Mizuta 2 AbstractPurpose: Hypofractionated irradiation is often used in precise radiotherapy instead of conventional multi-fractionated irradiation. We propose a novel mathematical method for selecting a hypofractionated or multi-fractionated irradiation regime based on physical dose distribution adding to biological consideration.Methods and Materials: The linear quadratic (LQ) model was employed for the radiation effects on tumor and normal tissues, especially OARs. Based on the assumption that the OAR receives a fraction of the dose intended for the tumor, the minimization problem for the damage effect on the OAR was treated under the constraint that the radiation effect on the tumor is fixed.Results: For an N-time fractionated irradiation regime, the constraint of tumor lethality was described by an N-dimensional hypersphere. The total dose of the fractionated irradiations was considered for minimizing the damage effect on the OAR under the hypersphere condition. It was found that the advantage of hypofractionated or multi-fractionated irradiation therapies depends on the magnitude of the ratio of  parameters for the OAR and the tumor in the LQ model and the ratio of the dose for the OAR and the tumor.Conclusions: The present mathematical method shows that the multi-fractionated irradiation Mizuta 3 with a constant dose is better if the ratio of  for the OAR and the tumor is less than the ratio of the dose for the OAR and the tumor, while hypofractionated irradiation is better otherwise.

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Clock genes are expressed throughout the body, although how they oscillate in unrestrained animals is not known. Here, we show an in vivo imaging technique that enables long-term simultaneous imaging of multiple tissues. We use dual-focal 3D tracking and signal-intensity calibration to follow gene expression in a target area. We measure circadian rhythms of clock genes in the olfactory bulb, right and left ears and cortices, and the skin. In addition, the kinetic relationship between gene expression and physiological responses to experimental cues is monitored. Under stable conditions gene expression is in phase in all tissues. In response to a long-duration light pulse, the olfactory bulb shifts faster than other tissues. In Cry1−/− Cry2−/− arrhythmic mice circadian oscillation is absent in all tissues. Thus, our system successfully tracks circadian rhythms in clock genes in multiple tissues in unrestrained mice.

BackgroundWe performed a dosimetric comparison of spot-scanning proton therapy (SSPT) and intensity-modulated radiation therapy (IMRT) for hepatocellular carcinoma (HCC) to investigate the impact of tumor size on the risk of radiation induced liver disease (RILD).MethodsA number of alternative plans were generated for 10 patients with HCC. The gross tumor volumes (GTV) varied from 20.1 to 2194.5 cm3. Assuming all GTVs were spherical, the nominal diameter was calculated and ranged from 3.4 to 16.1 cm. The prescription dose was 60 Gy for IMRT or 60 cobalt Gy-equivalents for SSPT with 95% planning target volume (PTV) coverage. Using IMRT and SSPT techniques, extensive comparative planning was conducted. All plans were evaluated by the risk of RILD estimated using the Lyman-normal-tissue complication probability model.ResultsFor IMRT the risk of RILD increased drastically between 6.3–7.8 cm nominal diameter of GTV. When the nominal diameter of GTV was more than 6.3 cm, the average risk of RILD was 94.5% for IMRT and 6.2% for SSPT.ConclusionsRegarding the risk of RILD, HCC can be more safely treated with SSPT, especially if its nominal diameter is more than 6.3 cm.

Quantitative assessment of airway caliber is generally confined to indirect physiologic methods or to radiographic techniques. Fiberoptic bronchoscopy provides a direct view of airways, permitting quantification of airway caliber by image analysis. We investigated the characteristics of a bronchoscopic imaging system, determined its limitations in quantification and the corrections necessary for accurate assessment of image dimension, validated the methodology with airway models, and applied the technique to airways in vivo. The system comprised a bronchoscope, videocamera, videocassette recorder (VCR), computer with a frame grabber, and image-analysis program. Image quantification was affected by two sources of distortion: (1) Distance distortion: a loss of image resolution with increasing distance between the object and bronchoscope, requiring determination of the operational distance range. (2) Radial distortion: a progressive reduction in image size from the center to the periphery of the bronchoscopic field of view (FOV), requiring correction of airway dimension according to airway size and location in FOV. Validation of the methodology with different sized airway models indicated an underestimation of measured diameters, which normalized with distortion correction. We provide an example of quantitative videobronchoscopy with measurements of in vivo airway narrowing due to vagal stimulation in the anesthetized dog. Measurements of airway narrowing made with videobronchoscopy were also compared with those made with high-resolution computer-assisted tomography (HRCT) which suggested that the two technologies provide unique but complementary perspectives on airway dimensions. We conclude that videobronchoscopy and image analysis provide a novel and accurate method for the quantification of airway caliber.

The results suggested that by properly adjusting irradiation control parameters, gated proton spot-scanning beam therapy can be robust to target motion. This is an important first step toward establishing treatment plans in real patient geometry.

Purpose: In accurate proton spot-scanning therapy, continuous target tracking by fluoroscopic X-ray during irradiation is beneficial not only for respiratory moving tumors of lung and liver but also for relatively stationary tumors of prostate. Implanted gold markers have been used with great effect for positioning the target volume by a fluoroscopy, especially for the cases of liver and prostate with the targets surrounded by water-equivalent tissues.However, recent studies have revealed that gold markers can cause a significant underdose in proton therapy. This paper focuses on prostate cancer and explores the possibility that multiple-field irradiation improves the underdose effect by markers on Tumor Control Probability (TCP). Methods:A Monte Carlo simulation was performed to evaluate the dose distortion effect. A spherical gold marker was placed at several characteristic points in a water phantom. Markers were with two different diameters of 2 mm and 1.5 mm, both visible on fluoroscopy. Three beam arrangements of SFUD (single-field uniform dose)were examined: one lateral field, two opposite lateral fields, and three fields (two opposite lateral fields + anterior field). The Relative Biological Effectiveness (RBE) was set to 1.1 and a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in 37 fractions. The ratios of TCP to that without the marker (TCP r ) were compared with the parameters of the marker sizes, number of fields, and marker positions. To take into account the dependence of biological parameters in TCP model,  values of 1.5, 3, and 10 Gy (RBE) were considered.Results: It was found that the marker of 1.5 mm diameter does not affect the TCPs with all  values when two or more fields are used. On the other hand, if the marker size is 2 mm, more than two irradiation fields are required to suppress the decrease in TCP from TCP r by less than 3%. This is especially true when multiple (two or three) markers are used for alignment of a patient. Conclusions:It is recommended that 1.5 mm markers be used to avoid the reduction of TCP as well as to spare the surrounding critical organs, as long as the markers are visible on X-ray fluoroscopy. When 2 mm markers are implanted, more than two fields should be used and the markers should not be placed close to the distal edge of any of the beams.

This paper reports on Monte Carlo simulations of electrons in liquid water using a set of electron collision cross sections constructed with data published recently. The track history of electrons having initial energy ranged from 1keV to 10keV is investigated looking at the ionization and excitation processes. The results show that the ratio of the ionization and excitation events per track history is unique independent of the initial electron energy above a couple of hundred eV and these inelastic processes occur with low energy electrons frequently below 100eV. In particular, the excitation processes are dominated by the electrons below 50eV. Flight distance distributions between the inelastic collisions are also discussed.