Development of Automated Delivery Quality Assurance Analysis Software for Helical Tomotherapy.

BACKGROUND: To develop a fully automated in-house gamma analysis software for the "Cheese" phantom-based delivery quality assurance (QA) of helical tomotherapy plans. METHODS: The developed in-house software was designed to automate several procedures, which need to be manually performed using commercial software packages. The region of interest for the analysis was automatically selected by cropping out film edges and thresholding dose values (>10% of the maximum dose). The film-measured dose was automatically aligned to the computed dose using an image registration algorithm. An optimal film scaling factor was determined to maximize the percentage of pixels passing gamma (gamma passing rate) between the measured and computed doses (3%/3 mm criteria). This gamma analysis was repeated by introducing setup uncertainties in the anterior-posterior direction. For 73 tomotherapy plans, the gamma analysis results using the developed software were compared to those analyzed by medical physicists using a commercial software package. RESULTS: The developed software successfully automated the gamma analysis for the tomotherapy delivery quality assurance. The gamma passing rate (GPR) calculated by the developed software was higher than that by the clinically used software by 3.0%, on average. While, for 1 of the 73 plans, the GPR by the manual gamma analysis was higher than 90% (pass/fail criteria), the gamma analysis using the developed software resulted in fail (GPR < 90%). CONCLUSIONS: The use of automated and standardized gamma analysis software can improve both the clinical efficiency and veracity of the analysis results. Furthermore, the gamma analyses with various film scaling factors and setup uncertainties will provide clinically useful information for further investigations.

A New Approach to Quantify and Grade Radiation Dermatitis Using Deep-Learning Segmentation in Skin Photographs.

AIMS: Objective evaluation of radiation dermatitis is important for analysing the correlation between the severity of radiation dermatitis and dose distribution in clinical practice and for reliable reporting in clinical trials. We developed a novel radiation dermatitis segmentation system based on convolutional neural networks (CNNs) to consistently evaluate radiation dermatitis. MATERIALS AND METHODS: The radiation dermatitis segmentation system is designed to segment the radiation dermatitis occurrence area using skin photographs and skin-dose distribution. A CNN architecture with a dilated convolution layer and skip connection was designed to estimate the radiation dermatitis area. Seventy-three skin photographs obtained from patients undergoing radiotherapy were collected for training and testing. The ground truth of radiation dermatitis segmentation is manually delineated from the skin photograph by an experienced radiation oncologist and medical physicist. We converted the skin photographs to RGB (red-green-blue) and CIELAB (lightness (L∗), red-green (a∗) and blue-yellow (b∗)) colour information and trained the network to segment faint and severe radiation dermatitis using three different input combinations: RGB, RGB + CIELAB (RGBLAB) and RGB + CIELAB + skin-dose distribution (RGBLAB_D). The proposed system was evaluated using the Dice similarity coefficient (DSC), sensitivity, specificity and normalised Matthews correlation coefficient (nMCC). A paired t-test was used to compare the results of different segmentation performances. RESULTS: Optimal data composition was observed in the network trained for radiation dermatitis segmentation using skin photographs and skin-dose distribution. The average DSC, sensitivity, specificity and nMCC values of RGBLAB_D were 0.62, 0.61, 0.91 and 0.77, respectively, in faint radiation dermatitis, and 0.69, 0.78, 0.96 and 0.83, respectively, in severe radiation dermatitis. CONCLUSION: Our study showed that CNN-based radiation dermatitis segmentation in skin photographs of patients undergoing radiotherapy can describe radiation dermatitis severity and pattern. Our study could aid in objectifying the radiation dermatitis grading and analysing the reliable correlation between dosimetric factors and the morphology of radiation dermatitis.

The effect of hip dysplasia on some biochemical parameters, oxidative stress factors and hematocrit levels in dogs.

In this study, it was aimed to investigate the effect of hip dysplasia on some biochemical parameters, oxidative stress factors and hematocrit values in dogs. Hematocrit values (HTC), serum calcium (Ca), phosphorus (P) levels, serum alkaline phosphatase (ALP), creatine kinase (CK) activities and oxidative stress factors were evaluated in a total of 27 dogs with healthy hip joints (n: 11) and hip dysplasia (n: 16). There was no statistically significant difference between the two groups in terms of HCT, Ca and P values (p˃0.05). ALP and CK activities were found to be statistically significantly increased in the group with hip dysplasia compared to the control group with a healthy hip joint (p˂0.05). While malondialdehyde (MDA) level, one of the oxidative stress factors, was increased in the group with hip dysplasia, decreased glutathione (GSH) levels, catalase (CAT) and glutathione peroxidase (GSH-Px) activities were significantly decreased. There was no significant difference between the two groups in terms of superoxide dismutase (SOD) level. As a result, it was determined that oxidative stress factors differ in dogs with hip dysplasia compared to dogs with the healthy hip joint.

New mesh-type phantoms and their dosimetric applications, including emergencies.

Committee 2 of the International Commission on Radiological Protection (ICRP) has constructed mesh-type adult reference computational phantoms by converting the voxel-type ICRP Publication 110 adult reference computational phantoms to a high-quality mesh format, and adding those tissues that were below the image resolution of the voxel phantoms and therefore not included in the Publication 110 phantoms. The new mesh phantoms include all the necessary source and target tissues for effective dose calculations, including the 8-40-µm-thick target layers of the alimentary and respiratory tract organs, thereby obviating the need for supplemental organ-specific stylised models (e.g. respiratory airways, alimentary tract organ walls and stem cell layers, lens of the eye, and skin basal layer). To see the impact of the new mesh-type reference phantoms, dose coefficients for some selected external and internal exposures were calculated and compared with the current reference values in ICRP Publications 116 and 133, which were calculated by employing the Publication 110 phantoms and the supplemental stylised models. The new mesh phantoms were also used to calculate dose coefficients for industrial radiography sources near the body, which can be used to estimate the organ doses of the worker who is accidentally exposed by an industrial radiography source; in these calculations, the mesh phantoms were deformed to reflect the size of the worker, and also to evaluate the effect of posture on dose coefficients.

Loss of Keratin 17 induces tissue-specific cytokine polarization and cellular differentiation in HPV16-driven cervical tumorigenesis in vivo.

Despite preventive human papilloma virus (HPV) vaccination efforts, cervical cancer remains a leading cause of death in women worldwide. Development of therapeutic approaches for cervical cancer are hampered by a lack of mechanistic insight during tumorigenesis. The cytoskeletal protein Keratin 17 (KRT17;K17) is robustly expressed in a broad array of carcinomas, including in cervical tumors, where it has both diagnostic and prognostic value. In this study, we have established multiple functional roles for K17 in the promotion of cervical tumorigenesis in vivo using the established HPV16tg mouse model for cervical squamous cell carcinoma. In HPV16tg/+;Krt17-/-relative to HPV16tg/+ reference female mice, onset of cervical lesions is delayed and closely paralleled by marked reductions in hyperplasia, dysplasia and vascularization. In addition, loss of Krt17 is associated with a cytokine polarization and recruitment of effector immune cells to lesion-prone cervical epithelia. Further, we observed marked enhancement of terminal differentiation in HPV16tg/+;Krt17-/-cervical epithelium accompanied by a stimulation and expansion in the expression of p63, a known basal/reserve cell marker in this tissue. Altogether, the data suggest that the loss of Krt17 may foster an overall protective environment for lesion-prone cervical tissue. In addition to providing new insights into the immunomodulatory and cellular mechanisms of cervical tumorigenesis, these findings may help guide the development of future therapies including vaccines.

The reference phantoms: voxel vs polygon.

The International Commission on Radiological Protection (ICRP) reference male and female adult phantoms, described in Publication 110, are voxel phantoms based on whole-body computed tomography scans of a male and a female patient, respectively. The voxel in-plane resolution and the slice thickness, of the order of a few millimetres, are insufficient for proper segmentation of smaller tissues such as the lens of the eye, the skin, and the walls of some organs. The calculated doses for these tissues therefore present some limitations, particularly for weakly penetrating radiation. Similarly, the Publication 110 phantoms cannot represent 8-40-µm-thick target regions in respiratory or alimentary tract organs. Separate stylised models have been used to represent these tissues for calculation of the ICRP reference dose coefficients (DCs). ICRP Committee 2 recently initiated a research project, the ultimate goal of which is to convert the Publication 110 phantoms to a high-quality polygon-mesh (PM) format, including all source and target regions, even those of the 8-40-µm-thick alimentary and respiratory tract organs. It is expected that the converted phantoms would lead to the same or very similar DCs as the Publication 110 reference phantoms for penetrating radiation and, at the same time, provide more accurate DCs for weakly penetrating radiation and small tissues. Additionally, the reference phantoms in the PM format would be easily deformable and, as such, could serve as a starting point to create phantoms of various postures for use, for example, in accidental dose calculations. This paper will discuss the current progress of the phantom conversion project and its significance for ICRP DC calculations.

Detection of extrapulmonary tuberculosis with gallium-67 scan and computed tomography.

We evaluated 23 patients with extrapulmonary tuberculosis (TB) with 67Ga imaging to assess its usefulness in the diagnosis of this condition. We performed computed tomography (CT) in 17 patients to assess CT features of extrapulmonary TB in comparison with findings from 67Ga scans. Nineteen of 23 patients (83%) had positive findings on 67Ga scans. One of five patients with tuberculous mediastinal lymphadenopathy, two patients with cervical lymphadenitis and a patient with renal TB had negative 67Ga scans. It was observed that the detection of previously unrecognized primary foci of TB, without concomitant pulmonary TB, was possible using 67Ga imaging in five patients (22%). The 67Ga scan was relatively sensitive for the localization of extrapulmonary TB. It is suggested that the 67Ga scan could serve as a screening method, when followed by CT and ultrasonography, for the initial detection of occult tuberculous lesions, especially in patients with prolonged fever.

Estrous cycle dependence of nitrosomethylurea (NMU)-induced preneoplastic lesions in rat mammary gland.

Virgin 50-55-day-old rats exhibiting regular estrous cycles were injected i.v. with the direct acting carcinogen 1-nitroso-1-methylurea (NMU) on the morning of proestrus, estrus, or diestrus. Rats were killed at weekly intervals following NMU administration to identify source and number of microscopically identifiable dysplasias. Terminal end bud (TEB) abnormalities appeared within 1 week following NMU administration, with a significantly greater number of abnormal TEBs in mammary glands of rats injected on proestrus (PE) and estrus (E) than on diestrus (DE). Ductal (DH) and ductal alveolar hyperplasias (DAH) and hyperplastic alveolar nodules (HAN) appeared during week 3, with significantly more of each type of lesion appearing by 6 weeks after NMU injection. HAN were most numerous in glands from rats injected on estrus. Adenocarcinomas arose from both the proximal and distal ductal network; at 10 and 12 weeks post NMU, significantly more tumors were found in rats injected on proestrus than diestrus and estrus. These results support the theory that the hormonal environment at the time of NMU administration significantly alters early development of mammary tumors in the rat.

Necrotic areas in VX2 carcinoma of rabbits. Correlation of magnetic resonance imaging and pathologic appearance.

RATIONALE AND OBJECTIVES: To assess the potential of magnetic resonance imaging (MRI) for evaluating the evolution of tumor necrosis, the authors evaluated 28 VX2 carcinomas inoculated in the thigh muscles of rabbits. METHODS: MRI of VX2 carcinomas at 2.0 T was done with spin-echo technique 1 week (14 tumors) and 3 weeks (14 tumors) after the inoculation of tumor cells. T1- and T2-weighted images were obtained with 500/30 and 2,500/80 sequences; the authors also performed enhanced T1-weighted images with contrast medium. MRI and histopathologic findings were compared. RESULTS: Enhanced T1-weighted images with gadolinium-DTPA (Gd-DTPA) (dimeglumine gadopentetate) could depict necrosis in almost all tumors (27/28) and were the most sensitive technique followed by T2- and T1-weighted images. T2-weighted images best permitted the evaluation of the characteristics of necrotic areas in VX2 carcinomas, followed by T1-weighted images with contrast enhancement, and unenhanced T1-weighted images. On T2-weighted images, low-intensity areas of necrotic areas correspond to areas of early necrosis, isointense areas corresponded to areas of intermediate necrosis, and high-intensity areas corresponded to the late phase of necrosis. CONCLUSIONS: MRI is useful in depicting necrosis and characterizing different phases of necrosis in VX2 carcinomas.

Incompatibility of water-soluble contrast media and intravascular pharmacologic agents. An in vitro study.

In vitro incompatibilities between nine water-soluble contrast media and 21 intravascular pharmacologic agents were investigated using naked-eye observation and a centrifuge. Most of the previously reported incompatibilities were verified, and a few new incompatibilities were discovered: phentolamine mesylate with diatrizoate sodium, diatrizoate meglumine, ioxaglate, and iothalamate; diatrizoate meglumine with diazepam and meperidine hydrochloride; and diatrizoate sodium with meperidine hydrochloride. There were no incompatibilities when the pharmacologic agents investigated were mixed with ioxithalamate, iopromide, iopamidol, and iohexol.

An experimental study on thrombogenicity of various metallic microcoils with or without thrombogenic coatings.

RATIONALE AND OBJECTIVES: Various metallic microcoils have been used as effective embolic materials (stainless steel, tungsten, and platinum). It also has been reported in several articles that the thrombogenicity of coils increased after soaking in thrombin solutions. To compare the thrombogenicity, the authors performed in vitro study, measuring whole blood clotting time (WBCT) of the various microcoils with and without coating with thrombin, gelatin, or both gelatin and thrombin. METHODS: Stainless steel, tungsten, and platinum microcoils were used in the study. For thrombin coating, the microcoils were soaked in 4 U/mL thrombin solution for 5 minutes, dried for 30 minutes, then soaked and dried again. For gelatin coating, the microcoils were soaked in 10% gelatin solution for 15 minutes, dried for 30 minutes, then soaked and dried again. For dual coating with both gelatin and thrombin, they were soaked in 10% gelatin solution first for 15 minutes, dried for 45 minutes, and soaked in 4 U/mL thrombin solution for 5 minutes, and dried. The authors introduced 1 mL of fresh blood immediately into the test tube containing the microcoil, and measured the time taken for complete coagulation of the 1 mL blood (WBCT). RESULTS: Untreated stainless steel, tungsten, and platinum microcoils reduced WBCT from 15.76 minutes to 7.15, 5.64, and 7.27 minutes, respectively. Stainless steel microcoils after soaking in thrombin, gelatin, and both gelatin and thrombin solutions showed WBCT of 5.77, 5.82, and 4.44 minutes, respectively. Tungsten microcoils after soaking in thrombin, gelatin, and both gelatin, and thrombin solutions showed WBCT of 3.25, 4.95, and 3.67 minutes, respectively. Platinum microcoils after soaking in thrombin, gelatin, and both gelatin and thrombin solutions showed WBCT of 5.70, 10.01, and 6.27 minutes, respectively. CONCLUSIONS: Untreated tungsten microcoils showed superior clot promoting activity compared with untreated stainless steel and platinum microcoils. Clot promoting activity of microcoils was increased after coating with thrombin, or both gelatin and thrombin compared with untreated microcoils.

Experimental tissue damage after subcutaneous injection of water soluble contrast media.

Various water soluble contrast media (WSCM) were injected subcutaneously into 970 hind feet of 485 rats. Gross morphologic changes were seen after the injection and analyzed as a function of various physicochemical characteristics of WSCM. The WSCM of larger volume, higher osmolality, higher iodine content, and meglumine salts rather than sodium salts caused more severe tissue damage; younger rats showed more severe tissue damage by WSCM of high osmolality.

An experimental study of embolic effect according to infusion rate and concentration of suspension in transarterial particulate embolization.

RATIONALE AND OBJECTIVES: The authors evaluate the embolic effect according to infusion rate and concentration of particulate suspension, focusing on arterial occlusion level. METHODS: The renal arteries of 14 rabbits were embolized with 150 to 250 microns polyvinyl alcohol (PVA) particles, divided into four groups according to two different infusion rates (1 mg/second and 0.1 mg/second) and two different concentrations of suspension (10 mg/mL and 2.5 mg/mL). Arteriograms obtained immediately and a week after embolization were assessed for occlusion level. For the nephrograms obtained a week after embolization, the opacifying areas were graded from 0 to 4. Median coronal sections of each kidney specimen were investigated for the presence of peripheral infarct grossly and for the presence of PVA particles in the small artery microscopically. RESULTS: Arteriograms showed various occlusion levels. Using a 0 to 4 grading system, the opacifying area of the nephrogram obtained 1 week after embolization was noted to be smaller in the low infusion rate group (P < 0.05). In gross and microscopic pathologic examination, the number of cases with peripheral infarct or PVA particles in the small artery (< 300 microns) was greater in the group with the low infusion rate and low concentration (P < 0.05). CONCLUSIONS: In transarterial particulate embolization, slower infusion of more diluted suspension provides for a more distal arterial occlusion.

Doppler sonography in experimentally induced acute renal failure in rabbits. Resistive index versus serum creatinine levels.

RATIONALE AND OBJECTIVES: The purpose of this study is to investigate the temporal relation between the change in the resistive index (RI) from renal Doppler sonography and that of serum creatinine values in the course of experimentally induced reversible acute renal failure (ARF) in rabbits. METHODS: Reversible ARF was induced in 10 New Zealand white rabbits by injecting a glycerol solution (6.0 mL/kg) into the thigh muscle. Doppler sonography was performed before injection, and 6, 12, and 24 hours, and 3, 5, 7, and 14 days after injection of glycerol. Blood samples for measuring serum creatinine levels were obtained in the same time sequence. Three rabbits, which died during the course of the experiment, were excluded from the study group. RESULTS: The RI elevated rapidly after glycerol injection, peaked at 12 hours, and then decreased to normal values by 7 days. Conversely, serum creatinine values were elevated and peaked at 1 day and then decreased to normal by 14 days. The change in the RI preceded the change in serum creatinine levels in the course of reversible ARF. There was a weak linear correlation between RI and serum creatinine levels, with a correlation coefficient of 0.33. CONCLUSION: Doppler sonography with measurement of resistive index may be useful in predicting the course of ARF.

Methods for mitigating soft-tissue injury after subcutaneous injection of water soluble contrast media.

RATIONALE AND OBJECTIVES: Water soluble contrast media may cause tissue injury by extravasation during intravenous injection during various radiologic examinations. The authors attempted to find out what kind of management could mitigate tissue injury when extravasation of water soluble contrast media occurs. METHODS: Sodium and meglumine ioxithalamate was injected subcutaneously into 240 hind feet of 120 rats that were divided into six groups according to the methods of experimental management. Experimental managements included the following: no further management (control), injection of distilled water, injection of normal saline, injection of hydrocortisone, hot water application, and cold water application. Gross morphologic changes in each group were compared with those in the control group. RESULTS: Only the saline injection group showed statistically significant decrease of tissue injury compared with the control group. CONCLUSIONS: Saline injection lessens the degree of soft-tissue injury at contrast media extravasation sites in rats.

Microcholangiography. Normal microbiliary system and its alteration after extrahepatic bile duct obstruction.

The authors used microcholangiography to demonstrate the feasibility of the technique and the features of the normal and the obstructed biliary systems. Furthermore, they attempted to explain the pathophysiology of cholangiography-related septicemia with this technique. Extrahepatic bile ducts (EHBD) of 40 rabbits were ligated, and microcholangiography was carried out with infusion of barium suspension immediately as well as one, three, and five days after ligation. Microradiographic technique was used and the findings were correlated with histopathologic features. The intrahepatic microbiliary system such as interlobular bile ducts and ductules were well visualized. After EHBD ligation, ductules were tortuously dilated. The histologically observed ductular proliferation in many hepatobiliary diseases could be attributed in part to the tortuosity of bile ductules, particularly when biliary obstruction is present. Regurgitation of barium into hepatic sinusoids was demonstrated in 36 rabbits (90%) and probably was caused by rupture of interlobular bile ducts and ductules.

Transcatheter renal arterial embolization with the mixture of ethanol and iodized oil (Lipiodol).

We induced experimental renal arterial embolization with the radiopaque solution of ethanol and iodized oil (Lipiodol) in 35 rabbits to evaluate the capability of the mixture to induce renal ablation. Serial renal angiography and plain abdominal radiography were performed immediately, one week and two weeks after embolization. Neither pure Lipiodol nor a 50% ethanol solution caused renal embolization. However, infusion of 50% and 75% ethanol-Lipiodol solutions resulted in embolization equal to that caused by absolute ethanol. The 50% ethanol-Lipiodol solution was so radiopaque that we could easily observe the embolization process during fluoroscopy. Renal arterial embolization with the 50% ethanol-Lipiodol solution was successful in three patients with hypernephroma. Our results suggest that a 50% ethanol-Lipiodol solution is radiopaque and an effective agent for renal arterial embolization.

The role of contrast-enhanced MR imaging in the diagnosis of neurocysticercosis.

Pre- and postcontrast MR images of 17 patients with the diagnosis of neurocysticercosis were reviewed to evaluate the role of gadopentetate dimeglumine in MR imaging of this disease. The MR images, which were obtained on either a 0.5-T or 2.0-T superconducting system, revealed a total of 92 cysticerci in 17 patients. On contrast-enhanced T1-weighted images, 23 parenchymal cysticerci showed contrast enhancement. Ring-shaped enhancement was seen in only 6% (3/54) of cysticerci with intensity paralleling the CSF, while it was noted in 67% (16/24) of the cysticerci with intensity higher than CSF. Nodular enhancement was seen in granulomatous lesions with surrounding edema (29%, 4/14). Of 18 cysticerci with surrounding edema, 17 showed contrast enhancement. Basal meningeal enhancement, indicating meningitis, was observed in three patients. The results indicate that contrast enhancement usually occurs in patients in whom precontrast MR findings have shown active inflammatory reaction in the degenerating stage of the worm. Thus, postcontrast imaging is useful in a limited number of patients with neurocysticercosis; it should be used selectively in those whose clinical or precontrast MR studies show meningitis, granulomatous lesions, or cysts with surrounding edema.

Comparative evaluation of brain CT and ELISA in the diagnosis of neurocysticercosis.

This study compares the results of cysticercus-specific IgG antibody levels, as measured by enzyme-linked immunosorbent assay (ELISA), with brain CT findings in suspected neurocysticercosis and to assess the clinical significance of ELISA. One hundred twenty-three neurologic patients were examined by both brain CT and ELISA. Sensitivity and specificity of ELISA in confirmed cases were 94% and 91%, respectively. Patients with multiple cysts without enhancement on CT, which were thought to represent viable cysticerci, were positive by ELISA. Those with cysts with enhancement or poorly defined low densities or enhancing nodules, which represented cysticerci on degeneration, were also positive by ELISA. Those with multiple spotty calcifications, which represent cysticerci in the inactive stage, were negative by ELISA. Those with mixed CT findings of the above, which represent the various stages of infection in a patient, were positive by ELISA. Those with only enhancing nodules with surrounding edema, which were thought to be other inflammatory granulomas, were negative by ELISA. If patients with only hydrocephalus on CT are positive by ELISA, they can be confidently diagnosed as having ventricular cysticercosis. The results indicate that ELISA is useful as a complementary diagnostic tool, especially in patients with equivocal CT findings of neurocysticercosis. Provision of etiologic information on a biologic basis was the advantage of this serologic test.