**7. Acknowledgements**

302 Advances in Cancer Therapy

experimental technique to a clinically feasible adjunct procedure that can be integrated into a standard morphologic imaging protocol. It does provide unique non-invasive functional information on the properties of tumors related to microcirculation (distribution volume, permeability, and perfusion). This information can improve diagnostic characterization, the follow-up of therapy, and tumor staging; and it provides tools to facilitate advanced molecular imaging. Preclinical and clinical studies suggest that a successful antivascular treatment results in a decrease in the rate of enhancement along with a decreased amplitude and a slower washout, and that poor response can result in persistent abnormal

Generally, PET measures of tumor perfusion have used (15O)-labeled radiotracers. The socalled steady state method requires inhalation of 15O-CO2 and the dynamic method requires an intravenous bolus injection of 15O-H2O (Jennings et al., 2008). A requirement for quantification of perfusion using dynamic methods is an accurate determination of an arterial input function, which can be obtained non-invasively in a purely arterial region of

In X-ray CT, the tissue contrast is based on variable attenuation coefficients of the object absorbing the X-rays. Hemodynamic parameters may be extracted from dynamic changes in X-ray attenuation caused by the intravenous injection of an iodinated contrast agent. Perfusion CT data can deliver quantitative hemodynamic information, such as blood volume, blood flow, permeability surface-area product and mean transit time (MTT)

There are several different ultrasonic approaches designed specifically to measure blood flow including transit time, continuous-wave Doppler, pulsed and color Doppler, and power Doppler flowmeters, requiring the use of microbubbles (filled with air, perfluorocarbon, sulfur hexafluoride or nitrogen), which expand and contract because of pressure from the acoustical transmit pulse, and the primary mode of echogenicity is the impedance mismatch between the microbubble–blood interface, making them significantly more echogenic than normal tissue. Typical parameters that are estimated using Doppler ultrasound include: percent intratumor contrast agent uptake, enhancement timing and pattern, percent blood volume fraction, red blood cell velocity, and perfusion; depending on

Heterogeneities in blood flow and oxygenation are key characteristics of solid tumors and constitute a therapeutic challenge when these tumors are treated with radiotherapy or systemic therapies. Because oxygen stabilizes DNA lesions, tumors become increasingly resistant to radiotherapy and to several forms of chemotherapy when the tumor pO2 decreases below a threshold of 10 mmHg. In the past decades, basic and preclinical researches have identified several adjuvant treatments aimed at transiently increasing tumor oxygenation at the time of radiotherapy. Their identification was based on an increasing

enhancement (Gillies et al., 2002).

interest, such as the aorta.

(Jennings et al., 2008).

**6. Conclusions** 

**5.2.4 Doppler ulstrasound** 

the type of study and tracer used (Jennings et al., 2008).

**5.2.3 Computed tomography** 

**5.2.2 Positron emission tomography** 

Works at the authors' labs are supported by grants from the European Research Council (FP7/2007-2013 ERC Independent Researcher Starting Grant 243188 TUMETABO to P.S.), the Belgian *Fonds National de la Recherche Scientifique* (F.R.S.-FNRS), the *Communauté Française de Belgique* (ARC 09/14-020), the *Fondation Belge Contre le Cancer* (200-2008), the *Fonds Joseph Maisin*, the Saint-Luc Foundation, and the *Pôle d'Attraction Interuniversitaire* PAI VI (P6/38). B.F.J. and P.S. are F.R.S.-FNRS Research Associates. For any correspondence contact P.S.; email: pierre.sonveaux@uclouvain.be.
