Brain tumor segmentation based on region of interest-aided localization and segmentation U-Net.

Since magnetic resonance imaging (MRI) has superior soft tissue contrast, contouring (brain) tumor accurately by MRI images is essential in medical image processing. Segmenting tumor accurately is immensely challenging, since tumor and normal tissues are often inextricably intertwined in the brain. It is also extremely time consuming manually. Late deep learning techniques start to show reasonable success in brain tumor segmentation automatically. The purpose of this study is to develop a new region-of-interest-aided (ROI-aided) deep learning technique for automatic brain tumor MRI segmentation. The method consists of two major steps. Step one is to use a 2D network with U-Net architecture to localize the tumor ROI, which is to reduce the impact of normal tissue's disturbance. Then a 3D U-Net is performed in step 2 for tumor segmentation within identified ROI. The proposed method is validated on MICCAI BraTS 2015 Challenge with 220 high Gliomas grade (HGG) and 54 low Gliomas grade (LGG) patients' data. The Dice similarity coefficient and the Hausdorff distance between the manual tumor contour and that segmented by the proposed method are 0.876 ±0.068 and 3.594±1.347 mm, respectively. These numbers are indications that our proposed method is an effective ROI-aided deep learning strategy for brain MRI tumor segmentation, and a valid and useful tool in medical image processing.

Theoretical derivation and clinical dose-response quantification of a unified multi-activation (UMA) model of cell survival from a logistic equation.

OBJECTIVE: To theoretically derive a unified multiactivation (UMA) model of cell survival after ionising radiation that can accurately assess doses and responses in radiotherapy and X-ray imaging. METHODS: A unified formula with only two parameters in fitting of a cell survival curve (CSC) is first derived from an assumption that radiation-activated cell death pathways compose the first- and second-order reaction kinetics. A logit linear regression of CSC data is used for precise determination of the two model parameters. Intrinsic radiosensitivity, biologically effective dose (BED), equivalent dose to the traditional 2 Gy fractions (EQD2), tumour control probability, normal-tissue complication probability, BED50 and steepness (Γ50) at 50% of tumour control probability (or normal-tissue complication probability) are analytical functions of the model and treatment (or imaging) parameters. RESULTS: The UMA model has almost perfectly fit typical CSCs over the entire dose range with R2≥0.99. Estimated quantities for stereotactic body radiotherapy of early stage lung cancer and the skin reactions from X-ray imaging agree with clinical results. CONCLUSION: The proposed UMA model has theoretically resolved the catastrophes of the zero slope at zero dose for multiple target model and the bending curve at high dose for the linear quadratic model. More importantly, it analytically predicts dose-responses to various dose-fraction schemes in radiotherapy and to low dose X-ray imaging based on these preclinical CSCs. ADVANCES IN KNOWLEDGE: The discovery of a unified formula of CSC over the entire dose range may reveal a common mechanism of the first- and second-order reaction kinetics among multiple CD pathways activated by ionising radiation at various dose levels.

[Observation of the short-term effect of tympanoplasty（type â ） in dry and wet ears with chronic otitis media].

Objective:To explore the difference of short-term effect of transear endoscopic tympanoplasty （type Ⅰ） in the dry and wet ear of chronic otitis media. Methods:Patients with chronic suppurative otitis media were prospectively recruited in the Department of Otorhinolaryngology Head and Neck Surgery, Shaanxi Provincial People's Hospital from July 2018 to July 2020. Two otoscopicians independently judged the condition of tympanic membrane and tympanic mucosa before operation. One hundred and ten patients were divided into dry ear group （n=78） and wet ear group（n=32）. The healing rate of tympanic membrane and the degree of hearing improvement were recorded at postoperative 1 month, 3 months and 6 months. Results:Six months after operation, the healing rate of dry ear group was 97.4% （76/78）, and that of wet ear group was 96.9%（31/32） 6 months after operation, there was no significant difference in tympanic membrane healing rate between the two groups （P>0.05）. The hearing of the patients in both groups was improved, and the air conduction hearing in the dry ear group increased by （10.57±8.73） dB, and decreased by （6.44±4.98） dB after operation. In the wet ear group, the air conduction hearing increased by （8.91±11.79） dB, and decreased by （6.89±6.99） dB after operation. There was no significant difference in the degree of hearing improvement between the two groups（P>0.05）. Conclusion:For quiescent chronic otitis media without ossicular chain lesions, the preoperative wet ear state is not a taboo in tympanoplasty （typeⅠ）, and the postoperative tympanic membrane healing rate and hearing improvement are the same as those in dry ear surgery, and can reduce the preoperative waiting time of patients, reduce the use of antibiotics.

A unified multi-activation (UMA) model of cell survival curves over the entire dose range for calculating equivalent doses in stereotactic body radiation therapy (SBRT), high dose rate brachytherapy (HDRB), and stereotactic radiosurgery (SRS).

PURPOSE: Application of linear-quadratic (LQ) model to large fractional dose treatments is inconsistent with observed cell survival curves having a straight portion at high doses. We have proposed a unified multi-activation (UMA) model to fit cell survival curves over the entire dose range that allows us to calculate EQD2 for hypofractionated SBRT, SRT, SRS, and HDRB. METHODS: A unified formula of cell survival S = n / e D D o + n - 1 using only the extrapolation number of n and the dose slope of Do was derived. Coefficient of determination, R2 , relative residuals, r, and relative experimental errors, e, normalized to survival fraction at each dose point, were calculated to quantify the goodness in modeling of a survival curve. Analytical solutions for α and ß, the coefficients respectively describe the linear and quadratic parts of the survival curve, as well as the α/ß ratio for the LQ model and EQD2 at any fractional doses were derived for tumor cells undertaking any fractionated radiation therapy. RESULTS: Our proposed model fits survival curves of in-vivo and in-vitro tumor cells with R2  > 0.97 and r < e. The predicted α, ß, and α/ß ratio are significantly different from their values in the LQ model. Average EQD2 of 20-Gy SRS of glioblastomas and melanomas metastatic to the brain, 10-Gy × 5 SBRT of the lung cancer, and 7-Gy × 5 HDRB of endometrial and cervical carcinomas are 36.7 (24.3-48.5), 114.1 (86.6-173.1),, and 45.5 (35-52.6) Gy, different from the LQ model estimates of 50.0, 90.0, and 49.6 Gy, respectively. CONCLUSION: Our UMA model validated through many tumor cell lines can fit cell survival curves over the entire dose range within their experimental errors. The unified formula theoretically indicates a common mechanism of cell inactivation and can estimate EQD2 at all dose levels.

Experimental Investigation of Stability of Silica Nanoparticles at Reservoir Conditions for Enhanced Oil-Recovery Applications.

To be effective enhanced oil-recovery (EOR) agents, nanoparticles must be stable and be transported through a reservoir. However, the stability of a nanoparticle suspension at reservoir salinity and temperature is still a challenge and how it is affected by reservoir rocks and crude oils is not well understood. In this work, for the first time, the effect of several nanoparticle treatment approaches on the stability of silica nanoparticles at reservoir conditions (in the presence of reservoir rock and crude oil) was investigated for EOR applications. The stability of nanoparticle suspensions was screened in test tubes at 70 °C and 3.8 wt. % NaCl in the presence of reservoir rock and crude oil. Fumed silica nanoparticles in suspension with hydrochloric acid (HCl), polymer-modified fumed nanoparticles and amide-functionalized silica colloidal nanoparticles were studied. The size and pH of nanoparticle suspension in contact with rock samples were measured to determine the mechanism for stabilization or destabilization of nanoparticles. A turbidity scanner was used to quantify the stability of the nanoparticle suspension. Results showed that both HCl and polymer surface modification can improve nanoparticle stability under synthetic seawater salinity and 70 °C. Suspensions of polymer-modified nanoparticles were stable for months. It was found that pH is a key parameter influencing nanoparticle stability. Rock samples containing carbonate minerals destabilized unmodified nanoparticles. Crude oil had limited effect on nanoparticle stability. Some components of crude oil migrated into the aqueous phase consisting of amide-functionalized silica colloidal nanoparticles suspension. Nanoparticles modification or/and stabilizer are necessary for nanoparticle EOR application.

Knockdown of lncRNA ZNRD1-AS1 inhibits progression of bladder cancer by regulating miR-194 and ZEB1.

BACKGROUND: Bladder cancer (BC) is a common urinary neoplasm with high incidence worldwide. Long noncoding RNA zinc ribbon domain containing 1 antisense RNA 1 (ZNRD1-AS1) has been reported to be upregulated in BC. However, the exact role of ZNRD1-AS1 as well as its mechanism remains poorly understood. METHODS: Zinc ribbon domain containing 1 antisense RNA 1, and its potential downstream genes microRNA-194 (miR-194) and zinc finger E-box binding homeobox 1 (ZEB1) levels were detected via quantitative real-time polymerase chain reaction or western blot. Cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were detected to assess the influences of ZNRD1-AS1, miR-194 and ZEB1 on BC cells by colony formation, cell counting kit-8 (CCK-8), transwell analysis or western blot. The relationship between miR-194 and ZNRD1-AS1 or ZEB1 was analyzed by luciferase activity analysis. The xenograft experiment was performed to assess the function of ZNRD1-AS1 in vivo. RESULTS: Zinc ribbon domain containing 1 antisense RNA 1level was upregulated in BC. ZNRD1-AS1 silence repressed proliferation, migration, invasion and EMT in BC cells. MiR-194 was identified as a target of ZNRD1-AS1, and miR-194 upregulation repressed proliferation, migration, invasion, and EMT by ZNRD1-AS1 sponging. ZEB1 was targeted via miR-194 and its interference impeded proliferation, migration, invasion, and EMT. Moreover, ZNRD1-AS1 regulated ZEB1 expression via miR-194. Besides, inhibition of ZNRD1-AS1 attenuated tumor growth by miR-194/ZEB1 axis in vivo. CONCLUSION: Knockdown of ZNRD1-AS1 suppressed BC cell development in vitro and in vivo via targeting miR-194 to regulate ZEB1, indicating a novel avenue for treatment of BC.

Insight into the surfactin production of Bacillus velezensis B006 through metabolomics analysis.

Bacillus velezensis B006 is a biocontrol agent which functions through effective colonization and surfactin production. To reveal the surfactin-producing mechanism, gas chromatography-mass spectrometry based untargeted metabolomics was performed to compare the metabolite profiles of strain B006 grown in industrial media M3 and M4. Based on the statistical and pathway topology analyses, a total of 31 metabolites with a fold change of less than - 1.0 were screened as the significantly altered metabolites, which distributed in 15 metabolic pathways. Fourteen amino acids involving in the metabolisms of alanine/aspartate/glutamate, glycine/serine/threonine, arginine/proline, glutathione/cysteine/methionine and valine/leucine/isoleucine as well as succinic acid in TCA cycle were identified to be the hub metabolites. Aminoacyl-tRNA biosynthesis, glycerolipid metabolism, and pantothenate/CoA biosynthesis also contributed to surfactin production. To the best of our knowledge, this study is the first to investigate the metabolic pathways of B. velezensis on surfactin production, and will benefit the optimization of commercial fermentation for higher surfactin yield.

Long Noncoding RNA NEAT1 Promotes Proliferation and Invasion via Targeting miR-181a-5p in Non-Small Cell Lung Cancer.

Long noncoding RNAs (lncRNAs) have been implicated in various biological processes and pathological conditions, including tumorigenesis. However, the exact roles of NEAT1 and its underlying mechanisms in non-small cell lung cancer (NSCLC) remain largely unclear. In the present study, lncRNA NEAT1 was detected to be significantly upregulated in NSCLC tissues and closely associated with advanced TNM stages, lymph node metastasis, distant metastasis, and poor prognosis. Further experiments revealed that lncRNA NEAT1 silencing inhibited cell proliferation and invasion in vitro. In addition, mechanistic analysis showed that lncRNA NEAT1 upregulated the miR-181a-5p-targeted gene HMGB2 through acting as a competitive "sponge" of miR-181a-5p. In conclusion, our study suggested that lncRNA NEAT1 plays an oncogenic role in NSCLC progression and provides potential mechanisms by which lncRNA NEAT1 contributes to this disease.

Relationship between dosimetric leaf gap and dose calculation errors for high definition multi-leaf collimators in radiotherapy.

BACKGROUND AND PURPOSE: Dosimetric leaf gap (DLG) is a parameter to model the round-leaf-end effect of multi-leaf collimators (MLC) that is important for treatment planning dose calculations in radiotherapy. In this study we investigated on the relationship between the DLG values and the dose calculation errors for a high-definition MLC. MATERIALS AND METHODS: Three sets of experiments were conducted: (1) physical DLG measurements using sweeping-gap technique, (2) DLG adjustment based on spine radiosurgery plan measurements, and (3) DLG verification using films and ion-chambers (IC). All experiments were conducted on a Varian Edge machine equipped with HD120 MLC for 6X, 6XFFF, and 10XFFF (FFF: flattening filter free). The Analytical Anisotropic Algorithm was used for all dose calculations. RESULTS: The measured physical DLGs were 0.39 mm, 0.27 mm, and 0.42 mm for 6X, 6XFFF, and 10XFFF respectively. The calculated doses were lower by 4.2% (6X), 3.7% (6XFFF), and 6.8% (10XFFF) than the measured, while the adjusted DLG values with minimum errors were 1.1 mm, 0.9 mm, and 1.5 mm. The IC measurement errors were < 1%, and the film gamma pass rates (3%/3 mm) were greater than 97% for the spine plans. CONCLUSIONS: The calculated doses were systematically lower than measured doses with the physical DLG values. It was necessary to increase the DLG values to minimize the dose calculation uncertainty. The optimal DLG values may be specific to individual MLCs and beams and, thus, careful evaluation and verification are warranted.

The Relative Effects of Manual Versus Automatic Exposure Control on Radiation Dose to Vital Organs in Total Hip Arthroplasty.

INTRODUCTION: Technologic advances have reduced medical radiation exposure while maintaining image quality. The purpose of this study was to determine the effects of the presence of total hip arthroplasty implants, compared with native hips, on radiation exposure of the most radiosensitive organs when manual and automatic exposure control settings are used. METHODS: Detection probes were placed at six locations (stomach, sigmoid colon, right pelvic wall, left pelvic wall, pubic symphysis, and anterior pubic skin) in a cadaver. Radiographs were obtained with the use of manual and automatic exposure control protocols, with exposures recorded. A total hip arthroplasty implant was placed in the cadaver, probe positioning was confirmed, and the radiographs were repeated, with exposure values recorded. RESULTS: The control probe placed at the stomach had values ranging from 0.00 mSv to 0.01 mSv in protocols with and without implants. With the manual protocol, exposures in the pelvis ranged from 0.36 mSv to 2.74 mSv in the native hip and from 0.33 mSv to 2.24 mSv after implant placement. The increases in exposure after implant placement, represented as relative risk, were as follows: stomach, 1.000; pubic symphysis, 0.818; left pelvic wall, 1.381; sigmoid colon, 1.550; right pelvic wall, 0.917; and anterior pubic skin, 1.015. With automatic exposure control, exposures in the pelvis ranged from 0.07 mSv to 0.89 mSv in the native hip and from 0.21 mSv to 1.15 mSv after implant placement. With automatic exposure control, the increases in exposure after implant placement, represented as relative risk, were as follows: stomach, 1.000; pubic symphysis, 1.292; left pelvic wall, 1.476; sigmoid colon, 2.182; right pelvic wall, 3.000; and anterior pubic skin, 1.378. DISCUSSION: The amount of radiation to which patients are exposed as a result of medical procedures or imaging, and whether exposure is associated with an increased risk of malignant transformation, are the subject of ongoing debate. We found that after insertion of a total hip arthroplasty implant, exposure values increased threefold at some anatomic locations and surpassed 1 mSv, the generally accepted threshold for concern. CONCLUSION: Radiation exposure to radiosensitive organs increased up to threefold after total hip implantation with automatic exposure control and up to approximately 1.5 times with the manual protocol. Doses were greater with manual exposures than with automatic exposure control (except at the control probe on the stomach, where exposure was negligible, as expected). However, after implant placement, doses increased more with automatic exposure control than with manual exposure. This difference can be attributed to increased scatter and the difficulty of dose modification because of the density of the implant. Current radiographic protocols should be reassessed to determine if the benefits of frequent radiographs outweigh the newly demonstrated risks.

Image-guided high-dose-rate intracavitary brachytherapy in the treatment of medically inoperable early-stage endometrioid type endometrial adenocarcinoma.

PURPOSE: The purpose of this case series is to describe the treatment and outcomes of a cohort of patients with inoperable early-stage endometrioid endometrial cancer with 3D image-guided high-dose-rate (HDR) intracavitary brachytherapy. MATERIALS AND METHODS: A review was performed of patients with early-stage endometrial cancer who underwent primary radiation treatment between 2010 and 2016. Staging and treatment planning were performed CT, pelvic ultrasound, and pelvic MRI. Gross tumor volume (GTV) was defined as the MRI or ultrasound demonstrated endometrial stripe width, with the entire uterine corpus, cervix, and proximal vagina representing the clinical target volume (CTV). Dosimetry calculations were performed in each fraction of HDR brachytherapy. RESULTS: Eight patients received external beam radiation therapy followed by intracavitary HDR brachytherapy. Seven patients underwent intracavitary HDR brachytherapy alone. In all patients, mean cumulative dose to 90% (D90) of GTV was 95.99 Gy in equivalent dose in 2 Gy fractions (EQD2, α/ß = 10). Mean cumulative D90 EQD2 to CTV was 51.64 Gy. Average follow-up was 29 months. Four patients died from concurrent disease(s) at an average of 2.83 years after completion of treatment. Except for 1 (6.6%) patient who recurred at 9 months following completion of treatment, all patients remained disease-free for the remainder of follow-up. CONCLUSIONS: In patients who are poor surgical candidates and have early-stage endometrioid type endometrial carcinoma, image-guided HDR intracavitary brachytherapy carries minimal side effects and a high response rate.

Expression profile of apoptosis-related genes potentially explains early recurrence after definitive chemoradiation in esophageal squamous cell carcinoma.

Definitive chemoradiation is a curative treatment option for patients with locoregional esophageal squamous cell carcinoma (ESCC) who are not suitable for surgical resection, but many tend to develop local recurrence. The purpose of the study was to investigate factors affecting local recurrence of the tumor. Seventy-two patients with stage II-III thoracic ESCC who received definitive concurrent chemoradiation (CRT) and completely responded to the treatment were enrolled into this study. The case patients were 49 patients who recurred locally within 24 months after definitive CRT and 23 patients who did not have a local recurrence within 24 months were considered as controls. We investigated whether dysregulation of apoptosis-related genes was associated with early tumor recurrence. Quantitative real-time polymerase chain reaction showed upregulation of BCLAF1 and downregulation of BAG4, CARD6, IGF1R, and TNF in the tissues of case patients, as compared with controls. Among the patients with recurrent ESCC, those with tumors which exhibited more than twofold upregulated BCLAF1 and more than twofold downregulated BAG4 and TNF had a decreased time interval to local recurrence. Three gene pairs of the downregulated genes showed a significant correlation with local recurrence: BAG4 and CARD6, BAG4 and TNF, CARD6, and TNF. The patients with T3-4 disease and those with tumor >3 cm in length had a trend toward early local recurrence, though the associations were not reached statistical significance. Upregulation of BCLAF1 and downregulation of BAG4 and TNF was independently associated with early local recurrence in multivariate analysis (P < 0.05). This study supports the involvement of apoptosis-related genes in early tumor recurrence after definitive chemoradiation in patients with stage II-III thoracic ESCC.

Use of image-guided stereotactic body radiation therapy in lieu of intracavitary brachytherapy for the treatment of inoperable endometrial neoplasia.

PURPOSE: Retrospective analysis of patients with invasive endometrial neoplasia who were treated with external beam radiation therapy followed by stereotactic body radiation therapy (SBRT) boost because of the inability to undergo surgery or brachytherapy. METHODS AND MATERIALS: We identified 11 women with stage I-III endometrial cancer with a median age of 78 years that were not candidates for hysterectomy or intracavitary brachytherapy secondary to comorbidities (91%) or refusal (9%). Eight patients were American Joint Committee on Cancer (AJCC) stage I (3 stage IA, 5 stage IB), and 3 patients were AJCC stage III. Patients were treated to a median of 4500 cGy at 180 cGy per fraction followed by SBRT boost (600 cGy per fraction×5). RESULTS: The most common side effect was acute grade 1 gastrointestinal toxicity in 73% of patients, with no late toxicities observed. With a median follow-up of 10 months since SBRT, 5 patients (45%) experienced locoregional disease progression, with 3 patients (27%) succumbing to their malignancy. At 12 and 18 months from SBRT, the overall freedom from progression was 68% and 41%, respectively. Overall freedom from progression (FFP) was 100% for all patients with AJCC stage IA endometrial carcinoma, whereas it was 33% for stage IB at 18 months. The overall FFP was 100% for International Federation of Obstetrics and Gynecology grade 1 disease. The estimated overall survival was 57% at 18 months from diagnosis. CONCLUSION: In this study, SBRT boost to the intact uterus was feasible, with encouragingly low rates of acute and late toxicity, and favorable disease control in patients with early-stage disease. Additional studies are needed to provide better insight into the best management of these clinically challenging cases.

Repeat stereotactic body radiation therapy for patients with pulmonary malignancies who had previously received SBRT to the same or an adjacent tumor site.

OBJECTIVES: Retrospective analysis of patients with recurrences at or closely adjacent to the site of prior lung stereotactic body radiation therapy (SBRT) who received repeat SBRT. MATERIALS AND METHODS: Nine patients with non-small cell lung cancer (n = 8) or oligometastatic colonic adenocarcinoma (n = 1) were treated with image-guided lung SBRT to a median of 60 Gy (range, 30-60) in a median of 3 fractions (3-5). Patients developed in-field relapse (n = 3) or recurrence adjacent (≤ 3.5 cm away) to the previous tumor location (n = 6) and received 2 nd lung SBRT to a median of 60 Gy. RESULTS: Median follow-up after 2 nd SBRT was 22 months (4-40). All completed prescribed course of repeat SBRT and acute toxicity was limited. There was no grade >3 late toxicity. 3 (33.3%) patients developed Grade 3 late reactions: 2 pulmonary and 1 chest wall pain. Late pulmonary toxicity included 2 (22.2%) patients with Grade 3 and 3 (33.3%) with Grade 2. One patient (11.1%) had late Grade 3 and 1 (11.1%) Grade 2 chest wall pain. 1 (11.1%) developed Grade 2 late brachial plexopathy. No myelopathy was observed. Two patients developed progression of tumors treated by 2 nd SBRT. Local recurrence free survival and overall survival was 75% and 68.6%, respectively at 2 years. Relative volume of ipsilateral lung receiving 5 Gy (V5) and V10 were lower for 2 nd SBRT. CONCLUSION: Repeat image-guided SBRT for patients with small peripheral recurrences was feasible and severe toxicity was not observed. Additional studies are needed to evaluate the safety and efficacy of lung reirradiation using 2 nd SBRT.

Clinical results of a pilot study on stereovision-guided stereotactic radiotherapy and intensity modulated radiotherapy.

Real-time stereovision-guidance has been introduced for efficient and convenient fractionated stereotactic radiotherapy (FSR) and image-guided intensity-modulated radiation therapy (IMRT). This first pilot study is to clinically evaluate its accuracy and precision as well as impact on treatment doses. Sixty-one FSR patients wearing stereotactic masks (SMs) and nine IMRT patients wearing flexible masks (FMs), were accrued. Daily target reposition was initially based-on biplane-radiographs and then adjusted in six degrees of freedom under real-time stereovision guidance. Mean and standard deviation of the head displacements measured the accuracy and precision. Head positions during beam-on times were measured with real-time stereovisions and used for determination of delivered doses. Accuracy ± ± precision in direction with the largest errors shows improvement from 0.4 ± 2.3 mm to 0.0 ± 1.0 mm in the inferior-to-superior direction for patients wearing SM or from 0.8 ± 4.3 mm to 0.4 ± 1.7 mm in the posterior-to-anterior direction for patients wearing FM. The image-guidance increases target volume coverage by >30% for small lesions. Over half of head position errors could be removed from the stereovision-guidance. Importantly, the technique allows us to check head position during beam-on time and makes it possible for having frameless head refixation without tight masks.

Cord dose specification and validation for stereotactic body radiosurgery of spine.

Effective dose to a portion of the spinal cord in treatment segment, rather than the maximum point dose in the cord surface, was set as the dose limit in stereotactic-body radiosurgery (SBRS) of spine. Such a cord dose specification is sensitive to the volume size and position errors. Thus, we used stereotactic image guidance to minimize phantom positioning errors and compared the results of a 0.6-cm(3) Farmer ionization chamber and a 0.01-cm(3) compact ionization chamber to determine the detector size effect on 9 SBRS cases. The experimental errors ranging from 2% to 7% were estimated by the deviation of the mean dose in plans to the chamber with spatial displacements of 0.5 mm. The mean and measured doses for the large chamber to individual cases were significantly (approximately 17%) higher than the doses with the compact chamber placed at the same point. Our experimental results shown that the mean doses to the volume of interest could represent the measured cord doses. For the 9 patients, the mean doses to 10% of the cord were about 10 Gy, while the maximum cord doses varied from 11.6 to 17.6 Gy. The mean dose, possibly correlated with the cord complication, provided us an alternative and reliable cord dose specification in SBRS of spine.

Purification, characterization, and gene cloning of an alkaline serine protease from a highly virulent strain of the nematode-endoparasitic fungus Hirsutella rhossiliensis.

Hirsutella rhossiliensis OWVT-1 has substantial potential as a biocontrol agent against plant-parasitic nematodes. Serine proteases have emerged as a potentially useful factor in the nematode-fungus interactions. When grown in liquid culture with the nematode Panagrellus redivivus as the sole nitrogen source, an extracellular alkaline protease (Hasp) was produced by the OWVT-1. The purified Hasp killed the juveniles of the soybean-cyst nematode (Heterodera glycines) and degraded proteins of the nematode cuticle. The molecular mass of Hasp was estimated to be 33 kDa. The optimum pH and temperature for enzyme activity were pH 9 and 75 degrees C. The amino acid sequence obtained by the N-terminal sequence analysis was applied for the primer design to isolate the Hasp cDNA gene, which consists of 1170 bp open reading frame. Analysis of the cDNA and corresponding genomic sequence revealed that Hasp included four exons (279, 186, 513, and 192 bp) divided by three introns (65, 99, and 93 bp). Southern blotting showed that Hasp was a single-copy gene in the genome. The deduced amino acid sequence was very similar to other serine proteases of endoparasitic and egg-parasitic fungi of nematodes and of entomopathogenic fungi but was less similar to the serine proteases of nematode-trapping fungi. In a phylogenetic analysis of the amino acid sequences of serine proteases, the serine protease of H. rhossiliensis OWVT-1 clustered with the serine proteases of parasites of nematode eggs rather than with those of the trapping fungi.

Examining margin reduction and its impact on dose distribution for prostate cancer patients undergoing daily cone-beam computed tomography.

PURPOSE: To examine the dosimetric impact of margin reduction and quantify residual error after three-dimensional (3D) image registration using daily cone-beam computed tomography (CBCT) for prostate cancer patients. METHODS AND MATERIALS: One hundred forty CBCTs from 5 prostate cancer patients were examined. Two intensity-modulated radiotherapy plans were generated on CT simulation on the basis of two planning target volume (PTV) margins: 10 mm all around the prostate and seminal vesicles except 6 mm posteriorly (10/6) and 5 mm all around except 3 mm posteriorly (5/3). Daily CBCT using the Varian On-Board Imaging System was acquired. The 10/6 and 5/3 simulation plans were overlaid onto each CBCT, and each CBCT plan was calculated. To examine residual error, PlanCT/CBCT intensity-based 3D image registration was performed for prostate localization using center of mass and maximal border displacement. RESULTS: Prostate coverage was within 2% between the 10/6 and 5/3 plans. Seminal vesicle coverage was reduced with the 5/3 plan compared with the 10/6 plan, with coverage difference within 7%. The 5/3 plan allowed 30-50% sparing of bladder and rectal high-dose regions. For residual error quantification, center of mass data show that 99%, 93%, and 96% of observations fall within 3 mm in the left-right, anterior-posterior, and superior-inferior directions, respectively. Maximal border displacement observations range from 79% to 99%, within 5 mm for all directions. CONCLUSION: Cone-beam CT dosimetrically validated a 10/6 margin when soft-tissue localization is not used. Intensity-based 3D image registration has the potential to improve target localization and to provide guidelines for margin definition.

A technique of quantitatively monitoring both respiratory and nonrespiratory motion in patients using external body markers.

The purpose of this study was to develop a technique that could quantitatively monitor the nonrespiratory motion of a patient during stereotactic body radiotherapy (SBRT). Multiple infrared external markers were placed on the patient's chest and abdominal surface to obtain patient motion signals. These motion signals contained both respiratory and nonrespiratory motion information. The respiratory motion usually has much larger amplitude on the abdominal surface than on the chest surface. Assuming that the nonrespiratory motion is a rigid body translation, we have developed a computer algorithm to derive both the respiratory and nonrespiratory motion signals instantly from two sets of motion signals. In first-order approximation, the respiratory motion was represented by the motion signal on the abdominal surface, and the nonrespiratory motion was represented by the motion signal on the chest surface subtracting its respiratory component. The algorithm was retrospectively tested on 24 patients whose motion signals were recorded during a gated-CT simulation procedure. The result showed that the respiratory noise in the nonrespiratory motion signal was reduced to less than 1 mm for almost all patients, demonstrating that the technique was able to detect nonrespiratory motion with a sensitivity of about 1 mm. It also showed that 50% of the patients had > or =2 mm, and 2 patients had > or =3 mm slow drift during the 15-25 min simulation procedure, suggesting that nonrespiratory motion could exist during prolonged treatment. This technique can potentially be used to control the nonrespiratory motion during SBRT. However, further validation is required for its clinical use.

Comparison of similarity measures for rigid-body CT/Dual X-ray image registrations.

A set of experiments were conducted to evaluate six similarity measures for intensity-based rigid-body 3D/2D image registration. Similarity measure is an index that measures the similarity between a digitally reconstructed radiograph (DRR) and an x-ray planar image. The registration is accomplished by maximizing the sum of the similarity measures between biplane x-ray images and the corresponding DRRs in an iterative fashion. We have evaluated the accuracy and attraction ranges of the registrations using six different similarity measures on phantom experiments for head, thorax, and pelvis. The images were acquired using Varian Medial System On-Board Imager. Our results indicated that normalized cross correlation and entropy of difference showed a wide attraction range (62 deg and 83 mm mean attraction range, omega(mean)), but the worst accuracy (4.2 mm maximum error, e(max)). The gradient-based similarity measures, gradient correlation and gradient difference, and the pattern intensity showed sub-millimeter accuracy, but narrow attraction ranges (omega(mean)=29 deg, 31 mm). Mutual information was in-between of these two groups (e(max)=2.5 mm, omega(mean)= 48 deg, 52 mm). On the data of 120 x-ray pairs from eight IRB approved prostate patients, the gradient difference showed the best accuracy. In the clinical applications, registrations starting with the mutual information followed by the gradient difference may provide the best accuracy and the most robustness.