Which compartments of the optic nerve and its sheath are associated with intracranial pressure? An exploratory study.

BACKGROUND AND PURPOSE: The optic nerve sheath diameter (ONSD) is a commonly used estimate of intracranial pressure (ICP). The rationale behind this is that pressure changes in the cerebrospinal fluid affect the optic nerve subarachnoid space (ONSAS) thickness. Still, possible effects on other compartments of the optic nerve sheath (ONS) have not been studied. This is the first study ever to analyze all measurable compartments of the ONS for associations with elevated ICP. METHODS: We measured changes in ICP and changes in ONS compartments in 75 patients treated with invasive ICP monitoring at the Karolinska University Hospital. Associations between changes in ICP and changes in ONS compartments were estimated with generalized estimating equations. The potential to identify elevated ICP was assessed with the area under the receiver operating characteristic curve (AUROC) for ONS compartments associated with ICP changes. RESULTS: Both ONSAS and perioptic dura mater thickness were significantly associated with changes in ICP in multivariable modeling. ONSAS was the only compartment that independently predicted changes in ICP, with an AUROC of 0.69 for predicting ICP increase. Still, both the perioptic dura mater thickness and the optic nerve diameter added value in predicting ICP changes in multivariable modeling. CONCLUSIONS: The results from this study challenge the current understanding of the mechanism behind the association between ICP and ONSD. Contrary to the common opinion that ONSAS is the only affected compartment, this study shows a more complex picture. It suggests that all ONS compartments may add value in predicting changes in ICP.

Performance of Subcutaneous Continuous Glucose Monitoring in Adult Critically Ill Patients Receiving Vasopressor Therapy.

Background: Subcutaneous continuous glucose monitoring (CGM) may facilitate glucose control in the ICU. We aimed to assess the accuracy of CGM (Dexcom G6) against arterial blood glucose (ABG) in adult critically ill patients receiving intravenous insulin infusion and vasopressor therapy. We also aimed to assess feasibility and tolerability of CGM in this setting. Methods: We included ICU patients receiving mechanical ventilation, insulin, and vasopressor therapy. Numerical accuracy was assessed by the mean absolute relative difference (MARD), overall, across arterial glucose strata, over different noradrenaline equivalent infusion rates, and over time since CGM start. MARD <14% was considered acceptable. Clinical accuracy was assessed using Clarke Error Grid (CEG) analysis. Feasibility outcome included number and duration of interrupted sensor readings due to signal loss. Tolerability outcome included skin reactions related to sensor insertion or sensor adhesives. Results: We obtained 2946 paired samples from 40 patients (18 with type 2 diabetes) receiving a median (IQR) maximum noradrenaline equivalent infusion rate of 0.18 (0.08-0.33) µg/kg/min during CGM. Overall, MARD was 12.7% (95% CI 10.7-15.3), and 99.8% of CGM readings were within CEG zones A and B. MARD values ≥14% were observed when ABG was outside target range (6-10 mmol/L [108-180 mg/dL]) and with noradrenaline equivalent infusion rates above 0.10 µg/kg/min. Accuracy improved with time after CGM start, reaching MARD values <14% after 36 h. We observed four episodes of interrupted sensor readings due to signal loss, ranging from 5 to 20 min. We observed no skin reaction related to sensor insertion or sensor adhesives. Conclusions: In our ICU cohort of patients receiving vasopressor infusion, subcutaneous CGM demonstrated acceptable overall numerical and clinical accuracy. However, suboptimal accuracy may occur outside glucose ranges of 6-10 mmol/L (108-180 mg/dL), during higher dose vasopressor infusion, and during the first 36 h after CGM start.

Sex differences in the diagnostic value of optic nerve sheath diameter for assessing intracranial pressure.

The optic nerve sheath diameter (ONSD) can predict elevated intracranial pressure (ICP) but it is not known whether diagnostic characteristics differ between men and women. This observational study was performed at the Karolinska University Hospital in Sweden to assess sex differences in diagnostic accuracy for ONSD. We included 139 patients (65 women), unconscious and/or sedated, with invasive ICP monitoring. Commonly used ONSD derived measurements and associated ICP measurements were collected. Linear regression analyses were performed with ICP as dependent variable and ONSD as independent variable. Area under the receiver operator characteristics curve (AUROC) analyses were performed with a threshold for elevated ICP ≥ 20 mmHg. Analyses were stratified by sex. Optimal cut-offs and diagnostic characteristics were estimated. The ONSD was associated with ICP in women. The AUROCs in women ranged from 0.70 to 0.83. In men, the ONSD was not associated with ICP and none of the AUROCs were significantly larger than 0.5. This study suggests that ONSD is a useful predictor of ICP in women but may not be so in men. If this finding is verified in further studies, this would call for a re-evaluation of the usage and interpretation of ONSD to estimate ICP.

Optic nerve sheath diameter in intracranial hypertension: Measurement external or internal of the dura mater?

BACKGROUND AND PURPOSE: Optic nerve sheath diameter (ONSD) is a promising metric to estimate intracranial pressure (ICP). There is no consensus whether ONSD should be measured external (ONSDext) or internal (ONSDint) of the dura mater. Expert opinion favors ONSDint, though without clear evidence to support this. Adjustments of ONSD for eye diameter (ED) and optic nerve diameter (OND) have been suggested to improve precision. We examined the diagnostic accuracy of ONSDext and ONSDint for estimating ICP, unadjusted as well as adjusted for ED and OND. METHODS: We performed an observational cohort study, measuring ONSDext and ONSDint in patients with invasive ICP monitoring at Karolinska University Hospital in Stockholm, Sweden. We used ONSDext and ONSDint unadjusted as well as adjusted for ED and for OND. We compared the area under the receiver operator characteristics curve (AUROC) for these methods. Thresholds for elevated ICP were set at ≥20 and ≥22 mmHg, respectively. RESULTS: We included 220 measurements from 100 patients. Median ONSDext and ONSDint were significantly different at 6.7 and 5.2 mm (p = .00). There was no significant difference in AUROC for predicting elevated ICP between ONSDext and ONSDint (.67 vs. .64, p = .31). Adjustment for ED yielded better diagnostic accuracy (AUROC, cutoff, sensitivity, specificity) for ONSDext/ED (.76, .29, .81, .62) and ONSDint/ED (.71, .24, .5, .89). CONCLUSIONS: ONSDext and ONSDint differ significantly and are not interchangeable. However, there were no significant differences in diagnostic accuracy between ONSDext and ONSDint. Adjustment for ED may improve diagnostic accuracy of ONSD.

Optic nerve sheath diameter is associated with outcome in severe Covid-19.

Neurological symptoms are common in Covid-19 and cerebral edema has been shown post-mortem. The mechanism behind this is unclear. Elevated intracranial pressure (ICP) has not been extensively studied in Covid-19. ICP can be estimated noninvasively with measurements of the optic nerve sheath diameter (ONSD). We performed a cohort study with ONSD ultrasound measurements in severe cases of Covid-19 at an intensive care unit (ICU). We measured ONSD with ultrasound in adults with severe Covid-19 in the ICU at Karolinska University Hospital in Sweden. Patients were classified as either having normal or elevated ONSD. We compared ICU length of stay (ICU-LOS) and 90 day mortality between the groups. 54 patients were included. 11 of these (20.4%) had elevated ONSD. Patients with elevated ONSD had 12 days longer ICU-LOS (95% CI 2 to 23 p = 0.03) and a risk ratio of 2.3 for ICU-LOS ≥ 30 days. There were no significant differences in baseline data or 90 day mortality between the groups. Elevated ONSD is common in severe Covid-19 and is associated with adverse outcome. This may be caused by elevated ICP. This is a clinically important finding that needs to be considered when deciding upon various treatment strategies.

Optic nerve sheath diameter measurement by ultrasound: Evaluation of a standardized protocol.

BACKGROUND AND PURPOSE: Treatment of elevated intracranial pressure (ICP) is central to neurocritical care, but not all patients are eligible for invasive ICP-monitoring. A promising noninvasive option is ultrasound measurement of the optic nerve sheath diameter (ONSD). However, meta-analyses of ONSD for elevated ICP show wide confidence intervals. This might be due to baseline variations, inter-rater variability, and varying measurement methods. No standardized protocol has been validated. Corrections for eyeball diameter (ED) and optic nerve diameter (OND) may compensate for baseline variations. We evaluated a protocol and compared two different measurement methods for ONSD ultrasound. METHODS: Two operators, blinded to each other's measurements, measured ONSD, ED, and OND twice in 20 patients. ONSD was measured with two different methods in use: internal (ONSDint) or external (ONSDext) of the dura mater. Intra-class correlation (ICC) was calculated for inter-rater and intra-rater reliability. RESULTS: ICCs for inter-rater reliability of ONSDext and ONSDint (95% confidence interval) were 0.96 (0.93, 0.98) and 0.88 (0.79, 0.94), respectively. ICCs for intra-rater reliability of ONSDext and ONSDint were 0.97 (0.94, 0.99) and 0.93 (0.87, 0.96), respectively. There was no significant bias or difference in intra-rater reliability between operators. CONCLUSIONS: ONSD can be measured with an excellent inter- and intra-rater reliability and low risk of inter-rater bias, when using this protocol. ONSDext yields a higher inter- and intra-rater reliability than ONSDint. Corrections for ED and OND can be performed reliably.

Postinjury Sepsis-Associations With Risk Factors, Impact on Clinical Course, and Mortality: A Retrospective Observational Study.

OBJECTIVES: Overall outcomes for trauma patients have improved over time. However, mortality for postinjury sepsis has been reported to be unchanged. Estimate incidence of and risk factors for sepsis in ICU patients after major trauma and the association between sepsis, mortality, and clinical course. DESIGN SETTING AND PATIENTS: ICU in a large urban trauma center in Sweden with a well-developed trauma system. Retrospective cohort study of trauma patients admitted to the ICU for more than 24 hours were included. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was 30-day mortality. Secondary outcomes were 1-year mortality and impact on clinical course. In total, 722 patients with a median Injury Severity Score of 26 (interquartile range, 18-38) were included. Incidence of sepsis was 22%. Septic patients had a four-fold increase in length of stay and need for organ supportive therapy. The overall 30-day mortality rate was 9.3%. After exclusion of early trauma-related deaths in the first 48 hours, the 30-day mortality rate was 6.7%. There was an association between sepsis and this adjusted 30-day mortality (day 3 odds ratio, 2.1 [95% CI, 1.1-3.9]; day 4 odds ratio, 3.1 [95% CI, 1.5-6.1]; day 5 odds ratio, 3.0 [95% CI, 1.4-6.2]). Septic patients had a 1-year mortality of 17.7% (nonseptic 11.0%). Development of sepsis was independently associated with age, spine and chest injury, shock, red cell transfusion, and positive blood alcohol concentration at admission. The risk of sepsis increased, in a dose-dependent manner, with the number of transfusions. CONCLUSIONS: Postinjury sepsis was associated with a complicated clinical course and with mortality after exclusion of early, trauma-related deaths.

Temporal patterns of organ dysfunction after severe trauma.

BACKGROUND: Understanding temporal patterns of organ dysfunction (OD) may aid early recognition of complications after trauma and assist timing and modality of treatment strategies. Our aim was to analyse and characterise temporal patterns of OD in intensive care unit-admitted trauma patients. METHODS: We used group-based trajectory modelling to identify temporal trajectories of OD after trauma. Modelling was based on the joint development of all six subdomains comprising the sequential organ failure assessment score measured daily during the first two weeks post trauma. Further, the time for trajectories to stabilise and transition to final group assignments were evaluated. RESULTS: Six-hundred and sixty patients were included in the final model. Median age was 40 years, and median ISS was 26 (IQR 17-38). We identified five distinct trajectories of OD. Group 1, mild OD (n = 300), median ISS of 20 (IQR 14-27), had an early resolution of OD and a low mortality. Group 2, moderate OD (n = 135), and group 3, severe OD (n = 87), were fairly similar in admission characteristics and initial OD but differed in subsequent OD trajectories, the latter experiencing an extended course and higher mortality. In group 3, 56% of the patients developed sepsis as compared with 19% in group 2. Group 4, extreme OD (n = 40), received most blood transfusions, had the highest proportion of shock at admission and a median ISS of 41 (IQR 29-50). They experienced significant and sustained OD affecting all organ systems and a 28-day mortality of 30%. Group 5, traumatic brain injury with OD (n = 98), had the highest mortality of 35% and the shortest time to death for non-survivors, median 3.5 (IQR 2.4-4.8) days. Groups 1 and 5 reached their final group assignment early, > 80% of the patients within 48 h. In contrast, groups 2 and 3 had a prolonged time to final group assignment. CONCLUSIONS: We identified five distinct trajectories of OD after severe trauma during the first two weeks post-trauma. Our findings underline the heterogeneous course after trauma and describe some potentially important clinical insights that are suggested by the groupings and temporal trajectories.

Comparison of the sepsis-2 and sepsis-3 definitions in severely injured trauma patients.

PURPOSE: To evaluate the performance of the new SOFA-based sepsis definition in trauma patients. MATERIALS AND METHODS: A single-centre, retrospective, observational study. Primary outcome was 30-day mortality including a censoring analysis for early deaths. The primary outcome was evaluated with logistic regression, receiver operating characteristics (ROC) curves and Kaplan-Meier survival analyses. RESULTS: 722 severely injured patients were included between 2007 and 2016. 315 patients fulfilled the sepsis-2 criteria and 148 fulfilled the sepsis-3 criteria during the first ten days in the ICU. The odds ratios for 30-day mortality were 0.7 (CI 0.4-1.2) for sepsis-2 and 1.5 (CI 0.8-2.6) for sepsis-3. When censoring patients dying at day 1, sepsis-3 became associated with 30-day mortality whereas sepsis-2 did not. This finding was persistent and enhanced through continuing day-by-day censoring of early deaths. The same pattern was seen for the ROC curves analyses, censoring of early deaths resulted in significant discriminatory properties for sepsis-3 but not for sepsis-2. CONCLUSIONS: The sepsis-3 definition identifies much fewer patients and is more strongly associated with adverse outcomes than the sepsis-2 definition. The sepsis-3 definition seems to be useful in the post trauma setting.

National Early Warning Score vs Rapid Response Team criteria-Prevalence, misclassification, and outcome.

PURPOSE: The purpose of this study was to examine the prevalence of deviating vital parameters in general ward patients using rapid response team (RRT) criteria and National Early Warning Score (NEWS), assess exam duration, correct calculation and classification of risk score as well as mortality and adverse events. METHODS: Point prevalence study of vital parameters according to NEWS and RRT criteria of all adult patients admitted to general wards at a Scandinavian university hospital with a mature RRT. PRIMARY OUTCOME: prevalence of at-risk patients fulfilling at least one RRT criteria, total NEWS of 7 or greater or a single NEWS parameter of 3 (red NEWS). SECONDARY OUTCOMES: mortality in-hospital and within 30 days or adverse events within 24 hours. RESULTS: We assessed 598 (75%) of 798 admitted patients and examiners captured a fulfilled RRT calling criterion in 50 patients (8.4%), 36 (6.0%) had NEWS ≥ 7, 34 with a red NEWS parameter. Red NEWS occurred in 112 patients (18.7%). Secondary outcomes were fulfilled in 49 patients (8.2%). Mortality overall was 6.5% within 30 days, 1.8% in hospital. In 134 patients (22.4%) the manual calculation of score for NEWS was incorrectly performed by examiner. CONCLUSION: Even with a mature RRT in place, we captured patients with failing physiology in general wards reflecting afferent limb failure. Manual calculation of NEWS is frequently incorrect, possibly leading to misclassification of patients at risk.

Anisotropic scattered data interpolation for pushbroom image rectification.

This paper deals with fast and accurate visualization of pushbroom image data from airborne and spaceborne platforms. A pushbroom sensor acquires images in a line-scanning fashion, and this results in scattered input data that need to be resampled onto a uniform grid for geometrically correct visualization. To this end, we model the anisotropic spatial dependence structure caused by the acquisition process. Several methods for scattered data interpolation are then adapted to handle the induced anisotropic metric and compared for the pushbroom image rectification problem. A trick that exploits the semiordered line structure of pushbroom data to improve the computational complexity several orders of magnitude is also presented.

Blood flow computation in phase-contrast MRI by minimal paths in anisotropic media.

In this paper, anisotropic Fast Marching is employed to compute blood flow trajectories as minimal paths in 3D phase-contrast MRI images. Uncertainty in the estimated blood flow vectors is incorporated in a tensor which is used as metric for the anisotropic Fast Marching. A flow connectivity distribution is computed simultaneously to the Fast Marching. Based on the connectivity distribution the most likely flow trajectories can be identified. Results are presented for several PC MRI data sets and the capability of the method to indicate uncertainty of the flow trajectories is shown.

Probabilistic 4D blood flow tracking and uncertainty estimation.

Phase-Contrast (PC) MRI utilizes signal phase shifts resulting from moving spins to measure tissue motion and blood flow. Time-resolved 4D vector fields representing the motion or flow can be derived from the acquired PC MRI images. In cardiovascular PC MRI applications, visualization techniques such as vector glyphs, streamlines, and particle traces are commonly employed for depicting the blood flow. Whereas these techniques indeed provide useful diagnostic information, uncertainty due to noise in the PC-MRI measurements is ignored, which may lend the results a false sense of precision. In this work, the statistical properties of PC MRI flow measurements are investigated and a probabilistic flow tracking method based on sequential Monte Carlo sampling is devised to calculate flow uncertainty maps. The theoretical derivations are validated using simulated data and a number of real PC MRI data sets of the aorta and carotid arteries are used to demonstrate the flow uncertainty mapping technique.

Accuracy of low-dose chest CT in intensive care patients.

In this prospective study, we set out to determine the accuracy of low-dose computerized tomography (LDCT) of the chest in intensive care patients. Fifteen adult intensive care patients were examined with a standard-dose CT protocol (average radiation dose = 6.7 mSv), chosen as the reference standard, followed by a non-contrast-enhanced LDCT protocol (average radiation dose = 0.59 mSv). Each examination was then read by two separate groups of radiologists blinded to both the purpose and the protocol of the study. In the small group examined, the results showed 100% accuracy in the diagnosis of pneumomediastinum, pericardial effusion, and pleural effusion, and 90% accuracy in the diagnosis of pneumothorax and consolidation. There were no false-positive findings, and the few false-negative findings were unlikely to lead to any clinical interventions. Our examination protocol, while providing a tenfold reduction of the radiation dose, nevertheless remained accurate enough for resolving certain clinical questions common in the intensive care patient. Thus, we suggest that protocols aimed at reducing the radiation dose in chest CT could be applied to the intensive care patient for resolving some specific questions, without compromising the diagnostic yield of the examinations.

Probabilistic 4D blood flow mapping.

Blood flow and tissue velocity can be measured using phase-contrast MRI. In this work, the statistical properties of 4D phase-contrast images are derived, and a novel probabilistic blood flow mapping method based on sequential Monte Carlo sampling is presented. The resulting flow maps visualize and quantify the uncertainty in conventional flow visualization techniques such as streamlines and particle traces.

The culprit lesion and its consequences: combined visualization of the coronary arteries and delayed myocardial enhancement in dual-source CT: a pilot study.

OBJECTIVE: To assess combined analysis of coronary arteries and delayed myocardial contrast enhancement based on co-registration of coronary CT angiography and late-phase CT and automatic segmentation. MATERIALS AND METHODS: Co-registration and late enhancement segmentation were applied to coronary CT angiography and late-phase CT images from six pigs with acute myocardial infarction (MI) and six patients with chronic MI. MI size was quantified by manual delineation, the established 3SD method, and a new mixture model approach. Correspondence between coronary artery lesions and MI was assessed visually from fused segmentation results. RESULTS: Co-registration was successful in all cases. There was substantial agreement in the number of segments diagnosed with MI, comparing manual delineation and the mixture model for animal (κ = 0.839) and patient studies (κ = 0.770). There were no significant differences between the two methods (P > 0.05). In patients there was a discrepancy between the segmental distribution of MI and empirical coronary artery perfusion in 10/96 segments when compared with the true coronary branching pattern. CONCLUSION: The mixture model approach is well suited for automated assessment of MI size from late-phase cardiac CT. Fusion imaging eliminates the need for empirical knowledge of the anatomical relationship between the coronary artery lesion and the area of myocardial ischaemia.

Multiple hypothesis template tracking of small 3D vessel structures.

A multiple hypothesis tracking approach to the segmentation of small 3D vessel structures is presented. By simultaneously tracking multiple hypothetical vessel trajectories, low contrast passages can be traversed, leading to an improved tracking performance in areas of low contrast. This work also contributes a novel mathematical vessel template model, with which an accurate vessel centerline extraction is obtained. The tracking is fast enough for interactive segmentation and can be combined with other segmentation techniques to form robust hybrid methods. This is demonstrated by segmenting both the liver arteries in CT angiography data, which is known to pose great challenges, and the coronary arteries in 32 CT cardiac angiography data sets in the Rotterdam Coronary Artery Algorithm Evaluation Framework, for which ground-truth centerlines are available.

Standardized evaluation methodology and reference database for evaluating coronary artery centerline extraction algorithms.

Efficiently obtaining a reliable coronary artery centerline from computed tomography angiography data is relevant in clinical practice. Whereas numerous methods have been presented for this purpose, up to now no standardized evaluation methodology has been published to reliably evaluate and compare the performance of the existing or newly developed coronary artery centerline extraction algorithms. This paper describes a standardized evaluation methodology and reference database for the quantitative evaluation of coronary artery centerline extraction algorithms. The contribution of this work is fourfold: (1) a method is described to create a consensus centerline with multiple observers, (2) well-defined measures are presented for the evaluation of coronary artery centerline extraction algorithms, (3) a database containing 32 cardiac CTA datasets with corresponding reference standard is described and made available, and (4) 13 coronary artery centerline extraction algorithms, implemented by different research groups, are quantitatively evaluated and compared. The presented evaluation framework is made available to the medical imaging community for benchmarking existing or newly developed coronary centerline extraction algorithms.

A comprehensive approach to the analysis of contrast enhanced cardiac MR images.

Current magnetic resonance imaging (MRI) technology allows the determination of patient-individual coronary tree structure, detection of infarctions, and assessment of myocardial perfusion. Joint inspection of these three aspects yields valuable information for therapy planning, e.g., through classification of myocardium into healthy tissue, regions showing a reversible hypoperfusion, and infarction with additional information on the corresponding supplying artery. Standard imaging protocols normally provide image data with different orientations, resolutions and coverages for each of the three aspects, which makes a direct comparison of analysis results difficult. The purpose of this work is to develop methods for the alignment and combined analysis of these images. The proposed approach is applied to 21 datasets of healthy and diseased patients from the clinical routine. The evaluation shows that, despite limitations due to typical MRI artifacts, combined inspection is feasible and can yield clinically useful information.

Multiple channel detection of steady-state visual evoked potentials for brain-computer interfaces.

In this paper, novel methods for detecting steady-state visual evoked potentials using multiple electroencephalogram (EEG) signals are presented. The methods are tailored for brain-computer interfacing, where fast and accurate detection is of vital importance for achieving high information transfer rates. High detection accuracy using short time segments is obtained by finding combinations of electrode signals that cancel strong interference signals in the EEG data. Data from a test group consisting of 10 subjects are used to evaluate the new methods and to compare them to standard techniques. Using 1-s signal segments, six different visual stimulation frequencies could be discriminated with an average classification accuracy of 84%. An additional advantage of the presented methodology is that it is fully online, i.e., no calibration data for noise estimation, feature extraction, or electrode selection is needed.