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 (v_e), tumor plasma volume fraction (v_p) and volume-normalized contrast agent transfer rate between tumor plasma and interstitium (K_TRANS/V_T).

Materials and Methods

Obtained v_e, v_p and K_TRANS/V_T maps were estimated from gadolinium diethylenetriamine penta-acetic acid DCE T₁-weighted gradient-echo images at resolutions of 469, 938 and 2500 μm. These parameter maps were compared at each resolution to histologically determined tumor type, and the high-resolution 469-μm maps were compared with automated cell counting using Otsu's method and a color-thresholding method for estimated intracellular (V_{intracellular}) and extracellular (V_{extracellular}) space fractions.

Results

The top five K_TRANS/V_T values obtained from each tumor at 469 and 938 μm resolutions are significantly different from those obtained at 2500 μm (P<.0001) and from one another (P=.0014). Using these top five K_TRANS/V_T values and the corresponding tumor EES volume fractions v_e, we can statistically differentiate invasive ductal carcinomas from noninvasive papillary carcinomas for the 469- and 938-μm resolutions (P=.0017 and P=.0047, respectively), but not for the 2500-μm resolution (P=.9008). The color-thresholding method demonstrated that v_e measured by DCE MRI is statistically similar to histologically determined EES. The V_{extracellular} obtained from the color-thresholding method was statistically similar to the v_e measured with DCE MRI for the top 10 K_TRANS/V_T values (P>.05). DCE MRI-based K_TRANS/V_T 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 K_TRANS/V_T. Thus, an appropriate resolution window is essential for DCE MRI tumor diagnosis. Within this resolution window, the top K_TRANS/V_T values with corresponding v_e are diagnostic for the tumor types analyzed in this study.     

Efficient CO2 Insertion and Reduction Catalyzed by a Terminal Zinc Hydride Complex

The terminal zinc hydride complex [Tntm]ZnH ( 2 ; Tntm=tris(6‐tert‐butyl‐3‐thiopyridazinyl)methanide) is an efficient hydrosilylation catalyst of CO₂ at room temperature without the need of Lewis acidic additives. The inherent electrophilicity of the system leads to selective formation of the monosilylated product (MeO)₃SiO₂CH (at room temperature with a TOF of 22.2 h^?1 and at 45 °C with a TOF of 66.7 h^?1). In absence of silanes, the intermediate formate complex [Tntm]Zn(O₂CH) ( 3 ) is quantitatively formed within 5 min. All complexes were fully characterized by ¹H and ¹³C NMR spectroscopy and single‐crystal X‐ray diffraction analyses. Density functional theory (DFT) calculations reveal a high positive charge on zinc and the increased preference of the ligand to adopt a κ³‐coordination mode.     

Macromolecular salen catalyst with largely enhanced catalytic activity

A dinuclear copper(II) Schiff-base complex was immobilized in a poly(acrylate) matrix by emulsion polymerization. The spheric microbeads were used for aerobic catalytic oxidation of 3,5-di-tert-butylcatechol into 3,5-di-tert-butylquinone in methanol at ambient temperature to study the contribution of the macromolecular matrix to the overall rate acceleration of the reaction. The polymeric catalyst catalyzes the oxidation about 1 order of magnitude faster (kcat/knon = 470,000) than its low molecular weight analogue (kcat/knon = 60,000).     

Liposome electrokinetic capillary chromatography in the study of analyte-phospholipid membrane interactions. Application to pesticides and related compounds

Interactions between low-molar mass analytes and phospholipid membranes were studied by liposome electrokinetic capillary chromatography (LEKC). The analytes were pesticides, some degradation products, and compounds associated with the manufacture of pesticides. Negatively charged liposome dispersions with different zwitterionic lipids (PC) were applied to the determination of retention factors (k) of 15 charged and uncharged compounds. The liposome dispersions consisted of 80:20 mol% of 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/POPS, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/POPS. Retention factors were calculated from the effective electrophoretic mobilities of the analytes under LEKC and CZE conditions and from the effective electrophoretic mobilities of the liposomes, determined by CZE with a polyacrylamide-coated capillary. Determining the liposome mobilities in this way proved to be a good alternative to the conventional method employing a liposome marker compound. The log k values of the analytes for the different liposome dispersed phases were correlated with one another. In addition, correlation curves were determined between log k and calculated octanol-water partition coefficients. The results showed that the zwitterionic phospholipid in the liposome has a major impact on the interactions between the tested compounds and the lipid membranes.     

Using HPTLC/DESI-MS for peptide identification in 1D separations of tryptic protein digests

Desorption electrospray ionization mass spectrometry (DESI-MS) was investigated as a method to detect and identify peptides from tryptic digests of cytochrome c and myoglobin separated on ProteoChrom HPTLC Silica gel 60 F(254s) plates and ProteoChrom HPTLC Cellulose sheets. Full-scan mass spectra and data-dependent tandem mass spectra were acquired in separate plate scans and used to identify peptide ions. Peptide distributions along the development lane were mapped for each separated protein digest. Signal levels ranged over several orders of magnitude. In general, highest signal levels were obtained for the peptides with the highest R (f) values on a plate, while peptides with very low R (f) values were often not detected. Sequence coverages for cytochrome c were 58% for the digest separated on the silica gel plate and 72% for the separation on the cellulose sheet; myoglobin sequence coverages were 62% and 68% on silica gel and cellulose, respectively. Weak correlations between peptide hydrophilicity and R (f) values on the silica gel and cellulose plates were found, with the more hydrophilic peptides having lower R (f) values.