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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

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↗

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↗

Non-invasive in vivo imaging with radiolabelled FIAU for monitoring cancer gene therapy using herpes simplex virus type 1 thymidine kinase and ganciclovir.

An experimental cancer gene therapy model was employed to develop a non-invasive imaging procedure using radiolabelled 2'-fluoro-2'-deoxy-5-iodo-1-beta- d-arabinofuranosyluracil (FIAU) as an enzyme substrate for monitoring retroviral vector-mediated herpes simplex virus type 1 thymidine kinase gene ( HSV1-tk) transgene expression. Iodine-131 labelled FIAU was prepared by a no-carrier-added (n.c.a.) synthesis process and lyophilised to give "hot kits". The labelling yield was over 95%, with a radiochemical purity of more than 98%. The stability of [(131)I]FIAU in the form of lyophilised powder (the hot kit) was much better than that in the normal saline solution. The shelf life of the final [(131)I]FIAU hot kit product is as long as 4 weeks. Cellular uptake of [(131)I]FIAU after different periods of storage was investigated in vitro with HSV1-tk-retroviral vector transduced NG4TL4-STK and parental non-transduced NG4TL4 murine sarcoma cell lines over an 8-h incubation period. The NG4TL4-STK cells accumulated more radioactivity than NG4TL4 cells in all conditions, and accumulation increased with time up to 8 h. The kinetic profile of the cellular uptake of n.c.a. [(131)I]FIAU formulated from the lyophilised hot kit or from the stock solution was qualitatively similar. For animal model cancer gene therapy studies, FVB/N mice were inoculated subcutaneously with the HSV1-tk(+) and tk(-) sarcoma cells into the flank to produce tumours. Biodistribution studies showed that tumour/blood ratios were 2, 3.5, 8.2 and 386.8 at 1, 4, 8 and 24 h post injection, respectively, for the HSV1-tk(+) tumours, and 0.5, 0.5, 0.7 and 5.4, respectively, for the HSV1-tk(-) tumours. Radiotracer clearance from blood was completed in 24 h and was bi-exponential. A significant difference in radioactivity accumulation was revealed among the HSV1-tk(+) tumours, the tk(-) tumours and other tissues. At 24 h p.i., higher activity retention was observed in HSV1-tk(+) tumours (9.67%+/-3.89%ID/g) than in HSV1-tk(-) tumours (0.48%+/-0.19%ID/g). After seven consecutive daily treatments with the prodrug ganciclovir, planar gamma camera imaging showed HSV1-tk(+) tumour regression at day 4, and complete tumour regression at day 7. These results clearly demonstrate that the simplified n.c.a. synthesis process developed in this study is reliable and that the [(131)I]FIAU product is useful for in vivo monitoring of HSV1-tk gene transfer, expression and gene therapy.

Animals↗

An imaging co-registration system using novel non-invasive and non-radioactive external markers.

We present a system of image co-registration and its validation in phantom and volunteer studies. The system co-registered images via six novel non-invasive and non-radioactive external markers. The fiducial markers were attached with sponge bases on the skin surface of the phantom and the volunteers in a non-collinear and non-coplanar array. The subjects were scanned with a 1.5-T magnetic resonance (MR) imager using 2D spin-echo T1-weighted (SE) and 3D spoiled gradient recalled pulse sequences (SPGR) and with a positron emission tomography (PET) scanner for transmission imaging (TI) and emission imaging (EI). The sponge bases created radiolucent gaps with good contrast between the fiducial markers and skin surface. They made the markers visible with clear edge boundaries on both PET and MR images. The images to be registered were rescaled, interpolated, reformatted and followed by point-to-point registration for coordinate determination and the estimation of geometrical transformation and fiducial registration errors (FREs) via the fiducial markers. The images formed four matched pairs of inter-modality (SE-TI, SPGR-TI, SE-EI and SPGR-EI) and two pairs of intra-modality (SE-SPGR, TI-EI) imaging for direct co-registration. The parameters for direct co-registration of SE-TI and SPRG-TI were subsequently used as a bridge and applied for indirect co-registration of SE with EI (SE-EI(TI)) and SPGR with EI (SPGR-EI(TI)), respectively. The overall FREs of the phantom were, respectively, 1.50 mm for inter-modality and 1.10 mm for intra-modality direct co-registration. Those of volunteers were, respectively, 1.79 mm for inter-modality and 1.21 mm for intra-modality direct co-registration. For indirect co-registration, the overall FREs of the phantom were 2.53 mm (SE-EI(TI)) and 2.28 (SPGR-EI(TI)) mm; those of volunteers were 2.84 mm (SE-EI(TI)) and 2.81 mm (SPGR-EI(TI)). The errors of direct co-registration were smaller than those of indirect co-registration; the errors of phantom studies, MR-EI and SPGR-PET were smaller than those of the volunteer studies, MR-TI and SE-PET, respectively (all P<0.01, paired-difference test). In conclusion, motion artefacts, imaging blurring and spatial resolution of imaging remained the key factors affecting the accuracy of co-registration. High-accuracy indirect co-registration is provided by using non-invasive and non-radioactive external fiducial markers. The errors were less than 3 mm for both phantom and volunteer studies. The system is applicable for imaging co-registration of inter-modality non-dual imaging, inter-modality multi-tracer imaging and intra-modality multiple parameter images in clinical practice.

Brain↗

Infrared spectrometry based 13C-octanoic acid breath test in measuring human solid gastric emptying.

BACKGROUND AND AIMS: Because of the convenience of non-dispersive infrared spectrometry (NDIRS), we attempted to validate the usefulness of NDIRS compared with scintigraphy in human solid gastric emptying (GE) measurement, and tried to establish the normal range of solid GE based on NDIRS. METHODS: Twelve healthy volunteers (three men, nine women) were recruited for simultaneous scintigraphy and 13C-octanoic acid breath test (13C-OABT) studies. Stomach half-emptying time (t1/2) and lag phase (tlag) were the two main GE parameters measured and correlated. The breath samples were analyzed using NDIRS every 10-15 min for a total of 6 h, while scintigraphy was taken minute by minute for the first 30 min, then hourly for 4 h. Another 32 healthy volunteers (19 men, 13 women) received only the 13C-OABT to measure their solid GE. RESULTS: A significant correlation for t1/2 was found between the breath test and scintigraphy (r = 0.85, P = 0.001), while tlag was also positively correlated (r = 0.73, P = 0.007). The reference range of t1/2B based on all 44 subjects was 89.4-185.1 min (135.9 +/- 21.1 min (mean +/- SD)), while the range for tlagB was 37.1-117.8 min (81.9 +/- 17.4 min). No demographic characteristics were found to influence the GE parameters. CONCLUSIONS: 13C-octanoic acid breath test determined by NDIRS is a simple, non-invasive and reliable measurement, which may provide an 'office-based' tool to detect solid GE.

Abdomen↗

Technetium-99m-sestamibi scintimammography to detect breast cancer in patients with paraffinomas or siliconomas after breast augmentation.

As the mechanism of (99)mTc-MIBI scintimammography is different from that of anatomic modalities, the detection of breast cancer should not be affected by prior breast augmentation. The aim of this study was to compare the diagnostic accuracy of (99)mTc-MIBI scintimammography for breast cancer in patients with or without paraffinomas or siliconomas. Twenty-eight women with a history of paraffin or silicone injection into the breasts and 17 without were included. All patients received intravenous injection of 1110 MBq (99)mTc-MIBI and were subsequently examined using high-resolution planar and SPECT imaging 5 minutes after the injection. In the 45 patients with 87 breasts, 21 abnormal breasts were found at scintigraphy. The sensitivity, specificity, and accuracy to detect cancer in these breasts with paraffinomas or siliconomas were 100% (5/5), 92% (46/50), and 93% (51/55), respectively. For the breasts without paraffinomas or siliconomas, the sensitivity, specificity, and accuracy were 92% (11/12), 95% (19/20), and 94% (30/32), respectively, not significantly different (p = 0.51, 0.66, and 0.86, respectively). (99)mTc-MIBI scintimammography is both sensitive and specific for the detection of breast cancer, whether or not paraffinomas or siliconomas are present. The accuracy of scintimammography did not seem to be affected by prior breast augmentation.

Adult↗

Early prediction of response to intravenous iron supplementation by reticulocyte haemoglobin content and high-fluorescence reticulocyte count in haemodialysis patients.

BACKGROUND: Optimal response to recombinant human erythropoietin (rHuEpo) in haemodialysis (HD) patients requires provision of sufficient available iron. However, a balance between iron requirements and supplements remains a challenge in clinical practice. Reticulocyte parameters, i.e. reticulocyte haemoglobin content (CHr) and reticulocytes in a high-fluorescence intensity region (HFR), have been shown to be accurate predictors of iron-deficient erythropoiesis as compared with traditional markers. Therefore, the aim of this study was to appraise the diagnostic power of these two parameters in the early prediction of response to intravenous iron (IVFE) medications in HD patients receiving rHuEpo. METHODS: Sixty-five HD patients with a serum ferritin level of <500 microg/l and on rHuEpo therapy for >6 months were enrolled for IVFE supplementation (100 mg iron saccharate three times a week for 4 weeks, then 100 mg every 2 weeks for 5 months). Haemoglobin, haematocrit, serum ferritin, transferrin saturation, reticulocyte count, percentage of hypochromic red cells, CHr and HFR were measured before and following iron supplementation. Response was defined as a rise in haematocrit of >3% and/or a reduction in rHuEpo dose of >30% over the baseline values at the end of the study. RESULTS: Forty-two patients had a dramatic response to IVFE therapy with a 13.5% increase in mean haematocrit and a 38% reduction in rHuEpo dose at the end of the study (P<0.001). This paralleled a statistically significant rise in CHr and HFR (P<0.001). Univariate analyses showed that ferritin (P<0.010) and CHr (P<0.001) at baseline, changes in CHr (DeltaCHr(2W), P<0.001) and HFR (DeltaHFR(2W), P<0.010) at 2 weeks, as well as changes in CHr (DeltaCHr(4W), P<0.001) and HFR (DeltaHFR(4W), P<0.001) at 4 weeks, strongly correlated with response to IVFE supplementation. Stepwise discriminant analysis disclosed that DeltaCHr(4W) in conjunction with DeltaHFR(4W) exhibited an r(2) value of 0.531 (P<0.001) to predict response to IVFE therapy. Analyses by receiver operating characteristic curves and logistic regression further revealed that DeltaCHr(4W) at a cut-off value of >1.2 pg and DeltaHFR(4W) of >500/microl were more specific to the status of iron-deficient erythropoiesis following IVFE medications. Combined use of the two cut-off values allowed for the highest accuracy in the early prediction of the response to IVFE therapy, with a sensitivity of 96% and a specificity of 100%. CONCLUSIONS: Our study shows that changes in CHr and HFR at either 2 or 4 weeks are superior to the conventional erythrocyte and iron metabolism indices and may serve as reliable parameters to detect iron-deficient erythropoiesis in HD patients undergoing rHuEpo therapy. During aggressive IVFE treatment, early identification of non-responsiveness and subsequent discontinuation of treatment can avoid the inadvertent iron-related toxicity due to over-treatment.

Anemia, Iron-Deficiency↗