Dissertations / Theses on the topic 'Diagnostic imaging. eng'

Orientador: Leda Maria Pescinini Salzedas
Banca: Ana Maria Pires Soubhia
Banca: Ana Lucia Alvares Capelozza
Resumo: O consumo abusivo de álcool interfere no metabolismo ósseo podendo causar a osteoporose, e o fluoreto de sódio tem sido usado para reduzir o risco de fratura na osteoporose. Não há relatos do efeito sinérgico dessas substâncias no tecido ósseo. A densitometria óssea é um método preciso para avaliação do conteúdo mineral ósseo. O objetivo deste estudo foi realizar a análise densitométrica óssea em fêmur de rato submetidos ao consumo de fluoreto e ao consumo crônico de álcool com e sem consumo prévio de fluoreto. Os 105 ratos foram divididos em 5 grupos conforme a dieta líquida: água (Controle C) e fluoreto (Grupo F) "ad libitum" por um período de 90 dias; água (Grupo CA) e fluoreto (Grupo FA) por 30 dias antes do consumo de aguardente de cana (40o GL) em concentrações crescentes de 30% e 60% durante 20 dias, e pura por 40 dias até eutanásia do animal; água por 60 dias e a seguir fluoreto por 30 dias (Grupo CF). Os animais foram sacrificados após 3, 10 e 28 dias de completada a dieta, os fêmures esquerdos foram dissecados e submetidos à análise densitométrica no sistema DXA. Os valores obtidos de conteúdo de massa óssea (CMO) e densidade mineral óssea (DMO) foram submetidos à análise de variância e teste de Tukey para comparação entre os grupos, sendo verificada diferença estatística entre os grupos no CMO e DMO. A ordem decrescente de DMO foi: F, CF, C, FA, CA, sendo observada diferença estatística entre os grupos F e CA. O grupo F apresentou os maiores valores de CMO e DMO, e os grupos FA e CA apresentaram menores médias de CMO e DMO comparados aos C, F e CF. Podemos concluir que o uso de NaF de maneira prolongada aumenta a densidade óssea e que o uso crônico de álcool diminui os valores de CMO e DMO, mesmo com o uso prévio de NaF, sendo encontrado valores intermediários após consumo das duas substâncias.
Abstract: The abusive alcohol consumption intervenes with the bone metabolism being able to cause osteoporosis and the sodium fluorid has been used to reduce the risk of breaking in osteoporosis. There are not reports of the synergistic effect of such substances on bone tissue. The aim of this study was to analysis bone density in the rat femur submitted to the use of fluoride and the chronic consumption of alcohol with and without pre-fluoride. The 105 rats had been divided in 5 groups in agreement the liquid diet: water (Control C) and fluorid (Fluorid F) "ad libitum" for a period of 90 days; water (water and alcohol CA) and fluorid (fluorine and alcohol FA) per 30 days before the consumption of sugar cane brandy (40°GL) in increasing concentrations of 30% and 60% during 20 days, and pure for 40 days until euthanasia of the animal; water per 60 days and to follow fluorid per 30 days (fluorid 30 days CF). The animals were sacrificed after 3, 10 and 28 days of completion of the diet, the left femurs were dissected and submitted for analysis in the DXA standard system. The values obtained of bone mass content (BMC) and bone mineral density (BMD) were submitted to the analysis of variance and test Tukey for comparison between groups, and found statistical difference between the groups in the BMC and BMD. The order of decreasing BMD was: F, CF, C, FA, CA, and observed statistical difference between the groups F and CA. The group F presented the highest values of BMC and BMD, and the FA and CA groups had lower average BMC and BMD compared to C, F and CF. We can conclude that the use of NaF on a prolonged increases bone density and that the chronic use of alcohol lowers the values of BMC and BMD, even with the previous use of NaF, and intermediate values found after consumption of the both substances.
Mestre

Orientador: Maria Jaqueline Mamprim
Banca: Maria Denise Lopes
Banca: Franklin de Almeida Sterman
Resumo: A ultra-sonografia é um método de grande utilidade na Medicina Veterinária, apresentando grande valia no diagnóstico gestacional em cadelas, por ser um método precoce, acompanhar o desenvolvimento e a viabilidade embrionária e fetal. Entretanto possui algumas limitações para estimar a idade fetal, quando comparada com a Medicina Humana, principalmente devido a grande variação do porte nos cães. Foi realizado acompanhamento ultra-sonográfico em 27 cadelas prenhes de diferentes raças distribuídas em grupos segundo o peso corpóreo, com o objetivo de estudar a utilização do exame ultra-sonográfico como método de diagnóstico e acompanhamento gestacional, avaliando o desenvolvimento embrionário e fetal (organogênese), além de comparar os métodos de avaliação da idade gestacional e dias anteriores ao parto propostos por diversos autores, sendo utilizados para os cálculos as mensurações da vesícula embrionária, crânio, corpo e coração em três diferentes fases gestacionais, visando auxiliar o médico veterinário na escolha dos cálculos mais indicados para cada fase gestacional nos diferentes grupos de cadelas.
Abstract: Ultrasonography is a useful technique in veterinary medicine, showing high value in gestational diagnosis in bitches, because its use for early pregnancy detection as well as easiness to follow embrionary and fetal viability and development. However, as compared with human medicine, veterinary ultrasound technique has some limitations in estimating fetal age mainly because the high variation in size of dogs. Ultrasound accompaniments of 27 pregnant, all age and breed bitches separated in groups, were performed, with the objective of studying the ultrasound as a technique for gestational diagnosis and further observation, evaluating both embrionary and fetal development (organogenesis), and comparing previous evaluation techniques of gestational age on days before parturition proposed by different author. Mensurations of embryonic vesicles, skull, body size and heart at three different gestational stages were achieved, to help practitioners in choosing the most accurate estimation method at each gestational stage in different groups of bitches.
Mestre

Orientador: Maria Jaqueline Mamprim
Banca: Lucy Mary
Banca: Ribeiro Muniz
Banca: Nilva Maria
Banca: Esteves Mascarenhaz
Resumo: exame radiográfico e a ultra-sonografia foram avaliados como técnicas de imagem no diagnóstico de ruptura do ligamento cruzado cranial (LCCr) em cães. Verificou-se sexo, raça, peso e idade dos animais atendidos no Hospital Veterinário (HV) da Faculdade de Medicina Veterinária e Zootecnia (FMVZ)-UNESP, Botucatu-SP. Num período de 12 meses, 31 cães com suspeita de ruptura do LCCr foram submetidos a exames radiográficos e ultra-sonográficos com objetivo de verificar sinais compatíveis com a lesão. Os casos positivos foram encaminhados para cirurgia, no intuito de confirmar o diagnóstico O e reparar a lesão. Foram verificados por meio de artrotomia 23 casos de ruptura total e dois casos de ruptura parcial do LCCr. Não houve diferença significativa entre machos e fêmeas, bem como entre animais inteiros ou castrados. Os cães sem raça definida foram os mais acometidos, seguidos pelo boxer, pit bull, pastor alemão e rottweiler. O animal mais leve pesava 8,4kg e o mais pesado 71kg, sendo a média igual a 27,9kg. Cães com peso igual ou inferior a 15kg apresentaram uma ocorrência menor da doença quando comparados aos animais com peso acima de 15,1kg. A faixa etária variou entre 12 meses a 13 anos, não sendo verificada variação considerável ao compararmos animais jovens e maduros. O exame radiográfico diagnosticou corretamente a lesão em 84% (21) dos casos, e quatro (16%) animais tiveram resultado falso-negativo. O exame ultra-sonográfico foi capaz de diagnosticar acertadamente 76% dos casos, e fornecer diagnóstico favorável nos 24% restantes, apresentando 100% de resultados positivos. No presente trabalho pudemos concluir que tanto o exame radiográfico quanto a ultra-sonografia são modalidades que podem contribuir de forma positiva no diagnóstico da ruptura do LCCr em cães.
Abstract: Radiographic and ultrasonographic examination was evaluated as image techniques in diagnostic of cranial cruciate ligament (CCL) rupture in dogs. Was determined the sex, breed, body weight and age of the animals taken care in the Hospital Veterinarian (HV) of the Faculdade de Medicina Veterinária e Zootecnia (FMVZ)-UNESP, Botucatu-SP. In a period of 12 months, 31 dogs with supposed CCL rupture were examined radiographic and ultrasonographically with objective to verify compatible signals with the injury. Positive cases had been directed for surgery, in intention to confirm the diagnostic and to repair the injury. Had been verified by artrotomy 23 cases of total rupture and two cases of partial rupture of the CCL. Did not have significant difference between males and females, as well as between intact or neutered animals. Mixed breeds had been affected, followed for boxer, pit bull, german shepherddog and rottweiler. The animal lightest weighed 8,4kg and the heaviest 71kg, mean body weight was 27,9kg. Dogs with equal or inferior weight 15kg had presented a lesser occurrence of the illness when compared with the animals with weight above of 15,1kg. Age varied enters 12 months and 13 years, without considerable variation between mature and young animals. Radiology correctly identified the injury in 84% of the cases, and four (16%) animals had false-negative resulted. In 76% of cases, ultrasonography correctly identified, and to supply to favorable diagnosis in 24% remains, presenting 100% of positive results. In the present study we could conclude that as radiology how ultrasonography are modalities diagnostics that can contribute of positive form in the diagnosis of the rupture of the CCL in dogs.
Mestre

Breast cancer is the most common cancer in women worldwide. In 2009, a novel imaging modality called Shear Wave Elastography (SWE), an ultrasound technique visualising the elasticity of tissue, was introduced to the field of clinical breast imaging. Because malignant tissues are generally stiffer than benign tissues, SWE supports the differentiation of benign / malignant solid breast lesions. However, no standard has yet been defined for the application and the evaluation of results. Furthermore, image evaluation has to be carried out directly from the ultrasound system, complicating long-term and multi-centre studies. This PhD thesis investigated the influences from the imaging process and image evaluation on SWE measurements. Various parameters were appraised with regard to their diagnostic performance, in order to define the best clinical standard. To define more complex image analysis, taking the parameters investigated into account, algorithms were devised to enable automatic assessment of B-mode and SWE images. In this work, influences from the imaging process and image evaluation on the SWE measurements were demonstrated. The influences investigated included: the impact from the region of interest and the imaging plane used; the individual variation in breast composition; the number of images considered and the pressure applied during imaging. The algorithms described within this work achieved a diagnostic accuracy similar to that of manual assessment by a radiology expert. This thesis demonstrated influences from the imaging process and image evaluation on the SWE measurements obtained. Taking these influences into consideration would complicate the clinical application of SWE imaging. However, automatic image evaluation as presented here would overcome this issue. Using the guidelines defined in this PhD thesis also allows for comparison of results taken from different imaging sites.

This study investigated radiographers' infection control practice within the Diagnostic Imaging Department. The investigation was carried out in three phases. Structured observations were carried out in four hospitals to determine the frequency and identify the situations in which infection control procedures were performed. Bacterial analysis was performed on equipment in one hospital to identify levels of contamination associated with the lack of cleaning witnessed during the observational study. Finally Focus Group discussions were used in two hospitals to establish the opinions and attitudes of radiographers regarding infection control, and to identify factors that prevented as well as those that facilitated these practices. Radiographers' compliance with infection control practice was low. Hand decontamination prior to patient contact was observed on only (n=34) 4% of occasions, and afterwards on (n=145) 17% of occasions. Infection control practice was frequently inappropriate when radiographers were dealing with situations involving immunosuppressed patients, those with open wounds, and in the handling of needles. Equipment was cleaned on only (n=30) 4% of occasions. It was found that 56% of the pieces of equipment were found to have unacceptable levels of bacterial contamination. However, after simple decontamination the measure of bacterial load was significantly reduced. The Focus Group discussions indicated that radiographers had good levels of knowledge regarding infection control, but issues such as lack of time and resources, low perceived risk of infection and the culture of the departments and NHS trusts had a negative effect on compliance rates. For maximum compliance it is thought that a multifaceted intervention should be implemented. The researcher believes the use of Quality Circles would develop a culture that would encourage compliance with infection control protocols. Better compliance with infection control protocols achieved through changes in education, procedures and culture in the Diagnostic Imaging Department are, therefore, vital to protect both patients and staff.

This thesis describes a series of investigations into the use of optic nerve head (ONH) imaging in primary open-angle glaucoma (POAG), and its relation to visual function. Accurate diagnosis is a key issue in POAG, particularly the difficult task of separating those with early disease from those healthy individuals who display signs of POAG. The purpose of this work is to improve diagnostic methods in glaucoma through use of ONH imaging and its relationship with visual field (VF) loss. First, the performance of a group of expert clinicians evaluating ONH photographs for glaucomatous damage was investigated. The results showed that even when their assessments are combined discrimination between eyes with and without POAG (based on VF loss) is far from perfect, highlighting the need for improvements in diagnosis. The possibility of combining structural and functional data to aid diagnosis was then considered. This requires VF loss and ONH damage to be strongly topographically related. The strength of this relationship was evaluated in 185 patients with POAG. 10,000 computer-generated maps between the ONH and VF were tested and the topographic relationship measured with each of these was compared to that using a published structure-based map. The weak topographic relationships found suggest that the application of these maps to individual patients is limited with current measures. The next chapter describes how a multispectral imaging (MSI, also called hyperspectral imaging) system was set-up for spatial evaluation of ONH oxygenation using a Beer-Lambert law model. Test-retest repeatability was tested and found to be acceptable for the purposes of the following studies. The MSI system was then used for an investigation of the relationship between ONH oxygenation and VF loss. 33 eyes of 18 patients underwent VF testing, MSI and HRT3 imaging. Superior-inferior asymmetries in VF sensitivity were compared to superior-inferior asymmetries in ONH oxygenation measured by MSI and in neuroretinal rim (NRR) area measured by HRT3. This way we take advantage of the typical progression of POAG and each eye acts as its own reference, negating the effect of a wide normal range and overlap between health and disease. This study found, for the first time, a strong association between ONH oxygenation and VF sensitivity. A re-analysis of the 33 ONH oxygenation maps was then performed to assess oxygenation only in the area of the NRR as defined by the HRT. Superior-inferior asymmetries in NRR oxygenation were then compared to superior-inferior asymmetries in VF loss, and the associations found were similarly strong. This study shows that MSI is capable of detecting areas of NRR deemed healthy tissue by structural imaging techniques, which are in fact poorly oxygenated and associated with VF defects. These findings show that NRR oxygenation measured by MSI is strongly related to VF loss. This important information complements existing technologies and may aid in the future diagnosis and management of patients with POAG.

Orientador: Sheila Canavese Rahal
Banca: Marcia Rita Fernandes Machado
Banca: José Morceli
Resumo: O trabalho teve por objetivos avaliar, por meio de estudos goniométricos, radiográficos e tomográficos, medidas aferidas dos membros pélvicos de pacas criadas em cativeiro, de forma a fornecer informações para esta espécie. Foram utilizadas nove pacas (Cuniculus paca) adultas, sendo três fêmeas e seis machos, com peso médio variando de 5,9 até 8,2 kg. O valor médio do arco de movimento para articulação do joelho foi de 77,34 ±13,48º e o da articulação tarsocrural de 99,09 ±8,42º, porém a articulação coxofemoral apresentou valores de 67,38 ±6,16º até 81,00 ±7,52º. Pela avaliação radiográfica, a média do ângulo de Norberg foi de 132,33 ±2,29º e 129,22 ±2,72º para os membros pélvicos direito e esquerdo, respectivamente. Os valores do ângulo de inclinação apresentaram variação de 142,44 ±4,82º até 145,44 ±4,09º para o método A de Hauptman, de 129,78 ±3,84º até 133,22 ±2,58º para o método B de Hauptman e de 144,94 ±3,13º até 148,22 ±3,25º para o método de Montavon. O valor médio do comprimento do ligamento patelar (L) foi 15,87 ±1,14 mm, e o do comprimento longitudinal da patela (P) de 27,26 ±1,93mm, sendo a proporção L:P de 0,59 ±0,06, na mensuração radiográfica em projeção mediolateral. Pela aferição tomográfica, a média do comprimento patela no plano coronal foi 2,93 ±0,17cm e no plano sagital variou de 2,78 ±0,30cm até 2,89 ±0,20cm. A média do ângulo de anteversão, mensurado por tomografia, foi de 28,56 ±5,56º até 32,91 ±2,62º. A conformação óssea das pacas apresenta muitas semelhanças com a do porquinho da índia, porém foram detectadas apenas duas lúnulas e uma fabela lateral. Os valores obtidos servirão de base para futuros estudos comparativos com outras espécies de roedores ou mamíferos.
Abstract: The aim of this study was to evaluate the hind limbs of pacas raised in captivity using goniometrical, radiographical and computed tomography (CT) studies to establish data about this specie. Nine mature pacas (Cuniculus paca), 3 females and 6 males, weighing 5.9-8.2 kg were used. Mean values of range of motion of knee and tarsus were 77.34 ±13.48º and 99.09 ±8.42º, respectively, and range of motion of hip joint ranged from 67.38 ±6.16º to 81.00 ±7.52º. Radiographically, Norberg angle had mean values of 132.33 ±2.29º and 129.22±2.72º for right and left hind limbs, respectively. Angles of Inclination ranged from 142.44 ±4.82º to 145.44 ±4.09º for Hauptman A method, from 129.78 ±3.84º to 133.22 ±2.58º for Hauptman B method, and from 144.94 ±3.13º to 148.22 ±3.25º for Montavon method. The mean values of patellar ligament length (L) and longitudinal length of the patella (P) were 15.87 ±1.14mm and 27.26 ±1.93mm, respectively, and the length ratio between the patellar tendon and the patella (L:P) was 0.59 ±0.06, measured on the mediolateral radiographs. Length of the patella in the coronal plane was 2.93 ±0.17cm, and in the sagittal plane ranged from 2.78 ±0.30cm to 2.89 ±0,20cm using CT measurements. Average values for the femoral head and neck anteversion angles measured by CT were from 28.56 ±5.56º to 32.91 ±2.62º. The bone structure of the pacas has similarity to the guinea pigs, but two lunulae and one lateral fabela were observed. The data obtained may be used to future studies comparing the pacas to other rodent species or mammals.
Mestre

This overview reports 31 studies, which have been performed by the author since 1989 to define the diagnostic value of thermometry and infrared imaging in rehabilitation and rheumatology. Some investigations were designed to characterise either treatment modalities, to clarify the role of temperature measurements as a method for follow-up or treatment monitoring in certain diseases. Thermal imaging has an important impact in assisting the diagnosis of many diseases. A relationship between temperature and clinical signs was established in the following disorders: epicondylitis (correlation of hot spots with pain provocated by firm pressure or resisted movement, and pressure threshold), complex regional pain syndrome (elevated temperature is paralleled by swelling and pain, temperature elevation of the hand after radius fracture after plaster removal predicts typical X-ray changes), thoracic outlet syndrome (high correlation of the region of paresthesia and low temperature readings), muscular inactivity, acute stage of Herpes zoster and Raynaud's phenomenon. Thermal imaging is of little value for the assessment of disability in patients with knee pain and of questionable value in patients with carpal tunnel syndrome or fibromyalgia. Painful tendon insertions or acupuncture points on the auricle cannot be detected by thermal imaging. Temperature signs in epicondylitis, complex regional pain syndrome and thoracic outlet can be successfully used for treatment monitoring. This might be also the case in radiotherapy of malignant breast disease. Infrared thermography, performed immediately after physical exercise can help to identify activated muscles. The value of thermal imaging for monitoring patients with lymphedema remains questionable. Temperature signs in epicondylitis, complex regional pain syndrome and thoracic outlet can be successfully used for treatment monitoring. This might be also the case in radiotherapy of malignant breast disease. Infrared thermography, performed immediately after physical exercise can help to identify activated muscles. The value of thermal imaging for monitoring patients with lymphedema remains questionable. On the other hand as a result of these studies, it became quite clear that the heat regulatory system is connected with other regulation systems of the body. Many of these influence the perfusion of vessels, which can result in temperature changes on the surface. In addition to the circulation system, pain and muscle function are the most important links to temperature regulation. Therefore any change or therapeutic modification of these systems might be seen on thermal images.

Thesis (Ph.D)--Electrical and Computer Engineering, Georgia Institute of Technology, 2009.
Committee Chair: Hasler, Paul; Committee Co-Chair: Degertekin, Levent; Committee Member: Anderson, David; Committee Member: Ayazi, Farrokh; Committee Member: Brand, Oliver; Committee Member: Hesketh, Peter. Part of the SMARTech Electronic Thesis and Dissertation Collection.

As opposed to current Intraoperative Ultrasound (IOUS) systems and their relatively large probes and limited superficial high frequency imaging, the use of a biopsy needle with an integrated transducer that is capable of minimally invasive and high-resolution ultrasound imaging is proposed. Such a design would overcome the compromise between resolution and penetration depth which is associated with the use of a probe on the skins surface. It is proposed that during interventional procedures, a transducer array positioned at the tip of a biopsy needle could provide real-time image guidance to the clinician with regards to the needle position within the tissue, and aid in the safe navigation of needles towards a particular target such as a tumour in tissues such as the breast, brain or liver, at which point decisions surrounding diagnosis or treatment via in vivo tissue characterisation could be made. With this objective, challenges exist in the manufacturing these miniature scale devices and theirincorporation into needle packages. The reliable realisation of miniature ultrasound transducer arrays on fine-scale piezoelectric composites, and establishing interconnects to these devices which also fit into suitably sized biopsy needles are two such hurdles. In this thesis, the fabrication of miniature 15 MHz ultrasound transducers is presented. The first stage of development involved the production of single element transducers in needles ~2 mm inner diameter, using various piezoelectric materials as the active material. These devices were tested andcharacterised, and the expertise developed during their fabrication was used as the foundation upon which to design a wafer-scale fabrication process for the production of multiple 15 MHz transducer arrays. This process resulted in a 16 element 15 MHz array connected to a flexible printed circuit board and integrated into a breast biopsy needle. Characterisation tests demonstrated functionality of each of the 16 elements, both individually and combined as an array. To explore potential applications for these devices, the single element transducers were tested in fresh and Thiel embalmed cadaveric brain tissue. Plasticine targets were embedded in these brain models and the needle transducers were tested as navigational real-time imaging tools to detect these targets within the brain tissue. The results demonstrated feasibility of such devices to determine the location of the target as the needle devices were advanced or withdrawn from the tissue, showing promise for future devices enabling neurosurgical guidance of interventional tools in the brain. The application of breast imaging was also considered. Firstly, Thiel embalmed cadaveric breasts were assessed as viable breast models for ultrasound imaging. Following this, anatomical features, with diagnostic significance in relation to breast cancer i.e. axillary lymph nodes and milk ducts, were imaged using a range of ultrasound frequencies (6 – 40 MHz). This was carried out to determinepotential design parameters (i.e. operational frequency) of an interventional transducer in a biopsy needle probe which would best visualise these features and aid current breast imaging and diagnosis procedures.

Epileptic syndromes with continuous spikes and waves during slow sleep (CSWS) are age-related epileptic encephalopathy characterized by the development of various psychomotor regressions in close temporal concordance with the appearance of the electroencephalogram (EEG) pattern of CSWS (Tassinari et al. 2000). This EEG pattern consists in sleep-related activation and diffusion of spike-wave discharges during usually more than 85% of non-rapid eye movement (non-REM) sleep (Tassinari et al. 2000).

A minority of the CSWS cases has been associated to cortical or thalamic lesions (symptomatic cases), while in the other cases, the aetiology is unknown. We reported two families combining benign childhood epilepsy with centro-temporal spikes (BCECS), which is the most common form of idiopathic epilepsy in childhood, and cryptogenic epilepsy with CSWS in first-degree relatives. As idiopathic epilepsies are by definition epilepsies related to a genetic predisposition, these data suggests the existence of a continuum ranging from asymptomatic carriers of centro-temporal spikes to cryptogenic epilepsies with CSWS. This hypothesis is further supported by common clinical characteristics between BCECS and epilepsies with CSWS (Fejerman et al. 2000).

Epileptic syndromes with CSWS are characterized by an acute phase defined by the emergence of psychomotor deficits, various types of seizures and CSWS activity at around three to eight years of age (Holmes and Lenck-Santini, 2006; Veggiotti et al. 2001). This acute phase is followed by a recovery phase in which patients’ clinical condition improves together with the remission of CSWS pattern, which spontaneously occur at around 15 years of age but may be prompted by using antiepileptic drugs (AED) including corticosteroids (Holmes and Lenck-Santini, 2006; Veggiotti et al. 2001). This biphasic evolution suggests that CSWS activity largely contributes to the psychomotor deficits observed in these patients (Holmes and Lenck-Santini, 2006; Van Bogaert et al. 2006). However, some authors still consider CSWS activity as an epiphenomenon reflecting the underlying brain pathology, rather than the direct cause of the psychomotor regression (Aldenkamp and Arends, 2004). The pathophysiological mechanisms of how CSWS activity could actually lead to psychomotor regression are still poorly understood.

Functional cerebral imaging techniques such as positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), represent unique ways to non-invasively study the impact of epileptic activity on normal brain function. The PET technique using [18F]-fluorodeoxyglucose (FDG) gives information about the regional neuronal glucose consumption via the neurometabolic coupling while the fMRI technique studies the regional perfusional changes directly related to specific events of interest via the neurovascular coupling. We applied both FDG-PET and EEG combined with fMRI (EEG-fMRI) techniques to epileptic children with CSWS to better approach the functional repercussions of CSWS activity on neurophysiological functions and to determine the potential pathophysiological link between CSWS activity and psychomotor regression.

In a first FDG-PET study, we determined the regional cerebral glucose metabolic patterns at the acute phase of CSWS in 18 children. We found three types of metabolic patterns: the association of focal hypermetabolism with distinct hypometabolism in 10 patients, focal hypometabolism without any associated area of increased metabolism in five children, and the absence of any significant metabolic abnormality in three patients. The hypermetabolic brain areas were anatomically related to an EEG focus. This anatomical relationship was clearly less consistent for hypometabolic regions. The metabolic abnormalities involved mainly the associative cortices. The metabolic heterogeneity found in these children could be due to the use of corticosteroids before PET as it was significantly associated with the absence of focal hypermetabolism. At the group level, patients with at least one hypermetabolic brain areas showed significant increased metabolism in the right parietal region that was associated to significant hypometabolism in the prefrontal cortex. This finding was interpreted as a phenomenon of remote inhibition of the frontal lobes by highly epileptogenic and hypermetabolic posterior cortex. This hypothesis was supported by effective connectivity analyses which demonstrated the existence of significant changes in the metabolic relationship between these brain areas in this group of children compared to the control group or to the group of children without any significant hypermetabolic brain area.

This remote inhibition hypothesis would be reinforced by the demonstration, at the recovery phase of CSWS, of a common resolution of hypermetabolism at the site of epileptic foci and hypometabolism in distant connected brain areas. We thus performed a second FDG-PET study to determine the evolution of cerebral metabolism in nine children recovering from CSWS. At the acute phase of CSWS, all children had a metabolic pattern characterized by the association of focal hypermetabolism with distinct focal hypometabolic areas. The evolution to CSWS recovery was characterized by a complete or almost complete regression of both hypermetabolic and hypometabolic abnormalities. At the group level, the altered effective connectivity found at the acute phase between focal hypermetabolism (centro-parietal regions and right fusiform gyrus) and widespread hypometabolism (prefrontal and orbito-frontal cortices, temporal lobes, left parietal cortex, precuneus and cerebellum) markedly regressed at recovery. These results were of particular interest because they strongly suggested that the metabolic abnormalities observed during the acute phase of CSWS were mainly related to the neurophysiological effects of CSWS activity and not to the underlying cause of the epileptic disease. Moreover, this study confirmed that phenomena of remote inhibition do occur in epileptic syndromes with CSWS.

EEG-fMRI is a functional cerebral imaging technique that allows non-invasive mapping of haemodynamic changes directly associated to epileptic activity. In a first EEG-fMRI study, we determined the clinical relevance of the perfusional changes linked to interictal epileptic discharges in a group of seven children with pharmacoresistant focal epilepsy. This study showed that the EEG-fMRI technique is a promising tool to non-invasively localize the epileptic focus and its repercussion on normal brain function in children with epilepsy. Then, to further demonstrate the involvement of CSWS activity in the neurophysiological changes detected by FDG-PET, we used the EEG-fMRI technique to study the perfusional changes directly related to the epileptic activity in an epileptic girl with CSWS. This patient developed a cognitive and behavioural regression in association with a major increase in frequency and diffusion of the spike-wave discharges during the awake state (spike index: 50-75%) and non-REM sleep (spike index: 85-90%). The patient’s neuropsychological profile was dominated by executive dysfunction and memory impairment. During runs of secondarily generalized spike-wave discharges, EEG-fMRI demonstrated deactivations in the lateral and medial fronto-parietal cortices, posterior cingulate gyrus and cerebellum together with focal relative activations in the right frontal, parietal and temporal cortices. These results suggested that the neuropsychological impairment in this case could be related to specific cortical dysfunction secondary to the spread of the epileptic activity from focal hypermetabolic foci.

Taken together, both FDG-PET and EEG-fMRI investigations performed in epileptic children with CSWS have shown increases in metabolism/perfusion at the site of the epileptic focus that were associated to decreases in metabolism/perfusion in distinct connected brain areas. These data highly suggest that the neurophysiological effects of CSWS activity are not restricted to the epileptic focus but spread to connected brain areas via a possible mechanism of surrounding and/or remote inhibition. This mechanism is characterised by an epilepsy-induced inhibition of neurons that surround or are remote from the epileptic focus and connected with it via cortico-cortical or polysynaptic pathways (Witte and Bruehl, 1999). The existence of surrounding and remote inhibition phenomena have been well documented in different types of animal models of focal epilepsy using various functional cerebral imaging methods such as autoradiography or optical imaging (Bruehl et al. 1998; Bruehl and Witte, 1995; Witte et al. 1994). Their occurrence in human epilepsy have also been suspected in temporal or extra-temporal lobe epilepsies using FDG-PET, EEG-fMRI or single photon emission computed tomography (SPECT) (Blumenfeld et al. 2004; Schwartz and Bonhoeffer, 2001; Van Paesschen et al. 2003; Van Paesschen et al. 2007). Moreover, the demonstration of the regression of distant hypometabolic areas after surgical resection or disconnection of the epileptic focus further suggest that such inhibition mechanism do occur in epilepsy (Bruehl et al. 1998; Jokeit et al. 1997). On a clinical point of view, the demonstration of the existence of such inhibition mechanisms in epilepsies with CSWS brings new important insights for the understanding of the pathophysiological mechanisms involved in the psychomotor regression observed in these conditions. Indeed, these data highly suggest that the psychomotor regression is not only related to the neurophysiological impairment at the site of the epileptic foci but also to epilepsy-induced neurophysiological changes in distant connected brain areas.

Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished

Akutni pankreatitis predstavlja zbirni pojam dinamičkih, lokalnih i sistemskih patofizioloških procesa nastalih iznenadnim prodorom aktivnih litičkih pankreasnih enzima u žlezdani parenhim. Cilj istraživanja je da se Utvrditi senzitivnost difuzione sekvence magnetne rezonance (DWI) radi utvrđivanja morfoloških promena parenhima kod akutnog pankreatitisa. Poređenje difuzione mape i difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom i kod pacijenata sa morfološki urednim parenhimom pankreasa na magnetnoj rezonanci. Utvrditi da li postoje statistički značajne razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom u odnosu na pol. Utvrditi da li postoje statistički značajne razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom u odnosu na godine. Odrediti prelomnu tačku difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom. Studija je bila prospektivnog karaktera i obuhvatilo je 30 ispitanika sa morfološki urednim parenhimom pankreasa i 30 sa dijagnozom akutnog pankreatitisa unutar 72 sata od početka simptoma. Svi pacijenti su pregledani magnetnom rezonancom u Centru za radiologiju, Kliničkog Centra Vojvodine. Rezultati ukazuju da postoje razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom i kontrolne grupe. Takođe smo dokazali da difuzioni koeficijent zavisi od pola i starosti i utvrdili smo prelomnu tačku difuzije za rano dijagnostikovanje akutnog pankreatitisa.
Acute pancreatitis is defined as cumulative term of dynamic local and general pathophysiological processes caused by sudden penetration of active lithic pancreatic enzymes in the glandular parenchyma. Goal of this research is to note the changes (sensitivity) in values of diffusion weighted images (DWI) in acute pancreatitis and to determine morphological changes in glandular parenchyma of pancreas. Comparation of DWI between patients with acute pancreatitis and patients with normal pancreatic parenchyma based on magnetic resonance (MRI). We also want to determine whether there were statistically significant differences of DWI in patients with acute pancreatitis in relation to sex and age. One of our goals also was to determine breakpoint of DWI as a sure sign of acute pancreatitis. This was prospective study and included 30 patients with morphologically healthy parenchyma of the pancreas (control group) and 30 with the diagnosis of acute pancreatitis – in first 72 hours of the onset of symptoms. All patients were examined on MRI in department of Radiology of Clinical Center of Vojvodina. Our results indicate that was a big difference of DWI between patients with acute pancreatitis and control group. We prove that DWI depends on the sex and age. 1,77x10-6mm/s2 was breakpoint which indicates acute pancreatitis.

Aims of the study: The aim of this pilot study was to examine whether a full phase III study would be beneficial in determining whether thermal imaging can be used as a diagnostic tool to detect distal ulna and radius fractures in children who attend the emergency department with an injury to their wrist when compared with the gold standard of X-rays. Methods: Following ethical approval and informed consent, patients meeting the inclusion criteria with injuries to their distal forearms were recruited in to this investigation. The pilot study design was a quasi-experimental controlled trial of 67 patients evaluating whether thermal imaging could detect fractures in children’s distal ulna and radius. All patients enrolled into this trial were treated in accordance with the European Thermography Association standard for carrying out diagnostic studies using infra imaging (Clark & DeCalci-Goff, 1997). All of the children enrolled into this study had thermal images taken of their injured arm (case) and their uninjured arm (control). The thermal imaging took place alongside the X-ray, ensuring that the same person conducted the positioning of the child’s wrist, thus ensuring consistency in image capture. The child was then treated appropriately in accordance to the X-ray results. The data from the thermal imaging was not analysed for six-months post the child’s attendance at the ED in order to reduce the chances of interpreter bias. Results: The results from this study found that there was a statistically significant difference in surface temperature of the injured arm when compared to the control (mean difference 0.90°C, 95% CI: 0.72 to 1.07, p < 0.0001). The magnitude of the difference is significant enough to suggest that a pathological change had taken place. Thirty one out of thirty four children diagnosed with fractures on X-ray showed a surface temperature difference of 1°C or greater when compared with the control (mean difference = 1.28, 95%CI .889 to 1.689). When the fracture group was compared with the injured non-fractured group, a mean difference of 1.084 °C (95% CI = 0.62 to 1.54,p<0.0001) was found. When compared with radiographs, thermal imaging returned a sensitivity of 91.18 % with a specificity of 87.85%; the sensitivity is increased to 96.7 % when the clinical examination is taken into account. In this study the likelihood ratio for the positive test was calculated to be 7.52 %. The negative likelihood ratio was calculated to be 0.1 %. Conclusion: This study has shown that thermal imaging may be useful in detecting fractures of the distal ulna and radius in children’s wrists, however its diagnostic accuracy is questionable, returning a sensitivity of only 91.8% when compared with X-rays (96.8%) however,when used alongside clinical examination the results demonstrate a sensitivity of up to 96.7%. This study has demonstrated that thermal imaging can detect quantifiable differences in temperature, between an uninjured wrist, a soft tissue injury and a fracture. However its accuracy in diagnosing a fracture cannot be guaranteed and does not reach the accuracy of X-rays, which are consdered to be the current diagnostic gold standard. A full phase III multi centered study would be useful in determining whether thermal imaging could be a useful adjunct to the diagnosis of fractures within the wider health care setting, to elucidate whether thermal imaging has a role in reducing the amount of unnecessary X-rays carried out on children with suspected fractures to their wrists.

Introduction: Computed electrocardiographic imaging (CEI) is a method that uses ST- segment deviations from the 12-lead electrocardiogram (ECG) and has been tested on a small number of patients.Aim: To extend the testing material of the CEI method and deduce a threshold using ECGs recorded pre- and during acute occlusion. The performance of the CEI and ST elevation myocardial infarction (STEMI) criteria will be compared. Method: Two CEI images were generated from each of 99 patients before and during complete occlusion in the left anterior descending (LAD), right coronary artery (RCA) and left circumflex coronary artery (LCx). Result: The sensitivity and specificity of STEMI criteria was 61% and 96% respectively for the whole occlusion group. The sensitivities and specificities were 74 %, 97% (LAD); 60%, 94% (RCA); 35%, 100% (LCx) respectively, for STEMI criteria. A threshold of 998 units was deduced from the CEI method. Conclusion: The CEI method has similar diagnostic performance of an occlusion as STEMI criteria.

UVOD: Maligni tumori reproduktivnih organa nalaze se među vodećim uzrocima obolevanja i umiranja od malignih bolesti žena, kako u svetu, tako i u Srbiji. Jedan od najvažnijih puteva širenja ovih bolesti je limfogeni, a konvencionalna radiološka dijagnostika limfnih čvorova kod ovih pacijentkinja je neprecizna. Funkcionalna radiološka dijagnostika, uključujući i magnentno rezonantnu sekvencu difuzionog kretanja (DWI) i iz nje izvedenu ADC mapu koja omogućava kvantitativnu analizu difuzionih osobina unutar limfnog čvora, daju obećavajuće rezultate u mogućnosti razlikovanja benignih od maligno izmenjenih limfnih čvorova male karlice i ingvinuma kod pacijentkinja obolelih od malignih tumora ženskih polnih organa. CILJ: Cilj studije je 1. utvrđivanje dijagnostičkih mogućnosti magnetnorezonantne sekvence difuzionog kretanja (DWI) u razlikovanju benignih od maligno izmenjenih limfnih čvorova male karlice i ingvinuma kod pacijentkinja obolelih od malignih tumora ženskih polnih organa, poređenjem preoperativno načinjenog magnetnorezonantnog pregleda i postoperativnog patohistološkog nalaza; 2. analiza povezanosti osobina metastatski izmenjenih limfnih čvorova na sekvenci difuzionog kretanja (DWI) i gradusa primarnog tumora, i 3. utvrđivanje uticaja tehničkih karakteristika sekvenci difuzinonog kretanja (DWI) na magnetnorezonantu procenu metastatske infiltracije karličnih i ingvinalnih limfnih čvorova i postoperativnog patohistološkog nalaza. MATERIJAL I METODE: Istraživanje je sprovedeno u periodu od 2013. do 2016.godine, kao prospektivna klinička studija u Centru za radiologiju, na Operativnom odeljenju Zavoda za ginekologiju, Klinike za ginekologiju i akušerstvo i u Zavodu za patologiju Kliničkog Centra Vojvodine u Novom Sadu. Studija je obuhvatila 80 pacijentkinja obolelih od malignih tumora vulve, vagine, grlića materice, tela materice i jajnika. Na osnovu lokalizacije malignog tumora sve ispitanice su razvrstane u 5 grupa: grupa A- 3 žene obolele od carcinoma vulve, grupa B- 1 žena obolela od karcinoma vagine, grupa C-32 pacijentkinje obolele od karcinoma grlića materice, grupa D- 30 pacijentkinja obolelih od malignih tumora tela materice i grupa E- 14 žena obolelih od malignih tumora jajnika. Procena stadijuma bolesti definitivno je izvršena posle operacije na osnovu histopatološkog pregleda kompletnog hirurškog materijala uključujući i pregled uklonjenih limfnih čvorova na osnovu aktuelne FIGO klasifikacije stadijuma bolesti zasebno za svaku pojedinačnu lokalizaciju malignog tumora. Svim pacijentkinjama je preoperativno načinjen magnetnorezonantni pregled male karlice na uređaju za magnetnu rezonancu 1.5 T General Electric Signa HDx u Centru za radiologiju, Kliničkog centra Vojvodine. Kod istih pacijentkinja naknadno je sprovedeno standardno hirurško lečenje po protokolu hirurškog lečenja za dato maligno ginekološko oboljenje sa karličnom i/ili ingvinalnom limfadenektomijom. Postoperativno je izvršena patohistološka analiza hirurški uklonjenog materijala i limfnih čvorova razdvojenih po anatomskim grupama u karlici i ingvinalnoj regiji. REZULTATI: Ukupno 2320 limfnih čvorova je mapirano i patohistološki pregledano kod 80 pacijenata. Metastaze u limfnim čvorovima patohistološki su verifikovane kod 28 pacijenata (35%). Kod ovih 28 (35%) pacijentkinja, 152 (27,28%) od ukupno 557 limfnih čvorova bilo je metastatski izmenjeno na patohistološkom pregledu. Metastaze u limfnim čvorovima utvrđene su kod 2 pacijentkinje (7,14%) sa karcinomom vulve, 11 (39,28%) sa karcinomom cerviksa, 9 (32,14%) sa tumorima tela materice, te 6 (21,42%) sa tumorima jajnika. Od 28 pacijentkinja kod kojih su utvrđeni pozitivni limfni čvorovi, 14 pacijentkinja (50%) imalo je dobro diferentovan primarni tumor, 8 (28,57%) srednje diferentovan, dok je 6 (21,42%) imalo loše diferentovan primarni tumor. Od ukupno 152 metastatski izmenjena limfna čvora u našoj studiji, 8 limfnih čvorova (5,26%) pripadalo je ingvinalnoj grupi od čega 5 (3,289%) površnoj ingvinalnoj, a 3 ( 1,97%) dubokoj ingvinalnoj grupi, 8 (5,26%) parametrijalnoj grupi, 48 (31,58%) opturatornoj grupi, 40 (26,31%) spoljašnjoj ilijačnoj grupi, 36 (23,684%) unutrašnjoj ilijačnoj grupi, dok je 12 (7,89%) pripadalo zajedničkoj ilijačnoj grupi karličnih limfnih čvorova. Kraći prečnik limfnog čvora nije pokazao značajnu razliku između metastatskih ( mean ± SD, 8,3 ± 5.4 mm, raspon , 4.5-30 mm ) i limfnih čvorova koji nisu bili metastatski izmenjeni ( 6,3 mm ± 1,5 , 4,5-9,6 mm ; P= 0,191 ). Izmerena ADC vrednost bila je značajno niža kod metastatski izmenjenih limfnih čvorova (mean ± SD , ADC: 0,8725 x 10-3 mm2/s ± 0,0125) nego kod limfnih čvorova koji nisu bili metastatski izmenjeni (mean ± SD, ADC: 1,116 x 10- 3 mm2/s ± 0,1848; P=0,001). Prosečne vrednosti ADC kod b =800 s/mm2 i b =1200 s/mm2 nisu se značajno razlikovale između metastaski izmenjenih limfnih čvorova (mean ± SD, ADC: 0,8575 ± 0,0125 x 10-3 mm2/s, ADC:0,8859 ± 0,0125 x 10-3 mm2/s) i limfnih čvorova koji nisu metastatski izmenjeni (mean ± SD, ADC:1,0345 ± 0,1222 x 10-3 mm2/s, ADC:1,1125 ± 1638 x 10-3 mm2/s; P =0,657 i P = 0,877). Ako se koristi vrednost ADC od 0,860 x 10- 3 mm2 / s kao kritična vrednost za razlikovanje metastatskih od limfnih čvorova koji nisu metastatski izmenjeni, senzitivnost DWI MR iznosila je 89%, specifičnost 85% i ukupna tačnost 86%. Pozitivna prediktivna vrednost (PPV) DWI MR u detekciji limfnih metastaza u karličnoj i ingvinalnoj regiji iznosila je 30%. Negativna prediktivna vrednost (NPV) testa iznosila je 99%. Pozitivna prediktivna vrednost (PPV) MR zasnovana na kriterijumu ADC vrednosti značajno je veća u odnosu na sve kriterijuma veličine (P < 0,001). Negativna prediktivna vrednost MR zasnovanoj na kriterijumima veličine limfnog čvora i na ACD vrednosti nisu se međusobno statistički značajno razlikovali (P<0,05). Performanse dijagnostičke metode (MR) bile su značajno bolje za minimalnu ADC vrednost od svih kriterijuma baziranih na veličini limfnih čvorova ( P=0.001 za minimalnu ADC vrednost u odnosu na sve druge kriterijume). MRI na osnovu definisanog modela koji kombinuje kriterijum ADC vrednosti sa kriterijumom veličine ima sledeće dijagnostičke performanse za diferencijaciju malignih od benignih limfnih čvorova: senzitivnost od 95%, specifičnost 92%, sveukupna tačnost od 92,5%, pozitivnu prediktivnu vrednost od 46% i negativnu prediktivnu vrednost od 99.6%. ZAKLJUČAK: Kriterijum veličine limfnog čvora nije dovoljno precizan pokazatelj metastatske invazije limfnih čvorova. Sekvenca difuzionog kretanja (DWI) uvek se mora analizirati zajedno sa ADC mapom i visoko rezolutivnim T1 i T2 otežanim magnetnorezonantnim sekvencama. Studijom je dokazan visok stepen povezanosti između preoperativnog određivanja metastaske infiltracije karličnih i ingvinalnih limfnih čvorova malignih tumora ženskih polnih organa primenom sekvence difuzionog kretanja (DWI) i postoperativnog patohistološkog nalaza. Uz graničnu ADC vrednost od 0,860 x 10-3 mm2/ s, senzitivnost MRI DWI u otkrivanju metastatskih limfnih čvorova iznosi 89%, a specifičnost 85%. Kombinacija ADC vrednosti i morfoloških karakteristika limfnih čvorova konvencionalnim magnentno rezonantnim pregledom je najprecizniji prediktor postojanja metastatske infiltracije karličnih i ingvinalnih limfnih čvorova kod pacijentkinja sa malignim tumorima ženskih polnih organa. Tehničke karakteristike sekvenci difuzionog kretanja (DWI) u smislu razlike u visokim b vrednostima ne utiču na magnentno rezonantnu procenu metastatske infiltracije karličnih i ingvinalnih limfnih čvorova kod pacijentkinja sa malignim tumorima ženskih polnih organa. Studijom nije utvrđena statistički značajna razlika između preoperativno utvrđenih ADC vrednosti metastatski izmenjenih limfnih čvorova i stepena histološke diferencijacije ovih tumora. Sekvenca difuzionog kretanja (DWI) je brza, jednostavna, neinvazivna metoda koja značajno doprinosi dijagnostičkim mogućnostima magnetne rezonance u razlikovanju benignih od malignih limfnih čvorova male karlice i ingvinuma.
INTRODUCTION: Malignant tumors of reproductive organs are among the leading causes of morbidity and mortality in women, both in Serbia and worldwide. Lymphatic spread is one of the most important pathways of tumor dissemination. However, conventional lymph node imaging in these patients is imprecise. Functional imaging, including diffusion-weighted magnetic resonance imaging (DWI MRI) and derived ADC map which allows quantitative analysis of diffusion parameters within a lymph node, provide promising results in discrimination benign from malignant pelvic and inguinal lymph nodes in patients with gynecological malignancies. AIM: Aim of the study was: 1. To assess diagnostic performances of DWI MRI in differentiation between benign and malignant pelvic and inguinal lymph nodes in patients with gynecological malignancies, by comparison of preoperative magnetic resonance and postoperative histopathological findings. 2. To analyze correlation between DWI characteristics of metastatic lymph nodes and grade of the primary tumor, and 3. To evaluate the influence of technical characteristics of DWI sequences on MR assessment of metastatic pelvic and inguinal lymph node and postoperative histopathological findings. MATERIAL and METHODS: The prospective clinical study was conducted in Center for Radiology, Surgery Department of Clinic for Gynecology and Obstetrics and Pathology Department of Clinical Center of Vojvodina from 2013 to 2016. It comprised 80 patients with malignant tumors of vulva, vagina, uterine cervix and body and ovaries. Based on the localization of the tumor, all patients were divided into 5 groups: group A-3 patients with vulvar cancer, group B- 1 patient with vaginal cancer, group C- 32 patients with cervical cancer, group D- 30 patients with uterine body tumors and group E- 14 patients with malignant ovarian tumors. Staging of the disease was performed after surgery based on histopathological examination of complete surgical specimen, including examination of removed lymph nodes, based on current FIGO classification separately for each primary tumor location. Preoperatively, all patients underwent MRI examination (1.5 T General Electric Signa HDx) at Center for Radiology, Clinical Center of Vojvodina. The same patients underwent standard surgical treatment according to the treatment protocol regarding the tumor type and stage, with complete pelvic and/or inguinal lymphadenectomy. Histopathological examination of surgically removed material and lymph nodes separated in pelvic and inguinal anatomic groups was performed after the surgery. RESULTS: The total of 2320 of lymph nodes were mapped and histopathologically examined in 80 patients included in the study. Metastases in lymph nodes were histopathologically confirmed in 28 patients (35%). In these 28(35%) patients, in 152 (27,28%) out of 557 lymph nodes histopathological examination confirmed metastases. Lymph node metastases were confirmed in 2 patients (7.14%) with vulvar cancer, 11 (39.28%) with cervical cancer, 9 (32.14%) with uterine body tumors and 6 (21.42%)patients with ovarian tumors. In 28 patients with positive lymph nodes, 14 patients (50%) had well differentiated primary tumor, 8 (28.57%) moderately differentiated, while 6 (21.42%) patients had poorly differentiated primary tumor. Out of 152 metastatic lymph nodes in our study, 8 lymph nodes (5.26%) were inguinal ( 5 (3.289%) superficial inguinal and 3 ( 1.97%) deep inguinal group), 8 (5.26%) were parametrial, 48 (31. 58%) obturatory, 40 (26.31%) external iliac, 36 (23.684%) internal iliac, while 12 (7. 89%) belonged to common iliac pelvic lymph nodes group. Shorter lymph node axis did not show significant difference between metastatic ( mean ± SD, 8.3 ± 5.4 mm, range , 4.5-30 mm ) and benign lymph nodes ( 6.3 mm ± 1.5 , 4.5-9.6 mm ; P= 0.191 ). Measured ADC values were significantly lower in metastatic (mean ± SD , ADC: 0.8725 x 10-3 mm2/s ± 0.0125) than benign lymph nodes (mean ± SD, ADC: 1.116 x 10-3 mm2/s ± 0.1848; P=0.001). Mean ADC values at b =800 s/mm2 and b =1200 s/mm2 did not differ significantly between metastatic (mean ± SD, ADC: 0.8575 ± 0.0125 x 10-3 mm2/s, ADC:0.8859 ± 0,0125 x 10-3 mm2/s) and benign lymph nodes (mean ± SD, ADC:1.0345 ± 0.1222 x 10-3 mm2/s, ADC:1.1125 ± 1638 x 10-3 mm2/s; P =0.657 i P = 0.877). If ADC value of 0.860 x 10- 3 mm2 / s is determined as a cut off value for discrimination of benign and malignant lymph nodes, DWI MRI sensitivity was 89%, specificity 85% and overall accuracy was 86%. Positive predictive value (PPV) of DWI MR in detection of pelvic and inguinal lymph node metastases was 30%. Negative predictive value (NPV) of the test was 99%. MRI PPV based on ADC value criteria was significantly higher compared to all size-based criteria (P < 0,001). MRI NPV based on size based and ADC values criteria did not differ significantly (P<0,05). Performances of diagnostic method (MRI) were significantly better for minimal ADC value compared to all lymph node size-based criteria ( P=0.001 for minimal ADC value compared to all other criteria). Combination of ADC value criteria and size-based criteria yields MRI the following diagnostic performances in discrimination between benign and malignant lymph nodes: sensitivity 95%, specificity 92%, overall accuracy 92.5%, positive predictive value 46% and negative predictive value 99.6%. CONCLUSION: Lymph node size is not sufficiently precise criteria for determination of metastatic lymph node involvement. DWI sequence always needs to be evaluated together with ADC map and high resolution T1W and T2W magnetic resonance sequences. The study shows high correlation between preoperative assessment of pelvic and inguinal lymph node metastases from gynecological malignancies using MRI DWI and postoperative histopathological findings. With a cut off ADC value of 0.860 x 10-3 mm2/ s, sensitivity of MRI DWI in metastatic lymph node detection is 89%, while specificity is 85%. Combination of ADC values and morphological lymph nodes characteristics assessed by conventional MRI is the most precise predictor of metastatic pelvic and inguinal lymph node invasion in patients with gynecological malignancies. Technical characteristics of DWI i.e. different high b-values do not influence MR assessment of metastatic pelvic and inguinal lymph node involvement in patients with gynecological malignancies. The study did not confirm statistically significant difference between preoperatively measured ADC valued of metastatic lymph nodes and histological grade of primary tumors. DWI MRI sequence is fast, simple, noninvasive method which aids significantly to MRI diagnostic performances in discrimination between benign and malignant pelvic and inguinal lymph nodes.

Uvod: Termin - temporomandibularne disfunkcije (TMD) obuhvata veći broj oboljenja TMZ, mastikatorne muskulature i okolnih struktura. Epidemiološke studije pokazuju da 50-75% osoba u toku života ima neki znak poremećaja funkcije mastikatornog sistema. TMD se najčešće javljaju između 20-40 godine života. Najznačajniji znaci i simptomi TMD su bol u predelu maseteričnog mišića, TMZ, regiona temporalnog mišića, ograničeno otvaranje usta i zvučne pojave (kliktaji i krepitacije). Bol u predelu TMZ je najčešći razlog javljanja pacijenta lekaru. Cilj Utvrđivanje validnosti kliničkog nalaza TMD dobijenog korišćenjem RDC/TMD (engl. Research Diagnostic Criteria/ Temporomandibular Disorders) i nalaza na MR pregledu radi utvrđivanja prisustva disfunkcije u cilju blagovremenog i adekvatnog kliničkog zbrinjavanja. Istraživanje je sprovedeno kao prospektivna studija u Centru za Imidžing dijagnostiku, Institutu za Onkologiju Vojvodine u Sremskoj Kamenici, u periodu od januara 2011. do maja 2013. godine. Istraživanjem je obuhvaćeno 200 ispitanica (400TMZ) koje su došle na zakazani MR pregled endokranijuma nevezano za eventualnu patologiju TMZ tj. zbog neurološke simptomatologije. Ispitanicama je prvo snimljen MR endokranijuma zbog osnovnog oboljenja a zatim je pregled nastavljen snimanjem oba TMZ. Snimanje je izvedeno na aparatu Siemens (Erlangen, SR Nemačka) jačine magnetnog polja 3Tesla – Siemens AVANTO 3T, istog dana, nakon obavljenog kliničkog pregleda. Svakoj ispitanici urađen je parasagitalni (Slika 8) i koronalni presek TMZ kroz oba kondila sa sledećim parametrima snimanja: proton density sekvenca, vreme repeticije (TR) 1850 ms, vreme ehoa (TE) 15 ms, vidno polje (FOV) 13 cm, kao i matrica 128 x 256. Debljina preseka prilikom snimanja MR bila je manja od 2 mm. Prilikom snimanja svakoj ispitanici je bio stavljen osmokanalni zapreminski kalem (engl. head matrix coil) da bi signal u antero-posteriornom pravcu na dobijenim snimcima bio ujednačen. Ukupno vreme snimanja oba TMZ iznosilo je 4 minuta. Na osnovu MR pregleda, najveći broj TMZ je bio bez patoloških promena, njih 198 (49,5%). Prednja dislokacija diska sa redukcijom je ustanovljena kod 46 TMZ (11,5%), sledili su prednja dislokacija diska bez redukcije (18 TMZ (4,5%)), zadnja dislokacija 4 TMZ (1%) I osteoartritis kod 100 TMZ (25%)). Kombinacija poremećaja dislokacije diska sa redukcijom i osteoartritisa ustanovljena je kod 20 TMZ (5%), dislokacije diska bez redukcije i osteoartritisa kod 6 TMZ (1,5%), dok je kombinacija zadnje dislokacije i osteoartritisa detektovana kod 8 TMZ (2%). Rezultati Najčešći oblik diska bio je bikonkavan i identifikovan je kod 278 (69,5%) TMZ, slede biplanaran kod 76 (19%), hemikonveksan kod 20 (5%) i bikonveksan kod 14 TMZ (3,5%). Zaključak Na osnovu MR pregleda 51 % TMZ je imalo patološki nalaz. Korelacija dijagnoza postavljenih na osnovu RDC/TMD i MR pregleda pokazala je umereno dobro slaganje dijagnoza. MR pregled je detektovao dislokaciju diska kod 18% ispitanica koje nisu imale tegobe. Korelacija dijagnoza dislokacije diska postavljenih na osnovu RDC/TMD i MR pregleda je pokazala umereno dobro slaganje. Dijagnoza dislokacije diska sa i bez redukcije, na RDC/TMD ima visoku specifičnost i nisku senzitivnost u poređenju sa dijagnozom postavljenom na MR pregledu. Primenom RDC/TMD, postoji mala verovatnoća za postavljanje lažno pozitivne dijagnoza dislokacije diska sa i bez redukcije. Korelacija dijagnoza degenerativnih promena postavljenih na osnovu RDC/TMD i MR pregleda pokazala je slabo slaganje dijagnoza. RDC/TMD nije optimalna metoda za dijagnostiku degenerativnih promena temporomandibularnih zglobova.
Introduction  The term temporomandibular disorders (TMD) encompasses a large number of diseases of TMJ, masticatory musculature and surrounding structures. Epidemiological studies show that 50-75% of people have some type of impaired function of the masticatory system in the course of their lives. TMJ most commonly occurs between the ages of 20 to 40. The most important signs and symptoms of TMD are the pains in the area of masseter muscle; TMJ; temporal muscle; with limited mouth opening and sound phenomena (clicking and crepitus). Pain in the TMJ is the most common reason for a patient’s visit to a doctor. The aim   To determine the validity of the clinical findings of TMD obtained by using RDC / TMD (Research Diagnostic Criteria / Temporomandibular Disorders) and MRI examination findings which could determine the presence of a disorder and therefore provide prompt and adequate clinical care. Materials and Methods  The research was conducted as a prospective study at the Diagnostic Imaging Center, Oncology Institute of Vojvodina in Sremska Kamenica in the period from January 2011 to May 2013. The study included 200 subjects (400 TMJs) who came for a scheduled MRI of endocranium not related to potential TMJ pathology i.e. having neurological symptoms. Firstly, the subjects underwent the MRI of the endocranium due to their underlying diseases and then the examination continued with MRI of both TMJs. The imaging was performed using Siemens device (Erlangen, Germany) with the magnetic field strength 3Tesla - Siemens Avanto 3T the same day after theirclinical examination. Each subject underwent a parasagital and coronal cross section of TMJ through both condyles with the following imaging parameters: proton density sequence, repetition time (TR) 1850 ms, echo time (TE) 15 ms, field of view (FOV) 13 cm and a matrix of 128 x 256. The section thickness during MRI was less than 2 mm. During imaging, 8-channel head matrix coil was placed on each subject so that the signal in antero-posterior direction at the obtained images was uniform. Total imaging time for both TMJs was 4 minutes.Results   Based on the MRI examination, the largest number of TMJs had no pathological changes - 198 of them (49.5%). Anterior disc displacement with reduction was found in 46 TMJs (11.5%), followed by the anterior disc displacement without reduction (18 TMJs (4.5%)), posterior displacement of TMJ 4 (1%) and osteoarthritis in 100 TMJs (25 %)). The combination of disorders of disc displacement with reduction and osteoarthritis was found in 20 TMJs (5%), disc displacement without reduction and osteoarthritis in 6 TMJs (1.5%), while the combination of the posterior displacement and osteoarthritis was found in 8 TMJs (2%). The most common shape of a disc was biconcave and was identified in 278 (69.5%) TMJs, followed by biplanar in 76 (19%), hemiconvex 20 (5%) and biconvex in 14 TMJs (3.5%).Conclusion   Based on the MRI examination, 51% of TMJs had pathological findings. Correlation of diagnoses which was determined based on RDC / TMD and MRI examination was moderately present. MRI examination detected disc displacement in 18% of subjects who did not have any problems. Correlation of diagnoses of disc displacement which was determined based on RDC / TMD and MRI examination showed moderately good results. The diagnosis of disc displacement with andwithout reduction on the RDC / TMD has a high specificity and low sensitivity compared with the diagnosis from the MRI examination. When applying the RDC / TMD there is little chance of setting a false positive diagnosis of disc displacement with and without reduction. The correlation of the degenerative changes diagnoses which were set based on the RDC / TMD and MRI examination showed poor results. RDC / TMD is not an optimal method for the diagnosing the degenerative changes of temporomandibular joints.

Uvod: Dijabetes melitus (DM) je oboljenje koje poprima karakteristike globalne epidemije. Sve ţešše oboljevaju pacijenti mlaŤeg ţivotnog doba. Simptomi DM tip 2 su blagi, ţesto neprimetni, te se oboljenje otkriva kada se veš manifestuju komplikacije. Dijabetesna nefropatija (DN) je jedna od mnogobrojnih komplikacija dijabetes melitusa tip 2, koja se završava terminalnom bubreţnom insuficijencijom. DN se ţesto neblagovremeno dijagnostikuje, zbog ţega se kasno zapoţinje leţenje. Rano otkrivanje DN od kljuţnog je znaţaja, jer omogušava primenu terapijskih postupaka usmerenih na oţuvanje preostalih zdravih nefrona i prevenciju terminalne bubreţne slabosti. Cilj: Prikazati poremešaj difuzije molekula vode unutar bubrega kod DN, koriššenjem mapa prividnog koeficijenta difuzije, kvantifikacijom vrednosti prividnog koeficijenta difuzije (ADC) i frakcione anizotropije (FA). Materijal i metode: U prospektivnu studiju bilo je ukljuţeno 10 zdravih dobrovoljaca i 91 pacijent oboleo od DM tip 2. Pacijenti oboleli od DM tip 2 podeljeni su u ţetiri grupe na osnovu vrednosti procenjene jaţine glomerularne filtracije (JGF) (grupe: I JGF ≥ 90, II 89-60, III 59-30, IV ≤ 29 ml/min/1,73m²). Svim ispitanicima uraŤen je MR pregled bubrega, uz primenu DWI (b=0 i b=400 s/mm²) i DTI (b=1000 s/mm²) sekvence, na aparatu jaţine 1.5T. ADC i FA vrednosti raţunate su u šest regija od interasa, po tri u korteksu i meduli svakog bubrega. Dobijene vrednosti komparirane su sa laboratorijskim parametrima bubreţne funkcije (urea, kreatinin, mokrašna kiselina) i procenjenom JGF. Rezultati: Ne postoje statistiţki znaţajne razlike ADC i FA vrednosti parenhima, korteksa i medule levog i desnog bubrega kod zdravih dobrovoljaca i DM pacijenata. Kod DM pacijenata ADC je veša u korteksu nego u meduli (p=0,00), a FA vrednost je veša u meduli nego u korteksu (p=0,284). Urea, kreatinin i cistatin C imaju negativnu korelaciju sa ADC korteksa, medule i parenhima (p<0,05), a JGF ima pozitivnu korelaciju sa ADC korteksa, medule i parenhima, kao i sa FA medule (p<0,05) kod DM pacijenata. Na osnovu Post hoc testa za ADC, kod DM pacijenata postoje razlike izmeŤu I i IV grupe, izmeŤu II i IV grupe i III i IV grupe (p≤0,05). IzmeŤu godina ţivota, teţine, BMI, JGF, HbA1c, uree i ŠUK-a, postoji razlika DM pacijenata i zdravih dobrovoljaca (p<0,05). Niţa je vrednost FA medule DM pacijenata u odnosu na zdrave dobrovoljce (p<0,05). Postoji razlika ADC korteksa, medule i parenhima izmeŤu zdravih dobrovoljaca i DM pacijenata IV grupe, kao izmeŤu DM pacijenata I i II grupe u odnosu na IV grupu. TakoŤe postoji razlika izmeŤu FA medule zdravih dobrovoljaca i DM pacijenata I i IV grupe (p<0,05). Regresiona analiza pokazala je uticaj kreatinina na ADC desnog bubrega i ADC oba bubrega, dok procenjena JGF i cistatin C imaju uticaj na ADC desnog i levog bubrega, ADC oba bubrega i FA levog bubrega (p<0,05). Traktografija je prikazala narušenu arhitektoniku kod pacijenata sa oštešenom bubreţnom funkcijom. Zakljuţak: Postoji korelacija laboratorijskih parametara bubreţne funkcije i procenjene JGF sa ADC i FA vrednostima bubrega, što ukazuje na ulogu funkcionalnog magnetno rezonantnog imidţinga u dijagnostici dijabetesne nefropatije. Neophodna su dalja istraţivanja koja še doprineti standardizaciji MR protokola i potvrdi znaţaja MR biomarkera u dijagnostici DN. Na osnovu naših rezultata vrednost FA medule osetljiviji je parametar od ADC vrednosti u otkrivanju ranog oštešenja bubrega u sklopu dijabetes melitusa.
Introduction: Diabetes mellitus (DM) is a disease that takes on the characteristics of a global epidemic. Patients of younger age are more and more commonly affected. Symptoms of type 2 DM are mild, often imperceptible, and therefore the disease is usually detected when complications are already manifested. Diabetic nephropathy (DN) is one of the many complications of type 2 diabetes mellitus that leads to terminal renal failure. Diagnosis of DN is often late, causing the delay of the treatmen. Early detection of DN is crucial because it allows the application of therapeutic procedures aimed at preserving the remaining healthy nephrons and preventing terminal renal failure. Objective: To investigate a diffusion of water molecule within a kidney in DN using apparent diffusion coefficient maps, by quantification of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in diabetic patients with DM type 2. Material and methods: The prospective study comprised 10 healthy volunteers and 91 DM type 2 patients. DM patients were divided into four groups based on the values of the estimated glomerular filtration (eGFR) (groups: I eGFR ≥ 90, II 89-60, III 59-30, IV ≤ 29 ml/min/1.73m²). All subjects were scanned by 1.5T MR using DWI (b=0 and b=400 s/mm²) and DTI (b=1000 s/mm²) sequences. ADC and FA values were calculated in six regions of interest, three in cortex and three in medulla of each kidney. Obtaned values were compared to laboratory parameters of renal function (urea, creatinine, uric acid) and eGFR. Results: There were no statistically significant differences between ADC and FA values of parenchyma, cortex and medulla of the left and the right kidney in healthy volunteers and DM patients. In DM patients, the ADC value was higher in the cortex than in the medulla (p=0.00) and the FA value was higher in the medulla than in the cortex (p=0.284). The negative correlation was found between urea, creatinine and cystatin C with ADC cortex, medulla and parenchyma (p<0.05), and the eGFR was positively correlated with ADC cortex, medulla and parenchyma, and with FA medulla (p<0.05) in DM patients. Based on the Post hoc test for ADC, in DM patients there were differences between I and IV group, between II and IV group, III and IV group (p≤0,05). Regarding age, weight, BMI, GFR, HbA1c, urea, and glucose in the serum, there was a difference between DM patients and healthy volunteers (p<0.05). The FA of medulla in DM patients was lower than of healthy volunteers (p<0.05). There were differences in ADC of cortex, medulla, and parenchyma between healthy volunteers and DM patients of IV group, as well as between DM patients of I and II group compared to IV group. There were differences of medulla FA values between healthy volunteers and group I, accompanied by healthy and IV group of DM patients (p<0.05). Regression analysis showed the influence of creatinine on ADC of right kidney and ADC of both kidneys, while eGFR and cystatin C have an effect on ADC of right and left kidney, ADC of both kidneys and FA of left kidney (p<0.05). The tractography showed the disturbed architectonics in patients with impaired renal function. Conclusion: There is correlation of laboratory parameters of renal function and eGFR with ADC and FA values of the kidney, indicating the role of functional magnetic resonance imaging in the diagnosis of DN. Further research that will contribute to standardizing the MR protocol and confirming the importance of MRI biomarker in the diagnosis of DN are needed. Based on our results, the values of medulla FA is more sensitive parameter than the ADC value in detecting early kidney damage in the context of diabetes mellitus.

UVOD: Hronične inflamatorne bolesti se ispoljavaju kao Kronova bolest i ulcerozni kolitis. Njihova značajnost ogleda se u hronicitetu kao i u stepenu u kom ograničavaju rast i razvoj dece i omladine. Brojne su posledice ovih oboljenja: dugotrajno izostajanje sa nastave, ograničavanje životnih aktivnosti i pojava komplikacija koje neretko zahvataju i druge organske sisteme. Etiologija je i dalje nerazjašnjenja navodeći kao značajan hronični inflamatorni proces u genetski uslovljenih pojedinaca a provociranih nekim infektivnim agensom. Početkom 21. veka genetska istraživanja su otkrila osnovu nasleđivanja hroničnih inflamatornih oboljenja povezanih sa NOD2 genom. Kako je u pitanju organskim sistem koji je ograničeno pristupačan kliničkom pregledu, osnovu dijagnostike čine radiološke metode. Kako je potrebno sprečiti kontinuirano izlaganje štetnom dejstvu rendgenskog zračenja istraživanja se usmeravaju ka UZ i magnetnoj rezonanca. Naše istraživanje se baziralo na mogućnostima ovih dveju metoda u svakodnevnom radu za dijagnostiku i dalje praćenje hroničnih inflamatornih bolesti creva. CILJEVI: Utvrditi senzitivnost i specifičnost ultrazvučne dijagnostike i magnetne resonance kod upalnih oboljenja creva u dečjem i adolescentnom uzrastu. Definisati i uporediti prednosti i ograničenja ultrazvučne dijagnostike sa dijagnostikom magnetne rezonace kod upalnih obolenja creva u dečjem i adolescentnom uzrastu. MATERIJAL I METODE: U istraživanje je uključeno 62. dece i adolescenata u toku prvog ataka bolesti ili ponovljenim fazama bolesti ili tokom redovnog praćenja u remisiji. Obuhvaćeni uzrast je od 4. do 18. godina. Potom su razvrstani u grupe na osnovu vrste pregleda i prisustva zadebljanja crevnog zida na A i B (pregled UZ), gde je A grupa imala zabeleženo zadebljanje crevnog zida preko 3 mm, a kod dece u grupi B debljina crevnog zida je bila između 2,5-3 mm. Sa druge strane na osnovu pregleda magnetnom rezonancom podeljeni su u A1 i B1 grupe, takođe po kriterijumu zadebljanja crevnog zida većeg od 3 mm (A1), odnosno između 2,5-3 mm (B1). Istraživanje je sprovedeno na Institutu za zdravstvenu zaštitutu dece i omladine Vojvodine i Institutu za radiologiju Kliničkog centra Vojvodine. Prvi pregled načinjen je UZ a potom je načinjen pregled magnetnom rezonanacom. Podaci su obrađivani retrospektivno i prospektivno. Kriterijumi za uključivanje u studiju pored uzrasta bili su radiološki: zadebljanje crevnog zida >3mm, postojanje narušene arhitektonike crevnog zida, zadebljanje pojedinih crevnih segmenata-dužina segmenta, znaci fibroze, odsustvo peristaltike, izražena hiperemija na kolor Doppleru, transmuralni znaci upale, uvećani mezenterijalni limfni nodusi kao i kontrolni pregledi kod dece sa ranije ustanovljenom dijagnozom. Načinjena je endoskopija sa biopsijom radi postavljanja definitivne dijagnoze, potom se pristupilo statističkoj obradi dobijenih podataka. Izračunate su prosečne i standardne devijacije i frekvencije kao i pripadajući procenti. Određivane su maksimalne i minimalne vrednosti, medijane i interkvartalni raspon. Dobijeni podaci prikazani su u grafikonima i tabelama. Za parametrijske varijable upotrebljavan je Man – Vitni U test. Za kategoričke vrednosti upotrebljeni su χ2 i Fišerov test. Nadalje su određivane senzitivnost, specifičnost kao i pozitivne i negativne prediktivne vrednosti. Veze između dva parametra uspostavljene su pomoću Pirsonove korelacione analize i linearnim regresionim modelom. Upotrebljen je program za obradu podataka SPSS 21 Statistics,a kao statistički značajne vrednosti uzete su vrednosti p<0,05. REZULTATI: Nakon statističke obrade nije zabeležena signifikantnost u pogledu zastupljenosti hroničnih inflamatornih bolesti među polovima. Statistička značajnost pronađena je u pogledu uzrasta dece u akutnoj fazi kao i remisiji bolesti. Statistička značajnost je dobijena za posmatranu debljinu crevnog zida, hiperemiju creva, prisustvo fibroze u digestivnom traktu. Primećeno je da UZ bolje razgraničava decu sa akutnim oboljenjem po pitanju zahvaćenosti segmenata. Ostala posmatrana obeležja nisu nakon statističke obrade imala statistički značaju razliku kada se procenjuju ultrazvučno ili magnetnom rezonancom. ZAKLJUČAK: Inicijalne hipoteze ovog istraživanja su nakon obrade podataka i potvrđene. Određivanjem senzitivnosti i specifičnosti UZ i MR dobijene su sledeće vrednosti: senzitivnost UZ je 88,4% naspram 92,3% koliko ima pregled magnetnom rezonancom. U pogledu specifičnosti UZ ima 88% a magnetna rezonanca 91,6%. Verifikovano je da magnetna rezonanca bolje razvrstava decu u akutnoj fazi bolesti kao i decu u remisiji. Rezultati pozitivnih i negativnih verovatnoća odnosa ne predviđaju neuspeh nijednim od ova dva pregleda.
INTRODUCTION: Chronic inflammatory diseases are manifested through two clinical entities: Crohn's disease and ulcerative colitis. Their significance lies in the chronicity and the degree to which they restrict the growth and development of children and youth. There are many consenquences that come with the very nature of the disease, in addition to long-term absence from school, limiting life activities and the occurrence of complications that often affect other organ systems. The etiology of the disease has long been in favor of the theory that a chronic inflammatory process in genetically conditioned individual is provoking an inflammation due to a certain infectious agent. However, a step closer was made regarding the etiology of the disease - when the genetic basis of inheritance studies have revealed chronic inflammatory bowel diseases were associated with NOD2 gene. It is particularly important to prevent continuous exposure to the harmful effects of X-rays. Therefore, numerous studies have been made towards the validation of complementarity, accuracy and diagnostic capabilities of ultrasound and magnetic resonance imaging as noninvasive techniques. Our research was based on the capabilities of these two methods in their daily work for diagnosis and follow-up of chronic inflammatory bowel disease. OBJECTIVES: The objectives were to determine the sensitivity and specificity of ultrasound and magnetic resonance imaging in inflammatory bowel disease in children and adolescents. Furthermore, the aim was to define and compare the advantages and limitations between ultrasound diagnosis and magnetic resonance in inflammatory bowel disease in children and adolescents. MATERIAL AND METHODS: The study included 62 children and adolescents during the first attack of disease or recurrent stages of the disease, or during regular monitoring in remission. Patients included children of both sexes, aged 4-18. Then they were sorted into groups based on the type of the examination and the presence of a thickening of the intestinal wall into groups A and B - in these groups children were examined by ultrasound, A group had observed thickening of the intestinal wall > 3 mm whereas children in group B had had thickening of the intestinal wall between 2,5-3 mm. Based on the review of MRI children were divided into groups A1 and B1, also according to the criterion of bowel wall thickening greater than 3mm (A1) and between 2,5-3mm (B1). The research was conducted at the Institute for Health Protection of Children and Youth and the Institute of Radiology, Clinical Center of Vojvodina. The first review was made by ultrasound, followed by the review of magnetic resonance. Data were analyzed retrospectively and prospectively. Criteria for inclusion in the study were: thickening of the intestinal wall greater than 3 mm, the existence of disturbed intestinal wall architectural structure, no clear distinction of layers, abnormal thickening of certain intestinal segments, signs of fibrosis, the absence of peristalsis, expressed hyperemia on color Doppler, transmural inflammation, increased mesenterial lymph nodes as well as check-ups for children with previously established diagnosis. Endosccopy with biopsy has made for the definitive diagnosis and then we approached statistical analysis of the data obtained. The data are presented in graphs and tables. For parametric variables we used Man - Whitney U test. For categorical values χ2 and Fisher's test were used. Further the sensitivity, specificity and positive and negative predictive values were determined. Relationship between these two parameters were established using Pearson correlation analysis and linear regression model. For data processing we used the program SPSS Statistics 21, statistically significant values were taken p values <0.05. RESULTS: After statistical analysis there was no for the number of chronic inflammatory diseases between the sexes. Statistical significance was found in terms of age of the children during the acute phase as well as remission. Statistical significance was obtained for the observed thickness of the intestinal wall, intestinal hyperemia, the presence of fibrosis in the digestive tract. It was noted that US better demarcates children with acute disease in terms of involvement of segments. Other features are not observed as significant after the statistical analysis. CONCLUSION: The initial hypothesis of this study, after data processing were confirmed. By determining the sensitivity and specificity of ultrasound MRI results we came to the following results: sensitivity of ultrasound was 88,4% versus 92,3%, for magnetic resonance. In terms of specifics UZ has a 88% and 91,6% of magnetic resonance imaging. The classification of children in the acute phase of the disease as well as children in remission was better when MRI was used. The results of positive and negative predictions do not predict the probability of failure in neither of these methods.

Uvod: Implementacija brojnih neuroradioloških modaliteta je značajno uticala na način i efikasnost sprovođenja dijagnostike tumora mozga. Na osnovu neinvazivno dobijenih podataka može se postaviti diferencijalna dijagnoza, ali do sada nije potvrđena nijedna neuroradiološka metoda koja može samostalno i konačno da postavi definitivnu patohistološku (PH) dijagnozu. Stereotaksična biopsija je neurohirurška procedura kojom se, bez bitnog narušavanja integriteta i funkcije moždanog tkiva, može obezbediti reprezentativni uzorak intrakranijalne tumorske promene radi sprovođenja PH i drugih specifičnih analiza, u cilju postavljanja tačne dijagnoze i potom primene adekvatnog lečenja. Cilj: Cilj ove studije je da se utvrditi mogućnost uzorkovanja reprezentativnog tkiva za postavljanje PH dijagnoze uz pomoć stereotaksične biopsije kod pacijenata sa tumorom mozga, kao i da se utvrdi vrsta i učestalost eventualnih komplikacija same procedure i postojanje korelacije između PH nalaza dobijenog stereotaksičnom biopsijom i rezultata sprovedenih neuroradioloških ispitivanja. Materijal i metode: Sprovedeno istraživanje je bilo kliničko, prospektivno, a uzorak je činilo ukupno 50 pacijenata koji su bili hospitalizovani na Klinici za neurohirurgiju KCV zbog dijagnostikovane tumorske promene mozga i postavljene indikacije za stereotaksičnu biopsiju, u periodu od septembra 2016. godine do januara 2018. godine. Svi pacijenti koji su uključeni u studiju su u sklopu sprovedene dijagnostičke obrade imali načinjen magnetno rezonanantni (MRI) pregled glave na osnovu kojeg su se određivale morfološke karakteristike tumora i vršila procena prirode tumorske promene mozga, a kod ukupno 25 pacijenata je dodatno načinjena MR spektroskopija (MRS) dijagnostikovane tumorske promene sa ciljem određivanja biohemijskog profila i dodatne procene i karakterizacije tkiva. Nakon sprovedene detaljne onkološke obrade i adekvatne pripreme, se sprovodila kompjuterizovanom tomografijom (CT) navođena stereotaksična biopsija sa ramom u cilju uzorkovanja adekvatnog tkiva za PH analizu. U toku istraživanja procena uspešnosti uzorkovanja reprezentativnog tkiva se vršila pregledom bioptata od strane patologa, a nakon procedure se kliničkim pregledom i kontrolnim CT pregledom glave utvrđivao stepen komplikacija. Rezultati: Dobijeni rezultati su pokazali da su fokalni neurološki deficit i moždani sindrom bili najčešći klinički simptomi i znaci kod pacijenata kod kojih je indikovana stereotaksična biopsija tumora mozga. Prema MRI nalazu najzastupljenije su bile difuzne tumorske promene sa 36% udela u uzorku, zatim solitarne sa 34% i multifokalne sa 20%, a potom multicentrične tumorske promene koje su predstavljale 10% uzorka. Takođe, na osnovu MRI i MRS nalaza je oko 80% tumora procenjeno kao najverovatnije glijalnog porekla. U 95,9% slučaja je postavljena precizna PH dijagnoza. Nepromenjeno stanje svesti i neurološki nalaz su imali 92% pacijenata nakon biopsije, a kod 3 pacijenta (6%) je došlo do razvoja prolaznog neurološkog deficita, dok je jedan pacijent (2%) razvio trajan neurološki deficit. Ukupan morbiditet vezan za proceduru je stoga 2%, a nije zabeležen ni jedan smrtni slučaj (mortalitet 0%) tokom sprovođenja studije. Zaključak: Stereotaksična biopsija je dokazana i veoma pouzdana procedura sa malim brojem komplikacija i niskom stopom morbiditeta i mortaliteta, kojom se omogućava dobijanje reprezentativnog uzorka tumorskog tkiva za postavljanje sigurne patohistološke dijagnoze. Intraoperativna PH analiza dela uzorka tkiva dodatno poboljšava uspešnost pri uzorkovanju i postavljanju definitivne PH dijagnoze. Savremene neuroradiološke metode imaju visoku specifičnost u razlikovanju biološke prirode tumorskih promena, ali se ne mogu koristi nezavisno od PH analize uzorka tkiva
Introduction: The implementation of numerous neuroradiological techniques has significantly influenced the way and the efficiency in which the diagnosis of brain tumor is established. Based on non-invasive imaging data, a differential diagnosis can be made, but no neuroradiological method has been established so far, which can finally make a definitive diagnosis. Stereotactic biopsy is a neurosurgical procedure that can provide a representative sample of any intracranial tumor in order to performe histopathological and other specific examinations, and to set the exact diagnosis and then apply adequate treatment, but without significantly impairing the integrity and function of brain tissue. Objective: The aim of this study is to determine the diagnostic value of stereotactic biopsy and ability of providing the representative tissue in order to establish a pathohistological diagnosis in patients with brain tumors. Also, the aim is to determine the type and frequency of possible complications of the procedure itself and the correlation between the pathohistological findings obtained and the results of the conducted neuroradiological examinations. Materials and methods: This research was clinical, prospective and included a total of 50 patients who were hospitalized at the Clinical Center of Vojvodina, from September 2016 to January 2018, due to diagnosed brain tumor for which the stereotactic biopsy is indicated. In all patients magnetic resonance (MRI) examination of the head was used to determine morphological characteristics and assesse the nature of the brain tumor tissue, and in a total of 25 patients MR spectroscopy was additionally made with the goal of determining the biochemical profile and additional tissue assessment and characterization. After detailed oncological assessment, completed laboratory and radiological diagnostics, a CT guided framebased stereotactic biopsy was performed for the purpose of sampling tumor tissue for pathohistological analysis. During the research, the success rate of biopsy in providing the representative tissue and establishing the diagnosis was performed by a pathologist, and after the procedure, a clinical and a control head CT examination was used to review the rate of complications. Results: The results obtained showed that focal neurological deficit and psychoorganic syndrome were the most common clinical symptoms and signs in this study. According to MRI, the most common were diffuse brain tumors with 36% of the sample, then solitary with 34% and multifocal with 20%, followed by multicentric tumors representing 10% of the study sample. Also, based on MRI and MRS findings, approximately 80% of tumors are estimated to be most likely of glial origin. In 95.9% of cases, a complete pathohistological (PH) diagnosis was established. The unchanged neurological status was observed in 92% of patients after biopsy, and 3 patients (6%) developed a transient neurological deficit, while only one patient (2%) developed a permanent neurological deficit. The total morbidity associated with the procedure is therefore 2%, and no deaths (mortality 0%) related to the procedure during the study is recorded. Conclusion: Stereotactic biopsy is highly reliable procedure with a small number of complications and a low morbidity and mortality rate, which allows us to acquire the representative sample of brain tumor tissue and to establish a pathohistological diagnosis. Intraoperative PH analysis of acquired tissue samples further enhances the sampling performance and the setting of definitive PH diagnosis. Modern neuroradiological modalities have a high specificity in distinguishing the biological nature of brain tumors, but they still can not be used independently of the pathohistological analysis of the tissue sample.

UVOD: Početak multiple skleroze (MS) u dečijem uzrastu je dijagnostički i terapijski izazov. I ako rani početak MS-a uglavnom ukazuje na dobru kratkoročnu prognozu, neka deca razviju tešku onesposobljenost, fizičku ili kognitivnu, a više od 50% obolelih uđe u sekundarno progresivnu formu bolesti pre 30. godine života. Rana dijagnoza je neophodna za uvođenje imunomodulatorne terapije, kojom se obezbeđuje dobra dugoročna prognoza. CILJ: Analiza parametara koji bi omogućili ranu dijagnozu multiple skleroza sa ranim početkom u odnosu na simptome, sprovedene dijagnostičke procedure i tok bolesti. Sagledavanje inicijalnih kliničkih manifestacija multiple skleroze, prisustva ologoklonaliteta, nalaza MRI endokranijuma i njihovih osobenosti u dečijoj populaciji uz komparaciju sa inicijalnim kliničkim manifestacijama kod pacijenata obolelih od multiple skleroze u odraslom dobu. MATERIJALI METODE: Ova retrospektivno/ prospektivna studija obuhvata pacijente lečene na Klinici za neurologiju KCV u Novom Sadu u periodu od dvanaest godina, od januara 2003. godine do januara 2015. godine sa znacima i simptomima inicijalne demijelinacione bolesti CNS. Od ove kohorte izdvojeno je dve grupe pacijenata; prva grupa pacijenata kod kojih je bolest nastala pre 18. godine života, i druga grupa uzrasta od 20-55 godina. Pacijenti su epidemiološki obrađeni prema godinama početka bolesti, polu, porodičnoj istoriji, simptomima na početku bolesti (inicijalni simptom), toku bolesti- pojavi drugog relapsa i vremena do pojave drugog relapsa, nalazu MRI, nalazu evociranih potencijala i prisustvo oligoklonalnih traka u likvoru. Tokom praćenja beleži se vreme do drugog relapsa i tip relapsa. Tražila se korelacija između kliničkih i dijagnostičkih rezultata sa brzinom pojave drugog relapsa. Za testiranje razlika između grupa korišćen je Pirsonov hi-kvadrat test, a za testiranje jačine povezanosti korišćeno je Kramerovo V. Neparametrijski podaci su obrađivani Men-Vitni U testom. REZULTATI: Od ukupnog broja ispitanika, u grupi pacijenata sa ranim početkom MS-a odnos ženskog i muškog pola je bio 1,3:1, a u grupi pacijenata sa uobičajenim početkom MS-a 2,2:1. Iz dobijenih rezultata vidimo da ima manje nego što je očekivano pacijenata rođenih u mesecima decembru 4,6% i januaru (5,9%), a više nego što je očekivanu u mesecima martu (11,3%) i julu (10,6%), što nije statistički značajno (p=0,726). Prema manifestaciji bolesti kod dece 17,6% ima polisimptomatski početak, a kod odraslih 37,6% ima polisimptomatski početak.Polisimptomatski početak statistički je značajno više zastupljen kod odraslih pacijenata (p=0,020).Poremećaj piramidnog sistema (P=0,010) i senzorne smetnje (P=0,006) su zastupljeniji kao inicijalni stimptom u grupi odraslih.Nisu nađene statistički značajne razlike u zastupljenosti optičkog neuritisa (p=0,366 ili p>0,05) i ataksije /stablarne simptomatologije (p= 0,791) u ove dve grupe. Najčešći inicijalni simptom kod dece, gotovo u istoj razmeri su optički neuritis (35,3%) i ataksija (35,3%). U grupi odraslih pacijenata senzorne smetnje (41,6%) su najčešći inicijalni simptom, odmah za njim sledi piramidna simptomatologija (37,6%). Prema nalazu broja lezija na MRI pregledu, u grupi ispitanika sa ranim početkom MS-a više su zastupljeni oni sa manje od 4 lezije, nego što je to slučaj u grupi odraslih. Odnos broja pacijenata sa 4-10 i preko 10 lezija simetričan je u obe grupe. Korelacija između doba početka MS-a i broja lezija viđenih na MRI je statistički značajna i neznatna (P=0,06). Nije nađena statistička značajnost u prisustvu lezija u korpusu kalozumu između ove dve grupe pacijenata ( P=0,920). Primenom Fišerovog dvostranog egzaktnog testa koji je u ovom slučaju statistički značajan (p=0,034), možemo reći da se grupa sa ranim početkom MS-a i ona sa uobičajenim početkom statistički značajno razlikuju, tumefaktivne lezije su prisutnije kod ispitanika sa ranim početkom MS-a. Pozitivni oligoklonali su zastupljeniji u grupi odraslih pacijenata ( P= 0,018). U našoj grupi ispitanika kada smo pratili vreme pojave drugog pogoršanja, najkraće godinu dana, u grupi dece 11 pacijenata (21,6%) nije imalo pogoršanje , dok je 40 pacijenata imalo pogoršanje (78,4%),. Medijana kod grupe dece za pojavu drugog šuba bolesti je 12 meseci. U grupi odraslih 22 pacijenta ( 21,8%) nije imalo drugi relaps tokom perioda praćenja, dok je njih 79 (78,2%) imalo drugi relaps. Prosečno vreme u grupi odraslih pacijenata do drugog relapsa je 9 meseci. U grupi dece ne postoje značajne razlike u odnosu broja lezija viđenih na inicijalnom MRI pregledu i vremenu pojave drugog relapsa ( p=0,884) Kod odraslih postoji značajna razlika u vremenu relapsa između grupe sa manje od 4 lezije i grupe sa 4-10 lezija (p=0,09).Korelirali smo pacijente sa pozitivnim i negativnim ologoklonalnim trakama u likvoru u obe grupe sa vremenom nastanka prvog pogoršanja, pri toj korelaciji nije dobijena statistički značajna razlika ni u grupi dece ( P= 0,598) ni u grupi odraslih (P=0,133). Kod ispitanika sa ranim početkom češća je pozitivna porodična anamneza, u vidu prisustva MS i drugih imunoloških bolesti( P =0,042). ZAKLJUČAK: Polisimptomatski početak je češći kod odraslih, pozitivne oliogoklonalne trake su ređe pozitivne kod dece, kod dece je najčešći inicijalni simptom optički neuritis a kod odraslih senzitivne i motorne smetnje. Manje od 4 lezije se češće javljaju kod dece na inicijalnom MRI pregledu, što je najverovatnije povezano sa vremenom stvarnog početka bolesti i njenom kliničkom manifestacijom. Kod pacijenta sa ranim početkom MS-a duži je period do drugog pogoršanja. U grupi dece ne postoje statistički značajne razlike u odnosu broja lezija viđenih na inicijalnom MRI pregledu i vremenu pojave drugog relapsa. Kod odraslih postoji značajna razlika u vremenu relapsa između grupe sa manje od 4 lezije i grupe sa 4-10 lezija. Inicijalne manifestacije MS-a u dečijem uzrastu ne razlikuje se u mnogome od MS-a kod odraslih po karakteristikama i toku bolesti.
INTRODUCTION: Тhe onset of multiple sclerosis (MS) in childhood poses diagnostic and therapeutic challenges. Althougth the onset of MS in childhood typically predicts a fevoruable short/term prognosis, some children are severy disabled. Etiher physically or cognitively, and more then 50% are predicted to enter the secondary-progressive phase of the disease by the age of 30 years. Immunomodulatory therapies for MS and their safe application in children can improve long-therm prognosis. AIM: We saught to identifay clinical and diagnostic features in children wich inplicate to early diagnosis of MS in children. We aimd to determine the clinical features, cerebro spinal fluid, magnetic resonance imagin (MRI) features of children and their comparation with adult MS patients. METHODS: In this retrospective/prospective study we present data from 152 patients with clinical isolated syndrom (CIS) for the first time, which are obtained throught Clinic of Neurology , Clinical Centre of Vojvodina, Novi Sad from January 2003 to January 2015g. Patients were divided into two grups - in first group patients 51 with early onset of disease before 18 years, and second group patients with adult onset desease (20-55 year). Patients wer observed for a minimum one year. The common presenting symptoms, gender, MRI finding, oligoclonal band (OCB) and Visual evoked potential findings, corse of disease, family history were compared between the two groups and with thime of second relaps. To test the difference between groups was used Chi-square Pearson product moment test, and to test the strength of connection used is a Kramer V. Population data are processed Men-Whitney U test. RESULTS: Of the total number of respondents, in the Group of patients with early beginning MS the ratio of women and men was 1.3:1, and in the group of adult MS patients 2, 2:1. From the results we can see that fewer than expected has patients born in the months December ( 4.6%) and January (5.9%), and higher than expected in a March (11.3%) and July (10.6%), which is not statistically significant (p = 0,726). According to the manifestation of disease in children 17.6% has a polifocal onset, and in adults 37.6% has a polifocal onset. Polifocal beginning is significantly over represented in adult MS patients (p = 0,020). Motor disorder (P = 0,010) and sensory disabilities (P = 0.006) are more present as the initial manifestation illness in the adult. They not found statistically significant differences in the representation of optic neuritis (p = 0,366 or p > 0.05) and ataxia (p = 0.791) in these two groups. The most common initial symptom in children, almost in the same scale are the optical neuritis (35.3%) and ataxia 6 (35.3%). In a group of adult patients sensory disturbances (41.6%) are the most common initial symptom, right behind him follows a motor disturbens (37.6%). According to the number of lesions on the MRI exam, in a group of subjects with early MS more are they less than four lesions, than is the case in the group adults. The ratio of the number of patients with 4-10 and over 10 symmetrical lesions in both groups. Correlation between the time of the beginning of the MS and the number of lesions seen on MRI is statistically significant and insignificant (P = 0.06). There was no statistical significance in the presence of lesions in the corpus callosum indicates between these two groups of patients (P = 0,920). Application of Fisher the exact test case that is in this case a statistically significant (p = 0.034). We can say that the group with the early start of MS and the one with the usual beginning of significantly different, tumefactiv lesions are present in patients with early onset MS, Positive oligoclonal bands are more present in a group with adult MS patients (P = 0.018). In our group of respondents when we track time appear another relapse, minimum one year, 11 children (21,6%) had no deterioration, while the 40 children had worsening (78,4%). The median at groups of children for the appearance of second relapse is 12 months. In the adult these 22 (21,8%) had another relapse for tracking period, while 79 (78.2%) had another relapse. The average amount of time in the adult patients relapse to another is 9 months. In a group of children there are no statistically significant differences in the relative number of lesions seen on the initial MRI examination and time show up another relapse (p = 0,884). In adults there is a significant difference in relapse time between groups with fewer than four lesions and groups with 4-10 lesions (p = 0.09). Pressures are patients with positive and negative ologoclonal bands in the cerebrospinal fluid in both groups with the time of occurrence of the first downturn, when the correlation is not get statistically significant difference in the children (P = 0.598) or in a group of adults (P = 0,133). In patients with early starting stacks is a negative family history, and often the presence of MS and other immunological diseases (P = 0,042). CONCULSIONS: Polisifocal beginning is more common in adults, positive oliogoklonalne bands are less positive in children, with children being the most common initial symptom is optic neuritis, in adult sensitive and motor disturbances. Tumefactiv lesions are present in patients with early onset MS. Less than four lesions are more common in children on the initial MRI examination, which is probably connected with the time of the real onset of the disease and its clinical manifestation n the group of children there are no statistically significant differences in relation to the number of lesions seen on MRI at the initial examination and the timing of another relapse. For adults there is a significant difference in time of relapse between the groups with less than 4 lesions and groups with 4-10 lesions. Children onset MS does not significantly differ from that it has been typically seen in adults in terms of major clinical manifestations and course of disease.

Wang, Jing.
Thesis Ph.D. Chinese University of Hong Kong 2014.
Includes bibliographical references (leaves 123-151).
Abstracts also in Chinese.
Title from PDF title page (viewed on 19, September, 2016).

碩士
國立中央大學
天文研究所
104
In a planetary magnetosphere, Energetic Neutral Atoms (ENAs) are generated by charge exchange collisions between energetic ions and neutral gas. The INCA (Ion and Neutral CAmera) instrument onboard the MIMI experiment of the Cassini spacecraft provides ENA images for hydrogen and oxygen for energies between 10 keV and 220 keV depending on the mode. An important discovery of INCA concerns the appearance of source regions of hydrogen ENAs rotating around Saturn outside the orbit of Enceladus. The intensity of the ENA flux tends to brighten up in the midnight to dawn sector, which might be associated with the higher occurrence of energetic charged particles injection events in this region. In this study, we examine the time evolution of a cloud of energetic ions in drift motion relative to the rotating magnetosphere. Besides the dispersal of the energetic ions as a function of their energies, the charge exchange interaction with the neutral cloud created by Enceladus has been simulated. To figure out the possible processes that affect the temporal and spatial variations of ENAs, we examined the effects of an extra noon to mid-night electric field, partial corotation of the plasma and a magnetic field deduced from MAG magnetic field measurements, respectively. A comparison with observational results will be presented.

Glaucoma is characterized by progressive optic nerve head (ONH) deformation and retinal nerve fiber layer (RNFL) thinning but the relative sequence of ONH and RNFL changes in glaucoma remains largely uncertain. It has been proposed that structural damage of the optic nerve can often be detected before detectable functional loss. Therefore, investigating structural changes of the ONH and RNFL is of importance and relevance in the monitoring and management of glaucoma progression. Spectral domain optical coherence tomography (OCT), scanning laser polarimetry (SLP) and confocal scanning laser ophthalmoscopy (CSLO) are the three prevailing digital imaging technologies for measurement of RNFL thickness, RNFL retardance and ONH parameters, respectively. Although these instruments have been extensively investigated for detection of glaucomatous damage, less is known about their relative performance for detection of change in glaucoma progression. Although previous studies on non- human primates showed that disruption of the microtubule structure of the retinal ganglion cell axons detected by SLP as reduction of RNFL retardance, as well as ONH surface deformation detected by CSLO, could be detected prior to reduction of RNFL thickness measured with OCT, clinical data corroborating this observation are lacking. The sequence of change of RNFL thickness, RNFL retardance and ONH parameters has not been investigated in human glaucoma.
This research project aimed to investigate the performance of OCT, SLP and CLSO for change detection of RNFL and ONH damages, determine the relative sequence of change of RNFL retardance and RNFL thickness and ONH deformation, and evaluate if ocular biomechanical properties, measured as corneal hysteresis by the ocular response analyzer (ORA, Reichert Inc.), influence the detection of ONH and RNFL progression in glaucoma patients. We hypothesized that ONH deformation and loss of RNFL retardance could be detected before detectable RNFL thinning and that the baseline corneal hysteresis would be a risk factor for ONH and RNFL damage in glaucoma.
In the first study, we analyzed 184 eyes of 116 patients with glaucoma and 43 normal eyes of 23 healthy individuals followed for a mean of 4.6 years. All subjects had RNFL retardance and RNFL thickness measurements obtained with GDx ECC (Carl Zeiss Meditec) and Cirrus HD-OCT (Carl Zeiss Meditec), respectively, at 4-month intervals. Progressive reduction of RNFL retardance and RNFL thickness were evaluated with Guided Progression Analysis (GPA, Carl Zeiss Meditec) with reference to the RNFL retardance change map and RNFL thickness change map, respectively. Twenty seven eyes of 26 patients showed progressive RNFL thinning whereas 8 eyes of 8 patients had RNFL retardance reduction in the latest follow-up visit. Seven eyes of 7 patients had progressive RNFL thinning and reduction of RNFL retardance detected by both instruments; all had progressive RNFL thinning evident before reduction of RNFL retardance and the mean lag time was 13.4 months (range: 4.0-37.6 months). The survival time of eyes detected with RNFL thinning was significantly shorter than the survival time of eyes detected with reduction of RNFL retardance (P=0.001). No eyes in the normal group showed progressive RNFL changes during follow-up. Collectively, we showed that at a comparable specificity (100%, 95% confidence interval: 96.3%-100%), progressive RNFL thinning was detected more often than progressive reduction of RNFL retardance and the former preceded the latter in eyes with both progressive RNFL thinning and reduction of RNFL retardance.
In the second study using a similar study design, we investigated the sequence of change of ONH surface depression detected by CSLO (HRT 3, Heidelberg Engineering) and RNFL thinning detected by OCT (Cirrus HD-OCT, Carl Zeiss Meditec) in 146 eyes of 90 glaucoma patients followed at approximately 4-month intervals for an average of 5.4 years. Significant ONH surface depression and RNFL thinning were defined with reference to Topographic Change Analysis (TCA, Heidelberg Engineering) and Guided Progression Analysis (GPA, Carl Zeiss Meditec), respectively. At a specificity of 94.3% (95% confidence interval: 86.2%-97.8%) for both RNFL thinning and ONH surface depression (determined in a normal group comprising 70 eyes from 35 normal subjects), 57 eyes (39.0%) had ONH surface depression, 46 eyes (31.5%) had RNFL thinning, and 23 eyes (15.8%) had both in the glaucoma group. Among these 23 eyes, 19 (82.6%) had ONH surface depression detected prior to RNFL thinning and the median lag time was 15.8 months (range, 4.0-40.8 months). Although only 7.0% of eyes (4/57) had RNFL thinning at the onset of ONH surface depression, 45.7% (21/46) had ONH surface depression at the onset of RNFL thinning. The survival time of eyes with ONH surface depression was significantly shorter than the survival time of eyes detected with RNFL thinning (P=0.002). With reference to the HRT TCA and OCT GPA, ONH surface depression occurred before RNFL thinning in a significant proportion of patients with glaucoma at a comparable specificity.
Of note, a significant proportion of eyes had ONH surface depression without any detectable progressive RNFL thinning in the second study, and vice versa. Investigating whether the risk factors for ONH surface depression and RNFL progression are different is therefore important. In the final study, we investigated if baseline corneal hysteresis is a risk factor for progressive ONH surface depression and RNFL thinning. Following the same cohort of 146 eyes of 90 glaucoma patients for an average of 6.8 years, we detected that 65 eyes (44.5%) had progressive ONH surface depression, 55 eyes (37.7%) had progressive RNFL thinning and 20 eyes (13.7%) had visual field progression (based on the EMGT criteria). After adjusting for ages, CCT, baseline diastolic IOP, average IOP during follow-up, baseline disc area and baseline MD in the cox proportional hazards model, baseline corneal hysteresis was significantly associated with ONH surface depression (HR=0.70, P=0.008), visual field progression (HR=0.56, P=0.019), but not with progressive RNFL thinning (HR=0.96, P=0.751). For each 1-mmHg decrease of baseline CH, the hazards for ONH surface depression and visual field progression increased by 30% and 44%, respectively.
In summary, at a comparable level of specificity, progressive ONH surface depression detected by CSLO could be observed prior to progressive RNFL thinning detected by OCT, which preceded identified reduction of RNFL retardance detected by SLP. For eyes with concomitant ONH surface depression, RNFL thinning and visual field progression, ONH surface depression always preceded visual field progression. Our finding indicates that a time window for therapeutic intervention may exist upon detection of ONH surface depression before irreversible RNFL and visual field loss and that measurement of CH would be useful to predict ONH surface depression and visual field progression.
Further studies are required to investigate the sequence of optic nerve head change and RNFL progression with the same instrument. Whether IOP lowering treatment initiated at the time of ONH deformation would be effective to prevent or slow down RNFL and visual field loss needs to be further investigated. A more reliable and accurate measure of the ocular biomechanical properties is necessary for evaluation of their contribution to glaucoma progression.
青光眼是一種進展性視神經病變，其特徵為﹕視神經乳頭變形，神經纖維層（RNFL）的變薄以及相應的視野缺損。然而，青光眼結構性改變和功能性變化發生的相對順序仍不清楚。視神經結構性改變被認為要早於功能性改變的發生。因此，研究視乳頭的結構性改變具有重要意義，有助於早期診斷青光眼的進展及隨訪青光眼患者。目前主要用於RNFL厚度，RNFL阻滯性以及視乳頭參數的影像學掃描儀器為頻域OCT，鐳射偏振光掃描器（SLP）和共聚焦鐳射掃描眼底鏡（CSLO）。儘管這三種儀器已經廣泛用於青光眼損傷的檢測，但在青光眼患者結構性變化的應用並不常見。既往在非人靈長類動物的實驗中，通過破壞神經節細胞軸突中的微小管結構，從而發現RNFL的阻滯性以及視乳頭的變化要先於RNFL厚度變化的發生。然而在臨床研究中並未得到證實。同時，在青光眼患者中，RNFL厚度變化，RNFL阻滯減少以及視神經頭參數改變之間的先後順序並未得到證實。
本次實驗研究的目的在於探討OCT，SLP及CSLO在診斷青光眼病人RNFL及視乳頭進展的能力，確定RNFL厚度變化，RNFL阻滯性減少以及視神經頭參數改變之間的相對順序，以及評估眼反應分析儀（ORA）測得的角膜粘滯性（CH）是否影響視乳頭及RNFL厚度的進展。我們假設：視神經乳頭的變形，RNFL阻滯性的減少要先於RNFL厚度的變化，基線角膜粘滯性的測量會影響視乳頭及RNFL進展的檢測。116個青光眼病人的184隻眼以及23個正常對照的43隻眼被納入第一個研究中。所有受試物件均接受每4個月一次的OCT以及SLP RNFL的掃描，平均隨訪時間為4.6年。通過OCT及SLP中Guided Progression Analysis（GPA, Carl Zeiss Meditec）程式，一系列RNFL厚度及粘滯性圖被自動分析從而獲得RNFL厚度及粘滯性的變化結果。26個青光眼患者的27隻眼表現為RNFL厚度的進行性變薄，8個患者的8隻眼表現為RNFL粘滯性的減少。其中7個患者的7隻眼同時表現為RNFL厚度變薄及粘滯性的減少，所有這7隻眼的RNFL變薄的發生要早於RNFL粘滯性的減少，兩者間隔時間平均為13.4月（4.0-37.6月）。RNFL厚度變薄者的生存概率明顯小於RNFL粘滯性減少的青光眼患者（P=0.001）。隨訪中，我們未發現正常對照組中RNFL厚度變薄或者粘滯性改變者。總體說來，在同一特異性水準（100%），RNFL厚度的變化頻率高於粘滯性的改變，RNFL厚度的變薄要早於粘滯性減少的發生。
採用相同於第一個研究的研究方法，我們研究CSLO測得的視乳頭表面凹陷以及測得OCT的RNFL厚度變化發生的相對順序。90個青光眼患者的146隻眼以及35個正常對照物件的70隻眼被納入第二個研究中。所有受試物件均接受4個月一次的CSLO及OCT掃描從而獲得一系列的視神經頭表面的拓撲圖像以及RNFL厚度圖。CSLO TCA及OCT GPA程式自動對比基線及隨訪中所獲得的視神經頭表面的拓撲圖像以及RNFL厚度圖，從而獲得視乳頭表面凹陷及RFNL進展報告。平均隨訪5.4年後，CSLO及OCT在診斷視神經頭及RNFL進展的特異性為94.3%，57只青光眼患眼（39.0%）表現為顯著性視乳頭表面凹陷，46隻眼（31.5%）表現為RFNL厚度的進行性變薄，而23隻眼（15.8%）同時表現為視乳頭面凹陷和RFNL的進行性變薄。在這23只眼中，19隻眼（82.6%）變現為視乳頭表面凹陷先於RFNL厚度變薄的發生，間隔時間的中值為15.8個月（4.0-40.8月）。儘管在顯著性視乳頭表面凹陷發生時，僅有7.0%的患眼表現為RNFL厚度的變薄；但是，在RNFL厚度發生顯著性變薄時已有45.7%的患眼表現為視乳頭表面凹陷。視乳頭表面凹陷患眼的生存概率差於RNFL厚度變薄患眼（P=0.002）。在青光眼患者的隨訪中，CLSO TCA測得的視乳頭表面凹陷要早於OCT GPA測得的RNFL厚度的變化。
最後的一個研究目在於評估眼反應分析儀（ORA）測得的基線角膜粘滯性（CH）是否為視乳頭表面凹陷及RNFL厚度變薄的危險因素。平均隨訪同一人群即第二個研究中的90個青光眼患者的146眼6.8年，65隻眼（44.5%）被檢測出具有進行性視乳頭表面凹陷，55隻眼（37.7%）表現為進行性RNFL厚度的變薄，20隻眼（13.7%）表現為進行性視野的缺損（基於EMGT標準）。基線CH與視乳頭表面凹陷，視野進展間具有顯著性相關關係（HR=0.70，P=0.008及HR=0.56，P=0.019），但CH與進行性RNFL厚度變薄間並無顯著性相關關係（HR=0.96，P=0.751）。每1毫米汞柱基線CH的降低，發生視乳頭表面凹陷及視野缺損的危險性將增加30%及44%。CH的測量值與青光眼進展的危險性具有顯著相關關係。
總之，在具有可比性特異性水準下，CSLO檢測的進展性視乳頭表面凹陷的發生要先於OCT檢測的進行性RNFL厚度的變薄，後者的發生早於SLP測得的RNFL粘滯性的改變。對於同時有視乳頭表面凹陷，RNFL厚度變薄及RNFL粘滯性改變的青光眼患眼，視乳頭表面凹陷的發生要早於視野的進展。我們的實驗研究表明了在青光眼患者發生視乳頭表面凹陷時，治療的時間窗的存在有助於避免不可逆的RNFL缺失及視野的缺損。角膜粘滯性的測量對於預測視乳頭表面凹陷及視野進展具有重要意義。
展望未來的研究中，用同一種儀器進行視乳頭及神經纖維層的隨訪，從而得出相對的變化次序很有必要。研究在視乳頭或者神經纖維層發生變化時進行眼壓的干預是否能避免視功能的進一步損傷顯得尤為重要。用於測量角膜生物學特性的更為準確，可信度更高的儀器真正研發中，以及進一步探討角膜生物學特性與青光眼進展之間的關係。
Xu, Guihua.
Thesis Ph.D. Chinese University of Hong Kong 2015.
Includes bibliographical references (leaves 116-145).
Abstracts also in Chinese.
Title from PDF title page (viewed on 18, October, 2016).
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.