Myriam Edjlali’s research while affiliated with Hôpital Raymond-Poincaré – Hôpitaux universitaires Paris Ile-de-France Ouest and other places

Aims FGFR ‐fused central nervous system (CNS) tumours are rare and are usually within the glioneuronal and neuronal tumours or the paediatric‐type diffuse low‐grade glioma spectrum. Among this spectrum, FGFR2 fusion has been documented in tumours classified by DNA‐methylation profiling as polymorphous low‐grade neuroepithelial tumours of the young (PLNTY), a recently described tumour type. However, FGFR2 fusions have also been reported in glioneuronal tumours, highlighting the overlapping diagnostic criteria and challenges. Methods We investigated the FGFR2 fusion landscape in a French national series of tumours sent to the RENOCLIP‐LOC network. We comprehensively analysed histology, radiology and molecular data including DNA‐methylation profiling for 16 FGFR2 ‐fused glioneuronal tumours. Results Most tumours were located in the temporal or parietal lobe with a median age at diagnosis of 7 years [1–44]. Epilepsy was the most frequent symptom. Five patients had tumour progression or recurrence with a median progression‐free survival of 22.6 months. Histological phenotypes corresponding to PLNTY, GG, MVNT or unclassified tumours were recorded. Epigenetic profiling could not properly distinguish epigenetic clusters related to the GG and PLNTY methylation classes among FGFR2 ‐fused glioneuronal tumours. However, a neuroradiological review identified strikingly distinct neuroradiological patterns. Conclusion While delineating tumour types among the FGFR2 ‐fused glioneuronal tumour spectrum, by histopathology or DNA‐methylation profiling, remains challenging, neuroimaging data revealed two distinct patterns that could correlate to PLNTY and ganglioglioma. However, more series including extensive histo‐radio‐molecular data are needed to confirm this hypothesis.

BACKGROUND Most common malignant brain tumors are metastases (BM) and glioblastoma (GBM). Stereotactic and fractionated radiotherapy are modalities of choice for treatment of these malignancies. As a delayed complication of these treatments, radiation necrosis can occur several months and even years after the completion of radiotherapy. Distinguishing between tumor recurrence and radionecrosis solely through conventional MRI and functional MRI can be challenging at times. This challenge can result in delays in clinical decision-making or require utilization of additional imaging modalities such as PET for more accurate diagnosis. The aim of this study was to distinguish radionecrosis from tumor progression of post-radiotherapy brain tumors (BM and GBM) thanks to computer analysis comparing follow-up MRI exam to initial MRI exam, with DOPA PET as a gold standard. Developed method is a classification task at the patient level. MATERIAL AND METHODS This retrospective study included 16 patients with GBM and BM, whom had total of 17 lesions. Lesions were split into 3 subsets: 5 lesions of radionecrosis, 10 lesions of tumor progression, 2 lesions with mixed radionecrosis and progression. We analyzed 2 time points: baseline M0 exam - the first time showing enhancing part of the lesion on a post-radiotherapy MRI exam; follow-up M1 exam - MR time point exam on which the lesion clearly showed expansion. DOPA PET MRI was done at the time of M1 exam and served as a gold standard. Specific preprocessing steps were implemented. Firstly, automatic lesion segmentation and elastic co-registration were done, where M2 was aligned to M1 images. Then, rigid co-registration of M2 and DOPA was applied to the M1 images, after which center of the lesion was computed. The analysis of deformation vector field was performed. On the slice showing the maximum area of the lesion, the radius (mm) from the centre of mass of the lesion mask for M0 and M1 was calculated, and the absolute and relative variations for each 360º angle between M0 and M1 were studied and compared with the mean DOPA uptake per angle (Bq/ml). RESULTS Tumor recurrence and radionecrosis can be distinguished thanks to their growth patterns. The mean standard deviation on angular variation showed lower values for radionecrosis (4.69, IQR 3.37 - 4.49) compared to tumor progression (11.72, IQR 6.3 - 13.54), which goes in concordance with DOPA uptake on PET exam: lower in radionecrosis (4459.43 IQR 4466.55 - 4804.67) compared to progression (6099.02, IQR 4559.19 - 7328.72). CONCLUSION This fully-automatable proof-of-concept computational model showed that application of auto-segmentation and elastic co-registration in the analysis of tumor’s growth could have with certainty distinguish radionecrosis from tumor progression thanks to the analysis of their growth by obtained deformation vector fields. Further validation on bigger number of lesions is needed.

Vascular inflammation is widely recognized as an important factor in the atherosclerotic process, particularly in terms of plaque development and progression. Conventional tests, such as measuring circulating inflammatory biomarkers, lack the precision to identify specific areas of vascular inflammation. In this context, noninvasive imaging modalities can detect perivascular fat changes, serving as a marker of vascular inflammation. This review aims to provide a comprehensive overview of the key concepts related to perivascular carotid fat and its pathophysiology. Additionally, we examine the existing literature on the association of pericarotid fat with features of plaque vulnerability and cerebrovascular events. Finally, we scrutinize the advantages and limitations of the noninvasive assessment of pericarotid fat.

A novel methylation class, “neuroepithelial tumor, with PLAGL1 fusion” (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as “mixed subependymomas-ependymomas” with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.

Spontaneous ICH is usually intraparenchymal or subarachnoid in location. Intraparenchymal hemorrhages, encompassing lobar or centrally located hematomas, have diverse underlying causes, with cerebral amyloid angiopathy, characterized by lobar hemorrhage, being the most common. Hypertension is the second most common cause with a predilection for the basal ganglia, pons, and cerebellum. Subarachnoid hemorrhage is linked to aneurysm rupture in 85% of cases. Other relatively common causes of spontaneous intracranial hemorrhage include hemorrhagic conversion of ischemic infarction, cerebral arteriovenous malformations, dural arteriovenous fistulas, venous sinus thrombosis, cavernous malformations, reversible cerebral vasoconstriction syndrome, coagulopathy, and underlying tumors. Computed tomography followed by CT angiography is used for initial assessment of spontaneous ICH. However, MRI is more sensitive than CT for the detection of ICH and plays an important role in their etiology characterization. In this paper, the authors present a logical approach to imaging spontaneous intracranial hemorrhage including identifying prognostic factors, determining etiology, and establishing treatment.

Purpose The assessment of multiple sclerosis (MS) lesions on follow-up magnetic resonance imaging (MRI) is tedious, time-consuming, and error-prone. Automation of low-level tasks could enhance the radiologist in this work. We evaluate the intelligent automation software Jazz in a blinded three centers study, for the assessment of new, slowly expanding, and contrast-enhancing MS lesions. Methods In three separate centers, 117 MS follow-up MRIs were blindly analyzed on fluid attenuated inversion recovery (FLAIR), pre- and post-gadolinium T1-weighted images using Jazz by 2 neuroradiologists in each center. The reading time was recorded. The ground truth was defined in a second reading by side-by-side comparison of both reports from Jazz and the standard clinical report. The number of described new, slowly expanding, and contrast-enhancing lesions described with Jazz was compared to the lesions described in the standard clinical report. Results A total of 96 new lesions from 41 patients and 162 slowly expanding lesions (SELs) from 61 patients were described in the ground truth reading. A significantly larger number of new lesions were described using Jazz compared to the standard clinical report (63 versus 24). No SELs were reported in the standard clinical report, while 95 SELs were reported on average using Jazz. A total of 4 new contrast-enhancing lesions were found in all reports. The reading with Jazz was very time efficient, taking on average 2min33s ± 1min0s per case. Overall inter-reader agreement for new lesions between the readers using Jazz was moderate for new lesions (Cohen kappa = 0.5) and slight for SELs (0.08). Conclusion The quality and the productivity of neuroradiological reading of MS follow-up MRI scans can be significantly improved using the dedicated software Jazz.

In recent years, ultra-high-field magnetic resonance imaging (MRI) applications have been rapidly increasing in both clinical research and practice. Indeed, 7-Tesla (7T) MRI allows improved depiction of smaller structures with high signal-to-noise ratio, and, therefore, may improve lesion visualization, diagnostic capabilities, and thus potentially affect treatment decision-making. Incremental evidence emerging from research over the past two decades has provided a promising prospect of 7T magnetic resonance angiography (MRA) in the evaluation of intracranial vasculature. The ultra-high resolution and excellent image quality of 7T MRA allow us to explore detailed morphological and hemodynamic information, detect subtle pathological changes in early stages, and provide new insights allowing for deeper understanding of pathological mechanisms of various cerebrovascular diseases. However, along with the benefits of ultra-high field strength, some challenges and concerns exist. Despite these, ongoing technical developments and clinical oriented research will facilitate the widespread clinical application of 7T MRA in the near future. In this review article, we summarize technical aspects, clinical applications, and recent advances of 7T MRA in the evaluation of intracranial vascular disease. The aim of this review is to provide a clinical perspective for the potential application of 7T MRA for the assessment of intracranial vascular disease, and to explore possible future research directions implementing this technique.

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T1 by up to 15 times compared to conventional T1-weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T2-weighted spin echo (T2-wSE) and/or fluid attenuated inversion recovery (T2-FLAIR) images. The small changes in T1 or T2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T1 maps. There is a nearly linear relationship between signal and T1 in the middle domain (mD) of the two sequences which includes T1s between the nulling T1s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T2-wSE and T2-FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T1-bipolar filters; to explain their targeting, signal, contrast, boundaries, T1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences.