5 Hz) frequency RR-interval-and blood pressure-oscillations and determined parasympathetically mediated RR-interval-high-frequency modulation, mainly sympathetically mediated RR-interval-low-frequency modulation, sympathetically mediated blood pressure-low-frequency modulation, and the ratios of sympathetic and parasympathetic RR-interval-modulation as an index of sympathetic-parasympathetic balance. Cerebral MS-lesions were analyzed on imaging scans. We performed a VLSM-analysis correlating parameters of autonomic dysfunction with cerebral MS-lesion sites. The VLSM-analysis showed associations between increased RR-interval low-frequency/high-frequency ratios and lesions most prominently in the left insular, hippocampal, and right frontal inferior opercular region, and a smaller lesion cluster in the right middle cerebellar peduncle. Increased blood pressure-low-frequency powers were associated with lesions primarily in the right posterior parietal white matter and again left insular region. Our data indicate associations between a shift of cardiovascular sympathetic-parasympathetic balance toward increased sympathetic modulation and left insular and hippocampal lesions, areas of the central autonomic network. The VLSM-analysis further distinguished between right inferior fronto-opercular lesions disinhibiting cardiac sympathetic activation and right posterior parietal lesions increasing sympathetic blood pressure modulation.

Transient naming deficits associated with insular lesions in a patient with encephalitis.

We describe a patient with acute herpes simplex encephalitis with left-hemispheric hippocampal, parahippocampal and insular lesions. Although prototypic language areas were unaffected, the patient suffered from an inability to name objects or animals displayed on pictures. This deficit was transient and gradually disappeared 8 weeks after the initial diagnosis. Our findings are in line with a previous report showing similar deficits in a patient with a comparable lesion pattern and support the hypothesis that left insular lesions can produce severe naming deficits. Using FDG-PET we ruled out that functional deactivation in classical language areas account for the observed naming deficits.

Supratentorial lesions contribute to trigeminal neuralgia in multiple sclerosis.

Background It has been proposed that multiple sclerosis lesions afflicting the pontine trigeminal afferents contribute to trigeminal neuralgia in multiple sclerosis. So far, there are no imaging studies that have evaluated interactions between supratentorial lesions and trigeminal neuralgia in multiple sclerosis patients. Methods We conducted a retrospective study and sought multiple sclerosis patients with trigeminal neuralgia and controls in a local database. Multiple sclerosis lesions were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed a voxel-wise subtraction analysis. Secondly, we conducted a voxel-wise non-parametric analysis using the Liebermeister test. Results From 12,210 multiple sclerosis patient records screened, we identified 41 patients with trigeminal neuralgia. The voxel-wise subtraction analysis yielded associations between trigeminal neuralgia and multiple sclerosis lesions in the pontine trigeminal afferents, as well as larger supratentorial lesion clusters in the contralateral insula and hippocampus. The non-parametric statistical analysis using the Liebermeister test yielded similar areas to be associated with multiple sclerosis-related trigeminal neuralgia. Conclusions Our study confirms previous data on associations between multiple sclerosis-related trigeminal neuralgia and pontine lesions, and showed for the first time an association with lesions in the insular region, a region involved in pain processing and endogenous pain modulation.

Lesion mapping of stroke-related erectile dysfunction.

Acute ischaemic stroke in brain areas contributing to male sexual function may impair erectile function depending on the lesion site. This study intended to determine associations between stroke-related erectile dysfunction and cerebral ischaemic lesion sites using voxel-based lesion mapping. In 52 males (mean age 60.5 ± 10.5 years) with first-ever ischaemic strokes, we assessed erectile function after and retrospectively 3 months prior to the stroke using scores of the 5-item International Index of Erectile Function-5 questionnaire. We assessed cardiovascular risk factors and determined clinical stroke severity and infarct volumes as well as total brain volume by neuroimaging. We calculated correlations between patient age, clinical stroke severity, infarct volumes as well as brain volumes and the difference between erectile dysfunction scores before and after stroke. Moreover, we compared patient age, prevalence of cardiovascular risk factors, clinical stroke severity, infarct volumes and brain volumes of patients with unchanged and deteriorated erectile function after stroke. The infarcts were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed subtraction analyses of lesions. In a voxel-based lesion analysis, the difference between erectile dysfunction scores before and after stroke was correlated with the lesion site using t-test statistics. Finally, we conducted a region of interest-based multivariate linear regression analysis that was adjusted for potential confounding factors including patient age, clinical stroke severity, imaging modality, lesion size and brain volume. In 32 patients (61.5%) erectile dysfunction scores declined after the stroke and therefore had stroke-related erectile dysfunction. Deterioration of erectile dysfunction scores was not associated with patient age, clinical stroke severity, infarct volume, brain volume, and cardiovascular risk factors. The voxel-wise subtraction analysis showed associations between stroke-related erectile dysfunction and lesion sites in the right occipito-parietal cortex and thalamus, as well as in the left insula and adjacent temporo-parietal areas. Using voxel-wise t-test statistics, we showed associations between deterioration of erectile function and lesion sites in the right occipital and thalamic region, and the left parietal association area. The linear regression analysis showed that stroke-related erectile dysfunction remained associated with lesions of the right occipital and left parietal association areas after adjusting for confounding factors. In conclusion, our voxel-wise analysis indicates that deteriorating erectile function after stroke is associated with lesions in the right occipito-parietal and thalamic areas integrating visual and somatosensory information, as well as lesions in the left insular and adjacent parieto-temporal areas contributing to generating and mapping visceral arousal states.

Neuroanatomic Correlates of Female Sexual Dysfunction in Multiple Sclerosis.

OBJECTIVE: This study intended to determine associations between alterations of female sexual arousal as well as vaginal lubrication and the site of cerebral multiple sclerosis (MS) lesions. METHODS: In 44 women with MS (mean age: 36.5 ± 9.9 years), we assessed their medical history and evaluated sexual function using the Female Sexual Function Index scores for arousal and vaginal lubrication. We determined potential confounding factors of sexual dysfunction: age; disease duration; physical disability; depression; bladder or urinary dysfunction; and total volume of cerebral lesions. Arousal and lubrication scores were correlated with one another and with potential confounding factors. Cerebral MS lesions were recorded on imaging scans. A voxel-based lesion symptom mapping (VLSM) analysis adjusted for confounding variables was performed correlating cerebral sites of MS lesions with arousal and lubrication scores. RESULTS: Decreased arousal scores correlated with decreased lubrication scores; decreased lubrication scores were associated with bladder or urinary symptoms. Arousal and lubrication scores were not associated with any other variables. Multivariate VLSM analysis, including arousal and lubrication scores as covariables of interest, showed right occipital lesions associated with impaired arousal and left insular lesions associated with decreased lubrication. Impaired lubrication remained associated with left insular lesions after adjustment for bladder or urinary dysfunction. INTERPRETATION: Our data indicate that impaired female sexual arousal is associated with MS lesions in the occipital region, integrating visual information and modulating attention toward visual input. Impaired lubrication correlated with lesions in the left insular region, contributing to mapping and generating visceral arousal states. Ann Neurol 2016;80:490-498.