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.

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.

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.

Longitudinal MRI findings in patients with newly diagnosed glioblastoma after intraoperative radiotherapy.

BACKGROUND AND PURPOSE: Post-radiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20-40 Gy) in glioblastoma. METHODS: INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV. RESULTS: Overall, 11/15 (73.3%) INTRAGO patients (median age 60 years) were included. Distant failure was observed in 7/11 (63.6%) patients, local tumor recurrence in one patient (9.1%). On the first follow-up MRI all but one patient demonstrated enhancement of varying patterns around the resection cavity which were: in 2/11 (18.2%) patients thin and linear, in 7/11 (63.6%) combined linear and nodular, and in 1/11 (9.1%) voluminous, indistinct, and mesh-like. In the course of treatment, most patients developed the latter two patterns (8/11 [72.7%]). INTRAGO patients demonstrated more often combined linear and nodular and/or voluminous, indistinct, mesh-like components (8/11 [72.7%]) in comparison to control patients (3/12 [25%], P = 0.02). INTRAGO patients demonstrated significantly increasing enhancing lesion (P = 0.001) and T2 lesion volumes (P < 0.001) in the longitudinal non-parametric analysis in comparison to the control group. rCBV showed no significant differences between both groups. CONCLUSIONS: High doses of radiotherapy to the tumor cavity result in more pronounced enhancement patterns/volumes and T2 lesion volumes. These results will be useful for the response evaluation of patients exposed to high doses of radiotherapy in future studies.

Longitudinal imaging and evaluation of SAH-associated cerebral large artery vasospasm in mice using micro-CT and angiography.

Longitudinal in vivo imaging studies characterizing subarachnoid hemorrhage (SAH)-induced large artery vasospasm (LAV) in mice are lacking. We developed a SAH-scoring system to assess SAH severity in mice using micro CT and longitudinally analysed LAV by intravenous digital subtraction angiography (i.v. DSA). Thirty female C57Bl/6J-mice (7 sham, 23 SAH) were implanted with central venous ports for repetitive contrast agent administration. SAH was induced by filament perforation. LAV was assessed up to 14 days after induction of SAH by i.v. DSA. SAH-score and neuroscore showed a highly significant positive correlation (rsp = 0.803, p < 0.001). SAH-score and survival showed a negative significant correlation (rsp = -0.71, p < 0.001). LAV peaked between days 3-5 and normalized on days 7-15. Most severe LAV was observed in the internal carotid (Δmax = 30.5%, p < 0.001), anterior cerebral (Δmax = 21.2%, p = 0.014), middle cerebral (Δmax = 28.16%, p < 0.001) and basilar artery (Δmax = 23.49%, p < 0.001). Cerebral perfusion on day 5 correlated negatively with survival time (rPe = -0.54, p = 0.04). Arterial diameter of the left MCA correlated negatively with cerebral perfusion on day 3 (rPe = -0.72, p = 0.005). In addition, pseudoaneurysms arising from the filament perforation site were visualized in three mice using i.v. DSA. Thus, micro-CT and DSA are valuable tools to assess SAH severity and to longitudinally monitor LAV in living mice.

Open-Label Phase II Evaluation of Imatinib in Primary Inoperable or Incompletely Resected and Recurrent Glioblastoma.

PURPOSE: Preclinical studies indicated that imatinib may have single-agent activity in glioblastoma through inhibition of tyrosine kinase activity and also that it might enhance the efficacy of radiotherapy. We therefore sought to investigate clinical efficacy in patients with newly diagnosed and recurrent glioblastoma in combination with radiotherapy. METHODS: We conducted a nonrandomized, 2-arm, open-label phase II trial including patients aged 18 years or older with an ECOG performance status of 0-2 that were either newly diagnosed (arm A) with a measurable tumor (i.e., after incomplete resection or biopsy) or that were diagnosed with progression of a glioblastoma after initial therapy (arm B). Patients in arm A received 600 mg/day imatinib in combination with hypofractionated radiotherapy (2.5 Gy per fraction, 22 fractions). Patients in arm B received 600 mg/day imatinib alone or in combination with re-irradiation at various doses. In case tumor progression occurred, CCNU was added (2 cycles, 100 mg/m2) to imatinib. The primary end point was progression-free survival (PFS). The secondary end point was safety, defined as per Common Terminology Criteria for Adverse Events (version 2.0). Overall survival (OS) was analyzed as an exploratory end point. RESULTS: Fifty-one patients were enrolled, of which 19 were included in arm A and 32 in arm B. The median follow-up was 4 (0.5-30) months in arm A and 6.5 (0.3-51.5) months in arm B. The median PFS was 2.8 months (95% CI 0-8.7) in arm A and 2.1 months (95% CI 0-11.8) in arm B. The median OS was 5.0 (0.8-30) months (95% CI 0-24.1) in arm A and 6.5 (0.3-51.5) months (95% CI 0-32.5) in arm B. The major grade 3 events were seizure (present in 17 patients), pneumonia (11 patients), and vigilance decrease (7 patients). CONCLUSIONS: Imatinib showed no measurable activity in patients with newly diagnosed or recurrent glioblastoma.

Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO): An Open-Label, Dose-Escalation Phase I/II Trial.

BACKGROUND: The median time to recurrence of glioblastoma (GB) following multimodal treatment is ∼7 mo. Nearly all cancers recur locally, suggesting that augmenting local treatments may improve outcomes. OBJECTIVE: To investigate whether intraoperative radiotherapy (IORT) to the resection cavity is safe and effective. METHODS: INTRAGO was a phase I/II trial to evaluate the safety and tolerability of IORT with 20 to 40 Gy of low-energy photons in addition to standard radiochemotherapy (ClinicalTrials.gov ID, NCT02685605). The primary endpoint was safety as per occurrence of dose-limiting toxicities. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also performed an exploratory analysis of the local PFS (L-PFS), defined as recurrence within 1 cm of the treated margin. RESULTS: Fifteen patients were treated at 3 dose levels. Of these, 13 underwent incomplete resection, 6 had unresected satellites, and 3 did not receive per-protocol treatment (PPT). The MGMT promoter was unmethylated in 10 patients. The median follow-up was 13.8 mo. The majority of grade 3 to 5 adverse events were deemed unrelated to IORT. Five cases of radionecrosis were observed, 2 were classified as grade 3 events. Other grade 3 events judged related to radiotherapy (external-beam radiotherapy and/or IORT) were wound dehiscence (n = 1), CSF leakage (n = 1), cyst formation (n = 1). No IORT-related deaths occurred. The median PFS was 11.2 mo (95% confidence interval [CI]: 5.4-17.0) for all patients and 11.3 mo (95% CI: 10.9-11.6) for those receiving PPT. The median L-PFS was 14.3 mo (95% CI: 8.4-20.2) for all patients and 17.8 mo (95% CI: 9.7-25.9) for those receiving PPT. The median OS was 16.2 mo (95% CI: 11.1-21.4) for all patients and 17.8 mo (95% CI: 13.9-21.7) for those receiving PPT. CONCLUSION: These data suggest that IORT is associated with manageable toxicity. Considering the limitations of a 15-patient phase I/II trial, further studies aimed at assessing an outcome benefit are warranted.

Study Protocol: Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma (Gamma-GBM).

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. OBJECTIVE: To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor. METHODS: Gamma-GBM is a single center, open-label, prospective, single arm, phase II study that includes patients with newly diagnosed GBM (intraoperative via frozen sections) who underwent STR (residual tumor will be identified by native and contrast enhanced T1-weighted magnetic resonance imaging scans). All patients will receive SRS with 15 Gy (prescribed to the 50% isodose enclosing all areas of residual tumor) early (within 24-72 h) after surgery. Thereafter, all patients undergo standard-of-care therapy for GBM (radiochemotherapy with 60 Gy external beam radiotherapy [EBRT] plus concomitant temozolomide and 6 cycles of adjuvant temozolomide chemotherapy). The primary outcome is median progression-free survival, secondary outcomes are median OS, occurrence of radiation induced acute (<3 wk), early delayed (<3 mo), and late (>3 mo post-SRS) neurotoxicity and incidence of symptomatic radionecrosis. EXPECTED OUTCOMES: We expect to detect efficacy and safety signals by the immediate application of SRS to standard-of-care therapy in newly diagnosed GBM. DISCUSSION: Early postoperative SRS to areas of residual tumor could bridge the therapeutic gap between surgery and adjuvant therapies.

Heterogeneity of glioblastoma with gliomatosis cerebri growth pattern on diffusion and perfusion MRI.

BACKGROUND AND PURPOSE: Gliomatosis cerebri (GC) is a rare growth pattern of glioblastoma whose diffuse nature is reflected by unspecific, relatively uniform findings on conventional MRI. In the present study we sought to evaluate the additional value of diffusion (DWI) and perfusion weighted (PWI) MRI for a more detailed characterization. METHODS: We analyzed the MRI findings in patients with histologically proven glioblastoma with GC growth pattern with a specific emphasis on T2 lesion pattern, volume, relative apparent diffusion coefficient (rACD), and relative cerebral blood volume (rCBV) and compared these to age-/gender-matched patients with localized glioblastoma. RESULTS: Overall, 16 patients (median age 59.5 years, 4 male) were included in the study. Of these, 8 patients had a glioblastoma with GC growth pattern, and 8 a classical localized growth pattern. While the median rADC (1.27 [IQR 1.12-1.41]) within the T2 lesion was significant lower in glioblastoma with GC growth pattern compared to localized glioblastoma (1.74 [IQR 1.45-1.96]; p = 0.003), the median T2 lesion volume and rCBV within the T2 lesion did not differ significantly. Furthermore, six patients with glioblastoma with GC growth pattern showed focal areas with significantly reduced rADC (p = 0.043), and/or increased rCBV (p = 0.028). CONCLUSIONS: Lower rADC in glioblastoma with GC growth pattern might reflect the diffuse tumor cell infiltration whereas focal areas with decreased rADC and/or increased rCBV probably indicate high tumor cell density and/or abnormal tumor vessels which may be useful for biopsy guidance.

Imaging of Orthotopic Glioblastoma Xenografts in Mice Using a Clinical CT Scanner: Comparison with Micro-CT and Histology.

PURPOSE: There is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated. MATERIALS AND METHODS: 2.5x106 U87MG cells were orthotopically implanted in NOD/SCID/ᵞc-/- mice (n = 9). Mice underwent contrast-enhanced (300 µl Iomeprol i.v.) imaging using a micro-CT (80 kV, 75 µAs, 360° rotation, 1,000 projections, scan time 33 s, resolution 40 x 40 x 53 µm) and a clinical CT scanner (4-row multislice detector; 120 kV, 150 mAs, slice thickness 0.5 mm, feed rotation 0.5 mm, resolution 98 x 98 x 500 µm). Mice were sacrificed and the brain was worked up histologically. In all modalities tumor volume was measured by two independent readers. Contrast-to-noise ratio (CNR) and Signal-to-noise ratio (SNR) were measured from reconstructed CT-scans (0.5 mm slice thickness; n = 18). RESULTS: Tumor volumes (mean±SD mm3) were similar between both CT-modalities (micro-CT: 19.8±19.0, clinical CT: 19.8±18.8; Wilcoxon signed-rank test p = 0.813). Moreover, between reader analyses for each modality showed excellent agreement as demonstrated by correlation analysis (Spearman-Rho >0.9; p<0.01 for all correlations). Histologically measured tumor volumes (11.0±11.2) were significantly smaller due to shrinkage artifacts (p<0.05). CNR and SNR were 2.1±1.0 and 1.1±0.04 for micro-CT and 23.1±24.0 and 1.9±0.7 for the clinical CTscanner, respectively. CONCLUSION: Clinical CT scanners may reliably be used for in vivo imaging and volumetric analysis of brain tumor growth in mice.

Intra-individual diagnostic image quality and organ-specific-radiation dose comparison between spiral cCT with iterative image reconstruction and z-axis automated tube current modulation and sequential cCT.

OBJECTIVES: To prospectively evaluate image quality and organ-specific-radiation dose of spiral cranial CT (cCT) combined with automated tube current modulation (ATCM) and iterative image reconstruction (IR) in comparison to sequential tilted cCT reconstructed with filtered back projection (FBP) without ATCM. METHODS: 31 patients with a previous performed tilted non-contrast enhanced sequential cCT aquisition on a 4-slice CT system with only FBP reconstruction and no ATCM were prospectively enrolled in this study for a clinical indicated cCT scan. All spiral cCT examinations were performed on a 3rd generation dual-source CT system using ATCM in z-axis direction. Images were reconstructed using both, FBP and IR (level 1-5). A Monte-Carlo-simulation-based analysis was used to compare organ-specific-radiation dose. Subjective image quality for various anatomic structures was evaluated using a 4-point Likert-scale and objective image quality was evaluated by comparing signal-to-noise ratios (SNR). RESULTS: Spiral cCT led to a significantly lower (p < 0.05) organ-specific-radiation dose in all targets including eye lense. Subjective image quality of spiral cCT datasets with an IR reconstruction level 5 was rated significantly higher compared to the sequential cCT acquisitions (p < 0.0001). Consecutive mean SNR was significantly higher in all spiral datasets (FBP, IR 1-5) when compared to sequential cCT with a mean SNR improvement of 44.77% (p < 0.0001). CONCLUSIONS: Spiral cCT combined with ATCM and IR allows for significant-radiation dose reduction including a reduce eye lens organ-dose when compared to a tilted sequential cCT while improving subjective and objective image quality.

The neglected need for psychological intervention in patients suffering from incidentally discovered intracranial aneurysms.

OBJECTIVES: Previous studies demonstrated a conspicuously elevated rate of psychiatric disorders in patients with incidental intracranial aneurysms. This study was designed to analyze the impact of this observation on the post-interventional rates of PTSD, depressions and anxiety disorders in this collective. METHODS: Physically unaffected iA patients with an unremarkable medical history were included in this two center study. Pre-interventional psychiatric histories, rates of post-interventional depressions, subjective trauma, PTSD, and pre-interventional fears were determined by questionnaires (Beck Depression Inventory (BDI), Impact of Event Scale (IES), civilian Post-traumatic-Stress-Disorder (PTSD) Check List (PCL-C)). Benign meningioma (M) patients served as controls. RESULTS: 58 M and 45 iA patients were enrolled. Significantly higher rates of PTSD, elevated trauma scores, and moderate/severe depressions (PTSD: p=0.0017; IES: p=0.0038; BDI: p=0.0301) were demonstrated in the iA collective. After excluding patients with a positive pre-interventional psychiatric history those differences were not reproducible. 70% of the iA patients reported an improvement of their unspecific pre-interventional symptoms, while 30% would have rated a psychological consultation as helpful. CONCLUSION: The data identifies the early psychological consultation as a relevant and by affected patients accepted treatment modification when trying to improve the outcome after treatment of incidental aneurysms.

Image Quality of 3rd Generation Spiral Cranial Dual-Source CT in Combination with an Advanced Model Iterative Reconstruction Technique: A Prospective Intra-Individual Comparison Study to Standard Sequential Cranial CT Using Identical Radiation Dose.

OBJECTIVES: To prospectively intra-individually compare image quality of a 3rd generation Dual-Source-CT (DSCT) spiral cranial CT (cCT) to a sequential 4-slice Multi-Slice-CT (MSCT) while maintaining identical intra-individual radiation dose levels. METHODS: 35 patients, who had a non-contrast enhanced sequential cCT examination on a 4-slice MDCT within the past 12 months, underwent a spiral cCT scan on a 3rd generation DSCT. CTDIvol identical to initial 4-slice MDCT was applied. Data was reconstructed using filtered backward projection (FBP) and 3rd-generation iterative reconstruction (IR) algorithm at 5 different IR strength levels. Two neuroradiologists independently evaluated subjective image quality using a 4-point Likert-scale and objective image quality was assessed in white matter and nucleus caudatus with signal-to-noise ratios (SNR) being subsequently calculated. RESULTS: Subjective image quality of all spiral cCT datasets was rated significantly higher compared to the 4-slice MDCT sequential acquisitions (p<0.05). Mean SNR was significantly higher in all spiral compared to sequential cCT datasets with mean SNR improvement of 61.65% (p*Bonferroni0.05<0.0024). Subjective image quality improved with increasing IR levels. CONCLUSION: Combination of 3rd-generation DSCT spiral cCT with an advanced model IR technique significantly improves subjective and objective image quality compared to a standard sequential cCT acquisition acquired at identical dose levels.

The Preinterventional Psychiatric History as a Major Predictor for a Reduced Quality of Life After Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND: A significantly increased rate of positive preinterventional psychiatric histories in the unruptured aneurysm collective was demonstrated previously. The current study was designed to analyze the influence of the preinterventional psychiatric status on the outcome after treatment of unruptured intracranial aneurysms. METHODS: Patients treated due to meningioma World Health Organization °I and unruptured intracranial aneurysms in 2 German neurosurgical centers between 2007 and 2013 were screened for exclusion criteria including malignant/chronic diseases, recurrence of the tumor/aneurysm, and neurologic deficits among others. The preinterventional psychiatric histories and the rates of postinterventional headaches, sleeping disorders, symptoms of chronic fatigue syndrome, and quality of life (QOL) were determined by questionnaires that were mailed to the patients in a printed version. RESULTS: A total of 58 M patients and 45 iA patients who met the inclusion criteria returned the questionnaires; 10 M (17.2%) and 17 iA patients (37.8%) had a positive psychiatric history. The overall Incidental aneurysm collective demonstrated significantly lower overall QOL scores (P = 0.003) and significant greater rates of chronic fatigue syndrome (P = 0.009) compared with the M collective. After we excluded all patients with positive pre-interventional psychiatric histories, those differences were no longer reproducible. Subjectively, the patients did not realize any significant changes in their QOL after successful aneurysm treatment. CONCLUSIONS: The results of the current study demonstrate the importance of taking the preinterventional psychiatric history into considerations when evaluating the outcome after unruptured aneurysm treatment. The unfavorable outcome of the aneurysm group seems to be caused by factors that are not related the aneurysm diagnosis or treatment itself.

Missing relationship of moyamoya and persistent primitive artery in Europeans. Another distinctive feature or artifact?

PURPOSE: Previous studies found higher incidence of persistent primitive arteries in Asian moyamoya (MM) patients than in the general population, which was thought to be a characteristic trait of the MM entity in general. We analyzed incidence of persistent primitive arteries and demographics of patients with European MM treated in one single center. First, we compared our large dataset to existing literature and second, we raised the question whether European MM demonstrates similar high prevalence of persistent primitive arteries as it was previously presented within Asian MM. METHODS: All European MM on whom revascularization surgery was performed from 1999 to 2013 were included. Demographics and associated diseases were obtained by retrospective chart review. Two independent readers evaluated 122 MM angiograms to determine the occurrence of persistent primitive arteries as well as the Suzuki score. RESULTS: We identified 112 cases with MM disease, 10 with MM syndrome. Mean age at time of diagnosis was 38.2 (range 6-64 years); a peak incidence in early childhood was not observed. Ninety (73.8%) were women, associated systemic diseases were found in four patients. Seven cases (5.7%) presented with unilaterally affected vessels. The majority of patients (71; 58.2%) were graded Suzuki Score 3. One 14-year-old boy with moyamoya presented with a primitive trigeminal artery (0.89%). CONCLUSIONS: We did not find a bimodal age distribution, but only a second peak during adulthood. Unlike previous studies on Asian moyamoya patients, our collective does not exhibit a higher prevalence of persistent primitive arteries than the normal population.

Morphology and function: MR pineal volume and melatonin level in human saliva are correlated.

PURPOSE: To investigate the relation between circadian saliva melatonin levels and pineal volume as determined by MRI. Plasma melatonin levels follow a circadian rhythm with a high interindividual variability. MATERIALS AND METHODS: In 103 healthy individuals saliva melatonin levels were determined at four time points within 24 h and MRI was performed once (3.0 Tesla, including three-dimensional T2 turbo spin echo [3D-T2-TSE], susceptibility-weighted imaging [SWI]). Pineal volume as well as cyst volume were assessed from multiplanar reconstructed 3D-T2-TSE images. Pineal calcification volume tissue was determined on SWI. To correct for hormonal inactive pineal tissue, cystic and calcified areas were excluded. Sleep quality was assessed with the Landeck Inventory for sleep quality disturbance. RESULTS: Solid and uncalcified pineal volume correlated to melatonin maximum (r = 0.28; P < 0.05) and area under the curve (r = 0.29; P < 0.05). Of interest, solid and uncalcified pineal volume correlated negatively with the sleep rhythm disturbances subscore (r = -0.17; P < 0.05) despite a very homogenous population. CONCLUSION: Uncalcified solid pineal tissue measured by 3D-T2-TSE and SWI is related to human saliva melatonin levels. The analysis of the sleep quality and pineal volume suggests a linkage between better sleep quality and hormonal active pineal tissue.

A Low Cost Metal-Free Vascular Access Mini-Port for Artifact Free Imaging and Repeated Injections in Mice.

PURPOSE: Small injection ports for mice are increasingly used for drug testing or when administering contrast agents. Commercially available mini-ports are expensive single-use items that cause imaging-artifacts. We developed and tested an artifact-free, low-cost, vascular access mini-port (VAMP) for mice. PROCEDURES: Leakage testing of the VAMP was conducted with high speed bolus injections of different contrast agents. VAMP-induced artifacts were assessed using a micro-CT and a small animal MRI (9.4T) scanner ex vivo. Repeated contrast administration was performed in vivo. RESULTS: With the VAMP there was no evidence of leakage with repeated punctures, high speed bolus contrast injections, and drawing of blood samples. In contrast to the tested commercially available ports, the VAMP did not cause artifacts with MRI or CT imaging. CONCLUSIONS: The VAMP is an alternative to commercially available mini-ports and has useful applications in animal research involving imaging procedures and contrast agent testing.