Biomedical subjects

Milica Medved

Publications and source records attributed to Milica Medved.

10 recordsLinked to original sources

PubMed2006

Multi-slice DCE-MRI data using P760 distinguishes between metastatic and non-metastatic rodent prostate tumors.

An intermediate molecular weight contrast agent P760 was used to investigate the ability of multi-slice dynamic contrast-enhanced MRI (DCE-MRI) to distinguish metastatic from non-metastatic rodent prostate tumors. Non-metastatic AT2.1 and metastatic AT3.1 prostate tumors originally derived from the Dunning prostate cancer model were implanted on the hind leg of Copenhagen rats. Multi-sliced DCE-MRI data were acquired on a SIGNA 1.5 T scanner and analyzed using a recently developed empirical mathematical model. The P760 multi-slice DCE-MRI data in combination with the empirical mathematical model successfully distinguished between metastatic and non-metastatic rodent prostate tumors. Specifically, fitting the data with the empirical model showed that metastatic tumors had significantly faster contrast media uptake (p<0.001) and slower washout rates (p<0.01) than non-metastatic tumors.

Algorithms↗

PubMed2006

High spectral and spatial resolution MRI of breast lesions: preliminary clinical experience.

OBJECTIVE: In previous research, high spectral and spatial resolution (HiSS) echo-planar spectroscopic imaging (EPSI) was successfully applied to the human breast, obtaining improved contrast, anatomic detail, and sensitivity to contrast agents. To test HiSS in the clinical setting, we used HiSS MRI to image 30 women with suspicious breast lesions. SUBJECTS AND METHODS: Women with suspicious breast lesions were scanned before and after contrast administration using EPSI at 1.5 T (0.63-mm in-plane resolution, 2.6-Hz spectral resolution). Images with intensity proportional to the water signal peak height in each voxel were synthesized and compared with standard clinical fat-saturated and early dynamic subtraction images. Pre- and postcontrast HiSS images were compared to assess the effect of the contrast agent on water resonance structure. RESULTS: HiSS images scored significantly better than standard clinical images in lesion conspicuity, margin definition, and internal definition, even though they were acquired before contrast agent injection. Fat suppression was more complete and uniform and detail was shown on HiSS images more clearly than on conventional fat-saturation images. Thus, HiSS images often allowed easier evaluation of the lesion. Contrast agent-affected changes were often spatially and spectrally inhomogeneous. CONCLUSION: HiSS scans were successfully integrated into standard clinical examinations and provided diagnostically useful images before contrast agent injection. Thus, it might be possible to characterize suspicious lesions on the basis of precontrast high-resolution spectral information. This information and information about the effect of contrast agents could potentially improve the specificity of breast MRI.

Adult↗

PubMed2004

Phase II study of the Flk-1 tyrosine kinase inhibitor SU5416 in advanced melanoma.

PURPOSE: Vascular endothelial growth factor (VEGF) expression is prognostic in melanoma, and the activity of VEGF is mediated in part through the receptor tyrosine kinase Flk-1. A Phase II study of SU5416, a preferential inhibitor of Flk-1, was carried out in patients with metastatic melanoma to determine clinical response, tolerability, and changes in tumor vascular perfusion. EXPERIMENTAL DESIGN: Patients with documented progressive disease and </=1 prior therapy were eligible. Central nervous system metastases were allowed if stable off medication. SU5416 (145 mg/m(2)) was administered via a central catheter twice weekly for 8 weeks. Premedication with dexamethasone, diphenhydramine, and a H(2) blocker was required because of the Cremophor vehicle. Tumor vascular perfusion was assessed before treatment and during week 8 by dynamic contrast magnetic resonance imaging, and plasma was analyzed for VEGF. RESULTS: Thirty-one patients were enrolled. Two-thirds had received prior therapy, 21 had visceral metastasis, and 14 had an elevated lactate dehydrogenase. Mean absolute lymphocyte counts were decreased (P = 0.002), and glucose levels were increased (P = 0.001) posttherapy, presumably because of steroid premedication. Four vascular adverse events were observed. Of 26 evaluable patients, 1 experienced a partial response, 1 had stable disease, and 5 had a mixed response. Dynamic contrast magnetic resonance imaging in 5 evaluable patients showed decreased tumor perfusion at week 8 (P = 0.024), and plasma VEGF levels were elevated compared with pretherapy (P = 0.008). CONCLUSIONS: SU5146 appears to be relatively well tolerated in this population. Although the modest clinical activity and potential effects on tumor vascularity may support additional exploration of VEGF as a target in melanoma, effects from steroid premedication limit further investigation of this agent.

Adult↗

PubMed2004

Semiquantitative analysis of dynamic contrast enhanced MRI in cancer patients: Variability and changes in tumor tissue over time.

PURPOSE: To evaluate variability of a simplified method for measuring semiquantitative DCE-MRI parameters in patients with cancer and to explore effects of treatment with a putative anti-angiogenic compound. MATERIALS AND METHODS: A total of 19 patients enrolled on treatment trials with the putative anti-angiogenic agent SU5416 underwent contrast enhanced examinations, and 11 had a second examination eight weeks post therapy. Contrast media concentration as a function of time was calculated using changes in signal and literature baseline T(1) values in normal muscle or liver reference tissue. Semiquantitative DCE-MRI parameters, including the area under the contrast concentration vs. time curve (AUC), were calculated for regions-of-interest in normal liver and muscle, and in tumors. RESULTS: The coefficients of variation for pretherapy parameters in normal tissue were 11% to 37%. No significant changes were detected in normal liver over two months of therapy. In tumors and muscle, a significant decrease in the AUC and maximum contrast concentration was observed. CONCLUSION: Variability of semiquantitative DCE-MRI parameters utilizing a method based on known T(1) values in a reference tissue is low enough to detect changes in tumors during therapy. Use of this method as a pharmacodynamic marker should be further investigated.

Angiogenesis Inhibitors↗

PubMed2004

New model for analysis of dynamic contrast-enhanced MRI data distinguishes metastatic from nonmetastatic transplanted rodent prostate tumors.

Dynamic contrast-enhanced MRI (DCEMRI) data were acquired from metastatic and nonmetastatic tumors in rodents to follow the uptake and washout of a low-molecular-weight contrast agent (Gd-DTPA) and a contrast agent with higher molecular weight (P792). The concentration vs. time curves calculated for the tumor rims and centers were analyzed using the two-compartment model (TCM) and a newly developed empirical mathematical model (EMM). The EMM provided improved fits to the experimental data compared to the TCM. Parameters derived from the empirical model showed that the contrast agent washout rate was significantly slower in metastatic tumors than in nonmetastatic tumors for both Gd-DTPA (P < 0.03) and P792 (P < 0.04). The effects of the tumor on blood flow in "normal" tissue immediately adjacent to the tumors were evident: Gd-DTPA uptake and washout rates were much lower in muscle near the tumor (P < 0.05) than normal muscle farther from the tumor. The results suggest that accurate fits of DCEMRI data provide kinetic parameters that distinguish between metastatic and relatively benign cancers. In addition, a comparison of the dynamics of Gd-DTPA and P792 provides information regarding the microenvironment of tumors.

Animals↗

PubMed2004

Fourier components of inhomogeneously broadened water resonances in breast: a new source of MRI contrast.

High spectral and spatial resolution (HiSS) MR data were acquired at 1.5 T using echo-planar spectroscopic imaging from patients with suspicious breast lesions. The water resonances in small voxels are inhomogenously broadened and often have distinct components. Images were calculated with intensity proportional to the Fourier components of the water resonance in each voxel at different offsets from the peak frequency. The results demonstrate that in breast the off-peak Fourier component images of water are qualitatively different from those derived from the peak height of the water resonance. These differences most likely reflect underlying anatomy or physiology. In conventional images, the superposition of the various Fourier components of the water signal may cause loss of detail. The synthesis of water Fourier component images from high spectral and spatial resolution data may provide a new form of contrast, and increase sensitivity to subvoxel physiology and anatomy.

Body Water↗

PubMed2004

Estimating the arterial input function using two reference tissues in dynamic contrast-enhanced MRI studies: fundamental concepts and simulations.

In dynamic contrast-enhanced MRI (DCE-MRI) studies, an accurate knowledge of the arterial contrast agent concentration as a function of time is crucial for the estimation of kinetic parameters. In this work, a novel method for estimating the arterial input function (AIF) based on the contrast agent concentration-vs.-time curves in two different reference tissues is described. It is assumed that the AIFs of the two tissues have the same shape, and that simple models with two or more compartments, and unknown kinetic parameters, can describe their tracer concentration-vs.-time curves. Based on the principle of self-consistency, one can relate the two tracer concentration-vs.-time curves to estimate their common underlining AIF, together with the kinetic parameters of the two tissues. In practice, the measured concentration-vs.-time curves have noise, and the AIFs of the two tissues are not exactly the same due to different dispersion effects. These factors will produce errors in the AIF estimate. Simulation studies show that despite the two error sources, the double-reference-tissue method provides reliable estimates of the AIF.

Arteries↗

PubMed2003

The effect of varying spectral resolution on the quality of high spectral and spatial resolution magnetic resonance images of the breast.

PURPOSE: To evaluate the effect of varying spectral resolution on image quality of high spectral and spatial resolution (HiSS) images. MATERIALS AND METHODS: Eight women with suspicious breast lesions and six healthy volunteers were scanned using echo-planar spectroscopic imaging (EPSI) at 1.5 Tesla with 0.75- to 1-mm in-plane resolution and 2.3- to 2.6-Hz spectral resolution. Time domain data were truncated to obtain proton spectra in each voxel with varying (2.6-83.3 Hz) resolution. Images with intensity proportional to water signal peak heights were synthesized. Changes in water signal line shape following contrast injection were analyzed. RESULTS: Fat suppression is optimized at approximately 10-Hz spectral resolution and is significantly improved by removal of wings of the fat resonance. This was accomplished by subtracting a Lorentzian fit to the fat resonance from the proton spectrum. The water resonance is often inhomogeneously broadened, and very high spectral resolution is necessary to resolve individual components. High spectral resolution is required for optimal contrast in anatomic features with very high T(2)* (e.g., within a lesion) and for detection of often subtle effects of contrast agents on water signal line shape. CONCLUSION: Despite a trade-off between the spectral resolution and signal-to-noise ratio, it is beneficial to acquire data at the highest spectral resolution currently attainable at 1.5 Tesla.

Breast↗

PubMed2002

Breast MR imaging with high spectral and spatial resolutions: preliminary experience.

The authors evaluated magnetic resonance (MR) imaging with high spectral and spatial resolutions (HSSR) of water and fat in breasts of healthy volunteers (n = 6) and women with suspicious lesions (n = 6). Fat suppression, edge delineation, and image texture were improved on MR images derived from HSSR data compared with those on conventional MR images. HSSR MR imaging data acquired before and after contrast medium injection showed spectrally inhomogeneous changes in the water resonances in small voxels that were not detectable with conventional MR imaging.

Adult↗

PubMed1999

Convection in horizontally vibrated granular material.

We report observations of convective motion in a container filled with granular material when it is vibrated in the horizontal direction. We find that the roughness of the boundaries and the container dimensions play an important role in determining the shape and number of the convection cells. When the container bottom and lateral walls are rough, the system typically exhibits four counter-rotating rolls stacked in two pairs on top of each other; for very low filling height, it is possible to observe a single row of rolls arranged laterally along the bottom of the container. With smooth walls, on the other hand, we find that the system typically forms only a single pair of counter-rotating convection rolls that originate in the two upper corners of the vibrated material; when the filling height is increased to a level that depends on the container width, we observe a transition to the four-roll state. (c) 1999 American Institute of Physics.

Journal Article↗