Involvement of the posterior tool processing network during explicit retrieval of action tool and semantic tool knowledge: an fMRI study.

Our ability to understand how to interact with familiar objects is supported by conceptual tool knowledge. Conceptual tool knowledge includes action tool and semantic tool knowledge which are supported by the ventro-dorsal and the ventral pathways, respectively. This apparent functional segregation has been recently called into question. In a block-design fMRI study, 35 participants were asked to complete manipulation, function, and association judgment tasks about pairs of familiar objects. Our results showed that lateral occipitotemporal cortex in the ventral pathway was more sensitive to manipulation and function judgment tasks compared with association judgment tasks. Functional connectivity analyses revealed distinct coupling patterns between inferior parietal lobule, lateral occipitotemporal cortex, and fusiform gyrus. Taken together, these data indicate that action tool and semantic tool knowledge are both supported by ventral and ventro-dorsal pathways. Moreover, the explicit retrieval of these representations is supported by the functional coupling of common and distinct brain regions of the posterior tool processing network varying according to the kind of relations to be retrieved.

Subject-Specific Activation of Central Respiratory Centers during Breath-Holding Functional Magnetic Resonance Imaging.

BACKGROUND: Voluntary breath-holding (BH) triggers responses from central neural control and respiratory centers in order to restore breathing. Such responses can be observed using functional MRI (fMRI). OBJECTIVES: We used this paradigm in healthy volunteers with the view to develop a biomarker that could be used to investigate disorders of the central control of breathing at the individual patient level. METHOD: In 21 healthy human subjects (mean age±SD, 32.8 ± 9.9 years old), fMRI was used to determine, at both the individual and group levels, the physiological neural response to expiratory and inspiratory voluntary apneas, within respiratory control centers in the brain and brainstem. RESULTS: Group analysis showed that expiratory BH, but not inspiratory BH, triggered activation of the pontine respiratory group and raphe nuclei at the group level, with a significant relationship between the levels of activation and drop in SpO2. Using predefined ROIs, expiratory BH, and to a lesser extent, inspiratory BH were associated with activation of most respiratory centers. The right ventrolateral nucleus of the thalamus, right pre-Bötzinger complex, right VRG, right nucleus ambiguus, and left Kölliker-Fuse-parabrachial complex were only activated during inspiratory BH. Individual analysis identified activations of cortical/subcortical and brainstem structures related to respiratory control in 19 out of 21 subjects. CONCLUSION: Our study shows that BH paradigm allows to reliably trigger fMRI response from brainstem and cortical areas involved in respiratory control at the individual level, suggesting that it might serve as a clinically relevant biomarker to investigate conditions associated with an altered central control of respiration.

Cortical inflammation and brain signs of high-risk atherosclerosis in a non-human primate model.

Atherosclerosis is a chronic systemic inflammatory disease, inducing cardiovascular and cerebrovascular acute events. A role of neuroinflammation is suspected, but not yet investigated in the gyrencephalic brain and the related activity at blood-brain interfaces is unknown. A non-human primate model of advanced atherosclerosis was first established using longitudinal blood samples, multimodal imaging and gene analysis in aged animals. Non-human primate carotid lesions were compared with human carotid endarterectomy samples. During the whole-body imaging session, imaging of neuroinflammation and choroid plexus function was performed. Advanced plaques were present in multiple sites, premature deaths occurred and downstream lesions (myocardial fibrosis, lacunar stroke) were present in this model. Vascular lesions were similar to in humans: high plaque activity on PET and MRI imaging and systemic inflammation (high plasma C-reactive protein levels: 42 ± 14 µg/ml). We also found the same gene association (metabolic, inflammatory and anti-inflammatory markers) as in patients with similar histological features. Metabolic imaging localized abnormal brain glucose metabolism in the frontal cortex. It corresponded to cortical neuro-inflammation (PET imaging) that correlated with C-reactive protein level. Multimodal imaging also revealed pronounced choroid plexus function impairment in aging atherosclerotic non-human primates. In conclusion, multimodal whole-body inflammation exploration at the vascular level and blood-brain interfaces identified high-risk aging atherosclerosis. These results open the way for systemic and central inflammation targeting in atherosclerosis in the new era of immunotherapy.

Neural correlates of verbal working memory in children with epilepsy with centro-temporal spikes.

BACKGROUND: Previous functional magnetic resonance imaging (fMRI) studies have identified brain systems underlying different components of working memory (WM) in healthy subjects. The aim of this study was to compare the functional integrity of these neural networks in children with self-limited childhood epilepsy with centro-temporal spikes (ECTS) as compared to healthy controls, using a verbal working memory task (WMT). METHODS: Functional MRI of WM in seventeen 6-to-13 year-old children, diagnosed with ECTS, and 17 sex- and age-matched healthy controls were conducted at 3 T. To estimate BOLD responses during the maintenance of low, medium, and high WMT loads, we used a Sternberg verbal WMT. Neuropsychological testing prior to scanning and behavioral data during scanning were also acquired. RESULTS: Behavioral performances during WMT, in particular accuracy and response time, were poorer in children with ECTS than in controls. Increased WM load was associated with increased BOLD signal in all subjects, with significant clusters detected in frontal and parietal regions, predominantly in the left hemisphere. However, under the high load condition, patients showed reduced activation in the frontal, temporal and parietal regions as compared to controls. In brain regions where WM-triggered BOLD activation differed between groups, this activation correlated with neuropsychological performances in healthy controls but not in patients with ECTS, further suggesting WM network dysfunction in the latter. CONCLUSION: Children with ECTS differ from healthy controls in how they control WM processes during tasks with increasing difficulty level, notably for high WM load where patients demonstrate both reduced BOLD activation and behavioral performances.

Social cognition, behaviour and therapy adherence in frontal lobe epilepsy: a study combining neuroeconomic and neuropsychological methods.

Social behaviour of healthy humans and its neural correlates have been extensively studied in social neuroscience and neuroeconomics. Whereas it is well established that several types of epilepsies, such as frontal lobe epilepsy, lead to social cognitive impairments, experimental evidence on how these translate into behavioural symptoms is scarce. Furthermore, it is unclear whether social cognitive or behavioural disturbances have an impact on therapy adherence, which is critical for effective disease management, but generally low in these patients. In order to investigate the relationship between social cognition, social behaviour, and therapy adherence in patients with frontal lobe epilepsies (FLE), we designed a study combining conventional neuropsychological with behavioural economic and functional magnetic resonance imaging (fMRI) methodology. Fifteen patients and 15 healthy controls played a prisoners' dilemma game (an established game to operationalize social behaviour) while undergoing fMRI. Additionally, social cognitive, basic neuropsychological variables, and therapy adherence were assessed. Our results implicate that social behaviour is indeed affected and can be quantified using neuroeconomic methods in patients with FLE. Impaired social behaviour in these patients might be a consequence of altered brain activation in the medial prefrontal cortex and play a role in low therapy adherence. Finally, this study serves as an example of how to integrate neuroeconomic methods in neurology.

Early limbic microstructural alterations in apathy and depression in de novo Parkinson's disease.

BACKGROUND: Whether structural alterations underpin apathy and depression in de novo parkinsonian patients is unknown. The objectives of this study were to investigate whether apathy and depression in de novo parkinsonian patients are related to structural alterations and how structural abnormalities relate to serotonergic or dopaminergic dysfunction. METHODS: We compared the morphological and microstructural architecture in gray matter using voxel-based morphometry and diffusion tensor imaging coupled with white matter tract-based spatial statistics in a multimodal imaging case-control study enrolling 14 apathetic and 13 nonapathetic patients with de novo Parkinson's disease and 15 age-matched healthy controls, paired with PET imaging of the presynaptic dopaminergic and serotonergic systems. RESULTS: De novo parkinsonian patients with apathy had bilateral microstructural alterations in the medial corticostriatal limbic system, exhibiting decreased fractional anisotropy and increased mean diffusivity in the anterior striatum and pregenual anterior cingulate cortex in conjunction with serotonergic dysfunction. Furthermore, microstructural alterations extended to the medial frontal cortex, the subgenual anterior cingulate cortex and subcallosal gyrus, the medial thalamus, and the caudal midbrain, suggesting disruption of long-range nondopaminergic projections originating in the brainstem, in addition to microstructural alterations in callosal interhemispheric connections and frontostriatal association tracts early in the disease course. In addition, microstructural abnormalities related to depressive symptoms in apathetic and nonapathetic patients revealed a distinct, mainly right-sided limbic subnetwork involving limbic and frontal association tracts. CONCLUSIONS: Early limbic microstructural alterations specifically related to apathy and depression emphasize the role of early disruption of ascending nondopaminergic projections and related corticocortical and corticosubcortical networks which underpin the variable expression of nonmotor and neuropsychiatric symptoms in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

Basal ganglia involvement in ARX patients: The reason for ARX patients very specific grasping?

The ARX (Aristaless Related homeoboX) gene was identified in 2002 as responsible for XLAG syndrome, a lissencephaly characterized by an almost complete absence of cortical GABAergic interneurons, and for milder forms of X-linked Intellectual Disability (ID) without apparent brain abnormalities. The most frequent mutation found in the ARX gene, a duplication of 24 base pairs (c.429_452dup24) in exon 2, results in a recognizable syndrome in which patients present ID without primary motor impairment, but with a very specific upper limb distal motor apraxia associated with a pathognomonic hand-grip, described as developmental Limb Kinetic Apraxia (LKA). In this study, we first present ARX expression during human fetal brain development showing that it is strongly expressed in GABAergic neuronal progenitors during the second and third trimester of pregnancy. We show that although ARX expression strongly decreases towards the end of gestation, it is still present after birth in some neurons of the basal ganglia, thalamus and cerebral cortex, suggesting that ARX also plays a role in more mature neuron functioning. Then, using morphometric brain MRI in 13 ARX patients carrying c.429_452dup24 mutation and in 13 sex- and age-matched healthy controls, we show that ARX patients have a significantly decreased volume of several brain structures including the striatum (and more specifically the caudate nucleus), hippocampus and thalamus as well as decreased precentral gyrus cortical thickness. We observe a significant correlation between caudate nucleus volume reduction and motor impairment severity quantified by kinematic parameter of precision grip. As basal ganglia are known to regulate sensorimotor processing and are involved in the control of precision gripping, the combined decrease in cortical thickness of primary motor cortex and basal ganglia volume in ARX dup24 patients is very likely the anatomical substrate of this developmental form of LKA.

Lesions in deep gray nuclei after severe traumatic brain injury predict neurologic outcome.

PURPOSE: This study evaluates the correlation between injuries to deep gray matter nuclei, as quantitated by lesions in these nuclei on MR T2 Fast Spin Echo (T2 FSE) images, with 6-month neurological outcome after severe traumatic brain injury (TBI). MATERIALS AND METHODS: Ninety-five patients (80 males, mean age = 36.7y) with severe TBI were prospectively enrolled. All patients underwent a MR scan within the 45 days after the trauma that included a T2 FSE acquisition. A 3D deformable atlas of the deep gray matter was registered to this sequence; deep gray matter lesions (DGML) were evaluated using a semi-quantitative classification scheme. The 6-month outcome was dichotomized into unfavorable (death, vegetative or minimally conscious state) or favorable (minimal or no neurologic deficit) outcome. RESULTS: Sixty-six percent of the patients (63/95) had both satisfactory registration of the 3D atlas on T2 FSE and available clinical follow-up. Patients without DGML had an 89% chance (P = 0.0016) of favorable outcome while those with bilateral DGML had an 80% risk of unfavorable outcome (P = 0.00008). Multivariate analysis based on DGML accurately classified patients with unfavorable neurological outcome in 90.5% of the cases. CONCLUSION: Lesions in deep gray matter nuclei may predict long-term outcome after severe TBI with high sensitivity and specificity.

Behavioral and fMRI responses to fearful faces are altered in benign childhood epilepsy with centrotemporal spikes (BCECTS).

OBJECTIVE: We hypothesized that children with benign childhood epilepsy with centrotemporal spikes (BCECTS) might have altered social cognitive skills and underlying neural networks. METHODS: We studied 13 patients with BCECTS and 11 age-matched controls using event-related functional magnetic resonance imaging (fMRI) with an emotional discrimination task consisting of viewing happy, fearful, scrambled, and neutral faces. Behavioral performance measured during the task was correlated with clinical variables and behavioral ratings. RESULTS: In comparison with age-matched controls, children with BCECTS performing a fearful faces detection task showed significantly reduced bilateral fMRI activation in the insular cortex, caudate, and lentiform nuclei, as well as increased response time. The percentage of errors made by children with BCECTS correlated negatively with age, a finding not observed in controls. In patients, accuracy positively correlated with time since the last seizure. The above abnormalities were not observed during happy faces detection task, except for a slower response in children with BCECTS as compared to controls. SIGNIFICANCE: Our study suggests that BCECTS is associated with altered social cognition network and function, particularly for the identification of fearful faces. The age dependency of some of these findings supports the view that a delayed maturation of spiking cortical regions might underlie the cognitive dysfunction observed in BCECTS.

Studying the neural bases of prism adaptation using fMRI: A technical and design challenge.

Prism adaptation induces rapid recalibration of visuomotor coordination. The neural mechanisms of prism adaptation have come under scrutiny since the observations that the technique can alleviate hemispatial neglect following stroke, and can alter spatial cognition in healthy controls. Relative to non-imaging behavioral studies, fMRI investigations of prism adaptation face several challenges arising from the confined physical environment of the scanner and the supine position of the participants. Any researcher who wishes to administer prism adaptation in an fMRI environment must adjust their procedures enough to enable the experiment to be performed, but not so much that the behavioral task departs too much from true prism adaptation. Furthermore, the specific temporal dynamics of behavioral components of prism adaptation present additional challenges for measuring their neural correlates. We developed a system for measuring the key features of prism adaptation behavior within an fMRI environment. To validate our configuration, we present behavioral (pointing) and head movement data from 11 right-hemisphere lesioned patients and 17 older controls who underwent sham and real prism adaptation in an MRI scanner. Most participants could adapt to prismatic displacement with minimal head movements, and the procedure was well tolerated. We propose recommendations for fMRI studies of prism adaptation based on the design-specific constraints and our results.

Intracellular Phosphate Dynamics in Muscle Measured by Magnetic Resonance Spectroscopy during Hemodialysis.

Of the 600-700 mg inorganic phosphate (Pi) removed during a 4-hour hemodialysis session, a maximum of 10% may be extracted from the extracellular space. The origin of the other 90% of removed phosphate is unknown. This study tested the hypothesis that the main source of phosphate removed during hemodialysis is the intracellular compartment. Six binephrectomized pigs each underwent one 3-hour hemodialysis session, during which the extracorporeal circulation blood flow was maintained between 100 and 150 ml/min. To determine in vivo phosphate metabolism, we performed phosphorous ((31)P) magnetic resonance spectroscopy using a 1.5-Tesla system and a surface coil placed over the gluteal muscle region. (31)P magnetic resonance spectra (repetition time =10 s; echo time =0.35 ms) were acquired every 160 seconds before, during, and after dialysis. During the dialysis sessions, plasma phosphate concentrations decreased rapidly (-30.4 %; P=0.003) and then, plateaued before increasing approximately 30 minutes before the end of the sessions; 16 mmol phosphate was removed in each session. When extracellular phosphate levels plateaued, intracellular Pi content increased significantly (11%; P<0.001). Moreover, ßATP decreased significantly (P<0.001); however, calcium levels remained balanced. Results of this study show that intracellular Pi is the source of Pi removed during dialysis. The intracellular Pi increase may reflect cellular stress induced by hemodialysis and/or strong intracellular phosphate regulation.

A phantom and animal study of temperature changes during fMRI with intracerebral depth electrodes.

BACKGROUND: MRI is routinely used in patients undergoing intracerebral electroencephalography (icEEG) in order to precisely locate the position of intracerebral electrodes. In contrast, fMRI has been considered unsafe due to suspected greater risk of radiofrequency-induced (RF) tissue heating at the vicinity of intracerebral electrodes. We determined the possible temperature change at the tip of such electrodes during fMRI sessions in phantom and animals. METHODS: A human-shaped torso phantom and MRI-compatible intracerebral electrodes approved for icEEG in humans were used to mimic a patient with four intracerebral electrodes (one parasagittal and three coronal). Six rabbits were implanted with one or two coronal electrodes. MRI-induced temperature changes at the tip of electrodes were measured using a fibre-optic thermometer. All experiments were performed on Siemens Sonata 1.5T scanner. RESULTS: For coronally implanted electrodes with wires pulled posteriorly to the magnetic bore, temperature increase recorded during EPI sequences reached a maximum of 0.6°C and 0.9°C in phantom and animals, respectively. These maximal figures were decreased to 0.2°C and 0.5°C, when electrode wires were connected to cables and amplifier. When electrode wires were pulled anteriorly to the magnetic bore, temperature increased up to 1.3°C in both phantom and animals. Greater temperature increases were recorded for the single electrode implanted parasagitally in the phantom. CONCLUSION: Variation of the temperature depends on the electrode and wire position relative to the transmit body coil and orientation of the constant magnetic field (B0). EPI sequence with intracerebral electrodes appears as safe as standard T1 and T2 sequence for implanted electrodes placed perpendicular to the z-axis of the magnetic bore, using a 1.5T MRI system, with the free-end wires moving posteriorly, in phantom and animals.

Multimodal convergence within the intraparietal sulcus of the macaque monkey.

The parietal cortex is highly multimodal and plays a key role in the processing of objects and actions in space, both in human and nonhuman primates. Despite the accumulated knowledge in both species, we lack the following: (1) a general description of the multisensory convergence in this cortical region to situate sparser lesion and electrophysiological recording studies; and (2) a way to compare and extrapolate monkey data to human results. Here, we use functional magnetic resonance imaging (fMRI) in the monkey to provide a bridge between human and monkey studies. We focus on the intraparietal sulcus (IPS) and specifically probe its involvement in the processing of visual, tactile, and auditory moving stimuli around and toward the face. We describe three major findings: (1) the visual and tactile modalities are strongly represented and activate mostly nonoverlapping sectors within the IPS. The visual domain occupies its posterior two-thirds and the tactile modality its anterior one-third. The auditory modality is much less represented, mostly on the medial IPS bank. (2) Processing of the movement component of sensory stimuli is specific to the fundus of the IPS and coincides with the anatomical definition of monkey ventral intraparietal area (VIP). (3) A cortical sector within VIP processes movement around and toward the face independently of the sensory modality. This amodal representation of movement may be a key component in the construction of peripersonal space. Overall, our observations highlight strong homologies between macaque and human VIP organization.

Assessment of white matter injury and outcome in severe brain trauma: a prospective multicenter cohort.

BACKGROUND: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). METHODS: In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n=38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. RESULTS: Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. CONCLUSIONS: White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score.

Correlation of diffusion and metabolic alterations in different clinical forms of multiple sclerosis.

Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients.

Implementation of an absolute brain 1H-MRS quantification method to assess different tissue alterations in multiple sclerosis.

Magnetic resonance spectroscopy has emerged as a sensitive modality to detect early and diffuse alterations in multiple sclerosis. Recently, the hypothesis of neurodegenerative pathogenesis has highlightened the interest for measurement of metabolites concentrations, to gain specificity, in a large brain volume encompassing different tissue alterations. Therefore, we proposed in this paper the implementation of an absolute quantification method based on localized spectroscopy at short (30 ms) and long (135 ms) echo time of a volume including normal appearing white matter, cortical gray matter, and lesions. First, methodological developments were implemented including external calibration, and corrections of phased-array coil sensitivity and cerebrospinal fluid volume contribution. Second, these improvements were validated and optimized using an original methodology based on simulations of brain images with lesions. Finally, metabolic alterations were assessed in 65 patients including 26 relapsing-remitting, 17 primary-progressive (PP), 22 secondary-progressive (SP) patients, and in 23 normal subjects. Results showed increases of choline, creatine, and myo-inositol concentrations in PP and SP patients compared to controls, whereas the concentration of N-acetyl compounds remained constant. The major finding of this study was the identification of Cho concentration and Cho/tNA ratio as putative markers of progressive onset, suggesting interesting perspectives in detection and followup of neurodegenerative processes.

Thalamus abnormalities during working memory in schizophrenia. An fMRI study.

We aimed to identify and compare cerebral activations in schizophrenia patients and controls during a working memory (WM) task at the same performance level for both a verbal and a spatial task. Whereas the performances of the patients (n=22) and controls (n=15) were similar, cerebral activations were significantly increased in the patients, particularly in the thalamus/basal ganglia for the two tasks and in regions of the prefrontal cortex and the cerebellum for the spatial task only. Our results suggest that stronger activations of deep brain structures in patients may be the result from a compensating mechanism for WM difficulties.

The left ventral occipito-temporal response to words depends on language lateralization but not on visual familiarity.

The sensitivity of the left ventral occipito-temporal (vOT) cortex to visual word processing has triggered a considerable debate about the role of this region in reading. One popular view is that the left vOT underlies the perceptual expertise needed for rapid skilled reading. Because skilled reading breaks down when words are presented in a visually unfamiliar format, we tested this hypothesis by analyzing vOT responses to horizontally presented words (familiar format) and vertically presented words (unfamiliar format). In addition, we compared the activity in participants with left and right cerebral dominance for language generation. Our results revealed 1) that the vOT activity during reading is lateralized to the same side as the inferior frontal activity during word generation, 2) that vertically and horizontally presented words triggered the same amount of activity in the vOT of the dominant hemisphere, but 3) that there was significantly more activity for vertically presented words in the vOT of the nondominant hemisphere. We suggest that the reading-related activity in vOT reflects the integration of general perceptual processes with language processing in the anterior brain regions and is not limited to skilled reading in the familiar horizontal format.

Rapid-clearance iron nanoparticles for inflammation imaging of atherosclerotic plaque: initial experience in animal model.

PURPOSE: To evaluate the use of a recently developed fast-clearing ultrasmall superparamagnetic iron oxide (USPIO) for detection of vascular inflammation in atherosclerotic plaque. MATERIALS AND METHODS: The study protocol was approved by the animal experimentation ethics committee. A recently introduced USPIO, P904, and a reference-standard USPIO, ferumoxtran-10, were tested in a rabbit model of induced aortic atherosclerosis. In vivo magnetic resonance (MR) angiography and T2*-weighted plaque MR imaging were performed at baseline and after administration of P904 and ferumoxtran-10 (administered dose for both, 1000 micromol of iron per kilogram of body weight) in 26 hyperlipidemic New Zealand white rabbits. The variation in vessel wall area over time was evaluated with nonparametric testing. Ex vivo MR imaging findings were compared with iron content at linear regression analysis. RESULTS: With in vivo MR imaging, plaque analysis was possible as early as 24 hours after P904 injection. The authors observed a 27.75% increase in vessel wall area due to susceptibility artifacts on day 2 (P = .04) and a 38.81% increase on day 3 (P = .04) after P904 administration compared with a 44.5% increase in vessel wall area on day 7 (P = .04) and a 34.8% increase on day 10 (P = .22) after ferumoxtran-10 administration. These susceptibility artifacts were correlated with intraplaque iron uptake in the corresponding histologic slices. The number of pixels with signal loss on the ex vivo MR images was linearly correlated with the logarithm of the iron concentration (P = .0001; R(2) = 0.93). CONCLUSION: Plaque inflammation in rabbits can be detected earlier with P904 than with ferumoxtran-10 owing to the faster blood pharmacokinetics and the early uptake of P904 in the reticuloendothelial system. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/252/2/401/DC1.

Chronic motor cortex stimulation for phantom limb pain: a functional magnetic resonance imaging study: technical case report.

OBJECTIVE AND IMPORTANCE: Chronic motor cortex stimulation has provided satisfactory control of pain in patients with central or neuropathic trigeminal pain. We used this technique in a patient who experienced phantom limb pain. Functional magnetic resonance imaging (fMRI) was used to guide electrode placement and to assist in understanding the control mechanisms involved in phantom limb pain. CLINICAL PRESENTATION: A 45-year-old man whose right arm had been amputated 2 years previously experienced phantom limb pain and phantom limb phenomena, described as the apparent possibility of moving the amputated hand voluntarily. He was treated with chronic motor cortex stimulation. INTERVENTION: Data from fMRI were used pre- and postoperatively to detect shoulder and stump cortical activated areas and the "virtual" amputated hand cortical area. These sites of preoperative fMRI activation were integrated in an infrared-based frameless stereotactic device for surgical planning. Phantom limb virtual finger movement caused contralateral primary motor cortex activation. Satisfactory pain control was obtained; a 70% reduction in the phantom limb pain was achieved on a visual analog scale. Postoperatively and under chronic stimulation, inhibiting effects on the primary sensorimotor cortex as well as on the contralateral primary motor and sensitive cortices were detected by fMRI studies. CONCLUSION: Chronic motor cortex stimulation can be used to relieve phantom limb pain and phantom limb phenomena. Integrated by an infrared-based frameless stereotactic device, fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication. Pain control mechanisms and cortical reorganization phenomena can be studied by the use of fMRI.