INTRODUÇÃO: A degeneração do disco intervertebral (DIV) é um processo crônico e apontado como o maior causador de cervicalgia e lombalgia. Esse processo geralmente conta com a degradação da matriz extracelular, expressão de citocinas inflamatórias e fatores angiogênicos e axonogênicos. Entretanto, muito pouco se sabe sobre esse processo em DIVs assintomáticos durante o envelhecimento, principalmente no segmento cervical. O objetivo desse estudo foi de delinear o perfil de moléculas relacionadas à degeneração discal em DIVs cervicais e lombares. MÉTODOS: Discos intervertebrais humanos cervicais e lombares (C4-C6 e L4-S1) foram coletados em autópsia de 30 indivíduos presumivelmente assintomáticos e divididos em grupos jovem (GJ < 35 anos, n=60) e idoso (GI > 65 anos, n=60). O nível de degeneração foi constatado pela escala de Thompson, e foi correlacionado com a detecção imuno-histoquímica das moléculas de MMP-1, -2, -3, TIMP-1, IL-1beta, TNF-alfa, VEGF, NGF-beta e BDNF. RESULTADOS: Todos os DIVs mostraram algum grau de degeneração, embora mais acentuadas no GI. As moléculas empenhadas no estudo foram identificadas em ambos grupos. A detecção imuno-histoquímica foi prevalente no citoplasma das células nativas do DIV e na região de interseção entre a placa vertebral e o arranjo fibro-colágeno. O envelhecimento propiciou, no disco cervical, maior expressão de MMP-2, -3, VEGF, NGF-beta e BDNF, enquanto que no disco lombar, a maior expressão foi de MMP-1, -2 -3, TIMP-1, TNF-alfa, VEGF e NGF-beta. DISCUSSÃO: O envelhecimento de DIVs cervicais e lombares caracterizou-se por exibir um processo catabólico e extensivo remodelamento da matriz extracelular, os quais podem ser interpretados como eventos que antecipam a doença degenerativa discal. Esse processo é capaz de levar a angiogênese e axonogênese de modo a ampliar o metabolismo aeróbio do DIV e captar informação nociceptiva como forma de defesa, uma vez que até nos discos lombares de indivíduos jovens essa última característica pôde ser observada. Discos assintomáticos também exibem moléculas relacionadas à doença degenerativa discal e talvez a inibição de parte dessas possa resultar em terapia preventiva / INTRODUCTION: Degeneration of the intervertebral disc (DIV) is a chronic process that pointed as a major cause of neck and low back pain. This process generally includes an extracellular matrix degradation, expression of inflammatory cytokines, angiogenesis and axonogenesis factors. However, there is a little known about this process in asymptomatic DIVs during aging, especially in the cervical region. The aim of this study was to delineate the profile of molecules related to disc degeneration in the cervical and lumbar discs. METHODS: Human cervical and lumbar intervertebral discs (C4-C6 e L4-S1) were harvested at autopsy from 30 asymptomatic individuals, and divided according to age with young (GJ < 35 years old, n=60) and elderly (GI > 65 years old, n=60) groups. Gross degeneration was graded according to the Thompson scale and this was correlated to the immunohistochemical detection of molecules of MMP-1, -2, -3, TIMP-1, IL-1beta, TNF-alfa, VEGF, NGF-beta e BDNF. RESULTS: Discs from GJ were significantly less degenerated than those of GI. The molecules involved in the study were identified in both groups. The immunohistochemical detection was prevalent in the cytoplasm of native disc cells and the region between the vertebral plate and fibrous collagen arrangement (intersection). Aging provided in cervical disc, increased expression of MMP-2, -3, VEGF, NGF and BDNF-beta, whereas in the lumbar disc the highest expression of MMP-1, -2, -3, TIMP-1, TNF-alfa, VEGF and NGF-beta was seen. DISCUSSION: The aging of cervical and lumbar DIV was marked by catabolic process and a extensive remodeling on extracellular matrix which can be interpreted as a predict event of the degenerative disc disease. This process can lead to angiogenesis and axonogenesis in order to expand the aerobic metabolism of the DIV and get nociceptive information as a defense, since even in the lumbar discs of young individuals this last feature can be observed. Asymptomatic discs also exhibit molecules related to degenerative disc disease and perhaps the inhibition some of these can result in preventive therapy

INTRODUÇÃO: A degeneração do disco intervertebral (DIV) é um processo crônico e apontado como o maior causador de cervicalgia e lombalgia. Esse processo geralmente conta com a degradação da matriz extracelular, expressão de citocinas inflamatórias e fatores angiogênicos e axonogênicos. Entretanto, muito pouco se sabe sobre esse processo em DIVs assintomáticos durante o envelhecimento, principalmente no segmento cervical. O objetivo desse estudo foi de delinear o perfil de moléculas relacionadas à degeneração discal em DIVs cervicais e lombares. MÉTODOS: Discos intervertebrais humanos cervicais e lombares (C4-C6 e L4-S1) foram coletados em autópsia de 30 indivíduos presumivelmente assintomáticos e divididos em grupos jovem (GJ < 35 anos, n=60) e idoso (GI > 65 anos, n=60). O nível de degeneração foi constatado pela escala de Thompson, e foi correlacionado com a detecção imuno-histoquímica das moléculas de MMP-1, -2, -3, TIMP-1, IL-1beta, TNF-alfa, VEGF, NGF-beta e BDNF. RESULTADOS: Todos os DIVs mostraram algum grau de degeneração, embora mais acentuadas no GI. As moléculas empenhadas no estudo foram identificadas em ambos grupos. A detecção imuno-histoquímica foi prevalente no citoplasma das células nativas do DIV e na região de interseção entre a placa vertebral e o arranjo fibro-colágeno. O envelhecimento propiciou, no disco cervical, maior expressão de MMP-2, -3, VEGF, NGF-beta e BDNF, enquanto que no disco lombar, a maior expressão foi de MMP-1, -2 -3, TIMP-1, TNF-alfa, VEGF e NGF-beta. DISCUSSÃO: O envelhecimento de DIVs cervicais e lombares caracterizou-se por exibir um processo catabólico e extensivo remodelamento da matriz extracelular, os quais podem ser interpretados como eventos que antecipam a doença degenerativa discal. Esse processo é capaz de levar a angiogênese e axonogênese de modo a ampliar o metabolismo aeróbio do DIV e captar informação nociceptiva como forma de defesa, uma vez que até nos discos lombares de indivíduos jovens essa última característica pôde ser observada. Discos assintomáticos também exibem moléculas relacionadas à doença degenerativa discal e talvez a inibição de parte dessas possa resultar em terapia preventiva / INTRODUCTION: Degeneration of the intervertebral disc (DIV) is a chronic process that pointed as a major cause of neck and low back pain. This process generally includes an extracellular matrix degradation, expression of inflammatory cytokines, angiogenesis and axonogenesis factors. However, there is a little known about this process in asymptomatic DIVs during aging, especially in the cervical region. The aim of this study was to delineate the profile of molecules related to disc degeneration in the cervical and lumbar discs. METHODS: Human cervical and lumbar intervertebral discs (C4-C6 e L4-S1) were harvested at autopsy from 30 asymptomatic individuals, and divided according to age with young (GJ < 35 years old, n=60) and elderly (GI > 65 years old, n=60) groups. Gross degeneration was graded according to the Thompson scale and this was correlated to the immunohistochemical detection of molecules of MMP-1, -2, -3, TIMP-1, IL-1beta, TNF-alfa, VEGF, NGF-beta e BDNF. RESULTS: Discs from GJ were significantly less degenerated than those of GI. The molecules involved in the study were identified in both groups. The immunohistochemical detection was prevalent in the cytoplasm of native disc cells and the region between the vertebral plate and fibrous collagen arrangement (intersection). Aging provided in cervical disc, increased expression of MMP-2, -3, VEGF, NGF and BDNF-beta, whereas in the lumbar disc the highest expression of MMP-1, -2, -3, TIMP-1, TNF-alfa, VEGF and NGF-beta was seen. DISCUSSION: The aging of cervical and lumbar DIV was marked by catabolic process and a extensive remodeling on extracellular matrix which can be interpreted as a predict event of the degenerative disc disease. This process can lead to angiogenesis and axonogenesis in order to expand the aerobic metabolism of the DIV and get nociceptive information as a defense, since even in the lumbar discs of young individuals this last feature can be observed. Asymptomatic discs also exhibit molecules related to degenerative disc disease and perhaps the inhibition some of these can result in preventive therapy

La dégénérescence des disques intervertébraux (DD) est un processus naturel qui touche une grande partie de la population. Toutefois, elle peut devenir pathologique et ainsi être accélérée par de multiples facteurs et conduire à un dysfonctionnement précoce des disques lombaires. La DD est un phénomène asymptomatique, ce qui le rend délicat à diagnostiquer précocement. Dans ce cadre, le présent travail vise à développer une méthodologie de diagnostic de la DD utilisant imagerie médicale et modélisation biomécanique.Les disques intervertébraux (DIV) sont des articulations fibro-cartilagineuses qui lient les vertèbres du rachis entre elles. Ils ont pour rôle de supporter et redistribuer les chargements appliqués au rachis tout en assurant sa mobilité. Le DIV peut être assimilé d’un point de vue mécanique à un milieu poreux biologique dont le squelette est formé par la matrice extracellulaire (MEC) et la phase fluide par son contenu hydrique. C’est un milieu hétérogène et anisotrope. Possédant une pression osmotique interne élevée, les DIV ne sont pas vascularisés et possèdent un contenu hydrique important dans lesquels les nutriments cellulaires diffusent à partir des vertèbres adjacentes. Cette particularité rend le fonctionnement des disques très dépendant de la régulation en eau en particulier lorsque ces derniers sont soumis à des sollicitations mécaniques non physiologiques.L’une des clés dans l’élaboration d’un diagnostic fiable de la DD peut être de déterminer de manière objective certaines des caractéristiques internes au disque relatives à son hydratation. Dans le présent travail, une méthodologie de diagnostic quantitatif de la viabilité discale et plus largement de la DD est ainsi proposée. Cette méthodologie se base sur un couplage entre l’imagerie médicale et l’analyse par modélisation du comportement biomécanique du DIV. Un modèle physique biphasique du DIV est développé à l’aide de données déduites d’images IRM. Ce modèle tient compte de l’anisotropie du DIV et des effets induits par les déformations mécaniques sur le processus de transport nutritif.La partie mécanique du modèle est tout d’abord validée en utilisant des résultats d’essais de relaxation réalisés précédemment par l’équipe de biomécanique d’IRPHE. Le modèle est à même de reproduire la distribution de la porosité à l’intérieur du DIV et la perte d’eau suite à un effort mécanique. Cela permet de confirmer la fiabilité de la méthodologie de diagnostic développée pour les cas étudiés. En intégrant le couplage mécano-métabolique, la réponse biomécanique du DIV à des chargements quasi statiques et cycliques est ensuite analysée. / Intervertebral disc degeneration (DD) is a natural process affecting a large part of the population. However, it can be accelerated by several factors and then become associated to lumbar disc pathologies. Given that the DD is symptomless, it is complicated to diagnostic it early. In this context, the present work aims to develop a new methodology of DD diagnostic based on medical imaging and biomechanical modeling.The intervertebral discs (IVD) are fibro-cartilaginous joints that connect vertebrae together ensuring their relative motion. They support and distribute loads applied on the spine. Mechanically, the IVD can be assimilated to a biological porous media in which the solid phase is composed of the extracellular matrix (MEC) and the fluid phase is formed by water content. It is a non-homogeneous and anisotropic component. The IVD is nonvascularized and characterized by a high water content in which cell nutrients diffuses from the adjacent vertebrae. Given this latter particularity, the porosity of the IVD presents a key factor in in its functioning especially when exposed to mechanical non-physiological loads. One of the main keys in the elaboration of a reliable DD diagnostic is to determine objectively some of the IVD interne properties related to its water content. In the present work, a new quantitative methodology of DD diagnostic is proposed. This method is based on a coupling between the medical imaging and the IVD biomechanical behavior modeling. A biphasic IVD model is developed using data from MRI imaging. This model takes into account the anisotropy of the IVD and the effect of the mechanical deformation on the nutrient transport process.The mechanical part of the developed model was firstly validated using results of relaxation tests previously performed by the biomechanics staff of IRPHE. The model is able to predict water distribution within the IVD and the water loss as response to a mechanical load. These results confirm the reliability of the developed diagnostic methodology for the studied cases. The biomechanical response to quasi-static and cyclic loads is then analyzed. The present work proposes and evaluates a new methodology of DD quantitative diagnostic. It also analyzes and compares mechanical and metabolic responses to quasi-static and cyclic loads.

Abstract Earlier studies on lumbar degenerative imaging findings in magnetic resonance imaging (MRI) have been done mainly in adult populations and the associations of degenerative findings with low back pain (LBP) are controversial. Only a few studies have involved adolescents and young adults. Heritability has been acknowledged as the only explicit risk factor of disc degeneration (DD). This study investigated the prevalence and environmental determinant of lumbar degenerative findings in MRI and their association with low back symptoms among young adults. The data were based on two physical assessments, three questionnaires and one lumbar MRI that were executed on members of the Oulu Back Study (n=558), a subsample of Northern Finland Birth Cohort 1986, between 16 and 21 years of age. Prevalences of lumbar DD (54%), bulging (25%), protrusion (18%) and Schmorl’s node (17%) were high, whereas other degenerative findings were rare among young adults. Males had higher prevalence of DD and Schmorl’s nodes than females. DD and herniations were associated with low back symptoms. On the other hand, symptoms were present among subjects without DD or other abnormal findings on MRI. Of the environmental determinants, high body mass index and MRI-based obesity measurements of visceral adiposity were associated with lumbar DD among males. Waist circumference and smoking showed a comparable association with DD among males, but the level of physical activity was not associated with DD in either gender. Low back symptoms are more common among young adults with a higher degree of DD or presence of disc herniation. Smoking and overweight are associated with lumbar DD among young male adults. / Tiivistelmä Aikaisempia tutkimuksia magneettikuvantamisella (MK) todetuista lannerangan rappeumamuutoksista ja niiden yhteyksistä alaselkäkipuun on tehty lähinnä aikuisväestöllä ja tulokset ovat ristiriitaisia. Vain muutamia tutkimuksia on tehty alle 25-vuotiailla. Välilevyrappeuman mahdollisista riskitekijöistä vain perimästä on vahvaa näyttöä. Tässä tutkimuksessa tarkasteltiin MK:lla todettujen lannerangan rappeumamuutosten esiintyvyyttä, niihin vaikuttavia ympäristötekijöitä ja yhteyttä alaselkäoireisiin nuorilla aikuisilla. Tutkimuksen aineisto perustui kahteen kliiniseen tutkimukseen, kolmeen kyselyyn ja yhteen MK:een, jotka toteutettiin Pohjois-Suomen syntymäkohortti 1986:een kuuluville Oulun selkätutkimuksen koehenkilöille (n=558) 16-21 vuoden iässä. Lannerangan välilevyrappeumalla (54 %), välilevyn pullotuksilla (bulge; 25 %), sellaisilla välilevyn pullistumilla jotka eivät läpäisseet selkärangan takimmaista pitkittäissidettä (protruusio; 18 %) sekä päätelevyn läpi suuntautuvilla välilevyn pullistumilla (Schmorlin keräset; 17 %) oli korkea esiintyvyys nuorilla aikuisilla, kun taas muut kuvantamislöydökset olivat harvinaisia. Välilevyrappeuma ja Schmorlin keräset olivat yleisempiä miehillä. Sekä välilevyrappeuma että pullistumat olivat yhteydessä alaselkäoireisiin molemmilla sukupuolilla, mutta kaikilla oireisilla ei todettu poikkeavia löydöksiä MK:ssa. Ympäristötekijöistä korkea kehon painoindeksi ja MK:sta mitatut rasvan määrää mittaavat muuttujat olivat miehillä yhteydessä välilevyrappeumaan. Miehillä vyötärönympärys ja tupakointi olivat heikommin yhteydessä välilevyrappeumaan, kun taas liikunta-aktiivisuus ei ollut kummallakaan sukupuolella yhteydessä rappeumaan. Alaselkäoireet ovat yleisempiä nuorilla aikuisilla, joilla on vaikea-asteisempi välilevyrappeuma tai välilevyn pullistuma. Tupakointi ja ylipaino ovat yhteydessä lannerangan välilevyrappeumaan nuorilla aikuisilla miehillä.

O disco intervertebral é uma estrutura cuja função é receber, amortecer e distribuir o impacto das cargas impostas sobre a coluna vertebral. O aumento da idade e a postura adotada pelo indivíduo podem levar à degeneração do disco intervertebral. Atualmente, a Ressonância Magnética (RM) é considerada o melhor e mais sensível método não invasivo de avaliação por imagem do disco intervertebral. Neste trabalho foram desenvolvidos métodos quantitativos computadorizados para auxílio ao diagnóstico da degeneração do disco intervertebral em imagens de ressonância magnética ponderadas em T2 da coluna lombar, de acordo com a escala de Pfirrmann, uma escala semi-quantitativa, com cinco graus de degeneração. Os algoritmos computacionais foram testados em um conjunto de dados que consiste de imagens de 300 discos, obtidos de 102 indivíduos, com diferentes graus de degeneração. Máscaras binárias de discos segmentados manualmente foram utilizadas para calcular seus centroides, visando criar um ponto de referência para possibilitar a extração de atributos. Uma análise de textura foi realizada utilizando a abordagem proposta por Haralick. Para caracterização de forma, também foram calculados os momentos invariantes definidos por Hu e os momentos centrais para cada disco. A classificação do grau de degeneração foi realizada utilizando uma rede neural artificial e o conjunto de atributos extraídos de cada disco. Uma taxa média de acerto na classificação de 87%, com erro padrão de 6,59% e uma área média sob a curva ROC (Receiver Operating Characteristic) de 0,92 indicam o potencial de aplicação dos algoritmos desenvolvidos como ferramenta de apoio ao diagnóstico da degeneração do disco intervertebral. / The intervertebral disc is a structure whose function is to receive, absorb and transmit the impact loads imposed on the spine. Increasing age and the posture adopted by the individual can lead to degeneration of the intervertebral disc. Currently, Magnetic Resonance Imaging (MRI) is considered the best and most sensitive noninvasive method to imaging evaluation of the intervertebral disc. In this work were developed methods for quantitative computer-aided diagnosis of the intervertebral disc degeneration in MRI T2 weighted images of the lumbar column according to Pfirrmann scale, a semi-quantitative scale with five degrees of degeneration. The algorithms were tested on a dataset of 300 images obtained from 102 subjects with varying degrees of degeneration. Binary masks manually segmented of the discs were used to calculate their centroids, to create a reference point to enable extraction of attributes. A texture analysis was performed using the approach proposed by Haralick. For the shape characterization, invariant moments defined by Hu and central moments were also calculated for each disc. The rating of the degree of degeneration was performed using an artificial neural network and the set of extracted attributes of each disk. An average rate of correct classification of 87%, with standard error 6.59% and an average area under the ROC curve (Receiver Operating Characteristic) of 0.92 indicates the potential application of the algorithms developed as a diagnostic support tool to the degeneration of the intervertebral disc.

A tese propõem uma metodologia, em nível de pesquisa, por intermédio do desenvolvimento e da adaptação de ferramentas de apoio computadorizado, capaz de realizar a segmentação da imagem dos discos intervertebrais da região lombar da coluna vertebral humana, de maneira semiautomática reduzindo drasticamente o tempo gasto manualmente neste procedimento, sem perder sua acurácia e, ainda, garantindo maior reprodutibilidade em seus resultados. Foram utilizadas imagens sagitais de ressonância magnética ponderadas em T2 de 285 discos intervertebrais de 70 pacientes, classificados segundo o grau de severidade da degeneração discal definido pelo critério proposto por Pfirrmann. A classificação computacional dos discos foi realizada com base em atributos quantitativos extraídos dos histogramas de níveis de cinza e de informações de textura das imagens. O desempenho dos métodos computacionais de segmentação foi avaliado com base no Coeficiente de Jaccard, na distância de Hausdorff e no Erro Médio Quadrático. O desempenho dos métodos computacionais de classificação foi também avaliado com base em medidas similares à aplicação da sensibilidade, da especificidade e da área sob a curva ROC. A segmentação manual e a classificação por inspeção visual dos discos realizadas por três profissionais experientes foram utilizadas como padrão ouro para a comparação. Os principais resultados indicaram a médio de 63,22% para o Coeficiente de Jaccard, as médias de 0,044 das distâncias de Hausdoff e de 0,014 para o EMQ na comparação entre as imagens. Além disso, a segmentação semiautomatizada diferiu em uma taxa média de 30% em relação à segmentação manual e a classificação da degeneração discal, por redes neurais artificiais difere em menos de 2%, ao ser comparada ao procedimento de classificação manual realizado pelos especialistas. / The thesis proposes a methodology at the level of research through the development and adaptation of computerized support tools, able to perform the image segmentation of the intervertebral discs of the lumbar region of the human spine, semiautomatic way dramatically reducing time spent manually in this procedure, without losing its accuracy and also ensuring more reproducible in their results. Were used sagittal MRI T2- weighted of 285 intervertebral discs from 70 patients, classified according to the severity of disc degeneration defined by the criteria proposed by Pfirrmann. The computational classification of disks was based on quantitative attributes extracted from histograms of gray level images and the texture information. The performance of computational segmentation methods was evaluated based on Jaccard coefficient, Hausdorff distance and Mean Square Error. The performance of the computational classification methods was evaluated based on measures of sensitivity, specificity and the area under the ROC curve. The manual segmentation and visual inspection classification of the discs made by three experienced professionals were used as the gold standard for comparison. The main results showed an average Jaccard coefficient of 63.22%, the average Hausdoff of distances was 0.044 and 0.014 Mean Square Error average when comparing the images from both segmentation targets. Additionally, the targeting semiautomatic differed by an average of 30% compared with manual segmentation and classification of disc degeneration provided from an artificial neural networks differs by less than 2% when compared to manual sorting procedure performed by experts.

Abstract Low back pain (LBP) is a highly prevalent musculoskeletal condition and the leading cause for workplace absenteeism. Lumbar disc degeneration (DD) is considered as a contributing factor to LBP. The role of genetic factors in the development of lumbar DD has been demonstrated to be significant, with heritability estimates ranging from 64% to 81%. Modic change (MC), a distinct phenotype of lumbar DD, is a subchondral and vertebral bone marrow change revealed only by magnetic resonance imaging (MRI). MC has been associated with LBP in both clinical samples and the general population. The genetic background of MC is largely unknown, and the heritability of MC has not previously been assessed. The aim of this study was to assess the heritability of MC using a twin study, identify predisposing genetic factors for MC in a family-based design using whole-exome sequencing and to identify genetic loci associated with MC using genome-wide association study (GWAS) meta-analysis. An additional aim was to study the prevalence, incidence and morphology of MC. The data consisted of two general population samples, the Northern Finland Birth Cohort 1966 (NFBC1966) and TwinsUK from the United Kingdom, as well as two Finnish families from the Oulu region. MC was found to be partly heritable with a heritability estimate of 30%. Two novel candidate genes, HSPG2 and MAML1, were found co-segregating with MC in two Finnish families. Both genes are important in the growth and differentiation of chondrocytes. Finally, a genetic locus on chromosome 9 was found to be significantly associated with MC using genome-wide meta-analysis of NFBC1966 and TwinsUK. These results showed that genetic factors play a role in the development of MC. In conclusion, this thesis increased the knowledge on the genetics of MC. However, the specific roles of these genes need to be studied further. / Tiivistelmä Alaselkäkivun kansaterveydellinen merkitys on suuri, sillä jopa 84% aikuisista kärsii siitä elämänsä aikana. Selkäkivun vuoksi Suomessa kertyy yli 2 miljoona sairauslomapäivää vuodessa. Välilevyrappeumaa pidetään merkittävänä tekijänä alaselkäkivun synnyssä ja perinnölliset tekijät selittävät välilevyrappeuman synnystä jopa 74%. Modic-muutokset ovat selkärangan välilevyjen päätelevyjen ja subkondraalisen luun muutoksia, jotka voidaan havaita ainoastaan magneettikuvauksella. Niitä pidetään välilevyrappeuman alatyyppinä. Modic-muutosten on osoitettu olevan yhteydessä alaselkäkipuun, mutta etiologia tunnetaan huonosti. Perinnöllisyyden osuutta Modic-muutoksien synnyssä ei ole aiemmin tutkittu ja niiden taustalla vaikuttavat geneettiset tekijät ovat pääasiassa tuntemattomia. Tämän tutkimuksen tavoitteena oli arvioida perinnöllisyyden osuutta Modic-muutoksissa kaksoisaineistossa, tunnistaa Modic-muutoksille altistavia geneettisiä muutoksia perheaineistossa käyttäen eksomisekvensointia ja tunnistaa genomin alueita, jotka assosioituvat Modic-muutoksiin. Tutkimus perustui kahteen väestöperäiseen aineistoon: Pohjois-Suomen Syntymäkohorttiin 1966 ja TwinsUK-kaksosaineistoon Yhdistyneistä kuningaskunnista sekä kahteen pohjois-suomalaiseen perheeseen. Tutkimuksessa osoitettiin, että Modic-muutokset ovat perinnöllisiä ja, että perinnölliset tekijät selittävät noin 30% niiden ilmenemisestä. Lisäksi tutkimuksessa tunnistettiin kaksi uutta alttiusgeeniä; HSPG2- ja MAML1-geenit. Molemmilla geeneillä on tärkeä rooli rustosolujen kasvamisessa ja erilaistumisessa. Tutkimuksessa myös tunnistettiin kromosomista 9 genomin alue, joka assosioituu Modic-muutoksiin. Väitöskirjassani osoitettiin, että perinnöllisillä tekijöillä on merkitystä Modic-muutosten synnyssä. Kokonaisuudessaan tämä väitöskirja kasvattaa ymmärrystä Modic-muutoksista, mutta lisätutkimusta aiheesta tarvitaan.

A tese propõem uma metodologia, em nível de pesquisa, por intermédio do desenvolvimento e da adaptação de ferramentas de apoio computadorizado, capaz de realizar a segmentação da imagem dos discos intervertebrais da região lombar da coluna vertebral humana, de maneira semiautomática reduzindo drasticamente o tempo gasto manualmente neste procedimento, sem perder sua acurácia e, ainda, garantindo maior reprodutibilidade em seus resultados. Foram utilizadas imagens sagitais de ressonância magnética ponderadas em T2 de 285 discos intervertebrais de 70 pacientes, classificados segundo o grau de severidade da degeneração discal definido pelo critério proposto por Pfirrmann. A classificação computacional dos discos foi realizada com base em atributos quantitativos extraídos dos histogramas de níveis de cinza e de informações de textura das imagens. O desempenho dos métodos computacionais de segmentação foi avaliado com base no Coeficiente de Jaccard, na distância de Hausdorff e no Erro Médio Quadrático. O desempenho dos métodos computacionais de classificação foi também avaliado com base em medidas similares à aplicação da sensibilidade, da especificidade e da área sob a curva ROC. A segmentação manual e a classificação por inspeção visual dos discos realizadas por três profissionais experientes foram utilizadas como padrão ouro para a comparação. Os principais resultados indicaram a médio de 63,22% para o Coeficiente de Jaccard, as médias de 0,044 das distâncias de Hausdoff e de 0,014 para o EMQ na comparação entre as imagens. Além disso, a segmentação semiautomatizada diferiu em uma taxa média de 30% em relação à segmentação manual e a classificação da degeneração discal, por redes neurais artificiais difere em menos de 2%, ao ser comparada ao procedimento de classificação manual realizado pelos especialistas. / The thesis proposes a methodology at the level of research through the development and adaptation of computerized support tools, able to perform the image segmentation of the intervertebral discs of the lumbar region of the human spine, semiautomatic way dramatically reducing time spent manually in this procedure, without losing its accuracy and also ensuring more reproducible in their results. Were used sagittal MRI T2- weighted of 285 intervertebral discs from 70 patients, classified according to the severity of disc degeneration defined by the criteria proposed by Pfirrmann. The computational classification of disks was based on quantitative attributes extracted from histograms of gray level images and the texture information. The performance of computational segmentation methods was evaluated based on Jaccard coefficient, Hausdorff distance and Mean Square Error. The performance of the computational classification methods was evaluated based on measures of sensitivity, specificity and the area under the ROC curve. The manual segmentation and visual inspection classification of the discs made by three experienced professionals were used as the gold standard for comparison. The main results showed an average Jaccard coefficient of 63.22%, the average Hausdoff of distances was 0.044 and 0.014 Mean Square Error average when comparing the images from both segmentation targets. Additionally, the targeting semiautomatic differed by an average of 30% compared with manual segmentation and classification of disc degeneration provided from an artificial neural networks differs by less than 2% when compared to manual sorting procedure performed by experts.

O disco intervertebral é uma estrutura cuja função é receber, amortecer e distribuir o impacto das cargas impostas sobre a coluna vertebral. O aumento da idade e a postura adotada pelo indivíduo podem levar à degeneração do disco intervertebral. Atualmente, a Ressonância Magnética (RM) é considerada o melhor e mais sensível método não invasivo de avaliação por imagem do disco intervertebral. Neste trabalho foram desenvolvidos métodos quantitativos computadorizados para auxílio ao diagnóstico da degeneração do disco intervertebral em imagens de ressonância magnética ponderadas em T2 da coluna lombar, de acordo com a escala de Pfirrmann, uma escala semi-quantitativa, com cinco graus de degeneração. Os algoritmos computacionais foram testados em um conjunto de dados que consiste de imagens de 300 discos, obtidos de 102 indivíduos, com diferentes graus de degeneração. Máscaras binárias de discos segmentados manualmente foram utilizadas para calcular seus centroides, visando criar um ponto de referência para possibilitar a extração de atributos. Uma análise de textura foi realizada utilizando a abordagem proposta por Haralick. Para caracterização de forma, também foram calculados os momentos invariantes definidos por Hu e os momentos centrais para cada disco. A classificação do grau de degeneração foi realizada utilizando uma rede neural artificial e o conjunto de atributos extraídos de cada disco. Uma taxa média de acerto na classificação de 87%, com erro padrão de 6,59% e uma área média sob a curva ROC (Receiver Operating Characteristic) de 0,92 indicam o potencial de aplicação dos algoritmos desenvolvidos como ferramenta de apoio ao diagnóstico da degeneração do disco intervertebral. / The intervertebral disc is a structure whose function is to receive, absorb and transmit the impact loads imposed on the spine. Increasing age and the posture adopted by the individual can lead to degeneration of the intervertebral disc. Currently, Magnetic Resonance Imaging (MRI) is considered the best and most sensitive noninvasive method to imaging evaluation of the intervertebral disc. In this work were developed methods for quantitative computer-aided diagnosis of the intervertebral disc degeneration in MRI T2 weighted images of the lumbar column according to Pfirrmann scale, a semi-quantitative scale with five degrees of degeneration. The algorithms were tested on a dataset of 300 images obtained from 102 subjects with varying degrees of degeneration. Binary masks manually segmented of the discs were used to calculate their centroids, to create a reference point to enable extraction of attributes. A texture analysis was performed using the approach proposed by Haralick. For the shape characterization, invariant moments defined by Hu and central moments were also calculated for each disc. The rating of the degree of degeneration was performed using an artificial neural network and the set of extracted attributes of each disk. An average rate of correct classification of 87%, with standard error 6.59% and an average area under the ROC curve (Receiver Operating Characteristic) of 0.92 indicates the potential application of the algorithms developed as a diagnostic support tool to the degeneration of the intervertebral disc.