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Biomedical subjects

Ren-Shyan Liu

Publications and source records attributed to Ren-Shyan Liu.

At least 37 records · Page 2Linked to original sources

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↗

Statistical parametric mapping of brain SPECT perfusion abnormalities in patients with Alzheimer's disease.

Brain perfusion in 20 patients with mild Alzheimer's disease (AD), 20 patients with moderate AD and 20 control subjects (matched for age, gender and education) were assessed by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO). SPECT images were transformed to a standard size and shape for group comparisons by the voxel-based t test of the statistical parametric mapping techniques. Cerebral hypoperfusion in the left lower parietal area was found in mild AD patients. In moderate AD patients, significant cerebral hypoperfusion was located in bilateral posterior parietotemporal cortices, contiguous anterior occipital lobes, posterior cingulate gyri and, to a lesser extent, in frontal areas.

Aged↗

Selective hypoperfusion of anterior cingulate gyrus in depressed AD patients: a brain SPECT finding by statistical parametric mapping.

This study tests the hypothesis that depression in patients with Alzheimer's disease (AD) is due to a specific pathogenesis rather than a reactive phenomenon. Forty-three AD patients received a psychiatrist's interview, neuropsychological assessments, and a 99mTc-hexamethyl propyleneamine oxime single photon emission computed tomography (HMPAO-SPECT). Analysis by statistical parametric mapping (SPM) showed that the depressed group had selective hypoperfusion in the bilateral anterior and posterior cingulate gyri and precuneus. Using the Hamilton Depression Rating Scale as a parameter, an inverse correlation was found between cerebral perfusion and the severity of depression. The right anterior cingulate gyrus demonstrated a most significant reduction in perfusion. These locations are akin to the imaging findings in patients with primary depression, indicating a specific pathogenesis for depression in AD.

Aged↗

Crossover study of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET in Parkinson's disease patients.

UNLABELLED: 99mTc-TRODAT-1 ([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]) is a potential agent for dopamine transporter (DAT) SPECT, whereas 6-(18)F-fluoro-L-dopa ((18)F-FDOPA) PET has been used for the quantitative assessment of presynaptic nigrostriatal dopaminergic function. The current study investigated the relationship between the 2 imaging modalities in evaluating patients with Parkinson's disease (PD). METHODS: Twenty patients in whom PD was diagnosed by generally accepted criteria were recruited. In addition to visual inspection, specific uptake ratios (SURs) of (99m)Tc-TRODAT-1 in the striatum and putamen were measured bilaterally. For PET, all patients received 100 mg of carbidopa 90 min before (18)F-FDOPA (300 MBq) injection. Images were acquired between 120 and 150 min after injection, using a whole-body PET scanner with settings identical to those for the SPECT studies. The SURs for PET were calculated similarly to those for SPECT. Individual SURs of the striatum or putamen from SPECT were correlated with the corresponding PET values using linear regression. RESULTS: A consistent image pattern between SPECT and PET was achieved by visual inspection except for 3 cases. In 1 case (a patient with Hoehn and Yahr Scale I PD), the SPECT images were more compatible with the patient's clinical findings whereas PET showed nearly normal uptake. In the other 2 cases (both patients with Hoehn and Yahr Scale II PD), PET correlated better with the clinical findings. The caudate and putamen nuclei were more discernable on PET. An acceptable correlation of SUR, however, was found between SPECT and PET in both the striatum and the putamen (P < 0.01 for both). CONCLUSION: The comparability of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET suggests that (99m)Tc-TRODAT-1 SPECT may provide a reliable alternative to (18)F-FDOPA PET in the evaluation of clinical PD patients.

Aged↗

Clinical, 18F-dopa PET, and genetic analysis of an ethnic Chinese kindred with early-onset parkinsonism and parkin gene mutations.

We report on clinical (18)F-labeled 6-fluorodopa ((18)F-dopa) positron emission tomography (PET) and molecular genetic analyses of an ethnic Chinese family in which three siblings presented with early-onset Parkinson's disease. As described in some parkin patients, neither sleep benefit nor diurnal fluctuation was noted. Interestingly, depression, anxiety, and obsessive-compulsive disorders were manifest. The (18)F-dopa PET scans showed bilateral presynaptic dopaminergic dysfunction without marked lateralization. Molecular genetic analysis showed identical chromosome 6 haplotypes inherited by affected subjects, with alternate allelic deletions of parkin exons 3 and 4. Furthermore, mRNA analyses identified aberrantly spliced parkin transcripts, suggesting that unusual parkin protein isoforms may be expressed in the brain and retain some function.

Adult↗

Effect of 1-week losartan administration on bile duct-ligated cirrhotic rats with portal hypertension.

BACKGROUND/AIMS: Nitric oxide and angiotensin play important roles in the pathogenesis of the hemodynamic derangement in cirrhosis and portal hypertension. The hemodynamic effects of losartan, an angiotensin II type 1 receptor antagonist, in cirrhotic patients with portal hypertension are conflicting. This study was undertaken to explore the possible mechanism of action of losartan on portal hypertension in cirrhotic rats produced by bile duct ligation (CBL). METHODS: Three weeks after surgery, CBL and sham-operated rats randomly received vehicle or losartan (3 mg/kg per 12 h by gavage) for 1 week. Hemodynamic values, hormone levels, and aortic eNOS protein expression were measured after drug administration. RESULTS: In CBL rats, 1-week losartan treatment decreased portal pressure and ameliorated hyperdynamic circulation associated with a blunted vascular response to N(omega)-nitro-L-arginine methyl ester infusion. The hematocrit increased and the plasma volume, aldosterone, plasma renin activity, norepinephrine, and nitrate and nitrite levels decreased. The eNOS protein expression was reduced in CBL rats receiving losartan compared with those receiving vehicle. CONCLUSIONS: One-week losartan treatment in CBL rats decreased portal pressure and ameliorated hyperdynamic circulation. In addition to the suppression of renin-angiotensin axis, the reduced aortic eNOS protein expression may play a partial role for the mechanism of action of losartan in CBL rats.

Angiotensin II↗

Health examination and chromosome aberration analysis of residents living in 60Co-contaminated rebar buildings.

PURPOSE: To elucidate the results of health examination and chromosome aberration analysis of residents living in (60)Co-contaminated rebar buildings. MATERIAL AND METHODS: Medical surveillance including peripheral blood analysis, urine analysis, chest X-ray, blood biochemical analysis, electrocardiography, thyroid function test and physical examination was performed on 189 residents within 6 months after disclosure of radiation exposure. The annual dose for this group of residents varied from 2 to 95 mSv year(-1) (mean+/-1 SD = 18+/-21 mSv year(-1)) above the background exposure of the Taiwanese population. For chromosome analysis, 500-671 lymphocytes were scored for 136 residents, and the numbers of dicentrics and rings were counted and analysed. RESULTS: Medical surveillance showed that the most frequent abnormalities were elevation of the erythrocyte sedimentation rate occurring in 14.8% of those examined. Reduction of the negative charge on erthrocytes by ionizing radiation may cause an elevation of erythrocyte sedimentation rate. Statistical analysis of chromosome aberration data showed that the mean dicentric frequency for radiation-contaminated building residents (0.69+/-0.93 SD) was significantly higher than those for controls (0.33+/-0.49) (p <0.01). CONCLUSIONS: No radiation effects were found in the preliminary health examination. However, lymphocyte chromosome analysis of the radiation-contaminated building residents showed that prolonged low-dose-rate gamma exposure induced cytogenetic changes in humans.

Adolescent↗