Sepsis and delayed cerebral ischemia are associated and have a cumulative effect on poor functional outcome in aneurysmal subarachnoid hemorrhage.

Objective: Although sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association between sepsis and DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition. Methods: Patients admitted to our hospital between 11/2014 and 11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0-3 vs. 4-6). Propensity score matching (PSM) and multivariable logistic regressions were performed. Results: Of 238 patients with aSAH, 55 (23.1%) developed sepsis and 74 (31.1%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p < 0.01) and longer ICU stay (p = 0.046). Sepsis was independently associated with DCI (OR = 2.46, 95%CI: 1.28-4.72, p < 0.01). However, after exclusion of patients who developed sepsis before (OR = 1.59, 95%CI: 0.78-3.24, p = 0.21) or after DCI (OR = 0.85, 95%CI: 0.37-1.95, p = 0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56.3% (76/135) in patients with neither sepsis nor DCI, to 43.8% (21/48) in those with no sepsis but DCI, to 34.5% (10/29) with sepsis but no DCI and to 7.7% (2/26) in patients with both sepsis and DCI. Conclusion: Our study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies.

Sodium signal intensity of CSF using 1H-guided 23Na-MRI as a potential noninvasive biomarker in Alzheimer's disease.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is characterized by cognitive decline and mnestic deficits. The pathophysiology of AD is not fully understood, which renders the development of accurate tools for early diagnosis and effective therapies exceedingly difficult. In this study, we investigated the use of 23Na-MRI to measure the relative sodium signal intensities (rSSIs) in CSF in patients with AD and healthy controls. METHODS: We prospectively recruited 11 patients with biomarker-diagnosed early-stage AD, as well as 12 cognitively healthy age-matched controls. All participants underwent 23Na-MRI to measure rSSI. Statistical analyses were performed to compare CSF sodium signal intensities between groups and to evaluate the specificity and sensitivity of the rSSI in the diagnosis of AD. RESULTS: RSSIs in CSF were significantly higher in AD patients (mean = 68.6% ± 7.7%) compared to healthy controls (mean = 56.9% ± 5.5%) (p < .001). There was also a significant negative correlation between rSSI in CSF and hippocampus and amygdala volumes (r = -.54 and -.49, p < .05) as well as a positive correlation with total CSF volumes (r = .81, p < .05). Receiver operating characteristic analysis showed high diagnostic accuracy for rSSI in discriminating between AD patients and healthy controls (area under the curve = .94). CONCLUSION: Our study provides evidence that rSSI in CSF is increased in AD patients in comparison to healthy controls. rSSI may serve as a potential marker for early detection and monitoring of disease progression. Larger, longitudinal studies are needed to confirm our findings and to investigate the association between rSSI in CSF and the severity of cognitive impairment.

Cranial Computer Tomography with Photon Counting and Energy-Integrated Detectors: Objective Comparison in the Same Patients.

This study provides an objective comparison of cranial computed tomography (CT) imaging quality and radiation dose between photon counting detectors (PCCTs) and energy-integrated detectors (EIDs). We retrospectively analyzed 158 CT scans from 76 patients, employing both detector types on the same individuals to ensure a consistent comparison. Our analysis focused on the Computed Tomography Dose Index and the Dose-Length Product together with the contrast-to-noise ratio and the signal-to-noise ratio for brain gray and white matter. We utilized standardized imaging protocols and consistent patient positioning to minimize variables. PCCT showed a potential for higher image quality and lower radiation doses, as highlighted by this study, thus achieving diagnostic clarity with reduced radiation exposure, underlining its significance in patient care, particularly for patients requiring multiple scans. The results demonstrated that while both systems were effective, PCCT offered enhanced imaging and patient safety in neuroradiological evaluations.

Advanced Imaging of Shunt Valves in Cranial CT Scans with Photon-Counting Scanner.

This brief report aimed to show the utility of photon-counting technology alongside standard cranial imaging protocols for visualizing shunt valves in a patient's cranial computed tomography scan. Photon-counting CT scans with cranial protocols were retrospectively surveyed and four types of shunt valves were encountered: proGAV 2.0®, M.blue®, Codman Certas®, and proSA®. These scans were compared with those obtained from non-photon-counting scanners at different time points for the same patients. The analysis of these findings demonstrated the usefulness of photon-counting technology for the clear and precise visualization of shunt valves without any additional radiation or special reconstruction patterns. The enhanced utility of photon-counting is highlighted by providing superior spatial resolution compared to other CT detectors. This technology facilitates a more accurate characterization of shunt valves and may support the detection of subtle abnormalities and a precise assessment of shunt valves.

Three-Dimensional Visualization of Shunt Valves with Photon Counting CT and Comparison to Traditional X-ray in a Simple Phantom Model.

This study introduces an application of innovative medical technology, Photon Counting Computer Tomography (PC CT) with novel detectors, for the assessment of shunt valves. PC CT technology offers enhanced visualization capabilities, especially for small structures, and opens up new possibilities for detailed three-dimensional imaging. Shunt valves are implanted under the skin and redirect excess cerebrospinal fluid, for example, to the abdominal cavity through a catheter. They play a vital role in regulating cerebrospinal fluid drainage in various pathologies, which can lead to hydrocephalus. Accurate imaging of shunt valves is essential to assess the rate of drainage, as their precise adjustment is a requirement for optimal patient care. This study focused on two adjustable shunt valves, the proGAV 2.0® and M. blue® (manufactured by Miethke, Potsdam, Germany). A comprehensive comparative analysis of PC CT and traditional X-ray techniques was conducted to explore this cutting-edge technology and it demonstrated that routine PC CT can efficiently assess shunt valves' adjustments. This technology shows promise in enhancing the accurate management of shunt valves used in settings where head scans are already frequently required, such as in the treatment of hydrocephalus.

Photon Counting Computed Tomography for Accurate Cribriform Plate (Lamina Cribrosa) Imaging in Adult Patients.

Detailed visualization of the cribriform plate is challenging due to its intricate structure. This study investigates how computed tomography (CT) with a novel photon counting (PC) detector enhance cribriform plate visualization compared to traditionally used energy-integrated detectors in patients. A total of 40 patients were included in a retrospective analysis, with half of them undergoing PC CT (Naeotom Alpha Siemens Healthineers, Forchheim, Germany) and the other half undergoing CT scans using an energy-integrated detector (Somatom Sensation 64, Siemens, Forchheim, Germany) in which the cribriform plate was visualized with a temporal bone protocol. Both groups of scans were evaluated for signal-to-noise ratio, radiation dose, the imaging quality of the whole scan overall, and, separately, the cribriform plate and the clarity of volume rendering reconstructions. Two independent observers conducted a qualitative analysis using a Likert scale. The results consistently demonstrated excellent imaging of the cribriform plate with the PC CT scanner, surpassing traditional technology. The visualization provided by PC CT allowed for precise anatomical assessment of the cribriform plate on multiplanar reconstructions and volume rendering imaging with reduced radiation dose (by approximately 50% per slice) and higher signal-to-noise ratio (by approximately 75%). In conclusion, photon-counting technology provides the possibility of better imaging of the cribriform plate in adult patients. This enhanced imaging could be utilized in skull base-associated pathologies, such as cerebrospinal fluid leaks, to visualize them more reliably for precise treatment.

Primary results from the CLEAR study of a novel stent retriever with drop zone technology.

BACKGROUND: Challenges to revascularization of large vessel occlusions (LVOs) persist. Current stent retrievers have limited effectiveness for removing organized thrombi. The NeVa device is a novel stent retriever designed to capture organized thrombi within the scaffold during retrieval. OBJECTIVE: To evaluate the safety and effectiveness of revascularization of acute LVOs with the NeVa device. METHODS: Prospective, international, multicenter, single-arm, Investigational Device Exemption study to evaluate the performance of the NeVa device in recanalizing LVOs including internal carotid artery, M1/M2 middle cerebral artery, and vertebrobasilar arteries, within 8 hours of onset. Primary endpoint was rate of expanded Treatment in Cerebral Ischemia (eTICI) score 2b-3 within 3 NeVa passes, tested for non-inferiority against a performance goal of 72% with a -10% margin. Additional endpoints included first pass success and 90-day modified Rankin Scale (mRS) score 0-2. Primary composite safety endpoint was 90-day mortality and/or 24-hour symptomatic intracranial hemorrhage (sICH). RESULTS: From April 2021 to April 2022, 139 subjects were enrolled at 25 centers. Median National Institutes of Health Stroke Scale (NIHSS) score was 16 (IQR 12-20). In the primary analysis population (n=107), eTICI 2b-3 within 3 NeVa passes occurred in 90.7% (97/107; non-inferiority P<0.0001; post hoc superiority P<0.0001). First pass eTICI 2b-3 was observed in 73.8% (79/107), with first pass eTICI 2b67-3 in 69.2% (74/107) and eTICI 2c-3 in 48.6% (52/107). Median number of passes was 1 (IQR 1-2). Final eTICI 2b-3 rate was 99.1% (106/107); final eTICI 2b67-3 rate was 91.6% (98/107); final eTICI 2c-3 rate was 72.9% (78/107). Good outcome (90-day mRS score 0-2) was seen in 65.1% (69/106). Mortality was 9.4% (13/138) with sICH in 5.0% (7/139). CONCLUSIONS: The NeVa device is highly effective and safe for revascularization of LVO strokes and demonstrates superior first pass success compared with a predicate performance goal. TRIAL REGISTRATION NUMBER: NCT04514562.

Influence of neurovascular anatomy on perforation site in different mouse strains using the filament perforation model for induction of subarachnoid hemorrhage.

BACKGROUND: Filament perforation is a widely-used method to induce subarachnoid hemorrhage (SAH) in mice. Whereas the perforation site has been assumed to be in the branching of middle cerebral artery (MCA) and anterior cerebral artery (ACA), we recently observed more proximal perforations. METHODS: Filament perforation was performed in CD1- (n = 10) and C57Bl/6N-mice (n = 9) ex vivo. The filament was left in place and the perforation site was microscopically assessed. Digital subtraction angiography (DSA) was performed in CD1- (n = 9) and C57Bl/6J-mice (n = 29) and anatomical differences of the internal carotid artery (ICA) were determined. RESULTS: Whereas in C57Bl/6N-mice perforation occurred in the proximal intracranial ICA in 89% (n = 8), in CD1-mice the perforation site was in the proximal ICA in 50% (n = 5), in the branching between MCA and ACA in 40% (n = 4), and in the proximal ACA in 10% (n = 1). DSA revealed a stronger angulation (p<0.001) of the ICA in CD1-mice (163.5±2.81°) compared to C57Bl/6J-mice (124.5±5.49°). Body weight and ICA-angle showed no significant correlation in C57Bl/6J- (r = -0.06, pweight/angle = 0.757) and CD1-mice (r = -0.468, pweight/angle = 0.242). CONCLUSION: Filament perforation in mice occurs not only at the hitherto presumed branching between MCA and ACA, but seems to depend on mouse strain and anatomy as the proximal intracranial ICA may also be perforated frequently.

Multidisciplinary and standardized management of patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND: The appropriate management of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains uncertain. We aimed to evaluate the effect of implementing a standardized protocol for detection and management of DCI after aSAH on cerebral infarction and functional outcome. METHODS: We studied two cohorts of aSAH patients, one before (pre-implementation cohort: January 2012 to August 2014) and one after (post-implementation cohort: January 2016 to July 2018) implementation of a multidisciplinary approach, with standardized neurological and radiological assessment and risk-based medical treatment of DCI. We assessed the presence of new hypodensities on CT within 6 weeks after aSAH and categorized cerebral infarction into overall and DCI-related infarctions (hypodensities not within 48 h after IA repair and not attributable to aneurysm occlusion or intraparenchymal hematoma). Functional outcome was assessed at 3 months using the extended Glasgow outcome scale (eGOS), dichotomized into unfavorable (eGOS: 1-5) and favorable (eGOS: 6-8). We calculated odds ratios (OR) with corresponding 95% confidence intervals (CI's), and adjusted for age, WFNS grade, Fisher score, and treatment modality (aOR). RESULTS: In the post-implementation (n = 158) versus the pre-implementation (n = 143) cohort the rates for overall cerebral infarction were 29.1% vs 46.9% (aOR: 0.41 [0.24-0.69]), for DCI-related cerebral infarction 17.7% vs. 31.5% (aOR: 0.41 [0.23-0.76]), and for unfavorable functional outcome at 3 months 37.3% vs. 53.8% (aOR: 0.30 [0.17-0.54]). For patients with DCI, the rates for unfavorable functional outcomes at 3 months in the post-implementation versus the pre-implementation cohort were 42.3% vs. 77.8% (aOR: 0.1 [0.03-0.27]). CONCLUSIONS: A multidisciplinary approach with more frequent and standardized neurological assessment, standardized CT and CT perfusion monitoring, as well as tailored application of induced hypertension and invasive rescue therapy strategies, is associated with a significant reduction of cerebral infarction and unfavorable functional outcome after aneurysmal aSAH.

Comparative Analyses of the Impact of Different Criteria for Sepsis Diagnosis on Outcome in Patients with Spontaneous Subarachnoid Hemorrhage.

Data on sepsis in patients with a subarachnoid hemorrhage (SAH) are scarce. We assessed the impact of different sepsis criteria on the outcome in an SAH cohort. Adult patients admitted to our ICU with a spontaneous SAH between 11/2014 and 11/2018 were retrospectively included. In patients developing an infection, different criteria for sepsis diagnosis (Sepsis-1, Sepsis-3_original, Sepsis-3_modified accounting for SAH-specific therapy, alternative sepsis criteria compiled of consensus conferences) were applied and their impact on functional outcome using the modified Rankin Scale (mRS) on hospital discharge and in-hospital mortality was evaluated. Of 270 SAH patients, 129 (48%) developed an infection. Depending on the underlying criteria, the incidence of sepsis and septic shock ranged between 21-46% and 9-39%. In multivariate logistic regression, the Sepsis-1 criteria were not associated with the outcome. The Sepsis-3 criteria were not associated with the functional outcome, but in shock with mortality. Alternative sepsis criteria were associated with mortality for sepsis and in shock with mortality and the functional outcome. While Sepsis-1 criteria were irrelevant for the outcome in SAH patients, septic shock, according to the Sepsis-3 criteria, adversely impacted survival. This impact was higher for the modified Sepsis-3 criteria, accounting for SAH-specific treatment. Modified Sepsis-3 and alternative sepsis criteria diagnosed septic conditions of a higher relevance for outcomes in patients with an SAH.

Diffusion Restricted Lesions in the Splenium of the Corpus Callosum.

BACKGROUND/AIM: Various neurological disorders are associated with lesions predominantly or exclusively affecting the splenium of the corpus callosum (CC), such as Marchiafava-Bignami syndrome (MBS), reversible splenium lesion (RSL), and ischemic stroke (IS). The spectrum of symptoms is broad and clinical presentations may be indistinguishable. Therefore, we aimed to investigate the additional value of diffusion-weighted imaging (DWI) findings of splenial lesions in patients with MBS, RSL, and IS. PATIENTS AND METHODS: Overall, 23 patients (4 patients with MBS, 10 patients with RSL, and 9 patients with isolated IS in the splenium) were identified from a magnetic resonance imaging report database and analyzed with focus on lesion localization, shape, and size on DWI, as well as relative apparent diffusion coefficient (ADC). RESULTS: A focal hyperintensity in the splenium was observed on DWI in all patients. In MBS symmetrical boomerang-shaped lesions, in RSL central oval or round lesions, and in IS eccentric irregular lesions in the splenium were found. The median lesion size in MBS [6.25 (IQR=2.04-8.62) ml] was significantly larger than that in RSL [0.38 (IQR=0.09-0.92) ml, p=0.01], and in IS [0.09 (IQR=0.05-0.94) ml; p=0.01]. Regarding relative ADC values, no significant differences between MBS [0.32 (IQR=0.19-0.62)], RSL [0.22 (IQR=0.14-0.30)], and IS [0.27 (IQR=0.20-1.19)] were found. CONCLUSION: Diffusion restricted lesions in the splenium of the CC are best classified by localization, shape, and size, whereas relative ADC values are of limited value for differentiation of different neurological disorders.

Humanized three-dimensional scaffold xenotransplantation models for myelodysplastic syndromes.

Patient-derived xenograft (PDX) models have emerged as versatile preclinical platforms for investigation of functional pathomechanisms in myelodysplastic syndromes (MDS) and other myeloid neoplasms. However, despite increasingly improved methodology, engraftment efficiencies frequently remain low. Humanized three-dimensional scaffold models (ossicle xenotransplantation models) in immunocompromised mice have recently been found to enable improved engraftment rates of healthy and malignant human hematopoiesis. We therefore interrogated the feasibility of using four different three-dimensional ossicle-based PDX models for application with primary MDS samples. In a fully standardized comparison, we evaluated scaffold materials such as Gelfoam, extracellular matrix (ECM), and human or xenogenous bone substance in comparison to intrafemoral (IF) co-injection of bone marrow (BM)-derived mesenchymal stromal cells (MSCs) and CD34+ hematopoietic stem and progenitor cells (HSPCs). Our study included13 primary MDS patient samples transplanted in parallel according to these five different conditions. Engraftment of MDS samples was assessed by flow cytometry, immunohistological staining, and molecular validation. We determined that three-dimensional ossicle-based methods achieved higher relative rates of engraftment and enabled long-term retrievability of patient-derived MSCs from implanted ossicles. In summary, HSPCs and MSCs derived from MDS BM, which did not significantly engraft in NSG mice after intrafemoral injection, were able to colonize humanized scaffold models. Therefore, these models are promising new xenotransplantation techniques for addressing preclinical and functional questions of the interaction between hematopoiesis and the BM niche in MDS.

Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation.

Within the bone marrow microenvironment, endothelial cells (EC) exert important functions. Arterial EC support hematopoiesis while H-type capillaries induce bone formation. Here, we show that BM sinusoidal EC (BM-SEC) actively control erythropoiesis. Mice with stabilized ß-catenin in BM-SEC (Ctnnb1OE-SEC) generated by using a BM-SEC-restricted Cre mouse line (Stab2-iCreF3) develop fatal anemia. While activation of Wnt-signaling in BM-SEC causes an increase in erythroblast subsets (PII-PIV), mature erythroid cells (PV) are reduced indicating impairment of terminal erythroid differentiation/reticulocyte maturation. Transplantation of Ctnnb1OE-SEC hematopoietic stem cells into wildtype recipients confirms lethal anemia to be caused by cell-extrinsic, endothelial-mediated effects. Ctnnb1OE-SEC BM-SEC reveal aberrant sinusoidal differentiation with altered EC gene expression and perisinusoidal ECM deposition and angiocrine dysregulation with de novo endothelial expression of FGF23 and DKK2, elevated in anemia and involved in vascular stabilization, respectively. Our study demonstrates that BM-SEC play an important role in the bone marrow microenvironment in health and disease.

Intrathecal activation of CD8+ memory T cells in IgG4-related disease of the brain parenchyma.

IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4-restricted plasma cells into a variety of organs. Clinical presentation is heterogeneous, and pathophysiological mechanisms of IgG4-RD remain elusive. There are very few cases of IgG4-RD with isolated central nervous system manifestation. By leveraging single-cell sequencing of the cerebrospinal fluid (CSF) of a patient with an inflammatory intracranial pseudotumor, we provide novel insights into the immunopathophysiology of IgG4-RD. Our data illustrate an IgG4-RD-associated polyclonal T-cell response in the CSF and an oligoclonal T-cell response in the parenchymal lesions, the latter being the result of a multifaceted cell-cell interaction between immune cell subsets and pathogenic B cells. We demonstrate that CD8+ T effector memory cells might drive and sustain autoimmunity via macrophage migration inhibitory factor (MIF)-CD74 signaling to immature B cells and CC-chemokine ligand 5 (CCL5)-mediated recruitment of cytotoxic CD4+ T cells. These findings highlight the central role of T cells in sustaining IgG4-RD and open novel avenues for targeted therapies.

Cell Cycle Regulatory Protein Expression in Multinucleated Giant Cells of Giant Cell Tumor of Bone: do They Proliferate?

Cells of the monocyte macrophage lineage form multinucleated giant cells (GCs) by fusion, which may express some cell cycle markers. By using a comprehensive marker set, here we looked for potential replication activities in GCs, and investigated whether these have diagnostic or clinical relevance in giant cell tumor of bone (GCTB). GC rich regions of 10 primary and 10 first recurrence GCTB cases were tested using immunohistochemistry in tissue microarrays. The nuclear positivity rate of the general proliferation marker, replication licensing, G1/S-phase, S/G2/M-phase, mitosis promoter, and cyclin dependent kinase (CDK) inhibitor reactions was analyzed in GCs. Concerning Ki67, moderate SP6 reaction was seen in many GC nuclei, while B56 and Mib1 positivity was rare, but the latter could be linked to more aggressive (p = 0.012) phenotype. Regular MCM6 reaction, as opposed to uncommon MCM2, suggested an initial DNA unwinding. Early replication course in GCs was also supported by widely detecting CDK4 and cyclin E, for the first time, and confirming cyclin D1 upregulation. However, post-G1-phase markers CDK2, cyclin A, geminin, topoisomerase-2a, aurora kinase A, and phospho-histone H3 were rare or missing. These were likely silenced by upregulated CDK inhibitors p15INK4b, p16INK4a, p27KIP1, p53 through its effector p21WAF1 and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB.

Comparative analysis of machine learning algorithms for computer-assisted reporting based on fully automated cross-lingual RadLex mappings.

Computer-assisted reporting (CAR) tools were suggested to improve radiology report quality by context-sensitively recommending key imaging biomarkers. However, studies evaluating machine learning (ML) algorithms on cross-lingual ontological (RadLex) mappings for developing embedded CAR algorithms are lacking. Therefore, we compared ML algorithms developed on human expert-annotated features against those developed on fully automated cross-lingual (German to English) RadLex mappings using 206 CT reports of suspected stroke. Target label was whether the Alberta Stroke Programme Early CT Score (ASPECTS) should have been provided (yes/no:154/52). We focused on probabilistic outputs of ML-algorithms including tree-based methods, elastic net, support vector machines (SVMs) and fastText (linear classifier), which were evaluated in the same 5 × fivefold nested cross-validation framework. This allowed for model stacking and classifier rankings. Performance was evaluated using calibration metrics (AUC, brier score, log loss) and -plots. Contextual ML-based assistance recommending ASPECTS was feasible. SVMs showed the highest accuracies both on human-extracted- (87%) and RadLex features (findings:82.5%; impressions:85.4%). FastText achieved the highest accuracy (89.3%) and AUC (92%) on impressions. Boosted trees fitted on findings had the best calibration profile. Our approach provides guidance for choosing ML classifiers for CAR tools in fully automated and language-agnostic fashion using bag-of-RadLex terms on limited expert-labelled training data.

Crossed Cerebellar Diaschisis in Alzheimer's Disease Detected by Arterial Spin-labelling Perfusion MRI.

BACKGROUND: Crossed cerebellar diaschisis (CCD) is a phenomenon with depressed metabolism and hypoperfusion in the cerebellum. Using arterial spin-labelling perfusion weighted magnetic resonance imaging (ASL PWI), we investigated the frequency of CCD in patients with Alzheimer's disease (AD) and differences between patients with and without CCD. PATIENTS AND METHODS: In patients with AD who underwent a standardized magnetic resonance imaging including ASL PWI cerebral blood flow was evaluated in the cerebellum, and brain segmentation/volumetry was performed using mdbrain (mediaire GmbH, Berlin, Germany) and FSL FIRST (Functional Magnetic Resonance Imaging of the Brain Software Library). RESULTS: In total, 65 patients were included, and 22 (33.8%) patients were assessed as being CCD-positive. Patients with CCD had a significantly smaller whole brain volume (862.8±49.9 vs. 893.7±62.7 ml, p=0.049) as well as white matter volume (352.9±28.0 vs. 374.3±30.7, p=0.008) in comparison to patients without CCD. CONCLUSION: It was possible to detect CCD by ASL PWI in approximately one-third of patients with AD and was associated with smaller whole brain and white matter volume.

Evaluation of Sodium (23Na) MR-imaging as a Biomarker and Predictor for Neurodegenerative Changes in Patients With Alzheimer's Disease.

BACKGROUND/AIM: Sodium (23Na) MR imaging is a noninvasive MRI technique that has been shown to be sensitive to visualize biochemical information about tissue viability, their cell integrity, and cell function in various studies. The aim of this study was to evaluate differences in regional brain 23Na signal intensity between Alzheimer's disease (AD) and healthy controls to preliminarily evaluate the capability of 23Na imaging as a biomarker for AD. PATIENTS AND METHODS: A total of 14 patients diagnosed with AD were included: 12 in the state of dementia and 2 with mild cognitive impairment (MCI), and 12 healthy controls (HC); they were all scanned on a 3T clinical scanner with a double tuned 1H/23Na birdcage head coil. After normalizing the signal intensity with that of the vitreous humor, relative tissue sodium concentration (rTSC) was measured after automated segmentation in the hippocampus, amygdala, basal ganglia, white matter (WM) and grey matter (GM) in both cerebral hemispheres. RESULTS: Patients with AD showed a significant increase in rTSC in comparison to healthy controls in the following brain regions: WM 13.6%; p=0.007, hippocampus 12.9%; p=0.003, amygdala 18.9%; p=0.0007. CONCLUSION: 23Na-MRI has the potential to be developed as a useful biomarker for the diagnosis of AD.

MRI Detection of Changes in Tissue Sodium Concentration in Brain Metastases after Stereotactic Radiosurgery: A Feasibility Study.

BACKGROUND AND PURPOSE: To date, treatment response to stereotactic radiosurgery (SRS) in brain metastases (BM) can only be determined by MRI evaluation of contrast-enhancing lesions in a long-time follow-up. Sodium MRI has been a subject of immense interest in imaging research as the measure of tissue sodium concentration (TSC) can give valuable quantitative information on cell viability. We aimed to analyze the longitudinal changes of TSC in BM measured with 23 Na MRI before and after SRS for assessment of early local tumor effects. METHODS: Seven patients with a total of 12 previously untreated BM underwent SRS with 22 Gy. In addition to a standard MRI protocol including dynamic susceptibility-weighted contrast-enhanced perfusion, a 23 Na MRI was performed at three time points: (I) 2 days before, (II) 5 days, and (III) 40 days after SRS. Nine BMs were evaluated. The absolute TSC in the BM, the respective peritumoral edemas, and the normal-appearing corresponding contralateral brain area were assessed and the relative TSC were correlated to the changes in BM longest axial diameters. RESULTS: TSC was elevated in nine BM at baseline before SRS with a mean of 73.4 ± 12.3 mM. A further increase in TSC was observed 5 days after SRS in all the nine BM with a mean of 86.9 ± 13 mM. Eight of nine BM showed a mean 60.6 ± 13.3% decrease in the longest axial diameter 40 days after SRS; at this time point, the TSC also had decreased to a mean 65.1 ± 7.9 mM. In contrast, one of the nine BM had a 13.4% increase in the largest axial diameter at time point III. The TSC of this BM showed a further TSC increase of 80.1 mM 40 days after SRS. CONCLUSION: Changes in TSC using 23 Na MRI shows the possible capability to detect radiobiological changes in BM after SRS.

FLAIR Vascular Hyperintensities Indicate Slow Poststenotic Blood Flow in ICA Stenosis.

PURPOSE: Occlusion or significant stenosis of the internal carotid artery (ICA) in the cervical segment is commonly associated with a poststenotic decrease in the downstream blood flow and perfusion. Fluid attenuated inversion recovery (FLAIR) vascular hyperintensities (FVH) are a phenomenon that represents slow arterial blood flow. In this study, we investigated the frequency and extent of FVH in the distal ICA in patients with proximal ICA stenosis. METHODS: We analyzed the magnetic resonance imaging (MRI) findings in 51 patients with a total of 60 cervical ICA stenoses with special focus on the frequency and extent of FVH in the area of the petrous segment of the ICA on FLAIR images and correlated these with Doppler/duplex sonography results. RESULTS: In 46 (76.7%) patients with ICA stenosis, FVH could be detected in the petrous segment of the ICA: in 19 (41.3%) patients a thin hyperintense rim near the vessel wall (grade 1), in 24 (52.2%) patients a strong hyperintense rim near the vessel wall (grade 2), and in 3 (6.5%) patients a hyperintense filling of the entire lumen (grade 3) was observed. The extent of FVH in the ICA in the petrous segment showed a high negative correlation with the poststenotic flow velocity (Spearman correlation, R = -0.75, p < 0.001), and moderate correlation with the degree of ICA stenosis (Spearman correlation, R = 0.51, p< 0.001). CONCLUSION: An FVH in the petrous ICA is commonly seen among patients with steno-occlusive disease in proximal ICA and could therefore be useful to recognize a proximal ICA stenosis even on FLAIR images.