Comparison of T1-weighted landmark placement and ROI transfer onto diffusion-weighted EPI sequences for targeted tractography tasks in the optic nerve.

Diffusion-based tractography in the optic nerve requires sampling strategies assisted by anatomical landmark information (regions of interest [ROIs]). We aimed to investigate the feasibility of expert-placed, high-resolution T1-weighted ROI-data transfer onto lower spatial resolution diffusion-weighted images. Slab volumes from 20 volunteers were acquired and preprocessed including distortion bias correction and artifact reduction. Constrained spherical deconvolution was used to generate a directional diffusion information grid (fibre orientation distribution-model [FOD]). Three neuroradiologists marked landmarks on both diffusion imaging variants and structural datasets. Structural ROI information (volumetric interpolated breath-hold sequence [VIBE]) was respectively registered (linear with 6/12 degrees of freedom [DOF]) onto single-shot EPI (ss-EPI) and readout-segmented EPI (rs-EPI) volumes, respectively. All eight ROI/FOD-combinations were compared in a targeted tractography task of the optic nerve pathway. Inter-rater reliability for placed ROIs among experts was highest in VIBE images (lower confidence interval 0.84 to 0.97, mean 0.91) and lower in both ss-EPI (0.61 to 0.95, mean 0.79) and rs-EPI (0.59 to 0.86, mean 0.70). Tractography success rate based on streamline selection performance was highest in VIBE-drawn ROIs registered (6-DOF) onto rs-EPI FOD (70.0% over 5%-threshold, capped to failed ratio 39/16) followed by both 12-DOF-registered (67.5%; 41/16) and nonregistered VIBE (67.5%; 40/23). On ss-EPI FOD, VIBE-ROI-datasets obtained fewer streamlines overall with each at 55.0% above 5%-threshold and with lower capped to failed ratio (6-DOF: 35/36; 12-DOF: 34/34, nonregistered 33/36). The combination of VIBE-placed ROIs (highest inter-rater reliability) with 6-DOF registration onto rs-EPI targets (best streamline selection performance) is most suitable for white matter template generation required in group studies.

Ultrafast Brain MRI with Deep Learning Reconstruction for Suspected Acute Ischemic Stroke.

Background Deep learning (DL)-accelerated MRI can substantially reduce examination times. However, studies prospectively evaluating the diagnostic performance of DL-accelerated MRI reconstructions in acute suspected stroke are lacking. Purpose To investigate the interchangeability of DL-accelerated MRI with conventional MRI in patients with suspected acute ischemic stroke at 1.5 T. Materials and Methods In this prospective study, 211 participants with suspected acute stroke underwent clinically indicated MRI at 1.5 T between June 2022 and March 2023. For each participant, conventional MRI (including T1-weighted, T2-weighted, T2*-weighted, T2 fluid-attenuated inversion-recovery, and diffusion-weighted imaging; 14 minutes 18 seconds) and DL-accelerated MRI (same sequences; 3 minutes 4 seconds) were performed. The primary end point was the interchangeability between conventional and DL-accelerated MRI for acute ischemic infarction detection. Secondary end points were interchangeability regarding the affected vascular territory and clinically relevant secondary findings (eg, microbleeds, neoplasm). Three readers evaluated the overall occurrence of acute ischemic stroke, affected vascular territory, clinically relevant secondary findings, overall image quality, and diagnostic confidence. For acute ischemic lesions, size and signal intensities were assessed. The margin for interchangeability was chosen as 5%. For interrater agreement analysis and interrater reliability analysis, multirater Fleiss κ and the intraclass correlation coefficient, respectively, was determined. Results The study sample consisted of 211 participants (mean age, 65 years ± 16 [SD]); 123 male and 88 female). Acute ischemic stroke was confirmed in 79 participants. Interchangeability was demonstrated for all primary and secondary end points. No individual equivalence indexes (IEIs) exceeded the interchangeability margin of 5% (IEI, -0.002 [90% CI: -0.007, 0.004]). Almost perfect interrater agreement was observed (P > .91). DL-accelerated MRI provided higher overall image quality (P < .001) and diagnostic confidence (P < .001). The signal properties of acute ischemic infarctions were similar in both techniques and demonstrated good to excellent interrater reliability (intraclass correlation coefficient, ≥0.8). Conclusion Despite being four times faster, DL-accelerated brain MRI was interchangeable with conventional MRI for acute ischemic lesion detection. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Haller in this issue.

Treatment outcome of IDH1/2 wildtype CNS WHO grade 4 glioma histologically diagnosed as WHO grade II or III astrocytomas.

BACKGROUND: Isocitrate dehydrogenase (IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown. METHODS: Patients undergoing surgery (between 2016-2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2-3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors. RESULTS: This multi-center study included 157 patients (mean age 58 years (20-87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response. CONCLUSIONS: WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.

Gender differences in self-assessed performance and stress level during training of basic interventional radiology maneuvers.

OBJECTIVES: Gender differences have been reported to influence medical training. We investigated gender differences encountered during training in interventional radiology maneuvers. METHODS: Catheter handling was analyzed under standardized conditions in 64 participants naïve to endovascular procedures (26 women, 38 men). Objective (e.g., catheter pathway, catheter movements, required time) and subjective parameters (stress level) were recorded. The NASA-Task Load Index (NASA-TLX; 1-20 points) was used to assess participants' stress levels and perceived workload. RESULTS: In the easier tasks, no significant differences between male and female participants regarding catheter handling were observed. In the most complex task, female participants took themselves more time (688 ± 363 vs. 501 ± 230 s; p = 0.02), asked for help more frequently (n = 19 vs. n = 8) and earlier than men (203 ± 94 vs. 305 ± 142 s; p = 0.049), whereas men stood out by more agitated catheter handling (6.0 ± 1.8 vs. 4.8 ± 1.6 movements/s; p = 0.005). Overall, female participants perceived tasks to be more difficult (11.5 ± 4.2 vs. 9.6 ± 3.3; p = 0.016), perceived higher stress levels (8.9 ± 4.9 vs. 6.3 ± 4.4; p = 0.037), and rated their own performance lower (9.12 ± 3.3 vs. 11.3 ± 3.3; p = 0.009). However, female participants were able to correlate self-assessed with objective parameters correctly (r between -0.555 and -0.469; p = 0.004-0.018), whereas male participants failed to correctly rate their performance (p between 0.34 and 0.73). Stress levels correlated with objective parameters in males (r between 0.4 and 0.587; p < 0.005), but not in female participants. CONCLUSION: Perceived stress levels, self-evaluation skills, and catheter handling differ greatly between untrained male and female participants trying to solve interventional radiological tasks. These gender-specific differences should be considered in interventional radiology training. CLINICAL RELEVANCE STATEMENT: As psychological aspects may influence individual working strategies gender-specific differences in self-perception while learning interventional radiology maneuvers could be essential regarding success in teaching and treatment outcomes. KEY POINTS: • After performing standardized training, 38 male and 26 female volunteers showed significant differences regarding objective and self-assessed performance, as well as in perceived workload while performing simulated endovascular catheter maneuvers. • After solving simulated endovascular radiological tasks, female participants were able to self-assess their objective performance much more accurately than male participants. • Women took more time to solve simulated endovascular tasks and asked earlier and more frequently for help than men.

Initial experience on abdominal photon-counting computed tomography in clinical routine: general image quality and dose exposure.

OBJECTIVES: Photon-counting computed tomography has lately found its way into clinical routine. The new technique could offer substantial improvements regarding general image quality, image noise, and radiation dose reduction. This study evaluated the first abdominal examinations in clinical routine and compared the results to conventional computed tomography. METHODS: In this single-center retrospective study, 66 patients underwent photon-counting and conventional abdominal CT. Four radiologists assessed general image quality, image noise, and image artifacts. Signal-to-noise ratio and dose properties of both techniques within the clinical application were compared. An ex vivo phantom study revealed the radiobiological impact by means of DNA double-strand break foci in peripheral blood cells by enumerating γ-H2AX+53BP1 foci. RESULTS: General image quality in accordance with the Likert scale was found superior for photon-counting CT (4.74 ± 0.46 vs. 4.25 ± 0.54; p < 0.001). Signal-to-noise ratio (p < 0.001) and also dose exposure were higher for photon-counting CT (DLP: 419.2 ± 162.2 vs. 372.3 ± 236.6 mGy*cm; p = 0.0435). CT exposure resulted in significantly increased DNA damage in comparison to sham control (p < 0.001). Investigation of the average foci per cell and radiation-induced foci numbers revealed significantly elevated numbers (p = 0.004 and p < 0.0001, respectively) after photon-counting CT. CONCLUSION: Photon-counting CT in abdominal examinations showed superior results regarding general image quality and signal-to-noise ratio in clinical routine. However, this seems to be traded for a significantly higher dose exposure and corresponding double-strand break frequency. Optimization of standard protocols in further clinical applications is required to find a compromise regarding picture quality and dose exposure. KEY POINTS: • Photon-counting computed tomography promises to enhance the diagnostic potential of medical imaging in clinical routine. • Retrospective single-center study showed superior general image quality accompanied by higher dose exposure in initial abdominal PCCT protocols compared to state-of-the-art conventional CT. • A simultaneous ex vivo phantom study revealed correspondingly increased frequencies of DNA double-strand breaks after PCCT.

Detection of Endoleaks Following Thoracic and Abdominal Aortic Endovascular Aortic Repair-: A Comparison of Standard and Dynamic 4D-Computed Tomography Angiography.

PURPOSE: Endoleaks are a common complication after endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR). The detection and correct classification of endoleaks is essential for the further treatment of affected patients. However, standard computed tomography angiography (CTA) provides no hemodynamic information on endoleaks, which can result in misclassification in complex cases. The aim of this study was to compare standard CTA (sCTA) with dynamic, dual-energy CTA (dCTA) for detection and classification of endoleaks following EVAR or TEVAR. MATERIALS AND METHODS: This retrospective evaluation compared 69 sCTA diagnostic examinations performed on 50 different patients with 89 dCTA diagnostic examinations performed on 69 different patients. RESULTS: In total, 15.9% of sCTA examinations and 49.4% of dCTA examinations led to the detection of endoleaks. With sCTA, 20.0% of patients were diagnosed with endoleaks, while with dCTA, 37.7% of patients were diagnosed with endoleaks. With sCTA, mainly Type 1 endoleaks were detected, whereas, with dCTA, the types of detected endoleaks were more evenly distributed. In comparison with the literature, the frequencies of endoleak types detected with dCTA better reflect the natural distribution than the frequencies detected with standard CTA. CONCLUSION: Based on the retrospective comparative evaluation, dCTA could pose a valuable supplementary diagnostic tool resulting in a more accurate and realistic detection and classification of suspected endoleaks.

Glucosylceramide Synthase Inhibitors Induce Ceramide Accumulation and Sensitize H3K27 Mutant Diffuse Midline Glioma to Irradiation.

H3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation. Miglustat was included in the therapy protocol of two pediatric patients. The effect of H3.3K27 trimethylation on GSL composition was analyzed in ependymoma. GSI reduced the expression of the ganglioside GD2 in a concentration and time-dependent manner and increased the expression of ceramide, ceramide 1-phosphate, sphingosine, and sphingomyelin but not of sphingosine 1-phosphate. Miglustat significantly increased the efficacy of irradiation. Treatment with miglustat according to dose recommendations for patients with Niemann-Pick disease was well tolerated with manageable toxicities. One patient showed a mixed response. In ependymoma, a high concentration of GD2 was found only in the presence of the loss of H3.3K27 trimethylation. In conclusion, treatment with miglustat and, in general, targeting GSL metabolism may offer a new therapeutic opportunity and can be administered in close proximity to radiation therapy. Alterations in H3K27 could be useful to identify patients with a deregulated GSL metabolism.

Sex Disparities in Re-Employment in Stroke Patients With Large Vessel Occlusion Undergoing Mechanical Thrombectomy.

BACKGROUND: Strokes in the working-age population represent a relevant share of ischemic strokes and re-employment is a major factor for well-being in these patients. Income differences by sex have been suspected a barrier for women in returning to paid work following ischemic stroke. We aim to identify predictors of (not) returning to paid work in patients with large vessel occlusion treated with mechanical thrombectomy (MT) to identify potential areas of targeted vocational rehabilitation. METHODS: From 6635 patients enrolled in the German Stroke Registry Endovascular Treatment between 2015 and 2019, data of 606 patients of the working population who survived large vessel occlusion at least 90 days past MT were compared based on employment status at day 90 follow-up. Univariate analysis, multiple logistic regression and analyses of area under the curve were performed to identify predictors of re-employment. RESULTS: We report 35.6% of patients being re-employed 3 months following MT (median age 54.0 years; 36.1% of men, 34.5% of women [P=0.722]). We identified independent negative predictors against re-employment being female sex (odds ratio [OR], 0.427 [95% CI, 0.229-0.794]; P=0.007), higher National Institutes of Health Stroke Scale (NIHSS) score 24 hours after MT (OR, 0.775 [95% CI, 0.705-0.852]; P<0.001), large vessel occlusion due to large-artery atherosclerosis (OR, 0.558 [95% CI, 0.312-0.997]; P=0.049) and longer hospital stay (OR, 0.930 [95% CI, 0.868-0.998]; P=0.043). Positive predictors favoring re-employment were excellent functional outcome (modified Rankin Scale score of 0-1) at 90 day follow-up (OR, 11.335 [95% CI, 4.864-26.415]; P<0.001) and combined treatment with intravenous thrombolysis (OR, 1.904 [95% CI, 1.046-3.466]; P=0.035). Multiple regression modeling increased predictive power of re-employment status significantly over prediction by best single functional outcome parameter (National Institutes of Health Stroke Scale 24 hours after MT ≤5; R2: 0.582 versus 0.432; area under the receiver operating characteristic curve: 0.887 versus 0.835, P<0.001). CONCLUSIONS: There is more to re-employment after MT than functional outcome alone. In particular, attention should be paid to possible systemic barriers deterring women from resuming paid work. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03356392.

Impact of Sarcopenia and Bone Mineral Density on Implant Failure after Dorsal Instrumentation in Patients with Osteoporotic Vertebral Fractures.

Background and Objectives: Age-related loss of bone and muscle mass are signs of frailty and are associated with an increased risk of falls and consecutive vertebral fractures. Management often necessitates fusion surgery. We determined the impacts of sarcopenia and bone density on implant failures (IFs) and complications in patients with spondylodesis due to osteoporotic vertebral fractures (OVFs). Materials and Methods: Patients diagnosed with an OVF according to the osteoporotic fracture classification (OF) undergoing spinal instrumentation surgery between 2011 and 2020 were included in our study. The skeletal muscle area (SMA) was measured at the third lumbar vertebra (L3) level using axial CT images. SMA z-scores were calculated for the optimal height and body mass index (BMI) adjustment (zSMAHT). The loss of muscle function was assessed via measurement of myosteatosis (skeletal muscle radiodensity, SMD) using axial CT scans. The bone mineral density (BMD) was determined at L3 in Hounsfield units (HU). Results: A total of 68 patients with OVFs underwent instrumentation in 244 segments (mean age 73.7 ± 7.9 years, 60.3% female). The median time of follow-up was 14.1 ± 15.5 months. Sarcopenia was detected in 28 patients (47.1%), myosteatosis in 45 patients (66.2%), and osteoporosis in 49 patients (72%). The presence of sarcopenia was independent of chronological age (p = 0.77) but correlated with BMI (p = 0.005). The zSMAHT was significantly lower in patients suffering from an IF (p = 0.0092). Sarcopenia (OR 4.511, 95% CI 1.459-13.04, p = 0.0092) and osteoporosis (OR 9.50, 95% CI 1.497 to 104.7, p = 0.014) increased the likelihood of an IF. Using multivariate analysis revealed that the zSMAHT (p = 0.0057) and BMD (p = 0.0041) were significantly related to IF occurrence. Conclusion: Herein, we established sarcopenic obesity as the main determinant for the occurrence of an IF after instrumentation for OVF. To a lesser degree, osteoporosis was associated with impaired implant longevity. Therefore, measuring the SMA and BMD using an axial CT of the lumbar spine might help to prevent an IF in spinal fusion surgery via early detection and treatment of sarcopenia and osteoporosis.

[Periocular Necrobiotic Xanthogranuloma with Mono- and Biclonal Gammopathy]. / Periokuläres nekrobiotisches Xanthogranulom bei mono- und biklonaler Gammopathie.

Necrobiotic xanthogranuloma is a very rare disease with granulomatous lesions of the skin with possible association with paraproteinemia. We report two cases of orbital necrobiotic xanthogranuloma in patients with mono/biclonal gammopathy of undetermined significance. Both patients underwent successful conservative treatment.

MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo.

BACKGROUND: Vascular shear stress promotes endothelial cell sprouting in vitro. The impact of hemodynamic forces on microRNA (miRNA) and gene expression within growing vascular networks in vivo, however, remain poorly investigated. Arteriovenous (AV) shunts are an established model for induction of neoangiogenesis in vivo and can serve as a tool for analysis of hemodynamic effects on miRNA and gene expression profiles over time. METHODS: AV shunts were microsurgically created in rats and explanted on postoperative days 5, 10 and 15. Neoangiogenesis was confirmed by histologic analysis and micro-computed tomography. MiRNA and gene expression profiles were determined in tissue specimens from AV shunts by microarray analysis and quantitative real-time polymerase chain reaction and compared with sham-operated veins by bioinformatics analysis. Changes in protein expression within AV shunt endothelial cells were determined by immunohistochemistry. RESULTS: Samples from AV shunts exhibited a strong overexpression of proangiogenic cytokines, oxygenation-associated genes (HIF1A, HMOX1), and angiopoetic growth factors. Significant inverse correlations of the expressions of miR-223-3p, miR-130b-3p, miR-19b-3p, miR-449a-5p, and miR-511-3p which were up-regulated in AV shunts, and miR-27b-3p, miR-10b-5p, let-7b-5p, and let-7c-5p, which were down-regulated in AV shunts, with their predicted interacting targets C-X-C chemokine receptor 2 (CXCR2), interleukin-1 alpha (IL1A), ephrin receptor kinase 2 (EPHA2), synaptojanin-2 binding protein (SYNJ2BP), forkhead box C1 (FOXC1) were present. CXCL2 and IL1A overexpression in AV shunt endothelium was confirmed at the protein level by immunohistochemistry. CONCLUSIONS: Our data indicate that flow-stimulated angiogenesis is determined by an upregulation of cytokines, oxygenation associated genes and miRNA-dependent regulation of FOXC1, EPHA2 and SYNJ2BP.

Ceritinib-Induced Regression of an Insulin-Like Growth Factor-Driven Neuroepithelial Brain Tumor.

The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood-brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.

Irradiation Delays Tissue Growth but Enhances Osteogenic Differentiation in Vascularized Constructs.

BACKGROUND: Regenerative medicine is still deficient in the reconstruction after cancer due to impaired vascularization after radiotherapy and due to the need to substitute larger defects after tumor excision. Aiming at introducing regenerative medicine for reconstruction after cancer, we tested an axially vascularized bone construct in an experimental setting that mimics the clinical situation after tumor resection and adjuvant radiotherapy. METHODS: Twenty bone constructs were axially vascularized using microsurgically created arteriovenous loops and were implanted subcutaneously in Lewis rats. After 2 weeks, the animals were randomly allocated either to receive a clinically relevant single dose of external beam irradiation or not (n = 10 for each group). The animals were sacrificed either after 1 week or 10 weeks after irradiation (n = 5 for each time point). The constructs were tested for vascularization, tissue growth, cellular proliferation, cellular apoptosis, and osteogenic differentiation via histomorphometric, immunohistochemical, and polymerase chain reaction (PCR) analysis. One construct per group was subjected at 10 weeks to qualitative micro-computed tomography (CT) imaging. RESULTS: Tissue generation and cellular proliferation were significantly reduced at 1 week after irradiation, but no longer significantly different after 10 weeks.No significant differences in vascularization were detected at any time point. Apoptosis did not show any statistically significant differences between both groups at both time points. At the late time point, mature bone was considerably more in the irradiated group, but the results were not statistically significant. PCR analysis showed a significantly enhanced expression of osteocalcin in the irradiated group at 1 week. Micro-CT imaging showed that both constructs were adequately vascularized with no evident morphologic differences regarding vascular density or vascular distribution. CONCLUSIONS: Axially vascularized bone constructs can withstand clinically relevant doses of irradiation and retain their angiogenic and osteogenic potential in the long term. Irradiation led to a delayed tissue generation with a comparatively enhanced osteogenic differentiation within the constructs.

Evaluation of the apparent diffusion coefficient in patients with recurrent glioblastoma under treatment with bevacizumab with radiographic pseudoresponse.

BACKGROUND: Response Assessment in Neuro-Oncology Criteria (RANO), are used to asses response to first-line treatment of glioblastoma (GBM). Differentiation between response and pseudoresponse under treatment with Bevacizumab (BVZ) remains challenging. This study evaluates ADC changes in patients with radiographic pseudoresponse under treatment with (BVZ). METHODS: Patients (n=40) with recurrent GBM under-treatment with BVZ underwent MRI before, two and four months after treatment with BVZ. In patients with radiological pseudoresponse (n=11), ADC analyses were performed. Areas with decreasing T1 contrast enhancement (CE) and FLAIR signal decrease were manually selected and compared to size and position matched healthy contralateral brain parenchyma. RESULTS: Histogram based ADC (10-6×mm2/s) of these patients decreased significantly (P<0.005) from baseline MRI (T1-CE, FLAIR: 1124.9±160.3, 1098.4±226.2, respectively) to 2months (781.3±110.7, 783.3±103.3) and remained stable during 4months (777.0±138.5, 784.4±155.4, all mean±1 SD), despite progressive disease. Mean ADC values of the healthy contralateral brain tissue remained stable (P>0.05) (ADC values: baseline: 786.2±110.7, 2months: 781.1±76.2, 4months: 804.1±86.2). CONCLUSION: Treatment of GBM with BVZ leads to a decrease of ADC values in areas of pre-treatment T1-CE/FLAIR signal hyperintensity to levels of comparable with normal brain tissue. ADC values remained stable, even when progressive tumor growth was reported.

[Orbital Manifestation of IgG4-Related Disease: Three Case Reports]. / Orbitale Manifestation der IgG4-assoziierten Erkrankung: eine Fallserie.

IgG4-related orbital disease is rare. It belongs to an entity of a multisystemic disorder - IgG4-related disease - which has emerged recently. Differential diagnosis comprises idiopathic orbital inflammation, endocrine orbitopathy and orbital neoplasms. MRI imaging and orbital biopsy are essential in making the diagnosis. Patients respond well to systemic steroids. We now describe three clinically markedly different manifestations of IgG4-related orbital disease.

Faim2 contributes to neuroprotection by erythropoietin in transient brain ischemia.

Delayed cell death in the penumbra region of acute ischemic stroke occurs through apoptotic mechanisms, making it amenable to therapeutic interventions. Fas/CD95 mediates apoptotic cell death in response to external stimuli. In mature neurons, Fas/CD95 signaling is modulated by Fas-apoptotic inhibitory molecule 2 (Faim2), which reduces cell death in animal models of stroke, meningitis, and Parkinson disease. Erythropoietin (EPO) has been studied as a therapeutic strategy in ischemic stroke. Erythropoietin stimulates the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway, which regulates Faim2 expression. Therefore, up-regulation of Faim2 may contribute to neuroprotection by EPO. Male Faim2-deficient mice (Faim2-/- ) and wild-type littermates (WT) were subjected to 30 min of middle cerebral artery occlusion (MCAo) followed by 72 h of reperfusion. EPO was applied before (30 min) and after (24 and 48 h) MCAo. In WT mice application of EPO at a low dose (5000 U/kg) significantly reduced stroke volume, whereas treatment with high dose (90 000 U/kg) did not. In Faim2-/- animals administration of low-dose EPO did not result in a significant reduction in stroke volume. Faim2 expression as measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) increased after low-dose EPO but not with high dose. An extensive phenotyping including analysis of cerebral vessel architecture did not reveal confounding differences between the genotypes. In human post-mortem brain Faim2 displayed a differential expression in areas of penumbral ischemia. Faim2 up-regulation may contribute to the neuroprotective effects of low-dose erythropoietin in transient brain ischemia. The dose-dependency may explain mixed effects of erythropoietin observed in clinical stroke trials.

Diagnostic Accuracy of Simulated Low-Dose Perfusion CT to Detect Cerebral Perfusion Impairment after Aneurysmal Subarachnoid Hemorrhage: A Retrospective Analysis.

Purpose To evaluate diagnostic accuracy of low-dose volume perfusion (VP) computed tomography (CT) compared with original VP CT regarding the detection of cerebral perfusion impairment after aneurysmal subarachnoid hemorrhage. Materials and Methods In this retrospective study, 85 patients (mean age, 59.6 years; 62 women) with aneurysmal subarachnoid hemorrhage and who were suspected of having cerebral vasospasm at unenhanced CT and VP CT (tube voltage, 80 kVp; tube current-time product, 180 mAs) were included, 37 of whom underwent digital subtraction angiography (DSA) within 6 hours. Low-dose VP CT data sets at tube current-time product of 72 mAs were retrospectively generated by validated realistic simulation. Perfusion maps were generated from both data sets and reviewed by two neuroradiologists for overall image quality, diagnostic confidence and presence and/or severity of perfusion impairment indicating vasospasm. An interventional neuroradiologist evaluated 16 vascular segments at DSA. Diagnostic accuracy of low-dose VP CT was calculated with original VP CT as reference standard. Agreement between findings of both data sets was assessed by using weighted Cohen κ and findings were correlated with DSA by using Spearman correlation. After quantitative volumetric analysis, lesion volumes were compared on both VP CT data sets. Results Low-dose VP CT yielded good ratings of image quality and diagnostic confidence and classified all patients correctly with high diagnostic accuracy (sensitivity, 99.0%; specificity, 99.5%) without significant differences regarding presence and/or severity of perfusion impairment between original and low-dose data sets (Z = -0.447; P = .655). Findings of both data sets correlated significantly with DSA (original, r = 0.671; low dose, r = 0.667). Lesion volume was comparable for both data sets (relative difference, 5.9% ± 5.1 [range, 0.2%-25.0%; median, 4.0%]) with strong correlation (r = 0.955). Conclusion The results suggest that radiation dose reduction to 40% of original dose levels (tube current-time product, 72 mAs) may be performed in VP CT imaging of patients with aneurysmal subarachnoid hemorrhage without compromising the diagnostic accuracy regarding detection of cerebral perfusion impairment indicating vasospasm. © RSNA, 2018 Online supplemental material is available for this article.

Assessing abrasion of orthodontic surface sealants using a modified ophthalmic optical coherence tomography device.

OBJECTIVE: Optical coherence tomography (OCT) is a clinical standard in ophthalmology. Currently, its application in dentistry is gaining increasing interest. In this study, we tested the possibility to use a modified commercially available spectral domain OCT (SD-OCT) to assess the layer thickness of orthodontic surface sealants. MATERIALS AND METHODS: Reference samples of surface sealants for calibration and repeatability testing were measured using a micrometer screw. SD-OCT measurements were compared with micro-CT and light microscopic analyses. After validating the calibration of the SD-OCT, surface sealant layer thickness after aging (thermo cycling) and simulation of professional tooth cleaning (PTC) was assessed using the SD-OCT on 45 extracted teeth assigned to three test groups (n = 15 each): Light Bond™ Sealant, Pro Seal®, and Opal® Seal. RESULTS: SD-OCT showed excellent repeatability and accuracy for measurements of surface sealant layer thickness. Compared with micro-CT, SD-OCT showed better accordance with the reference measurements. The analysis of surface sealants after thermo cycling and PTC revealed poor resistance of Light Bond after only aging and demonstrated substantial wear of all sealants after aging and PTC. CONCLUSION: Imaging using commercially available ophthalmic SD-OCT might represent a suitable non-invasive methodology for longitudinal assessments of surface sealant layer thickness in vitro and in vivo. CLINICAL RELEVANCE: SD-OCT might be a suitable non-invasive method for longitudinal assessments of surface sealant durability in clinical trials.

Diagnostic performance of different perfusion algorithms for the detection of angiographical spasm.

PURPOSE: To assess the diagnostic utility of different perfusion algorithms for the detection of angiographical terial spasm. METHOD: During a 2-year period, 45 datasets from 29 patients (54.2±10,75y, 20F) with suspected cerebral vasospasm after aneurysmal subarachnoid hemorrhage were included. Volume Perfusion CT (VPCT), Non-enhanced CT (NCT) and angiography were performed within 6hours post-ictus. Perfusion maps were generated using a maximum slope (MS) and a deconvolution-based approach (DC). Two blinded neuroradiologists independently evaluated MS and DC maps regarding vasospasm-related perfusion impairment on a 3-point Likert-scale (0=no impairment, 1=impairment affecting <50%, 2=impairment affecting >50% of vascular territory). A third independent neuroradiologist assessed angiography for presence and severity of arterial narrowing on a 3-point Likert scale (0=no narrowing, 1=narrowing affecting <50%, 2=narrowing affecting>50% of artery diameter). MS and DC perfusion maps were evaluated regarding diagnostic accuracy for angiographical arterial spasm with angiography as reference standard. Correlation analysis of angiography findings with both MS and DC perfusion maps was additionally performed. Furthermor, the agreement between MS and DC and inter-reader agreement was assessed. RESULTS: DC maps yielded significantly higher diagnostic accuracy than MS perfusion maps (DC:AUC=.870; MS:AUC=.805; P=0.007) with higher sensitivity for DC compared to MS (DC:sensitivity=.758; MS:sensitivity=.625). DC maps revealed stronger correlation with angiography than MS (DC: R=.788; MS: R=694;=<0.001). MS and DC showed substantial agreement (Kappa=.626). Regarding inter-reader analysis, (almost) perfect inter-reader agreement was observed for both MS and DC maps (Kappa≥981). CONCLUSION: DC yields significantly higher diagnostic accuracy for the detection of angiographic arterial spasm and higher correlation with angiographic findings compared to MS.

Ischemic stroke and intracranial hemorrhage in patients with recurrent glioblastoma multiforme, treated with bevacizumab.

Bevacizumab (BVZ), a monoclonal antibody directed against vascular endothelial growth factor (VEGF), has been suspected to increase the incidence of ischemic stroke (IS) and intracranial hemorrhage (ICH) in GBM patients. Intracranial vascular events, such as IS and ICH, were retrospectively analyzed in 364 MRI scans of 82 patients with recurrent GBM (1st/2nd/3rd relapse). Out of these 82 patients, 40 were treated with BVZ (178 scans) in addition to basic treatment, whereas 42 patients matching for age and gender received basic treatment (186 scans). Distribution of typical vascular risk factors between both groups was analyzed retrospectively. In seven out of 82 patients (8%) vascular events were detected in MRI. Four vascular events were recorded in the BVZ-group (3 IS and 1 ICH), and 3 vascular events were found in the Control-group (1 IS and 2 ICH; p > 0.05 between both groups). Likewise, vascular risk factors (arterial hypertension, diabetes mellitus, obesity, former vascular event, hyperlipidemia, tobacco consumption and/or hypercholesterolemia) did not differ significantly between both groups. BVZ treatment does not seem to be associated with an increased risk for vascular events in patients with GBM in recurrence.