Response

In a Letter to the Editor, Dr. Hasan raises several concerns on our recently published articles examining age-related brain tissue changes in healthy adolescent and adult controls in various brain sites, and gender differences in those areas using T2-relaxometry procedures (1,2). Specifically, Dr. Hasan suggests that we could have extracted more information from our data, could have pooled adolescence and adult controls to get better information, and failed to explain conflicts from previously published T2-relaxation values of the corpus callosum in adult controls. In both adolescent and adult healthy control studies (1,2), we determined T2-relaxation values from various brain sites using normalized T2-relaxation maps of all individuals, and a set of regions-of-interest (ROIs) created from background images, derived from normalized images. Regional T2-relaxation values were compared between males and females, and were assessed for relationships between ageand site-specific T2-relaxation values. The first concern was that we did not report handedness of those healthy subjects in these studies, and did not compare leftand right-sided T2-relaxation values. The majority of our healthy adolescent and adult subjects were right-handed. Of 31 adolescent subjects (18 males), 4 subjects (3 males) were lefthanded, 25 (14 males) were right-handed, and 2 (one male) were ambidextrous (1). Of 60 healthy adult subjects (38 males), 10 subjects (4 males) were lefthanded, 45 subjects (32 males) were right-handed, and 5 subjects (2 males) were ambidextrous (2). However, the enormous set of data in the tables in these studies precluded comparison and presentation of additional left and right T2-relaxation value differences of those structures. Moreover, assessment of laterality differences was not the primary focus of those articles. In healthy adolescent subjects (1), left and right brain structural differences emerged on the midinsula, mid-occipital gray matter, rostral cerebellar cortex, and superior temporal white matter, and in healthy adult subjects (2), appeared on the anterior and mid-cingulate, frontal white matter, mid-insula, mid-temporal white matter, mid-occipital gray matter, posterior thalamus, putamen, superior temporal white matter, occipital white matter, and caudal cerebellar cortex in combined male-female data on reexamination; some of these structural laterality differences parallel those of a previously published study (3). The other suggestion was related to comparison and pooling of tabulated data from healthy adolescent and adult subjects. The reader points out that heterogeneity between genu and splenium of corpus callosum in adolescent subjects, also reported by others (4,5), is lost in our healthy adult subjects, which conflicts with previously published reports (6–9). We believe that this discrepancy arose from variable methodological issues between those and our studies. We used normalized T2-relaxation maps and a set of ROIs (rectangular volumes) to determine T2-relaxation values from the genu and posterior corpus callosum. However, in previously published atlas-based studies (7,8), the investigators sampled either the entire structure or larger areas within those sites to determine values from those sites. We chose an ROI approach to determine regional T2-relaxation values, since each structure is functionally, and often structurally, heterogeneous (10–13), and sampling from an entire or very large portion of a brain structure would be meaningless for functional implications in the neuroscience community. Since the corpus callosum is very heterogeneous anatomically (11–13), and onethird of the anterior corpus was sampled as genu, and the posterior one-third as splenium in earlier atlas-based studies (7,8), we believe that the discrepancies resulted from sampling differences. However, the large age-range in healthy adult controls and spatial normalization procedures may also have contributed to this disparity. Other concerns were the absence of pooling data from healthy adolescent and adult controls, and the selection of a linear model to examine age-related changes of T2-relaxation values of those areas. We agree that combining adolescent and adult data may provide more insight into brain changes across the life span. However, T2-relaxation values are echo-time dependent (14), and the two datasets were collected with different parameters, precluding such combining of data. We are aware that a linear model would not be appropriate if the pediatric and healthy adult data are pooled, since T2-relaxation values decrease with age in a developmental population, and those values increase with age with normal aging in healthy adults. It should be noted that when pediatric and adult control data were considered separately, a linear model did not deviate significantly for most of the brain sites, including the putamen, caudate, amygdala, hippocampus, insula, cingulate, thalamus, and corpus callosum, relationships that are apparent in figs. 1 and 2, as shown by Dr. Hasan in this reply to the Editor. Thus, we believe that the choice of a linear DOI 10.1002/jmri.24133 View this article online at wileyonlinelibrary.com. JOURNAL OF MAGNETIC RESONANCE IMAGING 38:506–507 (2013)