Exploring anterograde memory: a volumetric MRI study in patients with mild cognitive impairment.

BACKGROUND: The aim of this volumetric study was to explore the neuroanatomical correlates of the Free and Cued Selective Reminding Test (FCSRT) and the Delayed Matching-to-Sample-48 items (DMS-48), two tests widely used in France to assess verbal and visual anterograde memory. We wanted to determine to what extent the two tests rely on the medial temporal lobe, and could therefore be predictive of Alzheimer's disease, in which pathological changes typically start in this region. METHODS: We analysed data from a cohort of 138 patients with mild cognitive impairment participating in a longitudinal multicentre clinical research study. Verbal memory was assessed using the FCSRT and visual recognition memory was evaluated using the DMS-48. Performances on these two tests were correlated to local grey matter atrophy via structural MRI using voxel-based morphometry. RESULTS: Our results confirm the existence of a positive correlation between the volume of the medial temporal lobe and the performance on the FCSRT, prominently on the left, and the performance on the DMS-48, on the right, for the whole group of patients (family-wise error, P < 0.05). Interestingly, this region remained implicated only in the subgroup of patients who had deficient scores on the cued recall of the FCSRT, whereas the free recall was associated with prefrontal aspects. For the DMS-48, it was only implicated for the group of patients whose performances declined between the immediate and delayed trial. Conversely, temporo-parietal cortices were implicated when no decline was observed. Within the medial temporal lobe, the parahippocampal gyrus was prominently involved for the FCSRT and the immediate trial of the DMS-48, whereas the hippocampus was solely involved for the delayed trial of the DMS-48. CONCLUSIONS: The two tests are able to detect an amnestic profile of the medial temporal type, under the condition that the scores remain deficient after the cued recall of the FCSRT or decline on the delayed recognition trial of the DMS-48. Strategic retrieval as well as perceptual/attentional processes, supported by prefrontal and temporo-parietal cortices, were also found to have an impact on the performances. Finally, the implication of the hippocampus appears time dependent, triggered by a longer delay than the parahippocampus, rather than determined by the sense of recollection or the encoding strength associated with the memory trace.

Distinct and common cerebral activation changes during mental time travel in relapsing-remitting multiple sclerosis patients.

Mental time travel (MTT) entails the ability to mentally travel into autobiographical memory (AM) and episodic future thinking (EFT). While AM and EFT share common phenomenological and cerebral functional properties, distinctive characteristics have been documented in healthy and clinical populations. No report, to our knowledge, has informed on the functional underpinnings of MTT impairment in multiple sclerosis (MS) patients, hence the aim of this work. We studied 22 relapsing-remitting MS patients and 22 matched controls. Participants underwent an AM/EFT assessment using the Autobiographical Interview (Levine et al. 2002), followed by a functional MRI session. The latter consisted in AM and EFT tasks, distinguishing the construction and elaboration phases of events. The results showed impaired performance for AM and EFT in patients, accompanied by increased cerebral activations mostly located in the frontal regions, which extended to the parietal, lateral temporal and posterior regions during AM/EFT tasks, relative to healthy controls. Enhanced brain activations in MS patients were particularly evident during the EFT task and involved the hippocampus, frontal, external temporal, and cingulate regions. The construction phase required greater fronto-parieto-temporal activations in MS patients relative to both healthy controls, and the elaboration phase. Taking together, our results suggested the occurrence of cerebral activation changes in the context of MTT in MS patients, expressed by distinct and common mechanisms for AM and EFT. This study may provide new insights in terms of cerebral activation changes in brain lesion and their application to clinical settings, considering AM/EFT's central role in everyday life.

Towards a Hall effect magnetic tracking device for MRI.

This paper presents the first prototype of a magnetic tracking device for Magnetic Resonance Imaging. The unique relationship between the space coordinates of a MRI scanner bore and the magnetic field gradients used in MRI allows building a localization system based on an accurate measurement of these gradients. These gradients are measured thanks to a 3D Hall device with a footprint of only 50µm(2), integrated with its specific conditioning circuit in a low cost, low voltage 0.35µm CMOS process. The first experimental results show that a sub-millimeter localization is possible. It opens the way to the development of MRI compatible magnetic tracking systems integrable in a surgical tool.

Prefrontal cortex recruitment during naturalistic remote memory: a factorial block-event fMRI study.

Most classical neuroimaging studies of human memory require the subject to follow task instructions, discriminate stimuli, make a decision and, finally, press a button to respond. To which extent does such a cognitive sequence influence neural correlates of recognition memory especially with respect to the prefrontal cortex (PFC) is not clear yet. We set up a naturalistic recognition task. Personal photographs were mixed with photographs from family albums of people who were not known to the participant. The subjects alternated a recognition task (recognition and response) with a mere observational one (simple recognition). This factorial block-event functional MRI design allowed us to disentangle the regions related to memory (personal photographs vs. distracters under both conditions) from those related to the response (responding vs. observing) as well as to examine the interaction between the two factors. Only medial and left orbito-frontal regions were transiently active during successful recognition in the two task conditions. Memory and responding interacted in the left lateral PFC within the middle and inferior gyrus. These regions were more active for personal photographs than for distracters only when the subject had to respond. Sustained activations spread bilaterally whatever the task. Such a design that encompasses personal photographs, an observation period for recognition as well as a mixed-design may have led to a better isolation of the neural network underlying remote autobiographical memory. Recruitment within the PFC during retrieval was only limited to its medial and left anterior parts. Sustained activation did not differ between the discrimination and the observation period. This original design might be valuable for further dissociation between decision, self, autobiographical memory and the PFC.

Optimisation of a post-processing method to remove the pulse artifact from EEG data recorded during fMRI: an application to P300 recordings during e-fMRI.

In functional cerebral studies, it has been established that co-registered electroencephalography (EEG) measurements and functional magnetic resonance imaging (fMRI) were complementary. However, EEG data recorded inside an MRI scanner are heavily distorted, mainly by the most prominent artifact, the cardiac pulse artifact (PA). We describe an original algorithm which yields a high-quality PA filter and demonstrates how this tool can be used to improve the quality of P300 ERP measurements during event-related fMRI (e-fMRI) experiments. EEG data were acquired in interleaved mode during e-fMRI while six healthy volunteers performed a visual odd-ball task, involving Distractors, Target and Novel stimuli, to elicit P300 components. The PA was corrected with the original algorithm. The temporal variations in the PA were evidenced using a principal component analysis (PCA), on each EEG channel. The procedure yielded several PA templates, which were regressed from the EEG data. The PA removal procedure was optimised, and then implemented to improve the measured P300 components. Regressing the most adequate PA template resulted in a high-quality reduction in spectral power at frequencies associated with the cardiac PA. More reliable P300 component measurements were obtained, evidencing higher amplitudes for Novels (9.76-11.20 microV) than for to Targets (6.3-9.09 microV) in centro-parietal and prefrontal areas. The improvement of the processing of EEG data acquired simultaneously with fMRI data provides a new tool and casts perspectives to study the functional organisation of the brain.

Functional integration in schizophrenia: too little or too much? Preliminary results on fMRI data.

The disconnectivity hypothesis proposes that schizophrenia results from poor or miswired anatomical connections. Theoretically, its functional counterpart should be disintegration. Integration is thought to allow segregated neurons to interact as a coherent whole, referred to as the "core", while the non-interacting part of the brain is referred to as the "rest". In this study, it is suggested that schizophrenia is the result of rest noise interfering with core activity. Two possible causes are assessed: (i) defective core integration, making the core more vulnerable to noise from the rest, or (ii) the rest being too highly integrated, meaning that it can interfere with the core. These hypotheses were tested using fMRI data acquired from 13 stabilized medicated schizophrenic subjects compared to 11 matched controls. Subjects were required to perform a series of lexical decision and retrieval tasks in separate sessions. The brain was divided into 90 components. Integration was defined as the amount of information shared between the components of a sub-system. An iterative aggregation procedure made it possible to identify a core on the basis of the functional clustering index, which assesses the integration of the core relative to its integration with the rest. Correlation of component-pairs within the core was also compared between the two groups. This procedure was repeated for each subject and for each task. Cores did not differ between the two groups, either in terms of integration or in terms of functional clustering index. However, the core was still highly integrated with the rest and the rest was overly integrated in schizophrenic subjects. Both anomalies were correlated with the negative symptoms. These findings were consistent regardless of the task considered. Furthermore, within the core, anterior-posterior correlations were lower in patients (between the frontal and the parietal and posterior cingulate cortices), whereas frontal left-right correlations were excessive. No significant correlation was found with the medication. Thus, it appears that schizophrenia entails a deleterious combination of too much "noisy" integration (from the rest) and too little "significant" integration (anterior-posterior functional connectivity).

P300 recordings during event-related fMRI: a feasibility study.

Analysis of combined event-related potentials (ERP) and functional magnetic resonance imaging (fMRI) can provide a high temporal and high spatial resolution to study functional cerebral processes. However, EEG data recorded inside an MR scanner is heavily distorted by artifacts. It is important in cognitive studies to ensure that recorded data reflect the same brain activity, and this is achieved through interleaved electroencephalographic (EEG) and fMRI measurements. Here, we demonstrate the feasibility of recording P300 ERPs during fMRI using a three-stimulus visual oddball task and involving a small number of trials for each stimulus. Ten EEG channels were acquired interleaved with fMRI images in five healthy subjects. The stimuli, including rare targets "X," frequent repetitive distractors "O," and rare distractors referred to as novels, were randomly presented every 2 +/- 1 s. The post hoc filter presented here was designed and applied to EEG data to remove the cardiac pulse artifact. Interleaved EEG/fMRI acquisition evidenced two P300 ERPs evoked at Fz, Cz, and Pz by targets and novels. Novel-related ERPs were of higher amplitude than their target-related counterparts. The fMRI maps acquired concurrently showed stronger BOLD response for target condition. We have shown that interleaved acquisition allows to obtain reliable P300 data and fMRI results, likely to shed light on the anatomical location of brain regions involved in cognitive ERPs relevant to many disorders affecting CNS functions. These noninvasive multimodal neuroimaging techniques can be used to explore and better understand processes underlying the functional brain organization.

Where arousal meets attention: a simultaneous fMRI and EEG recording study.

In this fMRI study, we looked for the regions supporting interaction between cortical arousal and attention during three conditions: detection, observation, and rest. Arousal measurements were obtained from the EEG low-frequency (LF) power (5-9.5 Hz) recorded continuously together with fMRI. Whatever the condition, arousal was positively correlated with the fMRI signal of the right dorsal-lateral prefrontal and superior parietal cortices, closely overlapping regions involved in the maintenance of attention. Although the inferior temporal areas also presented a correlation with arousal during detection, path analysis suggests that this influence may be indirect, through the top-down influence of the previously mentioned network. However, those visual-processing areas could account for the correlation between arousal and performances. Lastly, the medial frontal cortex, frontal opercula, and thalamus were inversely correlated with arousal but only during detection and observation so that they could account for the control of arousal.

Determination of vessel cross section for flow rate quantification.

This study was motivated by the interest of measuring different cardiac parameters for which changes in the flow rate during a cardiac cycle needs to be determined at different positions along a vessel segment. These measurements result in a great number of images for which automatic contour detection is very helpful. A model-based algorithm for intraluminal contour detection has been developed in order to allow an accurate quantitative image analysis. The algorithm permits to select contours automatically on all the frames and slices of an imaging study. Images obtained on a flow phantom simulating the effects of blood circulation in large arteries have been used to validate the method. They were acquired with a specially designed interleaved multi slice and phase sequence, using a standard whole-body 2 Tesla NMR scanner. A potential in vivo application of the algorithm has been demonstrated on abdominal aorta images.

In vitro validation of MR measurements of arterial pulse-wave velocity in the presence of reflected waves.

A magnetic resonance imaging projective velocity encoding sequence was used to determine the pulse-wave velocity in an artery model. To this end, a well-defined flow phantom simulating flow propagation in large arteries was used. In order to validate the measurement method in the presence of large reflected waves, these were deliberately created in the phantom. The projective sequence was applied to two measurement sites and the wave velocity was determined from the spatial and temporal separations of the foot of the velocity waveform. A theoretical model describing reflection and attenuation phenomena was compared with experimental velocity waveforms. The model showed that reflections and attenuation can explain the important changes in velocity waveforms. The model also confirmed that in the presence of reflecting waves, the foot of the waveform can be used as a characteristic point for measurements through changes in the waveform.

Language functional neuro-imaging changes following focal left thalamic infarction.

The involvement of the left thalamus in language function has been largely demonstrated through the effects of thalamic lesion and/or stimulation upon language. However, the pathophysiological mechanisms underlying thalamic aphasias remain a matter of debate. We report here on changes in the pattern of brain activity in auditory word processing, verb generation and visual lexical decision in a patient who sustained left thalamic infarct following the surgery of intractable mesio-temporal epilepsy with left hippocampal sclerosis. To some extent, our findings exemplify the way the left thalamus brings on line the cortical networks involved in language processing, suggested in the term 'selective engagement'.

NMR studies in demyelinating and non-demyelinating experimental allergic encephalomyelitis. An approach involving a dehydration procedure.

The spinal cords of rats, involved as part of two distinct and reproducible experimental allergic encephalomyelitis animal models, presenting inflammatory white matter lesions with and without demyelination, were studied in vitro by NMR, before and after a dehydration procedure, in order to characterize demyelination. All the parameters of the T1 and T2 relaxation times were determined, as well as the initial proportion of the very quickly decaying component of the free induction decay, and the magnetization transfer ratio. The relaxation decays were fitted with the discrete and Contin methods. Magnetization transfer ratio measurements permitted first to evaluate the magnetization transfer at the apex, and secondly to decompose the post-irradiation curves into two components: a gaussian and a lorentzian line, with their relative proportions and widths. The results presented in this study clearly demonstrate that it is not possible to evidence demyelination in fresh spinal cord preparations by NMR. However, the dehydration procedure, which was introduced with the aim of reducing the amount of free water in our samples, seems sufficient to enable the detection of demyelination from the T2 relaxation spectra and magnetization transfer data. As a conclusion, we think that the NMR properties of water protons allow to achieve tissue characterization on condition that the parameters concerning free water and its exchanges are eliminated.

TO5 as a magnetization transfer contrast test object: characterization of the gels and determination of the real magnetization transfer.

Following the work of the European concerted action, "Tissue characterization by magnetic resonance spectroscopy and imaging," sets of five test objects (TO) were designed, produced, and distributed among European laboratories. The TO were designed to control the image quality of clincial magnetic resonance imaging in an independent and uniform mode. The fifth test object (TO5) was devoted to relaxation measurements and composed of 18 agarose tubes, inserted in an holder filled with a CuSO4 solution. These gels are subject to magnetization transfer (MT). The purpose of this paper is to characterize their MT parameters. An individual study of each gel was performed in a spectrometer, and an individual fit, as well as a global fit, was done on the two-pool model. The MT parameters found in each case are in agreement with the known properties of the agarose gels and given below. The real MT (transfer of magnetization from water to macromolecules) was computed, taking into account the "bleeding over" (direct saturation of the water magnetization). The maximum real MT ranges from 15 to 35% and can be obtained with almost the same saturation pulse conditions for all the gels. However, the saturating field required to reach the maximum MT is very high (46 microT) and unserviceable on a clinical device.

[Magnetic Resonance Imaging study of the role of the blood-brain barrier in the pathogenesis of experimental allergic encephalomyelitis: application to multiple sclerosis]. / Etude par imagerie de Résonance Magnétique du rôle de la barrière hémato-encéphalique dans la pathogenèse de l'encéphalomyélite allergique expérimentale: applications à la sclérose en plaques.

Nuclear magnetic resonance imaging (MRI) proved to be, from the first, a very sensitive method, allowing the visualisation of multiple sclerosis lesions, yet which never permitted to establish a non equivocal relationship between the semeiology of such lesions and the clinical signs. The multifocal aspect of disseminated multiple sclerosis lesions is probably one of several factors accounting for this discrepancy. The study of an autoimmune disease, experimental allergic encephalomyelitis (EAE), regarded as a suitable model for multiple sclerosis in humans, has been performed using MRI in order to unravel the pathogenesis of the disease and apprehend the mechanisms responsible for the formation of multiple sclerosis lesions. The study focused on the part played by the blood-brain barrier (BBB) in the induction process of an autoimmune disease, since the central nervous system is normally screened from immunological supervision, by this barrier. Models both of acute EAE, induced by active or passive transfer of the antigen (myelin basic protein-MBP)--and chronic EAE, induced by passive transfer of MBP-specific T cells and myelin glycoproteins or MOG-specific monoclonal antibodies, have been reproduced, and their evolution followed up using high field MRI. Every time, the crucial role of the BBB was evidenced by the synchronism existing between the clinical signs, the appearance of lesions, preferentially in the most sensitive or permeable areas, and the BBB breakdown encouraged by the action of adjuvants. The physiopathological study of EAE using MRI is suggestive of the concept of systemic disease for multiple sclerosis, according to a two-step process, involving, in a first stage some primary viral or bacterial infection, causing T-cells to be sensitized to the host's own proteins by molecular mimicry, and in a second stage some bacterial infection or accidental circumstances which, resulting in a BBB breakdown, would provide immunocompetent cells with an opportunity to reach their target.

Evaluation of RARE-MR urography in the assessment of ureterohydronephrosis.

OBJECTIVE: The goal of this prospective study was to evaluate the value of the fast imaging sequence called RARE-MR urography (RMU) for the diagnosis of ureterohydronephrosis. MATERIALS AND METHODS: Sixty-nine patients underwent this procedure. The results were compared with those obtained by intravenous urography (IVU) and ultrasonography (US). RESULTS: The accuracy of RMU in the detection of urinary tract dilatation and the localization of the level of obstruction was excellent (100%). The determination of the type of obstruction, intrinsic versus extrinsic, was 80% by IVU and 60% for RMU. The RMU sequence alone could not specify the nature of the obstruction. Functional information about the obstructed collecting system could not be obtained. CONCLUSION: The RMU technique may be considered in the following circumstances: contraindications to IVU (allergy to contrast medium, severe renal failure), impairment of renal excretion, and failure to locate the level of obstruction by US. The absence of ionizing radiations favors the promotion of this procedure to study ureterohydronephrosis during pregnancy.

Quantitative cerebral magnetic resonance imaging during ACTH treatment of multiple sclerosis.

Serial MR scans were performed with the 2DFT imaging method and the filtered backprojection imaging method on 12 patients with multiple sclerosis in acute phase, 4 in a relapsing/remitting form, and 8 in a progressive form, before, during and after ACTH treatment. Both T1 and T2mono relaxation times, obtained by fitting transverse magnetization decay curves with a monoexponential function within the apparently normal white matter and the areas of increased signal, were measured. With the backprojection method it was possible to fit the transverse magnetization decay curve with a biexponential function and obtain T2long and T2short relaxation times. The T2mono and T1 relaxation times of the apparently normal white matter were significantly different from those obtained for volunteers, but no significant differences were found before, during, or after treatment. The transverse magnetization decay curves of the areas of increased signal were better fitted by a biexponential function. No significant changes in these relaxation times were observed after ACTH treatment. These results argue against an anti-oedematous action of ACTH and may suggest that it has an immunosuppressant effect.

Nuclear magnetic resonance T2 relaxation times in multiple sclerosis.

An original method was used to carry out the mathematical analysis of T2 transverse magnetization decay curves and the measure of T2 relaxation times on multiple sclerosis (MS) patients. The presumably normal white matter (WM) of these patients presented higher T2 relaxation times (98.6 msec), in comparison with that found in a population sample (88 msec). In this case, magnetization decay curves remain mostly monoexponential and are characterized by a single T2. On the other hand, areas of increased signal (AIS) curves are always better fitted by a biexponential function characterized by a short (82 msec) and a long (greater than 200 msec) T2. The spreading out of long T2 varies from one AIS to another in the same patient and among different patients; values of long T2 also vary with time, but without any correlation with the clinical state. In fact, no correlation was been established between relaxation times and clinical parameters. Quantitative MRI therefore enables a different approach to interpret MRI images; results suggest that several histobiochemical parameters play a role in the pathogenesis of an AIS and that MS is a dynamic and constantly evolving disease.

In vivo determination of multiexponential T2 relaxation in the brain of patients with multiple sclerosis.

In vivo measurement of T2 relaxation times in multiple sclerosis (MS) lesions by magnetic resonance imaging (MRI) is potentially useful for the evaluation of the disease activity. Seven patients with definite MS were investigated over a period of three years (19 examinations), using a whole-body MRI scanner operating at 0.15 T with a specially designed high-power radio-frequency head coil. A modified CPMG sequence with a 180 degree pulse interval of TE = 6 msec and 128 echoes was used for the T2 relaxation measurement of the areas of increased signal (AIS) and white matter (WM). A biexponential T2 analysis of each pixel of the spin-echo images was computed. The T2 relaxation processes were found to be a monoexponential function in WM. The T2 relaxation times of apparently normal white matter in MS patients was significantly longer than in control subjects. The T2 relaxation curves of the AIS were found in most cases to fit a biexponential function characterized by a short and a long T2. T2 long relaxation times of AIS were spread out over a wide range (150-560 msec). The study of T2 long histograms shows that some AIS can be divided into two or three parts depending on the T2 long values. Each of these parts may correspond to a pathological process such as edema, demyelination and gliosis. Evolution of T2 relaxation times over a period of time cannot as yet be correlated with modifications in the clinical state.

Filtered backprojection and spectral width of MR signal.

Reconstructed images obtained by filtered backprojection are altered when the projections are distorted by an attenuation of the high frequency components of the demodulated magnetic resonance (MR) signal. This attenuation occurs if the spectral width of the MR signal is reduced by the bandwidth of the receiver radiofrequency coil as well as by the use of imperfect refocusing pulses. This signal spectrum has to be wide when the sampling bandwidth is wide, because the sampling time is very short, for instance in the case of very short interpulse delay such as 6 ms. A short interpulse delay is needed when many images are required, to enable the transverse magnetization decay of each pixel to be recorded accurately. This paper presents an analysis of backprojection reconstruction for such a case and demonstrates a contamination of each pixel by surrounding pixels. The consequence on the results of T2 measurement and biexponential decomposition of transverse magnetization decay curves are discussed. A method for correction of such artifacts is described.

Multiple sclerosis diagnosis: magnetic resonance imaging compared with other instrumental examinations.

Examination by magnetic resonance imaging (MRI), evoked potentials (EP) and cerebrospinal fluid (CSF) analyses was carried out on 97 definite, 20 probable and 40 possible multiple sclerosis (MS) patients (McAlpine's clinical criteria). MRI of only 4 transverse brain sections at the level of the ventricles and the analysis of the first 4 echoes showed periventricular or parenchymal lesions, or both, in 114 of the 117 definite and probable MS, and in 25 of the possible MS. MRI was more sensitive than the CSF analyses or EP; abnormalities more frequently appeared in known MS, and clinically asymptomatic lesions were seen. The MRI abnormalities were not, however, MS-specific; they were present in other neurological patients; none posed a question of differential diagnosis from MS. Complementary examinations, and especially MRI, should be a valuable adjunct for MS diagnosis, as long as the findings are viewed in the clinical context.