Automated Detection of Cerebral Aneurysms on TOF-MRA Using a Deep Learning Approach: An External Validation Study.

BACKGROUND AND PURPOSE: Cerebral aneurysms yield the risk of rupture, severe disability and death. Thus, early detection of cerebral aneurysms is crucial to ensure timely treatment, if necessary. AI-based software tools are expected to enhance radiologists' performance in detecting pathologies like cerebral aneurysms in the future. Our aim was to evaluate the diagnostic performance of an artificial intelligence-based software designed to detect intracranial aneurysms on TOF-MRA. MATERIALS AND METHODS: One hundred ninety-one MR imaging data sets were analyzed using the software mdbrain for the presence of intracranial aneurysms on TOF-MRA obtained using two 3T MR imaging scanners or a 1.5T MR imaging scanner according to our clinical standard protocol. The results were compared with the reading of an experienced radiologist as a criterion standard to measure the sensitivity, specificity, positive and negative predictive values, and accuracy of the software. Additionally, detection rates depending on size, morphology, and location of the aneurysms were evaluated. RESULTS: Fifty-four aneurysms were detected by the expert reader. The overall sensitivity of the software for the detection of cerebral aneurysms was 72.6%, the specificity was 87.2%, and the accuracy was 82.6%. The positive predictive value was 67.9%, and the negative predictive value was 88.5%. We observed a sensitivity of 100% for saccular aneurysms of >5 mm without signs of thrombosis and low detection rates for fusiform or thrombosed aneurysms of 33.3% and 16.7%, respectively. Of 8 aneurysms that were not included in the initial written reports but were detected by the expert reader, retrospectively, 4 were detected by the software. CONCLUSIONS: Our data suggest that the software can assist radiologists in reporting TOF-MRA. The software was highly reliable in detecting saccular aneurysms, while for fusiform or thrombosed aneurysms, further improvements are needed. Further studies are necessary to investigate the impact of the software on detection rates, interrater reliability, and reading times.

[Autologous hematopoietic stem cell transplantation for autoimmune diseases : Current indications and mode of action, a review on behalf of the EBMT Autoimmune Diseases Working Party (ADWP)]. / Autologe hämatopoetische Stammzelltransplantation bei Autoimmunerkrankungen : Aktuelle Indikationen und Wirkungsweise, ein Review der EBMT Autoimmune Diseases Working Party (ADWP).

The recent introduction of biologic and targeted synthetic disease-modifying drugs has led to more specificity in the treatment of autoimmune diseases; however, they require continuous or intermittent administration, are associated with cumulative risks for side effects, result in high costs and provide no cure. In contrast, high-dose chemotherapy followed by transplantation of autologous hematopoietic stem cells (AHSCT) has been demonstrated to induce clinical remission in various autoimmune diseases that can persist over many years without continued maintenance therapy. The principle behind AHSCT is an elimination of important components of the autoreactive immunological memory with subsequent regeneration of the complete immune system. Several studies have indicated that such an immune reset is associated with fundamental changes in the immune repertoire leading to an induction of tolerance against self-antigens. This article presents the current indications of AHSCT for autoimmune diseases based on the registry data of the European Society of Blood and Marrow Transplantation (EBMT) and discusses the results from mechanistic studies, which provide detailed insights into the mode of action of this treatment.

Is Histologic Thrombus Composition in Acute Stroke Linked to Stroke Etiology or to Interventional Parameters?

BACKGROUND AND PURPOSE: Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results. MATERIALS AND METHODS: Thrombi from 85 patients who had undergone mechanical thrombectomy for acute ischemic stroke between December 2016 and March 2018 were studied retrospectively. Thrombi were examined histologically. Preinterventional imaging features, stroke subtypes, and interventional parameters were re-analyzed. Statistical analysis was performed with the Kruskal-Wallis test, Mann-Whitney U test, or Spearman correlation as appropriate. RESULTS: Cardioembolic thrombi had a higher percentage of macrophages and a tendency toward more platelets than thrombi of large-artery atherosclerotic stenosis (P = .021 and .003) or the embolic stroke of undetermined source (P = .037 and .099) subtype. Thrombi prone to fragmentation required the combined use of contact aspiration and stent retrieval (P = .021) and were associated with an increased number of retrieving maneuvers (P = .001), longer procedural times (P = .001), and a higher lymphocyte content (P = .035). CONCLUSIONS: We interpreted the higher macrophage and platelet content in cardioembolic thrombi compared with large-artery atherosclerotic stenosis or embolic stroke of undetermined source thrombi as an indication that the latter type might be derived from an atherosclerotic plaque rather than from an undetermined cardiac source. The extent of thrombus fragmentation was associated with a more challenging mechanical thrombectomy and a higher lymphocyte content of the thrombi. Thus, thrombus fragmentation not only might be caused by the recanalization procedure but also might be a feature of a lymphocyte-rich, difficult-to-retrieve subgroup of thrombi.

Increased volumes of mildly elevated capillary transit time heterogeneity positively predict favorable outcome and negatively predict intracranial hemorrhage in acute ischemic stroke with large vessel occlusion.

OBJECTIVES: In patients with acute ischemic stroke, we aimed to investigate whether microvascular changes, as indexed by capillary transit time heterogeneity (CTH), contribute to the decline of the chance for favorable outcome over time and whether they are a predictor of an intracranial hemorrhage (ICH). METHODS: We retrospectively calculated CTH maps for 131 consecutive patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation who had a relevant MRI PWI-DWI mismatch and were treated with endovascular thrombectomy (ET). Multivariable logistic regressions were conducted with favorable outcome (mRS ≤ 2 after 3 months) and occurrence of an ICH as dependent variables and the volume of mildly elevated CTH as independent variable adjusted for age, successful recanalization, hypertension, diabetes, atrial fibrillation, NIHSS score on admission, DWI lesion volume, and symptom-onset-to-treatment time (OTT). RESULTS: A larger volume of mildly elevated CTH was a positive predictor of favorable outcome (OR 1.17; 1.03-1.33; p = 0.019) and a negative predictor of ICH (OR 0.83; 0.73-0.96; p = 0.009). As expected, successful recanalization (OR 5.54; 1.8-17; p = 0.003), low NIHSS on admission (OR 0.9; 0.82-1.00; p = 0.045), short OTT (OR 0.96; 0.94-0.99; p = 0.006), and low DWI volume (OR 0.68; 0.49-0.94; p = 0.021) were also predictors of favorable outcome, whereas other negative predictors of ICH were atrial fibrillation (OR 2.69; 1.10-6.57; p = 0.030), high NIHSS score on admission (OR 1.10 (1.01-1.19); p = 0.030), and large DWI volume (OR 1.51; 1.17-1.19; p = 0.002). CONCLUSION: An increased volume of mildly elevated CTH is a positive predictor of favorable outcome and a negative predictor for ICH in patients with acute ischemic stroke and mismatch undergoing ET. KEY POINTS: • The classification of potentially salvageable tissue and infarct core based on traditional net perfusion parameters (as Tmax or CBF) does not account for the microvascular distribution of blood. • However, the microvascular distribution of blood, as indexed by the capillary transit time heterogeneity (CTH), directly affects the availability of oxygen within the hypoperfused tissue and should therefore be respected in acute ischemic stroke imaging. • In our study, mildly elevated CTH is found to be a positive predictor for a favorable clinical outcome and a negative predictor for the occurrence of an intracranial hemorrhage in patients with acute ischemic stroke and homogenous mismatch who underwent ET.

Radiation exposure of image-guided intrathecal administration of nusinersen to adult patients with spinal muscular atrophy.

PURPOSE: To examine diagnostic reference levels (DRL) and achievable doses (AD) of image-guided and size-specific dose estimates (SSDE) and organ and effective doses of CT-guided intrathecal nusinersen administration to adult patients with spinal muscular atrophy (SMA). METHODS: This study involved a total of 60 image-guided intrathecal nusinersen treatments between August 2017 and June 2018. Patient cohort comprised 14 adult patients with the following SMA types: type 2 (n = 9) and type 3 (n = 5) with a mean age of 33.6 years (age range 25-57 years). DRL, AD, SSDE, organ, and effective doses were assessed with a dose-monitoring program based on the Monte Carlo simulation techniques. RESULTS: DRL and AD for computed tomography are summarised as follows: in terms of CT-dose index (CTDIvol), DRL 56.4 mGy and AD 36.7 mGy; in terms of dose-length product (DLP), DRL 233.1 mGy cm and AD 120.1 mGy cm. DRL and AD for fluoroscopic guidance were distributed as follows: in terms of dose-area product (DAP), DRL 239.1 µGy m2 and AD 135.2 mGy cm2. Mean SSDE was 9.2 mGy. Mean effective dose of the CT-guided injections was 2.5 mSv (median 2.0 mSv, IQR 1.3-3.2 mSv). Highest organ doses in the primary beam of radiation were the small intestine 12.9 mSv, large intestine 9.5 mSv, and ovaries 3.6 mSv. CONCLUSION: Radiation exposure of SMA patients measured as DRLs is generally not higher compared with patients without SMA despite severe anatomical hazards. Dose monitoring data may allow clinicians to stratify radiation risk, identify organs at risk, and adopt measures for specific radiation dose reduction.

Detection of early infarction signs with machine learning-based diagnosis by means of the Alberta Stroke Program Early CT score (ASPECTS) in the clinical routine.

PURPOSE: New software solutions emerged to support radiologists in image interpretation in acute ischemic stroke. This study aimed to validate the performance of computer-aided assessment of the Alberta Stroke Program Early CT score (ASPECTS) for detecting signs of early infarction. METHODS: ASPECT scores were assessed in 119 CT scans of patients with acute middle cerebral artery ischemia. Patient collective was differentiated according to (I) normal brain, (II) leukoencephalopathic changes, (III) infarcts, and (IV) atypical parenchymal defects (multiple sclerosis, etc.). ASPECTS assessments were automatically provided by the software package e-ASPECTS (Brainomix®, UK) (A). Subsequently, three neuroradiologists (B), (C), and (D) examined independently 2380 brain regions. Interrater comparison was performed with the definite infarct core as reference standard after best medical care (thrombolysis and/or thrombectomy). RESULTS: Interrater comparison revealed higher correlation coefficient of (B) 0.71, (C) 0.76, and of (D) 0.80 with definite infarct core compared to (A) 0.59 for ASPECTS assessment in the acute ischemic stroke setting. While (B), (C), and (D) showed a significant correlation for individual patient groups (I), (II), (III), and (IV), except for (D) (II), (A) was not significant in patient groups with pre-existing changes (II), (III), and (IV). The following sensitivities, specificities, PPV, NPV, and accuracies given in percent were achieved: (A) 83, 57, 55, 82, and 67; (B) 74, 76, 69, 83, and 77; (C) 80.8, 85.2, 76, 84, and 80; (D) 63, 90.7, 82, 79, and 80, respectively. CONCLUSION: For ASPECTS assessment, the examined software may provide valid data in case of normal brain. It may enhance the work of neuroradiologists in clinical decision making. A final human check for plausibility is needed, particularly in patient groups with pre-existing cerebral changes.

[Research consortium Neuroimmunology and pain in the research network musculoskeletal diseases]. / Forschungsverbund Neuroimmunologie und Schmerz (Neuroimpa) im Forschungsnetz Muskuloskelettale Erkrankungen.

BACKGROUND: The research consortium Neuroimmunology and Pain (Neuroimpa) explores the importance of the relationships between the immune system and the nervous system in musculoskeletal diseases for the generation of pain and for the course of fracture healing and arthritis. MATERIAL AND METHODS: The spectrum of methods includes analyses at the single cell level, in vivo models of arthritis and fracture healing, imaging studies on brain function in animals and humans and analysis of data from patients. RESULTS: Proinflammatory cytokines significantly contribute to the generation of joint pain through neuronal cytokine receptors. Immune cells release opioid peptides which activate opioid receptors at peripheral nociceptors and thereby evoke hypoalgesia. The formation of new bone after fractures is significantly supported by the nervous system. The sympathetic nervous system promotes the development of immune-mediated arthritis. The studies show a significant analgesic potential of the neutralization of proinflammatory cytokines and of opioids which selectively inhibit peripheral neurons. Furthermore, they show that the modulation of neuronal mechanisms can beneficially influence the course of musculoskeletal diseases. DISCUSSION: Interventions in the interactions between the immune system and the nervous system hold a great therapeutic potential for the treatment of musculoskeletal diseases and pain.

Immunomodulation by vitamin D.

Vitamin D exerts several immunological functions in addition to its homeostatic functions on calcium and bone metabolism. Current data show that relative vitamin D deficiency (< 75 nmol/l 25-hydroxyvitamin D) as well as acquired seasonal vitamin D deficiency (< 50 nmol/l) are frequent in Germany. As confirmed by our own data, UV exposure plays a major role for maintenance of vitamin D status, e.g., in patients with UV-triggered diseases, vitamin D deficiency is more frequent, even throughout the year. The beneficial impact of vitamin D on immune functions is highlighted by epidemiologic, genetic, and experimental evidence. In the past years, numerous publications have presented associations between vitamin D deficiency, on the one hand, and severity and prevalence of allergic asthma in children and adults, on the other hand.

11C-MET PET/MRI for detection of recurrent glioma.

INTRODUCTION: Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid 11C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. METHODS: Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid 11C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid 11C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. RESULTS: Hybrid 11C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for 11C-MET PET (96.77% and 73.68%), and for hybrid 11C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid 11C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing 11C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). CONCLUSION: This feasibility study showed that hybrid PET/MRI might strengthen RANO classification by adding metabolic information to conventional MRI information. Future studies should evaluate the clinical utility of the combined use of 11C-MET PET/MRI in larger patient cohorts.

Long-term follow-up of fertility and pregnancy in autoimmune diseases after autologous haematopoietic stem cell transplantation.

Issues of fertility and pregnancy require special attention in the long-term care of patients with autoimmune diseases (AD), who are candidates for haematopoietic stem cell transplantation (HSCT). In this single-centre observational study, we report fertility status and pregnancy outcomes in 15 patients (11 female and 4 male) after immunoablation with cyclophosphamide, antithymocyte globulin and autologous CD34+-selected HSCT for severe, refractory AD. The median follow-up after HSCT was 12 years (range 2-16 years). Impaired fertility was observed in six patients (five females and one male) before HSCT based on sexual hormone measurements. Higher age and cumulative cyclophosphamide dosage before HSCT correlated with fertility impairment. Median serum level of follicle-stimulating hormone (FSH) was significantly higher in female patients at 1 year after HSCT compared to baseline values, but premature ovarian failure developed in only one patient. Four women had five pregnancies and six healthy offsprings during follow-up, and no miscarriages were observed. The mothers were in treatment-free remissions during conception. No peripartal flare of their AD occurred. Although AD patients undergoing HSCT are at risk of developing infertility, pre-HSCT treatment and patients' age seem to have higher impact on long-term fertility status than HSCT itself. HSCT offers the opportunity to conceive during treatment-free remissions with favourable pregnancy outcomes.

T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis.

The transcription factor T-bet is highly expressed by Th cells isolated from the inflamed intestine of Crohn's disease patients, and has been regarded a critical driver of murine T cell-induced colitis. However, we show here that T-bet expression by Th cells is not required for the manifestation of T-cell-induced colitis in the presence of segmented filamentous bacteria and Helicobacter hepaticus. T-bet expression by Th cells controls their survival and localization, their repertoire of chemokine and chemokine receptor expression, the accumulation of monocytes and macrophages in the inflamed colon, and their differentiation to the M1 type, i.e., type 1 inflammation. Nevertheless, T-bet-deficient Th cells efficiently induce colitis, as reflected by weight loss, diarrhea, and colon histopathology. T-bet-deficient Th cells differentiate into Th1/17 cells, able to express IFN-γ and IL-17A upon restimulation. While neutralization of IL-17A exacerbated colitis induced by wild-type or T-bet-deficient Th cells, neutralization of IFN-γ completely abolished colitis.

Advanced MR Imaging in Neuro-oncology.

The value of magnetic resonance (MR) imaging for the clinical management of brain tumour patients has greatly increased in recent years through the introduction of functional MR sequences. Previously, MR imaging for brain tumours relied for the most part on contrast-enhanced T1-weighted MR sequences but today with the help of advanced functional MR sequences, the pathophysiological aspects of tumour growth can be directly visualised and investigated. This article will present the pathophysiological background of the MR sequences relevant to neuro-oncological imaging as well as potential clinical applications. Ultimately, we take a look at possible future developments for ultra-high-field MR imaging.

Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score Using Hypointense Vessels on Susceptibility Weighted Imaging Independently Predicts Outcome in Patients with Basilar Artery Occlusion.

PURPOSE: Appearance of hypointense vessels on susceptibility weighted imaging (SWI) has been reported to correlate with outcome in patients with ischemia of the anterior circulation. This study investigates the correlation between the appearance of hypointense vessels on SWI after recanalization therapy and outcome in patients with basilar artery occlusion. METHODS: Patients with basilar artery occlusion who were treated with endovascular recanalization or intravenous alteplase and received an MRI including SWI after therapy were retrieved from the hospital database for retrospective analysis. Posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pcASPECTS) was calculated based on regions displaying hypointense vessels on SWI and compared to lesions on diffusion weighted imaging (DWI). Subsequently, SWI based pcASPECTS was correlated with outcome determined with modified Rankin Scale (mRS), categorized as favorable outcome (mRS 0-2) or unfavorable outcome (3-6). RESULTS: Twenty-two MRI of patients with basilar artery occlusion were analyzed. In seven out of eight areas of the pcASPECTS hypointense vessels on SWI were significantly correlated to areas of restricted diffusion on DWI. In univariate analysis median pcASPECTS on SWI was significantly higher in patients with favorable outcome (7.5 vs. 5, p=0.02). In a multivariate analysis pcASPECTS on SWI was an independent predictor of favorable outcome (OR 2.02; CI [1.02;3,99]; p=0.04). CONCLUSION: pcASPECTS based on hypointense vessels on SWI after therapy predicts outcome in patients with basilar artery occlusion and might potentially be used as an additional imaging biomarker in the management of patients with stroke in the posterior circulation. This needs to be confirmed in larger prospective clinical trials.

[Towards more precision in the therapy of brain tumors. Possibilities and limits of MRI]. / Auf dem Weg zu mehr Präzision in der Hirntumortherapie : Möglichkeiten und Grenzen der MR-Bildgebung.

Due to the introduction of advanced functional and spectroscopic magnetic resonance (MR) sequences, MR imaging has gained significant importance in neuro-oncology. In contrast to recent years when neuro-oncological imaging was mostly limited to contrast-enhanced T1-weighted images, advanced MR methods provide direct visualization and assessment of tumor pathophysiology. This article summarizes the most relevant MR methods for neuro-oncological imaging and highlights the pathophysiological background as well as potential clinical applications. Ultimately, this article gives a glimpse into the future and introduces potential applications of ultra-high field MRI.

[Pathogenesis of systemic lupus erythematosus]. / Pathogenese des systemischen Lupus erythematodes.

Systemic lupus erythematosus (SLE) is an autoimmune disease with an extremely complex pathogenesis. Due to a genetic predisposition the disease can be induced by multiple stress factors involving epigenetic mechanisms and under the influence of the innate immune system. Defective clearance of immune complexes and apoptotic material together with enhanced neutrophil extracellular trap formation (NETosis) as well as up-regulation of type 1 interferon in particular, drive the adaptive immune system to a breakdown of self-tolerance. The result is a B cell hyperactivity, which leads to the generation of a multitude of different autoantibodies that are not only directed against nuclear antigens. Autoantibodies are the initiators for the involvement of many organs, which enhances further inflammatory cells and cytokines by participation of effector T-cells. Finally, an autoreactive immunological (plasma cell) memory is formed, which contributes to chronification and is associated with therapy-refractive courses of the disease. The depletion of the autoreactive immunological memory by immunoablation can lead to induction of self-tolerance and long-term remission.