Background. Distinction between tumor and treatment related changes is crucial for clinical management of patients with high-grade gliomas. Our purpose was to evaluate whether dynamic susceptibility contrast-enhanced (DSC) and dynamic contrast enhanced (DCE) perfusion-weighted imaging (PWI) metrics can effectively differentiate between recurrent tumor and posttreatment changes within the enhancing signal abnormality on conventional MRI. Methods. A comprehensive literature search was performed for studies evaluating PWI-based differentiation of recurrent tumor and posttreatment changes in patients with high-grade gliomas (World Health Organization grades III and IV). Only studies published in the "temozolomide era" beginning in 2005 were included. Summary estimates of diagnostic accuracy were obtained by using a random-effects model. Results. Of 1581 abstracts screened, 28 articles were included. The pooled sensitivities and specificities of each study's best performing parameter were 90% and 88% (95% CI: 0.85-0.94; 0.83-0.92) and 89% and 85% (95% CI: 0.78-0.96; 0.77-0.91) for DSC and DCE, respectively. The pooled sensitivities and specificities for detecting tumor recurrence using the 2 most commonly evaluated parameters, mean relative cerebral blood volume (rCBV) (threshold range, 0.9-2.15) and maximum rCBV (threshold range, 1.49-3.1), were 88% and 88% (95% CI: 0.81-0.94; 0.78-0.95) and , respectively. Conclusions. PWI-derived thresholds separating viable tumor from treatment changes demonstrate relatively good accuracy in individual studies. However, because of significant variability in optimal reported thresholds and other limitations in the existing body of literature, further investigation and standardization is needed before implementing any particular quantitative PWI strategy across institutions.
Confocal Raman micro-spectroscopy (CRMS) was used to measure time-course spectral images of live cells undergoing apoptosis without using molecular labels or other invasive procedures. Human breast cancer cells (MDA-MB-231) were exposed to 300 µM etoposide to induce apoptosis, and Raman spectral images were acquired from the same cells at 2-h intervals over a period of 6 h. The purpose-built inverted confocal Raman micro-spectrometer integrated an environmental enclosure and wide-field fluorescence imaging. These key instrumental elements allowed the cells to be maintained under sterile physiological conditions (37 • C, 5% CO 2 ) and enabled viability and apoptosis assays to be carried out on the cells at the end of CRMS measurements. The time-course spectral images corresponding to DNA Raman bands indicated an increase in signal intensity in apoptotic cells, which was attributed to DNA condensation. The Raman spectral images of lipids indicated a high accumulation of membrane phospholipids and highly unsaturated non-membrane lipids in apoptotic cells. This study demonstrates the potential of CRMS for label-free time-course imaging of individual live cells. This technique may become a useful tool for in vitro toxicological studies and testing of new pharmaceuticals, as well as other time-dependent cellular processes, such as cell differentiation, cell cycle and cell-cell interactions.
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