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Biomedical subjects

Ren-Shyan Liu

Publications and source records attributed to Ren-Shyan Liu.

At least 19 recordsLinked to original sources

Monitoring the growth effect of xenotransplanted human medulloblastoma in an immunocompromised mouse model using in vitro and ex vivo green fluorescent protein imaging.

INTRODUCTION: Medulloblastoma (MB) is one of the most common malignant brain tumors in children. It is a radiosensitive tumor. At 5 years after radical surgical excision and craniospinal axis irradiation, the tumor-free survival rate is from 50 to 70% [Halperin EC, Constine LS, Tarbell NJ, Kun LE. Pediatric radiation oncology (2005)]. CASE REPORT: In this study, we established xenotransplanted human MB (hMB) cells - isochromosome 17q - in a severe combined immunodeficiency (SCID) mouse model. We further transduced green fluorescent protein (GFP) into hMB cells to evaluate these hMB cells grafted in SCID mice. RESULTS: The result of an ex vivo GFP imaging system showed that a small lesion of the third-week-hMB-transplanted graft presented "green" signals with a clear tumor margin before any tumor-related symptoms were noted. We also demonstrated that the tumor progression could be monitored by GFP imaging for up to 12 weeks post-transplantation. CONCLUSIONS: This novel approach of GFP imaging assessment provides more accurate information of tumor status for experimental brain tumor studies. Because MB is sensitive to radiation and also response to chemotherapy, this SCID mouse model will be helpful for preclinical studies in the future.

Animals↗

PET imaging of brain astrocytoma with 1-11C-acetate.

PURPOSE: The purpose of this study was to assess the use of 1-(11)C-acetate (ACE) as a metabolic tracer for the detection and characterisation of astrocytomas. METHODS: Positron emission tomography (PET) studies with ACE and 2-(18)F-fluoro-2-deoxy-D-glucose (FDG) were performed sequentially in 26 patients with primary astrocytomas. Images were analysed by visual interpretation and determination of the tumour to cortex ratio (T/C ratio) and standardised uptake value (SUV). The tumour uptake was visually scored into three grades as compared with the contralateral cortex: clearly lower (-), almost equal (+) and clearly higher (++). RESULTS: There were 85% of astrocytomas with ++ ACE uptake, 15% with + ACE uptake and none with - ACE uptake. Only 19% of astrocytomas had ++ FDG uptake. Thirty-seven percent of high-grade astrocytomas had + FDG uptake and 37% had - FDG uptake. The sensitivity and specificity of the FDG T/C ratio in discriminating high-grade from low-grade astrocytomas were 79% and 100%, respectively, at the cutoff value of 0.75. Using 2.33 as the cutoff value of the ACE T/C ratio, the sensitivity and specificity were 42% and 86%, respectively. FDG was better than ACE in discriminating high-grade from low-grade astrocytomas. T/C ratios and SUVs of FDG uptake of tumours correlated with the histological grades, but those of ACE uptake did not. CONCLUSION: ACE appears to be a promising tracer for use in the detection of primary astrocytomas, but is of limited value in the differentiation of high- and low-grade astrocytomas. ACE is complementary to FDG for the diagnosis and characterisation of astrocytoma.

Acetates↗

Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging.

The aim of this study was to assess the efficacy human mesenchymal stem cells (hMSC) for targeting microscopic tumors and suicide gene or cytokine gene therapy. Immunodeficient mice were transplanted s.c. with human colon cancer cells of HT-29 Inv2 or CCS line, and 3 to 4 days later, i.v. with "tracer" hMSCs expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) and enhanced green fluorescent protein (EGFP) reporter genes. Subsequently, these tumors were examined for specificity and magnitude of HSV1-TK(+), EGFP(+) stem cell engraftment and proliferation in tumor stroma by in vivo positron emission tomography (PET) with (18)F-labeled 9-(4-fluoro-3-hydroxymethylbutyl)-guanine ([(18)F]-FHBG). In vivo PET images of tumors growing for 4 weeks showed the presence of HSV1-TK(+) tumor stroma with an average of 0.36 +/- 0.24% ID/g [(18)F]-FHBG accumulation. In vivo imaging results were validated by in situ correlative histochemical, immunofluorescent, and cytometric analyses, which revealed EGFP expression in vWF(+) and CD31(+) endothelial cells of capillaries and larger blood vessels, in germinal layer of dermis and hair follicles proximal to the s.c. tumor site. These differentiated HSV1-TK(+), GFP(+) endothelial cells had limited proliferative capacity and a short life span of <2 weeks in tumor fragments transplanted into secondary hosts. We conclude that hMSCs can target microscopic tumors, subsequently proliferate and differentiate, and contribute to formation of a significant portion of tumor stroma. PET imaging should facilitate clinical translation of stem cell-based anticancer gene therapeutic approaches by providing the means for in vivo noninvasive whole-body monitoring of trafficking, tumor targeting, and proliferation of HSV1-tk-expressing "tracer" hMSCs in tumor stroma.

Animals↗

Cognitive reserve: a SPECT study of 132 Alzheimer's disease patients with an education range of 0-19 years.

This study examines the associations between education, cerebral perfusion, and cognitive test performance among 132 patients with Alzheimer's disease. The participants had had between 0 and 19 years of formal schooling, and had either mild or moderate dementia according to the Clinical Dementia Rating Scale. Cerebral perfusion was evaluated by the (99m)Tc-hexamethylpropylene amine oxime single photon emission computed tomography. The Mini-Mental State Examination and the Cognitive Abilities Screening Instrument were used to assess cognitive performance. For patients at each clinical dementia severity level, statistical parametric mapping was used to examine voxel by voxel the association between education and cerebral perfusion, and Pearson's correlation coefficients were calculated between education and cognitive test scores. Years of formal schooling had negative associations with cerebral perfusion and positive associations with cognitive test scores. The brain regions showing a significant education effect on perfusion involved bilateral posterior association areas in mild dementia, and bilateral parieto-temporo-frontal areas in moderate dementia. The present findings indicate that the cognitive reserve effect starts at the low end of the education range. They also suggest that the main effect of more education is a more facile use of alternative brain circuits instead of locally increased synaptic connections.

Aged↗

Development of wavelet de-noising technique for PET images.

Positron emission tomography (PET) imaging provides the functional information and precise physiological uptake of radioactivity in a patient's body. But the shortcoming of PET is low signal to noise ratio (SNR) due to photon noise. The noise may influence image quality, and cause the mistake of clinical interpretation. The purpose of this research is to develop a wavelet de-noising technique to reduce the noise of PET images. By processing the image through the optimum wavelet parameters we selected, we keep the resolution and contrast but reduce almost half of coefficient of variation in the region of interest of PET images.

Humans↗

Capsule 13C-urea breath test for the diagnosis of Helicobacter pylori infection.

AIM: To compare the accuracy of capsule 13C-urea breath test (UBT) with conventional invasive methods for the diagnosis of Helicobacter pylori infection. METHODS: One hundred patients received CLO test, histological examination, culture and 100- or 50-mg capsule UBT for the diagnosis of H pylori infection. H pylori infection was defined as those with positive culture or positive results from both histology and CLO test. RESULTS: Both the sensitivity and specificity of the 100-mg capsule UBT (n = 50) were 100%. The sensitivity and specificity of the 50-mg capsule UBT (n = 50) were 96.4 and 100%, respectively. Taken together, the accuracy of capsule UBT (n = 100) was higher than that of CLO test, histology and culture (100% vs 92%, 91% and 89%, respectively; P = 0.035, 0.018 and 0.005, respectively). Our data showed that the optimal timing of sampling for 100- and 50-mg capsule UBT was 15-30 and 6-15 min, respectively. CONCLUSION: Capsule UBT has a higher accuracy compared with biopsy-based tests. It is an ideal method for the diagnosis of H pylori infection.

Adult↗

A novel in vitro retinal differentiation model by co-culturing adult human bone marrow stem cells with retinal pigmented epithelium cells.

Human retinal pigment epithelium (HRPE) cells are important in maintaining the normal physiology within the neurosensory retina and photoreceptors. Recently, transplantation of HRPE has become a possible therapeutic approach for retinal degeneration. By negative immunoselection (CD45 and glycophorin A), in this study, we have isolated and cultivated adult human bone marrow stem cells (BMSCs) with multilineage differentiation potential. After a 2- to 4-week culture under chondrogenic, osteogenic, adipogenic, and hepatogenic induction medium, these BMSCs were found to differentiate into cartilage, bone, adipocyte, and hepatocyte-like cells, respectively. We also showed that these BMSCs could differentiate into neural precursor cells (nestin-positive) and mature neurons (MAP-2 and Tuj1-positive) following treatment of neural selection and induction medium for 1 month. Furthermore, the plasticity of BMSCs was confirmed by initiating their differentiation into retinal cells and photoreceptor lineages by co-culturing with HRPE cells. The latter system provides an ex vivo expansion model of culturing photoreceptors for the treatment of retinal degeneration diseases.

Bone Marrow Cells↗

Malignancy of intracerebral lesions evaluated with 11C-methionine-PET.

Positron emission tomography (PET) allows examination of a variety of physiological parameter, including blood flow, glucose, amino acid and oxygen metabolism. However, correlation of PET scan findings and the degree of malignancy of intracerebral tumors continues to be controversial. Nine patients with primarily diagnosed intraparenchymal brain tumors were included in this study. We performed 11C-methionine-PET (met-PET) prior to surgical treatment and the differential absorption ratio (DAR) was calculated. All patients underwent open or stereotactic surgery and specimens for pathological diagnosis were obtained. The biological activity of each tumor was determined by calculation of the proliferation index from MIB-1 immunohistochemistry. The DAR of met-PET for individual tumors correlated with the histological diagnosis and degree of malignancy and this was further confirmed by good correlation with the MIB-1 proliferation index. We conclude that met-PET may be a reliable and effective preoperative evaluation to determine the type and malignancy of intraparenchymal brain lesions.

Aged↗

Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system.

The atypical teratoid/rhabdoid tumor, primary to the central nervous system, is a highly malignant and aggressive neoplasm of infancy and childhood. Although having distinct biological features and clinical outcomes, it is frequently misdiagnosed as primitive neuroectodermal tumor/medulloblastoma. To further distinguish the underlying pathogenesis and to identify biological markers for clinical use, an atypical teratoid/rhabdoid tumor-derived cell line was established and its gene expression pattern analyzed in comparison to the human astrocyte SVG12 cell line and the human DAOY medulloblastoma cell line using a complementary DNA microarray method. The osteopontin gene was found specifically upregulated in atypical teratoid/rhabdoid tumor cells. This specificity was confirmed by immunohistochemistry in pathological sections of tissues from atypical teratoid/rhabdoid tumor patients. Even though the role of osteopontin in the cytopathogenesis of atypical teratoid/rhabdoid tumor still needs to be determined, our data support that overexpressed osteopontin is a potential diagnostic marker for atypical teratoid/rhabdoid tumor.

Cell Line↗

Demonstration of large bladder diverticulum on bone scan.

A 74-year-old man underwent low anterior resection for rectal cancer. Technetium-99m methylene diphosphonate (MDP) bone scanning was performed as part of the patient's postoperative follow-up study. Scans revealed an area of increased tracer uptake in the left hemipelvis. Coronal single-photon emission computed tomography and caudal images clearly separated the lesion from the skeletal structures. Transverse magnetic resonance images showed a large diverticulum originating from the left lateral wall of the bladder. The pelvic findings on the bone scan were the result of tracer retained within this diverticulum.

Aged↗

Elevation of plasma and cerebrospinal fluid osteopontin levels in patients with atypical teratoid/rhabdoid tumor.

Osteopontin, a cancer metastasis-associated gene, is specifically up-regulated in central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT), but its biological behavior in the progression of CNS AT/RT has never been studied. We obtained plasma, cerebrospinal fluid (CSF), and brain tissue specimens from lobectomy or hemispherectomy samples from 39 patients (medulloblastoma, 16; AT/RT, 8; epilepsy, 6; hydrocephalus, 9). By enzyme-linked immunosorbent assay, the median osteopontin levels in plasma and CSF in AT/RT (852.0 and 1,175.0 ng/mL, respectively) were significantly higher than in medulloblastoma (492.5 and 524.5 ng/mL, respectively) and hydrocephalus and epilepsy (208.0 and 168.0 ng/mL, respectively) (P < .05). The results of real-time reverse transcriptase-polymerase chain reaction and immunohistochemical analysis demonstrated that osteopontin expression in AT/RT (n = 5) was significantly higher than in medulloblastoma (n = 8) samples. The differences in osteopontin expression in plasma, CSF, and tumor samples in AT/RT and medulloblastoma correlated with survival differences. In 5 patients with AT/RT, plasma osteopontin levels decreased after treatment but increased with relapse. Osteopontin might be a potential marker to aid in identifying AT/RT recurrence.

Adolescent↗

Longitudinal cerebral perfusion decrease in mild alzheimer's disease revealed by SPECT with statistical parametric mapping method.

Fifteen patients with mild Alzheimer's disease received baseline and follow-up technetium-99m hexamethylpropylene amine oxime SPECT examinations paired with neuropsychological assessments, including the Cognitive Ability Screening Instruments (CASI). The differences between baseline and follow-up SPECT images were analyzed by the voxel-based paired t test of the statistical parametric mapping technique. A simple regression analysis was also conducted to analyze the correlation between CASI sub-scores and both sets of SPECT images. In comparison with baseline images, cerebral perfusion at follow-up was significantly reduced in the left superior and middle temporal gyri, right middle and inferior temporal gyri, and right fusiform gyrus. A significant correlation was demonstrated between the list-generating fluency CASI sub-score and perfusion of the left fusiform gyrus. The visual construction sub-score was significantly correlated with perfusion of the right superior and medial frontal gyri.

Aged↗

Estimating the input function non-invasively for FDG-PET quantification with multiple linear regression analysis: simulation and verification with in vivo data.

A novel statistical method, namely Regression-Estimated Input Function (REIF), is proposed in this study for the purpose of non-invasive estimation of the input function for fluorine-18 2-fluoro-2-deoxy- d-glucose positron emission tomography (FDG-PET) quantitative analysis. We collected 44 patients who had undergone a blood sampling procedure during their FDG-PET scans. First, we generated tissue time-activity curves of the grey matter and the whole brain with a segmentation technique for every subject. Summations of different intervals of these two curves were used as a feature vector, which also included the net injection dose. Multiple linear regression analysis was then applied to find the correlation between the input function and the feature vector. After a simulation study with in vivo data, the data of 29 patients were applied to calculate the regression coefficients, which were then used to estimate the input functions of the other 15 subjects. Comparing the estimated input functions with the corresponding real input functions, the averaged error percentages of the area under the curve and the cerebral metabolic rate of glucose (CMRGlc) were 12.13+/-8.85 and 16.60+/-9.61, respectively. Regression analysis of the CMRGlc values derived from the real and estimated input functions revealed a high correlation (r=0.91). No significant difference was found between the real CMRGlc and that derived from our regression-estimated input function (Student's t test, P>0.05). The proposed REIF method demonstrated good abilities for input function and CMRGlc estimation, and represents a reliable replacement for the blood sampling procedures in FDG-PET quantification.

Algorithms↗

Presence of spinocerebellar ataxia type 2 gene mutation in a patient with apparently sporadic Parkinson's disease: clinical implications.

Among 242 patients with apparently sporadic Parkinson's disease, a 70-year-old man with a CAG repeat number of 37 in the SCA2 gene was identified. He has remained responsive to levodopa 14 years after onset and has had no overt signs suggesting cerebellar dysfunction. Although it is not possible to confirm if this patient has a de novo mutation of the SCA2 gene, this genetic defect seems to be contributing to his parkinsonian features and further supports the concept that apparently sporadic, late-onset, levodopa-responsive Parkinson's disease may have multiple causes.

Aged↗

Development and evaluation of MRI based Bayesian image reconstruction methods for PET.

A maximum a posteriori algorithm, which incorporates correlated magnetic resonance images into the processing of positron emission tomography reconstruction with the aim of improving image quality was developed. The line site map from MRI a priori is made up of a modified Markov random field or Canny edge detector with Gaussian smoothing filter. It is used in the MAP algorithm by a weighted line site method. We evaluate and compare the performance of these reconstruction methods. The results show that the Bayesian methods produce reconstructed images with less noise and better spatial resolution than those produced by the maximum likelihood-expectation maximization method.

Algorithms↗

A statistical method for evaluation quality of medical images: a case study in bit discarding and image compression.

Many studies have been performed on quality evaluation for subtle differences in medical images. However, only limited success has been achieved. In this paper, medical images were prior manipulated by denoising, lossy compression and filtering. The Moran statistics is then applied to extract spatial information of images and using Kolmogorov-Smirnov (KS) test to determine whether the manipulated and original images differ significantly. Results show that on average discarding 1-2 bits in T1 and CR images or 2-3 bits in T2 and body CT images are indistinguishable. This method is also applied to a reconstructed MR, body CT image and an electronic SMPTE (Society of Motion Picture and Television Engineer) phantom from lossy image compression software. Compression ratios of 16:1 for a MR image, 8-9:1 for a cropped body CT image, 7:1 and 5:1 for high- and low-resolution regions in electronic phantom is proved undifferentiated from original. The proposed method is useful for complementing the human visual system, to optimize the performance of image compression technique.

Data Interpretation, Statistical↗