Meet Zhenwu Zhuang, MD, MS, Senior Research Scientist, Cardiovascular Medicine

Prior to joining Yale, I worked at the Dartmouth-Hitchcock Medical Center from 1998 to 2009, conducting 3D imaging labs for clinical patients. However, doing this kind of routine clinical work didn't really challenge me because of my background as a radiologist.

In 2009, the Yale Translational Research Imaging Center (Y-TRIC) was recruiting people to focus on preclinical research and imaging under Y-TRIC director Albert Sinusas, MD, which aligned with my expertise. Through this position, I started to do animal work, staging mouse models of peripheral artery disease, as well as 3D high-resolution quantitative micro-CT imaging, leading to dozens of publications. Before working at Yale, I mostly conducted work in CT, MRI, and echocardiograms in radiology, but I did not have any experience in nuclear medicine. Dr. Sinusas had broad knowledge, and through his training, I learned more about molecular imaging.

I’m proud of my research focused on coronary artery microvascular disease. The disease is more prevalent among women before or after menopause, with patients often reporting symptoms of chest pain. Despite intensive standard clinical imaging examinations such as CT imaging, MRI, and even putting a catheter through the coronary artery, physicians only visualize macrovascular blockages. They cannot see the microscopic clots or the acute extracellular matrix changes occurring in the microvasculature.

I got the idea that there could be an acute tiny thrombosis, occluded in a small vessel, not a big vessel, which would prevent clinical imaging, no matter the modality, from properly visualizing it. To combat this, I developed the first mouse model of coronary microvascular disease and targeted coagulation factor XIII as an imaging biomarker for early detection. I began applying molecular imaging to this clinical disease to better reflect the problem.

The National Institutes of Health has a dedicated program called the Women's Ischemia Syndrome Evaluation (WISE). WISE is a landmark National Heart, Lung, and Blood Institute (NHLBI)-sponsored multicenter study launched in 1996 to improve the diagnosis, evaluation, and understanding of ischemic heart disease in women. In 2013, NIH ended the R21 exploratory grant application due to a lack of breakthrough findings.

I picked up the phone, called the program director, and said, “I just had this idea.” I still remember her saying, “No, no, I don’t think you get it. Worldwide, there’s no coronary microvascular disease model, no diagnosis, no treatment. Why do you think you can solve this?”

I said, “That’s the reason I called you. I think I have created the disease model, and I have the molecular imaging marker we can target.”

Then she started to gain interest. The project finally got funding from another program, and I’ve been on the molecular imaging path since then.

We’ve made a lot of progress in this area of research since then. For example, using SPECT/CT imaging, we can map out the exact areas of active microvascular clotting and localized endothelial damage in the mouse heart.

Going forward, we aim to shift coronary microvascular disease from a "diagnosis of exclusion" to a directly visualizable condition. In 2019, this research was published in the journal Theranostics.

My favorite part is the amount of cooperation and collaboration within my department. I like the Yale environment; there are always so many experts. Every day, I get to learn new things, and new information is always flooding my brain. I also like to challenge myself. In particular, I’m always eager to uncover unique findings in my field and either publish them or help other principal investigators disseminate their findings.

I like fishing, and I like planting vegetables in my home garden after work. After 7 p.m., the sun has set, and I usually like to come to the garden to study, which also inspires me to do some gardening. Similar to fishing, when I work in the yard, my mind is very peaceful just by interacting with nature.