Experiments were performed to determine whether changes in T2*-weighted MR images during and after hyperoxia differentiate tumors from normal tissue. Mammary adenocarcinomas implanted in the right hind limbs of rats were studied. Gradient echo images were obtained at 2 Tesla with an evolution time of 20 ms and a recycle time of 1 s. Breathing gas was either air or 100% O2. Significant increases in image intensity were observed in tumor centers and rims during hyperoxia while much smaller changes were detected in the surrounding muscle. The relaxation rate (1/T2*) in tumors decreased during hyperoxia by an average of 2.5 +/- 1.0 s-1, while in muscle the average change was an increase of 0.6 +/- 2.1 s-1. The largest decreases in relaxation rate were detected in non-necrotic tumor regions with relatively low density of blood vessels. Immediately following hyperoxia significant decreases in intensity were detected in tumors while much smaller decreases were detected in the surrounding muscle.

Dynamic MR images of the passage of gadopentetate dimeglumine through the kidneys of normal rats are obtained using a dual gradient-echo sequence. The amplitudes of gradient echoes are defined by local T1 and T2* values in the tissue. The ratio of these amplitudes, primarily defined by local T2*, can be used to differentiate between T1 and T2* effects. This is particularly important with regard to renal studies because, due to a highly inhomogeneous distribution of gadopentetate dimeglumine in the kidney, T2* shortening can impede MR data analysis. To study changes in the observed signal caused by gadopentetate dimeglumine, curves of MR renal intensity versus time were obtained in the cortex and medulla after administration of the contrast agent. Using T2* compensation, distinct temporal peaks were observed in the cortex and outer medulla, indicating a high concentration of gadopentetate dimeglumine in the vascular phase. The authors conclude that this technique can be a useful tool for studying renal function noninvasively.

Purpose: To assess the role of reoxygenation of hypoxic tumor cells in hypofractionated radiotherapy of prostate cancer. Methods: The considered radiobiological model is based on the assumption of two populations (compartments) of cells: oxygenated (aerobic) cells and hypoxic cells. After each fraction of radiation, some of the hypoxic cells reoxygenate while a fraction of initially aerobic cells becomes hypoxic. The kinetics of this process between successive treatments is described by coupled, first-order differential equations. To determine the effect of reoxygenation on cell kill in the treatment target, we utilize the linear-quadratic (LQ) model assuming different radiosensitivities for the aerobic and hypoxic cells. Results: Analytical solutions for the number of surviving malignant cells are obtained for special cases of slow and fast reoxygenation. The radiobiological effect of reoxygenation for different fractionation regimens is also evaluated numerically. Conclusions: In this study, a radiobiological model for kinetics of reoxygenation in tumors is used to evaluate different fractionation schedules in radiotherapy of prostate cancer. The obtained results indicate that in the case of low alpha/beta ratio for malignant cells (e.g., α=β = 1.5 Gy), treatment schedule with 4-10 fractions and dose per fraction >4-5 Gy can result in increased cell kill in the treatment target at the same level of rectal toxicity as compared to conventional fractionation. The findings of this study also suggest that radiotherapy of the prostate with 1-3 fractions can be radiobiologically inferior to treatments with greater number of fractions.

Purpose. To evaluate the effect of dose heterogeneity in the treatment target on biologically effective dose (BED) for frequently used hypofractionation regimens in stereotactic body radiation therapy (SBRT). Methods. In the case of non-uniform target dose, BED in the planning target volume (PTV) is determined by using the linear–quadratic model. An expression for BED is obtained for an arbitrary dose distribution in the PTV in the case of small variance of the target dose. Another analytical expression for BED is obtained by assuming a Gaussian dose distribution in the target. Results. Analytical expressions for BED as a function of the variance of the target dose have been derived. It is shown that a relatively small dose inhomogeneity (<5%–6%) can cause a significant reduction (i.e. >10%) in the corresponding BED and equivalent uniform dose (EUD) compared to the case of uniform target dose. Conclusions. Small variations in the absorbed dose can significantly reduce BED and EUD in the PTV. The effect of dose non-uniformity on BED increases with increasing dose per fraction. The observed reduction in BED compared to that for uniform target dose can be several times greater for SBRT than for standard fractionation with dose per fraction varying between 1.8 and 2 Gy.

Autopsy and pathology studies have shown that the caudal portion of the prostate gland harbors tumour in 64-75% of specimens examined. Accurate localization of the prostatic apex may be important in improving local control with external beam radiation therapy. We compared the location of the apex obtained with CT based treatment planning versus localization using retrograde urethrography in 32 consecutive patients. The prostatic apex, localized by CT and retrograde urethrography, was compared relative to the ischial tuberosities and the symphysis pubis. Discordance between the location of the prostatic apex as defined on CT scan and retrograde urethrography was found in 50% of patients evaluated. There was 31% discordance between the location of the prostatic apex as defined on CT and retrograde urethrography when data were analysed with the location of the prostatic apex 1 cm above the narrowing on urethrography, a definition others have suggested. The urethrogram defined prostatic apex, as compared with the CT definition, necessitated the treatment of more of the surrounding normal tissues in 31% of our cases, with four-field techniques. Comparison of dose-volume histograms of the bladder, rectum and penis irradiated for target volumes defined by CT versus retrograde urethrography showed that more penis was irradiated in some patients with the urethrogram defined prostatic apex; irradiation of the base of the penis could be relatively avoided by using a six-field treatment plan instead of the standard four-field box. There is discordance between the CT and urethrogram defined prostatic apex. Dose-volume histogram information suggests that differences in apex localization can significantly affect doses to normal adjacent prostatic tissues. Combining CT localization with the urethrogram localization of the prostatic apex optimizes radiotherapy planning and dose delivery.