Whole brain pattern of iron accumulation in REM sleep behavior disorder.

Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

Three-dimensional EPI with shot-selective CAIPIRIHANA for rapid high-resolution quantitative susceptibility mapping at 3 T.

PURPOSE: QSM provides insight into healthy brain aging and neuropathologies such as multiple sclerosis (MS), traumatic brain injuries, brain tumors, and neurodegenerative diseases. Phase data for QSM are usually acquired from 3D gradient-echo (3D GRE) scans with long acquisition times that are detrimental to patient comfort and susceptible to patient motion. This is particularly true for scans requiring whole-brain coverage and submillimeter resolutions. In this work, we use a multishot 3D echo plannar imaging (3D EPI) sequence with shot-selective 2D CAIPIRIHANA to acquire high-resolution, whole-brain data for QSM with minimal distortion and blurring. METHODS: To test clinical viability, the 3D EPI sequence was used to image a cohort of MS patients at 1-mm isotropic resolution at 3 T. Additionally, 3D EPI data of healthy subjects were acquired at 1-mm, 0.78-mm, and 0.65-mm isotropic resolution with varying echo train lengths (ETLs) and compared with a reference 3D GRE acquisition. RESULTS: The appearance of the susceptibility maps and the susceptibility values for segmented regions of interest were comparable between 3D EPI and 3D GRE acquisitions for both healthy and MS participants. Additionally, all lesions visible in the MS patients on the 3D GRE susceptibility maps were also visible on the 3D EPI susceptibility maps. The interplay among acquisition time, resolution, echo train length, and the effect of distortion on the calculated susceptibility maps was investigated. CONCLUSION: We demonstrate that the 3D EPI sequence is capable of rapidly acquiring submillimeter resolutions and providing high-quality, clinically relevant susceptibility maps.

Predicting dynamic, motion-related changes in B0 field in the brain at a 7T MRI using a subject-specific fine-trained U-net.

PURPOSE: Subject movement during the MR examination is inevitable and causes not only image artifacts but also deteriorates the homogeneity of the main magnetic field (B0 ), which is a prerequisite for high quality data. Thus, characterization of changes to B0 , for example induced by patient movement, is important for MR applications that are prone to B0 inhomogeneities. METHODS: We propose a deep learning based method to predict such changes within the brain from the change of the head position to facilitate retrospective or even real-time correction. A 3D U-net was trained on in vivo gradient-echo brain 7T MRI data. The input consisted of B0 maps and anatomical images at an initial position, and anatomical images at a different head position (obtained by applying a rigid-body transformation on the initial anatomical image). The output consisted of B0 maps at the new head positions. We further fine-trained the network weights to each subject by measuring a limited number of head positions of the given subject, and trained the U-net with these data. RESULTS: Our approach was compared to established dynamic B0 field mapping via interleaved navigators, which suffer from limited spatial resolution and the need for undesirable sequence modifications. Qualitative and quantitative comparison showed similar performance between an interleaved navigator-equivalent method and proposed method. CONCLUSION: It is feasible to predict B0 maps from rigid subject movement and, when combined with external tracking hardware, this information could be used to improve the quality of MR acquisitions without the use of navigators.

Recommended implementation of quantitative susceptibility mapping for clinical research in the brain: A consensus of the ISMRM electro-magnetic tissue properties study group.

This article provides recommendations for implementing QSM for clinical brain research. It is a consensus of the International Society of Magnetic Resonance in Medicine, Electro-Magnetic Tissue Properties Study Group. While QSM technical development continues to advance rapidly, the current QSM methods have been demonstrated to be repeatable and reproducible for generating quantitative tissue magnetic susceptibility maps in the brain. However, the many QSM approaches available have generated a need in the neuroimaging community for guidelines on implementation. This article outlines considerations and implementation recommendations for QSM data acquisition, processing, analysis, and publication. We recommend that data be acquired using a monopolar 3D multi-echo gradient echo (GRE) sequence and that phase images be saved and exported in Digital Imaging and Communications in Medicine (DICOM) format and unwrapped using an exact unwrapping approach. Multi-echo images should be combined before background field removal, and a brain mask created using a brain extraction tool with the incorporation of phase-quality-based masking. Background fields within the brain mask should be removed using a technique based on SHARP or PDF, and the optimization approach to dipole inversion should be employed with a sparsity-based regularization. Susceptibility values should be measured relative to a specified reference, including the common reference region of the whole brain as a region of interest in the analysis. The minimum acquisition and processing details required when reporting QSM results are also provided. These recommendations should facilitate clinical QSM research and promote harmonized data acquisition, analysis, and reporting.

Super-resolution QSM in little or no additional time for imaging (NATIve) using 2D EPI imaging in 3 orthogonal planes.

Quantitative Susceptibility Mapping has the potential to provide additional insights into neurological diseases but is typically based on a quite long (5-10 min) 3D gradient-echo scan which is highly sensitive to motion. We propose an ultra-fast acquisition based on three orthogonal (sagittal, coronal and axial) 2D simultaneous multi-slice EPI scans with 1 mm in-plane resolution and 3 mm thick slices. Images in each orientation are corrected for susceptibility-related distortions and co-registered with an iterative non-linear Minimum Deformation Averaging (Volgenmodel) approach to generate a high SNR, super-resolution data set with an isotropic resolution of close to 1 mm. The net acquisition time is 3 times the volume acquisition time of EPI or about 12 s, but the three volumes could also replace "dummy scans" in fMRI, making it feasible to acquire QSM in little or No Additional Time for Imaging (NATIve). NATIve QSM values agreed well with reference 3D GRE QSM in the basal ganglia in healthy subjects. In patients with multiple sclerosis, there was also a good agreement between the susceptibility values within lesions and control ROIs and all lesions which could be seen on 3D GRE QSMs could also be visualized on NATIve QSMs. The approach is faster than conventional 3D GRE by a factor of 25-50 and faster than 3D EPI by a factor of 3-5. As a 2D technique, NATIve QSM was shown to be much more robust to motion than the 3D GRE and 3D EPI, opening up the possibility of studying neurological diseases involving iron accumulation and demyelination in patients who find it difficult to lie still for long enough to acquire QSM data with conventional methods.

Unsupervised physiological noise correction of functional magnetic resonance imaging data using phase and magnitude information (PREPAIR).

Of the sources of noise affecting blood oxygen level-dependent functional magnetic resonance imaging (fMRI), respiration and cardiac fluctuations are responsible for the largest part of the variance, particularly at high and ultrahigh field. Existing approaches to removing physiological noise either use external recordings, which can be unwieldy and unreliable, or attempt to identify physiological noise from the magnitude fMRI data. Data-driven approaches are limited by sensitivity, temporal aliasing, and the need for user interaction. In the light of the sensitivity of the phase of the MR signal to local changes in the field stemming from physiological processes, we have developed an unsupervised physiological noise correction method using the information carried in the phase and the magnitude of echo-planar imaging data. Our technique, Physiological Regressor Estimation from Phase and mAgnItude, sub-tR (PREPAIR) derives time series signals sampled at the slice TR from both phase and magnitude images. It allows physiological noise to be captured without aliasing, and efficiently removes other sources of signal fluctuations not related to physiology, prior to regressor estimation. We demonstrate that the physiological signal time courses identified with PREPAIR agree well with those from external devices and retrieve challenging cardiac dynamics. The removal of physiological noise was as effective as that achieved with the most used approach based on external recordings, RETROICOR. In comparison with widely used recording-free physiological noise correction tools-PESTICA and FIX, both performed in unsupervised mode-PREPAIR removed significantly more respiratory and cardiac noise than PESTICA, and achieved a larger increase in temporal signal-to-noise-ratio at both 3 and 7 T.

Improved dynamic distortion correction for fMRI using single-echo EPI and a readout-reversed first image (REFILL).

The boundaries between tissues with different magnetic susceptibilities generate inhomogeneities in the main magnetic field which change over time due to motion, respiration and system instabilities. The dynamically changing field can be measured from the phase of the fMRI data and corrected. However, methods for doing so need multi-echo data, time-consuming reference scans and/or involve error-prone processing steps, such as phase unwrapping, which are difficult to implement robustly on the MRI host. The improved dynamic distortion correction method we propose is based on the phase of the single-echo EPI data acquired for fMRI, phase offsets calculated from a triple-echo, bipolar reference scan of circa 3-10 s duration using a method which avoids the need for phase unwrapping and an additional correction derived from one EPI volume in which the readout direction is reversed. This Reverse-Encoded First Image and Low resoLution reference scan (REFILL) approach is shown to accurately measure B0 as it changes due to shim, motion and respiration, even with large dynamic changes to the field at 7 T, where it led to a > 20% increase in time-series signal to noise ratio compared to data corrected with the classic static approach. fMRI results from REFILL-corrected data were free of stimulus-correlated distortion artefacts seen when data were corrected with static field mapping. The method is insensitive to shim changes and eddy current differences between the reference scan and the fMRI time series, and employs calculation steps that are simple and robust, allowing most data processing to be performed in real time on the scanner image reconstruction computer. These improvements make it feasible to routinely perform dynamic distortion correction in fMRI.

Unusual clinical spectra of childhood severe malaria during malaria epidemic in eastern Uganda: a prospective study.

BACKGROUND: In sub-Saharan Africa (SSA), malaria remains a public health problem despite recent reports of declining incidence. Severe malaria is a multiorgan disease with wide-ranging clinical spectra and outcomes that have been reported to vary by age, geographical location, transmission intensity over time. There are reports of recent malaria epidemics or resurgences, but few data, if any, focus on the clinical spectrum of severe malaria during epidemics. This describes the clinical spectrum and outcomes of childhood severe malaria during the disease epidemic in Eastern Uganda. METHODS: This prospective cohort study from October 1, 2021, to September 7, 2022, was nested within the 'Malaria Epidemiological, Pathophysiological and Intervention studies in Highly Endemic Eastern Uganda' (TMA2016SF-1514-MEPIE Study) at Mbale Regional Referral Hospital, Uganda. Children aged 60 days to 12 years who at admission tested positive for malaria and fulfilled the clinical WHO criteria for surveillance of severe malaria were enrolled on the study. Follow-up was performed until day 28. Data were collected using a customized proforma on social demographic characteristics, clinical presentation, treatment, and outcomes. Laboratory analyses included complete blood counts, malaria RDT (SD BIOLINE Malaria Ag P.f/Pan, Ref. 05FK60-40-1) and blood slide, lactate, glucose, blood gases and electrolytes. In addition, urinalysis using dipsticks (Multistix® 10 SG, SIEMENS, Ref.2300) at the bedside was done. Data were analysed using STATA V15.0. The study had prior ethical approval. RESULTS: A total of 300 participants were recruited. The median age was 4.6 years, mean of 57.2 months and IQR of 44.5 months. Many children, 164/300 (54.7%) were under 5 years, and 171/300 (57.0%) were males. The common clinical features were prostration 236/300 (78.7%), jaundice in 205/300 (68.3%), severe malarial anaemia in 158/300 (52.7%), black water fever 158/300 (52.7%) and multiple convulsions 51/300 (17.0%), impaired consciousness 50/300(16.0%), acidosis 41/300(13.7%), respiratory distress 26/300(6.7%) and coma in 18/300(6.0%). Prolonged hospitalization was found in 56/251 (22.3%) and was associated with acidosis, P = 0.041. The overall mortality was 19/300 (6.3%). Day 28 follow-up was achieved in 247/300 (82.3%). CONCLUSION: During the malaria epidemic in Eastern Uganda, severe malaria affected much older children and the spectrum had more of prostration, jaundice severe malarial anaemia, black water fever and multiple convulsions with less of earlier reported respiratory distress and cerebral malaria.

Pharmacological and metabolic parameters of [18F]flubrobenguane in clinical imaging populations.

BACKGROUND: Cardiac sympathetic nervous system molecular imaging has demonstrated prognostic value. Compared with meta-[11C]hydroxyephedrine, [18F]flubrobenguane (FBBG) facilitates reliable estimation of SNS innervation using similar analytical methods and possesses a more convenient physical half-life. The aim of this study was to evaluate pharmacokinetic and metabolic properties of FBBG in target clinical cohorts. METHODS: Blood sampling was performed on 20 participants concurrent to FBBG PET imaging (healthy = NORM, non-ischemic cardiomyopathy = NICM, ischemic cardiomyopathy = ICM, post-traumatic stress disorder = PTSD). Image-derived blood time-activity curves were transformed to plasma input functions using cohort-specific corrections for plasma protein binding, plasma-to-whole blood distribution, and metabolism. RESULTS: The plasma-to-whole blood ratio was 0.78 ± 0.06 for NORM, 0.64 ± 0.06 for PTSD and 0.60 ± 0.14 for (N)ICM after 20 minutes. 22 ± 4% of FBBG was bound to plasma proteins. Metabolism of FBBG in (N)ICM was delayed, with a parent fraction of 0.71 ± 0.05 at 10 minutes post-injection compared to 0.53 ± 0.03 for PTSD/NORM. While there were variations in metabolic rate, metabolite-corrected plasma input functions were similar across all cohorts. CONCLUSIONS: Rapid plasma clearance of FBBG limits the impact of disease-specific corrections of the blood input function for tracer kinetic modeling.

Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy.

BACKGROUND: Surgical resection followed by chemo-radiation postpones glioblastoma (GBM) progression and extends patient survival, but these tumours eventually recur. Multimodal treatment plans combining intraoperative techniques that maximise tumour excision with therapies aiming to remodel the immunologically cold GBM microenvironment could improve patients' outcomes. Herein, we report that targeted photoimmunotherapy (PIT) not only helps to define tumour location and margins but additionally promotes activation of anti-GBM T cell response. METHODS: EGFR-specific affibody molecule (ZEGFR:03115) was conjugated to IR700. The response to ZEGFR:03115-IR700-PIT was investigated in vitro and in vivo in GBM cell lines and xenograft model. To determine the tumour-specific immune response post-PIT, a syngeneic GBM model was used. RESULTS: In vitro findings confirmed the ability of ZEGFR:03115-IR700 to produce reactive oxygen species upon light irradiation. ZEGFR:03115-IR700-PIT promoted immunogenic cell death that triggered the release of damage-associated molecular patterns (DAMPs) (calreticulin, ATP, HSP70/90, and HMGB1) into the medium, leading to dendritic cell maturation. In vivo, therapeutic response to light-activated conjugate was observed in brain tumours as early as 1 h post-irradiation. Staining of the brain sections showed reduced cell proliferation, tumour necrosis, and microhaemorrhage within PIT-treated tumours that corroborated MRI T2*w acquisitions. Additionally, enhanced immunological response post-PIT resulted in the attraction and activation of T cells in mice bearing murine GBM brain tumours. CONCLUSIONS: Our data underline the potential of ZEGFR:03115-IR700 to accurately visualise EGFR-positive brain tumours and to destroy tumour cells post-conjugate irradiation turning an immunosuppressive tumour environment into an immune-vulnerable one.

Double-blind, placebo-controlled evaluation of biorest liposomal alendronate in diabetic patients undergoing PCI: The BLADE-PCI trial.

BACKGROUND: Diabetes mellitus (DM) is an important predictor of neointimal hyperplasia (NIH) and adverse clinical outcomes after percutaneous coronary intervention (PCI). LABR-312, a novel intravenous formulation of liposomal alendronate, has been shown in animal models to decrease NIH at vascular injury sites and around stent struts. The aim of the Biorest Liposomal Alendronate Administration for Diabetic Patients Undergoing Drug-Eluting Stent Percutaneous Coronary Intervention trial was to assess the safety, effectiveness, and dose response of LABR-312 administered intravenously at the time of PCI withDES in reducing NIH as measured by optical coherence tomography postprocedure in patients with DM. METHODS: Patients with DM were randomized to a bolus infusion of LABR-312 vs placebo at the time of PCI. Dose escalation of LABR-312 in the study arm was given: 0.01 mg, 0.03 mg, and 0.08 mg. The primary endpoint was the in-stent %NIH volume at 9 months as measured by optical coherence tomography. RESULTS: From September 2016 to December 2017, 271 patients with DM undergoing PCI were enrolled; 136 patients were randomized to LABR-312 infusion and 135 patients were randomized to placebo. At 9-month follow-up, no difference was seen in the primary endpoint of %NIH between LABR-312 and placebo (13.3% ± 9.2 vs 14.6% ± 8.5, P = .35). No differences were present with the varying LABR-312 doses. Clinical outcomes at 9 months were similar between groups. CONCLUSIONS: Among patients with DM undergoing PCI with drug-eluting stents, a bolus of LABR-312 injected systematically at the time of intervention did not result in a lower rate in-stent %NIH volume at 9-month follow-up.

Quantitative susceptibility mapping of the head-and-neck using SMURF fat-water imaging with chemical shift and relaxation rate corrections.

PURPOSE: To address the challenges posed by fat-water chemical shift artifacts and relaxation rate discrepancies to quantitative susceptibility mapping (QSM) outside the brain, and to generate accurate susceptibility maps of the head-and-neck at 3 and 7 Tesla. METHODS: Simultaneous Multiple Resonance Frequency (SMURF) imaging was extended to 7 Tesla and used to acquire head-and-neck gradient echo images at both 3 and 7 Tesla. Separated fat and water images were corrected for Type 1 (displacement) and Type 2 (phase discrepancy) chemical shift artefacts, and for the bias resulting from differences in T1 and T2∗ relaxation rates, recombined and used as the basis for QSM. A novel phase signal-based masking approach was used to generate head-and-neck masks. RESULTS: SMURF generated well-separated fat and water images of the head-and-neck. Corrections for chemical shift artefacts and relaxation rate differences removed overestimation of the susceptibility values, blurring in the susceptibility maps, and the disproportionate influence of fat in mixed voxels. The resulting susceptibility maps showed high correspondence between the paramagnetic areas and the locations of fatty tissues and the susceptibility estimates were similar to literature values. The proposed masking approach was shown to provide a simple means of generating head-and-neck masks. CONCLUSION: Corrections for Type 1 and Type 2 chemical shift artefacts and for fat-water relaxation rate differences, mainly in T1 , were shown to be required for accurate susceptibility mapping of fatty-body regions. SMURF made it possible to apply these corrections and generate high-quality susceptibility maps of the entire head-and-neck at both 3 and 7 Tesla.

Phase-based masking for quantitative susceptibility mapping of the human brain at 9.4T.

PURPOSE: To develop improved tissue masks for QSM. METHODS: Masks including voxels at the brain surface were automatically generated from the magnitude alone (MM) or combined with test functions from the first (PG) or second (PB) derivative of the sign of the wrapped phase. Phase images at 3T and 9.4T were simulated at different TEs and used to generate a mask, PItoh , with between-voxel phase differences less than π. MM, PG, and PB were compared with PItoh . QSM were generated from 3D multi-echo gradient-echo data acquired at 9.4T (21 subjects aged: 20-56y), and from the QSM2016 challenge 3T data using different masks, unwrapping, background removal, and dipole inversion algorithms. QSM contrast was quantified using age-based iron concentrations. RESULTS: Close to air cavities, phase wraps became denser with increasing field and echo time, yielding increased values of the test functions. Compared with PItoh , PB had the highest Dice coefficient, while PG had the lowest and MM the highest percentage of voxels outside PItoh. Artifacts observed in QSM at 9.4T with MM were mitigated by stronger background filters but yielded a reduced QSM contrast. With PB, QSM contrast was greater and artifacts diminished. Similar results were obtained with challenge data, evidencing larger effects of mask close to air cavities. CONCLUSION: Automatic, phase-based masking founded on the second derivative of the sign of the wrapped phase, including cortical voxels at the brain surface, was able to mitigate artifacts and restore QSM contrast across cortical and subcortical brain regions.

QSMxT: Robust masking and artifact reduction for quantitative susceptibility mapping.

PURPOSE: Quantitative susceptibility mapping (QSM) estimates the spatial distribution of tissue magnetic susceptibilities from the phase of a gradient-echo signal. QSM algorithms require a signal mask to delineate regions with reliable phase for subsequent susceptibility estimation. Existing masking techniques used in QSM have limitations that introduce artifacts, exclude anatomical detail, and rely on parameter tuning and anatomical priors that narrow their application. Here, a robust masking and reconstruction procedure is presented to overcome these limitations and enable automated QSM processing. Moreover, this method is integrated within an open-source software framework: QSMxT. METHODS: A robust masking technique that automatically separates reliable from less reliable phase regions was developed and combined with a two-pass reconstruction procedure that operates on the separated sources before combination, extracting more information and suppressing streaking artifacts. RESULTS: Compared with standard masking and reconstruction procedures, the two-pass inversion reduces streaking artifacts caused by unreliable phase and high dynamic ranges of susceptibility sources. It is also robust across a range of acquisitions at 3 T in volunteers and phantoms, at 7 T in tumor patients, and in an in silico head phantom, with significant artifact and error reductions, greater anatomical detail, and minimal parameter tuning. CONCLUSION: The two-pass masking and reconstruction procedure separates reliable from less reliable phase regions, enabling a more accurate QSM reconstruction that mitigates artifacts, operates without anatomical priors, and requires minimal parameter tuning. The technique and its integration within QSMxT makes QSM processing more accessible and robust to streaking artifacts.

Complete revascularization in stable multivessel coronary artery disease: A real world analysis from the British Columbia Cardiac Registry.

BACKGROUND: More than half of patients undergoing percutaneous coronary intervention (PCI) have multivessel disease (MVD). The prognostic significance of PCI in stable patients has recently been debated, but little data exists about the potential benefit of complete revascularization (CR) in stable MVD. We investigated the prognostic benefit of CR in patients undergoing PCI for stable disease. METHODS: We compared CR versus incomplete revascularization (IR) in 8,436 patients with MVD. The primary outcome was all-cause mortality at 5 years. RESULTS: A total of 1,399 patients (17%) underwent CR during the index PCI procedure for stable disease. CR was associated with lower mortality (6.2 vs. 10.7%, p < .001) and lower repeat revascularization at 5 years (12.7 vs. 18.4%, p < .001). Multivariable-adjusted analyses indicated that CR was associated with lower mortality (HR = 0.73, 95% CI: 0.58-0.91, p = .005) and repeat revascularization at 5 years (HR = 0.78, 95% CI: 0.66-0.93, p = .005). These findings were also confirmed in propensity-matched cohorts. Subgroup analyses indicated that CR conferred survival in older patients, male patients, absence of renal disease, greater angina (CCS Class III-IV) and heart failure (NYHA Class III-IV) symptoms, and greater burden of coronary disease. In sensitivity analyses where patients with subsequent repeat revascularization events were excluded, CR remained a strong predictor for lower mortality (HR = 0.69, 95% CI: 0.54-0.89, p = .004). CONCLUSIONS: In this study of stable patients with MVD, CR was an independent predictor of long-term survival. This benefit was specifically seen in higher risk patient groups and indicates that CR may benefit selected stable patients with MVD.

Personal perspectives: having the time to observe the patient.

Being a medically qualified patient can be an unpleasant experience for a person who is used to making decisions. For the most part, this applies to the vast majority of doctors and other healthcare professionals. Becoming passive and surrendering the decision-making process to others is alien to the medical culture we were taught. However, when as a hospitalised medically qualified patient, one sees fellow patients in difficulty, or deteriorating clinically, unnoticed by medical staff, the question of whether it is ethical to intervene arises. I report my views on this as a largely passive, but still actively thinking patient.

The Impact of Pre-Procedural Renal Impairment on Outcomes Following Percutaneous Coronary Intervention: An Analysis of 45,287 Patients From the British Columbia Cardiac Registry.

BACKGROUND: Renal disease confers a strong independent risk for morbidity and mortality after percutaneous coronary intervention (PCI). We evaluated the relationship between baseline pre-procedural renal function and outcomes following PCI. METHODS: We examined 45,287 patients who underwent PCI in British Columbia. We evaluated all-cause mortality and target vessel revascularisation (TVR) at 2 years. Pre-procedural renal impairment was categorised by creatinine clearance (CrCl, mL/min): CrCl≥90 (n=14,876), 90>CrCl≥60 (n=10,219), 60>CrCl≥30 (n=14,876), 30>CrCl≥0 (n=2,594) and dialysis (n=579). RESULTS: Declining CrCl values less than 60 mL/min were progressively associated with greater mortality: 60>eGFR≥30 (HR=2.01, 95% CI 1.71-2.37, p<0.001); 30>eGFR≥0 (HR=4.10, 95% CI 3.39-4.95, p<0.001); and dialysis (HR=6.22, 95% CI 5.07-7.63, p<0.001). A reduction in eGFR was not associated with TVR in non-dialysis patients. However, dialysis was a strong independent predictor for TVR (HR=1.69, 95% CI 1.37-2.08, p<0.001). This was confirmed in propensity-matched analyses where, dialysis was strongly associated with TVR (HR=1.53, 95% CI 1.24-1.89, p<0.001). This association was consistently seen in stratified analyses for diabetic versus non-diabetic patients; stent length >30 mm versus <30 mm; stent diameter >3 mm versus <3 mm; and receipt of bare metal stents versus drug-eluting stents. CONCLUSIONS: This study indicates the association with declining renal function and mortality in patients undergoing PCI. Whilst renal disease was not associated with increased TVR in non-dialysis patients, dialysis-dependence was a strong independent predictor for increased TVR.

Time to re-envisage integrity among nurse leaders.

AIM: This paper highlights integrity as a central tenet in the journey of ethical leadership among nurse leaders and dialogue as a way of working within integrity. BACKGROUND: Nurse leaders play a critical role in ensuring ethically sound, safe patient care by supporting staff and fostering positive working environments. Although there is an abundance of literature on leadership, no universally accepted leadership theory exists. Hence, it can be difficult to apply leadership theory and principals to real-life clinical practice. EVALUATION: From the literature, it is evident that integrity is a crucial aspect of leadership. This paper proposes suggestions for nurturing integrity and fostering open and honest dialogue. KEY ISSUES: Globally, public health care is complex and evolving and effective nursing leadership is paramount to meet public health needs and support health care systems. CONCLUSION: This paper explores integrity with leadership, re-envisaging personal and professional integrity as a portal to authentic leadership, which has human relationships and dialogue at its core. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse leaders need support in guiding the nursing profession and promoting ethically sound patient care. The true nature of leadership is dialogue, and nurturing a culture of listening and openness at different levels within an organisation is crucial.

Improved susceptibility weighted imaging at ultra-high field using bipolar multi-echo acquisition and optimized image processing: CLEAR-SWI.

PURPOSE: Susceptibility Weighted Imaging (SWI) has become established in the clinical investigation of stroke, microbleeds, tumor vascularization, calcification and iron deposition, but suffers from a number of shortcomings and artefacts. The goal of this study was to reduce the sensitivity of SWI to strong B1 and B0 inhomogeneities at ultra-high field to generate homogeneous images with increased contrast and free of common artefacts. All steps in SWI processing have been addressed - coil combination, phase unwrapping, image combination over echoes, phase filtering and homogeneity correction - and applied to an efficient bipolar multi-echo acquisition to substantially improve the quality of SWI. PRINCIPAL RESULTS: Our findings regarding the optimal individual processing steps lead us to propose a Contrast-weighted, Laplace-unwrapped, bipolar multi-Echo, ASPIRE-combined, homogeneous, improved Resolution SWI, or CLEAR-SWI. CLEAR-SWI was compared to two other multi-echo SWI methods and standard, single-echo SWI with the same acquisition time at 7 T in 10 healthy volunteers and with single-echo SWI in 13 patients with brain tumors. CLEAR-SWI had improved contrast-to-noise and homogeneity, reduced signal dropout and was not compromised by the artefacts which affected standard SWI in 10 out of 13 cases close to tumors (as assessed by expert raters), as well as generating T2* maps and phase images which can be used for Quantitative Susceptibility Mapping. In a comparison with other multi-echo SWI methods, CLEAR-SWI had the fewest artefacts, highest SNR and generally higher contrast-to-noise. MAJOR CONCLUSIONS: CLEAR-SWI eliminates the artefacts common in standard, single-echo SWI, reduces signal dropouts and improves image homogeneity and contrast-to-noise. Applied clinically, in a study of brain tumor patients, CLEAR-SWI was free of the artefacts which affected standard, single-echo SWI.

The traveling heads 2.0: Multicenter reproducibility of quantitative imaging methods at 7 Tesla.

OBJECT: This study evaluates inter-site and intra-site reproducibility at ten different 7 T sites for quantitative brain imaging. MATERIAL AND METHODS: Two subjects - termed the "traveling heads" - were imaged at ten different 7 T sites with a harmonized quantitative brain MR imaging protocol. In conjunction with the system calibration, MP2RAGE, QSM, CEST and multi-parametric mapping/relaxometry were examined. RESULTS: Quantitative measurements with MP2RAGE showed very high reproducibility across sites and subjects, and errors were in concordance with previous results and other field strengths. QSM had high inter-site reproducibility for relevant subcortical volumes. CEST imaging revealed systematic differences between the sites, but reproducibility was comparable to results in the literature. Relaxometry had also very high agreement between sites, but due to the high sensitivity, differences caused by different applications of the B1 calibration of the two RF coil types used were observed. CONCLUSION: Our results show that quantitative brain imaging can be performed with high reproducibility at 7 T and with similar reliability as found at 3 T for multicenter studies of the supratentorial brain.