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Erik C Wiener

Publications and source records attributed to Erik C Wiener.

5 recordsLinked to original sources

Spatial and temporal resolution effects on dynamic contrast-enhanced magnetic resonance mammography.

We tested the hypothesis that partial volume effects due to poor in-plane resolution and/or low temporal resolution used in clinical dynamic contrast-enhanced magnetic resonance imaging results in erroneous diagnostic information based on inaccurate estimates of tumor contrast agent extravasation and tested whether reduced encoding techniques can correct for dynamic data volume averaging. Image spatial resolution was reduced from 469 x 469 microm2 to those reported below by selecting a subset of k-space data. We then compared the top five K(trans)/V(T) "hot spots" obtained from the original data set, 469 x 469-microm in-plane spatial resolution and an 18-s temporal resolution processed by fast Fourier transform (FFT), with values obtained from data sets having in-plane spatial resolutions of 938 x 938, 1875 x 1875 and 2500 x 2500 microm2 and a temporal resolution of 18 s, or data sets with temporal resolutions of 36, 54 and 72 and a spatial resolution of 469 x 469 microm2, and found them to statistically differ from the parent data sets. We then tested four different post processing methods for improving the spatial resolution without sacrificing temporal resolution: zero-filled FFT, keyhole, reduced-encoding imaging by generalized-series reconstruction (RIGR) and two-reference RIGR (TRIGR). The top five values of K(trans)/V(T) obtained from data sets, the in-plane spatial resolutions of which were improved to 469 x 469 microm2 by zero-filling FFT, Keyhole and RIGR, statistically differed from those obtained from the original 469 x 469 microm2 FFT parent image data set. Only the 938 x 938 and 1875 x 1875 microm2 data sets reconstructed to 469 x 469 microm2 with TRIGR reconstruction method yielded values of the top five K(trans)/V(T) hot spots statistically the same as the original parent data set, 469 x 469 microm2 in-plane spatial and 18-s temporal-resolution FFT. That is, partial volume effects from data sets of different in-plane spatial resolution resulted in statistically different values of the top five K(trans)/V(T) hot spots relative to a high spatial and temporal resolution data set, and TRIGR reconstruction of these low resolution data sets to high resolution images provided statistically similar values with a savings in temporal resolution of 2 to 4 times.

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Characteristics of a new MRI contrast agent prepared from polypropyleneimine dendrimers, generation 2.

RATIONALE AND OBJECTIVES: Dendrimer-based magnetic resonance imaging (MRI) contrast agents offer many advantages including high levels of amplification. The objective of this research was to test the adequacy and viability of a new family of dendrimers for use as MRI contrast agents in vitro and in vivo. METHODS: Dendrimers based on 1,4-diaminobutane core polypropyleneimine (PPI) generation 2 and ammonia core polyamidoamine dendrimers had the free surface amines conjugated to a diethylenetriaminepentaacetic acid derivative followed by complex formation with gadolinium. Relaxivity measurements were made on an IBM Field Cycling Relaxometer. Biodistribution and pharmacokinetic studies were examined with the radiotracer 153Gd in rats and a counting window of 95 to 105 keV. MRI images were conducted at 4.7 T. RESULTS: The relaxivity of the PPI agent exceeded that of the corresponding generation polyamidoamine (PAMAM) agent. Uptake occurred in the liver, spleen, and kidney. Pharmacokinetic studies showed a biexponential decay with excretion half-lives of 3 hours and 33.6 days respectively. The agent increased the contrast enhancement, 1 hour after injection, of T1-weighted images by 52%. CONCLUSIONS: This PPI agent resulted in significant contrast signal enhancement. This family of agent may also provide a valuable contrast agent backbone.

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Identifying tumor vascular permeability heterogeneity with magnetic resonance imaging contrast agents.

RATIONALE AND OBJECTIVES: Dynamic contrast enhanced (DCE) MR mammography (MRM) uses tumor capillary density differences for prognosis. The heterogeneous response of permeability-surface area products (PS = Kp<-->t) was examined in mammary tumors, as a function of contrast agent size, to determine what effect ROI size might have on PS and prognosis. METHODS: DCE FLASH signal intensities were converted to gadolinium concentrations by a standard curve, which was fitted by a two-compartment model for the tumor's extravascular extracellular space (EES) volume fraction (ve), and the tumor volume normalized transfer rate between plasma and EES (Kp<-->t/VT). RESULTS: For Gd-DTPA ve = 9% to 13% Kp<-->t/VT = 0.01 to 0.06 minutes-1, and the macromolecular agent, PAMAM-TU-DTPA G = 4 ve = 0.8% to 1% Kp<-->t/VT = 0.008 to 0.04 minutes(-1). Significant differences in Kp<-->t/VT for local regions were found for both agents relative to the whole tumor and the macromolecular agent had greater dynamic range. CONCLUSIONS: Smaller ROI values or pixels should yield more accurate assessment of neovascularization.

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Biodistribution of a 153 Gd-folate dendrimer, generation = 4, in mice with folate-receptor positive and negative ovarian tumor xenografts.

RATIONALE AND OBJECTIVES: An important characteristic of targeted contrast agents is how they are tolerated in a biologic environment and their localization in the surrounding tissues in addition to target tissue. We evaluate the biodistribution of a gadolinium Gd 153-folate-dendrimer in high affinity folate-receptor (hFR) positive and negative ovarian tumor xenografts. METHODS: The 153Gd-folate-dendrimer chelate was prepared by exchanging 153Gd with nonradioactive gadolinium for 1 week, followed by extensive filtration. Athymic mice with hFR-positive (n = 3) and negative tumors (n = 3) were injected intravenously and counted using a whole-body counting system with a 80 to 150 keV counting window. RESULTS: The hFR-positive tumors accumulate 3.6% +/- 2.8% injected dose/g, whereas only background counts were found in hFR-negative tumors. The folate-dendrimer's tumor-to-blood ratio of 12.6, in hFR-positive tumors, was approximately 5.7 to 17.0 fold better than those obtained with monoclonal antibodies targeted to the folate receptor. CONCLUSIONS: Biodistribution studies confirm previous MRI findings and show that the accumulation of the folate-dendrimer requires the expression of the hFR.

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