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Tb Granulomas Revealed In 3-d For First Time Alters Model Of Their Growth And Shape

Patients with tuberculosis granulomas in their lungs were thought to be known by their shape for 70 years. In the 1940s and 1950s, researchers saw rounded features in thin slices of lung tissue, which they intuitively interpreted as meaning that the granulomas were spherical or ovoid.

AHRI and the University of Alabama at Birmingham have reached the conclusion that the long-standing paradigm is outdated. The study was conducted in South Africa, in Durban, KwaZulu-Natal. Historically, histology had a two-dimensional view of structures, similar to how a slice of a tree branch would appear rounded or oval after it was sliced.

Tb Granulomas Revealed In 3-d For First Time Alters Model Of Their Growth And Shape

Researchers used computed tomography, or microCT, to visualize the diseased lungs of tuberculosis patients in three dimensions. Several of the larger granulomas revealed a complex, branched shapes, as opposed to being round. A couple of the granulomas resembled ginger roots, another looked like cherry blossom buds before the blossoms appeared. There were marked differences in the shapes, volumes, and numbers of tuberculosis granulomas in lung sections.

Tb Granulomas Revealed In 3-d For First Time Alters Model Of Their Growth And Shape

Chronic inflammation leads to the accumulation of immune cells known as granulomas. Granulomas are normally necrotic in tuberculosis. They consist of a mass of dead formless tissue.

In addition to microCT, histology, and immunohistochemistry, the UAB team also built three-dimensional views of the vasculature and airways surrounding necrotic granulomas. Adrie Steyn is a professor of microbiology at UAB. Researchers were able to gain a unique perspective on tuberculosis granulomas, showing their spatial relationships to airways and veins. 

The granulomas are not easily recognizable, as they are often depicted as simple spheres, Steyn said. Furthermore, these necrotic granulomas are shaped by the bronchi and have complex, cylindrical, branched morphologies.

This type of visualization has three effects, according to Steyn. Two-dimensional evaluations bring to light the fact that multiple independent lesions may be mistakenly viewed as a single, structurally complex lesion. 

Second, obstructed bronchi do not have vascularization, so they become tolerant to anti-mycobacterial drugs since they are not exposed to the full concentration of blood-borne anti-mycobacterial drugs. Third, the study shows that the pathogen Mycobacterium tuberculosis reseeds the lung via the bronchogenic spread. Thus, Steyn’s findings justify the consideration of aerosolized antituberculosis drug delivery. 

Thus, Steyn’s findings justify the consideration of aerosolized antituberculosis drug delivery. It would be possible, using such an approach, to deliver high-concentration drugs directly into granulomas or cavities of the lungs, possibly reducing treatment times and toxicity. Mycobacterium tuberculosis causes about 1.3 million deaths worldwide annually. For the first time, Steyn and colleagues describe airways, granulomas, and vasculature in three dimensions in a bacterial pulmonary pathogen.

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The availability of human infected lung tissues in Durban is due to the region’s high tuberculosis prevalence. There is a resection clinic outside AHRI, which treats tuberculosis patients by removing diseased lobes. CAT scans are often used medically, but micro CTs have far finer resolution than these. Resolutions of as little as 12 microns were used, which is about as thick as a kitchen wrap. In addition to maintaining labs at the AHRI and UAB, Steyn is the director of AHRI’s Spectromalysis unit. Six or seven times a year, he visits UAB from his hometown, Durban.

According to a study published in the American Journal of Respiratory and Critical Care Medicine, the human tuberculous lung exhibits impressive heterogeneity in 3D granuloma morphology using CT analysis. An editorial was also published in the journal regarding Steyn’s study. We used microCT images of infected human lung tissue in conjunction with histochemistry and immunohistochemistry to obtain images of TB granulomas, internal airways, and vasculature.

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