J. psychiar. Res.. Vol. 18, No. 3, pp. 269-275. Printed in Great Britain.
1984.
0022-3956/&l Pergamon
$3.00 + .oO Press Ltd.
INTERHEMISPHERIC DIFFERENCES IN REGIONAL DENSITY OF THE NORMAL BRAIN JEFFREYA. COFFMAN*and SOLOMON BLOCH~ *Department of Psychiatry, University of Iowa Hospitals and Clinics, Iowa City, Iowa; *Department of Radiology, Spring Branch Memorial Hospital, Houston, Texas, U.S.A. (Received 19 September 1983; revked 29 January 1984) Summary-In a study of regional variations in cerebral X-ray attenuation as measured by computed tomography, a relationship between bone-related beam hardening and lateralized hemispheric density differences was sought. The CT scans of 22 normal right-handed individuals were evaluated by calculating regional mean attenuation values and regional left-right differences in attenuation, comparing these to regional measurements of skull thickness. A statistically insignificant number of significant correlations was found. This is interpreted to mean that observed left-right hemispheric density differences are not due to beam-hardening through bone. It was also found that left-right differences in density persisted over the entirety of the evaluated slices, suggesting that this finding is due to inherent hemispheric structural differences.
INTRODUCTION COMPUTED tomography (CT), as developed by HOUNSFDELD (1973), has attracted a great deal of attention among psychiatrists due to its ability to provide an image of the brain in a living individual (NMRALLAHand Co-, 1984). Most often, the technique has been used to replicate previously noted findings of ventricular enlargements which had been apparent by more invasive pneumoencephalographic methods. However the numerical data provided by CT, essentially a matrix of X-ray attenuation values which closely correspond to tissue density, afford other possible uses. A number of attempts have been made to enhance the utility of CT for in vivo tissue diagnosis utilizing various statistical measures including the mean and standard deviation (HUCKMANand ACKERMAN,1977; F&D and DUBLIN, 1979), coefficient of variation and skewness (KRAMERet al., 1977), and spatial autocorrelation function and gradient analysis (PULLANet al., 1978). Some interesting applications have appeared. For instance, NAESERet al. (1980) obtained regional mean CT number values which differentiated between demented and depressed elderly individuals. Golden and associates demonstrated differing patterns of left right asymmetry in CT values of schizophrenics and alcoholics when compared with controls (GOLDEN et al., 1980; GOLDEN et al., 1981a, b). Coffman and colleagues have replicated Golden et al.‘s findings in schizophrenics (COFFMANet al., 1984) and also have found that a different pattern of density is apparent in manics (COFFMAN and NASIULLAH, 1984). LARGENet al. (1983), utilizing a different technique, also found asymmetrical CT density values when comparing schizophrenics to controls. What seems to be present, then, in the values generated through the CT scanning process is a possible tool for the differentiation of one subtle disorder (in terms of pathology) from another. However, certain concerns ought to be raised regarding the potential validity
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of these values. Several processes other than variability in tissue density can affect the reported attenuation values. One of these processes is beam hardening (GADOand PHELPS, 1975; BROOKS and DICHIRO, 1976, 1978; JOSEPH and SPITAL, 1978). The primary effect of beam hardening artifact is to cause an elevation in attenuation values of brain regions near the skull which declines nonlinearly with increasing distance from the skull. It seemed to us remotely possible that the differences in left and right density values we had noted might be the results of altered levels of beam hardening artifact. As the primary determining factor in this artifact within the skull is bone thickness, we undertook an examination of the relationship of skull thickness to density values in concentric “strips” of several brain “slices”. MATERIALS AND METHODS
Subjects The subjects of this study were 22 normal individuals who had constituted the greatest portion of control groups in two previous studies (GOLDEN et al., 1981a b). Scans of these individuals were obtained from the files of the Radiology Department at the University of Nebraska Medical Center. The designation “normal” was applied to patients who had received CT scans as a part of diagnostic work-ups for vague complaints such as headaches and dizziness, whose CT scans had been read by a neuroradiologist as unequivocally normal, and whose diagnostic work-up revealed no neurologic or psychiatric abnormalities following extensive testing. No patient for whom even equivocal findings of neurologic disease were reported was considered normal. To limit any aging effects, no individual who was over 44 yr at the time of scanning was included in the study. All subjects were right-handed. Average age of the subjects was 30.73 (SD 7.19). Eight were female, while fourteen were male. Procedure All computed tomography scans for this study were obtained with an EM1 CT 1010 scanner and were administered by the Department of Radiology at the University of Nebraska Medical Center. Each scan consisted of about twelve slices each 8 mm thick. The X-ray source was moved through a 180” sweep posterior to the subject. A bone correction program was in use which tended to blunt the increase in attenuation values near the skull. For each subject three adjacent slices were selected for study. The lowest slice selected was that in which the lateral ventricles were most clearly seen while moving in a cephalad direction. The next two higher slices completed the group selected for study. No other slices were examined. For each of the slices chosen for study, the corresponding 160 by 160 Hounsfield number printout was obtained for analysis. On each printout the inner skull margin was delineated by identifying the band of Hounsfield numbers greater than 100. Using the inner margin of this band as a starting point, another ring boundary was delineated five numbers inward from the skull’s inner margin. This process was repeated, with additional ring boundaries demarcated five numbers away from the next outermost ring until seven rings were drawn. This left seven bands, of five Hounsfield number’s width each, encompassing most of each slice.
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Horizontal and vertical midlines were located and marked according to a previously established protocol (GOLDENet al., 1981b). These midlines served to divide each slice into quadrants. After the above boundaries had been defined, mean Hounsfield numbers (as well as their standard deviations) were calculated for each band in each quadrant. For each quadrant in each slice, an approximate measure of skull thickness was made using the photographic reproduction of the slice image. Each slice image was divided into quadrants corresponding to the quadrants used to subdivide the Hounsfield number printouts. Along a line bisecting each quadrant the thickness of the skull image was measured in millimeters. The measurement was made three times and then the mean of the three measurements was calculated. To account for differences in scale a multiplication factor of 3.33 was applied to give values corresponding to actual skull dimensions. RESULTS Means and standard deviations for the Hounsfield numbers in each of the 84 regions for each subject (seven regions per quadrant, 28 regions per slice) were determined. These values were then compared one at a time with each of the four skull thickness measurements for the slice to which they belonged. Correlations between the skull thickness measurements and the regional mean attenuation values were sought using a nonparametric method (Kendall’s tau rank-order correlation coefficients). Four correlations (all positive) out of 336 were found at the p < 0.01 level, which one would expect on a chance basis alone. It would then seem that the relationship between skull thickness as measured and regional mean attenuation values does not account for the major portion of any difference in attenuation values between hemispheres. Group regional mean attenuation values as well as group mean skull thickness measurements were calculated, along with their standard deviations. Review of the figures revealed that while 37 of 42 group mean attenuation values were greater on the left than on the right, five of six group mean skull measures were greater on the left than the right, again arguing against any relationship. A paired Student’s t-test (pairs consisting of corresponding regions in each slice) was applied to these left-right comparisons to assess the significance of the differences noted. Of the 5 mean attenuation values in which right sided values were greater than left, none were statistically significant at thep < 0.05 level. Of the 37 differences in favor of the left hemisphere, 20 were significant at the p < 0.05 level. These differences are shown graphically in Figs l-3. None of the two skull measure comparisons in which right measurements were greater than left achieved statistical significance @ < 0.05). Only one comparison in which left skull measures were greater than right was significant. To further test for the correlation of left-right regional attenuation differences and skull thickness, differences between the mean regional attenuation values for the previously described left hemisphere regions and corresponding right hemisphere regions were calculated. The left-right differences were then compared to the four skull thickness measurements for the slice in which the regional values had occurred. Correlations between the skull thickness measurements and the anterior and posterior left-right differences were sought through a nonparametric method (Kendall’s tau rank-order correlation coefficients). Two correlations (one positive and one negative) of 168 were found at thep < 0.01 level, not exceeding chance expectations.
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level
DISCUSSION
We were unable to demonstrate any relationship between skull thickness measures and regional CT attenuation values measured in concentric strips. We did observe that our attenuation values were elevated near the margins of the skull and that these elevations declined nonlinearly as one would expect of artifactual elevation due to beam hardening. In spite of this nonlinear variability in attenuation values a persistent left-right difference between comparable regions was noted. This suggests that a significant degree of asymmetry in tissue structure of normal individuals may be present. We were not entirely satisfied with our method of skull thickness measurement as it suffered from the partial volume effect and thus may be somewhat elevated. However the elevation should have been consistent. Short of necropsy we were unable to devise a more satisfactory approach. We feel that our results are supportive of the use of relatively large regions for computation of mean regional values. First of all with our demonstration of relatively rapid changes in attenuation values based on distance from the skull, the selection of a small
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FIO. 2. Variation in group mean regional attenuation values with distance from the skull for the intermediate level studied, Level B.
region for sampling within each other value would be artifactually Yet another support for the use areas less than 1.77 cm* Poisson
hemisphere might create a situation in which one or the different from the other simply due to spatial placement. of a CT value sample covering a larger region is that for noise makes the mean value unreliable (DIJERINCKX and
MACOVSKI, 1979, 1980).
In summary, we have found new evidence for cerebral asymmetry in normal individuals and have found no support for interpreting density value results reported previously as being due to beam hardening artifact. We feel that this is an important point to establish as those density measurements reported so far in psychiatric patients have noted subtle left-right differences, for which beam hardening artifact might have been held responsible. Our results do suggest caution in locating sampling sites for density measurements. Although beam hardening effects did not appear to affect relative left-right differences, the variability of values as a function of distance from the skull was impressive, and requires the attention of researchers utilizing these methods. We expect that much yet remains to be discovered regarding the asymmetrical hemispheres of the brain in health and disorder and feel that such fine structural assessments as CT density measurement can usefully be applied.
JEFFREY A. COFFMAN and SOLOMONBLOCH
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GOLDEN,C. J., GRABER,B., COWMAN,J., BERO, R., NE~LIN, D. and BLOW, S. Structural brain deficits in schizophrenia as identified by CT scan density parameters. Archsgen. Psychiut. 38,1014-1017. HOUNSFIELD,G. N. (1973) Computerized transverse axial scanning (tomography) Part I-Description of system, Part II-Clinical application. Br. J. Radiol. 46.1016-1022, 1023-1047. HUCKMAN,M. S. and ACKERMAN,L. V. (1977) Use of automated measurements of mean density as an adjunct to computed tomography. J. Comput. Assist. Tomog. 1.37-42. JOSEPH,P. M. and SPITAL,R. D. (1978) A method for correcting bone induced artifacts in computed tomography scanners. J. Comput. Assist. Tomog. 2, 100-108. KRAMER,R. A., YOSHIKAWA, B. M., SCHEIBE,P. 0. and JANETOS,G. P. (1977) Statistical profiles in computed tomography. Radiology 125.145147. NAESER, M. A., GEEHART,C. and LEVINE, H. L. (1980) Decreased computerized tomography numbers in patients with presenile dementia. Archs Neurol. 37,401. NAS~ALLAH, H. A. and COFFMAN,J. A. (1984) Computerized tomography in psychiatry: an overview. Psychiut. Ann. in press. PULLAN, B. R., FAWCITT,R. A. and ISHERWOOD,I. (1978) Tissue characterization by an analysis of the distribution of attenuation values in computed tomography scans: a preliminary report. J. Comput. Assist. Tomog. 2,49-54. REID, M. H. and D~_~LIN, A. B. (1979) Statistical detection of non-visible isodense subdural fluid collections. J. Comput. Assbt. Tomog. 3,491-496.