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The tilt experienced by the brain MR images may result in misalignment during image registration for medical applications. Manually correcting (or estimating) the tilt on a large scale is time-consuming, expensive, and needs brain anatomy expertise. Thus, there is a need for an automatic way of performing tilt correction in three orthogonal directions (<jats:italic>X<\/jats:italic>,<jats:italic>Y<\/jats:italic>,<jats:italic>Z<\/jats:italic>). The proposed work aims to correct the tilt automatically by measuring the pitch angle, yaw angle, and roll angle in<jats:italic>X<\/jats:italic>-axis,<jats:italic>Z<\/jats:italic>-axis, and<jats:italic>Y<\/jats:italic>-axis, respectively. For correction of the tilt around the<jats:italic>Z<\/jats:italic>-axis (pointing to the superior direction), image processing techniques, principal component analysis, and similarity measures are used. Also, for correction of the tilt around the<jats:italic>X<\/jats:italic>-axis (pointing to the right direction), morphological operations, and tilt correction around the<jats:italic>Y<\/jats:italic>-axis (pointing to the anterior direction), orthogonal regression is used. The proposed approach was applied to adjust the tilt observed in the T1- and T2-weighted MR images. The simulation study with the proposed algorithm yielded an error of 0.40\u00a0\u00b1\u00a00.09\u00b0, and it outperformed the other existing studies. The tilt angle (in degrees) obtained is ranged from 6.2\u00a0\u00b1\u00a03.94, 2.35\u00a0\u00b1\u00a02.61, and 5\u00a0\u00b1\u00a04.36 in<jats:italic>X<\/jats:italic>-,<jats:italic>Z<\/jats:italic>-, and<jats:italic>Y<\/jats:italic>-directions, respectively, by using the proposed algorithm. The proposed work corrects the tilt more accurately and robustly when compared with existing studies.<\/jats:p>","DOI":"10.1007\/s10278-020-00400-7","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T23:02:45Z","timestamp":1614207765000},"page":"760-771","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Content-Based Estimation of Brain MRI Tilt in Three Orthogonal Directions"],"prefix":"10.1007","volume":"34","author":[{"given":"Pooja","family":"Prabhu","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2458-3891","authenticated-orcid":false,"given":"A. K.","family":"Karunakar","sequence":"additional","affiliation":[]},{"given":"Sanjib","family":"Sinha","sequence":"additional","affiliation":[]},{"given":"N.","family":"Mariyappa","sequence":"additional","affiliation":[]},{"given":"G. 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