Assia Jaillard

Intravenous administration of 99mTc-HMPAO-labeled human mesenchymal stem cells after stroke: in vivo imaging and biodistribution.

Human mesenchymal stem cells (hMSC) are a promising source for cell therapy after stroke. To deliver these cells, an IV injection appears safer than a local graft. We aimed to assess the whole-body biodistribution of IV-injected 99mTc-HMPAO-labeled hMSC in normal rats (n = 9) and following a right middle cerebral artery occlusion (MCAo, n = 9). Whole-body nuclear imaging, isolated organ counting (at 2 and 20 h after injection) and histology were performed. A higher activity was observed in the right damaged hemisphere of the MCAo group [6.5 ± 0.9 × 10−3 % of injected dose (ID)/g] than in the control group (3.6 ± 1.2 × 10−3 %ID/g), 20 h after injection. In MCAo rats, right hemisphere activity was higher than that observed in the contralateral hemisphere at 2 h after injection (11.6 ± 2.8 vs. 9.8 ± 1.7 × 10−3 %ID/g). Following an initial hMSC lung accumulation, there was a decrease in pulmonary activity from 2 to 20 h after injection in both groups. The spleen was the only organ in which activity increased between 2 and 20 h. The presence of hMSC was documented in the spleen, liver, lung, and brain following histology. IV-injected hMSC are transiently trapped in the lungs, can be sequestered in the spleen, and are predominantly eliminated by kidneys. After 20 h, more hMSC are found in the ischemic lesion than into the undamaged cerebral tissue. IV delivery of hMSC could be the initial route for a clinical trial of tolerance.

Reliability of graph analysis of resting state fMRI using test-retest dataset from the Human Connectome Project

The exploration of brain networks with resting-state fMRI (rs-fMRI) combined with graph theoretical approaches has become popular, with the perspective of finding network graph metrics as biomarkers in the context of clinical studies. A preliminary requirement for such findings is to assess the reliability of the graph based connectivity metrics. In previous test-retest (TRT) studies, this reliability has been explored using intraclass correlation coefficient (ICC) with heterogeneous results. But the issue of sample size has not been addressed. Using the large TRT rs-fMRI dataset from the Human Connectome Project (HCP), we computed ICCs and their corresponding p-values (applying permutation and bootstrap techniques) and varied the number of subjects (from 20 to 100), the scan duration (from 400 to 1200 time points), the cost and the graph metrics, using the Anatomic-Automatic Labelling (AAL) parcellation scheme. We quantified the reliability of the graph metrics computed both at global and regional level depending, at optimal cost, on two key parameters, the sample size and the number of time points or scan duration. In the cost range between 20% to 35%, most of the global graph metrics are reliable with 40 subjects or more with long scan duration (14min 24s). In large samples (for instance, 100 subjects), most global and regional graph metrics are reliable for a minimum scan duration of 7min 14s. Finally, for 40 subjects and long scan duration (14min 24s), the reliable regions are located in the main areas of the default mode network (DMN), the motor and the visual networks.

Abnormal cortical sensorimotor activity during "Target" sound detection in subjects with acute acoustic trauma sequelae: an fMRI study.

The most common consequences of acute acoustic trauma (AAT) are hearing loss at frequencies above 3 kHz and tinnitus. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to visualize neuronal activation patterns in military adults with AAT and various tinnitus sequelae during an auditory “oddball” attention task. AAT subjects displayed overactivities principally during reflex of target sound detection, in sensorimotor areas and in emotion‐related areas such as the insula, anterior cingulate and prefrontal cortex, in premotor area, in cross‐modal sensory associative areas, and, interestingly, in a region of the Rolandic operculum that has recently been shown to be involved in tympanic movements due to air pressure. We propose further investigations of this brain area and fine middle ear investigations, because our results might suggest a model in which AAT tinnitus may arise as a proprioceptive illusion caused by abnormal excitability of middle‐ear muscle spindles possibly link with the acoustic reflex and associated with emotional and sensorimotor disturbances.

Neuropsychological Features of Dementia due to Dural Arteriovenous Malformation

We report two patients aged 65 and 61 years, who presented a subacute dementia with normal CT scan without contrast injection. Angiography showed a dural arteriovenous malformation. The patients improved dramatically with treatment of the malformation. Dementia was characterised by frontal dysfunction, emotional disorders, mnesic and praxic impairment. This neuropsychological pattern suggests a profile of global dementia in the field of vascular dementia.

The effect of eliprodil on the evolution of a focal cerebral ischaemia in vivo.

The purpose of the present study was to evaluate in vivo the effect of a non competitive antagonist of the NMDA receptor, eliprodil, on the size of a focal ischaemic insult and on its temporal evolution in a rat model, using a spin-echo diffusion magnetic resonance imaging multislice technique. Rats were either injected with 1 mg/kg i.v. of eliprodil or with the vehicle only (placebo) 5 min after middle cerebral artery occlusion, or not injected (controls). Ten coronal slices were acquired every hour, up to 7 h after occlusion of the artery, and the volume of hyperintense signals was measured at each time point and for each animal. Diffusion magnetic resonance images revealed that the administration of eliprodil reduced significantly (by 50% or more) the volume of ischaemia, up to 7 h after occlusion, particularly in the cortex of the ipsilateral hemisphere. The results show the potential efficacy of eliprodil to reduce the cerebral ischaemic volume after arterial occlusion, thus confirming the interest of glutamate receptor antagonists in the treatment of ischaemia.

L'imagerie par résonance magnétique cérébrale fonctionnelle en pratique clinique

In the last decade, functional MRI (fMRI) has become one of the most widely used functional imaging technique in neurosciences. However, its clinical applications remain limited. Despite methodological and practical issues, fMRI data has been validated by different techniques (magnetoencephalography, Wada test, electrical and magnetic stimulations, and surgical resections). In neurosurgical practice, fMRI can identify eloquent areas involved in motor and language functions, and may evaluate characteristics of postoperative neurological deficit including its occurrence, clinical presentation and duration. This may help to inform patients and to prepare postoperative care. fMRI may also identify epileptic foci. In neurological practice, fMRI may help to determine prognosis of recovery after stroke, appropriate medication, and rehabilitation. fMRI may help to identify patients at risk of developing Alzheimer disease. Finally, cerebrovascular reactivity imaging is an interesting approach that might provide new radiological insights of vascular function.

The “Hub Disruption Index,” a Reliable Index Sensitive to the Brain Networks Reorganization. A Study of the Contralesional Hemisphere in Stroke

Stroke, resulting in focal structural damage, induces changes in brain function at both local and global levels. Following stroke, cerebral networks present structural, and functional reorganization to compensate for the dysfunctioning provoked by the lesion itself and its remote effects. As some recent studies underlined the role of the contralesional hemisphere during recovery, we studied its role in the reorganization of brain function of stroke patients using resting state fMRI and graph theory. We explored this reorganization using the “hub disruption index” (κ), a global index sensitive to the reorganization of nodes within the graph. For a given graph metric, κ of a subject corresponds to the slope of the linear regression model between the mean local network measures of a reference group, and the difference between that reference and the subject under study. In order to translate the use of κ in clinical context, a prerequisite to achieve meaningful results is to investigate the reliability of this index. In a preliminary part, we studied the reliability of κ by computing the intraclass correlation coefficient in a cohort of 100 subjects from the Human Connectome Project. Then, we measured intra-hemispheric κ index in the contralesional hemisphere of 20 subacute stroke patients compared to 20 age-matched healthy controls. Finally, due to the small number of patients, we tested the robustness of our results repeating the experiment 1000 times by bootstrapping on the Human Connectome Project database. Statistical analysis showed a significant reduction of κ for the contralesional hemisphere of right stroke patients compared to healthy controls. Similar results were observed for the right contralesional hemisphere of left stroke patients. We showed that κ, is more reliable than global graph metrics and more sensitive to detect differences between groups of patients as compared to healthy controls. Using new graph metrics as κ allows us to show that stroke induces a network-wide pattern of reorganization in the contralesional hemisphere whatever the side of the lesion. Graph modeling combined with measure of reorganization at the level of large-scale networks can become a useful tool in clinic.

Speech recovery and language plasticity can be facilitated by Sensori-Motor Fusion training in chronic non-fluent aphasia. A case report study

ABSTRACT The rehabilitation of speech disorders benefits from providing visual information which may improve speech motor plans in patients. We tested the proof of concept of a rehabilitation method (Sensori-Motor Fusion, SMF; Ultraspeech player) in one post-stroke patient presenting chronic non-fluent aphasia. SMF allows visualisation by the patient of target tongue and lips movements using high-speed ultrasound and video imaging. This can improve the patient’s awareness of his/her own lingual and labial movements, which can, in turn, improve the representation of articulatory movements and increase the ability to coordinate and combine articulatory gestures. The auditory and oro-sensory feedback received by the patient as a result of his/her own pronunciation can be integrated with the target articulatory movements they watch. Thus, this method is founded on sensorimotor integration during speech. The SMF effect on this patient was assessed through qualitative comparison of language scores and quantitative analysis of acoustic parameters measured in a speech production task, before and after rehabilitation. We also investigated cerebral patterns of language reorganisation for rhyme detection and syllable repetition, to evaluate the influence of SMF on phonological-phonetic processes. Our results showed that SMF had a beneficial effect on this patient who qualitatively improved in naming, reading, word repetition and rhyme judgment tasks. Quantitative measurements of acoustic parameters indicate that the patient’s production of vowels and syllables also improved. Compared with pre-SMF, the fMRI data in the post-SMF session revealed the activation of cerebral regions related to articulatory, auditory and somatosensory processes, which were expected to be recruited by SMF. We discuss neurocognitive and linguistic mechanisms which may explain speech improvement after SMF, as well as the advantages of using this speech rehabilitation method.