Zografos Caramanos

Regional differences in the effects of task difficulty and motor output on blood flow response in the human anterior cingulate cortex : a review of 107 PET activation studies

WE reviewed 107 blood flow activation studies carried out with positron emission tomography and published between January 1993 and November 1996. These studies had reported their findings as peaks of significant difference in cerebral blood-flow (CBF) between two scans/tasks and had located the peaks in standardized stereotaxic space. We coded each task along several dimensions, including the type and rate of input and output, the types of cognitive processes, and the relative difficulty of tasks within a study. Based on this coding, a difference score (A–B) was calculated for each subtraction. Subsequently, the frequency distributions of the difference scores for subtractions yielding a peak in the anterior cingulate region (cingulate peak) were compared with those distributions obtained from subtractions without a cingulate peak (no cingulate-peak). The cingulate peak subtractions (n = 158) differed from the no cingulate peak subtractions (n = 229) in terms of difficulty level (p = 0.001) and the presence of a remote memory component (p = 0.01). Regional differences in the frequency distribution of certain task parameters, such as difficulty level, recent memory and the use of the hand for responding, were also observed when peaks found in the anterior cingulate cortex (ACC) were further classified as located in the rostral vs caudal ACC, supracallosal vs subcallosal ACC, and limbic vs paralimbic parts of the supracallosal ACC. We conclude that task difficulty plays a major role in modulating blood-flow response in the ACC, possibly interacting with other parameters such as the nature of the response and memory demands.

In vivo morphometry of the intrasulcal gray matter in the human cingulate, paracingulate, and superior‐rostral sulci: Hemispheric asymmetries, gender differences and probability maps

Volumes of the intrasulcal gray matter were measured in three cerebral sulci located on the medial wall of the human frontal lobe: cingulate sulcus (CS), paracingulate sulcus (PCS), and superior‐rostral sulcus (SRS). The measurements were carried out on T1‐weighted 3‐D high‐resolution magnetic‐resonance (MR) images acquired in 105 young right‐handed volunteers (42 female and 63 male). Before the measurement, the images were transformed into a standardized stereotaxic space (Talairach and Tournoux [1988] Human Brain: 3‐Dimensional Proportional System. An Approach to Cerebral Imaging. Stuttgart, New York: Georg Thieme Verlag), thus removing inter‐individual differences in brain size. The intrasulcal gray matter was segmented in a semi‐automatic manner. Significant gender differences were found in the volume of the CS (female > male) and the PCS (male > female). Hemispheric asymmetries were observed between the left and right volumes of the intrasulcal gray matter in the anterior (right > left) and posterior (left > right) segments of the CS, as well as between the left and right volumes of the PCS (left > right). There was no interaction between the asymmetries and gender. In addition, significant positive correlations were found between the left and right gray‐matter volumes in the anterior (r = 0.43) and posterior (r = 0.66) segments of the CS, whereas significant negative correlations were observed between the gray‐matter volumes of the anterior segment of the CS and those of the PCS (left hemisphere: r = −0.48; right hemisphere: r = −0.42). The observed hemispheric asymmetries in the CS and PCS gray‐matter volumes are consistent with the proposed role of these structures in the integration of emotions with cognition (CS) and in the control of speech/vocalization (PCS). The pattern of inter‐hemispheric correlations in the sulcal gray‐matter points to an increasing asynchrony in the foetal development of primary (CS), secondary (SRS), and tertiary (PCS) sulci, respectively. The presence of negative correlations between the two neighbouring sulci (CS and PCS) suggests that a process of compensation could underlie interactions between adjacent primary and tertiary sulci. Besides the above volumetric analysis, we also provide average (probability) maps of the three sulci; the use of such maps for the parcellation of the medial frontal lobe and localization of “peaks” obtained in blood‐flow activation studies is discussed.

Morphology, morphometry and probability mapping of the pars opercularis of the inferior frontal gyrus: an in vivo MRI analysis.

The pars opercularis occupies the posterior part of the inferior frontal gyrus. Electrical stimulation or damage of this region interferes with language production. The present study investigated the morphology and morphometry of the pars opercularis in 108 normal adult human cerebral hemispheres by means of magnetic resonance imaging. The brain images were transformed into a standardized proportional steoreotaxic space (i.e. that of Talairach and Tournoux) in order to minimize interindividual brain size variability. There was considerable variability in the shape and location of the pars opercularis across brains and between cerebral hemispheres. There was no significant difference or correlation between left and right hemisphere grey matter volumes. There was also no significant difference between sex and side of asymmetry of the pars opercularis. A probability map of the pars opercularis was constructed by averaging its location and extent in each individual normalized brain into Talairach space to aid in localization of activity changes in functional neuroimaging studies.

Axonal metabolic recovery in multiple sclerosis patients treated with interferon β-1b

Abstract Patients with multiple sclerosis (MS) can benefit from treatment with interferon β–1b. However, the mechanisms of action of this drug are incompletely understood and effects of interferon β–1b on axonal injury are not known. A measure of axonal injury can be obtained in vivo using magnetic resonance spectroscopy to quantify the resonance intensity of the neuronal marker, N-acetylaspartate (NAA). In a small pilot study, we performed combined magnetic resonance imaging and magnetic resonance spectroscopic imaging on 10 patients with relapsing-remitting MS before and 1 year after starting treatment with subcutaneous interferon β–1b. Resonance intensities of NAA relative to creatine (Cr) were measured in a large, central brain volume. These measurements were compared with those made in a group of 6 untreated patients selected to have a similar range of scores on the Expanded Disability Status Scale and mean NAA/Cr at baseline. NAA/Cr in the treated group [2.74 (0.16), mean (SD)] showed an increase of 5.5 % 12 months after the start of therapy [2.89 (0.24), p = 0.05], while NAA/Cr in the untreated group decreased, but not significantly [2.76 (0.1) at baseline, 2.65 (0.14) at 12 months, p > 0.1]. NAA/Cr had become significantly higher in the treated group at 12 months than in the untreated group (p = 0.03). Our data suggest that, in addition to losing axons, patients with chronic multiple sclerosis suffer from chronic, sublethal axonal injury that is at least partially reversible with interferon β–1b therapy.

Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes

Objective: To determine whether MRI volumetric measurement of the entorhinal cortex could detect structural damage and lateralize the seizure focus in patients with temporal lobe epilepsy in whom no measurable hippocampal abnormalities were found. Background: A reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy and hippocampal atrophy was recently shown. Methods: MRI volumetric analysis of the entorhinal cortex was performed using a T1-weighted three-dimensional gradient echo sequence in 24 control subjects and 22 patients with temporal lobe epilepsy and normal hippocampal volumes. Thirteen patients underwent surgery, with a mean postoperative follow-up of 36 months. Results: Group analysis (multivariate analysis of variance) showed a reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with left (p < 0.0001) and right temporal lobe epilepsy (p < 0.0001). Lateralization of the seizure focus could be done in 14 of 22 patients (64%) based on entorhinal cortex volumetry. Conclusion: Entorhinal cortex atrophy ipsilateral to the seizure focus supports the presence of structural damage in the mesial temporal lobe in patients with temporal lobe epilepsy and normal hippocampal volumes and emphasizes the participation of the entorhinal cortex in the pathogenesis of this disorder.

Magnetization transfer can predict clinical evolution in patients with multiple sclerosis

Abstract. The clinical course of multiple sclerosis (MS) is highly variable ranging from benign to aggressive, and is difficult to predict. Since magnetization transfer (MT) imaging can detect focal abnormalities in normal-appearing white matter (NAWM) before the appearance of lesions on conventional MRI, we hypothesized that changes in MT might be able to predict the clinical evolution of MS. We assessed MR data from MS patients who were subsequently followed clinically for 5 years. We computed the mean MT ratio (MTr) in gray matter, in lesions identified on T2-weighted MRI, and in NAWM, as well as in a thick central brain slice for each patient. Patients were divided into stable and worsening groups according to their change in Expanded Disability Status Scale (EDSS) scores over 5 years. We calculated the sensitivity, specificity, predictive value, and odds ratio of the baseline MTr measures in order to assess their prognostic utility. We found significant differences in baseline MTr values in NAWM (p = 0.005) and brain slice (p = 0.03) between clinically stable and worsening MS patients. When these MTr values were compared with changes in EDSS over 5 years, a strong correlation was found between the EDSS changes and MTr values in both NAWM (SRCC = −0.76, p < 0.001) and in the brain slice (SRCC = 0.59, p = 0.01). Baseline NAWM MTr correctly predicted clinical evolution in 15/18 patients (1 false positive and 2 false negatives), yielding a positive predictive value of 77.78 %, a negative predictive value of 88.89 %, and an odds ratio of 28. The relationship between 5-year changes in EDSS and MTr values in T2 weighted MRI lesions was weaker (SRCC = −0.43, p = 0.07). Our data support the notion that the quantification of MTr in the NAWM can predict the clinical evolution of MS. Lower MTr values predict poorer long-term clinical outcome. Abnormalities of MTr values in the NAWM are more relevant to the development of future patient disability than those in the T2-weighted MRI lesions.

T2 relaxometry can lateralize mesial temporal lobe epilepsy in patients with normal MRI.

In unselected patients with intractable temporal lobe epilepsy (TLE), approximately 15% do not have detectable hippocampal atrophy on MRI. The purpose of this study was to evaluate whether T2 relaxometry can identify hippocampal pathology and lateralize the epileptic focus in patients with intractable TLE, who do not demonstrate hippocampal atrophy on volumetric MRI (MRIV). We selected 14 patients with unilateral TLE who had unilateral atrophy and 11 patients with unilateral TLE who had no evidence of atrophy on MRIV. Images were acquired on a 1.5 T MR scan using a dual echo sequence with 23 contiguous oblique coronal slices in all patients and in 14 healthy subjects. Fitting a single exponential decay equation to the imaging data generated T2 maps. Averages of six slices containing the head, body, and tail of the hippocampus were used to calculate hippocampal T2 relaxation times (HT2). The epileptic focus was defined by history, video-EEG, and surgical response. All TLE patients with hippocampal atrophy and 9/11 (82%) patients with normal MRI had abnormally high HT2 ipsilateral to the epileptic focus. Bilateral abnormal HT2 were found in 6/14 (43%) of patients with unilateral hippocampal atrophy and 2/11 (18%) of patients with normal MRI. However, this increase was always greater ipsilateral to the epileptic focus. Qualitative hippocampal pathology showed gliosis and neuronal loss in 10/14 operated patients with hippocampal atrophy on MRIV and in 5/7 operated patients with normal MRI. In conclusion, hippocampal T2 mapping provides evidence of hippocampal damage in the majority of patients with intractable TLE who have no evidence of atrophy on MRI and can correctly lateralize the epileptic focus in most patients.

Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity?

Multiple sclerosis (MS), the most frequent demyelinating disease, is characterized by a variable disease course. The majority of patients starts with relapsing remitting (RR) disease; approximately 50–60% of these patients progress to secondary progressive (SP) disease. Only about 15% of the patients develop a progressive disease course from onset, termed primary progressive multiple sclerosis (PPMS); the underlying pathogenic mechanisms responsible for onset of the disease with either PPMS or relapsing remitting multiple sclerosis (RRMS) are unknown. Patients with PPMS do not show a female predominance and usually have a later onset of disease compared to patients with RRMS. Monozygous twins can be concordant or discordant for disease courses indicating that the disease course is not only genetically determined. Primary progressive multiple sclerosis and secondary progressive multiple sclerosis (SPMS) share many similarities in imaging and pathological findings. Differences observed among the different disease courses are more of a quantitative than qualitative nature suggesting that the different phenotypes are part of a disease spectrum modulated by individual genetic predisposition and environmental influences. In this review, we summarize the knowledge regarding the clinical, epidemiological, imaging, and pathological characteristics of PPMS and compare those characteristics with RRMS and SPMS.

Fatigue in multiple sclerosis: association with disease-related, behavioural and psychosocial factors

We determined biopsychosocial correlates of general, physical, and mental fatigue in MS patients, by evaluating the additional contribution of potentially modifiable factors after accounting for non-modifiable disease-related factors. Fifty-three ambulatory MS patients, along with 28 normal controls were recruited for a cross-sectional study. Subjects completed the Multidimensional Fatigue Inventory (MFI) and Fatigue Severity Scale. Potential correlates evaluated were: disease-related factors (disease duration and type, immunomodulating treatment, muscle strength, pain, forced vital capacity (FVC), respiratory muscle strength, body mass index, disability, fibromyalgia), behavioural factors (physical activity, sleep quality) and psychosocial factors (depression, stress, self-efficacy). Multivariate models were calculated for MFI General, Physical, and Mental Fatigue. Age-adjusted multivariate models with non-modifiable factors included the following predictors (P ≤ 0.10) of 1) MFI General and Mental Fatigue: none; and 2) MFI Physical Fatigue: FVC and disability. The following potentially modifiable predictors (P ≤ 0.10) made an additional contribution to the models 1) MFI General Fatigue: sleep quality, self-efficacy, pain; 2) MFI Physical Fatigue: self-efficacy, physical activity; and 3) MFI Mental Fatigue: stress, self-efficacy. Fatigue in MS is multidimensional. Correlates of general and physical fatigue are disease-related, behavioural and psychosocial factors. Correlates of mental fatigue are psychosocial factors. Potentially modifiable factors account for a considerable portion of fatigue. Multiple Sclerosis 2007; 13: 985—995. http://msj.sagepub.com

Magnetic resonance spectroscopy guided brain tumor resection : Differentiation between recurrent glioma and radiation change in two diagnostically difficult cases

BACKGROUND It is often difficult to differentiate a recurrent glioma from the effects of post-operative radiotherapy by means of conventional neurodiagnostic imaging. Proton magnetic resonance spectroscopic imaging (1H-MRSI), that allows in vivo measurements of the concentration of brain metabolites such as choline-containing phospholipids (Cho), may provide in vivo biochemical information helpful in distinguishing areas of tumor recurrence from areas of radiation effect. PATIENTS AND METHODS Two patients who had undergone resection and post-operative radiotherapy for a cerebral glioma became newly symptomatic. Computed tomographic (CT) and magnetic resonance imaging (MRI) performed after the intravenous infusion of contrast material, and in one case, [18F]fluorodeoxyglucose positron emission tomography (PET), could not differentiate between the possibilities of recurrent glioma and radiation effect. The patients underwent 1H-MRSI prior to reoperation and the 1H-MRSI results were compared to histological findings originating from the same locations. RESULTS A high Cho signal measured by 1H-MRSI was seen in areas of histologically-proven dense tumor recurrence, while low Cho signal was present where radiation changes predominated. CONCLUSIONS The differentiation between the recurrence of a cerebral glioma and the effects of post-operative irradiation was achieved using 1H-MRSI in these two patients whose conventional neurodiagnostic imaging was equivocal for such a distinction. Where these two conditions are present, metabolite images from 1H-MRSI, such as that based on Cho, can be co-registered with other imaging modalities such as MRI and may also be integrated with functional MRI or functional PET within a multimodal imaging-guided surgical navigation system to assure maximal resection of recurrent tumor while minimizing the risk of added neurological damage.