Postmortem magnetic resonance imaging to guide the pathologic cut: individualized, 3-dimensionally printed cutting boxes for fixed brains

Abstract

Interfacing magnetic resonance imaging (MRI) with pathology is critically important for understanding the pathologic basis of MRI signal changes in vivo and for clinicopathologic correlations. Postmortem MRI is an intermediate step in this process; unfortunately, however, relating the data to standard pathologic sections, which are relatively thick and often nonparallel, is both time-consuming and insufficiently accurate. The aim of this project was to develop technology to integrate postmortem, high-resolution, whole-brain MRI into the planning and execution of pathologic analysis through precise localization of the target and coordinates of cut. Compared with standard pathologic sectioning, the use of an individualized, 3-dimensionally printed cutting box-designed based on postmortem MRI of formalin-fixed whole brains-improved the speed, quality, and accuracy of radiologic-pathologic correlations and, specifically, the histopathologic localization of imaging findings. The technology described herein is easily implemented, applicable to any brain disorder, and potentially extendable to other organs. From the point of view of the pathologist, this technique can improve localization of small or subtle abnormalities, whereas from the point of view of the radiologist, it has the potential to improve understanding of MRI signal changes observed in diseases.

Figure 1

Illustration of the technique. (A–C) A dome-shaped container was fashioned for magnetic resonance imaging (MRI) of the postmortem brain; it was customized to reduce susceptibility artifacts and to fill a 7 tesla MRI receive coil (A, left panel). The postmortem brain was immersed in Fomblin and aspirated for air bubbles through the sprout by applying suction for ~30 minutes before imaging (A, middle and right panels). For Patient 1, individualized cutting boxes were designed and 3D-printed for the forebrain (B) and the brainstem-cerebellum (C). The surface of the fixed brain was rendered from the MRI sequence, and a mold was created to conform to the inferior surface of the brain (B) and posterior surface of the cerebellum (C).

Figure 2

Comparison of sectioning performance with and without the cutting box. (A) Comparisons of the gross appearance of the brain slices (anterior surface, starting from slice 2) and the corresponding coronal multigradient-echo (GRE, 2nd echo) magnetic resonance imaging (MRI) slices of the brain of Patient 1. Areas where the match was judged less accurate are indicated by asterisks (*). (B, C) The cutting lines and their accuracy with the cutting box for Patient 1 (B) and without the cutting box for Patient 2 (C) are superimposed on an axial MRI slice. The sectioning is much less accurate with the traditional cutting method (C).

Figure 3

Brainstem-cerebellum sectioning performance with the cutting box. Matches between the gross appearance of the slices (left) and corresponding transversal multigradient echo (GRE, 2nd echo) magnetic resonance image (MRI) slice of the brainstem-cerebellum are shown for Patient 1. White arrows indicate demyelinated lesions; in several of them, the central vein is prominent on the GRE MRI sequence. Areas where the match was judged less accurate are indicated by asterisks (*).

Figure 4

Multimodal magnetic resonance image (MRI)-histology examination. (A–E) A cortical multiple sclerosis lesion was barely visible on the in vivo scans (A, boxed area) but clearly visible on the postmortem 3D multigradient echo (GRE) scan (B, white box) and (C). White arrows indicate the extent of cortical lesions on the GRE MRI image (C), and in histologic sections with H&E staining (D) and myelin proteolipid protein immunohistochemistry (E). The red line in (C) indicates where the fixed tissue was broken during slicing; this is contour is evident in the right lower portion of (D).