Comparison of tumor histology to dynamic contrast enhanced magnetic resonance imaging-based physiological estimates.

PURPOSE: The purpose of this study was to compare histologically determined cellularity and extracellular space to dynamic contrast-enhanced magnetic resonance imaging (DCE MRI)-based maps of a two-compartment model's parameters describing tumor contrast agent extravasation, specifically tumor extravascular extracellular space (EES) volume fraction (ve), tumor plasma volume fraction (vp) and volume-normalized contrast agent transfer rate between tumor plasma and interstitium (KTRANS/VT). MATERIALS AND METHODS: Obtained ve, vp and KTRANS/VT maps were estimated from gadolinium diethylenetriamine penta-acetic acid DCE T1-weighted gradient-echo images at resolutions of 469, 938 and 2500 microm. These parameter maps were compared at each resolution to histologically determined tumor type, and the high-resolution 469-microm maps were compared with automated cell counting using Otsu's method and a color-thresholding method for estimated intracellular (Vintracellular) and extracellular (Vextracellular) space fractions. RESULTS: The top five KTRANS/VT values obtained from each tumor at 469 and 938 microm resolutions are significantly different from those obtained at 2500 microm (P<.0001) and from one another (P=.0014). Using these top five KTRANS/VT values and the corresponding tumor EES volume fractions ve, we can statistically differentiate invasive ductal carcinomas from noninvasive papillary carcinomas for the 469- and 938-microm resolutions (P=.0017 and P=.0047, respectively), but not for the 2500-microm resolution (P=.9008). The color-thresholding method demonstrated that ve measured by DCE MRI is statistically similar to histologically determined EES. The Vextracellular obtained from the color-thresholding method was statistically similar to the ve measured with DCE MRI for the top 10 KTRANS/VT values (P>.05). DCE MRI-based KTRANS/VT estimates are not statistically correlated with histologically determined cellularity. CONCLUSION: DCE MRI estimates of tumor physiology are a limited representation of tumor histological features. Extracellular spaces measured by both DCE MRI and microscopic analysis are statistically similar. Tumor typing by DCE MRI is spatial resolution dependent, as lower resolutions average out contributions to voxel-based estimates of KTRANS/VT. Thus, an appropriate resolution window is essential for DCE MRI tumor diagnosis. Within this resolution window, the top KTRANS/VT values with corresponding ve are diagnostic for the tumor types analyzed in this study.

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.

Effect of computed tomography display window and image plane on diagnostic certainty for characteristics of dysplastic elbow joints in dogs.

OBJECTIVE: To test the effects of computed tomography (CT) image plane and window settings on diagnostic certainty for CT characteristics associated with dysplastic elbow joints (elbow joint dysplasia) in dogs and to provide optimal display guidelines for these CT characteristics. SAMPLE POPULATION: CT images of 50 dysplastic elbow joints from 49 lame dogs and 10 elbow joints from 5 sound dogs. PROCEDURES: CT image data were obtained in transverse, sagittal, and dorsal planes. Each plane was examined by use of 3 Hounsfield unit (HU) window settings. Two veterinary radiologists independently evaluated sets of CT images for evidence of 7 CT characteristics. Effect of elbow joint status, image plane, and window settings on diagnostic certainty for these CT characteristics was tested by use of a visual analogue scale. RESULTS: Diagnostic certainty for abnormalities of the medial coronoid process (MCP) and radial incisure was highest in the transverse plane, subchondral defects or sclerosis of the trochlea humeri was highest in the dorsal plane, and joint incongruity was highest in the sagittal plane. Certainty for hypoattenuating subchondral defects or fissures was highest at 2,500 or 3,500 HUs, whereas certainty for subchondral sclerosis was highest at 1,500 HUs and lowest at 3,500 HUs. CONCLUSIONS AND CLINICAL RELEVANCE: Diagnostic certainty for CT characteristics of elbow joint dysplasia in dogs was affected by image display variables. Diagnostic certainty for altered subchondral bone density was primarily influenced by window settings, whereas structural MCP abnormalities and joint incongruity were influenced most by image plane.

Earthworm additions affect leachate production and nitrogen losses in typical midwestern agroecosystems.

Earthworms affect soil structure and the movement of agrochemicals. Yet, there have been few field-scale studies that quantify the effect of earthworms on dissolved nitrogen fluxes in agroecosystems. We investigated the influence of semi-annual earthworm additions on leachate production and quality in different row crop agroecosystems. Chisel-till corn (Zea mays L.)-soybean [Glycine max (L.) Merr.] rotation (CT) and ridge-till corn-soybean-wheat (Triticum aestivum L.) rotation (RT) plots were arranged in a complete randomized block design (n = 3) with earthworm treatments (addition and ambient) as subplots where zero-tension lysimeters were placed 45 cm below ground. We assessed earthworm populations semi-annually and collected leachate biweekly over a three-year period and determined leachate volume and concentrations of total inorganic nitrogen (TIN) and dissolved organic nitrogen (DON). Abundance of deep-burrowing earthworms was increased in addition treatments over ambient and for both agroecosystems. Leachate loss was similar among agroecosystems, but earthworm additions increased leachate production in the range of 4.5 to 45.2% above ambient in CT cropping. Although leachate TIN and DON concentrations were generally similar between agroecosystems or earthworm treatments, transport of TIN was significantly increased in addition treatments over ambient in CT cropping due to increased leachate volume. Losses of total nitrogen in leachate loadings were up to approximately 10% of agroecosystem N inputs. The coincidence of (i) soluble N production and availability and (ii) preferential leaching pathways formed by deep-burrowing earthworms thereby increased N losses from the CT agroecosystem at the 45-cm depth. Processing of N compounds and transport in soil water from RT cropping were more affected by management phase and largely independent of earthworm activity.

Genomic analyses of anaerobically induced genes in Saccharomyces cerevisiae: functional roles of Rox1 and other factors in mediating the anoxic response.

DNA arrays were used to investigate the functional role of Rox1 in mediating acclimatization to anaerobic conditions in Saccharomyces cerevisiae. Multiple growth conditions for wild-type and rox1 null strains were used to identify open reading frames with a statistically robust response to this repressor. These results were compared to those obtained for a wild-type strain in response to oxygen availability. Transcripts of nearly one-sixth of the genome were differentially expressed (P < 0.05) with respect to oxygen availability, the majority (>65%) being down-regulated under anoxia. Of the anaerobically induced genes, about one-third (106) contain putative Rox1-binding sites in their promoters and were significantly (P < 0.05) up-regulated in the rox1 null strains under aerobiosis. Additional promoter searches revealed that nearly one-third of the anaerobically induced genes contain an AR1 site(s) for the Upc2 transcription factor, suggesting that Upc2 and Rox1 regulate the majority of anaerobically induced genes in S. cerevisiae. Functional analyses indicate that a large fraction of the anaerobically induced genes are involved in cell stress (approximately 1/3), cell wall maintenance (approximately 1/8), carbohydrate metabolism (approximately 1/10), and lipid metabolism (approximately 1/12), with both Rox1 and Upc2 predominating in the regulation of this latter group and Upc2 predominating in cell wall maintenance. Mapping the changes in expression of functional regulons onto metabolic pathways has provided novel insight into the role of Rox1 and other trans-acting factors in mediating the physiological response of S. cerevisiae to anaerobic conditions.