Zhenwu Zhuang, MD, MS

Dr. Zhuang’s research interests include multi-modality imaging in the cardiovascular system, the neurovascular system, and tumors. Currently, his research is focusing on developing micro-imaging approaches (microCT and micro-SET) for the assessment of angiogenesis, arteriogenesis, and vascular remolding. Because of his interventional radiologist background, he is also interested in translational research to develop strategies for local gene or cellular therapies and evaluate the therapeutic efficacy using noninvasive imaging approaches for coronary microvascular disease, ischemic stroke, and cardiac arrest.

Specialized Terms: Angiogenesis; Arteriogenesis; Vascular/Cardiac Remolding; Vascular Integrity; MicroCT; Micro-SPECT; MR; Molecular Imaging; Interventional Cardiology/Radiology; Gene Therapy; Cell Therapy; Cardiac Repair; Phenotype; Cardiovascular Development; Lung; Tumor; Nanoparticle; Thrombosis; Fibrinolysis; Coronary microvascular disease; Factor XIII; cardiac arrest; ischemic stroke, and Alzheimer' disease (AD)

Novel molecular imaging for early detection of microthrombi in the microvasculature. The exact mechanism and importance of coronary microvascular disease (MVD), under conditions of ischemic injury, are still unclear. Based on two notions: 1) endothelial cells can be damaged and platelets can be activated by photosensitizers irradiated by a specific wavelength of the laser in the heart of a mouse; 2) coagulation factor XIII is required for the impairment of microvascular function progress, we are establishing a novel animal model of MVD and applying non-invasive imaging strategy to dynamically monitor cross-linking thrombi formation and to document subsequent cardiac function in rodents following ischemic injury.

Molecular Imaging of Histone Deacetylase 6 Activity as an Epigenetic Biomarker in Ischemic Stroke. Cerebral ischemic injury is thought to result from a cascade of events ranging from energy depletion, excitotoxicity, oxidative stress, neuroinflammation, and programmed cell death to neuron survival and growth. Despite advances in genetic mechanisms, tissue plasminogen activator (tPA) infusion, or mechanical thrombectomy, the clinical outcome of ischemic stroke remains disappointing. Different from genetic regulation, epigenetic dysregulation, which does not change the DNA sequence, could be a pathological hallmark of ischemic stroke, which in turn triggers multiple events at different stages after ischemic insult. HDAC6 is a unique histone deacetylase (HDACs) subtype and takes part in multiple pathological events of ischemic stroke. In preliminary studies, we found that levels of HDAC6 antigen and protein expression had increased in the ischemic region in the early stages of stroke in mice. We also found that an HDAC6 inhibitor, ACY-775, was effective in mitigating infarct size and improving neurological recovery in mice. Based upon these initial results, we hypothesize that HDAC6 is a specific biomarker for the severity of the cerebral ischemic injury and that suppression of HDAC6 activity can rescue neurons from hypoxic damage by an ischemic attack.

PET imaging of Pre-synaptic Vesicle Density for cognitive dysfunction in Cardiac Arrest.

Sudden cardiac arrest (CA) accounts for 50% of all cardiovascular deaths in the US. Despite advances in post-resuscitation care and management, only 10.8% of adult out-of-hospital CA (OHCA) victims survive hospital discharge, and up to 50% of survived patients exhibit cognitive deficits (learning/memory disabilities, executive function). It is well-accepted that cognitive dysfunction is associated with synaptic dysfunction and the inability to induce physiological long-term potentiation (LTP) in the CA1 region of the hippocampus after global ischemia. These deficits suggest that synaptic dysfunction in specific regions (such as the hippocampus or cortex) might be responsible for post-CA brain injury (PCABI). In addition, levels of impairment or recovery of neurologic function govern long-term outcomes after CA, and prediction of the potential for recovery is a heavy burden for physicians and patients’ families. A sensitive and reliable in vivo approach to assess the loss and partial restoration of synaptic function or density, if it can provide early information on the severity of synaptic dysfunction, monitor the neuron recovery, and predict the outcome.