Trial of Deferiprone in Parkinson's Disease.

BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants. CONCLUSIONS: In participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks. (Funded by the European Union Horizon 2020 program; FAIRPARK-II ClinicalTrials.gov number, NCT02655315.).

Quantitative susceptibility mapping demonstrates different patterns of iron overload in subtypes of early-onset Alzheimer's disease.

OBJECTIVES: We aimed to define brain iron distribution patterns in subtypes of early-onset Alzheimer's disease (EOAD) by the use of quantitative susceptibility mapping (QSM). METHODS: EOAD patients prospectively underwent MRI on a 3-T scanner and concomitant clinical and neuropsychological evaluation, between 2016 and 2019. An age-matched control group was constituted of cognitively healthy participants at risk of developing AD. Volumetry of the hippocampus and cerebral cortex was performed on 3DT1 images. EOAD subtypes were defined according to the hippocampal to cortical volume ratio (HV:CTV). Limbic-predominant atrophy (LPMRI) is referred to HV:CTV ratios below the 25th percentile, hippocampal-sparing (HpSpMRI) above the 75th percentile, and typical-AD between the 25th and 75th percentile. Brain iron was estimated using QSM. QSM analyses were made voxel-wise and in 7 regions of interest within deep gray nuclei and limbic structures. Iron distribution in EOAD subtypes and controls was compared using an ANOVA. RESULTS: Sixty-eight EOAD patients and 43 controls were evaluated. QSM values were significantly higher in deep gray nuclei (p < 0.001) and limbic structures (p = 0.04) of EOAD patients compared to controls. Among EOAD subtypes, HpSpMRI had the highest QSM values in deep gray nuclei (p < 0.001) whereas the highest QSM values in limbic structures were observed in LPMRI (p = 0.005). QSM in deep gray nuclei had an AUC = 0.92 in discriminating HpSpMRI and controls. CONCLUSIONS: In early-onset Alzheimer's disease patients, we observed significant variations of iron distribution reflecting the pattern of brain atrophy. Iron overload in deep gray nuclei could help to identify patients with atypical presentation of Alzheimer's disease. KEY POINTS: • In early-onset AD patients, QSM indicated a significant brain iron overload in comparison with age-matched controls. • Iron load in limbic structures was higher in participants with limbic-predominant subtype. • Iron load in deep nuclei was more important in participants with hippocampal-sparing subtype.

European recommendations on practices in pediatric neuroradiology: consensus document from the European Society of Neuroradiology (ESNR), European Society of Paediatric Radiology (ESPR) and European Union of Medical Specialists Division of Neuroradiology (UEMS).

Pediatric neuroradiology is a subspecialty within radiology, with possible pathways to train within the discipline from neuroradiology or pediatric radiology. Formalized pediatric neuroradiology training programs are not available in most European countries. We aimed to construct a European consensus document providing recommendations for the safe practice of pediatric neuroradiology. We particularly emphasize imaging techniques that should be available, optimal site conditions and facilities, recommended team requirements and specific indications and protocol modifications for each imaging modality employed for pediatric neuroradiology studies. The present document serves as guidance to the optimal setup and organization for carrying out pediatric neuroradiology diagnostic and interventional procedures. Clinical activities should always be carried out in full agreement with national provisions and regulations. Continued education of all parties involved is a requisite for preserving pediatric neuroradiology practice at a high level.

Advanced imaging in first episode psychosis: a systematic review.

First-episode psychosis (FEP) is defined as the first occurrence of delusions, hallucinations, or psychic disorganization of significant magnitude, lasting more than 7 days. Evolution is difficult to predict since the first episode remains isolated in one third of cases, while recurrence occurs in another third, and the last third progresses to a schizo-affective disorder. It has been suggested that the longer psychosis goes unnoticed and untreated, the more severe the probability of relapse and recovery. MRI has become the gold standard for imaging psychiatric disorders, especially first episode psychosis. Besides ruling out some neurological conditions that may have psychiatric manifestations, advanced imaging techniques allow for identifying imaging biomarkers of psychiatric disorders. We performed a systematic review of the literature to determine how advanced imaging in FEP may have high diagnostic specificity and predictive value regarding the evolution of disease.

Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML.

OBJECTIVES: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. MATERIALS AND METHODS: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. RESULTS: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. CONCLUSION: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. KEY POINTS: • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution "the milky way," and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.

Intraoperative MRI and FLAIR Analysis: Implications for low-grade glioma surgery.

PURPOSE: Intraoperative MRI (iMRI) offers the possibility of acquiring intraoperatively real-time images that will guide neurosurgeons when removing brain tumors. The objective of this study was to report the existence of FLAIR abnormalities on iMRI that may occur on the margin of a brain resection and may lead to misdiagnosis of residual tumor. METHODS: We retrospectively analyzed intraoperative MRI (iMRI) in 21 consecutive patients who underwent surgery for a low-grade glioma. Two readers independently reviewed iMRI images to search for the presence of a FLAIR hyperintensity surrounding the surgical cavity. For each patient, they were instructed to characterize FLAIR abnormalities on the margins of the resected area as (1) no FLAIR abnormality; (2) "linear FLAIR hyperintensity (LFH)", when a<5mm linear FLAIR hyperintensity was present; or (3) "nodular FLAIR hyperintensity (NFH)", in the case of a thick and nodular FLAIR hyperintensity. RESULTS: LFH were present on at least one surgical margin of one third of the patients analyzed with iMRI, and vanished on follow-up MRI, confirming its transient condition; whereas NFH were linked to persistence of pre-surgical abnormalities, such as residual tumor as confirmed or by histopathological analysis of a second surgery or by its remnant on follow-up MRI. CONCLUSION: Linear FLAIR hyperintensities can be present on surgical margins analyzed by iMRI and should not be mistaken for residual tumor.

Use of MRI to predict symptomatic haemorrhagic transformation after thrombolysis for cerebral ischaemia.

BACKGROUND AND OBJECTIVE: Predictors of symptomatic haemorrhagic transformation (s-HT) of cerebral ischaemia after intravenous recombinant tissue-plasminogen activator (rt-PA) were identified in studies using CT scans. We evaluated whether MRI can identify other predictors. METHOD: We analysed predictors of s-HT in a cohort of consecutive patients who received intravenous rt-PA for cerebral ischaemia after MRI at baseline. We used receiver operating characteristic curves considering an area under the curve (AUC) of 0.70 or higher as indicating acceptable discrimination. RESULTS: Of 944 patients, 49 patients (5.2%) developed s-HT. Clinical factors independently associated with s-HT were age (adjusted OR (adjOR) 1.03 for 1 year increase; 95% CI 1.01 to 1.05), excessive alcohol consumption (adjOR 3.13; 95% CI 1.32 to 7.42), recent transient ischaemic attack (adjOR 2.88; 95% CI 1.04 to 7.95) and baseline national institutes of health stroke scale score (adjOR 1.06 for 1 point increase; 95% CI 1.02 to 1.10). MRI predictors were vascular hyperintensities (adjOR 3.89; 95% CI 1.50 to 10.08), old infarcts (adjOR 2.01; 95% CI 1.11 to 3.66) and volume of diffusion-weighted imaging (DWI) abnormality (adjOR 1.02 for 1 cm3 increase; 95% CI 1.01 to 1.03). The only variable with an acceptable discrimination was volume of DWI abnormality (AUC 0.72; 95% CI 0.64 to 0.79), a value of 4 cm3 predicting s-HT with a 78% sensitivity and 58% specificity. Variables that can be assessed only with MRI did not predict s-HT. CONCLUSION: Although the volume of DWI abnormality predicts s-HT, other imaging characteristics that can only be assessed with MRI were not significantly associated with s-HT. Trial registration number NCT01614080.

Hypothalamic Structural and Functional Imbalances in Anorexia Nervosa.

The hypothalamus contains integrative systems that support life, including physiological processes such as food intake, energy expenditure, and reproduction. Here, we show that anorexia nervosa (AN) patients, contrary to normal weight and constitutionally lean individuals, respond with a paradoxical reduction in hypothalamic levels of glutamate/glutamine (Glx) upon feeding. This reversal of the Glx response is associated with decreased wiring in the arcuate nucleus and increased connectivity in the lateral hypothalamic area, which are involved in the regulation on a variety of physiological and behavioral functions including the control of food intake and energy balance. The identification of distinct hypothalamic neurochemical dysfunctions and associated structural variations in AN paves the way for the development of new diagnostic and treatment strategies in conditions associated with abnormal body mass index and a maladaptive response to negative energy balance.

Optical coherence tomography: a window to the optic nerve in clinically isolated syndrome.

In this study, we aimed to evaluate the association of asymptomatic optic nerve demyelinating lesion in patients presenting a clinically isolated syndrome with the asymptomatic retinal neuro-axonal loss previously reported at clinically isolated syndrome. We prospectively recruited 66 patients presenting a clinically isolated syndrome and 66 healthy control subjects matched according to age and gender. All patients underwent brain magnetic resonance imaging including 3D-double inversion recovery (DIR) sequence, optical coherence tomography examination and visual function evaluation, at 2.5-4.5 months after CIS. Evaluation criteria were presence and length of optic nerve DIR hypersignal, retinal layers (including ganglion cell inner plexiform layer and inner nuclear layer) thickness/volume, and low contrast monocular vision acuity (number of letters correctly identified). All clinically isolated syndrome eyes with past history of optic neuritis (CIS-ON) presented an optic nerve DIR hypersignal. We observed asymptomatic optic nerve DIR hypersignal in 22.2% of clinically isolated syndrome eyes without optic neuritis (CIS-NON). In comparison with healthy control, GCIPL volume (in mm3) was significantly lower in CIS-ON eyes [ß (95% confidence interval, CI) = -0.121 (-0.168 to -0.074); P < 0.0001], and to a lesser extent in CIS-NON [ß (95% CI) = -0.023 (-0.039 to -0.008); P = 0.004]. In comparison to healthy controls, eyes with asymptomatic optic nerve DIR hypersignal presented significantly lower macular ganglion cell inner plexiform layer volume [ß (95% CI) = -0.043 (-0.068 to -0.019); P = 0.001], and eyes without did not [ß (95% CI) = -0.016 (-0.034 to 0.003); P = 0.083]. Among CIS-NON, macular ganglion cell inner plexiform layer volume decrease was associated with asymptomatic optic nerve DIR hypersignal independently of optic radiations T2 lesions and primary visual cortex volumes (P = 0.012). Symptomatic optic nerve DIR hypersignal were significantly longer (13.8 ± 6.7 mm) than asymptomatic optic nerve hypersignal (10.0 ± 5.5 mm; P = 0.047). Length of optic nerve DIR hypersignal was significantly associated with thinner inner retinal layers (P ≤ 0.001), thicker inner nuclear layer (P = 0.017) and lower low contrast monocular vision acuity (P < 0.05). Compared to healthy control, low contrast monocular vision acuity was significantly lower in CIS-ON eyes (P < 0.0001) and CIS-NON eyes with (P = 0.03) or without asymptomatic optic nerve DIR hypersignal (P = 0.0005). Asymptomatic demyelinating optic nerve DIR hypersignal at the earliest clinical stage of multiple sclerosis is frequent and associated with asymptomatic retinal neuro-axonal loss reported at clinically isolated syndrome stage. Length of optic nerve DIR hypersignal is a biomarker of retinal neuro-axonal loss and visual disability at clinically isolated syndrome stage. Visual disability of clinically isolated syndrome eyes without clinical and subclinical optic nerve involvement might be due to missed optic nerve lesions on MRI. At the earliest clinical stage of multiple sclerosis, our results support considering optical coherence tomography as a window to the optic nerve rather than to the brain.

A Fully Automatic Method for Optic Radiation Tractography Applicable to Multiple Sclerosis Patients.

The optic radiations (OR) are white matter tracts forming the posterior part of the visual ways. As an important inter-individual variability exists, atlases may be inefficient to locate the OR in a given subject. We designed a fully automatic method to delimitate the OR on a magnetic resonance imaging using tractography. On 15 healthy subjects, we evaluated the validity of our method by comparing the outputs to the Jülich post-mortem histological atlas, and its reproducibility. We also evaluated its feasibility on 98 multiple sclerosis (MS) patients. We correlated different visual outcomes with the inflammatory lesions volume within the OR reconstructed with different methods (our method, atlas, TractSeg). Our method reconstructed the OR bundle in all healthy subjects (< 2 h for most of them), and was reproducible. It demonstrated good classification indexes: sensitivity up to 0.996, specificity up to 0.993, Dice coefficient up to 0.842, and an area under the receiver operating characteristic (ROC) curve of 0.981. Our method reconstructed the OR in 91 of the 98 MS patients (92.9%, < 6 h for most of patients). Compared to an atlas-based approach and the TractSeg method, the inflammatory lesions volume in the OR measured with our method better correlated with the visual cortex volume, visual acuity and mean peripapillar retinal nerve fiber layer thickness. Our method seems to be efficient to reconstruct the OR in healthy subjects, and seems applicable to MS patients. It may be more relevant than an atlas based approach.

Differences in cortical perfusion detected by arterial spin labeling in nonamnestic and amnestic subtypes of early-onset Alzheimer's disease.

OBJECTIVES: Early-onset Alzheimer's disease (EOAD) begins before the age of 65 and is characterized by a faster clinical course and the frequency of nonamnestic symptoms compared to late onset Alzheimer disease (LOAD). However, the pathophysiological process of EOAD remains unclear. We expected that ASL may show widespread cortical hypoperfusion in EOAD compared to LOAD and in nonamnestic EOAD compared to amnestic EOAD. METHODS: In this study, 26 EOAD patients (16 amnestic and 10 nonamnestic patients), 29 LOAD patients and 12 healthy controls underwent pseudo-continuous ASL and 3D FFE T1 sequences. Statistical comparisons between EOAD, LOAD and control groups were made after surface-based analysis of CBF maps in regressing out the cortical thickness. RESULTS: ASL showed a more severe hypoperfusion in nonamnestic EOAD patients compared to amnestic EOAD ones, with mean CBF values (± std) of 26.9 (± 3.8) and 46.6 (± 24.1) mL/100 g/min respectively (P = 0.014), located in the bilateral temporo-parietal neocortex, the precuneus, the posterior cingulate cortices (PCC) and frontal lobes. Comparison between EOAD and LOAD patients showed a trend to hypoperfusion in the left parietal lobe, PCC and precuneus in EOAD (P < 0.001 uncorrected). CONCLUSIONS: Different patterns of hypoperfusion between nonamnestic and amnestic EOAD subtypes were identified, with a more severe and extensive hypoperfusion in nonamnestic patients. A trend towards more severe hypoperfusion was detected in EOAD compared to LOAD. Further studies are needed to validate ASL as a potential tool for the distinction of EOAD subtypes and the prediction of the time course of the disease.

Texture parameters of R2* maps are correlated with iron concentration and red blood cells count in clot analogs: A 7-T micro-MRI study.

BACKGROUND AND PURPOSE: Previous studies have suggested that mechanical revascularization in acute ischemic stroke (AIS) patients could be affected by clot histology. In this 7-T micro-MRI study, we used R2* relaxometry of clot analogs to evaluate the relationship between texture parameters of R2* maps and clot constituents. MATERIALS AND METHODS: Twelve AIS clot analogs were experimentally generated to obtain a wide range of red blood cell concentrations. All clots underwent a MR acquisition using a 7-T micro-MR system. A 3D multi-echo gradient-echo sequence was performed and R2* maps were generated. First order and second order statistics of R2* histograms within the clots were calculated. Iron concentration in clots was measured using absorption spectrometry and red blood cell count (RBC) was obtained by histopathological analysis. RESULTS: RBC count was strongly correlated with iron concentration within clots (r=0.87, P<.001). Higher RBC count and iron concentration were significantly correlated with first order parameters including: (a) global positive shift of the R2* histogram with higher '10th percentile', 'median', 'mean' and '90th percentile'; (b) increase of the global magnitude of voxel values with higher 'total energy' and 'root mean squared'; (c) greater uniformity of the voxel values with higher 'uniformity' and lower 'entropy'. Second order statistical parameters confirmed that higher RBC count and iron concentration correlated with (a) greater concentration of high gray-level values in the image; (b) more "coarse" texture of R2* maps. CONCLUSIONS: Texture analysis of MRI-R2* maps can accurately estimate the red blood cell count and iron content of AIS clot analogs.

Optic nerve double inversion recovery hypersignal in patients with clinically isolated syndrome is associated with asymptomatic gadolinium-enhanced lesion.

BACKGROUND: Optic nerve involvement is not considered in dissemination in space (DIS) or time (DIT) of multiple sclerosis (MS) lesions. OBJECTIVES: To evaluate frequency of optic nerve involvement using three-dimensional (3D)-double inversion recovery (DIR) sequence in clinically isolated syndrome (CIS) and to measure its relationship with DIS and DIT (2010 and 2017 McDonald criteria). METHODS: From November 2013 to August 2016, 57 CIS patients underwent 3T-magnetic resonance imaging (3T-MRI) including 3D-DIR sequence and optical coherence tomography (OCT) at 3 months after CIS. We assessed signal abnormalities of the optic nerves on DIR sequence and collected data for DIS and DIT criteria according to 2010 and 2017 McDonald criteria. RESULTS: Among the 57 recruited patients, the presence of ⩾1 DIR hypersignal in optic nerve was observed in 36 (63%; 48 optic nerves) including asymptomatic hypersignal in 22 (38.5%; 25 optic nerves). Optic nerve involvement was significantly associated with DIT (p = 0.006) and MS according to 2010 criteria (p = 0.01) but was not significantly associated with presence of DIS criteria according to 2010 and 2017 McDonald criteria. We identified a significant (p < 0.001) temporal peripapillary retinal nerve fiber layer thinning on eyes with optic nerve involvement versus healthy controls. CONCLUSIONS: Optic nerve involvement is very frequent at the earliest clinical stage of MS. It is associated with the presence of asymptomatic gadolinium-enhancement and retinal axonal loss and may reflect the inflammatory disease activity level.

Imaging spectrum of Bing-Neel syndrome: how can a radiologist recognise this rare neurological complication of Waldenström's macroglobulinemia?

OBJECTIVES: Bing-Neel syndrome (BNS) is a rare neurological complication of Waldenström's macroglobulinemia. The aim of this study is to describe the spectrum of radiological manifestations of this syndrome and their prevalence in order to facilitate its early diagnosis. METHODS: Twenty-four patients with BNS were diagnosed between 1994 and 2016 in eight centres in France. We retrospectively examined the medical records of these patients as well as the corresponding literature, focusing on imaging studies. Recorded data were statistically analysed and radiological findings described. RESULTS: The mean age of our patients was 62.4 years (35-80 years). The vast majority of patients were men, with a male to female ratio of 9:1. Findings included parenchymal or meningeal involvement or both. The most common finding was leptomeningeal infiltration, either intracranial or spinal, with a prevalence reaching 70.8%. Dural involvement was present in 37.5% of patients. In 41.7% (10/24) of patients, there was parenchymal involvement with a higher prevalence of brain comparing to medullar involvement (33.3% and 23.1% respectively). High T2 signal of the parenchyma was identified in 41.7% of patients and high signal in diffusion was evident in 25% of them. Intraorbital or periorbital involvement was also detected in four cases. A proposition regarding the appropriate imaging protocol completed our study. CONCLUSION: BNS's diagnosis remains challenging. Central nervous system MRI findings in the setting of known or suspected Waldenström's macroglobulinemia appear to be highly suggestive of BNS and appropriate imaging protocols should be implemented for their depiction. KEY POINTS: • Diagnosis of Bing-Neel syndrome (BNS) remains challenging and recent expert recommendations include MRI in the diagnostic criteria for the syndrome. • The most common radiological manifestations of BNS are leptomeningeal/dural infiltration or parenchymal involvement of brain or spinal cord, but many atypical forms may exist with various presentations. • Appropriate imaging protocol for BNS should include enhanced MRI studies of both brain and spine.

Magnetic resonance imaging changes following natalizumab discontinuation in multiple sclerosis patients with progressive multifocal leukoencephalopathy.

BACKGROUND: Detecting early progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS) is clinically relevant. OBJECTIVE: Evaluating magnetic resonance imaging (MRI) changes following natalizumab (NTZ) discontinuation and preceding PML-IRIS. METHODS: MRIs (including diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), post-contrast T1-weighted sequences) were performed every week following PML diagnosis in 11 consecutive NTZ-PML patients. PML expansion, punctate lesions, contrast-enhancement, and mass-effect/edema were evaluated on each MRI sequence, following NTZ discontinuation. RESULTS: PML-IRIS occurred from 26 to 89 days after NTZ discontinuation. MRI changes prior to early PML-IRIS appeared significantly more pronounced using DWI compared to T2-FLAIR imaging (p < 0.003). Two DWI features (marked PML expansion, punctate lesions) systematically preceded contrast-enhancement. CONCLUSION: Subtle changes may occur on DWI preceding contrast-enhancement.

Thalamic alterations remote to infarct appear as focal iron accumulation and impact clinical outcome.

See Duering and Schmidt (doi:10.1093/awx135) for a scientific commentary on this article.Thalamic alterations have been observed in infarcts initially sparing the thalamus but interrupting thalamo-cortical or cortico-thalamic projections. We aimed at extending this knowledge by demonstrating with in vivo imaging sensitive to iron accumulation, one marker of neurodegeneration, that (i) secondary thalamic alterations are focally located in specific thalamic nuclei depending on the initial infarct location; and (ii) such secondary alterations can contribute independently to the long-term outcome. To tackle this issue, 172 patients with an infarct initially sparing the thalamus were prospectively evaluated clinically and with magnetic resonance imaging to quantify iron through R2* map at 24-72 h and at 1-year follow-up. An asymmetry index was used to compare R2* within the thalamus ipsilateral versus contralateral to infarct and we focused on the 95th percentile of R2* as a metric of high iron content. Spatial distribution within the thalamus was analysed on an average R2* map from the entire cohort. The asymmetry index of the 95th percentile within individual nuclei (medio-dorsal, pulvinar, lateral group) were compared according to the initial infarct location in simple and multiple regression analyses and using voxel-based lesion-symptom mapping. Associations between the asymmetry index of the 95th percentile and functional, cognitive and emotional outcome were calculated in multiple regression models. We showed that R2* was not modified at 24-72 h but showed heterogeneous increase at 1 year mainly within the medio-dorsal and pulvinar nuclei. The asymmetry index of the 95th percentile within the medio-dorsal nucleus was significantly associated with infarcts involving anterior areas (frontal P = 0.05, temporal P = 0.02, lenticular P = 0.01) while the asymmetry index of the 95th percentile within the pulvinar nucleus was significantly associated with infarcts involving posterior areas (parietal P = 0.046, temporal P < 0.001) independently of age, gender and infarct volume, which was confirmed by voxel-based lesion-symptom mapping. The asymmetry index of the 95th percentile within the entire thalamus at 1 year was independently associated with poor functional outcome (P = 0.04), poor cognitive outcome (P = 0.03), post-stroke anxiety (P = 0.04) and post-stroke depression (P = 0.02). We have therefore identified that iron accumulates within the thalamus ipsilateral to infarct after a delay with a focal distribution that is strongly linked to the initial infarct location (in relation with the pattern of connectivity between thalamic nuclei and cortical areas or deep nuclei), which independently contributes to functional, cognitive and emotional outcome.

Encoding and immediate retrieval tasks in patients with epilepsy: A functional MRI study of verbal and visual memory.

PURPOSE: Medial lobe temporal structures and more specifically the hippocampus play a decisive role in episodic memory. Most of the memory functional magnetic resonance imaging (fMRI) studies evaluate the encoding phase; the retrieval phase being performed outside the MRI. We aimed to determine the ability to reveal greater hippocampal fMRI activations during retrieval phase. MATERIALS AND METHODS: Thirty-five epileptic patients underwent a two-step memory fMRI. During encoding phase, subjects were requested to identify the feminine or masculine gender of faces and words presented, in order to encourage stimulus encoding. One hour after, during retrieval phase, subjects had to recognize the word and face. We used an event-related design to identify hippocampal activations. RESULTS: There was no significant difference between patients with left temporal lobe epilepsy, patients with right temporal lobe epilepsy and patients with extratemporal lobe epilepsy on verbal and visual learning task. For words, patients demonstrated significantly more bilateral hippocampal activation for retrieval task than encoding task and when the tasks were associated than during encoding alone. Significant difference was seen between face-encoding alone and face retrieval alone. CONCLUSIONS: This study demonstrates the essential contribution of the retrieval task during a fMRI memory task but the number of patients with hippocampal activations was greater when the two tasks were taken into account.

Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer.

OBJECTIVES: To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. METHODS: Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K trans, k ep, v e, v p) and their early variation (∆K trans, ∆k ep, ∆v e, ∆v p). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. RESULTS: Baseline DCE MRI parameters were not associated with the objective response. Early ∆K trans, ∆v e and ∆v p were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∆v e with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. CONCLUSIONS: DCE MRI and early ∆v e may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. KEY POINTS: • DCE MRI could predict the response of brain metastases from lung cancer • ∆v e was the best predictor of response • DCE MRI could be used to individualize patients' follow-up.