Biomedical subjects

Zhenghong Lee

Publications and source records attributed to Zhenghong Lee.

8 recordsLinked to original sources

PubMed2007

Gene expression studies of hepatitis virus-induced woodchuck hepatocellular carcinoma in correlation with human results.

The lack of good molecular markers for diagnosis as well as treatment assessment has rendered the hepatocellular carcinoma (HCC) a major challenge in health care. In this study, woodchucks were used as an animal model for hepatitis virus-induced HCC, and gene expression studies were performed using a human oligonucleotide microarray. An analysis approach combing supervised significant analysis of microarray (SAM), prediction analysis of microarray (PAM), and unsupervised hierarchical cluster methodologies statistically determined 211 upregulated and 78 downregulated genes between liver cancer and non-cancer liver tissues, and demonstrated > or = 93% accuracy in classifying the tissue samples. RT-PCR results confirmed the differential expression of selected sequenced woodchuck genes (SAT, IDH3B, SCD) in the microarray. Our study showed that differentially expressed genes were involved in transcription, RNA splicing, translation, cell cycle, metabolism, protein folding and degradation, apoptosis, immune response, metal binding, etc. Interestingly, some genes were involved with signaling pathways such as Ras/MAPK (MAPKAP1), Src-dependent pathways (CSK), hedgehog signaling pathway (HHIP), while Wnt signaling pathway may not be dominant in woodchuck HCC as shown by the downregulation of beta-catenin (TNNB1) and the upregulation of CXXC4 and CSNK2B. Numerous genes found in this study were also differentially expressed in human HCC and many other human cancers including breast, prostate and lung cancers, etc., serving as tumor suppressors, promoters, prognostic markers or chemotherapy targets. In conclusion, this study has demonstrated the robustness of the data analysis and the potential of using human microarrays on woodchuck samples. In particular, some of the differentially expressed genes in the woodchuck HCC can be further explored for possible molecular imaging targets or biological markers in human HCC.

Animals↗

PubMed2006

Cross-species hybridization of woodchuck hepatitis virus-induced hepatocellular carcinoma using human oligonucleotide microarrays.

AIM: To demonstrate the feasibility of using woodchuck samples on human microarrays, to provide insight into pathways involving positron emission tomography (PET) imaging tracers and to identify genes that could be potential molecular imaging targets for woodchuck hepatocellular carcinoma. METHODS: Labeled cRNA from woodchuck tissue samples were hybridized to Affymetrix U133 plus 2.0 GeneChips. Ten genes were selected for validation using quantitative RT-PCR and literature review was made. RESULTS: Testis enhanced gene transcript (BAX Inhibitor 1), alpha-fetoprotein, isocitrate dehydrogenase 3 (NAD+) beta, acetyl-CoA synthetase 2, carnitine palmitoyltransferase 2, and N-myc2 were up-regulated and spermidine/spermine N1-acetyltransferase was down-regulated in the woodchuck HCC. We also found previously published results supporting 8 of the 10 most up-regulated genes and all 10 of the 10 most down-regulated genes. CONCLUSION: Many of our microarray results were validated using RT-PCR or literature search. Hence, we believe that woodchuck HCC and non-cancerous liver samples can be used on human microarrays to yield meaningful results.

Animals↗

PubMed2006

Hexokinase and glucose-6-phosphatase activity in woodchuck model of hepatitis virus-induced hepatocellular carcinoma.

2-Deoxy-2-[(18)F]fluoro-D-glucose ([(18)F] FDG) is used for PET imaging of woodchuck (Marmota monax) model of hepatocellular carcinoma (HCC). The usefulness of FDG on this animal model needs to be validated according to the hypothesized mechanisms. In this study, two key enzymes involved in glucose or [(18)F] FDG metabolism, hexokinase (HK) and glucose-6-phophatase (G6Pase), were examined for their enzymatic activities in the woodchuck models of HCC, which has not been studied before. After dynamic PET scans, woodchuck liver tissue samples were harvested and the homogenate was centrifuged. The supernatant was used for HK activity assay and the microsomal pellet was used for G6Pase assay. HK and G6Pase activities were measured by means of colorimetric reactions via kinetic and end-point assays, respectively. Total protein content was measured by the Bradford method and used to normalize all enzyme activities. HK and G6Pase activities in woodchuck HCC will be used to correlate with in vivo PET imaging data. The woodchuck model of HCC had significantly increased levels of HK in the livers compared to the age-matching healthy woodchuck (7.96 +/- 1.27 vs. 2.74 +/- 0.66 mU/mg protein, P < 0.01) and significantly decreased levels of G6Pase compared to healthy woodchuck (40.35 +/- 19.28 vs. 237.01 +/- 17.32 mU/mg protein, P < 0.01), reflecting an increase in glycolysis. In addition, significant differences were found in HK and G6Pase activities between HCC liver region (HK: 7.96 +/- 1.27 mU/mg protein; G6Pase: 40.35 +/- 19.28 mU/mg protein) and surrounding normal liver region (HK: 2.98 +/- 0.92 mU/mg protein; G6Pase: 140.87 +/- 30.62 mU/mg protein) in the same woodchuck model of HCC (P < 0.01). Our study demonstrated an increased HK activity and a decreased G6Pase activity in liver of the woodchuck models of HCC as compared to normal woodchuck liver.

Animals↗

PubMed2005

Three-dimensional segmentation and skeletonization to build an airway tree data structure for small animals.

Quantitative analysis of intrathoracic airway tree geometry is important for objective evaluation of bronchial tree structure and function. Currently, there is more human data than small animal data on airway morphometry. In this study, we implemented a semi-automatic approach to quantitatively describe airway tree geometry by using high-resolution computed tomography (CT) images to build a tree data structure for small animals such as rats and mice. Silicon lung casts of the excised lungs from a canine and a mouse were used for micro-CT imaging of the airway trees. The programming language IDL was used to implement a 3D region-growing threshold algorithm for segmenting out the airway lung volume from the CT data. Subsequently, a fully-parallel 3D thinning algorithm was implemented in order to complete the skeletonization of the segmented airways. A tree data structure was then created and saved by parsing through the skeletonized volume using the Python programming language. Pertinent information such as the length of all airway segments was stored in the data structure. This approach was shown to be accurate and efficient for up to six generations for the canine lung cast and ten generations for the mouse lung cast.

Algorithms↗

PubMed2005

Multimodal and three-dimensional imaging of prostate cancer.

Accurate characterization of prostate cancer is crucial for treatment planning and patient management. Non-invasive SPECT imaging using a radiolabeled monoclonal antibody, 111In-labeled capromab pendetide, offers advantage over existing means for prostate cancer diagnosis and staging. However, there are difficulties associated with the interpretation of these SPECT images. In this study, we developed a 3D surface-volume hybrid rendering method that utilizes multi-modality image data to facilitate diagnosis of prostate cancer. SPECT and CT or MRI (or both) images were aligned either manually or automatically. 3D hybrid rendering was implemented to blend prostate tumor distribution from SPECT in pelvis with anatomic structures from CT/MRI. Feature extraction technique was also implemented within the hybrid rendering for tumor uptake enhancement. Autoradiographic imaging and histological evaluation were performed to correlate with the in-vivo SPECT images. Warping registration of histological sections was carried out to compensate the deformation of histology slices during fixation to help the alignment between histology and in-vivo images. Overall, the rendered volumetric evaluation of prostate cancer has the potential to greatly increase the confidence in the reading of radiolabeled monoclonal antibody scans, especially in patients where there is a high suspicion of prostate tumor metastasis.

Humans↗

PubMed2003

Automatic registration of MR and SPECT images for treatment planning in prostate cancer.

RATIONALE AND OBJECTIVES: To aid in surgical and radiation therapy planning for prostate adenocarcinoma, a general-purpose automatic registration method that is based on mutual information was used to align magnetic resonance (MR) images and single photon emission computed tomographic (SPECT) images of the pelvis and prostate. MATERIALS AND METHODS: The authors assessed the effects of various factors on alignment between pairs of MR and SPECT images, including the use of particular pulse sequences in MR imaging, image voxel intensity scaling, the use of different regions on the MR-SPECT histogram, spatial masking of nonoverlapping visual data between images, and multiresolution optimization. A mutual information algorithm was used as the cost function for automatic registration. Automatic registration was deemed acceptable when it resulted in a transformation with less than 2 voxel units (6 mm) difference in translation and less than 2 degree difference in rotation from that obtained with manual registration performed independently by nuclear medicine radiologists. RESULTS: Paired sets of MR and SPECT image volumes from four of five patients were successfully registered. For successful registration, MR images must be optimal and registration must be performed at full spatial resolution and at the full intensity range. Masking, cropping, and the normalization of mutual information, used to register partially overlapping MR-SPECT volumes, were not successful. Multiresolution optimization had little effect on the accuracy and speed of the registration. CONCLUSION: Automatic registration between MR and SPECT images of the pelvis can be achieved when data acquisition and image processing are performed properly. It should prove useful for prostate cancer diagnosis, staging, and treatment planning.

Adenocarcinoma↗

PubMed2002

Automatic MR volume registration and its evaluation for the pelvis and prostate.

A three-dimensional (3D) mutual information registration method was created and used to register MRI volumes of the pelvis and prostate. It had special features to improve robustness. First, it used a multi-resolution approach and performed registration from low to high resolution. Second, it used two similarity measures, correlation coefficient at lower resolutions and mutual information at full resolution, because of their particular advantages. Third, we created a method to avoid local minima by restarting the registration with randomly perturbed parameters. The criterion for restarting was a correlation coefficient below an empirically determined threshold. Experiments determined the accuracy of registration under conditions found in potential applications in prostate cancer diagnosis, staging, treatment and interventional MRI (iMRI) guided therapies. Images were acquired in the diagnostic (supine) and treatment position (supine with legs raised). Images were also acquired as a function of bladder filling and the time interval between imaging sessions. Overall studies on three patients and three healthy volunteers, when both volumes in a pair were obtained in the diagnostic position under comparable conditions, bony landmarks and prostate 3D centroids were aligned within 1.6 +/- 0.2 mm and 1.4 +/- 0.2 mm, respectively, values only slightly larger than a voxel. Analysis suggests that actual errors are smaller because of the uncertainty in landmark localization and prostate segmentation. Between the diagnostic and treatment positions, bony landmarks continued to register well, but prostate centroids moved towards the posterior 2.8-3.4 mm. Manual cropping to remove voxels in the legs was necessary to register these images. In conclusion, automatic, rigid body registration is probably sufficiently accurate for many applications in prostate cancer. For potential iMRI-guided treatments, the small prostate displacement between the diagnostic and treatment positions can probably be avoided by acquiring volumes in similar positions and by reducing bladder and rectal volumes.

Algorithms↗

PubMed2002

PET imaging-based evaluation of aerosol drugs and their delivery devices: nasal and pulmonary studies.

Three-dimensional (3-D) positron emission tomography (PET) imaging of inhaled radiolabeled aerosol in the nasal or pulmonary regions provides an in vivo measurement of drug distribution using the drug itself as the tracer. Repeated or dynamic PET scans over the time after inhalation provides us with further information about the fate of the deposited drug. These quantitative measurements are sufficient to describe the performance of a drug or device and they are obtained in a noninvasive fashion, which cannot be achieved by using any other methods. Using this PET-imaging paradigm, we conducted a sequence of drug studies to evaluate the performance of aerosol drugs and delivery devices; to compare the performance of similar drugs from different manufacturers; to assess the similarity between different formulations and propellants for the same drug; to appraise delivery devices such as spacers and nebulizers, etc. This paper reviews only the imaging and data analysis techniques developed for the above-mentioned studies that include multi-modality image registration, region definition and region-based data analysis, and nonregion-based data analysis. We separated the techniques into nasal and pulmonary studies because of the uniqueness of each group. Specific drugs or devices are not identified and no result about drug performance is given because the imaging and data analysis methodology, which is the focus of this paper, applies to all these studies regardless of the drugs or their delivery devices. The quantitative data are used as the scientific basis for evaluation although we also developed visualization techniques to enhance the results drawn from the data.

Administration, Inhalation↗