Mokhtar H. Gado

Depression Duration But Not Age Predicts Hippocampal Volume Loss in Medically Healthy Women with Recurrent Major Depression

This study takes advantage of continuing advances in the precision of magnetic resonance imaging (MRI) to quantify hippocampal volumes in a series of human subjects with a history of depression compared with controls. We sought to test the hypothesis that both age and duration of past depression would be inversely and independently correlated with hippocampal volume. A sample of 24 women ranging in age from 23 to 86 years with a history of recurrent major depression, but no medical comorbidity, and 24 case-matched controls underwent MRI scanning. Subjects with a history of depression (post-depressed) had smaller hippocampal volumes bilaterally than controls. Post-depressives also had smaller amygdala core nuclei volumes, and these volumes correlated with hippocampal volumes. In addition, post-depressives scored lower in verbal memory, a neuropsychological measure of hippocampal function, suggesting that the volume loss was related to an aspect of cognitive functioning. In contrast, there was no difference in overall brain size or general intellectual performance. Contrary to our initial hypothesis, there was no significant correlation between hippocampal volume and age in either post-depressive or control subjects, whereas there was a significant correlation with total lifetime duration of depression. This suggests that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss.

Amygdala core nuclei volumes are decreased in recurrent major depression.

THE amygdala is a key structure in the brains integration of emotional meaning with perception and experience.1 Patients with depression have impaired functioning in emotional tasks involving the amygdala,2 and have abnormal resting amygdala blood flow.3 To better understand the anatomical basis for these functional changes we measured the volumes of the total amygdala and of the core amygdala nuclei in 20 patients with a history of depression and 20 pair-wise matched controls. Depressed subjects had bilaterally reduced amygdala core nuclei volumes and no significant differences in total amygdala volumes or in whole brain volumes. Since patients with a depression history have bilateral hippocampal volume reduction4 the volume loss in this closely related structure suggests a shared effect on both structures, potentially glucocorticoid-induced neurotoxicity5 mediated by the extensive reciprocal glutamatergic connections.

The Effect of Hemodynamically Significant Carotid Artery Disease on the Hemodynamic Status of the Cerebral Circulation

Although the presence of a hemodynamically significant carotid artery lesion is commonly used as an indicator of impaired cerebral circulation, the effect of such lesions on cerebral perfusion pressure and cerebral blood flow has never been determined accurately. We used positron emission tomography (PET) to study 19 patients with unilateral hemodynamically significant carotid artery disease (greater than 66% diameter reduction) and no evidence of cerebral infarction. According to PET measurements in the cerebral hemisphere distal to the lesion, 7 patients had normal cerebral hemodynamics, 8 had reduced perfusion pressure with normal blood flow, and 4 had reduced blood flow. Neither the percent stenosis nor the residual lumen diameter in the carotid artery was a reliable indicator of the hemodynamic status of the cerebral circulation. However, a significant relationship was found between the PET measurements of cerebral hemodynamics and the arteriographic circulation pattern (p = 0.006). The role of hemodynamic factors in the pathogenesis and treatment of cerebrovascular disease cannot be determined from the severity of carotid artery disease alone.

Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus

&NA; Article abstract— Objective To determine the feasibility of using high-dimensional brain mapping (HDBM) to assess the structure of the hippocampus in older human subjects, and to compare measurements of hippocampal volume and shape in subjects with early dementia of the Alzheimer type (DAT) and in healthy elderly and younger control subjects. Background HDBM represents the typical structures of the brain via the construction of templates and addresses their variability by probabilistic transformations applied to the templates. Local application of the transformations throughout the brain (i.e., high dimensionality) makes HDBM especially valuable for defining subtle deformities in brain structures such as the hippocampus. Methods MR scans were obtained in 18 subjects with very mild DAT, 18 healthy elderly subjects, and 15 healthy younger subjects. HDBM was used to obtain estimates of left and right hippocampal volume and eigenvectors that represented the principal dimensions of hippocampal shape differences among the subject groups. Results Hippocampal volume loss and shape deformities observed in subjects with DAT distinguished them from both elderly and younger control subjects. The pattern of hippocampal deformities in subjects with DAT was largely symmetric and suggested damage to the CA1 hippocampal subfield. Hippocampal shape changes were also observed in healthy elderly subjects, which distinguished them from healthy younger subjects. These shape changes occurred in a pattern distinct from the pattern seen in DAT and were not associated with substantial volume loss. Conclusions Assessments of hippocampal volume and shape derived from HDBM may be useful in distinguishing early DAT from healthy aging.

Position of Cerebellar Tonsils in the Normal Population and in Patients with Chiari Malformation: A Quantitative Approach with Mr Imaging

Magnetic resonance imaging was used to define quantitatively the position of the cerebellar tonsils in the normal population and in patients with Chiari malformations. The average distance of the tonsillar tips from the foramen magnum was 2.9 ± 3.4 mm above the foramen in 82 subjects without posterior fossa abnormality or increased intracranial pressure, and 10.3 ± 4.6 mm below the foramen in 13 patients with Chiari malformations (p < 0.005). Consequently, extension of the tonsils below the foramen magnum is considered normal up to 3 mm, borderline between 3 and 5 mm, and clearly pathologic when it exceeds 5 mm.

Changes in hippocampal volume and shape across time distinguish dementia of the Alzheimer type from healthy aging.

Rates of hippocampal volume loss have been shown to distinguish subjects with dementia of the Alzheimer type (DAT) from nondemented controls. In this study, we obtained magnetic resonance scans in 18 subjects with very mild DAT (CDR 0.5) and 26 age-matched nondemented controls (CDR 0) 2 years apart. Large-deformation high-dimensional brain mapping was used to quantify and compare changes in hippocampal shape as well as volume in the two groups of subjects. Hippocampal volume loss over time was significantly greater in the CDR 0.5 subjects (left = 8.3%, right = 10.2%) than in the CDR 0 subjects (left = 4.0%, right = 5.5%) (ANOVA, F = 7.81, P = 0.0078). We used singular-value decomposition and logistic regression models to quantify hippocampal shape change across time within individuals, and this shape change in the CDR 0.5 and CDR 0 subjects was found to be significantly different (Wilkss lambda, P = 0.014). Further, at baseline, CDR 0.5 subjects, in comparison to CDR 0 subjects, showed inward deformation over 38% of the hippocampal surface; after 2 years this difference grew to 47%. Also, within the CDR 0 subjects, shape change between baseline and follow-up was largely confined to the head of the hippocampus and subiculum, while in the CDR 0.5 subjects, shape change involved the lateral body of the hippocampus as well as the head region and subiculum. These results suggest that different patterns of hippocampal shape change in time as well as different rates of hippocampal volume loss distinguish very mild DAT from healthy aging.

An extravascular component of contrast enhancement in cranial computed tomography. Part II. Contrast enhancement and the blood-tissue barrier.

The authors provide evidence of significant extravasation of contrast media responsible for the contrast enhancement of pathological tissue on computed tomography. The tissue-blood ratio of enhancement was calculated by the EMI scanner in 2 patients after injection of contrast material and prior to surgery; tumor-blood ratios for red blood cell and plasma tracers were calculated after surgery. The ratios of enhancement demonstrated the analogy between contrast enhancement and the leaking of radionuclide across the blood-brain barrier. This phenomenon may cause error if this technique is used for the measurement of cerebral blood volume. The area for complementary roles of CT and radionuclide brain imaging seems to be narrower than expected.

Periventricular white matter lucencies in senile dementia of the Alzheimer type and in normal aging

The significance of periventricular lucencies in the white matter on CT in demented patients is not understood. We studied the relationship of these changes to mental status of subjects with senile dementia of the Alzheimer type. A semiquantitative method showed more numerous and extensive lucencies in demented than in healthy elderly. Neuropathologic examination of five subjects with these changes and confirmed Alzheimers disease revealed diffuse white matter pallor without infarction. There were no hypertensive vascular changes, although limited hyaline thickening was present.

Functional anatomy of the cerebral cortex by computed tomography.

The authors describe the morphological characteristics that allow recognition of the individual computed tomography slice and determine its sequence in the series. In addition, each slice is “assembled” by defining the different cortical gyri, sulci, and cortical functional areas (based on Brodmanns maps). This work lays the foundation for correlative studies of location of lesions and the clinical picture.

An extravascular component of contrast enhancement in cranial computed tomography. Part I. The tissue-blood ratio of contrast enhancement.

One can calculate the tissue-blood ratio of enhancement by analyzing the quantitative aspects of the CT scans of the cranium and blood samples both before and after the injection of contrast medium. This ratio is equivalent to that between the iodine content of a given volume of tissue and an equal volume of blood. Analysis of 47 normal patients, including 27 with pathological brain lesions, indicated that there is significant extravasation of contrast medium in patients with such lesions.