Bildgebung des Retinoblastoms : Aktueller Stand der Technik und Ausblick in die Zukunft

Hintergrund Das Retinoblastom ist der häufigste bösartige Augentumor im Kindesalter und in bis zu 40 % der Fälle mit einem Tumorprädispositionssyndrom assoziiert (RB1-Mutation). Die Bildgebung ist ein wichtiger Bestandteil der diagnostischen Evaluation von Kindern mit Retinoblastom zum Zeitpunkt der Diagnose und im Follow-up. Ziel der Arbeit Diese Übersichtsarbeit soll den aktuellen Stand der Technik und wichtige diagnostische Aspekte der radiologischen Bildgebung von Kindern mit Retinoblastom aufzeigen mit einem kurzen Ausblick in die Zukunft. Zusätzlich wird ein Überblick über die allgemeine klinische Diagnostik und die Therapiemöglichkeiten gegeben. Material und Methoden Basis der Arbeit ist die Recherche in verschiedenen Literaturdatenbanken sowie eigene Erfahrungen in der Bildgebung des Retinoblastoms. Schlussfolgerung Hochaufgelöste MRT-Bildgebung ist die Bildgebungsmodalität der Wahl bei Kindern mit Retinoblastomen zum Zeitpunkt der Diagnose (Abklärung der Diagnose/möglicher Differenzialdiagnosen, Evaluation der Tumorausdehnung okulär und intrakraniell) und im Follow-up. CT-Untersuchungen sind trotz der charakteristischen Verkalkungen zur Diagnostik nicht mehr indiziert. Da Retinoblastome bis zu 40 % mit Tumorprädispositionssyndromen assoziiert sind, sollte stets auch eine genetische Abklärung erfolgen. = Background Retinoblastoma is the most common malignant eye tumor in children and is associated with tumor predisposition syndrome (RB1 mutation) in up to 40% of cases. Imaging is an important part of the diagnostic workup of children with retinoblastoma both during the initial diagnosis and follow-up. Objectives The goal of this review is to present the current state-of-the-art regarding imaging of children with retinoblastoma, including technical background and diagnostic clues with a brief discussion of future prospects. In addition, we summarize the general clinical diagnostic workup and therapeutic options. Materials and methods Review of the literature and our own experience in the imaging of retinoblastoma. Conclusion High-resolution magnetic resonance imaging (MRI) is the imaging modality of choice in children with retinoblastoma for diagnosis (estimation of diagnosis/differential diagnosis, evaluation of local and intracranial tumor extension) and during follow-up. Despite the characteristic calcifications, computed tomography (CT) examinations are no longer indicated in these patients. Due to the high association with tumor predisposition syndrome, genetic counselling is recommended

Cerebellar patients do not benefit from cerebellar or M1 transcranial direct current stimulation during force-field reaching adaptation

Several studies have identified transcranial direct current stimulation (tDCS) as a potential tool in the rehabilitation of cerebellar disease. Here, we tested whether tDCS could alleviate motor impairments of subjects with cerebellar degeneration. Three groups took part in this study: 20 individuals with cerebellar degeneration, 20 age-matched controls, and 30 young controls. A standard reaching task with force-field perturbations was used to compare motor adaptation among groups and to measure the effect of stimulation of the cerebellum or primary motor cortex (M1). Cerebellar subjects and age-matched controls were tested during each stimulation type (cerebellum, M1, and sham) with a break of 1 wk among each of the three sessions. Young controls were tested during one session under one of three stimulation types (anodal cerebellum, cathodal cerebellum, or sham). As expected, individuals with cerebellar degeneration had a reduced ability to adapt to motor perturbations. Importantly, cerebellar patients did not benefit from anodal stimulation of the cerebellum or M1. Furthermore, no stimulation effects could be detected in aging and young controls. The present null results cannot exclude more subtle tDCS effects in larger subject populations and between-subject designs. Moreover, it is still possible that tDCS affects motor adaptation in cerebellar subjects and control subjects under a different task or with alternative stimulation parameters. However, for tDCS to become a valuable tool in the neurorehabilitation of cerebellar disease, stimulation effects should be present in group sizes commonly used in this rare patient population and be more consistent and predictable across subjects and tasks. NEW & NOTEWORTHY Transcranial direct current stimulation (tDCS) has been identified as a potential tool in the rehabilitation of cerebellar disease. We investigated whether tDCS of the cerebellum and primary motor cortex could alleviate motor impairments of subjects with cerebellar degeneration. The present study did not find stimulation effects of tDCS in young controls, aging controls, and individuals with cerebellar degeneration during reach adaptation. Our results require a re-evaluation of the clinical potential of tDCS in cerebellar patients

Magnetic Resonance Imaging Can Reliably Differentiate Optic Nerve Inflammation from Tumor Invasion in Retinoblastoma with Orbital Cellulitis

PURPOSE To investigate the prevalence and magnetic resonance imaging (MRI) phenotype of retinoblastoma-associated orbital cellulitis. Additionally, this study aimed to identify postlaminar optic nerve enhancement (PLONE) patterns differentiating between inflammation and tumor invasion. DESIGN A monocenter cohort study assessed the prevalence of orbital cellulitis features on MRI in retinoblastoma patients. A multicenter case-control study compared MRI features of the retinoblastoma-associated orbital cellulitis cases with retinoblastoma controls. PARTICIPANTS A consecutive retinoblastoma patient cohort of 236 patients (311 eyes) was retrospectively investigated. Subsequently, 30 retinoblastoma cases with orbital cellulitis were compared with 30 matched retinoblastoma controls without cellulitis. METHODS In the cohort study, retinoblastoma MRI scans were scored on presence of inflammatory features. In the case-control study, MRI scans were scored on intraocular features and PLONE patterns. Postlaminar enhancement patterns were compared with histopathologic assessment of postlaminar tumor invasion. Interreader agreement was assessed, and exact tests with Bonferroni correction were adopted for statistical comparisons. MAIN OUTCOME MEASURES Prevalence of retinoblastoma-associated orbital cellulitis on MRI was calculated. Frequency of intraocular MRI features was compared between cases and controls. Sensitivity and specificity of postlaminar optic nerve patterns for detection of postlaminar tumor invasion were assessed. RESULTS The MRI prevalence of retinoblastoma-associated orbital cellulitis was 6.8% (16/236). Retinoblastoma with orbital cellulitis showed significantly more tumor necrosis, uveal abnormalities (inflammation, hemorrhage, and necrosis), lens luxation (all P < 0.001), and a larger eye size (P = 0.012). The inflammatory pattern of optic nerve enhancement (strong enhancement similar to adjacent choroid) was solely found in orbital cellulitis cases, of which none (0/16) showed tumor invasion on histopathology. Invasive pattern enhancement was found in both cases and controls, of which 50% (5/10) showed tumor invasion on histopathology. Considering these different enhancement patterns suggestive for either inflammation or tumor invasion increased specificity for detection of postlaminar tumor invasion in orbital cellulitis cases from 32% (95% confidence interval [CI], 16-52) to 89% (95% CI, 72-98). CONCLUSIONS Retinoblastoma cases presenting with orbital cellulitis show MRI findings of a larger eye size, extensive tumor necrosis, uveal abnormalities, and lens luxation. Magnetic resonance imaging contrast-enhancement patterns within the postlaminar optic nerve can differentiate between tumor invasion and inflammatory changes

Correlation of gene expression with magnetic resonance imaging features of retinoblastoma: a multi-center radiogenomics validation study

OBJECTIVES To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma. METHODS In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis. Expression data from each center were first separately processed and analyzed. The end product normalized expression values from different sites were subsequently merged by their Z-score to permit cross-sites validation analysis. The MRI features were non-parametrically correlated with expression of photoreceptorness (radiogenomic analysis), a gene expression signature informing on disease progression. Outcomes were compared to outcomes in a previous described cohort. RESULTS Thirty-six retinoblastoma patients were included, 15 were female (42%), and mean age was 24 (SD 18) months. Similar to the prior evaluation, this validation study showed that low photoreceptorness gene expression was associated with advanced stage imaging features. Validated imaging features associated with low photoreceptorness were multifocality, a tumor encompassing the entire retina or entire globe, and a diffuse growth pattern (all p < 0.05). There were a number of radiogenomic associations that were also not validated. CONCLUSIONS A part of the radiogenomic associations could not be validated, underlining the importance of validation studies. Nevertheless, cross-center validation of imaging features associated with photoreceptorness gene expression highlighted the capability radiogenomics to non-invasively inform on molecular subtypes in retinoblastoma. CLINICAL RELEVANCE STATEMENT Radiogenomics may serve as a surrogate for molecular subtyping based on histopathology material in an era of eye-sparing retinoblastoma treatment strategies. KEY POINTS - Since retinoblastoma is increasingly treated using eye-sparing methods, MRI features informing on molecular subtypes that do not rely on histopathology material are important. - A part of the associations between retinoblastoma MRI features and gene expression profiles (radiogenomics) were validated. - Radiogenomics could be a non-invasive technique providing information on the molecular make-up of retinoblastoma

MR Imaging of Adverse Effects and Ocular Growth Decline after Selective Intra-Arterial Chemotherapy for Retinoblastoma

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research

Adjuvant therapy for children treated by enucleation at diagnosis of retinoblastoma

Introduction Advanced localized retinoblastoma can be cured by enucleation, but extraocular spread of retinoblastoma cells is associated with a high mortality. Risk-stratified adjuvant treatment with chemotherapy and radiotherapy has been shown to reduce the risk for extraocular relapse in children with histopathological risk factors. Methods Data of 184 patients with retinoblastoma and primary enucleation were collected in a prospective, multicenter, observational study between 2013 and 2020. The clinical characteristics were evaluated as risk factors and progression-free and overall survival rates were compared. Results Seventy-one percent of 184 children with retinoblastoma treated with primary enucleation were diagnosed with low risk histopathological factors (pT1/pT2a) and received no adjuvant therapy. Children with intermediate risk (pT2b,pT3; 48 children, 26.0%) and high risk for metastasis (pT4; 5 children, 2.7%) received risk-stratified adjuvant treatment. None of the children with low risk or intermediate risk (pT1-pT3) relapsed, but two of five children with high-risk retinoblastoma (pT4) developed extraocular relapses and one deceased. The 2-year progression-free survival rate and 2-year overall survival rate was 100% for children with pT1-3 retinoblastoma. However, the 2-year progression-free survival rate and 2-year overall survival rate for children with pT4 was statistically notably reduced with 2 of 5 children developing progression and 1 death among the 5 children within 2 years after diagnosis. Conclusion Primary enucleation alone and with additional risk-stratified adjuvant chemotherapy treatment provides high cure rates in patients with pT1-3 retinoblastoma, but children with pT4 retinoblastoma remain at high risk to develop extraocular retinoblastoma. International prospective clinical trials are required to evaluate reduction of intensity of adjuvant chemotherapy in some risk groups (pT2, pT3) and intensification for pT4 retinoblastoma

Computed tomographyand magnetic resonance image-based analysis of the anatomical variations of the Sylvian fissure and characteristics of the middle cerebral artery

The aim of this cross sectional anatomical study is to determine the distribution of the defined anatomical variations of the Sylvian fissure (SF) in a normal population and to analyze its bilateral superposable presentation. Furthermore, we examined the course of the middle cerebral artery (MCA) and the division of the MCA branches in relation to the SF types. A total of 300 cranial CT scans - 100 CT angiography datasets and 86 MRIs of patients without intracranial pathologies - were reviewed. The SF was categorized in five types based on Yasargils description and our previous publication. The length, diameter and branches of the MCA were measured and compared to the SF types. SPSS 23.0 for Windows® was used for statistical analysis. We analyzed data of 300 patients (171 male, 129 female; mean age 51.6years). Symmetric and mirror-imaged coherence of the SF was found in 266 patients (88.7%, χ2(8)=3.04, p=0.932). The distribution of the SF types showed significant differences in patients younger than 60 years compared to older patients. A bifurcation was observed in 72.0%. A trifurcation was observed in 12.0% and a false bifurcation in 16.0% of patients. There was no significant difference of the measured diameters or length of the M1 segments according to the SF types. In this CT and MRI based anatomical study we could show that a twisted and narrow SF occurred more frequently in patients younger than 60 years of age. The SF has a high congruence intra-individually. The anatomical condition might influence the size and configuration of the proximal MCA, which in turn might influence the surgeon’s choice of the approach to the SF. Preoperative evaluation on the basis of the presented data, may help to decide for an appropriate approach to the SF

Stent-assisted treatment of ruptured intracranial aneurysms in the acute phase: A single center experience

Introduction: The purpose of this study was to analyze the results of patients with ruptured aneurysms who were treated with a specific microstent in the acute phase of subarachnoid hemorrhage. Methods: Data from patients with acutely-ruptured intracranial aneurysm treated with the Neuroform stent in the period between 2003 and 2016 were retrospectively assessed, addressing aneurysm occlusion and clinical outcome with a focus on periprocedural complications. Results: Twenty-nine consecutive patients with ruptured intracranial aneurysms were included in the analysis. Periprocedural hemorrhagic complications were stated in six patients, leading to death in four. Thromboembolic complications were observed in seven patients, among whom only one affected the clinical outcome with death due to basilar thrombosis. Immediate complete occlusion and occlusion with residual neck was achieved in 79.3% of cases. Conclusion: Stent-assisted coiling of acutely-ruptured aneurysms achieves good immediate aneurysm occlusion. Rates of intra- and periprocedural adverse events observed in this series were significant, but did not translate to corresponding morbidity and mortality in all cases. The retrospective analysis did not allow assessing the overall risks of endovascular therapy with stent use in ruptured and complex aneurysm when compared to the overall risks with other alternative options. Keywords: Aneurysm treatment, Subarachnoid hemorrhage, Cerebral ruptured aneurysm, Stent assisted coil embolization, Hemorrhagic complication