B1 mapping using an EPI-based double angle approach: A practical guide for correcting slice profile and B0 distortion effects.

PURPOSE: Aim of this study was to develop a reliable B1 mapping method for brain imaging based on vendor MR sequences available on clinical scanners. Correction procedures for B0 distortions and slice profile imperfections are proposed, together with a phantom experiment for deriving the approximate time-bandwidth-product (TBP) of the excitation pulse, which is usually not known for vendor sequences. METHODS: The double angle method was used, acquiring two gradient echo echo-planar imaging data sets with different excitation angles. A correction factor C (B1 , TBP, B0 ) was derived from simulations for converting double angle method signal quotients into bias-free B1 maps. In vitro and in vivo tests compare results with reference B1 maps based on an established in-house sequence. RESULTS: The simulation shows that C has a negligible B1 dependence, allowing for a polynomial approximation of C (TBP, B0 ). Signal quotients measured in a phantom experiment with known TBP reconfirm the simulation results. In vitro and in vivo B1 maps based on the proposed method, assuming TBP = 5.8 as derived from a phantom experiment, match closely the reference B1 maps. Analysis without B0 correction shows marked deviations in areas of distorted B0 , highlighting the importance of this correction. CONCLUSION: Double angle method-based B1 mapping was set up for vendor gradient echo-echo-planar imaging sequences, using a correction procedure for slice profile imperfections and B0 distortions. This will help to set up quantitative MRI studies on clinical scanners with release sequences, as the method does not require knowledge of the exact RF-pulse profiles or the use of in-house sequences.

A novel sequence to improve auditory functional MRI with variable silent delays.

PURPOSE: Auditory functional MRI (fMRI) often uses silent inter-volume delays for stimulus presentation. However, maintaining the steady-state of the magnetization usually requires constant delays. Here, a novel acquisition scheme dubbed "pre-Saturated EPI using Multiple delays in Steady-state" (SEPIMS) is proposed, using spin saturation at a fixed delay before each volume to maintain steady-state conditions, independent of previous spin history. This concept allows for variable inter-volume delays and thus for flexible stimulus design in auditory fMRI. The purpose was to compare the signal stability of SEPIMS and conventional sparse EPI (CS-EPI). METHODS: The saturation module comprises two non-selective adiabatic saturation pulses. The efficiency of the saturation and its effect on the SEPIMS signal stability is tested in vitro and in vivo. RESULTS: Data show that SEPIMS yields the same signal stability as CS-EPI, even for extreme variations between inter-volume delay durations. However, dual saturation pulses are required to achieve sufficiently high saturation efficiency in compartments with long T1 values. Importantly, spoiler gradient pulses after the EPI readout have to be optimized to avoid eddy-current-induced image distortions. CONCLUSION: The proposed SEPIMS sequence maintains high signal stability in the presence of variable inter-volume durations, thus allowing for flexible stimulus design.

A fast and novel method for amide proton transfer-chemical exchange saturation transfer multislice imaging.

Amide proton transfer-chemical exchange saturation transfer (APT-CEST) imaging provides important information for the diagnosis and monitoring of tumors. For such analysis, complete coverage of the brain is advantageous, especially when registration is performed with other magnetic resonance (MR) modalities, such as MR spectroscopy (MRS). However, the acquisition of Z-spectra across several slices via multislice imaging may be time-consuming. Therefore, in this paper, we present a new approach for fast multislice imaging, allowing us to acquire 16 slices per frequency offset within 8 s. The proposed fast CEST-EPI sequence employs a presaturation module, which drives the magnetization into the steady-state equilibrium for the first frequency offset. A second module, consisting of a single CEST pulse (for maintaining the steady-state) followed by an EPI acquisition, passes through a loop to acquire multiple slices and adjacent frequency offsets. Thus, the whole Z-spectrum can be recorded much faster than the conventional saturation scheme, which employs a presaturation for each single frequency offset. The validation of the CEST sequence parameters was performed by using the conventional saturation scheme. Subsequently, the proposed and a modified version of the conventional CEST sequence were compared in vitro on a phantom with different T1 times and in vivo on a brain tumor patient. No significant differences between both sequences could be found in vitro. The in vivo data yielded almost identical MTRasym contrasts for the white and gray matter as well as for tumor tissue. Our results show that the proposed fast CEST-EPI sequence allows for rapid data acquisition and provides similar CEST contrasts as the modified conventional scheme while reducing the scanning time by approximately 50%.

How stable is quantitative MRI? - Assessment of intra- and inter-scanner-model reproducibility using identical acquisition sequences and data analysis programs.

BACKGROUND: Quantitative MRI (qMRI) techniques allow assessing cerebral tissue properties. However, previous studies on the accuracy of quantitative T1 and T2 mapping reported a scanner model bias of up to 10% for T1 and up to 23% for T2. Such differences would render multi-centre qMRI studies difficult and raise fundamental questions about the general precision of qMRI. A problem in previous studies was that different methods were used for qMRI parameter mapping or for measuring the transmitted radio frequency field B1 which is critical for qMRI techniques requiring corrections for B1 non-uniformities. AIMS: The goal was to assess the intra- and inter-scanner reproducibility of qMRI data at 3 â€‹T, using two different scanner models from the same vendor with exactly the same multiparametric acquisition protocol. METHODS: Proton density (PD), T1, T2* and T2 mapping was performed on healthy subjects and on a phantom, performing each measurement twice for each of two scanner models. Although the scanners had different hardware and software versions, identical imaging sequences were used for PD, T1 and T2* mapping, adapting the codes of an existing protocol on the older system line by line to match the software version of the newer scanner. For T2-mapping, the respective manufacturer's sequence was used which depended on the software version. However, system-dependent corrections were carried out in this case. Reproducibility was assessed by average values in regions of interest. RESULTS: Mean scan-rescan variations were not exceeding 2.14%, with average values of 1.23% and 1.56% for the new and old system, respectively. Inter-scanner model deviations were not exceeding 5.21% with average values of about 2.2-3.8% for PD, 2.5-3.0% for T2*, 1.6-3.1% for T1 and 3.3-5.2% for T2. CONCLUSIONS: Provided that identical acquisition sequences are used, discrepancies between qMRI data acquired with different scanner models are low. The level of systematic differences reported in this work may help to interpret multi-centre data.

The pH sensitivity of APT-CEST using phosphorus spectroscopy as a reference method.

The pH value is a potential physiological marker for clinical diagnosis as it is altered in pathologies such as tumors. While intracellular pH can be measured noninvasively via phosphorus spectroscopy (31 P MRSI), Amide Proton Transfer-Chemical Exchange Saturation Transfer (APT-CEST) MRI has been suggested as an alternative method for pH quantification. To assess the suitability of APT-CEST contrast for pH quantification, two approaches (magnetization transfer ratio asymmetry [MTRasym ] and Lorentzian difference analysis [LDA]) for analyzing the Z-spectrum have been correlated with pH values obtained by 31 P MRSI. Fourteen patients with glioblastoma and 12 healthy controls were included. In contrast to MTRasym , the LDA is modeling the direct water saturation and the semi-solid magnetization transfer, allowing a separate evaluation of the aliphatic nuclear Overhauser effect and the APT-CEST. The results of our study show that the pH values obtained by 31 P MRSI correspond well with both methods describing the APT-CEST contrast. Two-sample t-test showed significant differences in MTRasym , LDA and pH obtained by 31 P MRSI for regions of interest in glioblastoma, contralateral control areas and normal appearing white matter (P < 0.001). A slightly improved correlation between the amide signal and pH was found after performing LDA (r = 0.78) compared with MTRasym (r = 0.70). While both methods can be used to monitor pH changes, the LDA approach appears to be better suited.

Improved signal-to-noise ratio in EPI sequences with highly asymmetric spin echo and highly asymmetric STEAM preparations (HASE-EPI and HASTEAM-EPI).

OBJECTIVE: Alternative versions of echo-planar imaging (EPI) sequences with standard spin echo (SE) or stimulated echo acquisition mode (STEAM) preparations are proposed, allowing for improved signal-to-noise ratio (SNR), especially in high-resolution imaging. The suitability of the proposed sequences, dubbed "highly asymmetric SE-EPI" (HASE-EPI) and "highly asymmetric STEAM-EPI" (HASTEAM-EPI), is tested in vivo, for anatomical imaging with [Formula: see text] weighting and diffusion-weighted imaging (DWI). MATERIALS AND METHODS: In HASE-EPI and HASTEAM-EPI, echo formation occurs prior to the EPI readout, rather than at k-space centre as in standard SE-EPI and STEAM-EPI. This allows for a constant preparation period, independent of the spatial resolution. The proposed sequences are compared to their standard counterparts, via simulations and experimentally via in vivo anatomical imaging and DWI. RESULTS: HASE-EPI and HASTEAM-EPI yield SNR improvements for large matrix sizes and fully sampled EPI readout. Simulations and in vivo results show a signal gain in HASE-EPI versus SE-EPI or HASTEAM-EPI versus STEAM-EPI for white and gray matter, particularly for higher spatial resolution with full readout in anatomical imaging and DWI. However, simulations also show that in the case of very long EPI-readout trains, HASE-EPI and HASTEAM-EPI are more prone to pixel broadening due to relaxation effects. DISCUSSION: In contrast to commonly used SE-EPI or STEAM-EPI, the proposed sequences facilitate the acquisition of anatomical imaging and DWI data with improved SNR, especially for full EPI readouts. However, the applicability of HASE-EPI and HASTEAM-EPI should be carefully assessed: while signal gains are less pronounced when using parallel imaging and/or reduced matrix sizes, there may be pixel broadening for very long EPI-readout trains.

Optimization of diffusion-weighted single-refocused spin-echo EPI by reducing eddy-current artifacts and shortening the echo time.

OBJECTIVE: The purpose of this work was to optimize the acquisition of diffusion-weighted (DW) single-refocused spin-echo (srSE) data without intrinsic eddy-current compensation (ECC) for an improved performance of ECC postprocessing. The rationale is that srSE sequences without ECC may yield shorter echo times (TE) and thus higher signal-to-noise ratios (SNR) than srSE or twice-refocused spin-echo (trSE) schemes with intrinsic ECC. MATERIALS AND METHODS: The proposed method employs dummy scans with DW gradients to drive eddy currents into a steady state before data acquisition. Parameters of the ECC postprocessing algorithm were also optimized. Simulations were performed to obtain minimum TE values for the proposed sequence and sequences with intrinsic ECC. Experimentally, the proposed method was compared with standard DW-trSE imaging, both in vitro and in vivo. RESULTS: Simulations showed substantially shorter TE for the proposed method than for methods with intrinsic ECC when using shortened echo readouts. Data of the proposed method showed a marked increase in SNR. A dummy scan duration of at least 1.5 s improved performance of the ECC postprocessing algorithm. CONCLUSION: Changes proposed for the DW-srSE sequence and for the parameter setting of the postprocessing ECC algorithm considerably reduced eddy-current artifacts and provided a higher SNR.

Quantitative in vivo T2 mapping using fast spin echo techniques - A linear correction procedure.

A method is presented for correcting the effects of stimulated and indirect echoes on quantitative T2 mapping data acquired with multiple spin echo techniques, such as turbo spin echo. In contrast to similar correction techniques proposed in the literature, the method does not require a priori knowledge of the radio frequency (RF) pulse profiles. In a first step, for the T2 mapping protocol under investigation, signal decay curves S(TE) are simulated for a range of different RF pulse profiles. The actual signal decay S(TE) is then measured on a phantom with known T2, so the approximate RF pulse profiles can be derived via comparison with the simulated decay curves. In a second step, with the RF pulses obtained from step one, signal decay curves S(TE) are simulated for different T2 values and fitted mono-exponentially, thus allowing to deduce the relationship between true T2 and the apparent T2 (T2app) values. Results show that this relationship is approximately linear, allowing for a direct correction of T2app maps. If the amplitude of the transmitted RF field (B1) does not exceed the nominal value by more than 10%, it is shown that a B1-independent correction of T2app maps yields sufficiently accurate results for T2. A B1-dependent version is also presented. The method is tested in vitro on a phantom with different T2 values and in vivo on healthy subjects.

Modelling the impacts of altered management practices, land use and climate changes on the water quality of the Millbrook catchment-reservoir system in South Australia.

Sustainable management of drinking water reservoirs requires taking into account the potential effects of their catchments' development. This study is an attempt to estimate the daily patterns of nutrients transport in the catchment - reservoir systems through the application of the ensemble of complementary models SWAT-SALMO. SWAT quantifies flow, nitrate and phosphate loadings originating in catchments before entering downstream reservoirs meanwhile SALMO determines phosphate, nitrate, and chlorophyll-a concentrations within the reservoirs. The study applies to the semi-arid Millbrook catchment-reservoir system that supplies drinking water to north-eastern suburbs of Adelaide, South Australia. The catchment hosts viti- and horticultural land uses. The warm-monomictic, mesotrophic reservoir is artificially aerated in summer. After validating the simulation results for both Millbrook catchment and reservoir, a comprehensive scenario analysis has been conducted to reveal cascading effects of altered management practices, land uses and climate conditions on water quality in the reservoir. Results suggest that the effect on reservoir condition in summer would be severe, most likely resulting in chlorophyll-a concentrations of greater than 40 µg/l if the artificial destratification was not applied from early summer. A 50% curbing of water diversion from an external pipeline to the catchment will slightly limit chlorophyll-a concentrations by 1.22% as an effect of reduced inflow phosphate loads. The simulation of prospective land use scenarios converting 50% of present pasture in the Millbrook catchment into residential and orchards areas indicates an increase of summer chlorophyll-a concentrations by 9.5-107.9%, respectively in the reservoir. Global warming scenarios based on the high emission simulated by SWAT-SALMO did result in earlier growth of chlorophyll-a but overall the effects on water quality in the Millbrook reservoir was not significant. However scenarios combining global warming and land use changes resulted in significant eutrophication effects in the reservoir, especially in the unmanaged condition with stratification in summer. This study has demonstrated that complementary model ensembles like SWAT-SALMO allow to comprehend more realistically cascading effects of distinct catchment processes on internal reservoir's processes, and facilitate integrated management scenarios.

Three-dimensional echo-planar cine imaging of cerebral blood supply using arterial spin labeling.

OBJECTIVE: Echo-planar imaging (EPI) with CYlindrical Center-out spatiaL Encoding (EPICYCLE) is introduced as a novel hybrid three-dimensional (3D) EPI technique. Its suitability for the tracking of a short bolus created by pseudo-continuous arterial spin labeling (pCASL) through the cerebral vasculature is demonstrated. MATERIALS AND METHODS: EPICYCLE acquires two-dimensional planes of k-space along center-out trajectories. These "spokes" are rotated from shot to shot about a common axis to encode a k-space cylinder. To track a bolus of labeled blood, the same subset of evenly distributed spokes is acquired in a cine fashion after a short period of pCASL. This process is repeated for all subsets to fill the whole 3D k-space of each time frame. RESULTS: The passage of short pCASL boluses through the vasculature of a 3D imaging slab was successfully imaged using EPICYCLE. By choosing suitable sequence parameters, the impact of slab excitation on the bolus shape could be minimized. Parametric maps of signal amplitude, transit time, and bolus width reflected typical features of blood transport in large vessels. CONCLUSION: The EPICYCLE technique was successfully applied to track a short bolus of labeled arterial blood during its passage through the cerebral vasculature.

Pott's Paraplegia in a 2 Years Female: A Rare Presentation at an Early Age.

Introduction: Potts disease is extrapulmonary skeletal tuberculosis mostly affecting the thoracolumbar spine. It destroys the disc space, adjacent vertebral bodies, and spinal elements, leading to cord compression and paraplegia. Methods: This is a case report study of a 29-month-old toddler who presented to our hospital with bilateral lower limb weakness. Results: On clinical, laboratory, and radiological examination, she was diagnosed with Pott's spine, started on antitubercular therapy, and planned for surgery in her follow-up. Conclusion: Tuberculosis of the spine is still prevalent in developing countries, mainly in children. Complications of the disease can be devastating because of its ability to cause bone destruction, spinal deformity, and paraplegia. So, in a tuberculosis-endemic region, clinical suspicion should be there for Potts disease when a child presents with paraplegia of the lower limbs. Children can develop tuberculosis which can spread to the spine despite vaccination. The prognosis of spinal tuberculosis is improved by early diagnosis and rapid intervention.

Cortical microstructural involvement in cerebral small vessel disease.

Background: In cerebral small vessel disease (CSVD), cortical atrophy occurs at a later stage compared to microstructural abnormalities and therefore cannot be used for monitoring short-term disease progression. We aimed to investigate whether cortical diffusion tensor imaging (DTI) and quantitative (q) magnetic resonance imaging (MRI) are able to detect early microstructural involvement of the cerebral cortex in CSVD. Materials and Methods: 33 CSVD patients without significant cortical or whole-brain atrophy and 16 healthy control subjects were included and underwent structural MRI, DTI and high-resolution qMRI with T2, T2* and T2' mapping at 3 T as well as comprehensive cognitive assessment. After tissue segmentation and reconstruction of the cortical boundaries with the Freesurfer software, DTI and qMRI parameters were saved as surface datasets and averaged across all vertices. Results: Cortical diffusivity and quantitative T2 values were significantly increased in patients compared to controls (p < 0.05). T2 values correlated significantly positively with white matter hyperintensity (WMH) volume (p < 0.01). Both cortical diffusivity and T2 showed significant negative associations with axonal damage to the white matter fiber tracts (p < 0.05). Conclusions: Cortical diffusivity and quantitative T2 mapping are suitable to detect microstructural involvement of the cerebral cortex in CSVD and represent promising imaging biomarkers for monitoring disease progression and effects of therapeutical interventions in clinical studies.

Impaired oxygen extraction and adaptation of intracellular energy metabolism in cerebral small vessel disease.

Background: We aimed to investigate whether combined phosphorous (31P) magnetic resonance spectroscopic imaging (MRSI) and quantitative T 2 ' mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pHi) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD). Materials and methods: 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3-dimensional 31P MRSI and oxygenation-sensitive quantitative T 2 ' mapping (1/ T 2 '  = 1/T2* - 1/T2) at 3 Tesla (T). PHi was measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative T 2 ' values were averaged across the entire white matter (WM). Furthermore, T 2 ' values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls. Results: Quantitative T 2 ' values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51 ± 16.94 vs. 138.19 ± 12.66 ms and 147.45 ± 18.14 vs. 137.99 ± 12.19 ms, p < 0.05). WM T 2 ' values correlated significantly with the WMH load (ρ=0.441, p = 0.006). Increased T 2 ' was significantly associated with more alkaline pHi (ρ=0.299, p < 0.05). Both T 2 ' and pHi were significantly positively correlated with vascular pulsatility in the distal carotid arteries (ρ=0.596, p = 0.001 and ρ=0.452, p = 0.016). Conclusions: This exploratory study found evidence of impaired cerebral OEF in SVD, which is associated with intracellular alkalosis as an adaptive mechanism. The employed techniques provide new insights into the pathophysiology of SVD with regard to disease-related consequences on the cellular metabolic state.

Qualitative and quantitative detectability of hypertrophic olivary degeneration in T2, FLAIR, PD, and DTI: A prospective MRI study.

Purpose: Hypertrophic olivary degeneration (HOD) is a pathology of the inferior olivary nucleus (ION) that occurs after injuries to the Guillain-Mollaret triangle (GMT). Lacking a diagnostic gold standard, diagnosis is usually based on T2 or FLAIR imaging and expert rating. To facilitate precise HOD diagnosis in future studies, we assessed the reliability of this rater-based approach and explored alternative, quantitative analysis. Methods: Patients who had suffered strokes in the GMT and a matched control group prospectively underwent an MRI examination including T2, FLAIR, and proton density (PD). Diffusion tensor imaging (DTI) was additionally performed in the patient group. The presence of HOD was assessed on FLAIR, T2, and PD separately by 3 blinded reviewers. Employing an easily reproducible segmentation approach, relative differences in intensity, fractional anisotropy (FA), and mean diffusivity (MD) between both IONs were calculated. Results: In total, 15 patients were included in this study. The interrater reliability was best for FLAIR, followed by T2 and PD (Fleiss κ = 0.87 / 0.77 / 0.65). The 3 raters diagnosed HOD in 38-46% (FLAIR), 40-47% (T2), and 53-67% (PD) of patients. False-positive findings in the control group were less frequent in T2 than in PD and FLAIR (2.2% / 8.9% / 6.7%). In 53% of patients, the intensity difference between both IONs on PD was significantly increased in comparison with the control group. These patients also showed significantly decreased FA and increased MD. Conclusion: While the rater-based approach yielded the best performance on T2 imaging, a quantitative, more sensitive HOD diagnosis based on ION intensities in PD and DTI imaging seems possible.

Anaesthesia for Antenatal Diagnosed Duodenal Atresia with Undiagnosed Persistent Pulmonary Hypertension of Neonate.

Conversion of fetal circulation to adult-type occurs immediately after birth but neonates with problems in the development of pulmonary vasculature are prone to revert back to fetal circulation. This phenomenon is known as flip-flop circulation which may be induced perioperatively and as such anesthesiologist are central to its management. We report a case of term neonate planned for repair of duodenal atresia that despite having no respiratory symptom preoperatively developed severe hypoxemia under anesthesia that was even unresponsive to 100% oxygen. The intraoperative hemodynamics of the neonate was managed along with supportive care successfully. A postoperative echocardiogram confirmed the evidence of persistent pulmonary hypertension of the newborn. Keywords: Duodenal atresia; flip flop circulation; neonates; persistent pulmonary hypertension of newborn.

Machine Learning Approach to Predict Positive Screening of Methicillin-Resistant Staphylococcus aureus During Mechanical Ventilation Using Synthetic Dataset From MIMIC-IV Database.

Background: Mechanically ventilated patients are susceptible to nosocomial infections such as ventilator-associated pneumonia. To treat ventilated patients with suspected infection, clinicians select appropriate antibiotics. However, decision-making regarding the use of antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) is challenging, because of the lack of evidence-supported criteria. This study aims to derive a machine learning model to predict MRSA as a possible pathogen responsible for infection in mechanically ventilated patients. Methods: Data were collected from the Medical Information Mart for Intensive Care (MIMIC)-IV database (an openly available database of patients treated at the Beth Israel Deaconess Medical Center in the period 2008-2019). Of 26,409 mechanically ventilated patients, 809 were screened for MRSA during the mechanical ventilation period and included in the study. The outcome was positivity to MRSA on screening, which was highly imbalanced in the dataset, with 93.9% positive outcomes. Therefore, after dividing the dataset into a training set (n = 566) and a test set (n = 243) for validation by stratified random sampling with a 7:3 allocation ratio, synthetic datasets with 50% positive outcomes were created by synthetic minority over-sampling for both sets individually (synthetic training set: n = 1,064; synthetic test set: n = 456). Using these synthetic datasets, we trained and validated an XGBoost machine learning model using 28 predictor variables for outcome prediction. Model performance was evaluated by area under the receiver operating characteristic (AUROC), sensitivity, specificity, and other statistical measurements. Feature importance was computed by the Gini method. Results: In validation, the XGBoost model demonstrated reliable outcome prediction with an AUROC value of 0.89 [95% confidence interval (CI): 0.83-0.95]. The model showed a high sensitivity of 0.98 [CI: 0.95-0.99], but a low specificity of 0.47 [CI: 0.41-0.54] and a positive predictive value of 0.65 [CI: 0.62-0.68]. Important predictor variables included admission from the emergency department, insertion of arterial lines, prior quinolone use, hemodialysis, and admission to a surgical intensive care unit. Conclusions: We were able to develop an effective machine learning model to predict positive MRSA screening during mechanical ventilation using synthetic datasets, thus encouraging further research to develop a clinically relevant machine learning model for antibiotics stewardship.

Multicenter Prospective Analysis of Hypertrophic Olivary Degeneration Following Infratentorial Stroke (HOD-IS): Evaluation of Disease Epidemiology, Clinical Presentation, and MR-Imaging Aspects.

Introduction: Ischemic and hemorrhagic strokes in the brainstem and cerebellum with injury to the functional loop of the Guillain-Mollaret triangle (GMT) can trigger a series of events that result in secondary trans-synaptic neurodegeneration of the inferior olivary nucleus. In an unknown percentage of patients, this leads to a condition called hypertrophic olivary degeneration (HOD). Characteristic clinical symptoms of HOD progress slowly over months and consist of a rhythmic palatal tremor, vertical pendular nystagmus, and Holmes tremor of the upper limbs. Diffusion Tensor Imaging (DTI) with tractography is a promising method to identify functional pathway lesions along the cerebello-thalamo-cortical connectivity and to generate a deeper understanding of the HOD pathophysiology. The incidence of HOD development following stroke and the timeline of clinical symptoms have not yet been determined in prospective studies-a prerequisite for the surveillance of patients at risk. Methods and Analysis: Patients with ischemic and hemorrhagic strokes in the brainstem and cerebellum with a topo-anatomical relation to the GMT are recruited within certified stroke units of the Interdisciplinary Neurovascular Network of the Rhine-Main. Matching lesions are identified using a predefined MRI template. Eligible patients are prospectively followed up and present at 4 and 8 months after the index event. During study visits, a clinical neurological examination and brain MRI, including high-resolution T2-, proton-density-weighted imaging, and DTI tractography, are performed. Fiberoptic endoscopic evaluation of swallowing is optional if palatal tremor is encountered. Study Outcomes: The primary endpoint of this prospective clinical multicenter study is to determine the frequency of radiological HOD development in patients with a posterior fossa stroke affecting the GMT at 8 months after the index event. Secondary endpoints are identification of (1) the timeline and relevance of clinical symptoms, (2) lesion localizations more prone to HOD occurrence, and (3) the best MR-imaging regimen for HOD identification. Additionally, (4) DTI tractography data are used to analyze individual pathway lesions. The aim is to contribute to the epidemiological and pathophysiological understanding of HOD and hereby facilitate future research on therapeutic and prophylactic measures. Clinical Trial Registration: HOD-IS is a registered trial at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020549.

Distribution of Cortical Diffusion Tensor Imaging Changes in Multiple Sclerosis.

PURPOSE: Diffuse cortical damage in relapsing-remitting multiple sclerosis (RRMS) is clinically relevant but cannot be directly assessed with conventional MRI. In this study, it was aimed to use diffusion tensor imaging (DTI) techniques with optimized intrinsic eddy current compensation to quantify and characterize cortical mean diffusivity (MD) and fractional anisotropy (FA) changes in RRMS and to analyze the distribution of these changes across the cortex. MATERIALS AND METHODS: Three-Tesla MRI acquisition, mapping of the MD providing information about the integrity of microstructural barriers and of the FA reflecting axonal density and surface-based analysis with Freesurfer were performed for 24 RRMS patients and 25 control subjects. RESULTS: Across the whole cortex, MD was increased in patients (p < 0.001), while surface-based analysis revealed focal cortical FA decreases. MD and FA changes were distributed inhomogeneously across the cortex, the MD increase being more widespread than the FA decrease. Cortical MD correlated with the Expanded Disability Status Scale (EDSS, r = 0.38, p = 0.03). CONCLUSION: Damage of microstructural barriers occurs inhomogeneously across the cortex in RRMS and might be spatially more widespread than axonal degeneration. The results and, in particular, the correlation with the clinical status indicate that DTI might be a promising technique for the monitoring of cortical damage under treatment in larger clinical studies.

A 14-year-old girl presenting with tuberculous intestinal perforation while in a temporary shelter after the 2015 earthquake in Nepal.

A 14-year-old Nepalese girl presented with fever, abdominal pain and vomiting. She was living with her family in a temporary settlement camp following the earthquake in Nepal in 2015. She had had abdominal pain for 2 months and fever for 1 month. Abdominal examination suggested acute peritonitis. At laparotomy, three ileal perforations were detected and histopathology demonstrated caseous granulomas. Her father had sputum-positive pulmonary tuberculosis. She was diagnosed with abdominal tuberculosis and responded well to anti-tuberculosis chemotherapy. Intestinal perforation is a rare complication of tuberculosis in children.

Future climate and land uses effects on flow and nutrient loads of a Mediterranean catchment in South Australia.

Mediterranean catchments experience already high seasonal variability alternating between dry and wet periods, and are more vulnerable to future climate and land use changes. Quantification of catchment response under future changes is particularly crucial for better water resources management. This study assessed the combined effects of future climate and land use changes on water yield, total nitrogen (TN) and total phosphorus (TP) loads of the Mediterranean Onkaparinga catchment in South Australia by means of the eco-hydrological model SWAT. Six different global climate models (GCMs) under two representative concentration pathways (RCPs) and a hypothetical land use change were used for future simulations. The climate models suggested a high degree of uncertainty, varying seasonally, in both flow and nutrient loads; however, a decreasing trend was observed. Average monthly TN and TP load decreased up to -55% and -56% respectively and were found to be dependent on flow magnitude. The annual and seasonal water yield and nutrient loads may only slightly be affected by envisaged land uses, but significantly altered by intermediate and high emission scenarios, predominantly during the spring season. The combined scenarios indicated the possibility of declining flow in future but nutrient enrichment in summer months, originating mainly from the land use scenario, that may elevate the risk of algal blooms in downstream drinking water reservoir. Hence, careful planning of future water resources in a Mediterranean catchment requires the assessment of combined effects of multiple climate models and land use scenarios on both water quantity and quality.