Synthesis and biophysical characteristics of riboflavin/HSA protein system on silver nanoparticles.

Novel l­Arginine­Dextran70 based-silver nanoparticles (SNPs) (SNPsArg), functionalized with Riboflavin (RF) and Human Serum Albumin (HSA) were characterized by UV-Vis absorption, Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM), fluorescence and circular dichroism spectroscopy, chemiluminescence and Neutral red assays. TEM analysis showed the formed faceted particles, large clumps/fused aggregates, nano-featured with the mean particle size of 41.60 nm. Chemiluminescence and Neutral red assays for in vitro antioxidant and cytotoxic activities of the SNPsArg/RF/HSA systems have been studied. It was pointed out that SNPsArg functionalized with RF and HSA resulted in a bio-nanosystem which leads to a high activity against oxygen free radicals, altered viability, morphology, apoptotic bodies and decreased cell density of L929 fibroblast cells. Results are relevant for understanding the redox properties of RF in the case of biological applications and especially for RF containing drugs.

An investigation of a PRESAGE® in vivo dosimeter for brachytherapy.

Determining accurate in vivo dosimetry in brachytherapy treatment with high dose gradients is challenging. Here we introduce, investigate, and characterize a novel in vivo dosimeter and readout technique with the potential to address this problem. A cylindrical (4 mm × 20 mm) tissue equivalent radiochromic dosimeter PRESAGE® in vivo (PRESAGE®-IV) is investigated. Two readout methods of the radiation induced change in optical density (OD) were investigated: (i) volume-averaged readout by spectrophotometer, and (ii) a line profile readout by 2D projection imaging utilizing a high-resolution (50 micron) telecentric optical system. Method (i) is considered the gold standard when applied to PRESAGE® in optical cuvettes. The feasibility of both methods was evaluated by comparison to standard measurements on PRESAGE® in optical cuvettes via spectrophotometer. An end-to-end feasibility study was performed by a side-by-side comparison with TLDs in an (192)Ir HDR delivery. 7 and 8 Gy was delivered to PRESAGE®-IV and TLDs attached to the surface of a vaginal cylinder. Known geometry enabled direct comparison of measured dose with a commissioned treatment planning system. A high-resolution readout study under a steep dose gradient region showed 98.9% (5%/1 mm) agreement between PRESAGE®-IV and Gafchromic® EBT2 Film. Spectrometer measurements exhibited a linear dose response between 0-15 Gy with sensitivity of 0.0133 ± 0.0007 ΔOD/(Gy ⋅ cm) at the 95% confidence interval. Method (ii) yielded a linear response with sensitivity of 0.0132 ± 0.0006 (ΔOD/Gy), within 2% of method (i). Method (i) has poor spatial resolution due to volume averaging. Method (ii) has higher resolution (∼1 mm) without loss of sensitivity or increased noise. Both readout methods are shown to be feasible. The end-to-end comparison revealed a 2.5% agreement between PRESAGE®-IV and treatment plan in regions of uniform high dose. PRESAGE®-IV shows promise for in vivo dose verification, although improved sensitivity would be desirable. Advantages include high-resolution, convenience and fast, low-cost readout.

Towards comprehensive characterization of Cs-137 Seeds using PRESAGE® dosimetry with optical tomography.

We describe a method to directly measure the radial dose and anisotropy functions of brachytherapy sources using polyurethane based dosimeters read out with optical CT. We measured the radial dose and anisotropy functions for a Cs-137 source using a PRESAGE® dosimeter (9.5cm diameter, 9.2cm height) with a 0.35cm channel drilled for source placement. The dosimeter was immersed in water and irradiated to 5.3Gy at 1cm. Pre- and post-irradiation optical CT scans were acquired with the Duke Large field of view Optical CT Scanner (DLOS) and dose was reconstructed with 0.5mm isotropic voxel size. The measured radial dose factor matched the published fit to within 3% for radii between 0.5-3.0cm, and the anisotropy function matched to within 4% except for θ near 0° and 180° and radii >3cm. Further improvements in measurement accuracy may be achieved by optimizing dose, using the high dynamic range scanning capability of DLOS, and irradiating multiple dosimeters. Initial simulations indicate an 8 fold increase in dose is possible while still allowing sufficient light transmission during optical CT. A more comprehensive measurement may be achieved by increasing dosimeter size and flipping the source orientation between irradiations.

TU-E-213CD-01: Image Guided Adaptive Brachytherapy for Cervical Cancer.

Image-guidance plays an important role in modern radiation therapy, predominantly in external beam planning and delivery. In contrast, brachytherapy is still largely based on systems originally developed in the early 20th century. In recent years, with the advent of high/pulsed dose rate (HDR/PDR) afterloading technology, advanced treatment planning systems and CT and MRI compatible applicators, image-guided adaptive brachytherapy treatments are now achievable. With image guidance, the target can be delineated more precisely, resulting in delivering more controlled doses of radiation to the target while sparing surrounding healthy tissue. GEC-ESTRO guidelines are crucial for implementing robust and standardized image guided adaptive brachytherapy (IGABT). They rely on MRI-guided planning for cervical cancer. MRI can be performed for each brachytherapy (BT) fraction to adaptively plan and deliver the desired radiation dose with less toxicity to surrounding tissues. MR imaging has its advantages, but also challenges and limitations (image artifacts and distortion related to magnetic nonlinearity, MR sequence selection, accuracy of 3D applicator reconstruction) that need addressed. Moreover, MRI technology is not readily available in most Radiation Oncology departments, making its implementation hard. In such settings, CT or US-based planning can be used despite lacking the desired soft tissue resolution to accurately depict the target. Hybrid approaches have been proposed, where a first BT fraction is planed based on MRI, and subsequent fractions are performed with CT-guidance. Moreover, new intracavitary/interstitial applicators are becoming available and data from centers using existent applicators is maturing. Regardless of the type of adaptive image guided and applicators used, there are still ongoing debates regarding the prescription, the relevance of point A dose, treatment planning in general, and the use of inverse planning in particular, role of model-based dose calculation algorithms, adaptive strategies, intrafraction variability, in-vivo dosimetry, dose summation with external beam treatments, to mention just some of the challenges raised by implementing this treatment technique. This symposium is proposing to address all of these issues and update the community at large on the status of image guided adaptive brachytherapy for cervical cancer. LEARNING OBJECTIVES: 1. To discuss the physics perspective of role of IGABT in management of cervical cancer. 2. To compare IGABT approaches: MRI, CT, US, and Hybrid 3. To present the advantages, challenges, and limitations of MRI for IGABT. 4. To discuss hot topics in IGABT including planning strategies, role of model-based dose calculation algorithms, new applicators, dose specification.

SU-D-BRB-06: Comprehensive Population-Averaged Arterial Input Function (AIF) for DCE-MRI of Head and Neck Cancer.

PURPOSE: To generate a composite population-averaged(PA)-AIF for quantitative analysis of DCE-MRI data in head and neck (H&N) patients that is based on the right (RT) and left (LT) carotids, two pre-treatment scans, and one post-treatment scan. METHODS: Twenty patients were imaged while undergoing concurrent chemoradiation (CRT) for H&N malignancies. The imaging protocol (1) included two baseline scans one week apart (Base1, Base2), and one scan 1 week post-CRT (Post). For each patient and time point, regions of interest (ROIs) in both the RT and LT carotids were drawn on coronal images. The plasma concentration curves of all ROIs were averaged and fit to a bi-exponential decay function to obtain the final PA- AIF (AvgAll). The ROIs were also divided by time point to obtain AvgBasel, AvgBase2, and AvgPost AIFs. The vascular transfer constant for both primary and nodes, Ktrans , was calculated (iCAD, Inc.) using the 4 AIFs, as well as the generic Weinmann's AIF. The median Ktrans values resulting from the AvgAll AIF were compared using Bland-Altman plots with the ones obtained from each individual time point. The Wilcoxon signed-rank test was used to compare the proposed AvgAll AIF and the generic AIF. RESULTS: The plasma parameters for the AvgAll AIF were a1,2=27.1135/17.6486 kg/liter, m 1,2=11.7525/0.2054 min-1 . The differences in Ktrans values using these coefficients vs. Weinmann's were statistically significant (p<0.0001). The median Ktrans values from the AvgBasel,AvgBase2, and AvgPost AIFs were, in most cases, not significantly different from the AvgAll values, indicating that the latter is appropriate foruse at all time points. CONCLUSIONS: A population-averaged AIF for H&N was generated that accounts for differences in RT vs. LT carotids, day-today AIF fluctuations, and treatment-induced AIF changes. It is not necessary to measure a post-treatment AIF to evaluate treatment-induced Ktrans changes.l. Craciunescu et al., MedPhys, 37, 6, 2683, 2010.

SU-D-213AB-05: Commissioning a CT Compatible LDR T&O Applicator Using Analytical Calculation with ID and 3D Dosimetry.

PURPOSE: To determine the characteristics of a new commercially available CT-compatible LDR Tandem and Ovoid (T&O) applicator using 3D dosimetry. METHODS: We characterized source attenuation through the asymmetric gold shielding in the buckets by measuring dose with diode and 3D dosimetry and compared to an analytical line integral calculation. For 3D dosimetry, a cylindrical PRESAGE dosimeter (9.5cm diameter, 9.2cm height) with a central 6mm channel bored for source placement was scanned with the Duke Large field of view Optical CT-Scanner (DLOS) before and after delivering a nominal 7.7Gy at a distance of 1 cm using a Cs-137 source loaded in the bucket. The optical CT scan time lasted approximately 15 minutes during which 720 projections were acquired at 0.5° increments, anda 3D dose distribution was reconstructed with a 0.5mm3 isotropic voxel size. The 3D dose distribution was applied to a CT-based T&O implant to determine effect of ovoid shielding on the dose delivered to ICRU 38 Point A as well as D2cc of the bladder, rectum, bowel, and sigmoid. RESULTS: Dose transmission through the gold shielding at a radial distance of 1-3cm from midplane of the source was 86.6%, 86.1, and 87.0% for analytical calculation, diode, and 3D dosimetry, respectively. For the gold shielding of the bucket, dose transmission calculated using the 3D dosimetrymeasurement was found to be lowest at oblique angles from the bucket witha minimum of ∼51%. For the patient case, attenuation from the buckets leadto a decrease in average Point A dose of ∼4% and decrease in D2cc to bladder, rectum, sigmoid, and bowel of 2%, 15%, 2%, and 7%, respectively. CONCLUSIONS: The measured 3D dose distribution provided unique insight to the dosimetry and shielding characteristics of the investigated applicator, the technique for which can be applied to commissioning of other brachytherapy applicators. John Adamovics is the owner of Heuris Pharma LLC. Partially supported by NIH Grant R01 CA100835-01.

Thermal characteristics of thermobrachytherapy surface applicators for treating chest wall recurrence.

The aim of this study was to investigate temperature and thermal dose distributions of thermobrachytherapy surface applicators (TBSAs) developed for concurrent or sequential high dose rate (HDR) brachytherapy and microwave hyperthermia treatment of chest wall recurrence and other superficial diseases. A steady-state thermodynamics model coupled with the fluid dynamics of a water bolus and electromagnetic radiation of the hyperthermia applicator is used to characterize the temperature distributions achievable with TBSAs in an elliptical phantom model of the human torso. Power deposited by 915 MHz conformal microwave array (CMA) applicators is used to assess the specific absorption rate (SAR) distributions of rectangular (500 cm(2)) and L-shaped (875 cm(2)) TBSAs. The SAR distribution in tissue and fluid flow distribution inside the dual-input dual-output (DIDO) water bolus are coupled to solve the steady-state temperature and thermal dose distributions of the rectangular TBSA (R-TBSA) for superficial tumor targets extending 10-15 mm beneath the skin surface. Thermal simulations are carried out for a range of bolus inlet temperature (T(b) = 38-43 degrees C), water flow rate (Q(b) = 2-4 L min(-1)) and tumor blood perfusion (omega(b) = 2-5 kg m(-3) s(-1)) to characterize their influence on thermal dosimetry. Steady-state SAR patterns of the R- and L-TBSA demonstrate the ability to produce conformal and localized power deposition inside the tumor target sparing surrounding normal tissues and nearby critical organs. Acceptably low variation in tissue surface cooling and surface temperature homogeneity was observed for the new DIDO bolus at a 2 L min(-1) water flow rate. Temperature depth profiles and thermal dose volume histograms indicate bolus inlet temperature (T(b)) to be the most influential factor on thermal dosimetry. A 42 degrees C water bolus was observed to be the optimal choice for superficial tumors extending 10-15 mm from the surface even under significant blood perfusion. Lower bolus temperature may be chosen to reduce the thermal enhancement ratio (TER) in the most sensitive skin where maximum radiation dose is delivered and to extend the thermal enhancement of radiation dose deeper. This computational study indicates that well-localized elevation of tumor target temperature to 40-44 degrees C can be accomplished by large surface-conforming TBSAs using appropriate selection of coupling bolus temperature.

On the Feasibility of Verification of 3D Dosimetry Near Brachytherapy Sources Using PRESAGE/Optical-CT.

PURPOSE: The feasibility of using the PRESAGE/Optical-CT system for 3D dosimetry verification around a brachytherapy source is investigated. METHOD AND MATERIALS: Brachytherapy dose distributions were obtained by irradiation of cylindrical PRESAGE volumes 6cm in diameter by 8cm height with a GammaMed 12i Ir-192 HDR unit (Varian Medical Systems). A narrow channel on the central axis was created by setting a steel catheter in the Presage during manufacture, enabling measurements close to the source (~3mm). RESULTS: Comparison of dose line profiles shows good agreement between PRESAGE and verified calculated dose calculation, in both high and low dose regions. CONCLUSION: The PRESAGE/Optical-CT shows good potential in verification of 3D dose distributions around brachytherapy sources.

Feasibility of optimizing the dose distribution in lung tumors using fluorine-18-fluorodeoxyglucose positron emission tomography and single photon emission computed tomography guided dose prescriptions.

The information provided by functional images may be used to guide radiotherapy planning by identifying regions that require higher radiation dose. In this work we investigate the dosimetric feasibility of delivering dose to lung tumors in proportion to the fluorine-18-fluorodeoxyglucose activity distribution from positron emission tomography (FDG-PET). The rationale for delivering dose in proportion to the tumor FDG-PET activity distribution is based on studies showing that FDG uptake is correlated to tumor cell proliferation rate, which is shown to imply that this dose delivery strategy is theoretically capable of providing the same duration of local control at all voxels in tumor. Target dose delivery was constrained by single photon emission computed tomography (SPECT) maps of normal lung perfusion, which restricted irradiation of highly perfused lung and imposed dose-function constraints. Dose-volume constraints were imposed on all other critical structures. All dose-volume/function constraints were considered to be soft, i.e., critical structure doses corresponding to volume/function constraint levels were minimized while satisfying the target prescription, thus permitting critical structure doses to minimally exceed dose constraint levels. An intensity modulation optimization methodology was developed to deliver this radiation, and applied to two lung cancer patients. Dosimetric feasibility was assessed by comparing spatially normalized dose-volume histograms from the nonuniform dose prescription (FDG-PET proportional) to those from a uniform dose prescription with equivalent tumor integral dose. In both patients, the optimization was capable of delivering the nonuniform target prescription with the same ease as the uniform target prescription, despite SPECT restrictions that effectively diverted dose from high to low perfused normal lung. In one patient, both prescriptions incurred similar critical structure dosages, below dose-volume/function limits. However, in the other patient, critical structure dosage from the nonuniform dose prescription exceeded dose-volume/function limits, and greatly exceeded that from the uniform dose prescription. Strict compliance to dose-volume/ function limits would entail reducing dose proportionality to the FDG-PET activity distribution, thereby theoretically reducing the duration of local control. Thus, even though it appears feasible to tailor lung tumor dose to the FDG-PET activity distribution, despite SPECT restrictions, strict adherence to dose-volume/function limits could compromise the effectiveness of functional image guided radiotherapy.

Pulsatile blood flow effects on temperature distribution and heat transfer in rigid vessels.

The effect of blood velocity pulsations on bioheat transfer is studied. A simple model of a straight rigid blood vessel with unsteady periodic flow is considered. A numerical solution that considers the fully coupled Navier-Stokes and energy equations is used for the simulations. The influence of the pulsation rate on the temperature distribution and energy transport is studied for four typical vessel sizes: aorta, large arteries, terminal arterial branches, and arterioles. The results show that: the pulsating axial velocity produces a pulsating temperature distribution; reversal of flow occurs in the aorta and in large vessels, which produces significant time variation in the temperature profile. Change of the pulsation rate yields a change of the energy transport between the vessel wall and fluid for the large vessels. For the thermally important terminal arteries (0.04-1 mm), velocity pulsations have a small influence on temperature distribution and on the energy transport out of the vessels (8 percent for the Womersley number corresponding to a normal heart rate). Given that there is a small difference between the time-averaged unsteady heat flux due to a pulsating blood velocity and an assumed nonpulsating blood velocity, it is reasonable to assume a nonpulsating blood velocity for the purposes of estimating bioheat transfer.

3D numerical reconstruction of the hyperthermia induced temperature distribution in human sarcomas using DE-MRI measured tissue perfusion: validation against non-invasive MR temperature measurements.

Essential to the success of optimized thermal treatment during hyperthermia is accurate modelling. Advection of energy due to blood perfusion significantly affects the temperature. Without accurate estimates of the magnitude of the local tissue blood perfusion, accurate estimates of the temperature distribution can not be made. It is shown here that the blood mass flow rate per unit volume of tissue in the Pennes' bio-heat equation can be modelled using a relative perfusion index (RPI) determined with dynamic-enhanced magnetic resonance imaging (DE-MRI). Temperature distributions in two patients treated with hyperthermia at Duke University Medical Center for high-grade leg tissue sarcomas are modelled, and the resultant temperatures are compared to measured temperatures using a non-invasive MR thermometry technique. Significant correlations are found between the DE-MRI perfusion images, the MR temperature images, and the numerical simulation of the temperature field. The correlation between DE-MRI measured values and advective heat loss in tissue is used to scale the perfusion distribution, thereby allowing the continuum model to account for the local thermal impact of vasculature in the tumour. Large vessels in tumour and neighbouring healthy tissue need to be taken into account in order to accurately describe the complete temperature distribution.

Three-dimensional tumor perfusion reconstruction using fractal interpolation functions.

It has been shown that the perfusion of blood in tumor tissue can be approximated using the relative perfusion index determined from dynamic contrast-enhanced magnetic resonance imaging (DE-MRI) of the tumor blood pool. Also, it was concluded in a previous report that the blood perfusion in a two-dimensional (2-D) tumor vessel network has a fractal structure and that the evolution of the perfusion front can be characterized using invasion percolation. In this paper, the three-dimensional (3-D) tumor perfusion is reconstructed from the 2-D slices using the method of fractal interpolation functions (FIF), i.e., the piecewise self-affine fractal interpolation model (PSAFIM) and the piecewise hidden variable fractal interpolation model (PHVFIM). The fractal models are compared to classical interpolation techniques (linear, spline, polynomial) by means of determining the 2-D fractal dimension of the reconstructed slices. Using FIFs instead of classical interpolation techniques better conserves the fractal-like structure of the perfusion data. Among the two FIF methods, PHVFIM conserves the 3-D fractality better due to the cross correlation that exists between the data in the 2-D slices and the data along the reconstructed direction. The 3-D structures resulting from PHVFIM have a fractal dimension within 3%-5% of the one reported in literature for 3-D percolation. It is, thus, concluded that the reconstructed 3-D perfusion has a percolation-like scaling. As the perfusion term from bio-heat equation is possibly better described by reconstruction via fractal interpolation, a more suitable computation of the temperature field induced during hyperthermia treatments is expected.

Discretizing large traceable vessels and using DE-MRI perfusion maps yields numerical temperature contours that match the MR noninvasive measurements.

The success of hyperthermia treatments is dependent on thermal dose distribution. However, the three-dimensional temperature distribution remains largely unknown. Without this knowledge, the relationship between thermal dose and outcome is noisy, and therapy cannot be optimized. Accurate computations of thermal distribution can contribute to an optimized therapy. The hyperthermia modeling group in the Department of Radiotherapy, University Medical Center Utrecht devised a Discrete Vasculature [Kotte et al., Phys. Med. Biol. 41, 865-884 (1996)] model that accounts for the presence of vessel trees in the computational domain. The vessel tree geometry is tracked using magnetic resonance (MR) angiograms to a minimum diameter between 0.6 and 1 mm. However, smaller vessels (0.2-0.6 mm) are known to account for significant heat transfer. The hyperthermia group at Duke University Medical Center has proposed using perfusion maps derived from dynamic-enhanced magnetic resonance imaging to account for the tissue perfusion heterogeneity [Craciunescu et al., Int. J. Hyperthermia 17, 221-239 (2001)]. In addition, techniques for noninvasive temperature measurements have been devised to measure temperatures in vivo [Samulski et al., Int. J. Hypertherminal, 819-829 (1992)]. In this work, a patient with high-grade sarcoma has been retrospectively modeled to determine the temperature distribution achieved during a hyperthermia treatment. Available for this model were MR depicted geometry, angiograms, perfusion maps, as necessary for accurate thermal modeling, as well as MR thermometry data for validation purposes. The vasculature assembly through modifiable potential program [Van Leeuwen et al., IEEE Trans. Biomed. Eng. 45, 596-604 (1998)] was used in order to incorporate the traceable large vessels. Temperature simulations were made using different approaches to describe perfusion. The simulated cases were the bioheat equation with constant perfusion rates per tissue type, perfusion maps alone, tracked vessel tree and perfusion maps, and generated vessel tree. The results were compared with MR thermometry data for a single patient data set, concluding that a combination between large traceable vessels and perfusion map yields the best results for this particular patient. The technique has to be repeated on several patients, first with the same type of malignancy, and after that, on patients having malignancies at other different sites.

Perturbations in hyperthermia temperature distributions associated with counter-current flow: numerical simulations and empirical verification.

Two numerical techniques are used to calculate the effect of large vessel counter-current flow on hyperthermic temperature distributions. One is based on the Navier-Stokes equation for steady-state flow, and the second employs a convective-type boundary condition at the interface of the vessel walls. Steady-state temperature fields were calculated for two energy absorption rate distributions (ARD) in a cylindrical tissue model having two pairs of counter-current vessels (one pair with equal diameter vessels and another pair with unequal diameters). The first assumed a uniform ARD throughout cylinder; the second ARD was calculated for a tissue cylinder inside an existing four antenna Radiofrequency (RF) array. A tissue equivalent phantom was constructed to verify the numerical calculations. Temperatures induced with the RF array were measured using a noninvasive magnetic resonance imaging technique based on the chemical shift of water. Temperatures calculated using the two numerical techniques are in good agreement with the measured data. The results show: 1) the convective-type boundary condition technique reduces computation time by a factor of ten when compared to the fully conjugated method with little quantitative difference (approximately 0.3 degree C) in the numerical accuracy and 2) the use of noninvasive magnetic resonance imaging (thermal imaging) to quantitatively access the temperature perturbations near large vessels is feasible using the chemical shift technique.

Experimental evaluation of the thermal properties of two tissue equivalent phantom materials.

Tissue equivalent radio frequency (RF) phantoms provide a means for measuring the power deposition of various hyperthermia therapy applicators. Temperature measurements made in phantoms are used to verify the accuracy of various numerical approaches for computing the power and/or temperature distributions. For the numerical simulations to be accurate, the electrical and thermal properties of the materials that form the phantom should be accurately characterized. This paper reports on the experimentally measured thermal properties of two commonly used phantom materials, i.e. a rigid material with the electrical properties of human fat, and a low concentration polymer gel with the electrical properties of human muscle. Particularities of the two samples required the design of alternative measuring techniques for the specific heat and thermal conductivity. For the specific heat, a calorimeter method is used. For the thermal diffusivity, a method derived from the standard guarded comparative-longitudinal heat flow technique was used for both materials. For the 'muscle'-like material, the thermal conductivity, density and specific heat at constant pressure were measured as: k = 0.31 +/- 0.001 W(mK)(-1), p = 1026 +/- 7 kgm(-3), and c(p) = 4584 +/- 107 J(kgK)(-1). For the 'fat'-like material, the literature reports on the density and specific heat such that only the thermal conductivity was measured as k = 0.55 W(mK)(-1).

Dynamic contrast-enhanced MRI and fractal characteristics of percolation clusters in two-dimensional tumor blood perfusion.

Dynamic contrast-enhanced magnetic resonance imaging (DE-MRI) of the tumor blood pool is used to study tumor tissue perfusion. The results are then analyzed using percolation models. Percolation cluster geometry is depicted using the wash-in component of MRI contrast signal intensity. Fractal characteristics are determined for each two-dimensional cluster. The invasion percolation model is used to describe the evolution of the tumor perfusion front. Although tumor perfusion can be depicted rigorously only in three dimensions, two-dimensional cases are used to validate the methodology. It is concluded that the blood perfusion in a two-dimensional tumor vessel network has a fractal structure and that the evolution of the perfusion front can be characterized using invasion percolation. For all the cases studied, the front starts to grow from the periphery of the tumor (where the feeding vessel was assumed to lie) and continues to grow toward the center of the tumor, accounting for the well-documented perfused periphery and necrotic core of the tumor tissue.