Dissertations / Theses on the topic 'Pediatric radiology'

This thesis establishes normal age-related changes in the magnetic resonance (MR) T1 and T2 relaxation time constants using data collected as part of the National Institutes of Health (NIH) MRI Study of Normal Brain Development. This ongoing multi-centre study of normal brain and behaviour development provides both longitudinal and cross-sectional data and has enabled us to investigate the relaxation time constant evolution in several brain regions for children within the range of 0-4.5 years. Due to the multi-centre nature of the study and the extended period of data collection, periodically scanned inanimate and human phantoms were used to assess intra and inter-site variability. The main finding of this thesis is the parametrization of the mono-exponential behaviour of both the T1 and T2 relaxation time constants from birth until 4.5 years of age. This behaviour is believed to reflect the rapid changes in water content as well as myelination processes observable during neonatal brain development. These results, comprising over 200 subject scans, represents a subset of a publicly available normative pediatric MRI database, providing a basis for comparison for studies assessing normal brain development and deviation due to various neurological disorders.

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A tomografia computadorizada (TC) é um dos métodos mais importantes de radiodiagnóstico, porém, pode resultar em altas doses absorvidas pelos pacientes quando comparado com exames radiográficos convencionais. O objetivo deste trabalho é avaliar as doses absorvidas pelos pacientes pediátricos nos procedimentos de tomografia computadorizada de crânio realizados em Recife, Brasil, utilizando o software de simulação computacional CALDose_XCT. Os parâmetros de irradiação para os procedimentos de TC de crânio pediátrico de 108 pacientes foram coletados e divididos nas seguintes faixas etárias: <1; 1 a 5; 5 a 10; e 10 a 15 anos de idade. Os valores de índice volumétrico de kerma ar em TC (CVOL) e produto kerma ar-comprimento para exames completos de TC (PKL,CT) foram estimados para cada exame e comparados com os níveis de referência internacional. Foram estimados os valores das doses absorvidos por órgãos relevantes (cristalino, cérebro, mucosa oral e glândulas salivares) utilizando o CALDose_XCT. Outra simulação foi realizada utilizando um fantoma de cabeça com inclinação de 18º para avaliar a redução da dose absorvida quando se utiliza a inclinação do gantry ou da cabeça do paciente. Os parâmetros de irradiação selecionados na maioria dos exames pediátricos avaliados não estão otimizados, já que foram observados valores maiores ou iguais aos parâmetros recomendados para exames em adultos. A maioria dos valores estimados de CVOL foram menores que os níveis de referência referência internacionais para exames pediátricos de TC. Por outro lado, situação inversa ocorreu com os valores de PKL,CT, devido ao uso de valores elevados de comprimento de varredura, em alguns casos maiores que a cabeça inteira do paciente. A maioria dos exames avaliados resultou em valores estimados de PKL,CT acima dos limites recomendados. A simulação da inclinação da cabeça dos pacientes pediátricos para exames de crânio resultou em redução da dose absorvida pelos olhos, mucosa oral e glândulas salivares, demostrando ser um método eficiente para otimização da proteção radiológica nestes procedimentos. Deste modo, ressalta-se a importância de implementação de um programa de garantia de qualidade no serviço, com o objetivo de otimizar os procedimentos e reduzir o detrimento para os pacientes pediátricos submetidos a exames de tomografia computadorizada.
The computed tomography (CT) is one of the most important methods for radio diagnostics, resulting, however, in high absorbed doses to the patients. The objective of this work is to evaluate the pediatric head CT examinations performed at one hospital in Recife, Brazil, and to estimate the mean absorbed doses to organs using the computational simulation software CALDose_XCT. The irradiation parameters used with 108 pediatric head CT examinations were registered and divided in the following age ranges: <1; 1 to 5; 5 to 10; and 10 to 15 years-old. The volume CT air kerma index (CVOL) and the air kerma-length product for full CT examinations (PKL,CT) were estimated to each examination and compared to international diagnostic reference levels. The mean absorbed doses to relevant organs (eye lens, brain, oral mucosa and salivary glands) were simulated using CALDose_XCT. Another simulation was made using a head phantom tilt of 18º, in order to evaluate the dose reduction to some organs using either the gantry or head tilt. The results showed that the irradiation parameters used in the most of the examinations are not optimized, since it was possible to observe tube potential and current-time product values higher than the recommended values to adult examinations. Most of the CVOL values were lower than the international reference levels for pediatric CT examinations. On the other hand, the contrary was observed with the PKL,CT, due to the use of large scan ranges, in some cases, bigger than the patient’s entire head. The simulation of the patient head tilt resulted in absorbed dose reduction to the eyes, oral mucosa and salivary glands, showing to be an efficient method to optimize the radiological protection of pediatric CT examinations. Thus, it can be highlighted the importance of a quality assurance program in the service, with the objective of optimizing the procedures and reducing the risk to the pediatric patients.

Thesis (MTech (Radiography))--Peninsula Technikon, 2004
The radiation risks associated with children are higher than the risk for adults. Children have growing organs and they have a longer life expectancy than that of adults. As a consequence the effects of damage from radiation could be greater than in adults. Children who receive radiation damage may pass genetic damage onto future generations. This study was carried out to investigate the optimal effective x-ray dose young children need to receive who have radiographic examination to the chest at Tygerberg Hospital, South Africa. Chest radiographs are documented as being the most common radiographic examination done on children. The age groups of children participating in this study were 0-1 year, 1-5 years and 5-10 years. A total of 67 children were involved and the absorbed doses for 134 views of the anterior-posteria (AP) chest and lateral chest were measured. Entrance surface dose (ESD) values were determined, and measured mean ESD (mGy) and the ESD range was reported for each age group. This was done by attaching thermolurninescent dosirneters (TLD pellets) to the patients skin at the entrance point of the x-ray beam. The results were compared to similar studies done in Ireland and Nigeria From the ESD values obtained the absorbed doses ofthe eyes, heart, liver, thyroid and genitals could be calculated by using the "Childdose" programme ofthe NRPB. The ESD dose levels for South Africa compare favourably with Ireland. However the Nigerian values differed greatly from those of Ireland and South Africa It was very encouraging to note the comparative results achieved at Tygerberg Hospital especially due to the fact that this was the first time such study had been conducted in the Tygerberg Hospital Radiology Department. The results also compare favourable with that achieved by a group working in the United Kingdom. This group does similar surveys every five years as part of their radiation protection programme. The results were also in line with the UNSCEAR document of2000. v This study could serve as a valuable source of reference to radiographers and radiologists when performing paediatric radiology especially as the radiation absorbed dose could be used as a baseline to create awareness of size of dose received, and to limit deleterious radiation doses to patients and to prevent unnecessary exposures. A second significant outcome of the study was the effect that added filters had on the x-ray beam generated. Experiments were done in which the filtration filters were added sequentially. It was found that if the filtration was increased to 2mmAl the dose to the patient decreased by more than 20%. At 50 and 60 kV the density of the x-ray image on film only increased by 2%. From these results it may be concluded that an increase in filtration thickness used for paediatric chest x-rays should be giVIng reduced dose readings and assisting with radiation protection ofthe patient.

Electrical Engineering
Ph.D.
Magnetic resonance based diffusion imaging has been gaining more utility and clinical relevance over the past decade. Using conventional echo planar techniques it is possible to acquire and characterize water diffusion within the central nervous system (CNS); namely in the form of Diffusion Weighted Imaging (DWI) and Diffusion Tensor Imaging (DTI). While each modality provides valuable clinical information in terms of the presence of diffusion, DWI, and its directionality, DTI, the techniques used for analysis are limited to assuming an ideal Gaussian distribution for water displacement with no intermolecular interactions. This assumption reduces the amount of relevant information that can be interpreted in a clinical setting. By measuring the excess kurtosis, or peakedness, of the Gaussian distribution it is possible to get a better understanding of the underlying cellular structure. The objective of this work is to provide mathematical and experimental evidence that Diffusion Kurtosis Imaging (DKI) can provide additional information about the micromolecular environment of the pediatric spinal cord by more completely characterizing the probabilistic nature of random water displacement. A novel DKI imaging sequence based on a 2D spatially selective radio frequency pulse providing reduced FOV imaging with view angle tilting (VAT) was implemented, optimized on a 3Tesla MRI scanner, and tested on pediatric subjects (normal:15; patients with spinal cord injury:5). Software was developed and validated in-house for post processing of the DKI images and estimation of the tensor parameters. The results show statistically significant differences in kurtosis parameters (mean kurtosis, axial kurtosis) between normal and patients. DKI provides incremental and new information over conventional diffusion acquisitions that can be integrated into clinical protocols when coupled with higher order estimation algorithms.
Temple University--Theses

Necrotising enterocolitis (NEC) is a potentially devastating intestinal inflammation of multifactorial aetiology in premature or otherwise vulnerable neonates. Because of the broad spectrum of presentations, diagnosis and timing of surgical intervention may be challenging, and imaging needs to be an integrated part of management. The first four studies included in this thesis used routinely collected, nationwide register data to describe the incidence of NEC in Sweden 1987‒2009, its variation with time, seasonality, space-time clustering, and associations with maternal, gestational, and perinatal factors, and the risk of intestinal failure in the aftermath of the disease. Early infant survival increased dramatically during the study period. The incidence rate of NEC was 0.34 per 1,000 live births, rising from 0.26 per 1,000 live births in the first six years of the study period to 0.57 in the last five. The incidence rates in the lowest birth weights were 100‒160 times those of the entire birth cohort. Seasonal variation was found, as well as space-time clustering in association with delivery hospitals but not with maternal residential municipalities. Comparing NEC cases with matched controls, some factors, positively associated with NEC, were isoimmunisation, fetal distress, caesarean section, persistent ductus arteriosus, cardiac and gastrointestinal malformations, and chromosomal abnormalities. Negative associations included maternal pre-eclampsia, maternal urinary infection, and premature rupture of the membranes. Intestinal failure occurred in 6% of NEC cases and 0.4% of controls, with the highest incidence towards the end of the study period. The last study investigated current practices and perceptions of imaging in the management of NEC, as reported by involved specialists. There was great consensus on most issues. Areas in need of further study seem mainly related to imaging routines, the use of ultrasound, and indications for surgery. Developing alongside the progress of neonatal care, NEC is a complex, multifactorial disease, with shifting patterns of predisposing and precipitating causes, and potentially serious long-term complications. The findings of seasonal variation, spacetime clustering, and negative associations with antenatal exposure to infectious agents, fit into the growing understanding of the central role of bacteria and immunological processes in normal maturation of the intestinal canal as well as in the pathogenesis of NEC. Imaging in the management of NEC may be developed through future studies combining multiple diagnostic parameters in relation to clinical outcome.

A grande utilização de exames de diagnóstico por imagem em crianças trouxe à tona a preocupação com a crescente dose de radiação absorvida na realização de um exame radiográfico. O objetivo desta pesquisa foi realizar avaliação das práticas de raios X na radiologia pediátrica, visando a otimização dos procedimentos radiológicos e a produção de imagens com qualidade para o diagnóstico com a menor dose ao paciente. A metodologia foi baseada no acompanhamento de exames pediátricos e medidas dosimétricas através do uso de dosímetros termoluminescentes TLDs e software específico (DoseCal) para a constatação da realidade dos serviços de radiologia pediátrica. Medidas de pacientes pediátricos em exames radiográficos de tórax foram realizadas em um hospital público de Curitiba e em uma clínica em Cascavel. Grupos com diferentes faixas etárias foram formados na avaliação de exames rotineiros de tórax nas projeções AP/PA e LAT, e ossos da face na projeção lateral, onde foram divididos em grupos de 0-1 ano, 1-5 anos, 5-10 anos e 10-15 anos. As doses obtidas através do software DoseCal foram comparadas entre si para determinar sua variabilidade. A DEP determinada pelos TLDs foi comparada com os valores de referência dados pela comunidade européia para verificar as doses utilizadas. Os valores de dose para crianças de até 1 ano apresentaram-se altos em comparação com os demais grupos avaliados, um fator justificado em partes pela limitação dos equipamentos utilizados. Na radiologia convencional os valores obtidos através dos TLDs foram satisfatórios, obedecendo a referência máxima descrita pela comissão européia. Na radiologia digital indireta obtivemos valores acima dos referenciados, fator este resultante da implantação e da adaptação das técnicas radiológicas a nova forma de captação de imagem. Concluí-se que o aprimoramento técnico das equipes em radiologia pediátrica é uma das melhores maneiras de se obter bons resultados na diminuição da dose.
The great use of examinations of diagnosis for image in children brought the concern with the increasing dose of radiation absorbed in the accomplishment of a radiographic examination. The objective of this research is to carry through evaluation of the practical ones of x-rays in pediatric radiology, aiming at to optimize the radiological rocedures and the production of images with quality for the diagnosis with the lesser dose to the patient. The methodology is based on the accompaniment of pediatric examinations and dosimetry measures through the use of dosemeters TLD and specific software (DoseCal) for the evidence of the reality in a radiology service. Measures of pediatric patients in radiographic examinations of thorax had been carried through in a public hospital in the Curitiba. Groups with different age groups had been formed in the evaluation of routine examinations of thorax in projections AP/PA and LAT, where they are divided in groups of 0-1 year, 1-5 years, 5-10 years and 10-15 years. Part of the carried through examinations had been evaluated with thermoluminescence dosemeters TLD-100 for the collection of the entrance surface dose (ESD). The measured doses are compared with the gotten ones with the DoseCal software, that makes the calculation of dose for each patient from the income of the device of rays X. The ESD is evaluated always that it has diagnostic quality in the radiographic image. The objective is to verify if the minimum requirements had been reached, for a good quality of image and bringing a small dose to the patient, as party to suit of to optimize procedures.

SAMMANFATTNING Nyckelord: barnröntgen, patientinformation, röntgensjuksköterska, barnkonventionen Bakgrund: För röntgensjuksköterskor är det utmanande att informera barnpatienter utifrån barnkonventionens riktlinjer, som är svensk lag sedan 2020.  Syfte: Syftet med denna enkätstudie var att ta reda på vilken patientinformation som röntgensjuksköterskan ansåg var viktig att ge till barnpatienter i samband med konventionell skelettröntgenundersökning samt vilka förutsättningar som var viktiga för att kunna tilldela den informationen. Ett ytterligare syfte var att ta reda på om röntgensjuksköterskan hade kännedom om barnkonventionen och dess betydelse i samband med barnröntgenundersökning samt om det fanns någon skillnad mellan röntgensjuksköterskor verksamma på sjukhus A och sjukhus B gällande deras uppfattning om information till barnpatienter.  Metod: En empirisk kvantitativ enkätstudie genomfördes. Urvalet bestod av röntgensjuksköterskor med erfarenhet att utföra konventionella skelettundersökningar på barn. Totalt 35 enkäter analyserades.  Resultat: Som viktigaste information valdes allmän strålsäkerhet och varför barnet ska ligga/sitta stilla. De viktigaste förutsättningarna för att ge information ansågs vara förberedda föräldrar, förberett röntgenlabb samt att vända sig till barnet vid samtal. Majoriteten svarade att röntgenmottagningarna inte erbjöd en barnanpassad miljö och instämde delvis till att kommunikationen skulle underlättas på ett barnanpassat labb. Röntgensjuksköterskorna instämmer till stor del att de har kännedom om barnkonventionens riktlinjer och att dessa har stor betydelse vid barnröntgenundersökningar. Ingen signifikant skillnad visades mellan sjukhusen. Slutsats: Respondenterna från sjukhusen enades om att viktigast att informera om var strålsäkerhet och vikten av att vara still. Röntgenmottagningarna ansågs inte ha en barnanpassad miljö. Röntgensjuksköterskornas kännedom om barnkonventionen behöver ständigt aktualiseras och diskuteras i vårdsammanhang.
ABSTRACT Key words: pediatric radiography, access to information, radiographer, Convention on the Rights of the Child Background: It is challenging for radiographers to inform pediatric patients based on the guidelines of the Convention on the Rights of the Child (CRC), Swedish law since 2020.  Purpose: The purpose was to find out what radiographers from two hospitals considered to be important information and conditions for providing it to pediatric patients undergoing x-ray examinations. The aim was also to investigate whether the radiographers carry knowledge of the CRC and its significance regarding child radiographs as well as to compare the perception of radiographers from hospital A and B on what information is of importance. Method: An empirical quantitative survey study was made.The sample included radiographers experienced in performing x-ray examinations of children. In total 35 surveys were analyzed.  Results: Information about general radiation safety and why the patient should keep still was considered most important.  The main conditions for providing information were considered to be a prepared lab, prepared parents and paying attention to the child. The majority replied that radiology clinics did not offer a child-friendly environment. The radiographers broadly agree that they are aware of the CRC’s guidelines and that these are of great importance in x-ray examinations. No significant difference was shown between the hospitals. Conclusion: Respondents agreed that informing pediatric patients about radiation safety and the importance of being still is most important. Radiology clinics were not considered to have a well-adapted environment. Radiographers’ knowledge of the CRC needs to be constantly updated.

Pas de résumé
The large-scale genomic studies performed recently has enabled the objective identification of numerous novel genomic alterations and highlighted that pediatric brain tumors often harbor quiet cancer genomes, with a single driver genomic alteration. This characteristic is of special interest in the current context of precision medicine development. Low-grade glioneuronal tumor group is highly heterogeneous and remains particularly challenging since it includes a broad spectrum of tumors, often poorly discriminated by their histopathological features and not completely molecularly characterized. We used targeted methods (IHC, FISH, targeted sequencing), and large scale genomic and epigenetic methodologies to perform an integrative analysis to further characterized papillary glioneuronal tumors (PGNT), midline gangliogliomas and dysembryoplastic neuroepithelial tumors (DNT). We demonstrated that PGNT is a distinct entity characterized by a PRKCA fusion. We highlighted that H3 K27M mutation can occur in association with BRAF V600E mutation in midline grade I glioneuronal tumors, showing that despite the presence of H3 K27M mutations, these cases should not be graded and treated as grade IV tumors because they have a better spontaneous outcome than classic diffuse midline H3 K27M-mutant glioma. The DNT study enable us 1) to specify that non-specific DNT corresponds to a clinico-histological tumor group encompassing diverse molecularly distinct entities and 2) to demonstrate that specific DNTs can be progressive tumors and harbored a distinct DNA methylation profile. Diagnosis and genomic profiling that can guide precision medicine require tissue acquisition by neurosurgical procedures that are often difficult or not possible. We validated a sample collection procedure and we developed methodologies to detect circulating tumor DNA (ctDNA) in CSF, plasma and urine to identify clinically relevant genomic alterations from a cohort of 235 pediatric patients with brain tumors. We optimized a method to process ctDNA and performed ultra-low pass whole genome sequencing (ULP-WGS) using unique molecular identifiers, confirming we can reliably construct sequencing libraries from CSF-, plasma- and urine-derived ctDNA. ULP-WGS has also been used to assess sequencing library quality, copy number variations (CNVs) and tumor fraction. The vast majority of samples undergoing ULPWGS exhibited no CNVs, consistent with either absence in the tumor or low levels of tumorderived cfDNA. To distinguish between these, we developed a hybrid capture sequencing panel allowing identification of specific mutations and fusions more common in pediatric brain tumors

The importance of monitoring, and where possible reducing, the level of radiation dose from diagnostic X-ray examinations has been recognised for many years and is becoming of increasing concern. Dose reduction is of particular concern in paediatric radiology, and there are specific problems associated with the monitoring and comparison of radiation doses to children. Any optimisation study relies on a framework of good dosimetry. Two techniques have been developed to improve the collection of patient dose data: the automation of survey techniques to increase the quantity of data collected; and a method of correcting for patient size which reduces one source of variability in the data. An optimisation strategy has been developed, consisting of theoretical simulations, experimental verification and clinical implementation. Monte Carlo techniques were used for the theoretical study, which investigated the effect of beam filtration on radiation dose and image quality for a wide range of parameters, specifically for a neonatal size phantom. Simulations included both radiography of bone in soft tissue and fluoroscopy of iodine and barium based contrast media. The results were assessed in terms of the beam spectra and the absorption and transmission characteristics of the phantom and image receptor. Experimental measurements of dose and contrast were made for a simple slab phantom corresponding to that simulated, and results showed good agreement with those predicted. A further set of experimental measurements were carried out using anthropomorphic phantoms in a clinical setting, which demonstrated how the theoretical predictions translated to clinical practice. A clinical trial of the use of a 0.1mm copper filter for fluoroscopic examinations of infants was performed, and the filter shown to give substantial dose reduction with no significant loss in image quality. Some general recommendations on dose quantities and the application of optimisation strategies to paediatric radiology have been made.

El abuso de sustancias en los países occidentales ha acontecido un problema de salud pública. Lamentablemente, estas sustancias de abuso son además una carga para las personas que no las consumen, por ello, la población pediátrica es especialmente vulnerable. Desde la década de los ochenta, la eventual presencia y disposición de una sustancia de abuso en el organismo y su correlación con efectos clínicos y/o subjetivos ha sido evaluada mediante el análisis de plasma u orina. Sin embargo, realizar estas determinaciones en fluidos y matrices biológicas diferentes a la sangre y la orina (de aquí su nombre “fluidos y matrices no convencionales”) resultan ser mucho más atractivas. Valoración de la exposición a sustancias de abuso durante el inicio de la gestación mediante el análisis de placenta. La determinación de sustancias de abuso en muestras de placenta obtenidas cómo material de descarte en mujeres que interrumpieron voluntariamente su embarazo sirvió para confirmar la transmisión de las drogas de abuso al feto durante el primer trimestre de gestación. Exposición pasiva a drogas de abuso mediante el análisis de cabello. En este trabajo se ha utilizado el análisis de cabello con el fin de esclarecer la prevalencia insospechada de exposición a cocaína en niños de edad preescolar visitados en un servicio de urgencias pediátrico sin presentar signos indicativos de una exposición a sustancias de abuso. Las muestras de cabello de 21 niños (23.3%) fueron positivas para cocaína (COC) (rango de concentración: 0,3 – 5.96 ng/mg cabello) y además una de ellas fue positiva para 3,4-metilendioximetanfetamina (MDMA) y otra para opiáceos. En el 88% de los casos positivos, también se halló la presencia de COC en la muestra de cabello del padre que acompañaba a su hijo a la visita hospitalaria. En vista de los resultados obtenidos, abogamos por el cribado mediante el análisis de cabello para esclarecer la presencia de COC y otras sustancias de abuso en niños pertenecientes a ambientes de elevado riesgo de exposición a sustancias de abuso. Valoración de la exposición pasiva a humo de tabaco mediante el análisis de dientes de leche. El uso de los dientes de leche, los cuales empiezan a formarse en la etapa prenatal puede informar acerca de la acumulación de nicotina (NIC) y otros metabolitos durante toda la infancia. Por ello, se ha desarrollado una metodología basada en la LC-MS-MS con el fin de poder detectar cantidades ínfimas de estos metabolitos en dientes de leche. Los resultados en 64 muestras de dientes mostraron que tan solo la NIC era capaz de discriminar estadísticamente entre los niños expuestos ambientalmente al humo de tabaco. Estos prometedores resultados abogan por la inclusión de la monitorización de los niveles de NIC en dientes en estudios epidemiológicos con el fin de categorizar la exposición acumulativa al humo de tabaco durante toda la infancia. Discusión y conclusiones. Esta tesis pone de manifiesto la alta exposición pasiva e insospechada a las principales sustancias de abuso tanto legal (tabaco) como ilegal (cocaína) gracias al empleo de biomarcadores detectados en matrices no convencionales como la placenta, el pelo y los dientes de leche en niños diferentes etapas de la infancia. En conclusión, con el fin de detectar la exposición a sustancias de abuso en las diferentes etapas de la infancia (incluyendo la etapa prenatal y la etapa postnatal) es recomendable utilizar diferentes matrices no convencionales (o alternativas) con el fin de minimizar la invasividad en la recogida de las muestras en comparación con las matrices utilizadas tradicionalmente.
The substance abuse in developed countries has become a public health problem. Unfortunately, these substances of abuse are also a burden for people who do not consume; therefore, the pediatric population is especially vulnerable. Since the eighties, the possible presence of a substance abuse in the body and its correlation with clinical effects and / or subjective effects has been assessed analyzing plasma or urine. However, the determination of this substances in biological fluids and matrices different than blood and urine (hence the name "non-conventional fluids and matrices") are much more attractive. For the non-invasiveness in the collection of the samples and the fact that can provide much more information about the exposure, biological matrices such as placenta, hair and teeth, are good matrices to assess chronic exposure to drugs of abuse during different stages of the childhood. Assessment of the exposure to substances of abuse during early gestation by analysis of the placenta. The determination of drugs of abuse in samples of placenta obtained as discard material in women who voluntarily terminated their pregnancy served to confirm the transmission of drugs of abuse to the fetus during the first trimester of gestation. Passive exposure to drugs of abuse using hair analysis. In this work we used hair analysis to clarify the unexpected prevalence of cocaine exposure in preschool children visited in the pediatric emergency department with no signs indicative of exposure to substances of abuse. Hair samples from 21 children (23.3%) were positive for cocaine (concentration range: 0.3 - 5.96 ng / mg of hair) and also one of them was positive for MDMA and another one for opiates. In 88% of positive cases, also found the presence of cocaine in the hair sample of the parent who accompanied his son to the hospital visit. In view of these results, we advocate screening by hair analysis to ascertain the presence of cocaine and other substances of abuse in children from high-risk environments of exposure to substances of abuse. Assessment of passive exposure to tobacco smoke by the analysis of dedicious teeth. We used decidious teeth, which begin to form in the prenatal stage, to report the accumulation of nicotine (NIC) and other metabolites throughout childhood. Therefore, we have developed a methodology based on LC-MS-MS in order to detect minute amounts of these metabolites in decidious teeth. The results obtained in 64 samples of teeth showed that only the NIC was able to discriminate statistically among children exposed to tobacco snuff environmentally. These promising results argue for the inclusion of monitoring NIC levels in teeth in epidemiological studies to categorize cumulative exposure to passive smoke throughout childhood. Discussion and conclusions. This thesis reveals the unsuspected high passive exposures to the main substances of abuse both legal (tobacco) and illegal (cocaine) by the use of biomarkers detected in non-conventional matrices such as the placenta, hair and teeth in children different stages of childhood. In conclusion, in order to detect exposure to substances of abuse in different stages of childhood (including prenatal and postnatal) is recommended to use different non-conventional matrices (or alternatives) in order to minimize the invasiveness collecting samples as compared with traditionally used matrices.

El cáncer infantil constituye un problema de salud mundial. El desarrollo de nuevos antineoplásicos y nuevos métodos para la planificación del tratamiento de radioterapia, han logrado aumentar la sobrevida, hasta en un 90% a más de 5 años en algunos tipos de tumores. La radioterapia es una modalidad de tratamiento importante en los niños con cáncer. Los efectos del tratamiento con radiaciones pueden ser evidentes inmediatamente después de finalizar el tratamiento con radioterapia o décadas después, por lo que no dejan de ser preocupantes los efectos secundarios de la radioterapia. La planificación del tratamiento debe ser meticulosa, logrando el control local del tumor con una mínima irradiación a tejidos normales. Algunas instituciones han iniciado a utilizar el PET para la planificación del tratamiento con radioterapia ya que provee datos basados en el metabolismo del tumor que aportan datos extras acerca del volumen a radiar. En pacientes pediátricos se requieren estudios que comparen las diferencias entre los volúmenes blanco con la utilización de TAC vs. Integración de imágenes PET/TAC.
Métodos: Se seleccionaron pacientes menores de 21 años, con diagnóstico de enfermedad de Hodgkin (EH); que contaran con PET/TAC de estadiaje y que hubieran recibido radioterapia supradiafragmática incluyendo mediastino. Posterior a que los pacientes finalizaron el tratamiento de radioterapia (planificado en base a la TAC de diagnóstico), se realizo una nueva planificación del tratamiento de radioterapia, delimitando los volúmenes tumorales en base a la integración de imágenes PET/TAC, se realizaron nuevas dosimetrías y se realizo la comparación de la dosimetría de planificación en base a la TAC diagnóstica vs. La planificación realizada en base a la integración PET/TAC.
Resultados: Se analizaron 22 pacientes pediátricos con un promedio de edad de 15 años, con EH y afectación ganglionar supradiafragmática incluyendo mediastino. Los 22 pacientes recibieron tratamiento multimodal con quimioterapia sistémica y RT. En todos los casos la RT se aplico posterior a la aplicación de tratamiento con quimioterapia. La dosis de radiación total aplicada fue en promedio de 23.3 Gy con un fraccionamiento de 1.8-2 Gy por día, 5 días a la semana. En 16 pacientes el volumen delimitado por PET/TAC fue mayor al delimitado por PET. En 8 de estos pacientes se detecto enfermedad en zonas que no fueron detectadas por TAC (4 en región cervical, 2 en región supraclavicular, 1 en región de mediastino y uno en región axilar). En 6 pacientes el volumen delimitado en base a la PET/TAC fue menor que el delimitado en base a la TAC. El volumen blanco promedio del PTV delimitado por TAC fue de 501.4 cm3 y el volumen promedio del PTV delimitado en base a la PET/TAC fue de 644.8 cm3.diferencia estadísticamente significativa. (p < 0.001). El volumen promedio coincidente entre el PTV basado en TAC y el PTV basado en PET/TAC fue de 360.5 cm3, el volumen promedio no coincidente se cuantifico en 360.5 cm3. La diferencia entre el volumen coincidente con el volumen del PTV basado en TAC y en PET/TAC fue estadísticamente significativa (p<0.001). Al analizar las dosis de radiación a los órganos críticos, se observó que el corazón, la glándula tiroides y la médula espinal recibían en mayor porcentaje de su volumen 5 Gy, 10Gy y 15 Gy, y que a la dosis de 20 Gy nuevamente corazón, fue de los órganos más afectados. EL pulmón izquierdo recibió 20Gy a un 14% de su volumen y el pulmón derecho a 11% de su volumen. En la planificación de RT basada en PET/TAC se encontró que en general los órganos críticos recibían irradiación mayor en mayor porcentaje de su volumen. Estas diferencias fueron estadísticamente significativas.
Childhood cancer is a worldwide health problem. The development of new antineoplastic and new methods for radiation treatment planning, have managed to increase survival, up to 90% over 5 years in some types of tumors. Radiotherapy is an important treatment modality in children with cancer. The effects of radiation therapy may be evident immediately after completion of treatment with radiotherapy or decades later, so that they are still worrisome side effects of radiotherapy. Treatment planning must be meticulous, achieving local tumor control with minimal normal tissue irradiation. Some institutions have begun to use PET for radiotherapy treatment planning as it provides data based on tumor metabolism that provide additional data about the volume to radiate. In pediatric studies are needed to compare the differences between the target volumes with the use of TAC vs. Image Integration PET / CT.
Methods: We selected patients younger than 21 years, diagnosed with Hodgkin's disease (HD) to count with PET / CT staging and who had received supradiaphragmatic radiotherapy including mediastinum. After the patients completed radiation treatment (planned on the basis of CT diagnosis), we made a new radiotherapy treatment planning and identified the tumor volumes based on the integration of imaging PET / CT, there were new dosimetry and were compared dosimetry planning based on diagnostic CT vs. The planning dosimetry based on the integration PET / CT.
Results: We analyzed 22 paediatric patients with a mean age of 15 years with EH and supradiaphragmatic including mediastinal lymph node involvement. The 22 patients received multimode treatment with systemic chemotherapy and RT. In all cases, the RT was applied after application of chemotherapy. The total applied radiation dose averaged 23.3 Gy with a fractionation of 1.8-2 Gy per day, 5 days a week. In 16 patients a limited volume by PET / CT was higher than defined by PET. In 8 of these
patients disease was detected in areas that were not detected by CT (4 in cervical region, 2 in supraclavicular region, mediastinum region 1 and one axillary). In 6 patients a limited volume based on PET / CT was lower than the defined based on the TAC. The average target volume defined by CT PTV was 501.4 cm3 and the average volume of PTV defined on the basis of PET / CT was 644.8 cm3.diferencia statistically significant. (p <0.001). In analyzing the radiation doses to critical organs, it was observed that the heart, thyroid and spinal cord received greater percentage of its volume 5 Gy, 10Gy and 15 Gy, and that a dose of 20 Gy heart again, was the most affected organs. The left lung received 20Gy to 14% of its volume and the right lung to 11% by volume. In RT planning based on PET / CT was found that in general the critical organs received more radiation in a greater percentage of its volume. These differences were statistically significant.

La falta de disponibilidad de presentaciones comerciales adecuadas para la posología pediátrica todavía supone un gran problema, especialmente relevante en medicamentos con margen terapéutico estrecho, ya que puede derivar en infra o sobredosificaciones; o en niños que sufren enfermedades crónicas, condenados a tomar medicamentos mal adaptados y sufrir las consecuencias que ello supone; o en las ocasiones en las que se presentan casos de intolerancias o alergias hacia determinados excipientes. Todo ello obliga a realizar un gran número de fórmulas magistrales. Evidentemente, para solventar este problema, las formas farmacéuticas líquidas siguen siendo la mejor alternativa a las formas farmacéuticas sólidas, ya que ofrecen una serie de ventajas: . Versatilidad para el ajuste de dosis, frecuentemente modificada en estos pacientes en función del peso o de la respuesta clínica. . Facilidad de administración. . Fiabilidad de la dosificación. . Posibilidad de administración por sonda nasogástrica. Sin embargo, la variabilidad en el diseño de fórmulas magistrales, la falta de uniformidad en el caso de las suspensiones y el inconveniente de la menor estabilidad de las formas líquidas, conlleva la posibilidad de errores de medicación en el manejo de las dosificaciones. De aquí que la terapéutica en pacientes pediátricos o pacientes con dificultades para deglutir, dependa en gran medida de la elaboración de formulaciones magistrales adecuadas. Algunas de las patologías que requieren la realización de estos preparados para pacientes pediátricos incluyen la hipertensión pulmonar persistente del neonato, la insuficiencia cardiaca congestiva, el síndrome de abstinencia neonatal o las convulsiones. Por tanto, a la vista de lo anterior, en este trabajo se han desarrollado y estudiado un total de trece fórmulas magistrales líquidas de administración oral: dos fórmulas de sildenafilo, cuatro de espironolactona, dos de furosemida, tres de metadona y dos de fenobarbital. En el desarrollo de las fórmulas también se ha tenido en cuenta a la población diabética. Una vez establecida la fórmula cuali-cuantitativa de cada una de las formulaciones, se desarrolló y validó un método sensible y rápido como técnica analítica de referencia para la cuantificación de cada principio activo, para lo cual se determinó la linealidad, la precisión y la exactitud del método analítico; asimismo se determinaron los límites de cuantificación y detección para cada uno de los principios activos objeto de estudio. Los controles físico-químicos y microbiológicos que se llevaron a cabo con el fin de caracterizar las diferentes fórmulas fueron: 1. Características organolépticas (aspecto, color, olor). 2. Cuantificación del principio activo 3. Determinación del pH 4. Comportamiento reológico y viscosidad 5. Tamaño de partícula (sólo en el caso de las suspensiones) 6. Estabilidad óptica acelerada (sólo en el caso de las suspensiones). 7. Análisis microbiológico (Ph.Eur.) Para establecer su estabilidad, las formulaciones se almacenaron a tres temperaturas (4, 25 y 40 ºC) durante un periodo máximo de 90 días y se determinaron aquellos parámetros susceptibles de cambio a diferentes tiempos prefijados. Por otro lado, se realizaron controles biofarmacéuticos con el objeto de determinar la influencia de los excipientes en los procesos de liberación (estudios in vitro- ensayos de disolución) y absorción (estudio de la absorción a través de intestino delgado de cerdo) del principio activo. Los resultados obtenidos en esta Tesis Doctoral hacen posible una correcta conservación y dosificación de los principios activos estudiados (sildenafilo, espironolactona, furosemida, metadona y fenobarbital) cuando se formulan en formas líquidas de administración oral; garantizando la continuidad, la calidad y la eficacia de tratamientos pediátricos tales como la hipertensión pulmonar persistente del neonato, la insuficiencia cardiaca congestiva, el síndrome de abstinencia neonatal y las convulsiones neonatales, según corresponda.
The lack of availability of age appropriate dosage forms is still a big problem, especially relevant in drugs with narrow therapeutic index, as it can lead to under-or overdosing; children with cronical diseases; or in cases of allergies to certain excipients. This requires a large number of pharmaceutical compounding. To solve this problem, the liquid dosage forms remain the best alternative to the solid dosage forms because they offer advantages: • Versatility for dosage adjustment in these patients • Easy administration. • Reliability dosing. • Possibility of gavage. However, the variability in their design and the lower stability of the liquid forms, leads to the possibility of medication errors in handling dosages. Hence the therapy in pediatric patients or patients with swallowing difficulties, depend largely on the development of appropriate formulations. Therefore, in this work thirteen liquid pharmaceutical compounding for oral administration: two formulations of sildenafil, four of spironolactone, two of furosemide, three of methadone and two of Phenobarbital have been developed, taking into account also the diabetic population. An analytical method has been developed and validated using appropriates analytical techniques for the quantification of each active ingredient (API). Linearity, precision, accuracy, and quantification and detection limits were determined. Physico-chemical and microbiological controls were performed in order to characterize the formulas: 1. Organoleptic properties 2. Quantification of the API 3. Determination of pH 4. Rheological behavior and viscosity 5. Particle size (for suspensions). 6. Optical stability (for suspensions). 7. Microbiological analysis (Ph.Eur) To establish the shelf life, the formulations were stored at three temperatures (4, 25 and 40 °C) for a maximum period of 90 days. The parameters that could change were determined at different times. Biopharmaceutical controls were performed to determine the influence of the excipients on the release (dissolution tests) and absorption (absorption studies through pig small intestine) processes of the API. Obtained results ensures the stability of sildenafil, spironolactone, furosemide, methadone and phenobarbital when formulated in oral liquid dosage forms; allowing continuity, quality and efficacy of pediatric therapies such as persistent pulmonar hypertension of the newborn, congestive heart failure, neonatal abstinence syndrome and neonatal seizures, as appropriate.

OBJECTIVE: Nuclear medicine provides important clinical information for diagnostic and therapeutic purposes. Use of medical imaging has gradually increased in the United States and this has raised health concerns about the potential future risks associated with radiation exposure in children. While studies have evaluated the adverse effects of imaging procedures, there is insufficient evidence about communicating radiation risks. The overall purpose of this paper is to review radiation risks in pediatric imaging using published evidence by the World Health Organization and to evaluate the knowledge and attitude of caregivers towards radiation risks in pediatric imaging. Specifically, we aim to determine whether an educational brochure improves parental knowledge of radiation and/or changes in attitude and perception to allow their children to undergo dental radiographs. METHODS: A prospective sample survey was performed of caregivers who presented with their child to the Boston University Pediatric Oral Healthcare Center. Parents or legal guardians (18 years or older) who accompanied a child were eligible for inclusion and approached for enrollment. Pre- and post-survey questionnaires were used to evaluate parents’ or guardians’ level of knowledge and attitude about the risks and benefits of dental radiographs. Parents were also asked their comfort level to allow their child to undergo dental radiographs. After completing the pre-survey questionnaire, parents were asked to read the English-language informational handout. Statistical analysis was performed through Microsoft Excel 2013. Descriptive analysis was conducted to summarize the survey responses. RESULTS: Among 30 parents who were surveyed, a small proportion (30%) of parents were very comfortable with dentist using dental radiographs on their child, versus 57% after reading the handout. Results showed that the informational handout improved the parental knowledge of risks and benefits of ionizing radiation. Most parents indicated that the handout was helpful and they reported increased level of comfort and willingness in their children receiving radiation imaging during dental treatment procedures. DISCUSSION: Educating parents or caregivers through an informational handout is a helpful resource in improving their knowledge and in relieving their concerns. Informing parents about the risks of ionizing radiation does not change parental willingness for their children to undergo dental radiographs.

In my thesis I deal with ionizing radiation, its origin, its effects and principles. I also deal with radiation protection and its principles, medical exposure and pediatric radiodiagnostics in terms of imaging methods and specifics of radiation protection in paediatrics. And whether all the methods used to reduce radiation exposure in children undergoing ionizing radiation are used. Part of the work is also devoted to the way of communication in this area and awareness, whether it is paid enough attention or this area is neglected in the Czech Republic.

L’Osteogenesi Imperfetta (OI) è un raro disordine del tessuto connettivo caratterizzato da un alto grado di fragility ossea. Negli ultimi anni, scoprendone le basi molecolari, abbiamo inizato a considerarla più etereogenea di quanto si pensasse. Il trattamento di questa condizione è basato sull’uso di farmaci che impediscono il riassorbimento osseo come I bisfosfonati (BPs), ma è ormai diventato evidente che l’uso dei BPs in alcuni sottotipi di OI può essere controproducente se non addirittura dannoso. Il recento riscontro di molteplici basi molecoari nella genesi dell’OI, quindi il coivolgimento di geni non solo legati all’assemblaggio e alla formazione del collagene, ma anche alla regolazione dello sviluppo degli osteoblasti, ha permesso di conoscere meglio dettagli del processo di formazione del collagene. Nuovi trattamenti specifici per deficit di singoli geni e in grado di colpire obiettivi cellulari specifici in pazienti affetti da OI sono in corso. Lo scopo di questo studio sfruttare l’ambito dell’imaging multimodale per comprendere meglio le caratteristiche dei nuofi sottotipi di OI, in modo da poter offrire al singolo paziente, una valutazione complessiva della loro condizione. In particolare considerando l’imaging multimodale nel senso più ampio siamo partiti dalla clinica, intesa come esame obiettivo per apparati ed esame dismorfologico, abbiamo integrato le immagini radiologiche classiche in grado di fornire informazioni dismorfiche fondamentali (come le immagini da raggi X, le densitometrie, le morfometrie e le risonanze magnetiche) e i reperti biochimici (routinari e sperimentali come dosaggi ELISA), arrivando così a selezionare gruppi di pazienti per i quali è stato possibile, passando attraverso conferme ottenute da studi istologici (valutati con microscopia ottica, elettronica e confocale) e studi di elettroforesi proteica mono e bi-dimensionale, ottenere una diagnosi molecolare tramite la polimerase chain reaction, RFLP, Mutation/polymorphism screening (DHPLC, DNA microarray e DNA sequencing) e quindi arrivando a una diagnosi specifica della condizione cercare di offrire il trattamento più adatto. In questo lavoro sono state prese in considerazione in particolare la storia clinica, gli aspetti fenotipici clinici, biologici e radiologici e gli aspetti molecolari di 23 pazienti affetti da OI V (1), OI VI (10), OI VII (1), OI VIII (2), OI XII (1). I risultati ottenuti hanno permesso di porre le basi per studi futuri che esplorino la reale incidenza delle forme non classiche di OI, e che identifichino il trattamento più adatto per ciascun sottotipo di OI, sulla base del difetto genetico e quindi della patogenesi della malattia.
Osteogenesis Imperfecta (OI) is a rare connective tissue defect characterised by high bone fragility. In the last years it has become more heterogeneous than it was believed to be, since its molecular basis are being discovered. The treatment of this condition is based on the use of anti-resorbitive drugs such as bisphosphonates (BPs), but it has clearly emerged that the use of BPs could be in a way harmful or at least ineffective in some OI types. The recent recognition of multiple molecular basis in the genesis of OI, involving not only genes related to collagen assembly and processing, but also the regulation of osteoblast development has illuminated the details of the collagen processing pathway. New therapies that would be specific for single-gene disorders and identify cellular targets in individuals with OI are ongoing trials. The aim of this research is take advantage of the multimodal imaging, in its wider meaning, to clarify the characteristics of the new OI subtypes in order to offer the best possible evaluation for each patient on the basis of their complex condition. In particular the multimodal imaging is intended as the physical examination and the dysmorphologic examination, integrated to classical radiologic imaging (X-rays, DXA, morphometry) and biological data (both routine and experimental assays through ELISA), leading to the development of groups of selected patients that are further studied with histological samples (using both optic, electronic and confocal microscopy) and protein mono and bidimensional electrophoresis to obtain a molecular diagnosis (DHPLC, DNA microarray e DNA sequencing) and therefore to outline a more targeted treatment. In this thesis the clinical history, the clinical phenotypes, the biological, radiological and molecular aspect of 23 patients affected by non classical forms of OI have been considered: OI V (1), OI VI (10), OI VII (1), OI VIII (2), OI XI (1). These results offer the basis for further studies aiming to calculate the incidence of non classical OI subtypes and identifying the best treatment for each subtype of OI, on the basis of the genetic defects and therefore of the patogenesis of the disease.

Die Multiple Sklerose (MS) ist die häufigste chronisch entzündliche Erkrankung des zentralen Nervensystems (ZNS). Zunehmend wird sie auch bei Kindern und Jugendlichen diagnostiziert. In wiefern Kinder und Jugendliche mit MS sich jedoch im Bezug auf Klinik und die neuroradiologische Präsentation von Erwachsenen unterscheiden ist bisher wenig untersucht. Ich konnte zeigen, dass die derzeit gültigen Diagnosekriterien nach McDonald in der Version von 2010 eine hohe diagnostische Sensitivität haben und gut auf pädiatrische Patienten anwendbar sind.  In der geschlechts- und altersbezogenen Analyse von klinischen und kernspin-tomographischen Daten zeigte sich, dass Jungen gleichen Alters und gleicher Krankheitsdauer eine höhere Läsionslast zeigen als Mädchen. Zudem konnten Ergebnisse bestätigt werden, die zeigen, dass die Erkrankungswahrscheinlichkeit für Jungen nach der Pubertät deutlich abnimmt, wohingegen sie für Mädchen ansteigt. Die Erkrankungswahrscheinlichkeit vor der Pubertät ist insgesamt sehr gering.   Zudem konnte ich in der pädiatrischen MS-Kohorte die Theorie der chronischen zerebrospinalen venösen Insuffizienz (CCSVI) widerlegen. Venöse Insuffizienzen zeigten sich als häufiges jedoch unspezifisches Phänomen.