Publications by authors named "Ana Saitovitch"

10 Publications

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Arterial spin labeling brain MRI study to evaluate the impact of deafness on cerebral perfusion in 79 children before cochlear implantation.

Neuroimage Clin 2021 27;29:102510. Epub 2020 Nov 27.

Service de radiologie pédiatrique, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris, APHP, Université de Paris, INSERM U1163, Institut Imagine, Paris, France; INSERM ERL "Developmental Trajectories & Psychiatry", Université Paris Saclay, Ecole Normale Supérieure Paris-Saclay, Université de Paris, CNRS, Centre Borelli, France.

Age at implantation is considered to be a major factor, influencing outcomes after pediatric cochlear implantation. In the absence of acoustic input, it has been proposed that cross-modal reorganization can be detrimental for adaptation to the new electrical input provided by a cochlear implant. Here, through a retrospective study, we aimed to investigate differences in cerebral blood flow (CBF) at rest prior to implantation in children with congenital deafness compared to normally hearing children. In addition, we looked at the putative link between pre-operative rest-CBF and the oral intelligibility scores at 12 months post-implantation. Finally, we observed the evolution of perfusion with age, within brain areas showing abnormal rest-CBF associated to deafness, in deaf children and in normally hearing children. In children older than 5 years old, results showed a significant bilateral hypoperfusion in temporal regions in deaf children, particularly in Heschl's gyrus, and a significant hyperperfusion of occipital regions. Furthermore, in children older than 5 years old, whole brain voxel-by-voxel correlation analysis between pre-operative rest-CBF and oral intelligibility scores at 12 months post-implantation, showed significant negative correlation localized in the occipital regions: children who performed worse in the speech perception test one year after implantation were those presenting higher preoperative CBF values in these occipital regions. Finally, when comparing mean relative perfusion (extracted from the temporal regions found abnormal on whole-brain voxel-based analysis) across ages in patients and controls, we observed that the temporal perfusion evolution was significantly different in deaf children than in normally hearing children. Indeed, while temporal perfusion increased with age in normally hearing children, it remained stable in deaf children. We showed a critical period around 4 years old, where in the context of auditory deprivation, there is a lack of synaptic activity in auditory regions. These results support the benefits of early cochlear implantation to maximize the effectiveness of auditory rehabilitation and to avoid cross-modal reorganization.
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http://dx.doi.org/10.1016/j.nicl.2020.102510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7777537PMC
November 2020

Rest Functional Brain Maturation during the First Year of Life.

Cereb Cortex 2021 Feb;31(3):1776-1785

INSERM UA10, Department of Pediatric Radiology, Hôpital Necker Enfants Malades, AP-HP, Imagine Institute (UMR 1163), Paris Descartes University, Sorbonne Paris Cité University, Paris 75015, France.

The first year of life is a key period of brain development, characterized by dramatic structural and functional modifications. Here, we measured rest cerebral blood flow (CBF) modifications throughout babies' first year of life using arterial spin labeling magnetic resonance imaging sequence in 52 infants, from 3 to 12 months of age. Overall, global rest CBF significantly increased during this age span. In addition, we found marked regional differences in local functional brain maturation. While primary sensorimotor cortices and insula showed early maturation, temporal and prefrontal region presented great rest CBF increase across the first year of life. Moreover, we highlighted a late and remarkably synchronous maturation of the prefrontal and posterior superior temporal cortices. These different patterns of regional cortical rest CBF modifications reflect a timetable of local functional brain maturation and are consistent with baby's cognitive development within the first year of life.
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http://dx.doi.org/10.1093/cercor/bhaa325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869100PMC
February 2021

Posterior Fossa Arachnoid Cyst in a Pediatric Population is Associated with Social Perception and Rest Cerebral Blood Flow Abnormalities.

Cerebellum 2020 Feb;19(1):58-67

INSERM U1000, Department of Pediatric Radiology, Hôpital Necker Enfants Malades, AP-HP, University René Descartes, Institut Imagine and UMR 1163, Paris, France.

Posterior fossa arachnoid cysts (PFAC) may produce not only neurological symptoms but also other symptoms still poorly understood such as behavioral and learning deficits, awkwardness, and difficulties in social interaction. These subtle social impairments have not been formally described and their underlying brain mechanisms remain unknown. In the present case-control study, we aimed to empirically characterize social impairments in a pediatric population with PFAC using eye tracking. In addition, we investigated putative functional cortical abnormalities in these children using arterial spin labeling magnetic resonance imaging. Overall, 15 patients with PFAC (3f, age = 9.4 ± 4 years) and 43 typically developing volunteer children (16f, age = 9.3 ± 3.6 years) were enrolled in this study. Eye tracking was used to record gaze patterns during visualization of social interaction scenes. Viewing times to faces of characters and non-social background were analyzed. A voxel-wise whole-brain analysis was performed to investigate rest cerebral blood flow (CBF) abnormalities. Significantly reduced viewing time to faces was observed in patients compared with controls (p < 0.01). A ROC curve analysis revealed that 30% of PFAC patients presented viewing time to the face lower than the cutoff, while none of the controls did. The whole-brain analysis revealed a significant decrease in rest CBF in PFAC patients compared with controls bilaterally in the superior temporal gyrus and the temporoparietal junction (TPJ) (p < 0.05 FWE). These results suggest that early life PFAC may have an impact on functional activity of the temporal lobe, which could be associated with social perception deficits.
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http://dx.doi.org/10.1007/s12311-019-01082-wDOI Listing
February 2020

Central nervous system complications in adult cystinosis patients.

J Inherit Metab Dis 2020 03 18;43(2):348-356. Epub 2019 Sep 18.

Department of Pediatric Radiology, Necker hospital, APHP, Inserm U1000, Imagine Institute, Paris Descartes University, Paris, France.

Little is known about the long-term progression of adult nephropathic cystinosis patients. Our objective was to study central nervous system complications in cystinosis patients in the era of early cysteamine treatment, using advanced neuroimaging techniques. Neurological examination and multimodal brain 3 Tesla MRI were performed in 21 adult cystinosis patients, including 18 infantile cystinosis patients, 20 controls matched for age and renal function, and 12 healthy controls. Differences in gray matter volume and rest cerebral blood flow (CBF) using arterial spin labeling sequence were investigated using whole-brain voxel-based approach. Median age was 33.8 years (18.7-65.8). Seven patients (38.9%) presented with at least one central nervous system clinical abnormality: two (11.1%) with seizures, three (16.7%) with memory defects, five (27.8%) with cognitive defect, and one (5.5%) with stroke-like episode. These patients had a worse compliance to treatment (compliance score 2 vs 1, P = .03) and received a lower median cysteamine dose (0.9 g/day vs 2.1 g/day, P = .02). Among patients with infantile cystinosis, 13 (72.2%) showed cortical atrophy, which was absent in controls, but it was not correlated with symptoms. Cystinosis patients showed a significant gray matter decrease in the middle frontal gyrus compared with healthy controls and a significant negative correlation between the cystine blood level and rest CBF was observed in the right superior frontal gyrus, a region associated with executive function. Compliance to cysteamine treatment is a major concern in these adult patients and could have an impact on the development of neurological and cognitive complications.
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http://dx.doi.org/10.1002/jimd.12164DOI Listing
March 2020

Neural and behavioral signature of human social perception.

Sci Rep 2019 06 25;9(1):9252. Epub 2019 Jun 25.

INSERM U1000, Department of Pediatric Radiology and IMAGINE Institute, INSERM UMR 1163, Paris Descartes University, Sorbonne Paris Cité, Hôpital Necker-Enfants Malades, Paris, France.

Social behavior is extremely variable among individuals, and the neural basis of this variability is still poorly understood. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is, social perception. For that purpose, we first used eye-tracking to measure social perception during the passive visualization of socially relevant movie clips. Second, we correlated eye-tracking data with measures of rest cerebral blood flow (CBF) obtained using arterial spin-labeling (ASL) MRI, an index of local rest brain function. The results showed a large interindividual variability in the number of fixations to the eyes of characters during passive visualization of movie clips displaying social interactions. Moreover, individual patterns remained stable across time, suggesting an individual signature of social behavior. Whole-brain analyses showed significant positive correlation between the number of fixations to the eyes and rest CBF: individuals who looked more to the eyes were those with higher rest CBF levels within the right superior temporal regions. Our results indicate the existence of a neural and behavioral signature associated with the interindividual variability in social perception.
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http://dx.doi.org/10.1038/s41598-019-44977-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593101PMC
June 2019

Anatomical and functional abnormalities on MRI in kabuki syndrome.

Neuroimage Clin 2019 19;21:101610. Epub 2018 Nov 19.

Service de radiologie pédiatrique, Hôpital Necker Enfants Malades, INSERM U1000, AP-HP, Université René Descartes, Pres Sorbonne Paris Cité, Institut Imagine, UMR 1163, France.

Kabuki syndrome (KS) is a rare congenital disorder (1/32000 births) characterized by distinctive facial features, intellectual disability, short stature, and dermatoglyphic and skeletal abnormalities. In the last decade, mutations in KMT2D and KDM6A were identified as a major cause of kabuki syndrome. Although genetic abnormalities have been highlighted in KS, brain abnormalities have been little explored. Here, we have investigated brain abnormalities in 6 patients with KS (4 males; M = 10.96 years, SD = 2.97 years) with KMT2D mutation in comparison with 26 healthy controls (17 males; M = 10.31 years, SD = 2.96 years). We have used MRI to explore anatomical and functional brain abnormalities in patients with KS. Anatomical abnormalities in grey matter volume were assessed by cortical and subcortical analyses. Functional abnormalities were assessed by comparing rest cerebral blood flow measured with arterial spin labeling-MRI. When compared to healthy controls, KS patients had anatomical alterations characterized by grey matter decrease localized in the bilateral precentral gyrus and middle frontal gyrus. In addition, KS patients also presented functional alterations characterized by cerebral blood flow decrease in the left precentral gyrus and middle frontal gyrus. Moreover, subcortical analyses revealed significantly decreased grey matter volume in the bilateral hippocampus and dentate gyrus in patients with KS. Our results strongly indicate anatomical and functional brain abnormalities in KS. They suggest a possible neural basis of the cognitive symptoms observed in KS, such as fine motor impairment, and indicate the need to further explore the consequences of such brain abnormalities in this disorder. Finally, our results encourage further imaging-genetics studies investigating the link between genetics, anatomical and functional brain alterations in KS.
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http://dx.doi.org/10.1016/j.nicl.2018.11.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413468PMC
December 2019

Cerebral blood flow changes after radiation therapy identifies pseudoprogression in diffuse intrinsic pontine gliomas.

Neuro Oncol 2018 06;20(7):994-1002

Hôpital Necker Enfants Malades, Pediatric Radiology Department, Paris, France.

Background: The interval between progression and death in diffuse intrinsic pontine glioma (DIPG) is usually <6 months. However, reports of longer patient survival following radiotherapy, in the presence of radiological signs of progression, suggest that these cases may be comparable to pseudoprogression observed in adult glioblastoma. Our aim was to identify such cases and compare their multimodal MRI features with those of patients who did not present the same evolution.

Methods: Multimodal MRIs of 43 children treated for DIPG were retrospectively selected at 4 timepoints: baseline, after radiotherapy, during true progression, and at the last visit. The patients were divided into 2 groups depending on whether they presented conventional MRI changes that mimicked progression. The apparent diffusion coefficient, arterial spin labeling cerebral blood flow (ASL-CBF), and dynamic susceptibility contrast perfusion relative cerebral blood volume (DSCrCBV) and flow (DSCrCBF) values were recorded for each tumor voxel, avoiding necrotic areas.

Results: After radiotherapy, 19 patients (44%) showed radiological signs that mimicked progression: 16 survived >6 months following so-called pseudoprogression, with a median of 8.9 months and a maximum of 35.6 months. All 43 patients exhibited increased blood volume and flow after radiotherapy, but the 90th percentile of those with signs of pseudoprogression had a greater increase of ASL-CBF (P < 0.001). Survival between the 2 groups did not differ significantly. During true progression, DSCrCBF and DSCrCBV values increased only in patients who had not experienced pseudoprogression.

Conclusions: Pseudoprogression is a frequent phenomenon in DIPG patients. This condition needs to be recognized before considering treatment discontinuation. In this study, the larger increase of the ASL-CBF ratio after radiotherapy accurately distinguished pseudoprogression from true progression.
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http://dx.doi.org/10.1093/neuonc/nox227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007230PMC
June 2018

Multimodal Magnetic Resonance Imaging of Treatment-Induced Changes to Diffuse Infiltrating Pontine Gliomas in Children and Correlation to Patient Progression-Free Survival.

Int J Radiat Oncol Biol Phys 2017 10 11;99(2):476-485. Epub 2017 Apr 11.

Pediatric Radiology Department, Hôpital Necker Enfants Malades, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité 1000, Paris, France; Imagine-Institut des Maladies Génétiques, UMR 1163, Paris, France; Université Paris Descartes, ComUE Sorbonne Paris Cité, Paris, France.

Purpose: To use multimodal magnetic resonance imaging (MRI) to quantify treatment-induced changes in the whole volume of diffuse infiltrating pontine gliomas and correlate them with progression-free survival (PFS).

Methods And Materials: This prospective study included 22 children aged 3.3 to 14.7 years (median, 5.9 years). Multimodal MRI was performed at 3 distinct time points: before treatment, the first week following radiation therapy (RT), and 2 months after RT. The imaging protocol included morphologic, multi b-value diffusion; arterial spin labeling; and dynamic susceptibility contrast-enhanced perfusion. Morphologic and multimodal data-lesion volume, diffusion coefficients, relative cerebral blood flow, and relative cerebral blood volume (rCBV)-were recorded at the 3 aforementioned time points. The Wilcoxon test was used to compare each individual parameter variation between time points, and its correlation with PFS was assessed by the Spearman test.

Results: Following RT, the tumors' solid component volume decreased by 40% (P<.001). Their median diffusion coefficients decreased by 20% to 40% (P<.001), while median relative cerebral blood flow increased by 60% to 80% (P<.001) and median rCBV increased by 70% (P<.001). PFS was positively correlated with rCBV measured immediately after RT (P=.003), and in patients whose rCBV was above the cutoff value of 2.46, the median PFS was 4.6 months longer (P=.001). These indexes tended to return to baseline 2 months after RT. Lesion volume before or after RT was not correlated with survival.

Conclusions: Multimodal MRI provides useful information about diffuse infiltrating pontine gliomas' response to treatment; rCBV increases following RT, and higher values are correlated with better PFS. High rCBV values following RT should not be mistaken for progression and could be an indicator of response to therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2017.04.007DOI Listing
October 2017

Tuning Eye-Gaze Perception by Transitory STS Inhibition.

Cereb Cortex 2016 06 5;26(6):2823-31. Epub 2016 Mar 5.

INSERM U1000, Department of Pediatric Radiology, Hôpital Necker Enfants Malades, AP-HP, University René Descartes, PRES Sorbonne Paris Cité, UMR 1163, Institut Imagine, Paris, France.

Processing eye-gaze information is a key step to human social interaction. Neuroimaging studies have shown that superior temporal sulcus (STS) is highly implicated in eye-gaze perception. In autism, a lack of preference for the eyes, as well as anatomo-functional abnormalities within the STS, has been described. To date, there are no experimental data in humans showing whether it is possible to interfere with eye-gaze processing by modulating STS neural activity. Here, we measured eye-gaze perception before and after inhibitory transcranial magnetic stimulation (TMS) applied over the posterior STS (pSTS) in young healthy volunteers. Eye-gaze processing, namely overt orienting toward the eyes, was measured using eye tracking during passive visualization of social movies. Inhibition of the right pSTS led participants to look less to the eyes of characters during visualization of social movies. Such effect was specific for the eyes and was not observed after inhibition of the left pSTS nor after placebo TMS. These results indicate for the first time that interfering with the right pSTS neural activity transitorily disrupts the behavior of orienting toward the eyes and thus indirectly gaze perception, a fundamental process for human social cognition. These results could open up new perspectives in therapeutic interventions in autism.
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http://dx.doi.org/10.1093/cercor/bhw045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869819PMC
June 2016

Atypical coordination of cortical oscillations in response to speech in autism.

Front Hum Neurosci 2015 27;9:171. Epub 2015 Mar 27.

Department of Neurosciences, University of Geneva Geneva, Switzerland.

Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism. This deficit predicts the severity of both verbal impairment and autism symptoms in the affected sample. Finally, we found that oscillation-based connectivity between auditory and other language cortices is altered in autism. These results suggest that the verbal disorder in autism could be associated with an altered balance of slow and fast auditory oscillations, and that this anomaly could compromise the mapping between sensory input and higher-level cognitive representations.
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http://dx.doi.org/10.3389/fnhum.2015.00171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376066PMC
April 2015