MRI-guided radiotherapy planning (MRIgRT) may be superior to CT-guided planning in some instances owing to its improved soft tissue contrast. However, MR images do not communicate tissue electron density information necessary for dose calculation and therefore must either be co-registered to CT or algorithmically converted to synthetic CT. No robust quality assessment of commercially available MR-CT registration algorithms is yet available; thus we sought to quantify MR-CT registration formally. Head and neck non-contrast CT and T2 MRI scans acquired with standard treatment immobilization techniques were prospectively acquired from 15 patients. Per scan, 35 anatomic regions of interest (ROIs) were manually segmented. MRIs were registered to CT rigidly (RIR) and by three commercially available deformable registration algorithms (DIR). Dice similarity coefficient (DSC), Hausdorff distance mean (HD mean) and Hausdorff distance max (HD max) metrics were calculated to assess concordance between MRI and CT segmentations. Each DIR algorithm was compared to DIR using the nonparametric Steel test with control for individual ROIs (n = 105 tests) and for all ROIs in aggregate (n = 3 tests). The influence of tissue type on registration fidelity was assessed using nonparametric Wilcoxon pairwise tests between ROIs grouped by tissue type (n = 12 tests). Bonferroni corrections were applied for multiple comparisons. No DIR algorithm improved the segmentation quality over RIR for any ROI nor all ROIs in aggregate (all p values >0.05). Muscle and gland ROIs were significantly more concordant than vessel and bone, but DIR remained non-different from RIR. For MR-CT co-registration, our results question the utility and applicability of commercially available DIR over RIR alone. The poor overall performance also questions the feasibility of translating tissue electron density information to MRI by CT registration, rather than addressing this need with synthetic CT generation or bulk-density assignment.

Epithelial‐mesenchymal transition (EMT) has been shown to play a key role in embryogenesis and cancer progression. We previously found that fibronectin (FN) carrying O‐GalNAc at a specific site is selectively expressed in cancer and fetal cells/tissues, and termed oncofetal FN (onfFN). Here, we show that (i) a newly‐established monoclonal antibody against FN lacking the O‐GalNAc, termed normalFN (norFN), is useful for isolation of onfFN, (ii) onfFN, but not norFN, can induce EMT in human lung carcinoma cells, (iii) onfFN has a synergistic effect with transforming growth factor (TGF)β1 in EMT induction.

Purpose: To assess oxygenation in abdominal organs with magnetic resonance imaging (MRI), a novel approach is presented to simultaneously measure both T₁‐ and ‐maps serially during a single dynamic MRI scan in response to an oxygen challenge.Materials and Methods: The proposed acquisition scheme consists of a multishot multiecho gradient echo planar imaging sequence (ms‐GEPI) interleaved with a multishot inversion recovery echo planar imaging (ms‐IR‐EPI) sequence. Respiratory motion compensation was accomplished with standard belt triggering and by acquiring all image data at the same phase of expiration. This respiratory‐triggered, free‐breathing, interleaved tissue oxygenation level‐dependent (TOLD) and blood oxygenation level‐dependent (BOLD) acquisition technique was validated on phantoms and seven healthy volunteers in response to an oxygen challenge.Results: Measurements of relaxation times both in vitro and in vivo were in good agreement with those obtained using conventional pulse sequences and reported in the literature. The interleaved sequence was able to measure oxygen‐induced relaxation time changes in human abdominal organs.Conclusion: The free‐breathing respiratory‐triggered interleaved T₁ and sequence successfully provided relaxation time maps of abdominal organs in a dynamic scan without the need for image registration. The simultaneous monitoring of tissue and blood oxygenation improves time efficiency and should enhance studies comparing dynamic T₁ and data within the abdomen. J. Magn. Reson. Imaging 2013;38:1230–1236.

Hypoxia is associated with prostate tumor aggressiveness, local recurrence, and biochemical failure. Magnetic resonance imaging (MRI) offers insight into tumor pathophysiology and recent reports have related transverse relaxation rate (R₂*) and longitudinal relaxation rate (R₁) measurements to tumor hypoxia. We have investigated the inclusion of oxygen-enhanced MRI for multi-parametric evaluation of tumor malignancy. Multi-parametric MRI sequences at 3 Tesla were evaluated in 10 patients to investigate hypoxia in prostate cancer prior to radical prostatectomy. Blood oxygen level dependent (BOLD), tissue oxygen level dependent (TOLD), dynamic contrast enhanced (DCE), and diffusion weighted imaging MRI were intercorrelated and compared with the Gleason score. The apparent diffusion coefficient (ADC) was significantly lower in tumor than normal prostate. Baseline R₂* (BOLD-contrast) was significantly higher in tumor than normal prostate. Upon the oxygen breathing challenge, R₂* decreased significantly in the tumor tissue, suggesting improved vascular oxygenation, however changes in R₁ were minimal. R₂* of contralateral normal prostate decreased in most cases upon oxygen challenge, although the differences were not significant. Moderate correlation was found between ADC and Gleason score. ADC and R₂* were correlated and trends were found between Gleason score and R₂*, as well as maximum-intensity-projection and area-under-the-curve calculated from DCE. Tumor ADC and R₂* have been associated with tumor hypoxia, and thus the correlations are of particular interest. A multi-parametric approach including oxygen-enhanced MRI is feasible and promises further insights into the pathophysiological information of tumor microenvironment.

We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5 T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort. Thirty patients with HNSCC who received curative-intent RT at MD Anderson Cancer Center, were included. Baseline and weekly MRI were obtained, and various ADC parameters were extracted from the regions of interest (ROIs). Baseline and weekly ADC parameters were correlated with response during and after RT, and the recurrence using the Mann-Whitney U test. The Wilcoxon signed-rank test was used to compare the weekly ADC versus baseline values. Weekly volumetric changes (Δvolume) for each ROI were correlated with ΔADC using Spearman’s Rho test. Recursive partitioning analysis (RPA) identified the optimal ΔADC threshold associated with different oncologic outcomes. There was a significant rise in all ADC parameters at different time points of RT compared to baseline for both gross primary disease (GTV-P) and gross nodal disease volumes (GTV-N). The increased ADC values for GTV-P were statistically significant only for primary tumors achieving complete remission (CR) during RT. RPA identified GTV-P ΔADC 5th percentile > 13% at the mid-RT as the most significant parameter associated with primary tumors’ CR during RT (p < 0.001). There was a significant decrease in residual volume of both GTV-P & GTV-N throughout the course of RT. A significant negative correlation between mean ΔADC and Δvolume for GTV-P at the 3rd and 4th week of RT was detected (r = −0.39, p = 0.044 & r = −0.45, p = 0.019, respectively). Assessment of ADC kinetics at regular intervals throughout RT seems to be correlated with RT response. Further studies with larger cohorts and multi-institutional data are needed for validation of ΔADC as a model for prediction of response to RT.