Detection of the Initiation of Medial Vascular Calcification in Coronary Artery Specimens of an HIV Patient with a Combination of 3D Tomographic Imaging and Histology
Authors: Wen Han , Miao Houxun , Larsen Thomas , Morales‐Martinez Alejandro , Yu Zu‐Xi , Bennett Eric , Boehm Manfred , Remaley Alan T. , Gharib Ahmed M. 
Published: June 2021

Histopathology protocols often involve a blanket search procedure that includes serial sectioning, processing and microscopy of a large number of slides. The objective of this study is, firstly, to obtain 3D scout scans of paraffin‐embedded human coronary artery samples using a fast x‐ray microtomography scanner, thereby replacing the blanket search with targeted sectioning and microscopy; secondly, to detect micro calcifications associated with typical atherosclerosis as well as other rare disease conditions.

The coronary artery specimens were from a deceased HIV patient. Intact paraffin blocks were scanned in a prototype scanner which yielded 3D volumes at 15 micrometer resolution in 15 minute scans. Digital virtual sections of the blocks were compared with subsequent histological sections of matching locations.

Tomographic cross‐sectional images showed the layered structure of the coronary wall. It revealed calcium deposits down to a single cell (10 micrometer) size. Two forms of calcifications were detected. One form consisted of clusters of bright (high density) dots often adjacent to porous dark (low density) patches, which were the loose calcifications and foam cells of typical atherosclerotic lesions. This form is illustrated by the tomographic cross‐section in Fig. 1a and the matching histological section in Fig. 1b. The latter was stained with H&E and Von Kossa stains to highlight calcifications. The second, rarer form was seen in over a dozen locations. It consisted of isolated dots of micro calcification in one or several cells in the internal elastic lamina of normal‐appearing vessel walls. Matching tomographic and histological sections are shown in Fig. 2a and 2b. Detection by the tomographic scan in intact paraffin blocks ruled out the possibility that these were particle contaminations during histological processing. It is speculated that this form is the initiation of medial vascular calcification which is related to diabetes and kidney disease, and some genetic vascular diseases such as arterial calcification due to deficiency of CD73 (ACDC) or generalized arterial calcification of infancy (GACI).

In conclusion, typical atherosclerosis as well as early stages of a rarer form of medial calcification were detected in the left anterior descending coronary artery of an HIV patient by a combination of a non‐invasive x‐ray tomographic scan and histology. The pathology‐dedicated tomo scanner had a scan time of 15 minutes compared to hours by typical bench‐top micro‐CT systems, which proved to be a useful scouting tool for targeted histological sectioning and microscopy.

Support or Funding Information

The study is supported by the Intramural Research Program of the National Institutes of Health.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.