Biomedical subjects

Hai-Ling Margaret Cheng

Publications and source records attributed to Hai-Ling Margaret Cheng.

7 recordsLinked to original sources

PubMed2007

Quantifying angiogenesis in VEGF-enhanced tissue-engineered bladder constructs by dynamic contrast-enhanced MRI using contrast agents of different molecular weights.

PURPOSE: To compare Gadomer, a macromolecular magnetic resonance (MR) contrast agent, and gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) for quantifying angiogenesis in tissue-engineered bladder constructs. MATERIALS AND METHODS: Constructs enhanced with vascular endothelial growth factor (VEGF) were grafted onto the bladder of 12 rabbits (N= 3/VEGF, VEGF = 0,10,15,20 ng/g tissue). After eight days dynamic contrast-enhanced MRI (DCE-MRI) was performed in each animal using Gadomer and Gd-DTPA, separated by a one-hour interval. DCE-MRI parameters were calculated from two-compartment pharmacokinetics (plasma volume fraction, v(p); transfer constant, K(trans)) and model-free analysis, area under the concentration-time curve (AUC). Histology assessment of microvessel density (MVD) and Evans blue permeability were compared to DCE-MRI. RESULTS: MVD was elevated (P < 0.05) at the highest VEGF but not among lower levels; permeability differences were absent. Contrast enhancement increased with VEGF and was better resolved with Gadomer than Gd-DTPA. Gadomer was the better assay for estimating plasma volume: v(p) provided the best distinction (P < 0.005), but both v(p) and AUC were correlated to MVD. With Gd-DTPA, only AUC distinguished MVD differences (P< 0.05). Changes in K(trans) were insignificant. CONCLUSION: Macromolecular contrast agents are valuable for monitoring angiogenesis in tissue-engineered bladder grafts. Compared to Gd-DTPA, Gadomer provides more accurate and precise quantification of microvessel function, and is better suited to pharmacokinetic analysis for accurate physiological quantification.

Analysis of Variance↗

PubMed2006

Dynamic contrast-enhanced MRI to quantify VEGF-enhanced tissue-engineered bladder graft neovascularization: pilot study.

Tissue engineered organs require an immediately perfused vascular tree. Currently, neovascularization assessment requires animal sacrifice and graft harvest. In this pilot study we assess whether neovascularization of an engineered urinary bladder construct is enhanced with vascular-derived endothelial growth factor (VEGF) and assessable non-invasively with dynamic contrast-enhanced MRI (DCE-MRI). Rabbit bladder acellular matrix was hybridized with hyaluronic acid (ACM-HA), fortified with one of three concentrations (0 ng, 10 ng, or 20 ng per gram of tissue) of vascular-derived endothelial growth factor (VEGF), and grafted onto bladders in nine rabbits (3 per VEGF concentration). At 1, 2 and 3 weeks, one rabbit from each VEGF group underwent DCE-MRI and graft harvest. Microvasculature was quantified with scrial optical transverse sectioning of CD31 stained whole mounts using PCl software. Masson trichrome and H&E staining were used to assess cellular proliferation and fibrosis. There was a significant difference in mean microvascular area (MVA) between the 10 and 20 ng VEGF groups (230187 vs 477894 microm2, P=0.014) but not between the 0 and 10 ng groups (210497 microm2, P=0.21). Gadolinium uptake increased with MVA and correlated with it on linear regression analysis (Pearson's correlation coefficient r=0.71). At three weeks, stromal cellularity was greatest, and fibrosis was least, in the high VEGF group. This preliminary work demonstrates improved neovascularization of bladder constructs with VEGF fortification of ACM-HA and the feasibility of MRI as a non-invasive method to assume angiogenesis in tissue engineered constructs.

Animals↗

PubMed2006

Rapid high-resolution T(1) mapping by variable flip angles: accurate and precise measurements in the presence of radiofrequency field inhomogeneity.

Rapid 3D mapping of T(1) relaxation times is valuable in diverse clinical applications. Recently, the variable flip angle (VFA) spoiled gradient recalled echo approach was shown to be a practical alternative to conventional methods, providing better precision and speed. However, the method is known to be sensitive to transmit field (B(1) (+)) inhomogeneity and can result in significant systematic errors in T(1) estimates, especially at high field strengths. The main challenge is to improve the accuracy of the VFA approach without sacrificing speed. In this article, the VFA method was optimized for both accuracy and precision by considering the influence of imperfect transmit fields, noise bias, and selection of flip angles. An analytic solution was developed for systematic B(1) (+)-induced T(1) errors and allows simple correction of T(1) measurements acquired with any imaging parameters. A noise threshold was also identified and provided a guideline for avoiding T(1) biases. Finally, it was shown that three flip angles were the most efficient for maintaining accuracy and high precision over large ranges of T(1). A rapid B(1) (+) mapping sequence was employed in all phantom experiments and high-field in vivo brain scans. Experimental results confirmed the theory and validated the accuracy of the proposed method.

Brain↗

PubMed2005

Dynamic Gd-DTPA enhanced MRI as a surrogate marker of angiogenesis in tissue-engineered bladder constructs: a feasibility study in rabbits.

PURPOSE: To evaluate the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess angiogenesis in tissue-engineered bladder constructs in a blinded animal study, and compare different analysis approaches and their correlation with microvessel density (MVD). MATERIALS AND METHODS: Constructs fortified with vascular endothelial growth factor (VEGF) for enhanced vascularity were grafted onto the bladder in nine rabbits. DCE-MRI of Gd-DTPA uptake was performed and analyzed using Tofts' model, the area under the concentration time curve (AUC), and the uptake slope. DCE-MRI parameters were compared to MVD determined with CD31 immunohistochemistry. RESULTS: Significantly increased MVD was found in the high VEGF group (20 ng/g of tissue) but not at low VEGF (10 ng/g) (2.3x increase, P = 0.035 vs. 1.1x over control). Enhanced permeability at low VEGF was suggested by elevated K(trans), but overall correlation to MVD was poor. Significant correlation to MVD was obtained with AUC(8min) (r = 0.705, P = 0.034). Furthermore, AUC(8min) provided the most precise discrimination between different VEGF preparations and was the only parameter to show a significant increase (P = 0.0058) consistent with MVD changes at high VEGF. CONCLUSION: Findings support DCE-MRI for evaluating angiogenesis in bladder constructs and suggest vessel changes other than density. Future studies should incorporate larger contrast agents and permeability assessment to devise an optimal DCE-MRI strategy.

Animals↗

PubMed2004

Usefulness of contrast kinetics for predicting and monitoring tissue changes in muscle following thermal therapy in long survival studies.

PURPOSE: To investigate Gd-DTPA kinetics as indicators of subacute and subchronic histopathological changes following focused ultrasound (FUS) thermal therapy for improved evaluation. MATERIALS AND METHODS: A total of 18 FUS lesions were created in the thigh muscle of five rabbits under magnetic resonance (MR) guidance at 1.5 Tesla. The rabbits were killed at different times: 40 hours, three days, and seven days. All lesions were analyzed histologically. An analysis of the uptake kinetics of Gd-DTPA, injected within two hours postheating and before sacrifice, was performed. The resulting kinetic maps, permeability (K(trans)) and leakage space (v(e)), were correlated to T(2)-weighted MR and histology. RESULTS: Images of K(trans) and v(e) better differentiate subacute and subchronic changes not visible on conventional MR in the days following therapy and are consistent with the histopathology observed. In particular, the border between nonviable and viable tissue is well demarcated. The extent of damage is best indicated on v(e), whereas the borders of inflammation are shown on K(trans). The total lesion extent is relatively stable over the 7 days posttherapy and can be predicted by v(e) or T(2)-weighted MR at early times after heating. CONCLUSION: Our results suggest that Gd-DTPA kinetics can complement conventional MR for improved evaluation of FUS thermal therapy by providing finer differentiation of necrotic states, inflammation, and repair processes.

Animals↗

PubMed2003

Prediction of subtle thermal histopathological change using a novel analysis of Gd-DTPA kinetics.

PURPOSE: To investigate Gd-DTPA kinetics as predictors of histopathological changes following focused ultrasound (FUS) thermal ablation for improved planning and assessment. MATERIALS AND METHODS: Twenty-nine FUS lesions were created in the thigh muscle of eight rabbits under MR-guidance at 1.5 Tesla. Three rabbits were killed at four hours; and 11 lesions were analyzed with histopathology. Temperature-sensitive MRI using proton-resonant frequency-shift was used for time-dependent temperature measurements. Analysis of the uptake kinetics of Gd-DTPA was performed after Gd-DTPA injection, within 20 minutes after heating and again at two hours after heating. The resulting kinetic maps, permeability (K(trans)) and leakage space (v(e)), were correlated to peak temperatures, T(2)-weighted MR, and histopathology. RESULTS: Images of K(trans) and v(e) reveal regions of histopathological change not visible on conventional post-therapy MR. At early times after heating, v(e) predicts the area of injury more accurately than T(2) (7 +/- 2% vs. 25 +/- 6% underestimation). A circular region of extensive structural/vascular disruption is indicated only on K(trans) maps. The sharp decrease in K(trans) at the boundary of this region occurs at 47.5 +/- 0.5 degrees C, and may be a better estimate of cell death than the conventional method of temperature threshold (55 degrees C for coagulation) used in therapy planning. CONCLUSION: Our results suggest Gd-DTPA kinetics can predict different histopathological changes following FUS ablation and may be valuable for early prediction.

Animals↗

PubMed2002

Tissue thermal conductivity by magnetic resonance thermometry and focused ultrasound heating.

PURPOSE: To investigate the combined use of magnetic resonance (MR) temperature imaging and focused ultrasound (FUS) for the noninvasive determination of tissue thermal properties. MATERIALS AND METHODS: Brief, spatial impulses of temperature elevation were created in tissue using a spherical, air-backed transducer operating at 1.68 MHz and measured using MR temperature imaging in a 1.5-Tesla clinical scanner. A novel technique based on thermal washout is applied in an analysis of the acquired MR temperature images to estimate tissue thermal conductivity and perfusion. RESULTS: Numerical simulations and experiments in vitro and in vivo demonstrate that thermal conductivity can be measured to within 10% of the true value with MR thermometry at 1.5 Tesla. With the temperature precision available at 1.5 Tesla, however, robust perfusion estimation is feasible only in highly perfused organs or tumors. CONCLUSION: This study has developed a method for determining tissue thermal properties specific to the patient and organ at the site of interest, and allows repeated application. This capability is relevant in thermal therapy planning of tumor ablation using MR-guided FUS systems.

Animals↗