Review of craniofacial pain syndromes involving the greater occipital nerve: relevant anatomy, clinical findings, and interventional management.

Craniofacial pain syndromes exhibit a high prevalence in the general population, with a subset of patients developing chronic pain that significantly impacts their quality of life and results in substantial disabilities. Anatomical and functional assessments of the greater occipital nerve (GON) have unveiled its implication in numerous craniofacial pain syndromes, notably through the trigeminal-cervical convergence complex. The pathophysiological involvement of the greater occipital nerve in craniofacial pain syndromes, coupled with its accessibility, designates it as the primary target for various interventional procedures in managing craniofacial pain syndromes. This educational review aims to describe multiple craniofacial pain syndromes, elucidate the role of GON in their pathophysiology, detail the relevant anatomy of the greater occipital nerve (including specific intervention sites), highlight the role of imaging in diagnosing craniofacial pain syndromes, and discuss various interventional procedures such as nerve infiltration, ablation, neuromodulation techniques, and surgeries. Imaging is essential in managing these patients, whether for diagnostic or therapeutic purposes. The utilization of image guidance has demonstrated an enhancement in reproducibility, as well as technical and clinical outcomes of interventional procedures. Studies have shown that interventional management of craniofacial pain is effective in treating occipital neuralgia, cervicogenic headaches, cluster headaches, trigeminal neuralgia, and chronic migraines, with a reported efficacy of 60-90% over a duration of 1-9 months. Repeated infiltrations, neuromodulation, or ablation may prove effective in selected cases. Therefore, reassessment of treatment response and efficacy during follow-up is imperative to guide further management and explore alternative treatment options. Optimal utilization of imaging, interventional techniques, and a multidisciplinary team, including radiologists, will ensure maximum benefit for these patients.

Combined vertebroplasty and pedicle screw insertion for vertebral consolidation: feasibility and technical considerations.

PURPOSE: To assess the feasibility and technical accuracy of performing pedicular screw placement combined with vertebroplasty in the radiological setting. METHODS: Patients who underwent combined vertebroplasty and pedicle screw insertion under combined computed tomography and fluoroscopic guidance in 4 interventional radiology centers from 2018 to 2023 were retrospectively assessed. Patient demographics, vertebral lesion type, and procedural data were analyzed. Strict intra-pedicular screw positioning was considered as technical success. Pain score was assessed according to the Visual Analogue Scale before the procedure and in the 1-month follow-up consultation. RESULTS: Fifty-seven patients (38 men and 19 women) with a mean age of 72.8 (SD = 11.4) years underwent a vertebroplasty associated with pedicular screw insertion for the treatment of traumatic fractures (29 patients) and neoplastic disease (28 patients). Screw placement accuracy assessed by post-procedure CT scan was 95.7% (89/93 inserted screws). A total of 93 pedicle screw placements (36 bi-pedicular and 21 unipedicular) in 32 lumbar, 22 thoracic, and 3 cervical levels were analyzed. Mean reported procedure time was 48.8 (SD = 14.7) min and average injected cement volume was 4.4 (SD = 0.9) mL. A mean VAS score decrease of 5 points was observed at 1-month follow-up (7.7, SD = 1.3 versus 2.7, SD = 1.7), p < .001. CONCLUSION: Combining a vertebroplasty and pedicle screw insertion is technically viable in the radiological setting, with a high screw positioning accuracy of 95.7%.

T1 Mapping From MPRAGE Acquisitions: Application to the Measurement of the Concentration of Nanoparticles in Tumors for Theranostic Use.

BACKGROUND: The measurement of the concentration of theranostic agents in vivo is essential for the assessment of their therapeutic efficacy and their safety regarding healthy tissue. To this end, there is a need for quantitative T1 measurements that can be obtained as part of a standard clinical imaging protocol applied to tumor patients. PURPOSE: To generate T1 maps from MR images obtained with the magnetization-prepared rapid gradient echo (MPRAGE) sequence. To evaluate the feasibility of the proposed approach on phantoms, animal and patients with brain metastases. STUDY TYPE: Pilot. PHANTOM/ANIMAL MODEL/POPULATION: Solutions containing contrast agents (chelated Gd3+ and iron nanoparticles), male rat of Wistar strain, three patients with brain metastases. FIELD STRENGTH/SEQUENCE: A 3-T and 7-T, saturation recovery (SR), and MPRAGE sequences. ASSESSMENT: The MPRAGE T1 measurement was compared to the reference SR method on phantoms and rat brain at 7-T. The robustness of the in vivo method was evaluated by studying the impact of misestimates of tissue proton density. Concentrations of Gd-based theranostic agents were measured at 3-T in gray matter and metastases in patients recruited in NanoRad clinical trial. STATISTICAL TESTS: A linear model was used to characterize the relation between T1 measurements from the MPRAGE and the SR acquisitions obtained in vitro at 7-T. RESULTS: The slope of the linear model was 0.966 (R2  = 0.9934). MPRAGE-based T1 values measured in the rat brain were 1723 msec in the thalamus. MPRAGE-based T1 values measured in patients in white matter and gray matter amounted to 747 msec and 1690 msec. Mean concentration values of Gd3+ in metastases were 61.47 µmol. DATA CONCLUSION: The T1 values obtained in vitro and in vivo support the validity of the proposed approach. The concentrations of Gd-based theranostic agents may be assessed in patients with metastases within a standard clinical imaging protocol using the MPRAGE sequence. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 1.

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were (a) positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, (b) severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, (c) neurologic manifestations, and (d) abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student t test or Wilcoxon test. P < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], P = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], P = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.

Machine learning assisted DSC-MRI radiomics as a tool for glioma classification by grade and mutation status.

BACKGROUND: Combining MRI techniques with machine learning methodology is rapidly gaining attention as a promising method for staging of brain gliomas. This study assesses the diagnostic value of such a framework applied to dynamic susceptibility contrast (DSC)-MRI in classifying treatment-naïve gliomas from a multi-center patients into WHO grades II-IV and across their isocitrate dehydrogenase (IDH) mutation status. METHODS: Three hundred thirty-three patients from 6 tertiary centres, diagnosed histologically and molecularly with primary gliomas (IDH-mutant = 151 or IDH-wildtype = 182) were retrospectively identified. Raw DSC-MRI data was post-processed for normalised leakage-corrected relative cerebral blood volume (rCBV) maps. Shape, intensity distribution (histogram) and rotational invariant Haralick texture features over the tumour mask were extracted. Differences in extracted features across glioma grades and mutation status were tested using the Wilcoxon two-sample test. A random-forest algorithm was employed (2-fold cross-validation, 250 repeats) to predict grades or mutation status using the extracted features. RESULTS: Shape, distribution and texture features showed significant differences across mutation status. WHO grade II-III differentiation was mostly driven by shape features while texture and intensity feature were more relevant for the III-IV separation. Increased number of features became significant when differentiating grades further apart from one another. Gliomas were correctly stratified by mutation status in 71% and by grade in 53% of the cases (87% of the gliomas grades predicted with distance less than 1). CONCLUSIONS: Despite large heterogeneity in the multi-center dataset, machine learning assisted DSC-MRI radiomics hold potential to address the inherent variability and presents a promising approach for non-invasive glioma molecular subtyping and grading.

Facial nerve tractography: A new tool for the detection of perineural spread in parotid cancers.

OBJECTIVES: To determine whether facial nerve MR tractography is useful in detecting PeriNeural Spread in parotid cancers. METHODS: Forty-five participants were enrolled. Thirty patients with surgically managed parotid tumors (15 malignant, 15 benign) were compared with 15 healthy volunteers. All of them had undergone 3T-MRI with diffusion acquisition and post-processing constrained spherical deconvolution-based tractography. Parameters of diffusion-weighted sequences were b-value 1,000 s/mm2, 32 directions. Two radiologists performed a blinded visual reading of tractographic maps and graded the facial nerve average pathlength and fractional anisotropy (FA). We also compared diagnostic accuracy of tractography with morphological MRI sequences to detect PeriNeural Spread. Non-parametric methods were used. RESULTS: Average pathlength was significantly higher in cases with PeriNeural Spread (39.86 mm [Quartile1: 36.27; Quartile3: 51.19]) versus cases without (16.23 mm [12.90; 24.90]), p<0.001. The threshold above which there was a significant association with PeriNeural Spread was set at 27.36 mm (Se: 100%; Sp: 84%; AUC: 0.96, 95% CI 0.904-1). There were no significant differences in FA between groups. Tractography map visual analyses directly displayed PeriNeural Spread in distal neural ramifications with sensitivity of 75%, versus 50% using morphological sequences. CONCLUSIONS: Tractography could be used to identify facial nerve PeriNeural Spread by parotid cancers. KEY POINTS: • Tractography could detect facial nerve PeriNeural Spread in parotid cancers. • The average pathlength parameter is increased in case of PeriNeural Spread. • Tractography could map PeriNeural Spread more precisely than conventional imaging.

Greater occipital nerve MR tractography: Feasibility and anatomical considerations.

BACKGROUND AND PURPOSE: To assess the feasibility of greater occipital nerve (GON) tractography using a fully automated tractography technique on the whole-neck volume, in comparison with anatomical knowledge. METHODS: Healthy subjects were consecutively included in this study if they had no history or symptoms of headache or brain disorder. A 3T MRI scanner with a 32 channel head coil was used. The following parameters for Diffusion Weighed (DWI) were used: b value of 1000 s/mm2, 32 directions, acquired voxel size: 2 mm isotropic. High-Order tractography with the Constrained Spherical Deconvolution (CSD) model was generated. Track-Weighted Imaging (TWI) maps were generated with MRTrix. Two radiologists performed blind evaluations of the GON pathways on TWI maps. RESULTS: A total of 20 healthy subjects were included (12 males and eight females, mean age 53.8 years old). In comparison with anatomical atlas, GON complete visualization (from C1-C2 origin to muscular emergence) was possible in 18 out of 20 healthy subjects. In two cases, GON was not visible in the cervical spine foramen. CONCLUSION: Tractography through TWI is a feasible technique to accurately depict GON. This technique may appear as a promising technique for therapeutic management of patients with occipital neuralgia.

The relationship between post-traumatic ossicular injuries and conductive hearing loss: A 3D-CT study.

PURPOSE: After a trauma, the conductive ossicular chain may be disrupted by ossicular luxation or fracture. Recent developments in 3D-CT allow a better understanding of ossicular injuries. In this retrospective study, we compared patients with post-traumatic conductive hearing loss (CHL) with those referred without CHL to evaluate the relationship between ossicular injuries and CHL. We also assessed the added value of 3D reconstructions on 2D-CT scan to detect ossicular lesions in patients surgically managed. METHODS: The CT scans were performed using a 40-section spiral CT scanner in 49 patients with post-traumatic CHL (n=29) and without CHL (n=20). Three radiologists performed independent blind evaluations of 2D-CT and 3D reconstructions to detect ossicular chain injury. We used the t-test to explore differences regarding the number of subjects with ossicular injury in the two groups. We also estimated the diagnostic accuracy and the inter-rater agreement of the 3D-CT reconstructions associated to 2D-CT scan. RESULTS: We identified ossicular abnormality in 14 patients out of 29 and in one patient out of 20 in the CHL and non-CHL groups respectively. There was a significant difference regarding the number of subjects with ossicular lesions between the two groups (P≤0.01). The diagnostic sensitivity of 3D-CT reconstructions associated with 2D-CT ranged from 66% to 100% and the inter-reader agreement ranged from 0.85 to 1, depending of the type of lesion. CONCLUSION: The relationship between ossicular lesion and the presence of CHL tightly correlated. 3D-CT reconstructions of the temporal bone are useful to assess patients in a post-traumatic context.

Refined modelling of the short-T2 signal component and ensuing detection of glutamate and glutamine in short-TE, localised, (1) H MR spectra of human glioma measured at 3 T.

Short-TE (1) H MRS has great potential for brain cancer diagnostics. A major difficulty in the analysis of the spectra is the contribution from short-T2 signal components, mainly coming from mobile lipids. This complicates the accurate estimation of the spectral parameters of the resonance lines from metabolites, so that a qualitative to semi-quantitative interpretation of the spectra dominates in practice. One solution to overcome this difficulty is to measure and estimate the short-T2 signal component and to subtract it from the total signal, thus leaving only the metabolite signals. The technique works well when applied to spectra obtained from healthy individuals, but requires some optimisation during data acquisition. In the clinical setting, time constraints hardly allow this. Here, we propose an iterative estimation of the short-T2 signal component, acquired in a single acquisition after measurement of the full spectrum. The method is based on QUEST (quantitation based on quantum estimation) and allows the refinement of the estimate of the short-T2 signal component after measurement. Thus, acquisition protocols used on healthy volunteers can also be used on patients without further optimisation. The aim is to improve metabolite detection and, ultimately, to enable the estimation of the glutamine and glutamate signals distinctly. These two metabolites are of great interest in the characterisation of brain cancer, gliomas in particular. When applied to spectra from healthy volunteers, the new algorithm yields similar results to QUEST and direct subtraction of the short-T2 signal component. With patients, up to 12 metabolites and, at least, seven can be quantified in each individual brain tumour spectrum, depending on the metabolic state of the tumour. The refinement of the short-T2 signal component significantly improves the fitting procedure and produces a separate short-T2 signal component that can be used for the analysis of mobile lipid resonances. Thus, in brain tumour spectra, distinct estimates of signals from glutamate and glutamine are possible. Copyright © 2016 John Wiley & Sons, Ltd.

Serum potassium concentration predicts brain hypoxia on CT after avalanche-induced cardiac arrest.

BACKGROUND: Brain anoxia after complete avalanche burial and cardiac arrest (CA) may occur despite adequate on-site triage. PURPOSE: To investigate clinical and biological parameters associated with brain hypoxia in a cohort of avalanche victims with whole body computed tomographic (CT) scan. METHODS: Retrospective study of patients with CA and whole body CT scan following complete avalanche burial admitted in a level-I trauma center. MAIN FINDINGS: Out of 19 buried patients with whole body CT scan, eight patients had refractory CA and 11 patients had pre-hospital return of spontaneous circulation. Six patients survived at hospital discharge and only two had good neurologic outcome. Twelve patients had signs of brain hypoxia on initial CT scan, defined as brain edema, loss of gray/white matter differentiation and/or hypodensity of basal ganglia. No clinical pre-hospital parameter was associated with brain anoxia. Serum potassium concentration at admission was higher in patients with brain anoxia as compared to patients with normal CT scan: 5.5 (4.1-7.2) mmol/L versus 3.3 (3.0-4.2) mmol/L, respectively (P<.01). A threshold of 4.35 mmol/L serum potassium had 100% specificity to predict brain anoxia on brain CT scan. CONCLUSIONS: Serum potassium concentration had good predictive value for brain anoxia after complete avalanche burial. This finding further supports the use of serum potassium concentration for extracorporeal life support insertion at hospital admission in this context.

Dynamic susceptibility contrast perfusion imaging in biopsy-proved adult medulloblastoma.

PURPOSE: Medulloblastoma (MB) is a high-grade rare brain tumor in adults, with heterogeneous imaging features and variable enhancing patterns. Diffusion and spectroscopy multimodal imaging have already been described in adult MB, yet perfusion has not been explored. This study aimed to evaluate vascularity in adult classic and desmoplastic MB, using perfusion-weighted dynamic susceptibility contrast (DSC) MRI and histopathology. METHODS: Six histologically proved MB patients were classified as classic (n=3) and desmoplastic (n=3). DSC perfusion MRI was performed in three centers and retrospectively evaluated. Postprocessing included automatic arterial input function, motion and contrast leakage correction. Region of interest (ROI) delineation was performed on three perfusion slices to obtain a total of three cerebral blood volume ratios (rCBV) that were averaged to serve as the main rCBV. Permeability was evaluated on K2 maps. RESULTS: Low rCBVs were observed in all cases (mean rCBV=1.19±0.39). rCBV values were lower than 2 for classic MB and lower than 1 for desmoplastic MB. All cases showed an increase of permeability on K2 maps. CONCLUSIONS: Our preliminary results suggest that MB exhibits rCBV values close to 1 and increased permeability on DSC perfusion imaging, especially in desmoplastic cases, which could be explained by fibrous matrix. This type of perfusion pattern contrasts with those given by other enhancing subtentorial tumors such as metastasis, high-grade gliomas or hemangioblastomas.

Reduced CMRO2 and cerebrovascular reserve in patients with severe intracranial arterial stenosis: a combined multiparametric qBOLD oxygenation and BOLD fMRI study.

Multiparametric quantitative blood oxygenation level dependent (mqBOLD) magnetic resonance Imaging (MRI) approach allows mapping tissular oxygen saturation (StO2 ) and cerebral metabolic rate of oxygen (CMRO2 ). To identify hemodynamic alteration related to severe intracranial arterial stenosis (SIAS), functional MRI of cerebrovascular reserve (CVR BOLD fMRI) to hypercapnia has been proposed. Diffusion imaging suggests chronic low grade ischemia in patients with impaired CVR. The aim of the present study was to evaluate how oxygen parameters (StO2 and CMRO2 ), assessed with mqBOLD approach, correlate with CVR in patients (n = 12) with SIAS and without arterial occlusion. The perfusion (dynamic susceptibility contrast), oxygenation, and CVR were compared. The MRI protocol conducted at 3T lasted approximately 1 h. Regions of interest measures on maps were delineated on segmented gray matter (GM) of middle cerebral artery territories. We have shown that decreased CVR is spatially associated with decreased CMRO2 in GM of patients with SIAS. Further, the degree of ipsilateral CVR reduction was well-correlated with the amplitude of the CMRO2 deficit. The altered CMRO2 suggests the presence of a moderate ischemia explained by both a decrease in perfusion and in CVR. CVR and mqBOLD method may be helpful in the selection of patients with SIAS to advocate for medical therapy or percutaneous transluminal angioplasty-stenting.

Imaging the microvessel caliber and density: Principles and applications of microvascular MRI.

Twenty years ago, theoretical developments were initiated to model the behavior of the NMR transverse relaxation rates in presence of vessels. These developments enabled the MRI-based mapping of mean vessel diameter, microvascular density, and vessel size index with comparable results to those obtained by a pathologist. The transfer of these techniques to routine clinical use has been hindered by the unavailability of the required sequences, namely fast gradient-echo spin-echo sequences. Based on the increasing accessibility of such sequences on MRI scanners over recent years, we review the principles governing microvascular MRI, the validation studies, and the applications that have been tested worldwide by several teams. We also provide some recommendations on how to measure microvessel caliber and density with MRI.

Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.

RATIONALE: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. AIMS: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. METHODS AND DESIGN: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. STUDY OUTCOMES: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. DISCUSSION: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.

Perfusion magnetic resonance imaging: comparison of semiologic characteristics in first-pass perfusion of brain tumors at 1.5 and 3 Tesla.

OBJECTIVES: To investigate whether using 3 Tesla (T) instead of 1.5T modifies the data obtained from first-pass perfusion in relation to the quantitative values of cerebral blood volume (CBV) and estimation of micro-vascular leakage (MVL). To describe the differences in data in the setting of neuro-oncology cases and propose explanations based on the discrepancies. MATERIAL AND METHODS: In total, 21 patients presenting an intracranial intra-axial space-occupying lesion underwent two MRI explorations, one at 1.5T and another at 3T, including a first-pass perfusion sequence using sequence parameters, defined by the manufacturer Philips. Using a gamma variate analysis, the ratio of cerebral blood volume (rCBV) in tumor, peritumoral, and normal appearing areas was first assessed. After a global analysis, a subgroup analysis was conducted according to the rCBV value measured at 1.5T. Lastly, MVL was assessed based on the signal intensity recorded above baseline after the passage of the contrast medium. RESULTS: At 3T, compared to 1.5T data that are currently the reference, rCBV was constantly and significantly over-evaluated (P=0.0041 for all tumors), while MVL was constantly and significantly under-evaluated (P<0.0001 for all tumors). DISCUSSION: The increase in magnetic field strength along with the associated modifications in sequence parameters led to variations in rCBV and MVL when measured using first-pass perfusion. In some cases, such as lymphomas, there was a loss of diagnostic information. It therefore appears necessary to optimize the acquisition parameters to allow for radiologic semiology to become relevant again.

Adult brainstem glioma differential diagnoses: an MRI-based approach in a series of 68 patients.

BACKGROUND: Brainstem gliomas are rare in adults. The diagnosis is often difficult, as some teams still consider brainstem biopsies dangerous and often avoid this procedure. The aim of this study was to describe differential diagnoses that can mimic brainstem glioma, to help clinicians avoid diagnostic and therapeutic mistakes, and to propose a diagnostic algorithm according to radiological presentations. METHODS: The French network of adult brainstem gliomas (GLITRAD) retrospectively collected all reported cases of differential diagnoses between 2006 and 2017. The inclusion criteria were as follows: age over 18 years, lesion epicenter in the brainstem, radiological pattern suggestive of a glioma and diagnostic confirmation (histopathological or not, depending on the disease). RESULTS: We identified a total of 68 cases. Most cases (58/68, 85%) presented as contrast-enhancing lesions. The most frequent final diagnosis in this group was metastases in 24/58 (41%), followed by central nervous system lymphoma in 8/58 (14%). Conversely, MRI findings revealed 10/68 nonenhancing lesions. The most frequent diagnosis in this group was demyelinating disease (3/10, 30%). CONCLUSION: The risk of diagnostic mistakes illustrates the need to consider the more systematic use of a brainstem biopsy when reasonably possible. However, we propose an MRI-based approach to the differential diagnosis of gliomas to limit the risk of misdiagnosis in cases where a biopsy is not a reasonable option.

PAR-1 Antagonism to Promote Gut Mucosa Healing in Crohn's Disease Patients: A New Avenue for CVT120165.

A new paradigm has been added for the treatment of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. In addition to resolving symptoms and inflammatory cell activation, the objective of tissue repair and mucosal healing is also now considered a primary goal. In the search of mediators that would be responsible for delayed mucosal healing, protease-activated receptor-1 (PAR-1) has emerged as a most interesting target. Indeed, in Crohn's disease, the endogenous PAR-1 agonist thrombin is drastically activated. Activation of PAR-1 is known to be associated with epithelial dysfunctions that hamper mucosal homeostasis. This review gathers the scientific evidences of a potential role for PAR-1 in mucosal damage and mucosal dysfunctions associated with chronic intestinal inflammation. The potential clinical benefits of PAR-1 antagonism to promote mucosal repair in CD patients are discussed. Targeted local delivery of a PAR-1 antagonist molecule such as CVT120165, a formulated version of the FDA-approved PAR-1 antagonist vorapaxar, at the mucosa of Crohn's disease patients could be proposed as a new indication for IBD that could be rapidly tested in clinical trials.

The potential clinical benefits and indications of PAR-1 antagonism to treat inflammatory bowel diseases are discussed.

Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial).

BACKGROUND AND PURPOSE: Brain metastasis impacts greatly on patients' quality of life and survival. The phase I NANO-RAD trial assessed the safety and maximum tolerated dose of systemic administration of a novel gadolinium-based nanoparticle, AGuIX, in combination with whole brain radiotherapy in patients with multiple brain metastases not suitable for stereotactic radiotherapy. MATERIALS AND METHODS: Patients with measurable brain metastases received escalating doses of AGuIX nanoparticles (15, 30, 50, 75, or 100 mg/kg intravenously) on the day of initiation of WBRT (30 Gy in 10 fractions) in 5 cohorts of 3 patients each. Toxicity was assessed using NCI Common Terminology Criteria for Adverse Events v4.03. RESULTS: Fifteen patients with 354 metastases were included. No dose-limiting toxic effects were observed up to AGuIX 100 mg/kg. Plasma elimination half-life of AGuIX was similar for all groups (mean 1.3 h; range 0.8-3 h). Efficient targeting of metastases (T1 MRI enhancement, tumor selectivity) and persistence of AGuIX contrast enhancement were observed in metastases from patients with primary melanoma, lung, breast, and colon cancers. The concentration of AGuIX in metastases after administration was proportional to the injected dose. Thirteen of 14 evaluable patients had a clinical benefit, with either stabilization or reduction of tumor volume. MRI analysis showed significant correlation between contrast enhancement and tumor response, thus supporting a radiosensitizing effect. CONCLUSION: Combining AGuIX with radiotherapy for patients with brain metastases is safe and feasible. AGuIX specifically targets brain metastases and is retained within tumors for up to 1 week; ongoing phase II studies will more definitively assess efficacy.

Increased Mucosal Thrombin is Associated with Crohn's Disease and Causes Inflammatory Damage through Protease-activated Receptors Activation.

BACKGROUND AND AIMS: Thrombin levels in the colon of Crohn's disease patients have recently been found to be elevated 100-fold compared with healthy controls. Our aim was to determine whether and how dysregulated thrombin activity could contribute to local tissue malfunctions associated with Crohn's disease. METHODS: Thrombin activity was studied in tissues from Crohn's disease patients and healthy controls. Intracolonic administration of thrombin to wild-type or protease-activated receptor-deficient mice was used to assess the effects and mechanisms of local thrombin upregulation. Colitis was induced in rats and mice by the intracolonic administration of trinitrobenzene sulphonic acid. RESULTS: Active forms of thrombin were increased in Crohn's disease patient tissues. Elevated thrombin expression and activity were associated with intestinal epithelial cells. Increased thrombin activity and expression were also a feature of experimental colitis in rats. Colonic exposure to doses of active thrombin comparable to what is found in inflammatory bowel disease tissues caused mucosal damage and tissue dysfunctions in mice, through a mechanism involving both protease-activated receptors -1 and -4. Intracolonic administration of the thrombin inhibitor dabigatran, as well as inhibition of protease-activated receptor-1, prevented trinitrobenzene sulphonic acid-induced colitis in rodent models. CONCLUSIONS: Our data demonstrated that increased local thrombin activity, as it occurs in the colon of patients with inflammatory bowel disease, causes mucosal damage and inflammation. Colonic thrombin and protease-activated receptor-1 appear as possible mechanisms involved in mucosal damage and loss of function and therefore represent potential therapeutic targets for treating inflammatory bowel disease.

Impaired fMRI activation in patients with primary brain tumors.

To characterize peritumoral BOLD contrast disorders, 25 patients referred for resection of primary frontal or parietal neoplasms (low-grade glioma (LGG) (n=8); high-grade glioma (HGG) (n=7); meningioma (n=10)) without macroscopic tumoral infiltration of the primary sensorimotor cortex (SM1) were examined preoperatively using BOLD fMRI during simple motor tasks. Overall cerebral BOLD signal was estimated using vasoreactivity to carbogen inhalation. Using bolus of gadolinium, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were estimated. In a 1cm(3) region-of-interest centered on maximal T-value in SM1 contralateral to movements, interhemispheric asymmetry was evaluated using interhemispheric ratios for BOLD and perfusion parameters. During motor tasks contralateral to the tumor, ipsitumoral sensorimotor activations were decreased in HGG and meningiomas, correlated to the distance between the tumor and SM1. Whereas CBV was decreased in ipsitumoral SM1 for HGG, it remained normal in meningiomas. Changes in basal perfusion could not explain motor activation impairment in SM1. Decreased interhemispheric ratio of the BOLD response to carbogen was the best predictor to model the asymmetry of motor activation (R=0.51). Moreover, 94.9+/-4.9% of all motor activations overlapped significant BOLD response to carbogen inhalation.