Differentiation of true-progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide by GLCM texture analysis of conventional MRI.

Twenty-two patients with pathologically confirmed glioblastoma who had received concurrent CCRT with TMZ underwent conventional MRI including T1-weighted imaging(T1WI), T2-weighted imaging(T2WI), fluid attenuated inversion recovery(FLAIR)and contrast-enhanced T1WI(T1Ce). Five GLCM texture maps of contrast, energy, entropy, correlation and homogeneity were generated for each MRI series. Of the aforementioned 5 texture features, the most significant features were contrast and correlation on T2WI with areas under ROC curve of 0.883 and 0.892, respectively, and they had the same sensitivity of 75%, specificity of 100%, accuracy of 86.4%, PPV of 100% and NPV of 76.9% in differentiation true progression from pseudoprogression.
Copyright © 2015. Published by Elsevier Inc.

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Simultaneous imaging of radiation-induced cerebral microbleeds, arteries and veins, using a multiple gradient echo sequence at 7 Tesla.

The purpose of this study was to implement and evaluate the utility of a multi-echo sequence at 7 Tesla (T) for simultaneous time-of-flight (TOF) MR-angiography (MRA) and susceptibility-weighted imaging (SWI) of radiation-induced cerebral microbleeds (CMBs), intracranial arteries, and veins.
A four-echo gradient-echo sequence was implemented on a 7T scanner. The first echo was used to create TOF-MRA images, while the remaining echoes were combined to visualize CMBs and veins on SWI images. The sequence was evaluated on eight brain tumor patients with known radiation-induced CMBs. Single-echo images were also acquired to visually and quantitatively compare the contrast-to-noise ratio (CNR) of small- and intermediate-vessels between acquisitions. The number of CMBs detected with each acquisition was also quantified. Statistical significance was determined using a Wilcoxon signed-rank test.
Compared with the single-echo sequences, the CNR of small and intermediate arteries increased 7.6% (P < 0.03) and 9.5% (P = 0.06), respectively, while the CNR of small and intermediate veins were not statistically different between sequences (P = 0.95 and P = 0.46, respectively). However, these differences were not discernible by visual inspection. Also the multi-echo sequence detected 18.3% more CMBs (P < 0.008) due to higher slice resolution.
The proposed 7T multi-echo sequence depicts arteries, veins, and CMBs on a single image to facilitate quantitative evaluation of radiation-induced vascular injury.
© 2014 Wiley Periodicals, Inc.

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Relaxation and exchange dynamics of hyperpolarized 129Xe in human blood.

(129) Xe-blood NMR was performed over the full blood oxygenation range to evaluate (129) Xe relaxation and exchange dynamics in human blood.
Hyperpolarized (129) Xe was equilibrated with blood and isolated plasma, and NMR was performed at 1.5 T.
The (129) Xe relaxation rate was found to increase nonlinearly with decreasing blood oxygenation. Three constants were extrapolated: rsO2 =  11.1, a "relaxivity index" characterizing the rate of change of (129) Xe relaxation as a function of blood oxygenation, and 1/T1oHb  =  0.13 s(-1) and 1/T1dHb = 0.42 s(-1) , the (129) Xe relaxation rates in oxygenated blood and deoxygenated blood, respectively. In addition, rate constants, ka =  0.022 ms(-1) and kb =  0.062 ms(-1) , were determined for xenon diffusing between red blood cells (RBCs) and plasma (hematocrit  =  48%). The (129) Xe-O2 relaxivity in plasma, rO2 = 0.075 s(-1) mM(-1) , and the (129) Xe relaxation rate in isolated plasma (without dissolved O2 ), 1/T1,b0 = 0.046 s(-1) , were also calculated. Finally, intrinsic (129) Xe-RBC relaxation rates, 1/T1,aoHb = 0.19 s(-1) and 1/T1,adHb = 0.84 s(-1) , in oxygenated blood and deoxygenated blood, respectively, were calculated.
The relaxation and exchange analysis performed in this study should provide a sound experimental basis upon which to design future MR experiments for dissolved xenon transport from the lungs to distal tissues.
© 2014 Wiley Periodicals, Inc.

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ROBUST: Lenalidomide-R-CHOP versus placebo-R-CHOP in previously untreated ABC-type diffuse large B-cell lymphoma.

Activated B cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), the major constituent of nongerminal center B cell-like (non-GCB) DLBCL, is associated with poorer survival outcomes than GCB-type DLBCL. In Phase II studies, lenalidomide combined with R-CHOP (R(2)-CHOP) improved outcomes relative to historical R-CHOP in newly diagnosed DLBCL, particularly in non-GCB cases. ROBUST (CC-5013-DLC-002) is a randomized, double-blind, global, Phase III study of oral lenalidomide (15 mg, days 1-14) plus R-CHOP21 × 6 versus placebo-R-CHOP21 × 6 in patients with previously untreated ABC-type DLBCL. Subtyping is done within 3 calendar days by central laboratory gene expression profiling of formalin-fixed paraffin-embedded biopsy tissue. The primary end point is progression-free survival. Secondary end points include response rates, overall survival and health-related quality of life.

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A phospholipid-PEG2000 conjugate of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeting heterodimer peptide for contrast-enhanced ultrasound imaging of angiogenesis.

The transition of a targeted ultrasound contrast agent from animal imaging to testing in clinical studies requires considerable chemical development. The nature of the construct changes from an agent that is chemically attached to microbubbles to one where the targeting group is coupled to a phospholipid, for direct incorporation to the bubble surface. We provide an efficient method to attach a heterodimeric peptide to a pegylated phospholipid and show that the resulting construct retains nanomolar affinity for its target, vascular endothelial growth factor receptor 2 (VEGFR2), for both the human (kinase insert domain-containing receptor – KDR) and the mouse (fetal liver kinase 1 – Flk-1) receptors. The purified phospholipid-PEG-peptide isolated from TFA-based eluents is not stable with respect to hydrolysis of the fatty ester moieties. This leads to the time-dependent formation of the lysophospholipid and the phosphoglycerylamide derived from the degradation of the product. Purification of the product using neutral eluent systems provides a stable product. Methods to prepare the lysophospholipid (hydrolysis product) are also included. Biacore binding data demonstrated the retention of binding of the lipopeptide to the KDR receptor. The phospholipid-PEG2000-peptide is smoothly incorporated into gas-filled microbubbles and provides imaging of angiogenesis in a rat tumor model.

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