Follow-up of cystic pineal glands in retinoblastoma patients does not increase detection of pineal trilateral retinoblastoma.

PURPOSE: To evaluate the effectiveness of baseline screening and follow-up with MRI to detecting trilateral retinoblastoma (TRb) and assessing the risk of TRb development. DESIGN: Prospective multicenter cohort study METHODS: A total of 607 retinoblastoma patients from 2012 through 2022 were included and followed up until 1-9-2023. At each center a neuroradiologist categorized pineal glands on baseline and follow-up scans into four groups: (A) normal, (B) cystic gland, (C) suspicious gland, or (D) TRb. Different follow-up schedules were assigned to each category. Categories (B) and (C) were followed-up with MRI after approximately 3-months and after another 3 months if suspicion remained. On each MRI, they measured the height and width, evaluated the aspect (solid, partly cystic and completely cystic) of the pineal gland and evaluated radiological features suspicious of pineal TRb. The effectiveness of the current TRb screening method was assessed by evaluating its sensitivity and specificity to detect TRb. Determining the TRb incidence was a secondary outcome measure. RESULTS: Heritable retinoblastoma patients had a risk of 3.78% to develop TRb. One out of four pineal TRbs was detected during a follow-up scan and four out of five non-pineal TRbs were detected on the baseline MRI. Screening for pineal TRb had a sensitivity of 25% and specificity of 100%, for non-pineal TRb the sensitivity was 80%. It required 494 follow-up scans to detect one pineal TRb. However, when restricting the follow-up to solely suspicious glands, only 22 scans were required to detect one pineal TRb. CONCLUSION: During extended follow-up after baseline MRI, only one pineal trilateral retinoblastoma was detected in our study. Follow-up after three months should be restricted to patients with a suspicious pineal gland defined as irregularly thickening of the cyst wall (>2mm), fine nodular aspect of the cyst wall or when a solid or cystic gland exceeds the upper 99% prediction interval for size; patients with an unsuspicious cystic gland should not be followed up. Baseline MRI screening was able to detect most non-pineal trilateral retinoblastomas.

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.

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.

Optic nerve thickening on high-spatial-resolution MRI predicts early-stage postlaminar optic nerve invasion in retinoblastoma.

OBJECTIVES: To assess the diagnostic accuracy of nerve thickening on MRI to predict early-stage postlaminar optic nerve invasion (PLONI) in retinoblastoma. Furthermore, this study aimed to incorporate measurements into a multiparametric model for radiological determination of PLONI. METHODS: In this retrospective multicenter case-control study, high-spatial-resolution 3D T2-weighted MR images were used to measure the distal optic nerve. Histopathology was the reference standard for PLONI. Two neuroradiologists independently measured the optic nerve width, height, and surface at 0, 3, and 5 mm from the most distal part of the optic nerve. Subsequently, PLONI was scored on contrast-enhanced T1-weighted and 3D T2-weighted images, blinded for clinical data. Optic nerve measurements with the highest diagnostic accuracy for PLONI were incorporated into a prediction model for radiological determination of PLONI. RESULTS: One hundred twenty-four retinoblastoma patients (median age, 22 months [range, 0-113], 58 female) were included, resulting in 25 retinoblastoma eyes with histopathologically proven PLONI and 206 without PLONI. ROC analysis of axial optic nerve width measured at 0 mm yielded the best area under the curve of 0.88 (95% confidence interval: 0.79, 0.96; p < 0.001). The optimal width cutoff was ≥ 2.215 mm, with a sensitivity of 84% (95% CI: 64, 95%) and specificity of 83% (95% CI: 75, 89%) for detecting PLONI. Combining width measurements with the suspicion of PLONI on MRI sequences resulted in a prediction model with an improved sensitivity and specificity of respectively up to 88% and 92%. CONCLUSION: Postlaminar optic nerve thickening can predict early-stage postlaminar optic nerve invasion in retinoblastoma. CLINICAL RELEVANCE STATEMENT: This study provides an additional tool for clinicians to help determine postlaminar optic nerve invasion, which is a risk factor for developing metastatic disease in retinoblastoma patients. KEY POINTS: • The diagnostic accuracy of contrast-enhanced MRI for detecting postlaminar optic nerve invasion is limited in retinoblastoma patients. • Optic nerve thickening can predict postlaminar optic nerve invasion. • A prediction model combining MRI features has a high sensitivity and specificity for detecting postlaminar optic nerve invasion.

MRI Features for Identifying MYCN-amplified RB1 Wild-type Retinoblastoma.

Background MYCN-amplified RB1 wild-type (MYCNARB1+/+) retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic subtype. Purpose To define the MRI phenotype of MYCNARB1+/+ retinoblastoma and evaluate the ability of qualitative MRI features to help identify this specific genetic subtype. Materials and Methods In this retrospective, multicenter, case-control study, MRI scans in children with MYCNARB1+/+ retinoblastoma and age-matched children with RB1-/- subtype retinoblastoma were included (case-control ratio, 1:4; scans acquired from June 2001 to February 2021; scans collected from May 2018 to October 2021). Patients with histopathologically confirmed unilateral retinoblastoma, genetic testing (RB1/MYCN status), and MRI scans were included. Associations between radiologist-scored imaging features and diagnosis were assessed with the Fisher exact test or Fisher-Freeman-Halton test, and Bonferroni-corrected P values were calculated. Results A total of 110 patients from 10 retinoblastoma referral centers were included: 22 children with MYCNARB1+/+ retinoblastoma and 88 control children with RB1-/- retinoblastoma. Children in the MYCNARB1+/+ group had a median age of 7.0 months (IQR, 5.0-9.0 months) (13 boys), while children in the RB1-/- group had a median age of 9.0 months (IQR, 4.6-13.4 months) (46 boys). MYCNARB1+/+ retinoblastomas were typically peripherally located (in 10 of 17 children; specificity, 97%; P < .001) and exhibited plaque or pleomorphic shape (in 20 of 22 children; specificity, 51%; P = .011) with irregular margins (in 16 of 22 children; specificity, 70%; P = .008) and extensive retina folding with vitreous enclosure (specificity, 94%; P < .001). MYCNARB1+/+ retinoblastomas showed peritumoral hemorrhage (in 17 of 21 children; specificity, 88%; P < .001), subretinal hemorrhage with a fluid-fluid level (in eight of 22 children; specificity, 95%; P = .005), and strong anterior chamber enhancement (in 13 of 21 children; specificity, 80%; P = .008). Conclusion MYCNARB1+/+ retinoblastomas show distinct MRI features that could enable early identification of these tumors. This may improve patient selection for tailored treatment in the future. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rollins in this issue.

Rare stroke mechanisms in 4154 consecutive patients: causes, predictors, treatment, and outcomes.

BACKGROUND: Rare mechanisms of stroke (RMS) in acute ischemic stroke (AIS) have rarely been studied applying a systematic approach. Our aim was to define the frequency, etiologies, predictors, and outcomes of RMS in a consecutive series of AIS. METHODS: Data from consecutive patients from 2003 to 2016 were derived from the Acute STroke Registry and Analysis of Lausanne (ASTRAL). Frequency of subcategories of RMS was calculated. In a case-control design, RMS were compared to strokes of all other mechanisms. Outcome was assessed with 3-month Rankin-shift and 12-month mortality and recurrence rates. RESULTS: Out of 4154 AISs, 222 (5.3%) were found to have a RMS (42.0% female, median age 66 years). The most frequent RMS etiologies were medical interventions (25.6%), active oncological disease (22.5%), and vasculitis (11.7%). In multivariate analysis, RMS patients were younger, had more preceding and bilateral strokes, and a higher admission temperature. They were associated with less traditional risk factors and more systemic disease (such as AIDS, coagulopathy, and cancer). RMS also had more early ischemic changes on plain CT, less revascularization treatments, and more symptomatic hemorrhagic transformations. They presented significantly higher 3-month disability (Rankin-shift-ORadj 1.74), 12-month recurrence (ORadj 1.99), and mortality rates (ORadj 2.41). CONCLUSIONS: RMS occurred in 5.3% of a large population of consecutive AISs and are most frequently related to medical interventions, cancer, and vasculitis. RMS patients have less traditional risk factors but more systemic comorbidities, hemorrhagic transformations, recurrences, and a worse long-term outcome. Identification of RMS has direct implications for early treatment and long-term outcome.

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.

Early-onset leukoencephalomyelopathy due to a biallelic NDUFV1 variant in a mid-forties patient.

We present a patient who developed, after an early-onset, a stable course of spastic paraplegia and ataxia for 4 decades and eventually succumbed to two episodes of postinfectious lactic acidosis. Diagnostic workup including muscle biopsy and postmortem analysis, oxymetric analysis, spectrophotometric enzyme analysis, and MitoExome sequencing revealed a necrotizing leukoencephalomyelopathy due to the so far unreported biallelic variant of the NDUFV1 gene (p.(Pro122Leu)). This case extends our understanding of NDUFV1 variants with a 14-fold longer lifetime than so far reported cases, and will foster sensitivity toward respiratory chain disease also in adult patients with sudden deteriorating neurological deficits.

Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG).

Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future.

Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas.

Vestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years follow-up were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1-73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3-9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications.

MR Imaging Features to Differentiate Retinoblastoma from Coats' Disease and Persistent Fetal Vasculature.

Retinoblastoma mimickers, or pseudoretinoblastoma, are conditions that show similarities with the pediatric cancer retinoblastoma. However, false-positive retinoblastoma diagnosis can cause mistreatment, while false-negative diagnosis can cause life-threatening treatment delay. The purpose of this study is to identify the MR imaging features that best differentiate between retinoblastoma and the most common pseudoretinoblastoma diagnoses: Coats' disease and persistent fetal vasculature (PFV). Here, six expert radiologists performed retrospective assessments (blinded for diagnosis) of MR images of patients with a final diagnosis based on histopathology or clinical follow-up. Associations between 20 predefined imaging features and diagnosis were assessed with exact tests corrected for multiple hypothesis testing. Sixty-six patients were included, of which 33 (50%) were retinoblastoma and 33 (50%) pseudoretinoblastoma patients. A larger eye size, vitreous seeding, and sharp-V-shaped retinal detachment were almost exclusively found in retinoblastoma (p < 0.001-0.022, specificity 93-97%). Features that were almost exclusively found in pseudoretinoblastoma included smaller eye size, ciliary/lens deformations, optic nerve atrophy, a central stalk between optic disc and lens, Y-shaped retinal detachment, and absence of calcifications (p < 0.001-0.022, specificity 91-100%). Additionally, three newly identified imaging features were exclusively present in pseudoretinoblastoma: intraretinal macrocysts (p < 0.001, 38% [9/24] in Coats' disease and 20% [2/10] in PFV), contrast enhancement outside the solid lesion (p < 0.001, 30% [7/23] in Coats' disease and 57% [4/7] in PFV), and enhancing subfoveal nodules (38% [9/24] in Coats' disease). An assessment strategy was proposed for MR imaging differentiation between retinoblastoma and pseudoretinoblastoma, including three newly identified differentiating MR imaging features.

Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. "Alive, with good vision and no comorbidity".

Retinoblastoma is lethal by metastasis if left untreated, so the primary goal of therapy is to preserve life, with ocular survival, visual preservation and quality of life as secondary aims. Historically, enucleation was the first successful therapeutic approach to decrease mortality, followed over 100 years ago by the first eye salvage attempts with radiotherapy. This led to the empiric delineation of a window for conservative management subject to a "state of metastatic grace" never to be violated. Over the last two decades, conservative management of retinoblastoma witnessed an impressive acceleration of improvements, culminating in two major paradigm shifts in therapeutic strategy. Firstly, the introduction of systemic chemotherapy and focal treatments in the late 1990s enabled radiotherapy to be progressively abandoned. Around 10 years later, the advent of chemotherapy in situ, with the capitalization of new routes of targeted drug delivery, namely intra-arterial, intravitreal and now intracameral injections, allowed significant increase in eye preservation rate, definitive eradication of radiotherapy and reduction of systemic chemotherapy. Here we intend to review the relevant knowledge susceptible to improve the conservative management of retinoblastoma in compliance with the "state of metastatic grace", with particular attention to (i) reviewing how new imaging modalities impact the frontiers of conservative management, (ii) dissecting retinoblastoma genesis, growth patterns, and intraocular routes of tumor propagation, (iii) assessing major therapeutic changes and trends, (iv) proposing a classification of relapsing retinoblastoma, (v) examining treatable/preventable disease-related or treatment-induced complications, and (vi) appraising new therapeutic targets and concepts, as well as liquid biopsy potentiality.

Extra-Axial Cavernoma of the Cerebellopontine Angle: A Case Study and Review of Literature.

BACKGROUND: Extra-axial cavernoma (EAC) at the cerebellopontine angle (CPA) is a rare clinical entity that can mimic radiologically several lesions encountered at this location. We report a case of EAC-CPA and present a review of the literature. METHODS: A PubMed research was conducted looking for EAC-CPA lesions described in literature. After reviewing all the relevant articles, the following data were extracted and organized into a single table: patients' symptoms, radiological characteristics, surgical procedure, histopathology, and outcome. RESULTS: Eighteen cases (including ours) were identified from these reports. Mean age at diagnosis was 42 with a male:female ratio of 2.6:1. The most commonly involved cranial nerves were the vestibulocochlear complex followed by the trigeminal nerve. The lesions were iso-to hypodense on computed tomography. On magnetic resonance imaging, the EAC-CPA can be solid or cystic. All lesions were approached using retrosigmoid craniotomies. Histologically, both intra- and extra-axial cavernomas are identical, consisting of devoid vascular sinusoids with endothelial lining. The outcome was favorable in 16/18 of the described cases. One case presented a worsened facial paresis and 1 patient died from excessive intraoperative bleeding and subsequent complications. CONCLUSIONS: Despite the fact that EAC-CPA are rarely encountered, it should be kept in mind in the list of differential diagnosis, preparing both the surgeon and anesthesiologist for the surgery of a vascular lesion. Specific radiological features, especially an associated developmental venous anomaly could point to the diagnosis.

Age, But Not Repeated Exposure to Gadoterate Meglumine, Is Associated With T1- and T2-Weighted Signal Intensity Changes in the Deep Brain Nuclei of Pediatric Patients.

OBJECTIVES: Current findings on gadolinium deposition in the pediatric brain due to repeated exposure to macrocyclic contrast agents are inconclusive and possibly confounded by brain maturation processes. We evaluated the longitudinal effects of repeated gadoterate meglumine exposure (Dotarem; Guerbet, Villepinte, France) on the T1- and T2-weighted signal intensity (SI) in pediatric patients, and assessed the magnitude of age-related increase in T1-weighted (and decrease in T2-weighted) SI in a control cohort without prior gadolinium exposure. MATERIALS AND METHODS: In this retrospective, double-cohort study, magnetic resonance imaging (MRI) data of 24 patients (0.7-16.4 years, M = 5.74, SD = 4.15) who received at least 10 doses of exclusively gadoterate meglumine were included in the longitudinal study. The MRI data of 190 controls (age range, 1-20 years; 10 patients/bin; bin width, 1 year) without any prior gadolinium-based contrast exposure were included in the control, cross-sectional study to assess the age-dependent SI changes in the regions of interest (ROIs). We measured SI (native), T1-weighted gradient echo, and T2-weighted fast spin-echo of 12 deep brain nuclei. The ROIs were measured at each of the first 11 MRI examinations of the contrast-exposed patients and in the control subject's MRI. Regions of interest's SIs, normalized by the pons, were analyzed with mixed effects models, accounting for the potential confounding factors, such as radiotherapy and chemotherapy. RESULTS: The number of gadoterate meglumine administrations had no effect on the SI increase in any of the ROIs (all P > 0.05), but age significantly correlated with increased SI in T1-weighted globus pallidus (GP; P < 0.01) and caudate (P < 0.05), and with decreased SI in T2-weighted GP (P < 0.001) and dentate nucleus (P < 0.005) in the contrast-exposed group. The cross-sectional analyses of the control cohort showed a significant age-dependent T1-weighted SI increase in multiple ROIs, including the GP and caudate, and decrease in the T2-weighted GP and dentate nucleus (P < 0.05). CONCLUSIONS: Repeated exposure to gadoterate meglumine was not associated with brain hyperintensity in the pediatric patients, whereas age importantly contributed to the SI changes in several deep brain nuclei.

Personalized Anatomic Eye Model From T1-Weighted Volume Interpolated Gradient Echo Magnetic Resonance Imaging of Patients With Uveal Melanoma.

PURPOSE: We present a 3-dimensional patient-specific eye model from magnetic resonance imaging (MRI) for proton therapy treatment planning of uveal melanoma (UM). During MRI acquisition of UM patients, the point fixation can be difficult and, together with physiological blinking, can introduce motion artifacts in the images, thus challenging the model creation. Furthermore, the unclear boundary of the small objects (eg, lens, optic nerve) near the muscle or of the tumors with hemorrhage and tantalum clips can limit model accuracy. METHODS AND MATERIALS: A dataset of 37 subjects, including 30 healthy eyes of volunteers and 7 eyes of UM patients, was investigated. In our previous work, active shape model was successfully applied to retinoblastoma eye segmentation in T1-weighted 3T MRI. Here, we evaluate this method in a more challenging setting, based on 1.5T MRI acquisition and different datasets of awake adult eyes with UM. The lens and cornea together with the sclera, vitreous humor, and optic nerve were automatically segmented and validated against manual delineations of a senior ocular radiation oncologist, in terms of the Dice similarity coefficient and Hausdorff distance. RESULTS: Leave-one-out cross validation (mixing both volunteers and UM patients) yielded median Dice similarity coefficient values (respective of Hausdorff distance) of 94.5% (1.64 mm) for the sclera, 92.2% (1.73 mm) for the vitreous humor, 88.3% (1.09 mm) for the lens, and 81.9% (1.86 mm) for the optic nerve. The average computation time for an eye was 10 seconds. CONCLUSIONS: To our knowledge, our work is the first attempt to automatically segment adult eyes, including patients with UM. Our results show that automated active shape model segmentation can succeed in the presence of motion, tumors, and tantalum clips. These results are promising for inclusion in clinical practice.

MR Imaging Features of Retinoblastoma: Association with Gene Expression Profiles.

Purpose To identify associations between magnetic resonance (MR) imaging features and gene expression in retinoblastoma. Materials and Methods A retinoblastoma MR imaging atlas was validated by using anonymized MR images from referral centers in Essen, Germany, and Paris, France. Images were from 39 patients with retinoblastoma (16 male and 18 female patients [the sex in five patients was unknown]; age range, 5-90 months; inclusion criterion: pretreatment MR imaging). This atlas was used to compare MR imaging features with genome-wide messenger RNA (mRNA) expression data from 60 consecutive patients obtained from 1995 to 2012 (35 male patients [58%]; age range, 2-69 months; inclusion criteria: pretreatment MR imaging, genome-wide mRNA expression data available). Imaging pathway associations were analyzed by means of gene enrichment. In addition, imaging features were compared with a predefined gene expression signature of photoreceptorness. Statistical analysis was performed with generalized linear modeling of radiology traits on normalized log2-transformed expression values. P values were corrected for multiple hypothesis testing. Results Radiogenomic analysis revealed 1336 differentially expressed genes for qualitative imaging features (threshold P = .05 after multiple hypothesis correction). Loss of photoreceptorness gene expression correlated with advanced stage imaging features, including multiple lesions (P = .03) and greater eye size (P < .001). The number of lesions on MR images was associated with expression of MYCN (P = .04). A newly defined radiophenotype of diffuse-growing, plaque-shaped, multifocal tumors displayed overexpression of SERTAD3 (P = .003, P = .049, and P = .06, respectively), a protein that stimulates cell growth by activating the E2F network. Conclusion Radiogenomic biomarkers can potentially help predict molecular features, such as photoreceptorness loss, that indicate tumor progression. Results imply a possible role for radiogenomics in future staging and treatment decision making in retinoblastoma.

Gamma knife radiosurgery for arteriovenous malformations: general principles and preliminary results in a Swiss cohort.

INTRODUCTION: Arteriovenous malformations (AVMs) are a type of vascular malformation characterised by an abnormal connection between arteries and veins, bypassing the capillary system. This absence of capillaries generates an elevated pressure (hyperdebit), in both the AVM and the venous drainage, increasing the risk of rupture. Management modalities are: observation, microsurgical clipping, endovascular treatment and radiosurgery. The former can be used alone or in the frame of a multidisciplinary approach. We review our single-institution experience with gamma knife radiosurgery (GKR) over a period of 5 years. MATERIALS AND METHODS: The study was open-label, prospective and nonrandomised. Fifty-seven consecutive patients, benefitting from 64 GKR treatments, were included. All were treated with Leksell Gamma Knife Perfexion (Elekta Instruments, AB, Sweden) between July 2010 and August 2015. All underwent stereotactic multimodal imaging: standard digital subtraction angiography, magnetic resonance imaging and computed tomography angiography. We report obliteration rates, radiation-induced complications and haemorrhages during follow-up course. RESULTS: The mean age was 46 years (range 13-79 years). The mean follow-up period was 36.4 months (median 38, range 12-75 months). Most common pretherapeutic clinical presentation was haemorrhage (50%). The most common Pollock-Flickinger score was between 1.01 and 1.5 (46%) and Spetzler-Martin grade III (46%). In 39 (60.1%) of cases, GKR was performed as upfront therapeutic option. The mean gross target volume (GTV) was 2.3 ml (median 1.2, range 0.03-11.3 ml). Mean marginal dose was 22.4 Gy (median 24, range 18-24 Gy). The mean prescription isodose volume (PIV) was 2.9 ml (median 1.8, range 0.065-14.6 ml). The overall obliteration rates (all treatments combined) at 12, 24, 36, 48 and 60 months were 4.8, 16.9%, 37.4, 63.6 and 78.4%, respectively. The main predictive factors for complete obliteration were: higher mean marginal dose (23.3 vs 21.0 Gy), lower GTV (mean 1.5 vs 3.5 ml) and absence of previous embolisation (at 60 months 61.8% prior embolisation compared with 82.4% without prior embolisation) (for all p <0.05). Eight (14%) patients experienced complications after GKR. Overall definitive morbidity rate was 3.1%. No patient died from causes related to GKR. However, during the obliteration period, one case of extremely rare fatal haemorrhage occurred. CONCLUSION: Radiosurgery is a safe and effective treatment modality for intracranial AVMs in selected cases. It can be used as upfront therapy or in the frame of a combined management. Obliteration rates are high, with minimal morbidity. The treatment effect is progressive and subsequent and regular clinical and radiological follow-up is needed to evaluate this effect.

Successful conservative treatment of massive choroidal relapse in 2 retinoblastoma patients monitored by ultrasound biomicroscopy and/or spectral domain optic coherence tomography.

PURPOSE: To report the occurrence and management of secondary choroidal infiltration in two retinoblastoma (rb) patients. METHODS: Fundus examination and imaging with spectral domain optical coherence tomography (SD-OCT), B-scan ultrasonography (B-scan), and ultrasound biomicroscopy (UBM). RESULTS: Case 1: A 19-month-old girl with multifocal unilateral group B rb pretreated with intravenous chemotherapy (IVC) was referred for further management. At 3.5 years of age, routine 3-Tesla magnetic resonance imaging (3T-MRI) revealed an asymptomatic pinealoblastoma that underwent resection and adjuvant intensive IVC. Concomitant ophthalmic follow-up revealed a recurrence 8.3 × 2.8 mm at the posterior pole nasally to the optic disc on B-scan, localized within the choroid on SD-OCT and 3T-MRI. With high dose IVC ongoing, total regression of the choroidal mass was confirmed on SD-OCT already after 3 weeks. At 6-month follow-up, choroidal and pineal tumors were in complete remission. Sadly, the child died of intravascular disseminated coagulation-like disease after the 5th IVC. Case 2: A heavily pretreated 20-month-old girl with bilateral rb was referred for persistent vitreous seeding in her remaining eye (OD). Three months after intravitreal chemotherapy and chemothermotherapy, a hemorrhagic mass was observed inferior to the primary tumor. Two weeks later, an underlying peripheral choroidal mass 16 × 6 mm was documented by UBM and confirmed by 3T-MRI. Complete resolution was achieved 3 weeks after combined intra-arterial chemotherapy (IAC) of melphalan-topotecan. No recurrence or metastasis was observed at 34-month follow-up. CONCLUSION: Isolated massive choroidal invasion can be treated conservatively with IVC or IAC in selected cases. SD-OCT, UBM, and B-scan ultrasonography are instrumental in the detection and follow-up of choroidal lesions.