Cheuk Y. Tang

Research

Dr. Tang is currently working on diagnostic technologies for Alzheimer's Disease and related research. There are currently no definative diagnostic techniques for AD. The neuropathological hallmark of AD are neuritic plaques and neurofibrillary tangles that can only be detected using histochemical staining techniques. Trangenic Mouse models have been developed that overexpress beta-amyloid plaques. Dr. Tang use both single transgenic (APPswe) which develop plaque deposits in both cortical and hippocampal areas at the age of 12 months and double transgenic (APP/PS1) which develop robust plaques at 6 months of age. Current research in treatment strategies can roughly be divided into methods that clear existing plaque deposits, methods that prevent the buildup of plaques and techniques that compensate for the neuronal deaths dues to the plaques. The former two require the quantification of plaque burden. The current gold standard using histological stains does not allow for longitudinal monitoring of plaque burden in-vivo, which is important if one want to study the efficacy of any treatment protocol. Conventional histological techniques are also time consuming and too costly to apply to the whole brain. Dr. Tang is developing MRI based technologies to visualize these beta-amyloid plaques for both ex-vivo and in-vivo applications.

For ex-vivo application Dr. Tang has developed a Micro MRI protocol which allows one to obtain isotropic resolutions down to 20 mm. These voxels are several orders of magnitude smaller (1:100,000) than conventional clincal MRI. Whole brain data with up to 512 images can be obtained in one scan and we have been able to observe plaque lesions at these resolutions. Additional advantages of using this approach is that the data is inherently in a digital format readily available for subsequent computerized quantification. In addition, a high resolution structural dataset is obtained for volumetric analysis.


Beta-amyloid plaques visualized as hypointense lesions in single transgenic mice (APPswe) at 25 micron resolution.


Double Transgenic (APP/PS1) at 20 micron resolution.


High-resolution 3D whole brain dataset (wild type).

For in-vivo applications Dr. Tang is researching ligands that can be used in conjunction with MRI contrast agents. These ligands (peptides) attach themselves to the beta-amyloid plaques when administered into the vascular system. When we bind MR contrast agents (e.g. Gadolinium Gd or Monocrystaline Iron Oxide Nanoparticles MION) to these peptides they stick to the plaque lesions and return an MRI detectable signal. The challenge here is the Blood Brain Barrier (BBB) which is a semi-permeable fence between the brain and the vascular system that prevents most large foreign molecules from entering the brain. This problem is targeted by using both osmotic agents as well as receptor mediated techniques. The development of this technology not only allows longitudinal monitoring of treatment strategies in animal models but are portable to human applications such as diagnosis and monitoring.

In addition, Dr. Tang collaborates with other researchers to apply these molecular imaging technologies for the development of novel diagnostic imaging modalities for other diseases such as autism, Niemann Pick's disease, Parkinson and prion diseases.


Dr. Tang is an investigator of the CONTE center team which aims to study the role of white matter disruptions in schizophrenia. These projects involved both human and mice models of the disease. Human imaging involves structural MRI, DTI, fMRI and MRSi on a 3T MRI. Mouse models include MAG, Quaking, NRG1 etc imaged using DTI in a 9.4T MRI.

Dr. Tang is also intensively involved with developing novel image analysis techniques for the use with Diffusion Tensor Imaging and functional MRI. His team has developed several software packages that integrate DTI with fMRI for the quantification of functional and structural connectivity. In addition to DTI fiber tracking, software for automated extraction of resting state brain networks have been developed. These techniques have been applied to disorders such as schizophrenia, brain lesions due to exposure to solvents, normal cognitive brain function correlates.