Measurement of bioreactor perfusion using dynamic contrast agent-enhanced magnetic resonance imaging.

Dynamic magnetic resonance imaging was used to monitor solute diffusion through aggregates of Chinese hamster ovary cells growing on macroporous carriers in a fixed-bed bioreactor. Diffusion-weighted (1)H magnetic resonance imaging (MRI) and scanning electron microscopy demonstrated that cell growth in the bioreactor was heterogeneous, with the highest cell densities being found at the periphery of the carriers. T(1)-weighted magnetic resonance imaging measurements of the inflow of a commonly used magnetic resonance contrast agent, gadolinium-diethylenetriaminopentaacetic acid (Gd-DTPA), showed that migration of the agent through the peripheral cell masses could be explained by diffusion. However, appearance of the contrast agent in the center of the carriers was too fast to be explained by simple diffusion and indicated that these regions were perfused by convective flow. The average diffusivity of Gd-DTPA through the cell mass was found to be (2.4 +/- 0.2) x 10(-10) m(2) sec(-) (mean +/- SEM). This technique will be useful in the characterization and development of high-cell-density bioreactor systems, in which solute transport plays a critical role in cell growth and physiology.     

Correlation of fine needle aspiration biopsy and dynamic contrast-enhanced 3D magnetic resonance imaging of the breast

OBJECTIVE: To correlate and assess the utility of dynamic contrast-enhanced three-dimensional gadolinium-enhanced magnetic resonance imaging (Gd-3DMRI) and fine needle aspiration biopsy (FNAB) findings in patients with suspected breast disease. STUDY DESIGN: Beginning in 1993, all patients who underwent percutaneous FNAB of the breast and had concurrent Gd-3DMRI evaluation of the breast were selected for this study. Findings for FNAB and Gd-3DMRI were stratified into two categories, positive and negative. Subsequent clinical management decisions, which included surgical intervention and/or clinical follow-up, were recorded for all patients. RESULTS: There were 69 FNABs in 59 patients with corresponding Gd-3DMRI evaluation. A positive result by both FNAB and Gd-3DMRI was found in 15 of 18 malignant cases. FNAB missed one case, and Gd-3DMRI missed two, and each of these was thought to be technical. Combining the methods yielded 100% sensitivity. False positive results on Gd-3DMRI (17 cases) were all confirmed to be benign by FNAB and subsequent tissue evaluation. All 32 cases with combined negative results by FNAB and Gd-3DMRI demonstrated a benign process, yielding a specificity of 100% (32/32). CONCLUSION: Our combined testing modalities showed a high degree of specificity and good sensitivity. FNAB used with dynamic contrast-enhanced Gd-3DMRI can contribute valuable information for physicians treating patients with suspected breast abnormalities.     

Estimating glomerular filtration rate in diabetes using serum cystatin C

Chronic kidney disease (CKD) is a major public health problem, especially for people with diabetes. Not only is it a risk factor for end-stage renal disease (ESRD) but it is also a major cardiovascular disease (CVD) risk factor. Methods that accurately and simply estimate glomerular filtration rate (GFR) are therefore needed to optimise the detection and management of CKD in people with diabetes. One of the main failures of commonly used creatinine-based methods for estimating renal function is that they lack applicability across the full range of GFR values and underestimate GFR levels >60 mL/min/1.73m(2). Methods for accurately estimating an early pathological decline in GFR (i.e. ΔGFR >3.3 mL/min/year before reaching a GFR <60 mL/min/1.73m(2)) are especially needed as appropriate interventions have been shown to retard progression to ESRD and reduce CVD risk in people with diabetes. In contrast, recent studies have suggested that estimates of GFR based on serum cystatin C concentration might provide a simple and accurate method for detecting and monitoring an early decline in renal function.     

An interventional magnetic resonance imaging technique for the molecular characterization of intraprostatic dynamic contrast enhancement

The biological characterization of an individual patient's tumor by noninvasive imaging will have an important role in cancer care and clinical research if the molecular processes that underlie the image data are known. Spatial heterogeneity in the dynamics of magnetic resonance imaging contrast enhancement (DCE-MRI) is hypothesized to reflect variations in tumor angiogenesis. Here we demonstrate the feasibility of precisely colocalizing DCE-MRI data with the genomic and proteomic profiles of underlying biopsy tissue using a novel MRI-guided biopsy technique in a patients with prostate cancer.     

Early therapy evaluation of combined cetuximab and irinotecan in orthotopic pancreatic tumor xenografts by dynamic contrast-enhanced magnetic resonance imaging

Early pancreatic cancer response following cetuximab and/or irinotecan therapies was measured by serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and during therapy. Groups 1 to 4 (n = 6/group) of SCID mice bearing orthotopic pancreatic adenocarcinoma xenografts expressing luciferase were treated with phosphate-buffered saline, cetuximab, irinotecan, or cetuximab combined with irinotecan, respectively, twice weekly for 3 weeks. DCE-MRI was performed on days 0, 1, 2, and 3 after therapy initiation, whereas anatomic magnetic resonance imaging was performed on days 0, 1, 2, 3, 6, and 13. Bioluminescence imaging was performed on days 0 and 21. At day 21, all tumors were collected for further histologic analyses (Ki-67 and CD31 staining), whereas tumor dimensions were measured by calipers. The Ktrans values in the 0.5 mm-thick peripheral tumor region were calculated, and the changes in Ktrans during the 3 days posttherapy were compared to tumor volume changes, bioluminescent signal changes, and histologic findings. The Ktrans changes in the peripheral tumor region after 3 days of therapy were linearly correlated with 21-day decreases in tumor volume (p < .001), bioluminescent signal (p = .050), microvessel densities (p = .002), and proliferating cell densities (p = .001). This study supports the clinical use of DCE-MRI for pancreatic cancer patients for early assessment of an anti-epidermal growth factor receptor therapy combined with chemotherapy.     

Model-based simulation of dynamic magnetic resonance imaging signals

This paper presents a model-based method to efficiently simulate dynamic magnetic resonance imaging signals. Using an analytical spatiotemporal object model, the method can approximate time-varying k-space signals such as those from objects in motion and/or during dynamic contrast enhancement. Both rigid-body and non-rigid-body motions can be simulated using the proposed method. In addition, it can simulate data with arbitrary data sampling order and/or non-uniform k-space trajectory. A set of simulated images were compared with real data acquired from a rat model on a 4.7 T scanner to verify the model. The efficient simulation method is expected to be useful for rapid testing of various imaging and image analysis algorithms such as image reconstruction, image registration, motion compensation, and kinetic parameter mapping.     

A liposomal system for contrast-enhanced magnetic resonance imaging of molecular targets

Pegylated paramagnetic and fluorescent immunoliposomes were designed to enable the parallel detection of the induced expression of molecular markers on endothelial cells with magnetic resonance imaging (MRI) and fluorescence microscopy. MRI is capable of three-dimensional noninvasive imaging of opaque tissues at near cellular resolution, while fluorescence microscopy can be used to investigate processes at the subcellular level. As a model for the expression of a molecular marker, human umbilical vein endothelial cells (HUVEC) were treated with the pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha) to upregulate the expression of the adhesion molecule E-selectin/CD62E. E-selectin-expressing HUVEC were incubated with pegylated paramagnetic fluorescently labeled liposomes carrying anti-E-selectin monoclonal antibody as a targeting ligand. Both MRI and fluorescence microscopy revealed the specific association of the liposomal MR contrast agent with stimulated HUVEC. This study suggests that this newly developed system may serve as a useful diagnostic tool to investigate pathological processes in vivo with MRI.     

Mechanisms of neonatal increase in glomerular filtration rate

To investigate the mechanisms responsible for the neonatal increase in glomerular filtration rate (GFR), renal function studies (whole kidney and micropuncture) were carried out in anesthesized fetal sheep (133-140 days gestation; term = 150 days) and lambs (12-18 days). Fetuses were delivered and placed in a water bath (39.5 degrees C), keeping the umbilical cord moist and intact. Lambs were studied on a thermostatically controlled heating pad. Animals were prepared for either blood flow studies or micropuncture measurements. Expected differences in blood composition and cardiovascular and renal function were observed between fetuses and lambs, and values obtained for most variables were similar to those measured in chronically catheterized unanesthetized animals. Fetal GFR was much lower than that of lambs (0.20 vs. 0.62 ml.min(-1).g kidney(-1), P < 0.001). Free-flow, stop-flow, and net filtration pressures (NFP) were lower in the fetuses than the lambs (NFP 20.8 vs. 23.8 mmHg, P < 0.001), as was the calculated ultrafiltration coefficient (0.014 vs. 0.022 ml.min(-1).g(-1).mmHg(-1), P < 0.001). Thus, we conclude that rises in both net filtration pressure and the ultrafiltration coefficient contribute to the large increase in GFR between fetal life and approximately 2 wk after birth.     

Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement

The systematic staging of chronic kidney disease (CKD) by glomerular filtration measurement and proteinuria has allowed the development of rational and appropriate management plans. One of the barriers to early detection of CKD is the lack of a precise, reliable and consistent measure of kidney function.The most common measure of kidney function is currently serum creatinine concentration. It varies with age, sex, muscle mass and diet, and interlaboratory variation between measurements is as high as 20%.The reference interval for serum creatinine concentration includes up to 25% of people (particularly thin, elderly women) who have an estimated glomerular filtration rate (eGFR) that is significantly reduced (< 60 mL/min/1.73 m). The recent publication of a validated formula (MDRD) to estimate GFR from age, sex, race and serum creatinine concentration, without any requirement for measures of body mass, allows pathology laboratories to "automatically" generate eGFR from data already acquired. Automatic laboratory reporting of eGFR calculated from serum creatinine measurements would help to identify asymptomatic kidney dysfunction at an earlier stage. eGFR correlates well with complications of CKD and an increased risk of adverse outcomes such as cardiovascular morbidity and mortality. We recommend that pathology laboratories automatically report eGFR each time a serum creatinine test is ordered in adults. As the accuracy of eGFR is suboptimal in patients with normal or near-normal renal function, we recommend that calculated eGFRs above 60 mL/min/1.73 m be reported by laboratories as "> 60 mL/min/1.73 m", rather than as a precise figure.     

Development of a dynamic imaging method for gravitropism in pea sprouts using clinical magnetic resonance imaging system

Although magnetic resonance imaging (MRI) is a useful technique, only a few studies have investigated the dynamic behavior of small subjects using MRI owing to constraints such as experimental space and signal amount. In this study, to acquire high-resolution continuous three-dimensional gravitropism data of pea (Pisum sativum) sprouts, we developed a small-bore MRI signal receiver coil that can be used in a clinical MRI and adjusted the imaging sequence. It was expected that such an arrangement would improve signal sensitivity and improve the signal-to-noise ratio (SNR) of the acquired image. All MRI experiments were performed using a 3.0-T clinical MRI scanner. An SNR comparison using an agarose gel phantom to confirm the improved performance of the small-bore receiver coil and an imaging experiment of pea sprouts exhibiting gravitropism were performed. The SNRs of the images acquired with a standard 32-channel head coil and the new small-bore receiver coil were 5.23±0.90 and 57.75±12.53, respectively. The SNR of the images recorded using the new coil was approximately 11-fold higher than that of the standard coil. In addition, when the accuracy of MR imaging that captures the movement of pea sprout was verified, the difference in position information from the optical image was found to be small and could be used for measurements. These results of this study enable the application of a clinical MRI system for dynamic plant MRI. We believe that this study is a significant first step in the development of plant MRI technique.