Multi T1-weighted contrast imaging and T1 mapping with compressed sensing FLAWS at 3 T.

OBJECTIVE: The Fluid And White matter Suppression (FLAWS) MRI sequence provides multiple T1-weighted contrasts of the brain in a single acquisition. However, the FLAWS acquisition time is approximately 8 min with a standard GRAPPA 3 acceleration factor at 3 T. This study aims at reducing the FLAWS acquisition time by providing a new sequence optimization based on a Cartesian phyllotaxis k-space undersampling and a compressed sensing (CS) reconstruction. This study also aims at showing that T1 mapping can be performed with FLAWS at 3 T. MATERIALS AND METHODS: The CS FLAWS parameters were determined using a method based on a profit function maximization under constraints. The FLAWS optimization and T1 mapping were assessed with in-silico, in-vitro and in-vivo (10 healthy volunteers) experiments conducted at 3 T. RESULTS: In-silico, in-vitro and in-vivo experiments showed that the proposed CS FLAWS optimization allows the acquisition time of a 1 mm-isotropic full-brain scan to be reduced from [Formula: see text] to [Formula: see text] without decreasing image quality. In addition, these experiments demonstrate that T1 mapping can be performed with FLAWS at 3 T. DISCUSSION: The results obtained in this study suggest that the recent advances in FLAWS imaging allow to perform multiple T1-weighted contrast imaging and T1 mapping in a single [Formula: see text] sequence acquisition.

Rehearsals using patient-specific 3D-printed aneurysm models for simulation of endovascular embolization of complex intracranial aneurysms: 3D SIM study.

BACKGROUND: In neurovascular treatment planning, endovascular devices to manage complex intracranial aneurysms requiring intervention are often selected based on conventional measurements and interventional neuroradiologist experience. A recently developed technology allows a patient-specific 3D-printed model to mimic the navigation experience. The goal of this study was to assess the effect of pre-procedure 3D simulation on procedural and clinical outcomes for wide-neck aneurysm embolization. MATERIALS & METHODS: In this unblinded, non-randomized, prospective, multicenter study conducted from November 18 through December 20, patients with complex intracranial aneurysms (neck > 4 mm or ratio < 21) were treated by WEB or flow diverter stents (FDS). The primary endpoint was concordance between simulation and procedure, 3D-printed model accuracy as well as embolization outcomes including complications, procedure times, and radiation dose were also assessed. Secondary endpoint was to compare versus a retrospective WEB cohort. RESULTS: Twenty-one patients were treated, 76% of cases by WEB and 24% by FDS. Concordance between post-simulation and real procedure efficiency was 0.85 [0.69 - 1.00] for size device selection and 0.93 [0.79 - 1.00] for wall-apposition/aneurysm neck closure. Geometrical accuracy of the 3D-printed model showed a mean absolute shift of 0.11 mm. Two complications without major clinical impact were reported with a post-operative mRS similar to pre-procedure mRS for all patients. CONCLUSIONS: Rehearsal using accurate 3D-printed patient-specific aneurysm models enabled optimization of embolization strategy, resulting in reduced procedure duration and cumulative fluoroscopy time which translated to reduced radiation exposure compared to procedures performed without simulation.

Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences. METHODS: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex. RESULTS: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p = 0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies. CONCLUSION: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.

Multiple sclerosis lesions segmentation from multiple experts: The MICCAI 2016 challenge dataset.

MRI plays a crucial role in multiple sclerosis diagnostic and patient follow-up. In particular, the delineation of T2-FLAIR hyperintense lesions is crucial although mostly performed manually - a tedious task. Many methods have thus been proposed to automate this task. However, sufficiently large datasets with a thorough expert manual segmentation are still lacking to evaluate these methods. We present a unique dataset for MS lesions segmentation evaluation. It consists of 53 patients acquired on 4 different scanners with a harmonized protocol. Hyperintense lesions on FLAIR were manually delineated on each patient by 7 experts with control on T2 sequence, and gathered in a consensus segmentation for evaluation. We provide raw and preprocessed data and a split of the dataset into training and testing data, the latter including data from a scanner not present in the training dataset. We strongly believe that this dataset will become a reference in MS lesions segmentation evaluation, allowing to evaluate many aspects: evaluation of performance on unseen scanner, comparison to individual experts performance, comparison to other challengers who already used this dataset, etc.

High-resolution multi-T1 -weighted contrast and T1 mapping with low B1>+ sensitivity using the fluid and white matter suppression (FLAWS) sequence at 7T.

PURPOSE: To demonstrate that fluid and white matter suppression (FLAWS) imaging can be used for high-resolution T1 mapping with low transmitted bias field ( B1+ ) sensitivity at 7T. METHODS: The FLAWS sequence was optimized for 0.8-mm isotropic resolution imaging. The theoretical accuracy and precision of the FLAWS T1 mapping was compared with the one of the magnetization-prepared two rapid gradient echoes (MP2RAGE) sequence optimized for low B1+ sensitivity. FLAWS images were acquired at 7T on six healthy volunteers (21 to 48 years old; two women). MP2RAGE and saturation-prepared with two rapid gradient echoes (SA2RAGE) datasets were also acquired to obtain T1 mapping references and B1+ maps. The contrast-to-noise ratio (CNR) between brain tissues was measured in the FLAWS-hco and MP2RAGE-uni images. The Pearson correlation was measured between the MP2RAGE and FLAWS T1 maps. The effect of B1+ on FLAWS T1 mapping was assessed using the Pearson correlation. RESULTS: The FLAWS-hco images were characterized by a higher brain tissue CNR ( CNRWM/GM=5.5 , CNRWM/CSF=14.7 , CNRGM/CSF=10.3 ) than the MP2RAGE-uni images ( CNRWM/GM=4.9 , CNRWM/CSF=6.6 , CNRGM/CSF=3.7 ). The theoretical accuracy and precision of the FLAWS T1 mapping ( acc=91.9%;prec=90.2% ) were in agreement with those provided by the MP2RAGE T1 mapping ( acc=90.0%;prec=86.8% ). A good agreement was found between in vivo T1 values measured with the MP2RAGE and FLAWS sequences (r = 0.91). A weak correlation was found between the FLAWS T1 map and the B1+ map within cortical gray matter and white matter segmentations ( rWM=-0.026 ; rGM=0.081 ). CONCLUSION: The results from this study suggest that FLAWS is a good candidate for high-resolution T1 -weighted imaging and T1 mapping at the field strength of 7T.

Multimodal brain imaging connectivity analyses of emotional and motivational deficits in depression among women.

BACKGROUND: Major depressive disorder (MDD) is characterized by impaired cortical-subcortical functional connectivity. Apathy adds to functional impairment, but its cerebral basis in MDD remains unknown. Our objective was to describe impairments in functional connectivity during emotional processing in MDD (with varying levels of congruency and attention), and to determine their correlation with apathy. METHODS: We used the Variable Attention Affective Task during functional MRI, followed by diffusion-weighted MRI, to assess 55 right-handed women (30 with MDD and 25 healthy controls) between September 2012 and February 2015. We estimated functional connectivity using generalized psychophysiologic interaction and anatomic connectivity with tract-based spatial statistics. We measured apathy using the Apathy Evaluation Scale. RESULTS: We found decreased functional connectivity between the left amygdala and the left anterior cingulate cortex (ACC) during negative stimuli in participants with MDD (t54 = 4.2; p = 0.035, family-wise error [FWE]-corrected). During high-attention stimuli, participants with MDD showed reduced functional connectivity between the right dorsolateral prefrontal cortex (dlPFC) and the right ACC (t54 = 4.06, pFWE = 0.02), but greater functional connectivity between the right dlPFC and the right amygdala (t54 = 3.35, p = 0.048). Apathy was associated with increased functional connectivity between the right dlPFC and the right ACC during high-attention stimuli (t28 = 5.2, p = 0.01) and increased fractional anisotropy in the right posterior cerebellum, the anterior and posterior cingulum and the bilateral internal capsule (all pFWE < 0.05). LIMITATIONS: Limitations included a moderate sample size, concomitant antidepressant therapy and no directed connectivity. CONCLUSION: We found that MDD was associated with impairments in cortical-subcortical functional connectivity during negative stimuli that might alter the recruitment of networks engaged in attention. Apathy-related features suggested networks similar to those observed in degenerative disorders, but possible different mechanisms.

Acute Stroke Management During the COVID-19 Pandemic: Does Confinement Impact Eligibility for Endovascular Therapy?

During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement. Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion. The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement. In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States). This study included 1600 patients treated by EVT for acute ischemic stroke. Date of EVT and symptom onset-to-groin puncture time were collected. Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures. Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test. The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), (P<0.001). In addition, there is a significant increase in mean stroke onset-to-groin puncture time (P<0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]). Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place.

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.

Patient and aneurysm factors associated with aneurysm rupture in the population of the ARETA study.

BACKGROUND AND PURPOSE: Identifying patients with intracranial aneurysms (IA) who have a high risk of rupture is critical to determine optimal management. ARETA (Analysis of Recanalization after Endovascular Treatment of intracranial Aneurysm) is a prospective, multicenter study, dedicated to evaluating endovascular treatment of IA. We aimed to identify factors associated with ruptured status, using this very large series of patients with ruptured and unruptured aneurysms. METHODS: Several analyses were conducted in the ARETA population: univariate and multivariate analyses in the whole population of patients and aneurysms to determine patient and aneurysm factors associated with aneurysm rupture, as well as a matched pair analysis (based on aneurysm size) conducted in the subgroup of patients with only one aneurysm to analyze the patient and aneurysm factors simultaneously. RESULTS: From December 2013 to May 2015, 1289 patients with 1761 aneurysms were included in ARETA. The multivariate analysis identified four patient factors: elevated blood pressure (EBP), no familial history, single IA, and active smoking, and four aneurysm factors: size≥5mm, narrow neck, irregular shape, and ACA/Acom location, associated with rupture status. In the matched pair analysis, five risk factors of rupture were identified: no familial history of aneurysm, narrow neck, active smoking, ACA/Acom location, and irregular shape. CONCLUSIONS: The most important patient factors associated with IA rupture are smoking and EBP. Given that size is a well-identified aneurysm factor, narrow neck also seems to be associated with aneurysm rupture. Further studies are needed to confirm this factor and determine underlying mechanisms. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942512.

Patch-based super-resolution of arterial spin labeling magnetic resonance images.

Arterial spin labeling is a magnetic resonance perfusion imaging technique that, while providing results comparable to methods currently considered as more standard concerning the quantification of the cerebral blood flow, is subject to limitations related to its low signal-to-noise ratio and low resolution. In this work, we investigate the relevance of using a non-local patch-based super-resolution method driven by a high resolution structural image to increase the level of details in arterial spin labeling images. This method is evaluated by comparison with other image dimension increasing techniques on a simulated dataset, on images of healthy subjects and on images of subjects scanned for brain tumors, who had a dynamic susceptibility contrast acquisition. The influence of an increase of ASL images resolution on partial volume effects is also investigated in this work.

Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase.

BACKGROUND: A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids. FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models, and some have been tested in phase 1 and 2 studies. In a phase 1 study, BIA 10-2474, an orally administered reversible FAAH inhibitor, was given to healthy volunteers to assess safety. METHODS: Single doses (0.25 to 100 mg) and repeated oral doses (2.5 to 20 mg for 10 days) of BIA 10-2474 had been administered to 84 healthy volunteers in sequential cohorts; no severe adverse events had been reported. Another cohort of participants was then assigned to placebo (2 participants) or 50 mg of BIA 10-2474 per day (6 participants). This report focuses on neurologic adverse events in participants in this final cohort. A total of 4 of the 6 participants who received active treatment consented to have their clinical and radiologic data included in this report. RESULTS: An acute and rapidly progressive neurologic syndrome developed in three of the four participants starting on the fifth day of drug administration. The main clinical features were headache, a cerebellar syndrome, memory impairment, and altered consciousness. Magnetic resonance imaging showed bilateral and symmetric cerebral lesions, including microhemorrhages and hyperintensities on fluid-attenuated inversion recovery and diffusion-weighted imaging sequences predominantly involving the pons and hippocampi. One patient became brain dead; the condition of two patients subsequently improved, but one patient had residual memory impairment, and the other patient had a residual cerebellar syndrome. One patient remained asymptomatic. CONCLUSIONS: An unanticipated severe neurologic disorder occurred after ingestion of BIA 10-2474 at the highest dose level used in a phase 1 trial. The underlying mechanism of this toxic cerebral syndrome remains unknown.

Measurement of magnetization transfer ratio (MTR) from cervical spinal cord: Multicenter reproducibility and variability.

BACKGROUND: Assessing the multicenter variability of magnetization transfer ratio (MTR) measurements in the spinal cord of healthy controls is the first step toward investigating its clinical use as a biomarker. PURPOSE: To analyze the between-session, between-participant, and between-scanner variability of MTR measurements in automatically extracted regions of interest in the cervical cord of healthy controls. STUDY TYPE: Control study. POPULATION: Forty-four participants, distributed across five MRI scanners (all from the same manufacturer). Ten participants were scanned twice in the same scanner, and 10 others were scanned twice in two different scanners. FIELD STRENGTH/SEQUENCE: 3D-gradient echo images, centered on C5, without and with magnetization transfer prepulse at 3T. ASSESSMENT: We calculated the mean MTR for different vertebral levels in the whole cord (WC), as well as in the white matter and gray matter, and determined the between-session, between-participant, and between-scanner variabilities. STATISTICAL TESTS: Coefficients of variation and intraclass correlations (ICCs) for the different variabilities and their associated confidence intervals. RESULTS: The MTR measurements for Levels C4-C6 (near the slab center) exhibited a mean value in WC of 34.6 pu and a pooled standard deviation of 0.9 pu. The between-session coefficient of variation was estimated as 2.3% (ICC = 0.63), the between-participant coefficient as 1.6% (ICC = 0.32), and the between-scanner coefficient as 0.7% (ICC = 0.05). The resulting aggregate coefficient of variation was 2.9%, which was sufficiently low to detect an MTR reduction of 1 pu between groups of about 45 participants (Type-I error rate: 0.05; Type-II error rate: 0.10). DATA CONCLUSION: The good between-scanner reproducibility and low overall variability in cervical spinal cord MTR measurements in a control population might pave the way for multicenter analyses in various neurological diseases with moderate cohort sizes. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1777-1785.

Focal and diffuse cervical spinal cord damage in patients with early relapsing-remitting MS: A multicentre magnetisation transfer ratio study.

BACKGROUND: Studies including patients with well-established multiple sclerosis (MS) have shown a significant and disability-related reduction in the cervical spinal cord (SC) magnetisation transfer ratio (MTR). OBJECTIVES: The objectives are to (1) assess whether MTR reduction is already measurable in the SC of patients with early relapsing-remitting multiple sclerosis (RRMS) and (2) describe its spatial distribution. METHODS: We included 60 patients with RRMS <12 months and 34 age-matched controls at five centres. Axial T2*w, sagittal T2w, sagittal phase-sensitive inversion recovery (PSIR), 3DT1w, and axial magnetisation transfer (MT) images were acquired from C1 to C7. Lesions were manually labelled and mean MTR values computed both for the whole SC and for normal-appearing SC in different regions of interest. RESULTS: Mean whole SC MTR was significantly lower in patients than controls (33.7 vs 34.9 pu, p = 0.00005), even after excluding lesions (33.9 pu, p = 0.0003). We observed a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2-C4). In the axial plane, we observed a greater mean MTR reduction at the SC periphery and barycentre. CONCLUSION: Cervical SC tissue damage measured using MTR is not restricted to macroscopic lesions in patients with early RRMS and is not homogeneously distributed.

USPIO-positive MS lesions are associated with greater tissue damage than gadolinium-positive-only lesions during 3-year follow-up.

BACKGROUND: Identifying in vivo the processes that determine lesion severity in multiple sclerosis (MS) remains a challenge. OBJECTIVES: To describe the dynamics of ultrasmall superparamagnetic iron oxide (USPIO) enhancement in MS lesions and the relationship between USPIO enhancement and microstructural changes over 3 years. METHODS: Lesion development was assessed at baseline, Months 3, 6, and 9, using magnetic resonance imaging (MRI) with gadolinium and USPIO. Microstructural changes were assessed at baseline, Months 3, 6, 9, 12, 18, 24, and 36, using relaxometry, magnetization transfer, and diffusion-weighted imaging. RESULTS: We included 15 patients with clinically isolated syndrome. In the 52 MRI scans acquired with USPIO, 22 lesions were USPIO and gadolinium positive, and 44 were USPIO negative but gadolinium positive. Lesions no longer exhibited sustained USPIO enhancement 3 months later. At baseline, lesions that were both USPIO and gadolinium positive had lower magnetization transfer ratio values (common language effect size = 0.84, p = 0.0005) and lower fractional anisotropy values (0.83, p = 0.001) than gadolinium-positive-only lesions. USPIO-positive lesions remained associated with greater damage than gadolinium-positive-only lesions throughout the 3-year follow-up. CONCLUSION: USPIO enhancement, mainly reflecting monocyte infiltration, is transient and is associated with persistent tissue damage after 3 years.

CT angiography for one-year follow-up of intracranial aneurysms treated with the WEB device: Utility in evaluating aneurysm occlusion and WEB compression at one year.

BACKGROUND AND PURPOSE: The WEB is an innovative flow disruption device for cerebral aneurysm embolization with rapidly expanding indications. Our purpose was to evaluate the diagnostic performance of computed tomography angiography (CTA) at 1-year follow-up of aneurysms treated with the WEB. MATERIALS AND METHODS: Between April 2014 and May 2016, the study prospectively included patients treated with the WEB at our institution, and followed up within 24hours by CTA and at 1year by CTA, time-of-flight magnetic resonance angiography (TOF MRA) and digital subtraction angiography (DSA). The diagnostic quality of imaging data was assessed based on the confidence index, artifacts, and WEB shape depiction. The imaging diagnostic performance was assessed using 3 criteria at 1year: aneurysm occlusion status and worsening, and WEB shape compression. Interobserver and intermodality agreement was determined by calculating κ values. RESULTS: The study ultimately included 16 patients (9 women, mean age 53±7.6years). CTA quality confidence was scored as 2/2, artifacts 0.4/2 and WEB shape depiction 1.9/2, superior to TOF MRA for the latter two criteria. Aneurysm occlusion was adequate in 93.7% of patients, with CTA showing excellent interobserver reproducibility and agreement with DSA on a 4-grade scale (κ=1.00), while TOF MRA yielded good reproducibility (κ=0.76) and agreement with DSA (κ=0.69). CTA also identified aneurysm occlusion worsening (43.7%) and WEB compression (81.2%) in excellent agreement with DSA (κ=0.85 and 1.00). CONCLUSIONS: CTA is a reproducible and reliable technique for the follow-up of aneurysms treated with the WEB device.

An a contrario approach for the detection of patient-specific brain perfusion abnormalities with arterial spin labelling.

In this paper, we introduce a new locally multivariate procedure to quantitatively extract voxel-wise patterns of abnormal perfusion in individual patients. This a contrario approach uses a multivariate metric from the computer vision community that is suitable to detect abnormalities even in the presence of closeby hypo- and hyper-perfusions. This method takes into account local information without applying Gaussian smoothing to the data. Furthermore, to improve on the standard a contrario approach, which assumes white noise, we introduce an updated a contrario approach that takes into account the spatial coherency of the noise in the probability estimation. Validation is undertaken on a dataset of 25 patients diagnosed with brain tumours and 61 healthy volunteers. We show how the a contrario approach outperforms the massively univariate general linear model usually employed for this type of analysis.

Dynamic contrast-enhanced MRI: Study of inter-software accuracy and reproducibility using simulated and clinical data.

PURPOSE: To test the reproducibility and accuracy of pharmacokinetic parameter measurements on five analysis software packages (SPs) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), using simulated and clinical data. MATERIALS AND METHODS: This retrospective study was Institutional Review Board-approved. Simulated tissues consisted of pixel clusters of calculated dynamic signal changes for combinations of Tofts model pharmacokinetic parameters (volume transfer constant [K(trans) ], extravascular extracellular volume fraction [ve ]), longitudinal relaxation time (T1 ). The clinical group comprised 27 patients treated for rectal cancer, with 36 3T DCE-MR scans performed between November 2012 and February 2014, including dual-flip-angle T1 mapping and a dynamic postcontrast T1 -weighted, 3D spoiled gradient-echo sequence. The clinical and simulated images were postprocessed with five SPs to measure K(trans) , ve , and the initial area under the gadolinium curve (iAUGC). Modified Bland-Altman analysis was conducted, intraclass correlation coefficients (ICCs) and within-subject coefficients of variation were calculated. RESULTS: Thirty-one examinations from 23 patients were of sufficient technical quality and postprocessed. Measurement errors were observed on the simulated data for all the pharmacokinetic parameters and SPs, with a bias ranging from -0.19 min(-1) to 0.09 min(-1) for K(trans) , -0.15 to 0.01 for ve , and -0.65 to 1.66 mmol.L(-1) .min for iAUGC. The ICC between SPs revealed moderate agreement for the simulated data (K(trans) : 0.50; ve : 0.67; iAUGC: 0.77) and very poor agreement for the clinical data (K(trans) : 0.10; ve : 0.16; iAUGC: 0.21). CONCLUSION: Significant errors were found in the calculated DCE-MRI pharmacokinetic parameters for the perfusion analysis SPs, resulting in poor inter-software reproducibility. J. Magn. Reson. Imaging 2016;43:1288-1300.

Pixantrone: a B-cell-depleting immunosuppressant for multiple sclerosis patients with active disease.

BACKGROUND: Mitoxantrone has been approved for patients with worsening relapsing-remitting (RR) or secondary progressive multiple sclerosis (SPMS), but its long-term use is limited by its cardiotoxicity. Pixantrone (PIX) is an analog of mitoxantrone. OBJECTIVES: The aim of this open-label, multicenter, noncomparative Phase I/II trial was to explore the immunosuppressive effect of PIX, its impact on clinical disease activity and cerebral gadolinium-enhanced (Gd(+)) lesions, and its safety. METHODS: Eighteen patients with active RRMS and SPMS (⩾ 1 cerebral Gd(+) lesion) despite approved immunomodulatory therapy received four intravenous PIX injections every 21 days. A neurological examination, hematology, lymphocyte subsets, and biochemistry were performed at Day 1, Weeks 3, 6 and 9, and Months 3, 6, 9 and 12. Echocardiography was performed before each infusion, at Months 3, 6 and 12. Cerebral MRI was performed at baseline, and at Months 6 and 12. RESULTS: CD19+ cells were reduced by 95% at Month 3 and by 47% at Month 12. Gd+ lesions were reduced by 86% at Month 12 (p = 0.01). The annual relapse rate was reduced by 87% (p < 10(-4)). Two patients experienced a transient reduction in left ventricular fraction. CONCLUSION: These preliminary data indicate the efficacy of PIX in active RRMS and SPMS.

Ultra-small superparamagnetic iron oxide enhancement is associated with higher loss of brain tissue structure in clinically isolated syndrome.

BACKGROUND: Macrophages are important components of inflammatory processes in multiple sclerosis, closely linked to axonal loss, and can now be observed in vivo using ultra-small superparamagnetic iron oxide (USPIO). In the present 1-year longitudinal study, we aimed to determine the prevalence and the impact on tissue injury of macrophage infiltration in patients after the first clinical event of multiple sclerosis. METHODS: Thirty-five patients, 32 years mean age, were imaged in a mean of 66 days after their first event using conventional magnetic resonance imaging, gadolinium (Gd) to probe blood-brain barrier integrity, USPIO to study macrophage infiltration and magnetization transfer ratio (MTR) to assess tissue structure integrity. Statistics were performed using two-group repeated-measures ANOVA. Any patient received treatment at baseline. RESULTS: At baseline, patients showed 17 USPIO-positive lesions reflecting infiltration of macrophages present from the onset. This infiltration was associated with local higher loss of tissue structure as emphasized by significant lower MTRnorm values (p<0.03) in USPIO(+)/Gd(+) lesions (n=16; MTRnormUSPIO(+)/Gd(+)=0.78 at baseline, MTRnormUSPIO(+)/Gd(+)=0.81 at M12) relative to USPIO(-)/Gd(+) lesions (n=67; MTRnormUSPIO(-)/Gd(+)=0.82 at baseline, MTRnormUSPIO(-)/Gd(+)=0.85 at M12). No interaction in MTR values was observed during the 12 months follow-up (lesion type × time). CONCLUSION: Infiltration of activated macrophages evidenced by USPIO enhancement, is present at the onset of multiple sclerosis and is associated with higher and persistent local loss of tissue structure. Macrophage infiltration affects more tissue structure while tissue recovery during the following year has a similar pattern for USPIO and Gd-enhanced lesions, leading to relative higher persistent local loss of tissue structure in lesions showing USPIO enhancement at baseline.

Optimization of brain perfusion image quality by cortical surface-based projection of arterial spin labeling maps in early-onset Alzheimer's disease patients.

OBJECTIVES: Arterial spin labelling (ASL) is a promising MRI sequence that allows noninvasive detection of cortical perfusion alterations in neurodegenerative disorders, but its interpretation remains difficult at an individual level. In this work, a cortical surface-based projection of ASL maps was applied in patients with early-onset Alzheimer's disease (EOAD) to improve the image quality and visual representation of perfusion data. METHODS: Eighteen patients referred from the reference centre for EOAD were assessed by MRI with ASL sequences. Data processing was applied on each examination including correction of partial volume effects and cortical projection of preprocessed ASL data. Cortical segmentation and perfusion display were qualitatively analyzed according to a three-point scale. RESULTS: All examinations were suitable for complete data processing. Quality of segmentation and of cortical surface-based perfusion maps was scored as optimal in 72 % in both cases. Cortical surface-based ASL maps provided a more global view than single slices and an accurate approach of brain perfusion in EOAD patients. CONCLUSION: Cortical surface-based analysis of ASL maps is technically feasible with a good image quality and may enable significant improvement in the detection of focal perfusion alterations in neurodegenerative disorders in the real-life clinical setting. KEY POINTS: • Arterial spin labelling is a promising sequence for assessing Alzheimer's disease. • Optimization of ASL brain perfusion image quality is crucial for image interpretation. • Cortical surface-based analysis may improve detection of perfusion alterations in a real-life clinical setting.