Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) is the most common MRI method in clinical environments for assessment of perfusion-related parameters. In this study, special emphasis was placed on the shape of the tissue residue function under different physiological conditions. DSC-MRI-based parameters assumed to reflect arterial delay and cerebral oxygen extraction were obtained by deconvolution of tissue and arterial contrast-agent concentration time curves. The established mean transit time (MTT) estimate was supplemented by biophysical modelling for extraction of the oxygen extraction capacity, quantified in terms of an apparent oxygen extraction fraction (AOEF) index. Eight healthy volunteers were examined during normal breathing and spontaneous hyperventilation. Whole-brain MTT and AOEF increased during hyperventilation in all volunteers (average increase 33 % and 30 %, respectively). The arterial delay, reflecting the inverse of arterial flow rate, was also prolonged in all volunteers, and the mean arterial delay was 63 % longer during hyperventilation. The corresponding whole-brain MTT estimates were 3.8 ± 0.7 s during normal breathing and 5.0 ± 1.3 s during hyperventilation (mean ± SD, n = 8). The applied Bézier curve deconvolution algorithm returned tissue residue functions of plausible shapes, i.e., without oscillations and negative values, and some indications that curve shape is relevant for improved assessment of oxygen extraction properties were demonstrated.

The cerebral blood flow, CBF, is an important clinical parameter in neuro-intensive care. The possibility to continuously monitor CBF, computed from referential ICP, rICP (calculated from measured intracranial pressure, ICP, and central venous pressure, CVP) and venous outflow resistance, Rv, could importantly improve patient care. For the CBF(1) method the pulsative part of CBF (with rICP increase due to vascular volume increase) gives the venous outflow resistance, Rv. The CBF max method finds Rv from the close correlation between rICP and Rv. For both CBF(1) and CBF max, rICP divided with Rv gives CBF. The parameters rICP, Rv and CBF were calculated from measurements of ICP increase, and of intracerebral venous volume increase in nine subjects, by the CBF(1) method. The result, together with the finding of a close correlation between rICP and Rv, which made CBF dependent on rICP only, gave confirmation of the theory for computation of CBF, with two methods for continuous monitoring of CBF from rICP, one (CBF(1)) using the systolic ICP increase to find Rv, and one (CBF max) using the relationship between Rv and rICP at rICP exceeding about 10 mmHg in this study.

The intracranial pressure (ICP) curve with its different peaks has been comprehensively studied, but the exact physiological mechanisms behind its morphology has not been revealed. If the pathophysiology behind deviations from the normal ICP curve form could be identified, it could be vital information to diagnose and treat each single patient. A mathematical model of the hydrodynamics in the intracranial cavity over single heart cycles was developed. A Windkessel model approach was generalized but the unsteady Bernoulli equation was utilized for blood flow and CSF flow. This is a modification of earlier models using the extended and simplified classical Windkessel analogies to a model that is based on mechanisms rooted in the laws of physics. The improved model was calibrated with patient data for cerebral arterial inflow, venous outflow, cerebrospinal fluid (CSF), and ICP over one heart cycle from 10 neuro-intensive care unit patients. A priori model parameter values were obtained by considering patient data and values taken from earlier studies. These values were used as an initial guess for an iterated constrained-ODE (ordinary differential equation) optimization problem with cerebral arterial inflow data as input into the system of ODEs. The optimization routine found patient-specific model parameter values that produced model ICP curves that showed excellent agreement with clinical measurements while model venous and CSF flow were within a physiologically acceptable range. The improved model and the automated optimization routine gave better model calibration results compared to previous studies. Moreover, patient-specific values of physiologically important parameters like intracranial compliance, arterial and venous elastance, and venous outflow resistance were determined. The model was used to simulate intracranial hydrodynamics and to explain the underlying mechanisms of the ICP curve morphology. Sensitivity analysis showed that the order of the three main peaks of the ICP curve was affected by a decrease in arterial elastance, a large increase in resistance to arteriovenous flow, an increase in venous elastance, or a decrease in resistance to CSF flow in the foramen magnum; and the frequency of oscillations were notably affected by intracranial elastance. In particular, certain pathological peak patterns were caused by these changes in physiological parameters. To the best of our knowledge, there are no other mechanism-based models associating the pathological peak patterns to variation of the physiological parameters.

The physiology underlying the intracranial pressure (ICP) curve morphology is not fully understood. Recent research has suggested that the morphology could be dependent on arterial cerebral inflow and the physiological and pathophysiological properties of the intracranial cavity. If understood, the ICP curve could provide information about the patient's cerebrovascular state important in individualizing treatment in neuro intensive care patients. A mathematical model based on known physiological properties of the intracranial compartment was created. Clinical measurements from ten neuro intensive care patients in whom intracranial arterial blood inflow, venous blood outflow and cerebrospinal fluid flow over the foramen magnum had been measured with phase contrast MRI, concomitant with ICP measurements were used to validate the model. In nine patients the mathematical model was able to create an ICP curve mimicking the measured by using arterial intracranial inflow and adjusting physiological parameters of the model. The venous outflow and cerebrospinal fluid (CSF) flow over the foramen magnum predicted by the model were within physiologically reasonable limits and in most cases followed the MRI measured values in close adjunct. The presented model could produce an ICP curve in close resemblance of the in vivo measured curves. This strengthens the hypothesis that the ICP curve is shaped by the arterial intracranial inflow and the physiological properties of the intracranial cavity.

Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications.

The underlying physiology of the intracranial pressure (ICP) curve morphology is still poorly understood. If this physiology is explained it could be possible to extract clinically relevant information from the ICP curve. The venous outflow from the cranial cavity is pulsatile, and in theory the pulsatile component of venous outflow from the cranial cavity should be attenuated with increasing ICP. In this study, we explored the relationship between ICP and the pulsatility of the venous outflow from the intracranial cavity. Thirty-seven neuro-intensive care patients that had been examined with phase-contrast magnetic resonance imaging regarding cerebral blood flow (CBF) through the internal carotid and vertebral arteries and venous flow in the internal jugular veins were retrospectively included. The pulsatility of the jugular flow was determined by calculating the venous pulsatile index. The results were correlated to clinical data registered in the patient data monitoring system, including ICP and cerebral perfusion pressure (CPP). CBF was 996 ± 298 ml/min, and the flow in the internal jugular veins equaled 67 ± 17% of the CBF, with a range of 22–97%. The venous pulsatile index correlated negatively to ICP (R = − 0.47 p = 0.003). The lowest flow in the internal jugular veins over the cardiac cycle (Fmin) was not correlated to ICP. Temperature, end-tidal CO2, MAP, and CPP were not correlated to venous pulsatility. An increase in ICP correlates to a lower pulsatility of the venous outflow from the cranial cavity. A lower pulsatility could be due to increased pressure requirements to compress intracranial veins with increasing ICP.

Continuous monitoring of intracranial pressure (ICP) was introduced in the 1950s. For correct ICP recordings, the zero-reference point for the external pressure gauge must be placed next to a head anatomical structure. We evaluated different anatomical points as zero reference for the ICP device at different head positions and their relation to brain centre (BC), foramen of Monro (Monro), and brain surface. Patients referred for neuroimaging due to e.g. headache all having normal 3D MRI scans were selected. Monro, BC, Orbit(O), external auditory meatus (EAM), and orbito-meatal (OM) line were identified and projected to mid-sagittal, or axial images. Each scan was evaluated like lying supine, 45° head elevations, upright, and 45° lateral position. Distances from skin to brain surface, BC, and Monro were measured. All values are presented as mean ± SD and/or range in millimetre. For conversion to mmHg, millimetre was multiplied by 0.074. Twenty MRI scans were examined. A zero reference at EAM or glabella was ideal at BC when head was strict supine or in the lateral position. At 45° head elevation, an overestimation of the BC-ICP by 4.8 ± 0.8 and in upright 5.6 ± 0.5 mmHg was found, and 45° lateral underestimated ICP-BC by 6.3 ± 1.0 mmHg. Monro was situated 45 ± 5 mm rostral to the mid-OM line and 24 (18–31) mm inferior and 13 (8–17) mm in front of BC. A zero-reference point aligned with the highest point of the head underestimated BC-ICP and Monro-ICP. If the ICP reading was added 5.9 or 6.3 mmHg, respectively, a deviation from BC-ICP was ≤ 1.8 mmHg and Monro-ICP was ≤ 0.9 mmHg in all head positions. EAM and glabella are defined anatomical structures representing BC when strict supine or lateral but with 12 mmHg variation with different head positions used in clinical practice. The OM line follows Monro at head elevation, but not when the head is turned. When the highest external point on the head is used, ICP values at brain surface as well as Monro and BC are underestimated. This underestimation is fairly constant and, when corrected for, provides the most exact ICP reading.

The anticoagulant warfarin is commonly monitored with prothrombin time (PT). Viscoelastic haemostatic assays (VHA) are primarily used in situations of acute bleeding to guide haemostatic therapy. Much research has focused on VHA monitoring of new oral anticoagulants. However, many patients are still anticoagulated with warfarin and effect of warfarin anticoagulation on VHA is uncertain. The aim of this study was to assess warfarin anticoagulation on three different VHA and compare these findings with prothrombin time (PT), coagulation factor analyses and a thrombin generation assay (TGA). Citrated whole blood was drawn from 80 patients admitted for routine PT-INR Owren. VHA analysis with ROTEM (EXTEM, INTEM and FIBTEM), ReoRox (Fibscreen 1 and 2) and Sonoclot (gbACT+) was performed. Blood was also drawn for plasma analysis with PT (PT-INR Owren and PT Quick), TGA and analysis of factors I, II, VII, IX and X. Extrinsically activated VHA, including ROTEM EXTEM and FIBTEM Clotting Time (CT) and ReoRox Fibscreen1 and 2 clot onset time 1 correlated moderately with PT-INR Owren , with R 0.66-0.71. These four variables were likely to be prolonged above reference interval in patients with prolonged PT-INR Owren >1.2. Two patients with normal ROTEM CTs had Owren PT-INRs >1.5. Warfarin affects extrinsically activated VHA variables of initial clotting. The role of VHA for clinical decision-making in patients planned for invasive procedures, such as spinal/epidural anaesthesia needs further study. None of the recent guidelines on regional anaesthesia include VHA testing to define adequate haemostasis.

OBJECTIVES:Constant infusion lumbar infusion test (LIT) is an important way to find which patients, of those with signs and symptoms corresponding to normal pressure hydrocephalus (NPH) who will improve from shunt operation. LIT is a stress test on the ability for cerebrospinal fluid re-absorbtion. The aim of this study is to show how the information from LIT can be improved by quantitative analysis and avoidance of methodological pitfalls. MATERIAL AND METHODS:The potential pitfalls, and the analysis method, are described in detail. The analysis was applied on pre-operative constant infusion LIT from 31 patients operated for NPH, with known outcome. The pre- and post-operative walking speed was used to grade pathology progression or improvement. RESULTS:The maximal, plateau, intra-spinal pressure at constant infusion LIT is an ambivalent indicator for NPH: while low maximal pressure indicates no cerebrospinal fluid (CSF) absorbtion pathology, too high pressure (≥47 mmHg) may mean no diagnosis, because of stenosis of the Sylvian aqueduct. When subjects with too high intra-spinal pressure were excluded, the new analysis gave a couple of diagnostic volume parameters, of which one appears to be an optimal LIT parameter for identifying NPH patients with 14% better accuracy than plateau pressure. CONCLUSION:By avoiding methodological pitfalls, and optimal analysis of the results from lumbar infusion test, the number of NPH patients who do not have a successful outcome after shunt operation may be further decreased.

Current methods to measure cerebral blood flow (CBF) in the neuro critical care setting cannot monitor the CBF continuously. In contrast, continuous measurement of intracranial pressure (ICP) is readily accomplished, and there is a component of ICP that correlates with arterial inflow of blood into the cranial cavity. This property may have utility in using continuous ICP curve analysis to continuously estimate CBF. We examined the data from 13 patients, monitored with an intraventricular ICP device determining the pulsatile amplitude ICPamp as well as the area under the ICP curve (AUCICP). Using an elastance measurement, the ICP curve was converted to craniospinal volume (AUCΔV). The patients were examined with Phase Contrast Magnetic Resonance Imaging (MRI), measuring flow in the carotid and vertebral arteries. This made it possible to calculate CBF for one cardiac cycle (ccCBFMRtot) and divide it into the pulsatile (ccCBFMRpuls) and non-pulsatile (ccCBFMRconst) flow. ICP derived data and MRI measurements were compared. Linear regression was used to establish wellness of fit and ANOVA was used to calculate the P value. No correlation was found between ICPamp and the ccICPMRpuls (P = 0.067). In contrast there was a correlation between the AUCICP and ccCBFMRpuls (R2 = 0.440 P = 0.013). The AUCΔV correlated more appropriately with the ccCBFMRpuls. (R2 = 0.688 P < 0.001). Our findings suggests that the pulsatile part of the intracranial pressure curve, especially when transformed into a volume curve, correlates to the pulsatile part of the CBF.

The intracranial pressure (ICP) curve with its different peaks has been extensively studied, but the exact physiological mechanisms behind its morphology are still not fully understood. Both intracranial volume change (ΔICV) and transmission of the arterial blood pressure have been proposed to shape the ICP curve. This study tested the hypothesis that the ICP curve correlates to intracranial volume changes.

Background Organ donation guidelines recommend a clear conventional bedside chest radiograph before lung transplantation despite only moderate accuracy for cardiopulmonary abnormalities. Purpose To evaluate the influence of donor image interpretation on lung transplantation outcome in recipients by following early and late complications, one-year survival, and to correlate imaging findings and blood gas analysis with lung transplantation outcome in recipients. Material and Methods In 35 lung donors from a single institution clinical reports and study reviews of imaging findings of the mandatory bedside chest radiographs and blood gas analyses were compared with clinical outcome in 38 recipients. Hospitalization time, peri- and postoperative complications, early complications (primary graft dysfunction, infection), 30-day and one-year survival, and forced expiratory volume in 1s percentage of predicted normal value (FEV1%) at one-year follow-up were analyzed. Results Findings in clinical reports and study reviews differed substantially, e.g. regarding reported decompensation, edema, infection, and atelectasis. No correlation was shown between imaging findings in clinical report or study review and blood gas analyses in the lung donors compared to postoperative outcome in recipients. Conclusion The interpretation of the mandatory chest radiograph in its present form does not influence one-year outcome in lung transplantation. Larger imaging studies or a change in clinical routine including computed tomography may provide evidence for future guidelines.

Purpose:The aim of the study was to retrospectively evaluate the diagnostic imaging that potential lung donors undergo, the reader variability of image interpretation and its relevance for donation, and the potential information gained from imaging studies not primarily intended for lung evaluation but partially including them.Materials and Methods:Bedside chest radiography and computed tomography (CT), completely or incompletely including the lungs, of 110 brain-dead potential organ donors in a single institution during 2007 to 2014 were reviewed from a donation perspective. Two chest radiologists in consensus analyzed catheters and cardiovascular, parenchymal, and pleural findings. Clinical reports and study review were compared for substantial differences in findings that could have led to a treatment change, triggered additional examinations such as bronchoscopy, or were considered important for donation.Results:Among 136 bedside chest radiographs, no differences between clinical reports and study reviews were found in 37 (27%), minor differences were found in 28 (21%), and substantial differences were found in 71 (52%) examinations (P<0.0001). In 31 of 42 (74%) complete or incomplete CT examinations, 50 of 74 findings with relevance for lung donation were not primarily reported (P<0.0001).Conclusions:The majority of donor patients undergo only chest radiography. A targeted imaging review of abnormalities affecting the decision to use donor lungs may be useful in the preoperative stage. With a targeted list, substantial changes were made from initial clinical interpretations. CT can provide valuable information on donor lung pathology, even if the lungs are only partially imaged.

The study focuses on three questions related to the clinical usefulness of microdialysis in severe brain trauma: (1) How frequently is disturbed cerebral energy metabolism observed in various types of lesions? (2) How often does the biochemical pattern indicate cerebral ischaemia and mitochondrial dysfunction? (3) How do these patterns relate to mortality? The study includes 213 consecutive patients with severe brain trauma (342 intracerebral microdialysis catheters). The patients were classified into four groups according to the type of lesion: extradural haematoma (EDH), acute subdural haematoma (SDH), cerebral haemorrhagic contusion (CHC) and no mass lesion (NML). Altogether about 150,000 biochemical analyses were performed during the initial 96 h after trauma. Compromised aerobic metabolism occurred during 38 % of the study period. The biochemical pattern indicating mitochondrial dysfunction was more common than that of ischaemia. In EDH and NML aerobic metabolism was generally close to normal. In SDH or CHC it was often severely compromised. Mortality was increased in SDH with impaired aerobic metabolism, while CHC did not exhibit a similar relation. Compromised energy metabolism is most frequent in patients with SDH and CHC (32 % and 49 % of the study period, respectively). The biochemical pattern of mitochondrial dysfunction is more common than that of ischaemia (32 % and 6 % of the study period, respectively). A correlation between mortality and biochemical data is obtained provided the microdialysis catheter is placed in an area where energy metabolism reflects tissue outcome in a large part of the brain.

Several studies have described hypercoagulability in neurosurgery with craniotomy for brain tumor resection. In this study, hydroxyethyl starch (HES) 130/0.42 was used for hemodynamic stabilization and initial blood loss replacement. HES can induce coagulopathy with thromboelastographic signs of decreased clot strength. The aim of this study was to prospectively describe perioperative changes in coagulation during elective craniotomy for brain tumor resection with the present fluid regimen.

Acute management of traumatic brain injury (TBI), in particular mild TBI, focuses on the detection of the 5–7 % who may be harboring potentially life-threatening intracranial hemorrhage (IH) using CT scanning. Guidelines intending to reduce unnecessary head CT scans using available clinical variables to detect those at high IH risk have shown varying results. Recently, the Scandinavian Neurotrauma Committee (SNC) derived a new set of high-IH risk variables for adults with TBI using an evidence-based literature review. Unlike previous guidelines, the SNC guideline incorporates serum values of the brain protein S100B with clinical variables.