Editors' ChoiceOrgan Transplantation

Finding a broken heart

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Science Translational Medicine  21 Feb 2018:
Vol. 10, Issue 429, eaas8962
DOI: 10.1126/scitranslmed.aas8962


A noninvasive imaging method identifies acute heart transplant rejection.

The gold standard for detection of acute heart transplant rejection currently requires invasive tissue biopsies and is not without complications. Motivated by the clinical need for a noninvasive method, researchers recently reported an exciting potential alternative. Knowing that tissue infiltration of T lymphocytes is a central process in acute transplant rejection, Liu and colleagues hypothesized that ultrasound molecular imaging could be combined with T lymphocyte–targeted nanobubbles to detect rejected heart transplants in rats. Ultrasound molecular imaging can facilitate earlier diagnosis of disease at the molecular level by identifying specific components—in this instance, T lymphocytes using targeted nanobubbles as an imaging contrast agent.

The results of their in vitro study indicate that targeted nanobubbles bearing an antibody could successfully adhere to T lymphocytes. Using allograft (heart transplant from one rat type to another rat type) and isograft (heart transplant from same rat type) models randomly assigned T lymphocyte–targeted or control (untargeted) nanobubbles, the study successfully showed a strong statistically significant signal from allograft rats given targeted nanobubbles. This was not seen in isograft rats, indicating the sensitivity of the potential detection method.

The study confirmed the findings of the imaging detection method with histology. Acute heart transplant rejection in the allografted rats was determined from the presence of inflammatory cell infiltration and myocyte damage, which was notably absent in the isografted rats. Immunohistochemistry on the myocardium further showed an increased T lymphocyte infiltration in allografts that was nearly nonexistent in isografts. Statistically, a close positive correlation between targeted nanobubble signal and numbers of T lymphocytes was shown, whereas no correlation was found for control-treated allografts.

This study focused on the potential of the ultrasound and targeted nanobubble detection method in rats, and further research is warranted in larger animals before this can be translated to the clinic. The promise of a new noninvasive gold standard for the detection of heart transplant rejection would be welcomed by the transplant community.

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