Biomedical subjects
Publications and source records attributed to L Lemieux.
Brain shrinkage with chronic alcoholism is well acknowledged. We have shown, with quantitative analysis of serial scans, an increase in hippocampal, cerebral, and cerebellar volume after abstinence from alcohol.
The amygdala are thought to play an important role in emotional information processing. First studies indicate a link between amygdala atrophy, fear and aggression and between amygdala hypertrophy and depression. To investigate a possible relationship between amygdala volumes, aggression and depression, we measured the amygdala of 62 patients with temporal lobe epilepsy (TLE) with and without aggressive behavior or depression and 20 healthy volunteers using quantitative magnetic resonance imaging (MRI). Amygdala volumes of female patients (n=26) were significantly larger than those of males (n=36) (left side: P=0.001; right side P=0.05). Depressed patients displayed significant enlargement of both amygdala (left side: P=0.008; right side: P=0.001) There was no significant finding relating to the factor aggression neither was there any significant interaction between aggression, dysthymia and gender.
Electroencephalographic (EEG) monitoring during functional magnetic resonance imaging (fMRI) experiments is increasingly applied for studying physiological and pathological brain function. However, the quality of the fMRI data can be significantly compromised by the EEG recording due to the magnetic susceptibility of the EEG electrode assemblies and electromagnetic noise emitted by the EEG recording equipment. We therefore investigated the effect of individual components of the EEG recording equipment on the quality of echo planar images. The artifact associated with each component was measured and compared to the minimum scalp-cortex distance measured in normal controls. The image noise originating from the EEG recording equipment was identified as coherent noise and could be eliminated by appropriate shielding of the EEG equipment. It was concluded that concurrent EEG and fMRI could be performed without compromising the image quality significantly if suitable equipment is used. The methods described and the results of this study should be useful to other researchers as a framework for testing of their own equipment and for the selection of appropriate equipment for EEG recording inside a MR scanner.
Studies of post-operative imaging data have mainly concentrated on brain atrophy following radiotherapy and/or chemotherapy. We have investigated the effect of conventional surgery on the unresected brain tissue based on the comparison of magnetic resonance images acquired pre- and post-operatively in 13 subjects with a history of mesio-temporal epilepsy. The pre- and post-operative scans were co-registered prior to volumetric analysis. The total brain volume (TBV) was calculated by semi-automated segmentation, and the total volume loss was the difference between the post-operative and pre-operative TBV. The total volume of resection was determined by manual delineation in the post-operative scan. The atrophy volume in the post-operative scan was calculated as the difference between the total volume loss and the resection volume. In 6 cases, there was generalised cerebral atrophy of the order 4-5% of the total brain volume. In addition to the automated volumetric technique, the images were assessed by two expert neuroradiologists. There was complete correspondence between their assessment and the automated technique. The causes and significance of this phenomenon are unknown but it requires further investigation as it may be related to seizure control and neuropsychological changes following epilepsy surgery.
In this work, we describe methodologies for serial volumetric measurements of hippocampi and cerebella. Serial scans were co-registered and intensity matched prior to the volumetric measurements. Manual drawing was used to define the boundaries of the hippocampi. For the cerebellar volumetric measurements, the brain was automatically segmented from the co-registered scans; manual drawing was used to define the boundary between the cerebellum and the cerebrum and brainstem. The operator was blinded to the nature of the subject (patient or normal control) and the chronological order of the scans. The coefficient of reliability of hippocampal volume measurements in a group of 20 controls was 0.078 cm(3) (3.1% of the mean baseline volume); for the cerebellum, the value was 3.8 cm(3) (3.0% of the mean baseline volume). We conclude that the methods presented are valid and that the software provides a useful integrated tool for the quantitative analysis of structural changes in serially acquired volume MRI data in prospective, blinded studies.
A case of fixation-off sensitivity (FOS) in an asymptomatic adult is presented and studied as a model for continuous epileptiform discharges. Video-electroencephalographic (EEG) revealed continuous bilateral occipital spike wave discharges during elimination of central vision, which were shown to be associated with transitory cognitive impairment demonstrated by neuropsychological testing. Functional MRI showed activation of parieto-occipital and frontal brain areas during the fixation-off discharges. This localization was confirmed with 64-channel EEG source analysis. The applied methods provided additional information on the pathophysiology of epileptiform discharges.
Recurrent episodes with interictal affective aggression are a rare but well-recognized problem in patients with temporal lobe epilepsy. They are referred to as episodic dyscontrol or, more precisely, as intermittent explosive disorder (IED). The amygdala play a crucial role in the affective evaluation of multimodal sensory input and the neurobiological mediation of aggressive behaviour. With hippocampal sclerosis, in the context of mesial temporal lobe sclerosis, being the most common cause of temporal lobe epilepsy, we hypothesized that the amygdala might be affected by the same pathogenic process in aggressive patients. We investigated 50 patients with temporal lobe epilepsy: 25 with and 25 without a history of IED. Data from clinical, electrophysiological, neuropsychological and psychometric investigations were obtained, as well as MRI scans for the quantitative assessment of possible amygdala pathology. We found no evidence of a higher prevalence of amygdala sclerosis in the aggressive patients. Hippocampal sclerosis was significantly less common in patients with temporal lobe epilepsy and IED. However, a significant subgroup of patients (20%) with temporal lobe epilepsy and aggressive behaviour had severe amygdala atrophy in the context of a history of encephalitis. Another subgroup of aggressive patients (28%) had different left temporal lesions affecting either the amygdala or periamygdaloid structures. IED was associated with left-sided or bilateral EEG and MRI abnormalities, low IQ and high scores in depression and anxiety.
The objective was to study fibre orientation in the cerebral white matter of a patient with a brain tumour using diffusion tensor imaging (DTI). A patient with a mild left hemiparesis and a tumour in the right frontal lobe and 20 healthy volunteers were scanned with a DTI sequence. The scans were spatially normalised and the fibre orientation in the patient compared with the fibre orientation in normal controls. DTI disclosed a change of the orientation of fibres in the patient compared with normal controls. In the normal appearing white matter adjacent to the tumour fibres deviated from the normal superior inferior orientation in the corona radiata by about 30 degrees. This finding was consistent with a displacement by distant mass effect rather than a destruction of fibres, in agreement with the neurological examination. In conclusion, DTI demonstrated a deviation of fibres in normal appearing white matter adjacent to a tumour. The technique will improve understanding of the effects of structural abnormalities on fibres. This will assist the interpretation of clinical findings and functional imaging studies and guide neurosurgical interventions.
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BACKGROUND: Previous studies indicated an important role of the amygdala for emotional information processing. We investigated a possible relationship between amygdala volumes, aggressive behavior, and dysthymia, in patients with temporal lobe epilepsy (TLE). METHODS: Patients with TLE with and without aggression or dysthymia and healthy volunteers were assessed using quantitative MRI. Amygdala volumes were measured in a blinded fashion and corrected for total brain volumes. RESULTS: There was a highly significant enlargement of left and right amygdala volumes in patients with dysthymia (right side, p < .000; left side, p = .001). We found a significant positive correlation between left amygdala volumes (p = .02) and a trend towards positive correlation between right amygdala volumes and depression (p = .06), as measured with the Beck Depression Inventory. Amygdala volumes of females were significantly larger than those of males (left side: p = .005; right side: p = .06). CONCLUSIONS: This is the second report of a relationship between amygdala volumes and depressed mood, confirming an earlier finding in patients with bipolar disease, and the first study reporting a correlation between amygdala volumes and depression. Increased processing of emotional information might increase amygdala blood flow and subsequently, result in amygdala enlargement.
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A new fast automated algorithm has been developed to segment the brain from T1-weighted volume MR images. The algorithm uses automated thresholding and morphological operations. It is fully three-dimensional and therefore independent of scan orientation. The validity and the performance of the algorithm were evaluated by comparing the automatically calculated brain volume with semi-automated measurements in 10 subjects, by calculating the brain volume from repeated scans in another 10 subjects, and by visual inspection. The mean and standard deviation of the difference between semi-automated and automated measurements were 0.56% and 2.8% of the mean brain volume, respectively, which is within inter-observer variability of the semi-automated method. The mean and standard deviation of the difference between the total volumes calculated from repeated scans were 0.40% and 1.2% of the mean brain volume, respectively. Good results were also obtained from a scan of abnormal brains.
EEG-triggered functional MRI (fMRI) offers the potential to localize the generators of scalp EEG events, such as interictal epileptiform discharges, using a biological measurement as opposed to relying solely on modelling techniques. Although recent studies have demonstrated these possibilities in a small number of patients, wider application has been limited by concerns about patient safety, severe problems due to pulse-related artefact obscuring the EEG trace, and lack of reproducibility data. We have systematically studied and resolved the issues of patient safety and pulse artefact and now report the application of the technique in 24 experiments in 10 consecutive patients with localization-related epilepsy and frequent interictal epileptiform discharges (spikes or spike wave). At least two experiments were performed for each patient. In each experiment, 10- or 20-slice snapshot gradient-echo planar images were acquired approximately 3.5 s after a single typical epileptiform discharge (activation image) and in the absence of discharges (control image). Between 21 and 50 epileptiform discharges were sampled in each experiment. The significance of functional activation was tested using the t test at 95% confidence on a pixel-by-pixel basis. Six of the 10 patients showed reproducible focal changes of the blood oxygen level-dependent (BOLD) signal, which occurred in close spatial relationship to the maximum of the epileptiform discharges in the concurrent EEG. No reproducible focal BOLD signal changes were observed in the remaining four patients. In conclusion, EEG-triggered fMRI is now a sufficiently developed technique to be more widely used in clinical studies, demonstrating that it can reproducibly localize the brain areas involved in the generation of spikes and spike wave in epilepsy patients with frequent interictal discharges.
PURPOSE: The nature of the resection in surgery for intractable medial temporal lobe epilepsy is likely to be a principal factor determining seizure and neuropsychological outcome. However, there is no universally accepted system for describing the characteristics of individual resections to allow comparison between patients and patient groups treated at different institutions. We therefore developed a technique of volumetric analysis of temporal lobe resections. METHODS: With comparison of coregistered pre- and postoperative, volumetric magnetic resonance imaging (MRI) scans in 10 subjects, the volumes of six temporal lobe substructures were determined by manual delineation in the pre- and post-operative images for each case, allowing the extent of resection to be determined. RESULTS: The substructures and their extent of resection were measured with acceptable repeatability in each case. CONCLUSIONS: We developed a reliable method for the quantitative description of temporal lobe resections. This will be of application in determining the relation between the anatomic nature of the resection in intractable epilepsy and the seizure and neuropsychological outcome.
PURPOSE: Diffusion tensor imaging allows the quantitative assessment of the microstructural organization of tracts in vivo (MR tractography). We used the new technique of MR tractography to demonstrate the effects of temporal lobectomy on the optic radiation. METHODS: Spatially normalised maps encoding magnitude of the bias (anisotropy) of diffusion of three patients with temporal lobe resections were compared with spatially normalised diffusion maps of 22 control subjects. All three patients were operated on for the treatment of medically intractable temporal lobe epilepsy and had a normal neurologic examination before surgery. One patient had an amygdalocorticectomy. Two patients had standard en bloc resections, one of whom developed a homonymous hemianopia after surgery. RESULTS: In the patient with hemianopia, a significant reduction of diffusion anisotropy (greater than mean+/-2 SD) consistent with wallerian degeneration was demonstrated in the optic radiation on the side of the temporal lobectomy, extending from the temporal to the occipital lobe. In the other patient with standard en bloc resection but clinically no hemianopia, the optic radiation was only marginally affected. In the third patient (amygdalocorticectomy), the diffusion anisotropy was within the normal range in the expected position of the optic radiation. CONCLUSIONS: Our findings show that MR tractography may be a useful tool to demonstrate wallerian degeneration in the optic radiation after temporal lobectomy in patients with hemianopia. This is the first time that this new method has been applied in postoperative imaging; it enables us to visualise the morphologic correlate of dysfunctional pathways after epilepsy surgery in vivo. The potential for using MR tractography to study other aspects of epilepsy is discussed.
PURPOSE: To demonstrate the integration of complementary functional and structural data acquired with magnetic resonance imaging (MRI) in a patient with localization-related epilepsy. METHODS: We studied a patient with partial and secondarily generalized seizures and a hemiparesis due to a malformation of cortical development (MCD) in the right hemisphere by using EEG-triggered functional MRI (fMRI), diffusion tensor imaging (DTI), and chemical shift imaging (CSI). RESULTS: fMRI revealed significant changes in regional blood oxygenation associated with interictal epileptiform discharges within the MCD. DTI showed a heterogeneous microstructure of the MCD with reduced fractional anisotropy, a high mean diffusivity, and displacement of myelinated tracts. CSI demonstrated low N-acetyl aspartate (NAA) concentrations in parts of the MCD. CONCLUSIONS: The applied MR methods described functional, microstructural, and biochemical characteristics of the epileptogenic tissue that cannot be obtained with other noninvasive means and thus improve the understanding of the pathophysiology of epilepsy.
Amyloid enhancing factor (AEF) is an activity that appears naturally during the course of persistent inflammation and precedes, by 24-48 h, AA amyloid deposition in appropriate murine models. AEF is defined by its biological properties, namely, when administered intravenously or intraperitoneally to a mouse, it primes the recipient for the rapid induction of AA amyloid when they are given an inflammatory stimulus. Available evidence indicates that AEF is protein in nature, but a specific molecular species (if a singular species exits) has not been identified. Past work (Ganowiak et al., Biochem. Biophys. Res. Commun. 199:306-312, 1994) has shown that AEF activity may be imparted to two different proteins (IAPP and beta-protein) provided each is organized in the form of an amyloid fibril. Since a characteristic property of proteins in amyloid fibrils is their beta-sheet organization, one possibility is that AEF activity, in part, depends on such organization, and other proteins with such properties may also have AEF activity. To investigate this possibility, silk, a protein which contains substantial beta-sheet content, was denatured in LiSCN and allowed to renature slowly under reducing conditions to form a gel. The denatured silk preparation was then sonicated thoroughly to permit intravenous injection and assessed for AEF activity. The modified silk, presented as small fibrils in a beta-sheet conformation as assessed by electron microscopy and circular dichroism, respectively. This silk at 0-50 micrograms/animal was administered intravenously as "AEF" followed immediately by subcutaneous AgNO3 as the inflammatory stimulus. Six days later the spleens were examined for the presence of AA amyloid and following Congo red staining, the amount of amyloid quantified by image analysis. Modified silk without an inflammatory stimulus, and non-sonicated modified silk, failed to induce AA amyloid. Sonicated modified silk followed by AgNO3 induced large quantities of splenic AA amyloid in a dose dependent fashion. Modified silk in quantities as small as 1-5 micrograms/animal can function as AEF. The AEF properties of the modified silk were stable at 4 degrees C for at least 4 weeks (the longest period tested). This procedure may provide a means of standardizing AEF preparations.
This study aimed to determine the parameters necessary for a study of stapedial reflexes in leprosy patients to ascertain if the facial nerve is involved more proximally than the stylomastoid foramen. It involved leprosy patients with and without facial nerve involvement and non-leprosy controls. Clinical examination of the patients' ears, a tympanogram and audiogram to exclude conductive and sensorineural deafness, followed by the measurement of a stapedial reflex and the acoustic reflex threshold, were carried out. The number of absent reflexes and the acoustic reflex thresholds did not differ between the three groups of subjects. A definitive study would be logistically impossible. Suggestions are made as to more exact patient selection in order to demonstrate any stapedial reflex changes due to leprosy. The findings of this study do not suggest that facial nerve pathology extends proximally to the stylomastoid foramen, unless such proximal involvement is subclinical to the detection methods used.