Clinical Imaging of Choroid Plexus in Health and in Brain Disorders: A Mini-Review

The choroid plexuses (ChPs) perform indispensable functions for the development, maintenance and functioning of the brain. Although they have gained considerable interest in the last years, their involvement in brain disorders is still largely unknown, notably because their deep location inside the brain hampers non-invasive investigations. Imaging tools have become instrumental to the diagnosis and pathophysiological study of neurological and neuropsychiatric diseases. This review summarizes the knowledge that has been gathered from the clinical imaging of ChPs in health and brain disorders not related to ChP pathologies. Results are discussed in the light of pre-clinical imaging studies. As seen in this review, to date, most clinical imaging studies of ChPs have used disease-free human subjects to demonstrate the value of different imaging biomarkers (ChP size, perfusion/permeability, glucose metabolism, inflammation), sometimes combined with the study of normal aging. Although very few studies have actually tested the value of ChP imaging biomarkers in patients with brain disorders, these pioneer studies identified ChP changes that are promising data for a better understanding and follow-up of diseases such as schizophrenia, epilepsy and Alzheimer’s disease. Imaging of immune cell trafficking at the ChPs has remained limited to pre-clinical studies so far but has the potential to be translated in patients for example using MRI coupled with the injection of iron oxide nanoparticles. Future investigations should aim at confirming and extending these findings and at developing translational molecular imaging tools for bridging the gap between basic molecular and cellular neuroscience and clinical research

Impact of the Thrombectomy Trials on the Management and Outcome of Large Vessel Stroke: Data From the Lyon Stroke Center

Introduction: Randomized trials (RT) have recently validated the superiority of thrombectomy over standard medical care, including intravenous thrombolysis (IVT). However, data on their impact on routine clinical care remains scarce.Methods: Using a prospective observational registry, we assessed: (1) the clinical and radiological characteristics of all consecutive patients treated with thrombectomy; (2) the outcome of all patients with M1 occlusion (treated with thrombectomy or IVT alone). Two periods were compared: before (2013–2014) and after (2015–2016) the publication of RT.Results: Endovascular procedures significantly increased between the two periods (N = 82 vs. 314, p < 0.0001). In 2015–2016, patients were older (median [IQR]: 69 [57-80]; vs. 66 [53-74]; p = 0.008), had shorter door-to-clot times (69 [47-95]; vs. 110 [83-155]; p < 0.0001) resulting in a trend toward shorter delay from symptom onset to reperfusion (232 [185-300]; vs. 250 [200-339]; p = 0.1), with higher rates of reperfusion (71 vs. 48%; p = 0.0001). Conversely, no significant differences in baseline NIHSS scores, ASPECTS, delay to IVT or intracranial hemorrhage were found. In 2015–2016, patients with M1 occlusion were treated with thrombectomy more often than in 2013–2014 (87 vs. 32%, respectively; p < 0.0001), with a significant improvement in clinical outcome (shift analysis, lower modified Rankin scale scores: OR = 1.68; 95% CI: 1.10–2.57; p = 0.017).Conclusion: Following the publication of RT, thrombectomy was rapidly implemented with significant improvements in intrahospital delay and reperfusion rates. Treatment with thrombectomy increased with better clinical outcomes in patients with M1 occlusion

Conventional MRI radiomics in patients with suspected early- or pseudo-progression

International audienceAbstract Background After radiochemotherapy, 30% of patients with early worsening MRI experience pseudoprogression (Psp) which is not distinguishable from early progression (EP). We aimed to assess the diagnostic value of radiomics in patients with suspected EP or Psp. Methods Radiomics features (RF) of 76 patients (53 EP and 23 Psp) retrospectively identified were extracted from conventional MRI based on four volumes-of-interest. Subjects were randomly assigned into training and validation groups. Classification model (EP versus Psp) consisted of a random forest algorithm after univariate filtering. Overall (OS) and progression-free survivals (PFS) were predicted using a semi-supervised principal component analysis, and forecasts were evaluated using C-index and integrated Brier scores (IBS). Results Using 11 RFs, radiomics classified patients with 75.0% and 76.0% accuracy, 81.6% and 94.1% sensitivity, 50.0% and 37.5% specificity, respectively, in training and validation phases. Addition of MGMT promoter status improved accuracy to 83% and 79.2%, and specificity to 63.6% and 75%. OS model included 14 RFs and stratified low- and high-risk patients both in the training (hazard ratio [HR], 3.63; P = .002) and the validation (HR, 3.76; P = .001) phases. Similarly, PFS model stratified patients during training (HR, 2.58; P = .005) and validation (HR, 3.58; P = .004) phases using 5 RF. OS and PFS forecasts had C-index of 0.65 and 0.69, and IBS of 0.122 and 0.147, respectively. Conclusions Conventional MRI radiomics has promising diagnostic value, especially when combined with MGMT promoter status, but with moderate specificity. In addition, our results suggest a potential for predicting OS and PFS

MRI Assessment of Ischemic Lesion Evolution within White and Gray Matter

International audienceBackground: In acute ischemic stroke (AIS), gray matter (GM) and white matter (WM) have different vulnerabilities to ischemia. Thus, we compared the evolution of ischemic lesions within WM and GM using MRI. Methods: From a European multicenter prospective database (I-KNOW), available T1-weighted images were identified for 50 patients presenting with an anterior AIS and a perfusion weighted imaging (PWI)/diffusion weighted imaging (DWI) mismatch ratio of 1.2 or more. Six lesion compartments were outlined: initial DWI (b = 1,000 s/mm2) lesion, initial PWI-DWI mismatch (Tmax >4 s and DWI-negative), final infarct mapped on 1-month fluid-attenuated inversion recovery (FLAIR) imaging, lesion growth between acute DWI and 1-month FLAIR, DWI lesion reversal at 1 month and salvaged mismatch. The WM and GM were segmented on T1-weighted images, and all images were co-registered within subjects to the baseline MRI. WM and GM proportions were calculated for each compartment. Results: Fifty patients were eligible for the study. Median delay between symptom onset and baseline MRI was 140 min. The percentage of WM was significantly greater in the following compartments: initial mismatch (52.5 vs. 47.5%, p = 0.003), final infarct (56.7 vs. 43.3%, p Conclusions: Ischemic lesions may extend preferentially within the WM. Specific therapeutic strategies targeting WM ischemic processes may deserve further investigation

Fast virtual histology of unstained mouse brains using in-line X-ray phase tomography

International audienceIntroductionWhole-brain imaging with cell resolution is one of the most important challenges in neuroscience. Conventional histology techniques are laborious and require tissue staining and sectioning. We have previously proposed an in-line phase contrast tomography set-up that identified mouse brain anatomy as clearly as histology in 44 min (1). The current work presents an optimized pipeline and demonstrates its potential for fast virtual histology in a mouse model of acute cerebral injury.MethodsSix mice (healthy: N=1, acute cerebral ischemia: N=5) were imaged in-vivo with MRI. Imaging of brains fixed with PFA4% was performed on beamline ID19 at ESRF at 19 keV selected from undulator radiation. An indirect detection-based detector with a LuAg scintillator, standard microscope optics and a 2048x2048 pixel CCD camera was positioned 1 m from the sample to have phase contrast. The pixel size was set to 7.5 µm. Acquisition time was 14 minutes per brain.ResultsFigure 1 shows 3 different virtual histologic slices of the healthy brain (Fig 1A;E;G). Minimum intensity projection (MinIP) resulted in angiography with sufficient resolution to visualize pial vessels (Fig 1B-C). T2-weighted MRI revealed abnormal hyperintense signals (Fig 1D, arrow), corresponding to a choroid plexus (CP) cyst as clearly depicted on phase contrast images (Fig 1E). CP layers were well resolved (Fig 1F). In the cerebellum, there was an excellent contrast between grey and white matter (Fig 1G-H), with detection of individual Purkinje cells (arrow in Fig 1I).In mice with ischemic injury, MRI showed an extensive lesion across the frontoparietal cortex (Fig 2A, plain line) with a well-delineated core (dotted line) and vasogenic edema along the ipsilateral external capsule (arrow). Native phase contrast images also discriminated the core/periphery of the lesion (Fig 2B). MinIP allowed further characterizing the lesion, with a disorganization of vessels in the core and avascularity in the periphery (Fig 1C). In addition, maximum intensity projection (Fig 2D) showed (i) enhanced cellularity on the ipsilateral side (Fig 2E, arrow), (ii) vessels rich in collagen such as carotids (Fig 2F) and (iii) upregulation of collagen in the ischemic cortex (Fig 2G-H) (2).ConclusionsThe proposed set-up of in-line phase contrast tomography allows fast virtual histology of the whole unstained brain, which is promising for phenotyping transgenic mouse and characterizing models of neurovascular diseases, with the potential to scan 30 brains in an 8-hours shift. Because it is non-destructive, this approach will be used for guiding further immunohistologic analysis of the brain.References1. Marinescu M and others. Mol Imaging Biol 2013;15(5):552-559.2. Hawkes CA and others. Exp Neurol 2013;250:270-281.AcknowledgementThis work was performed within the framework of the LABEX PRIMES (ANR-11-LABX-0063) of Université de Lyon and was supported by the European Synchrotron Research Facility (ESRF, project LS-2292) by allocation of beam time

MRI Assessment of Ischemic Lesion Evolution within White and Gray Matter

International audienceBackground: In acute ischemic stroke (AIS), gray matter (GM) and white matter (WM) have different vulnerabilities to ischemia. Thus, we compared the evolution of ischemic lesions within WM and GM using MRI. Methods: From a European multicenter prospective database (I-KNOW), available T1-weighted images were identified for 50 patients presenting with an anterior AIS and a perfusion weighted imaging (PWI)/diffusion weighted imaging (DWI) mismatch ratio of 1.2 or more. Six lesion compartments were outlined: initial DWI (b = 1,000 s/mm2) lesion, initial PWI-DWI mismatch (Tmax >4 s and DWI-negative), final infarct mapped on 1-month fluid-attenuated inversion recovery (FLAIR) imaging, lesion growth between acute DWI and 1-month FLAIR, DWI lesion reversal at 1 month and salvaged mismatch. The WM and GM were segmented on T1-weighted images, and all images were co-registered within subjects to the baseline MRI. WM and GM proportions were calculated for each compartment. Results: Fifty patients were eligible for the study. Median delay between symptom onset and baseline MRI was 140 min. The percentage of WM was significantly greater in the following compartments: initial mismatch (52.5 vs. 47.5%, p = 0.003), final infarct (56.7 vs. 43.3%, p Conclusions: Ischemic lesions may extend preferentially within the WM. Specific therapeutic strategies targeting WM ischemic processes may deserve further investigation

Characteristics of diffuse hemispheric gliomas, H3 G34-mutant in adults

International audienceBackgroundDiffuse hemispheric gliomas, H3 G34-mutant (DHG H3G34-mutant) constitute a distinct type of aggressive brain tumors. Although initially described in children, they can also affect adults. The aims were to describe the characteristics of DHG H3G34-mutant in adults and to compare them to those of established types of adult WHO grade IV gliomas.MethodsThe characteristics of 17 adult DHG H3G34-mutant, 32 H3.3 K27M-mutant diffuse midline gliomas (DMG), 100 IDH-wildtype and 36 IDH-mutant glioblastomas were retrospectively analyzed.ResultsMedian age at diagnosis in adult DHG H3G34-mutant was 25 years (range: 19-33). All tumors were hemispheric. For 9 patients (56%), absent or faint contrast enhancement initially suggested another diagnosis than a high-grade glioma, and diffusion-weighted imaging seemed retrospectively more helpful to suspect an aggressive tumor than MR-spectroscopy and perfusion MRI. All cases were IDH-wildtype. Most cases were immunonegative for ATRX (93%) and Olig2 (100%) and exhibited MGMT promoter methylation (82%). The clinical and radiological presentations of adult DHG H3G34-mutant were different from those of established types of adult grade IV gliomas. Median overall survival of adult DHG H3G34-mutant was 12.4 months compared to 19.6 months (p=.56), 11.7 months (p=.45) and 50.5 months (p=0.006) in H3.3 K27M-mutant DMG, IDH-wildtype and IDH-mutant glioblastomas, respectively.ConclusionsAdult DHG H3G34-mutant are associated with distinct characteristics compared to those of established types of adult WHO grade IV gliomas. The present study supports considering these tumors as a new type of WHO grade IV glioma in future classifications