Background Although local features of brain morphology have been widely investigated in neuroscience, the inter-regional relations in brain morphology have rarely been investigated, especially not for individual participants. New method In this paper, we proposed a novel framework for investigating this relation based on an individual's magnetic resonance imaging (MRI) data. The key idea was to estimate the probability density function (PDF) of local morphological features within a brain region to provide a global description of this region. Then, the inter-regional relations were quantified by calculating the similarity of the PDFs for pairs of regions based on the Kullback–Leibler (KL) divergence. Results For illustration, we applied this approach to a pre-post intervention study to investigate the longitudinal changes in morphological relations after long-term sleep deprivation. The results suggest the potential application of this new method for studies on individual differences in brain structure. Comparison with existing methods The current method can be employed to estimate individual morphological relations between regions, which have been largely ignored by previous studies. Conclusions Our morphological relation metric, as a novel quantitative biomarker, can be used to investigate normal individual variability and even within-individual alterations/abnormalities in brain structure.