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The purpose was to report clinical experience of a video-guided spirometry system in applying deep inhalation breath-hold (DIBH) radiotherapy for left-sided breast cancer, and to study the systematic and random uncertainties, intra- and interfraction motion and impact on cardiac dose associated with DIBH. The data from 28 left-sided breast cancer patients treated with spirometer-guided DIBH radiation were studied. Dosimetric comparisons between free-breathing (FB) and DIBH plans were performed. The distance between the heart and chest wall measured on the digitally reconstructed radiographs (DRR) and MV portal images, dDRR(DIBH) and dport(DIBH), respectively, was compared as a measure of DIBH setup uncertainty. The difference (Δd) between dDRR(DIBH) and dport(DIBH) was defined as the systematic uncertainty. The standard deviation of Δd for each patient was defined as the random uncertainty. MV cine images during radiation were acquired. Affine registrations of the cine images acquired during one fraction and multiple fractions were performed to study the intra- and interfraction motion of the chest wall. The median chest wall motion was used as the metric for intra- and interfraction analysis. Breast motions in superior-inferior (SI) direction and "AP" (defined on the DRR or MV portal image as the direction perpendicular to the SI direction) are reported. Systematic and random uncertainties of 3.8 mm and 2mm, respectively, were found for this spirometer-guided DIBH treatment. MV cine analysis showed that intrafraction chest wall motions during DIBH were 0.3mm in "AP" and 0.6 mm in SI. The interfraction chest wall motions were 3.6 mm in "AP" and 3.4 mm in SI. Utilization of DIBH with this spirometry system led to a statistically significant reduction of cardiac dose relative to FB treatment. The DIBH using video-guided spirometry provided reproducible cardiac sparing with minimal intra- and interfraction chest wall motion, and thus is a valuable adjunct to modern breast treatment techniques.
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Suspensão da Respiração , Inalação , Espirometria/métodos , Neoplasias Unilaterais da Mama/radioterapia , Gravação em Vídeo , Fracionamento da Dose de Radiação , Feminino , Coração/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Imagens de Fantasmas , Prognóstico , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
In our study, we used a mass spectrometry-based metabolomic approach to search for biomarkers that may act as early indicators of spontaneous preterm birth (sPTB). Samples were selected as a nested case-control study from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, New Zealand. Cervicovaginal swabs were collected at 20 weeks from women who were originally assessed as being at low risk of sPTB. Samples were analysed using gas chromatography-mass spectrometry (GC-MS). Despite the low amount of biomass (16-23 mg), 112 compounds were detected. Statistical analysis showed no significant correlations with sPTB. Comparison of reported infection and plasma inflammatory markers from early pregnancy showed two inflammatory markers were correlated with reported infection, but no correlation with any compounds in the metabolite profile was observed. We hypothesise that the lack of biomarkers of sPTB in the cervicovaginal fluid metabolome is simply because it lacks such markers in early pregnancy. We propose alternative biofluids be investigated for markers of sPTB. Our results lead us to call for greater scrutiny of previously published metabolomic data relating to biomarkers of sPTB in cervicovaginal fluids, as the use of small, high risk, or late pregnancy cohorts may identify metabolite biomarkers that are irrelevant for predicting risk in normal populations.
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Colo do Útero/metabolismo , Líquido Extracelular/metabolismo , Metaboloma , Metabolômica , Nascimento Prematuro/metabolismo , Vagina/metabolismo , Adulto , Biomarcadores , Estudos de Casos e Controles , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Idade Gestacional , Humanos , Mediadores da Inflamação/metabolismo , Metabolômica/métodos , Gravidez , Fatores de RiscoRESUMO
We investigated the sensitivity of the gamma index to two factors: the spatial resolution and the noise level in the measured dose distribution. We also examined how the choice of reference distribution and analysis software affect the sensitivity of gamma analysis to these two factors for quality assurance (QA) of intensity-modulated radiation therapy (IMRT) treatment plans. For ten clinical IMRT plans, the dose delivered to a transverse dose plane was measured with EDR2 radiographic film. To evaluate the effects of spatial resolution, each irradiated film was digitized using three different resolutions (71, 142, and 285 dpi). To evaluate the effects of image noise, 1% and 2% local Gaussian noise was added to the film images. Gamma analysis was performed using 2%/2 mm and 3%/3 mm acceptance criteria and two commercial software packages, OmniPro I'mRT and DoseLab Pro. Dose comparisons were performed with the treatment planning system (TPS)-calculated dose as the reference, and then repeated with the film as the reference to evaluate how the choice of reference distribution affects the results of dose comparisons. When the TPS-calculated dose was designated as the reference distribution, the percentage of pixels with passing gamma values increased with both increasing resolution and noise. For 3%/3 mm acceptance criteria, increasing the film image resolution by a factor of two and by a factor of four caused a median increase of 0.9% and 2.6%, respectively, in the percentage of pixels passing. Increasing the noise level in the film image resulted in a median increase in percentage of pixels passing of 5.5% for 1% added local Gaussian noise and 5.8% for 2% added noise. In contrast, when the film was designated as the reference distribution, the percentage of pixels passing decreased with increased film noise, while increased resolution had no significant effect on passing rates. Furthermore, the sensitivity of gamma analysis to noise and resolution differed between OmniPro I'mRT and DoseLab Pro, with DoseLab Pro being less sensitive to the effects of noise and resolution. Noise and high scanning resolution can artificially increase the percentage of pixels with passing gamma values in IMRT QA. Thus, these factors, if not properly taken into account, can potentially affect the results of IMRT QA by causing a plan that should be classified as failing to be falsely classified as passing. In designing IMRT QA protocols, it is important to be aware that gamma analysis is sensitive to these parameters.
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Raios gama , Neoplasias/radioterapia , Garantia da Qualidade dos Cuidados de Saúde , Radiometria/normas , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia de Intensidade Modulada/normas , Algoritmos , Humanos , Radiometria/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Razão Sinal-Ruído , SoftwareRESUMO
The purpose of this study was to determine the reproducibility of patient-specific, intensity-modulated radiation therapy (IMRT) quality assurance (QA) results in a clinical setting. Six clinical patient plans were delivered to a variety of devices and analyses, including 1) radiographic film; 2) ion chamber; 3) 2D diode array delivered and analyzed in three different configurations (AP delivery with field-by-field analysis, AP delivery with composite analysis, and planned gantry angle delivery); 4) helical diode array; and 5) in-house-designed multiple ion chamber phantom. The six clinical plans were selected from a range of treatment sites and were of various levels of complexity. Of note, three of the plans had failed at least preliminary evaluation with our in-house IMRT QA; the other three plans had passed QA. These plans were delivered three times sequentially without changing the setup, and then delivered two more times after breaking down and rebuilding the setup between each. This allowed for an investigation of reproducibility (in terms of dose, dose difference or percent of pixels passing gamma) of both the delivery and the physical setup. This study showed that the variability introduced from the setup was generally higher than the variability from redelivering the plan. Radiographic film showed the poorest reproducibility of the dosimeters investigated. In conclusion, the various IMRT QA systems demonstrated varying abilities to reproduce QA results consistently. All dosimetric devices demonstrated a reproducibility (coefficient of variation) of less than 4% in their QA results for all plans, with an average reproducibility of less than 2%. This work provides some quantification for the variability that may be seen for IMRT QA dosimeters.
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Medicina de Precisão/normas , Garantia da Qualidade dos Cuidados de Saúde/normas , Radiometria/instrumentação , Radiometria/normas , Planejamento da Radioterapia Assistida por Computador/instrumentação , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia de Intensidade Modulada/normas , Modelagem Computacional Específica para o Paciente/normas , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estados UnidosRESUMO
Efforts to mitigate radiation therapy (RT)-associated cardiotoxicity have focused on constraining mean heart dose. However, recent studies have shown greater predictive power with cardiac substructure dose metrics, such as the left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15Gy) ≥10%. Herein, we investigated the feasibility of LAD radiation sparing in contemporary intensity modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) lung cancer plans. Single institution retrospective analysis of 54 patients with locally advanced lung cancer treated with thoracic RT was conducted between February 2018 and August 2021. After excluding 33 (5 = non-IMRT/VMAT or intentionally LAD-optimized; 28 = LAD V15Gy <10%), 21 plans with LAD V15Gy ≥10% were identified for LAD reoptimization with intent to meet LAD V15Gy <10% while maintaining meeting organ at risk (OAR) metrics and target coverage with original plan parameters. Dosimetric variables were compared using paired t tests. Most patients (57.1%, 12/21) were treated with definitive RT, 8 of 21 patients (38.1%) with postoperative RT, and 1 with neoadjuvant RT. The median prescribed RT dose was 60 Gy (range, 50.4-66 Gy) in 30 fractions (range, 28-33 fractions). LAD reoptimized plans (vs original) led to significant reductions in mean LAD V15Gy (39.4% ± 13.9% vs 9.4% ± 13.0%; P < .001) and mean LAD dose (12.9 Gy ± 4.6 Gy vs 7.6 Gy ± 2.8 Gy; P < .001). Most (85.7%; 18/21) LAD reoptimized plans achieved LAD V15Gy <10%. There were no statistically significant differences in overall lung, esophageal, or spinal cord dose metrics. Only 1 reoptimization (1/21) exceeded an OAR constraint that was initially met in the original plan. To our knowledge, this is the first report describing the feasibility of LAD-optimized lung cancer RT planning using the newly identified LAD V15Gy constraint. We observed that LAD V15Gy <10% is achievable in more than 85% of plans initially exceeding this constraint, with minimal dosimetric tradeoffs. Our results support the feasibility of routine incorporation of the LAD as an OAR in modern thoracic IMRT/VMAT planning.
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PURPOSE: A left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15 Gy) ≥10% has been recently observed to be an independent risk factor of major adverse cardiac events and all-cause mortality in patients with locally advanced non-small cell lung cancer treated with radiation therapy. However, this dose constraint has not been validated in independent or prospective data sets. METHODS AND MATERIALS: The NRG Oncology/Radiation Therapy Oncology Group (RTOG) 0617 data set from the National Clinical Trials Network was used. The LAD coronary artery was manually contoured. Multivariable Cox regression was performed, adjusting for known prognostic factors. Kaplan-Meier estimates of overall survival (OS) were calculated. For assessment of baseline cardiovascular risk, only age, sex, and smoking history were available. RESULTS: There were 449 patients with LAD dose-volume data and clinical outcomes available after 10 patients were excluded owing to unreliable LAD dose statistics. The median age was 64 years. The median LAD V15 Gy was 38% (interquartile range, 15%-62%), including 94 patients (21%) with LAD V15 Gy <10% and 355 (79%) with LAD V15 Gy ≥10%. Adjusting for prognostic factors, LAD V15 Gy ≥10% versus <10% was associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.43; 95% confidence interval, 1.02-1.99; P = .037), whereas a mean heart dose ≥10 Gy versus <10 Gy was not (adjusted HR, 1.12; 95% confidence interval, 0.88-1.43; P = .36). The median OS for patients with LAD V15 Gy ≥10% versus <10% was 20.2 versus 25.1 months, respectively, with 2-year OS estimates of 47% versus 67% (P = .004), respectively. CONCLUSIONS: In a reanalysis of RTOG 0617, LAD V15 Gy ≥10% was associated with an increased risk of all-cause mortality. These findings underscore the need for improved cardiac risk stratification and aggressive risk mitigation strategies, including implementation of cardiac substructure dose constraints in national guidelines and clinical trials.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Vasos Coronários , Neoplasias Pulmonares/radioterapia , Estudos Prospectivos , Doses de Radiação , Dosagem RadioterapêuticaRESUMO
PURPOSE: Missing or discrepant imaging volume is a common challenge in deformable image registration (DIR). To minimize the adverse impact, we train a neural network to synthesize cropped portions of head and neck CT's and then test its use in DIR. METHODS: Using a training dataset of 409 head and neck CT's, we trained a generative adversarial network to take in a cropped 3D image and output an image with synthesized anatomy in the cropped region. The network used a 3D U-Net generator along with Visual Geometry Group (VGG) deep feature losses. To test our technique, for each of the 53 test volumes, we used Elastix to deformably register combinations of a randomly cropped, full, and synthetically full volume to a single cropped, full, and synthetically full target volume. We additionally tested our method's robustness to crop extent by progressively increasing the amount of cropping, synthesizing the missing anatomy using our network, and then performing the same registration combinations. Registration performance was measured using 95% Hausdorff distance across 16 contours. RESULTS: We successfully trained a network to synthesize missing anatomy in superiorly and inferiorly cropped images. The network can estimate large regions in an incomplete image, far from the cropping boundary. Registration using our estimated full images was not significantly different from registration using the original full images. The average contour matching error for full image registration was 9.9 mm, whereas our method was 11.6, 12.1, and 13.6 mm for synthesized-to-full, full-to-synthesized, and synthesized-to-synthesized registrations, respectively. In comparison, registration using the cropped images had errors of 31.7 mm and higher. Plotting the registered image contour error as a function of initial preregistered error shows that our method is robust to registration difficulty. Synthesized-to-full registration was statistically independent of cropping extent up to 18.7 cm superiorly cropped. Synthesized-to-synthesized registration was nearly independent, with a -0.04 mm of change in average contour error for every additional millimeter of cropping. CONCLUSIONS: Different or inadequate in scan extent is a major cause of DIR inaccuracies. We address this challenge by training a neural network to complete cropped 3D images. We show that with image completion, the source of DIR inaccuracy is eliminated, and the method is robust to varying crop extent.
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Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Algoritmos , Cabeça , Humanos , Imageamento Tridimensional , PescoçoRESUMO
PURPOSE: To develop and demonstrate the efficacy of a novel head-and-neck multimodality image registration technique using deep-learning-based cross-modality synthesis. METHODS AND MATERIALS: Twenty-five head-and-neck patients received magnetic resonance (MR) and computed tomography (CT) (CTaligned ) scans on the same day with the same immobilization. Fivefold cross validation was used with all of the MR-CT pairs to train a neural network to generate synthetic CTs from MR images. Twenty-four of 25 patients also had a separate CT without immobilization (CTnon-aligned ) and were used for testing. CTnon-aligned 's were deformed to the synthetic CT, and compared to CTnon-aligned registered to MR. The same registrations were performed from MR to CTnon-aligned and from synthetic CT to CTnon-aligned . All registrations used B-splines for modeling the deformation, and mutual information for the objective. Results were evaluated using the 95% Hausdorff distance among spinal cord contours, landmark error, inverse consistency, and Jacobian determinant of the estimated deformation fields. RESULTS: When large initial rigid misalignment is present, registering CT to MRI-derived synthetic CT aligns the cord better than a direct registration. The average landmark error decreased from 9.8 ± 3.1 mm in MRâCTnon-aligned to 6.0 ± 2.1 mm in CTsynth âCTnon-aligned deformable registrations. In the CT to MR direction, the landmark error decreased from 10.0 ± 4.3 mm in CTnon-aligned âMR deformable registrations to 6.6 ± 2.0 mm in CTnon-aligned âCTsynth deformable registrations. The Jacobian determinant had an average value of 0.98. The proposed method also demonstrated improved inverse consistency over the direct method. CONCLUSIONS: We showed that using a deep learning-derived synthetic CT in lieu of an MR for MRâCT and CTâMR deformable registration offers superior results to direct multimodal registration.
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Aprendizado Profundo , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Humanos , Imageamento por Ressonância Magnética , Imagem MultimodalRESUMO
The melanocortin peptides have an important role in regulating body weight and appetite. Mice that lack the desacetyl-α-MSH and α-MSH peptides (Pomctm1/tm1) develop obesity. This effect is exacerbated by a high fat diet (HFD). However, development of obesity in female Pomctm1/tm1 mice during chronic HFD conditions is not fully accounted for by the increased energy intake. We hypothesized that the protection against chronic HFD-induced obesity imparted by MSH peptides in females is mediated by sex-specific alterations in the gut structure and gut microbiota. We determined that female WT mice had reduced jejunum villus length and increased crypt depth in response to chronic HFD. WT males and Pomctm1/tm1 mice lacked this adaptation to a chronic HFD. Both Pomctm1/tm1 genotype and chronic HFD were significantly associated with gut microbiota composition. Sex-specific associations between Pomctm1/tm1 genotype and gut microbiota were observed in the presence of a chronic HFD. Pomctm1/tm1 females had significantly reduced fecal acetate and propionate concentrations when compared to WT females. We conclude that MSH peptides influence jejunum villus length, crypt depth and the structure of the gut microbiota. These effects favor reduced nutrient absorption and occur in addition to the recognized roles of desacetyl-α-MSH and α-MSH peptides in appetite control.
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Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hormônios Estimuladores de Melanócitos/metabolismo , Ácido Acético/metabolismo , Animais , Feminino , Genótipo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise Multivariada , Obesidade/metabolismo , Pró-Opiomelanocortina/metabolismo , Propionatos/metabolismo , RNA Ribossômico 16S/metabolismo , alfa-MSH/metabolismoRESUMO
Our understanding of the human gut microbiome has grown exponentially. Advances in genome sequencing technologies and metagenomics analysis have enabled researchers to study microbial communities and their potential function within the context of a range of human gut related diseases and disorders. However, up until recently, much of this research has focused on characterizing the gut microbiological community structure and understanding its potential through system wide (meta) genomic and transcriptomic-based studies. Thus far, the functional output of these microbiomes, in terms of protein and metabolite expression, and within the broader context of host-gut microbiome interactions, has been limited. Furthermore, these studies highlight our need to address the issues of individual variation, and of samples as proxies. Here we provide a perspective review of the recent literature that focuses on the challenges of exploring the human gut microbiome, with a strong focus on an integrated perspective applied to these themes. In doing so, we contextualize the experimental and technical challenges of undertaking such studies and provide a framework for capitalizing on the breadth of insight such approaches afford. An integrated perspective of the human gut microbiome and the linkages to human health will pave the way forward for delivering against the objectives of precision medicine, which is targeted to specific individuals and addresses the issues and mechanisms in situ.
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Infant adiposity may be related to later metabolic health. Maternal metabolite profiling reflects both genetic and environmental influences and allows elucidation of metabolic pathways associated with infant adiposity. In this multi-ethnic Asian cohort, we aimed to (i) identify maternal plasma metabolites associated with infant adiposity and other birth outcomes and (ii) investigate the maternal characteristics associated with those metabolites. In 940 mother-offspring pairs, we performed gas chromatography-mass spectrometry and identified 134 metabolites in maternal fasting plasma at 26-28 weeks of gestation. At birth, neonatal triceps and subscapular skinfold thicknesses were measured by trained research personnel, while weight and length measures were abstracted from delivery records. Gestational age was estimated from first-trimester dating ultrasound. Associations were assessed by multivariable linear regression, with p-values corrected using the Benjamini-Hochberg approach. At a false discovery rate of 5%, we observed associations between 28 metabolites and neonatal sum of skinfold thicknesses (13 amino acid-related, 4 non-esterified fatty acids, 6 xenobiotics, and 5 unknown compounds). Few associations were observed with gestational duration, birth weight, or birth length. Maternal ethnicity, pre-pregnancy BMI, and diet quality during pregnancy had the strongest associations with the specific metabolome related to infant adiposity. Further studies are warranted to replicate our findings and to understand the underlying mechanisms.
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Adiposidade/fisiologia , Biomarcadores/sangue , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Adulto , Peso ao Nascer/fisiologia , Índice de Massa Corporal , Dieta/métodos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Obesidade/sangue , Obesidade/fisiopatologia , Gravidez , Estudos Prospectivos , Dobras CutâneasRESUMO
Preterm infants are exposed to major perinatal, post-natal, and early infancy events that could impact on the gut microbiome. These events include infection, steroid and antibiotic exposure, parenteral nutrition, necrotizing enterocolitis, and stress. Studies have shown that there are differences in the gut microbiome during the early months of life in preterm infants. We hypothesized that differences in the gut microbial composition and metabolites in children born very preterm persist into mid-childhood. Participants were healthy prepubertal children aged 5-11 years who were born very preterm (≤32 weeks of gestation; n = 51) or at term (37-41 weeks; n = 50). We recorded the gestational age, birth weight, mode of feeding, mode of birth, age, sex, and the current height and weight of our cohort. We performed a multi'omics [i.e., 16S rRNA amplicon and shotgun metagenomic sequencing, SPME-GCMS (solid-phase microextraction followed by gas chromatography-mass spectrometry)] analysis to investigate the structure and function of the fecal microbiome (as a proxy of the gut microbiota) in our cross-sectional cohort. Children born very preterm were younger (7.8 vs. 8.3 years; p = 0.034), shorter [height-standard deviation score (SDS) 0.31 vs. 0.92; p = 0.0006) and leaner [BMI (body mass index) SDS -0.20 vs. 0.29; p < 0.0001] than the term group. Children born very preterm had higher fecal calprotectin levels, decreased fecal phage richness, lower plasma arginine, lower fecal branched-chain amino acids and higher fecal volatile (i.e., 3-methyl-butanoic acid, butyrolactone, butanoic acid and pentanoic acid) profiles. The bacterial microbiomes did not differ between preterm and term groups. We speculate that the observed very preterm-specific changes were established in early infancy and may impact on the capacity of the very preterm children to respond to environmental changes.
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Bacteriófagos , Microbioma Gastrointestinal , Criança , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , RNA Ribossômico 16S/genéticaRESUMO
Prediction of spontaneous preterm birth (sPTB) in asymptomatic women remains a great challenge; accurate and reproducible screening tools are still not available in clinical practice. We aimed to investigate whether the maternal serum metabolome together with clinical factors could be used to identify asymptomatic women at risk of sPTB. We conducted two case-control studies using gas chromatography-mass spectrometry to analyse maternal serum samples collected at 15- and 20-weeks' gestation from 164 nulliparous women from Cork, and 157 from Auckland. Smoking and vaginal bleeding before 15 weeks were the only significant clinical predictors of sPTB for Auckland and Cork subsets, respectively. Decane, undecane, and dodecane were significantly associated with sPTB (FDR < 0.05) in the Cork subset. An odds ratio of 1.9 was associated with a one standard deviation increase in log (undecane) in a multiple logistic regression which also included vaginal bleeding as a predictor. In summary, elevated serum levels of the alkanes decane, undecane, and dodecane were associated with sPTB in asymptomatic nulliparous women from Cork, but not in the Auckland cohort. The association is not strong enough to be a useful clinical predictor, but suggests that further investigation of the association between oxidative stress processes and sPTB risk is warranted.
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Metaboloma , Nascimento Prematuro/diagnóstico , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Espectrometria de Massas , Idade Materna , Gravidez , Nascimento Prematuro/sangueRESUMO
Colostrum is the first ingested sole nutritional source for the newborn infant. The vitamin profile of colostrum depends on the maternal vitamin status, which in turn is influenced by diet and lifestyle. Yet, the relationship between maternal vitamin status and colostrum vitamin composition has not been systematically reviewed. This review was conducted with the aim to generate a comprehensive overview on the relationship between maternal serum (plasma) vitamin concentration and corresponding colostrum composition. Three electronic databases, Embase (Ovid), Medline (Ovid), and Cochrane, were systematically searched based on predefined inclusion and exclusion criteria. Finally, a total of 11 eligible publications were included that examined the vitamins A, C, D, E, and K in both biological fluids. Maternal vitamin A, D, E, and K blood levels were unrelated to colostrum content of the respective vitamins, and serum vitamin A was inversely correlated with colostrum vitamin E. Colostrum versus maternal serum vitamins were higher for vitamins A, C, and K, lower for vitamin D, and divergent results were reported for vitamin E levels. Colostrum appears typically enriched in vitamin A, C, and K compared to maternal serum, possibly indicative of active mammary gland transport mechanisms. Inter-individual and inter-study high variability in colostrum's vitamin content endorses its sensitivity to external factors.
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Colostro/química , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Vitaminas/sangue , Adolescente , Adulto , Idoso , Dieta , Feminino , Humanos , Recém-Nascido , Lactação , Estilo de Vida , Metanálise como Assunto , Micronutrientes/administração & dosagem , Micronutrientes/sangue , Pessoa de Meia-Idade , Leite Humano/química , Ensaios Clínicos Controlados Aleatórios como Assunto , Recomendações Nutricionais , Adulto JovemRESUMO
The fetus undergoes a crucial period of neurodevelopment in utero. The maternal hair metabolome provides an integrated record of the metabolic state of the mother prior to, and during pregnancy. We investigated whether variation in the maternal hair metabolome was associated with neurodevelopmental differences across infants. Maternal hair samples and infant neurocognitive assessments (using the Bayley III Scales of Infant Development at 24 months) were obtained for 373 infant-mother dyads between 26-28 weeks' gestation from the Growing Up in Singapore Towards Healthy Outcomes cohort. The hair metabolome was analysed using gas chromatography-mass spectrometry. Intensity measurements were obtained for 276 compounds. After controlling for maternal education, ethnicity, and infant sex, associations between metabolites and expressive language skills were detected, but not for receptive language, cognitive or motor skills. The results confirm previous research associating higher levels of phthalates with lower language ability. In addition, scores were positively associated with a cluster of compounds, including adipic acid and medium-chain fatty acids. The data support associations between the maternal hair metabolome and neurodevelopmental processes of the fetus. The association between phthalates and lower language ability highlights a modifiable risk factor that warrants further investigation.
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Transtornos do Desenvolvimento da Linguagem/epidemiologia , Exposição Materna/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Desenvolvimento Infantil/fisiologia , Feminino , Feto , Cabelo/metabolismo , Humanos , Lactente , Transtornos do Desenvolvimento da Linguagem/induzido quimicamente , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Masculino , Metaboloma/genética , Mães , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Singapura/epidemiologiaRESUMO
PURPOSE: To denoise self-gated k-space sorted 4-dimensional magnetic resonance imaging (SG-KS-4D-MRI) by applying a nonlocal means denoising filter, block-matching and 3-dimensional filtering (BM3D), to test its impact on the accuracy of 4D image deformable registration and automated tumor segmentation for pancreatic cancer patients. METHODS AND MATERIALS: Nine patients with pancreatic cancer and abdominal SG-KS-4D-MRI were included in the study. Block-matching and 3D filtering was adapted to search in the axial slices/frames adjacent to the reference image patch in the spatial and temporal domains. The patches with high similarity to the reference patch were used to collectively denoise the 4D-MRI image. The pancreas tumor was manually contoured on the first end-of-exhalation phase for both the raw and the denoised 4D-MRI. B-spline deformable registration was applied to the subsequent phases for contour propagation. The consistency of tumor volume defined by the standard deviation of gross tumor volumes from 10 breathing phases (σ_GTV), tumor motion trajectories in 3 cardinal motion planes, 4D-MRI imaging noise, and image contrast-to-noise ratio were compared between the raw and denoised groups. RESULTS: Block-matching and 3D filtering visually and quantitatively reduced image noise by 52% and improved image contrast-to-noise ratio by 56%, without compromising soft tissue edge definitions. Automatic tumor segmentation is statistically more consistent on the denoised 4D-MRI (σ_GTV = 0.6 cm(3)) than on the raw 4D-MRI (σ_GTV = 0.8 cm(3)). Tumor end-of-exhalation location is also more reproducible on the denoised 4D-MRI than on the raw 4D-MRI in all 3 cardinal motion planes. CONCLUSIONS: Block-matching and 3D filtering can significantly reduce random image noise while maintaining structural features in the SG-KS-4D-MRI datasets. In this study of pancreatic tumor segmentation, automatic segmentation of GTV in the registered image sets is shown to be more consistent on the denoised 4D-MRI than on the raw 4D-MRI.
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Artefatos , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Técnicas de Imagem de Sincronização Respiratória/métodos , Adulto , Feminino , Humanos , Masculino , Neoplasias Pancreáticas/radioterapia , Reconhecimento Automatizado de Padrão/métodos , Radioterapia Guiada por Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Razão Sinal-Ruído , Técnica de SubtraçãoRESUMO
Gestational Diabetes Mellitus (GDM) is associated with an increased risk of perinatal morbidity and long term health issues for both the mother and offspring. Previous research has demonstrated associations between maternal diet and GDM development, but evidence in Asian populations is limited. The objective of our study was to examine the cross-sectional relationship between maternal dietary patterns during pregnancy and the risk of GDM in a multi-ethnic Asian cohort. Maternal diet was ascertained using 24-h dietary recalls from participants in the Growing up in Singapore towards healthy outcomes (GUSTO) study-a prospective mother-offspring cohort, and GDM was diagnosed according to 1999 World Health Organisation guidelines. Dietary patterns were identified using factor analysis, and multivariate regression analyses performed to assess the association with GDM. Of 909 participants, 17.6% were diagnosed with GDM. Three dietary patterns were identified: a vegetable-fruit-rice-based-diet, a seafood-noodle-based-diet and a pasta-cheese-processed-meat-diet. After adjusting for confounding variables, the seafood-noodle-based-diet was associated with a lower likelihood of GDM (Odds Ratio (95% Confidence Interval)) = 0.74 (0.59, 0.93). The dietary pattern found to be associated with GDM in our study was substantially different to those reported previously in Western populations.
RESUMO
PURPOSE: MRI is increasingly being used for radiotherapy planning, simulation, and in-treatment-room motion monitoring. To provide more detailed temporal and spatial MR data for these tasks, we have recently developed a novel self-gated (SG) MRI technique with advantage of k-space phase sorting, high isotropic spatial resolution, and high temporal resolution. The current work describes the validation of this 4D-MRI technique using a MRI- and CT-compatible respiratory motion phantom and comparison to 4D-CT. METHODS: The 4D-MRI sequence is based on a spoiled gradient echo-based 3D projection reconstruction sequence with self-gating for 4D-MRI at 3 T. Respiratory phase is resolved by using SG k-space lines as the motion surrogate. 4D-MRI images are reconstructed into ten temporal bins with spatial resolution 1.56 × 1.56 × 1.56 mm(3). A MRI-CT compatible phantom was designed to validate the performance of the 4D-MRI sequence and 4D-CT imaging. A spherical target (diameter 23 mm, volume 6.37 ml) filled with high-concentration gadolinium (Gd) gel is embedded into a plastic box (35 × 40 × 63 mm(3)) and stabilized with low-concentration Gd gel. The phantom, driven by an air pump, is able to produce human-type breathing patterns between 4 and 30 respiratory cycles/min. 4D-CT of the phantom has been acquired in cine mode, and reconstructed into ten phases with slice thickness 1.25 mm. The 4D images sets were imported into a treatment planning software for target contouring. The geometrical accuracy of the 4D MRI and CT images has been quantified using target volume, flattening, and eccentricity. The target motion was measured by tracking the centroids of the spheres in each individual phase. Motion ground-truth was obtained from input signals and real-time video recordings. RESULTS: The dynamic phantom has been operated in four respiratory rate (RR) settings, 6, 10, 15, and 20/min, and was scanned with 4D-MRI and 4D-CT. 4D-CT images have target-stretching, partial-missing, and other motion artifacts in various phases, whereas the 4D-MRI images are visually free of those artifacts. Volume percentage difference for the 6.37 ml target ranged from 5.3% ± 4.3% to 10.3% ± 5.9% for 4D-CT, and 1.47 ± 0.52 to 2.12 ± 1.60 for 4D-MRI. With an increase of respiratory rate, the target volumetric and geometric deviations increase for 4D-CT images while remaining stable for the 4D-MRI images. Target motion amplitude errors at different RRs were measured with a range of 0.66-1.25 mm for 4D-CT and 0.2-0.42 mm for 4D-MRI. The results of Mann-Whitney tests indicated that 4D-MRI significantly outperforms 4D-CT in phase-based target volumetric (p = 0.027) and geometric (p < 0.001) measures. Both modalities achieve equivalent accuracy in measuring motion amplitude (p = 0.828). CONCLUSIONS: The k-space self-gated 4D-MRI technique provides a robust method for accurately imaging phase-based target motion and geometry. Compared to 4D-CT, the current 4D-MRI technique demonstrates superior spatiotemporal resolution, and robust resistance to motion artifacts caused by fast target motion and irregular breathing patterns. The technique can be used extensively in abdominal targeting, motion gating, and toward implementing MRI-based adaptive radiotherapy.
Assuntos
Tomografia Computadorizada Quadridimensional/instrumentação , Imageamento por Ressonância Magnética/instrumentação , Movimento , Imagens de Fantasmas , Respiração , Humanos , Processamento de Imagem Assistida por ComputadorRESUMO
PURPOSE: The authors investigated the performance of several patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA) dosimeters in terms of their ability to correctly identify dosimetrically acceptable and unacceptable IMRT patient plans, as determined by an in-house-designed multiple ion chamber phantom used as the gold standard. A further goal was to examine optimal threshold criteria that were consistent and based on the same criteria among the various dosimeters. METHODS: The authors used receiver operating characteristic (ROC) curves to determine the sensitivity and specificity of (1) a 2D diode array undergoing anterior irradiation with field-by-field evaluation, (2) a 2D diode array undergoing anterior irradiation with composite evaluation, (3) a 2D diode array using planned irradiation angles with composite evaluation, (4) a helical diode array, (5) radiographic film, and (6) an ion chamber. This was done with a variety of evaluation criteria for a set of 15 dosimetrically unacceptable and 9 acceptable clinical IMRT patient plans, where acceptability was defined on the basis of multiple ion chamber measurements using independent ion chambers and a phantom. The area under the curve (AUC) on the ROC curves was used to compare dosimeter performance across all thresholds. Optimal threshold values were obtained from the ROC curves while incorporating considerations for cost and prevalence of unacceptable plans. RESULTS: Using common clinical acceptance thresholds, most devices performed very poorly in terms of identifying unacceptable plans. Grouping the detector performance based on AUC showed two significantly different groups. The ion chamber, radiographic film, helical diode array, and anterior-delivered composite 2D diode array were in the better-performing group, whereas the anterior-delivered field-by-field and planned gantry angle delivery using the 2D diode array performed less well. Additionally, based on the AUCs, there was no significant difference in the performance of any device between gamma criteria of 2%/2 mm, 3%/3 mm, and 5%/3 mm. Finally, optimal cutoffs (e.g., percent of pixels passing gamma) were determined for each device and while clinical practice commonly uses a threshold of 90% of pixels passing for most cases, these results showed variability in the optimal cutoff among devices. CONCLUSIONS: IMRT QA devices have differences in their ability to accurately detect dosimetrically acceptable and unacceptable plans. Field-by-field analysis with a MapCheck device and use of the MapCheck with a MapPhan phantom while delivering at planned rotational gantry angles resulted in a significantly poorer ability to accurately sort acceptable and unacceptable plans compared with the other techniques examined. Patient-specific IMRT QA techniques in general should be thoroughly evaluated for their ability to correctly differentiate acceptable and unacceptable plans. Additionally, optimal agreement thresholds should be identified and used as common clinical thresholds typically worked very poorly to identify unacceptable plans.