Publications by authors named "Ming-Huang Lin"

20 Publications

  • Page 1 of 1

Hypoperfusion of the infrapatellar fat pad and its relationship to MRI T2* relaxation time changes in a 5/6 nephrectomy model.

Sci Rep 2021 May 11;11(1):9924. Epub 2021 May 11.

Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, No.161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei, 11490, Taiwan.

The purpose of present study was to longitudinally investigate the alterations in infrapatellar fat pad (IPFP) vascularity in 5/6 nephrectomized rats by using dynamic contrast enhanced (DCE) MRI and IPFP degeneration by using MRI T2* relaxation time. Twelve male Sprague-Dawley rats were assigned to a control group and a 5/6 nephrectomy CKD group. The right knees of all rats were longitudinally scanned by 4.7 T MRI, and serial changes in the IPFP were assessed at 0, 8, 16, 30, and 44 weeks by DCE-MRI (parameters A, k and k) and MRI T2* mapping. After MRI measurements, knee specimens were obtained and evaluated histologically. The CKD group had IPFPs with lower blood volume A and lower permeability k values from 16 weeks (p < 0.05), lower venous washout k value from 30 weeks (p < 0.001), and significantly higher T2* values reflecting adipocyte degeneration beginning at 16 weeks (p < 0.05). The histopathological results confirmed the MRI findings. Hypoperfusion and adipocytes degeneration related to CKD were demonstrated in a rodent 5/6 nephrectomy model. DCE parameters and MRI T2* can serve as imaging biomarkers of fat pad degeneration during CKD progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-89336-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113578PMC
May 2021

pH Mapping of Skeletal Muscle by Chemical Exchange Saturation Transfer (CEST) Imaging.

Cells 2020 12 4;9(12). Epub 2020 Dec 4.

Biomedical Translation Research Center, Academia Sinica, Taipei 115, Taiwan.

Magnetic resonance imaging (MRI) is extensively used in clinical and basic biomedical research. However, MRI detection of pH changes still poses a technical challenge. Chemical exchange saturation transfer (CEST) imaging is a possible solution to this problem. Using saturation transfer, alterations in the exchange rates between the solute and water protons because of small pH changes can be detected with greater sensitivity. In this study, we examined a fatigued skeletal muscle model in electrically stimulated mice. The measured CEST signal ratio was between 1.96 ppm and 2.6 ppm in the z-spectrum, and this was associated with pH values based on the ratio between the creatine (Cr) and the phosphocreatine (PCr). The CEST results demonstrated a significant contrast change at the electrical stimulation site. Moreover, the pH value was observed to decrease from 7.23 to 7.15 within 20 h after electrical stimulation. This pH decrease was verified by P magnetic resonance spectroscopy and behavioral tests, which showed a consistent variation over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells9122610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762073PMC
December 2020

Effect of Renin-Angiotensin-Aldosterone System Blockade on Long-Term Outcomes in Postacute Kidney Injury Patients With Hypertension.

Crit Care Med 2020 12;48(12):e1185-e1193

Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

Objectives: Renal replacement therapy-requiring acute kidney injury frequently occurs in ICUs, which require evidence-based medical attention. However, in the postacute kidney injury patient population, the evidence regarding effective therapies to improve patient outcomes is lacking. Therefore, we aimed to examine whether the renin-angiotensin-aldosterone system blockade is effective in improving renal outcomes in postacute kidney injury patients who experienced temporary renal replacement therapy and have hypertension.

Design: A retrospective cohort study.

Setting: A nationwide database in Taiwan.

Patients: From January 1, 2000, to December 31, 2013, we identified 8,558 acute kidney injury patients with hypertension in the national registry database. All these patients experienced an acute kidney injury episode, which required temporary renal replacement therapy for at least once.

Interventions: Users (n = 3,885) and nonusers (n = 4,673) of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers.

Measurements And Main Results: We used Cox proportional hazards regression models to analyze hazard ratios for the commencement of end-stage renal disease and all-cause mortality for angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users (n = 3,885) and nonusers (n = 4,673).In a median follow-up of 4.3 years, 5,880 patients (68.7%) required long-term dialysis, and 4,841 patients (56.6%) died. Compared with postacute kidney injury patients who did not use angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users are marginally less likely to progress to end-stage renal disease (adjusted hazard ratio 0.95; 95% CI 0.90-1.01; p = 0.06) and significantly less likely to suffer from all-cause mortality (adjusted hazard ratio 0.93; 95% CI 0.87-0.98; p = 0.011).

Conclusions: In patients who experienced renal replacement therapy-requiring acute kidney injury and have hypertension, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use is associated with better survival outcomes compared with nonuser.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004588DOI Listing
December 2020

Cancer and mTOR inhibitors in kidney transplantation recipients.

PeerJ 2018 8;6:e5864. Epub 2018 Nov 8.

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Background: Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known.

Methods: In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014.

Results: Patients were divided into two groups: mTOR inhibitors users (study group, = 828) and mTOR inhibitors non-users (control group, = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60-1.09], = 0.16) and risk of death (HR 1.14, 95% CI [0.82-1.60], = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups.

Discussion: We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.5864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237112PMC
November 2018

Association of Anemia and Iron Parameters With Mortality Among Patients Undergoing Prevalent Hemodialysis in Taiwan: The AIM - HD Study.

J Am Heart Assoc 2018 08;7(15):e009206

3 Division of Nephrology Department of Medicine Taipei Veterans General Hospital Taipei Taiwan.

Background The Taiwan Health Insurance Bureau has conducted a bundled payment system for hemodialysis reimbursement since 1995. The maximum dose of erythropoiesis-stimulating agents allowed by insurance is capped at 20 000 U of epoetin or 100 μg of darbepoetin alfa per month. Nephrologists have avoided the use of high dosages of erythropoiesis-stimulating agents to achieve a hemoglobin level of 10 to 11 g/dL by iron supplementation. The clinical impact of these policies on patients' outcomes is unknown. The authors aimed to assess the AIM-HD (Association of Anemia, Iron parameters, and Mortality among the prevalent Hemodialysis patients) Study in Taiwan. Methods and Results The AIM-HD study was conducted based on the Taiwan Renal Registry Data System. From 2001 to 2008, the authors enrolled 42 230 patients undergoing hemodialysis who were older than 20 years and had received hemodialysis for more than 12 months. Patient follow-ups occurred until death or December 31, 2008. During a study period of 8 years, 12 653 (30.0%) patients died. After multivariate adjustment, the authors found that a hemoglobin level <10 g/dL was significantly associated with higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level between 300 and 800 ng/mL and transferrin saturation value between 30% and 50% were associated with the lowest all-cause mortality. Conclusions The authors recommend avoiding a low hemoglobin level and maintaining serum ferritin between 300 and 800 ng/mL and transferrin saturation between 30% and 50%, which were associated with lower risks of all-cause mortality among patients undergoing hemodialysis receiving the restricted erythropoiesis-stimulating agent doses but prompt intravenous iron supplementation in Taiwan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.118.009206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201445PMC
August 2018

Dipyridamole decreases dialysis risk and improves survival in patients with pre-dialysis advanced chronic kidney disease.

Oncotarget 2018 Jan 3;9(4):5368-5377. Epub 2017 Aug 3.

Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Introduction: Dipyridamole decreases proteinuria and improves renal function progression in patients with glomerular disease through its inhibition of platelet activation and enhanced nitric oxide expression. Few studies have evaluated the effects of dipyridamole on renal outcome or survival in CKD stage 5 patients who have not yet received dialysis (CKD 5 ND).

Materials And Methods: A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From January 1, 2000 to June 30, 2009, we enrolled 28,497 patients who had a serum creatinine > 6 mg/dL and a hematocrit < 28% and who were treated with erythropoiesis-stimulating agents (ESAs). All patients were further divided into two groups with or without dipyridamole use within 90 days after starting ESA therapy. Patient followed-up took place until dialysis, death before initiation of dialysis or December 31, 2009. The primary outcomes were long-term dialysis and death before initiating dialysis.

Results: The dipyridamole users and nonusers groups included 7,746 and 20,751 patients, respectively. We found that 20,152 patients (70.7%) required long-term dialysis and 5,697 patients (20.0%) died before a progression to end-stage renal disease required dialysis. After propensity score-matching, dipyridamole users were associated with lower risks for long-term dialysis (adjusted HR, 0.96; 95% CI, 0.93-0.99) and death (adjusted HR, 0.91; 95% CI, 0.85-0.97) compared with nonusers.

Conclusions: Dipyridamole exhibited a protective effect in reducing the risk for long-term dialysis and death among CKD 5 ND patients. Randomized studies are needed to validate this association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.19850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797055PMC
January 2018

Knee subchondral bone perfusion and its relationship to marrow fat and trabeculation on multi-parametric MRI and micro-CT in experimental CKD.

Sci Rep 2017 06 8;7(1):3073. Epub 2017 Jun 8.

Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

The pathogenesis of chronic kidney disease (CKD) is multifactorial. In the progression of CKD arthropathy, arteriosclerosis may alter the knee subchondral bone marrow by altering blood flow through the bone vasculature. Herein, multi-parametric MRI assessment, including dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), magnetic resonance spectroscopy (MRS), MRI T2*, contrast enhanced MR angiography (CE-MRA), and micro-CT were applied in a rodent nephrectomy model to: 1) investigate the blood perfusion of subchondral bone marrow and its relationship to fat water content and trabeculation pattern in CKD and 2) demonstrate the feasibility of using multi-parametric MRI parameters as imaging biomarkers to evaluate the disease's progression. Two groups of rats in our study underwent either 1) no intervention or 2) 5/6 nephrectomy. We found that in the CKD group, perfusion amplitude A and elimination constant k values were significantly decreased, and vascular permeability k was significantly increased. MRS showed that fat fraction (FF) was significantly lower, water fraction (WF) was significantly higher in the CKD group. Micro-CT showed a significant loss of trabecular bone. Knee subchondral bone marrow perfusion deficiency in experimental CKD may be associated with decreased fat content, increased water content, and sparse trabeculation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-03059-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465086PMC
June 2017

Lung Cancer-Targeting Peptides with Multi-subtype Indication for Combinational Drug Delivery and Molecular Imaging.

Theranostics 2017 10;7(6):1612-1632. Epub 2017 Apr 10.

Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.

Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (LCC) or small cell lung cancer (SCLC). Therefore, we aimed to identify targeting peptides with diagnostic and therapeutic utility that possess broad subtype specificity for SCLC and non-small cell lung cancer (NSCLC). We performed phage display biopanning of H460 LCC cells to select broad-spectrum lung cancer-binding peptides, since LCC has recently been categorized as an undifferentiated tumor type within other histological subcategories of lung cancer. Three targeting phages (HPC1, HPC2, and HPC4) and their respective displayed peptides (HSP1, HSP2, and HSP4) were able to bind to both SCLC and NSCLC cell lines, as well as clinical specimens, but not to normal pneumonic tissues. optical imaging of phage homing and magnetic resonance imaging (MRI) of peptide-SPIONs revealed that HSP1 was the most favorable probe for multimodal molecular imaging. Using HSP1-SPION, the T2-weighted MR signal of H460 xenografts was decreased up to 42%. In contrast to the tight binding of HSP1 to cancer cell surfaces, HSP4 was preferentially endocytosed and intracellular drug delivery was thereby effected, significantly improving the therapeutic index of liposomal drug . Liposomal doxorubicin (LD) conjugated to HSP1, HSP2, or HSP4 had significantly greater therapeutic efficacy than non-targeting liposomal drugs in NSCLC (H460 and H1993) animal models. Combined therapy with an HSP4-conjugated stable formulation of liposomal vinorelbine (sLV) further improved median overall survival (131 vs. 84 days; = 0.0248), even in aggressive A549 orthotopic models. Overall, these peptides have the potential to guide a wide variety of tailored theranostic agents for targeting therapeutics, non-invasive imaging, or clinical detection of SCLC and NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.17573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436516PMC
February 2018

Targeted Superparamagnetic Iron Oxide Nanoparticles for In Vivo Magnetic Resonance Imaging of T-Cells in Rheumatoid Arthritis.

Mol Imaging Biol 2017 04;19(2):233-244

Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Road, Nangkang, Taipei, 11529, Taiwan.

Purpose: The purpose of the study is to develop a targeted nanoparticle platform for T cell labeling and tracking in vivo.

Procedures: Through carboxylation of the polyethylene glycol (PEG) surface of SPION, carboxylated-PEG-SPION (IOPC) was generated as a precursor for further conjugation with the targeting probe. The IOPC could readily cross-link with a variety of amide-containing molecules by exploiting the reaction between 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide and N-hydroxysuccinimide. The subsequent conjugation of monoclonal anti-CD3 antibody with IOPC made it possible to construct a magnetic resonance imaging (MRI) contrast agente (CA) that targets T cells, named IOPC-CD3.

Results: IOPC-CD3 was found to have high transverse relaxivity, good targeting selectivity, and good safety profile in vitro. The utility of this newly synthesized CA was explored in an in vivo rodent collagen-induced arthritis (CIA) model of rheumatoid arthritis. Serial MRI experiments revealed a selective decrease in the signal-to-noise ratio of the femoral growth plates of CIA rats infused with IOPC-CD3, with this finding being consistent with immunohistochemical results showing the accumulation of T cells and iron oxide nanoparticles in the corresponding region.

Conclusions: Together with the abovementioned desirable features, these results indicate that IOPC-CD3 offers a promising prospect for a wide range of cellular and molecular MRI applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11307-016-1001-6DOI Listing
April 2017

Change in T2* relaxation time of Hoffa fat pad correlates with histologic change in a rat anterior cruciate ligament transection model.

J Orthop Res 2015 Sep 18;33(9):1348-55. Epub 2015 May 18.

Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

The Hoffa fat pad (infrapatellar fat pad) is a source of post-traumatic anterior knee pain, and Hoffa disease is a syndrome leading to chronic inflammation of the fat pad. Herein, change in T2* relaxation time of the fat pad was measured in a rodent anterior cruciate ligament transection (ACLX) model in order to (i) examine the causal relationship of anterior cruciate ligament (ACL) deficiency and Hoffa disease and (ii) demonstrate the feasibility of using T2* as an imaging biomarker to monitor disease progression. Three groups of male Sprague Dawley rats (n = 6 each group), received either (i) no intervention; (ii) sham surgery at the right knee; or (iii) right ACLX. T2* relaxation time was measured and histology was examined in the Hoffa fat pad after surgery. At 13 and 18 weeks after surgery, T2* values were significantly higher in the right fat pad than the left (p < 0.001) and significantly higher in the ACLX group than the control and sham groups (p < 0.001). Histology showed fibrosis and degeneration of adipocytes in the right knees of the ACLX group. We conclude that ACL deficiency and Hoffa disease are causally related and that MRI T2* value can serve as an imaging biomarker of Hoffa disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.22914DOI Listing
September 2015

Androgenic alopecia is associated with less dietary soy, lower [corrected] blood vanadium and rs1160312 1 polymorphism in Taiwanese communities.

PLoS One 2013 30;8(12):e79789. Epub 2013 Dec 30.

Department of Epidemiology, School of Public Health, National Defense Medical Center, Taipei, Taiwan ; Division of Environmental Health and Occupational Medicine, National Health Research Institutes, MiaoLi, Taiwan.

Background: Although the genetic basis of androgenic alopecia has been clearly established, little is known about its non-genetic causes, such as environmental and lifestyle factors.

Objective: This study investigated blood and urine heavy metals concentrations, environmental exposure factors, personal behaviors, dietary intakes and the genotypes of related susceptibility genes in patients with androgenic alopecia (AGA).

Design: Age, AGA level, residence area, work hours, sleep patterns, cigarette usage, alcohol consumption, betel nut usage, hair treatments, eating habits, body heavy metals concentrations and rs1998076, rs913063, rs1160312 and rs201571 SNP genotype data were collected from 354 men. Logistic regression analysis was performed to examine whether any of the factors displayed odds ratios (ORs) indicating association with moderate to severe AGA (≥ IV). Subsequently, Hosmer-Lemeshow, Nagelkerke R(2) and accuracy tests were conducted to help establish an optimal model.

Results: Moderate to severe AGA was associated with the AA genotype of rs1160312 (22.50, 95% CI 3.99-126.83), blood vanadium concentration (0.02, 95% CI 0.01-0.04), and regular consumption of soy bean drinks (0.23, 95% CI 0.06-0.85), after adjustment for age. The results were corroborated by the Hosmer-Lemeshow test (P = 0.73), Nagelkerke R(2) (0.59), accuracy test (0.816) and area under the curve (AUC; 0.90, 0.847-0.951) analysis.

Conclusions: Blood vanadium and frequent soy bean drink consumption may provide protect effects against AGA. Accordingly, blood vanadium concentrations, the AA genotype of rs1160312 and frequent consumption of soy bean drinks are associated with AGA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079789PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875420PMC
September 2014

Sequential change in T2* values of cartilage, meniscus, and subchondral bone marrow in a rat model of knee osteoarthritis.

PLoS One 2013 18;8(10):e76658. Epub 2013 Oct 18.

Imaging Research Center, Taipei Medical University, Taipei, Taiwan ; Department of Medical Imaging, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.

Background: There is an emerging interest in using magnetic resonance imaging (MRI) T2* measurement for the evaluation of degenerative cartilage in osteoarthritis (OA). However, relatively few studies have addressed OA-related changes in adjacent knee structures. This study used MRI T2* measurement to investigate sequential changes in knee cartilage, meniscus, and subchondral bone marrow in a rat OA model induced by anterior cruciate ligament transection (ACLX).

Materials And Methods: Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group). Group 1 was the normal control group. Groups 2 and 3 received ACLX and sham-ACLX, respectively, of the right knee. T2* values were measured in the knee cartilage, the meniscus, and femoral subchondral bone marrow of all rats at 0, 4, 13, and 18 weeks after surgery.

Results: Cartilage T2* values were significantly higher at 4, 13, and 18 weeks postoperatively in rats of the ACLX group than in rats of the control and sham groups (p<0.001). In the ACLX group (compared to the sham and control groups), T2* values increased significantly first in the posterior horn of the medial meniscus at 4 weeks (p = 0.001), then in the anterior horn of the medial meniscus at 13 weeks (p<0.001), and began to increase significantly in the femoral subchondral bone marrow at 13 weeks (p = 0.043).

Conclusion: Quantitative MR T2* measurements of OA-related tissues are feasible. Sequential change in T2* over time in cartilage, meniscus, and subchondral bone marrow were documented. This information could be potentially useful for in vivo monitoring of disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076658PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799892PMC
August 2014

Neurovascular abnormalities in humans and mice with Huntington's disease.

Exp Neurol 2013 Dec 10;250:20-30. Epub 2013 Sep 10.

Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Functional and Micro-Magnetic Resonance Imaging Core Facility, Academia Sinica, Taipei 11529, Taiwan.

Cerebral microvascular aberrations have recently become recognized as a source of pathologies in neurodegenerative disorders, but this concept has not been fully examined with respect to Huntington's disease (HD). A novel in vivo technique, three-dimensional microscopic magnetic resonance angiography (μMRA), allows visualization of the neurovascular system in exquisite detail and provides quantitative structural and functional information. This technique was applied in the present study, in parallel with immunohistological analysis and behavioral assessment, to a well-characterized mouse model of HD (R6/2). Dynamic contrast-enhanced magnetic resonance imaging was used to examine the integrity of the blood-brain barrier (BBB). The μMRA findings revealed an increase in vessel volume fraction and cerebral blood volume in the brains of R6/2 mice at the age of 7weeks when no apparent motor dysfunction was detected. Collagen IV immunostaining disclosed an enhancement in vessel density, but not in vessel size of the microvasculature in the mouse HD brain. This change in neurovasculature worsened with disease progression, with no apparent disruption in the BBB. Most importantly, immunohistological assays of human tissues revealed that the vessel densities in the cortex, caudate/putamen, and substantia nigra were higher in HD patients than in non-HD human subjects. The early onset of such vessel aberrations could be used as a biomarker for the early diagnosis of HD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.expneurol.2013.08.019DOI Listing
December 2013

Visualization of rodent brain tumor angiogenesis and effects of antiangiogenic treatment using 3D ΔR2-μMRA.

Angiogenesis 2013 Oct 5;16(4):785-93. Epub 2013 Jun 5.

Institute of Biomedical Sciences, Academia Sinica, N123, 128 Sec. 2, Academia Road, Nankang, Taipei, 11529, Taiwan, ROC.

Understanding of structural and functional characteristics of the vascular microenvironment in gliomas and the impact of antiangiogenic treatments is essential for developing better therapeutic strategies. Although a number of methods exist in which this process can be studied experimentally, no single noninvasive test has the capacity to provide information concerning both microvascular function and morphology. The purpose of present study is to demonstrate the feasibility of using a novel three-dimensional ΔR2-based microscopic magnetic resonance angiography (3D ΔR2-μMRA) technique for longitudinal imaging of tumor angiogenesis and monitoring the effects of antiangiogenic treatment in rodent brain tumor models. Using 3D ΔR2-μMRA, a generally consistent early pattern of vascular development in gliomas was revealed, in which a single feeding vessel was visualized first (arteriogenesis), followed by sprouting angiogenesis. Considerable variability of the tumor-associated vasculature was then noted at later stages of tumor evolution. ΔR2-μMRA revealed that anti-vascular endothelial growth factor treatment induced a rapid and significant alteration of the intratumoral angiogenic phenotype. In summary, 3D ΔR2-μMRA enables high-resolution visualization of tumor-associated vessels while simultaneously providing functional information on the tumor microvasculature. It can serve as a useful tool for monitoring both the temporal evolution of tumor angiogenesis and the impact of antiangiogenic therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10456-013-9355-8DOI Listing
October 2013

Manganese-enhanced MRI of rat brain based on slow cerebral delivery of manganese(II) with silica-encapsulated Mn x Fe(1-x) O nanoparticles.

NMR Biomed 2013 Sep 22;26(9):1176-85. Epub 2013 Mar 22.

Department of Chemistry, National Taiwan University, Taipei, Taiwan.

In this work, we report a monodisperse bifunctional nanoparticle system, [email protected] -RITC, as an MRI contrast agent [core, manganese iron oxide (MIO); shell, amorphous silica conjugated with rhodamine B isothiocyanate (RITC)]. It was prepared by thermal decomposition and modified microemulsion methods. The nanoparticles with varying iron to manganese ratios displayed different saturated magnetizations and relaxivities. In vivo MRI of rats injected intravenously with [email protected] nanoparticles exhibited enhancement of the T1 contrast in brain tissue, in particular a time-delayed enhancement in the hippocampus, pituitary gland, striatum and cerebellum. This is attributable to the gradual degradation of [email protected] nanoparticles in the liver, resulting in the slow release of manganese(II) [Mn(II)] into the blood pool and, subsequently, accumulation in the brain tissue. Thus, T1-weighted contrast enhancement was clearly detected in the anatomic structure of the brain as time progressed. In addition, T2*-weighted images of the liver showed a gradual darkening effect. Here, we demonstrate the concept of the slow release of Mn(II) for neuroimaging. This new nanoparticle-based manganese contrast agent allows one simple intravenous injection (rather than multiple infusions) of Mn(II) precursor, and results in delineation of the detailed anatomic neuroarchitecture in MRI; hence, this provides the advantage of the long-term study of neural function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nbm.2932DOI Listing
September 2013

Temporal MRI characterization of gelatin/hyaluronic acid/chondroitin sulfate sponge for cartilage tissue engineering.

J Biomed Mater Res A 2013 Aug 22;101(8):2174-80. Epub 2012 Dec 22.

Functional and Micro-Magnetic Resonance Imaging Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

A tri-copolymer sponge consisting of gelatin, hyaluronic acid, and chondroitin sulfate (GHC) was designed to mimic the cartilage environment in vivo for cartilage regeneration. The present study aimed to temporally characterize the magnetic resonance relaxation time of GHC constructs in vivo in a rodent heterotopic model. GHC sponges with cells (GHCc) or without cells (GHC) implanted in rat leg muscle were monitored using MRI (4.7 T MR scanner) on day 0, 7, 14, and 21 after implantation. The results revealed that the transverse relaxation time (T2) of GHC constructs decreased significantly over time when compared to the T2 of GHCc constructs. However, the longitudinal relaxation time (T1) of GHCc and GHC constructs remained stable. Moreover, hematoxylin and eosin and immunohistochemical staining with antibodies to S100 protein, and types I and II collagen showed that normal morphology, phenotype, and function of chondrocytes were preserved in the GHCc construct. Thus, we concluded that GHC constructs adequately support chondrocyte growth and function. On top of that, T2 may be a useful tool for monitoring cartilage regeneration in GHC constructs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm.a.34522DOI Listing
August 2013

An event-related potential study of semantic style-match judgments of artistic furniture.

Int J Psychophysiol 2011 Nov 3;82(2):188-95. Epub 2011 Sep 3.

Institute of Applied Arts, National Chiao Tung University, Hsinchu City, Taiwan.

This study investigates how semantic networks represent different artistic furniture. Event-related potentials (ERPs) were recorded while participants made style-match judgments for table and chair sets. All of the tables were in the Normal style, whereas the chairs were in the Normal, Minimal, ReadyMade, or Deconstruction styles. The Normal and Minimal chairs had the same rates of "match" responses, which were both higher than the rates for the ReadyMade and Deconstruction chairs. Compared with Normal chairs, the ERPs elicited by both ReadyMade chairs and Deconstruction chairs exhibited reliable N400 effects, which suggests that these two design styles were unlike the Normal design style. However, Minimal chairs evoked ERPs that were similar to the ERPs of Normal chairs. Furthermore, the N400 effects elicited by ReadyMade and Deconstruction chairs showed different scalp distributions. These findings reveal that semantic networks represent different design styles for items of the same category.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpsycho.2011.08.007DOI Listing
November 2011

In vivo cerebromicrovasculatural visualization using 3D DeltaR2-based microscopy of magnetic resonance angiography (3DDeltaR2-mMRA).

Neuroimage 2009 Apr 29;45(3):824-31. Epub 2008 Dec 29.

Interdisciplinary MRI/MRS Lab, Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, ROC.

This study proposed a novel methodology for depicting cerebral small vessels including veins, arterioles, and venules, called 3DDeltaR(2)-mMRA (three-dimensional, steady-state DeltaR(2)-based, and flow-independent microscopic magnetic resonance angiography). The DeltaR(2) map calculated by a fast spin-echo imaging technique before and after the injection of an iron-oxide contrast agent was used to delineate the relative cerebral blood volume, primarily to microvasculature. The proposed 3DDeltaR(2)-mMRA method, which employs 3D reconstruction techniques, can simultaneously provide high-resolution 3D information on the cerebral anatomy, in vivo microvascular architecture, and hemodynamic response, which can be used to evaluate pathological microvascular changes over time in cerebromicrovascular disease. Since spin-echo-based DeltaR(2) imaging was applied, the inflow effects, susceptibility artifacts, and the overestimation of vessel size in brain were reduced. A well-defined three-vessel occlusion model in the rat was performed to evaluate the capability of the proposed method in evaluating alterations to the microvasculature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2008.12.030DOI Listing
April 2009

Dynamic changes in vascular permeability, cerebral blood volume, vascular density, and size after transient focal cerebral ischemia in rats: evaluation with contrast-enhanced magnetic resonance imaging.

J Cereb Blood Flow Metab 2008 Aug 14;28(8):1491-501. Epub 2008 May 14.

Interdisciplinary MRI/MRS Lab, Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, ROC.

Postischemic cerebral blood flow and blood volume changes have been associated with angiogenesis; nevertheless, the spatiotemporal changes in vascular permeability, vascular density, and vessel size have not been investigated. Here we report a prolonged increase in vascular permeability from day 3 to day 21 after ischemia, in particular in the reperfused outer cortical layers and leptomeninges. Increased cerebral blood volume (CBV) was observed from day 3 to day 14, whereas increased blood volume in small vessels, primarily capillaries, was noticed from day 7 to day 14 in the reperfused cortex. An initial decrease in vascular density and a reciprocal increase in vessel size were observed within the reperfused cortex at days 1 and 3 after ischemia. Immunohistological analysis confirmed a similar decrease in microvessel density and an increase in vessel size in vessels with a diameter greater than 30 microm. These large-sized vessels exhibited intense basic fibroblast growth factor and endothelial nitric oxide synthase immunoreactivity, suggesting the growth of collateral vessels. By contrast, a late increase in vascular density was noticed in the reperfused outer cortex at days 14 and 21 after ischemia. Together, these findings suggest that the early phase of CBV increase is likely because of the improvement in collateral circulation, whereas the late phase of CBV increase is attributed to the surge of angiogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/jcbfm.2008.42DOI Listing
August 2008

Merging molecular and anatomical information: a feasibility study on rodents using microPET and MRI.

Nucl Med Commun 2007 Oct;28(10):804-12

Department of Radiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, ROC.

Objective: The use of the micro positron emission tomography (microPET) technique provides a powerful means for molecular imaging on small animals, while its inferior spatial resolution offers insufficient anatomical information which impedes the interpretations of the scans. To improve this limitation, it often relies on a clinical magnetic resonance imaging (MRI) for providing anatomical details. In this study, we designed and developed a new image co-registration platform which contains a stereotactic frame and external fiducial markers for microPET and MRI studies. The image co-registration accuracies were also validated by this new platform using various imaging protocols for microPET and MRI.

Methods: The microPET images were reconstructed by filtered back-projection (FBP) and ordered subset expectation maximization (OSEM) methods. Two MRI pulse sequences, two-dimensional T1-weighted fast spin-echo (FSE) and three-dimensional spoiled gradient recalled (SPGR), were employed in the studies. Two MRI scanning protocols were proposed for small animal imaging: the whole-body high-speed mode and the partial high-resolution mode.

Results: Reconstructed images from two different modalities were integrated by point-to-point registration via the external fiducials. Four inter-modality matched co-registration pairs (FBP-FSE, FBP-SPGR, OSEM-FSE, OSEM-SPGR) were obtained for both the high speed and high resolution modes. Co-registration accuracy was given as the average fiducial registration error (FRE) between the centroids of six markers from the registered images. The overall systemic FREs were about 0.50 mm.

Conclusions: From the inter-modality FRE comparison, MRI imaging with FSE performed better than that with SPGR sequence, due to its higher signal-to-noise ratio and less magnetic susceptibility effects. In the microPET perspective, the OSEM was superior to the FBP, as a result of fewer image artifacts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MNM.0b013e3282d25a0dDOI Listing
October 2007
-->