The goal of this research study was to create an artificial annulus fibrosus similar to that of the natural intervertebral disc, as well as find preliminary results for vertebral endplate connection and nucleus pulposus internal pressure, for the correction of disc degeneration in the spine. The three-part composite samples needed to demonstrate good shock absorption and load distribution while maintaining strength and flexibility, and removing the need for metal in the body, something of which no current total disc replacement or spinal fusion surgery can offer. For this study, the spinal disc was separated into its three different components, the annulus fibrosus, the nucleus pulposus, and the vertebral endplates, each playing a vital role in the function of the disc. Two low-cost materials were selected, a Covestro polyurethane and cellulose nanocrystals, for the purpose of creating a polymer composite spinal disc implant. A methodology was established for creating the cast composite material for use as an annulus fibrosus, while also investigating its mechanical properties. The same composite material was used to acquire preliminary results for vertebral endplate connection to the synthesized annulus, however no additional material was used to determine or mimic the mechanical properties of these endplates, due to time constraints. Also because of time constraints, the nucleus used in this study was only comprised of water with no other additives for preliminary testing since the natural nucleus is comprised of about 80-90% water. These properties were then compared to the mechanical properties of the natural disc, so that they could be finely tuned to emulate the natural disc. It is shown in this study that the composite material, when swelled in water, was able to mimic the annulus fibrosus in tensile strength and modulus, however showed higher compressive strength and modulus than ideal. The samples also did not undergo any permanent deformation within the realm of force actually introduced to the natural disc. The vertebral endplates showed decent adhesion to the synthesized annulus, however there were slight defects that became failure concentrators during compression testing. The nucleus showed promising results maintaining good internal pressure to the system causing better compressive load distribution, with barreling of the samples. / Master of Science / Spinal disc degeneration is a very prevalent problem in today’s society, effecting anywhere from 12% to 35% of a given population. It usually occurs in the lumbar section of the spine, and when severe enough, can cause bulging and herniation of the intervertebral disc itself. This can cause immense lower back pain in individual’s stricken with this disease, and in the US, medical costs associated with lower back pain to exceed $100 billion. Current solutions to this problem include multiple different treatment options of which, spinal fusion surgery and total disc replacement (TDR) are among the most common. Although these treatments cause pain relief for the majority of patients, there are multiple challenges that come with these options. For example, spinal fusion surgery severely limits the mobility of its patients by fusing two vertebrae together, disallowing any individual movement, and TDR can cause hypermobility in among the vertebrae and offer little to no shock absorption of loads. Therefore, a better treatment option is needed to relieve the pain of the patients, as well as maintain equal motion, shock absorption, and load cushioning to that of the normal intervertebral disc and remaining biocompatible. The goal of this research study was to create a three-component system, like that of the natural intervertebral disc, for the use of spinal disc replacement and to replace current options. The fabricated system was comprised of the three components found in the natural intervertebral disc; the annulus fibrosus, the nucleus pulposus, and the vertebral endplates. Because the system will need to go in-body, the materials used were all characterized as biocompatible materials; the polyurethane currently being used in medical devices and implants, and the cellulose nanocrystals (CNCs) coming from natural cellulose in sources such as wood and plants. The results determined that the mechanical properties of the system can be fine-tuned in order to mimic the natural strength and cushioning capabilities of the natural disc, based on CNC content added to the polyurethane, and when all three components of the system are added together, the compressive stress-strain is most similar to the natural disc in compression. However, the system did show failure in the connection between the annulus fibrosus and vertebral endplates, causing herniation of the nucleus similar to the initial problem attempting to be solved. For this, more ideal fabrication methods should be researched in the future including 3D printing techniques, injection molding, and roll milling. As well as alternate fabrication techniques, cell grow and viability should be determined to show that cells don’t die once the system in implanted.

It is possible that interruption of nociceptive input from intervertebral discs can be modulated through bilateral L1 and L2 dorsal root ganglia (DRG) blockade. In order to test this hypothesis, we prospectively collected data from patients with low-lumbar pain, accurately diagnosed as discogenic using provocation discography. Methods Twelve patients were recruited with a mean (SD) symptom duration of 13.7 (8.2) years. Bilateral DRG blocks of L1 and L2 were performed using methylprednisolone 80 mg, clonidine 75 µg and 0.5% bupivacaine 4 ml in each patient. Results Analysis of Brief Pain Inventories showed no significant change in pain scores. Conclusion We conclude that blocks of this nociceptive pathway in humans using bilateral DRG blocks has no therapeutic value.

Due to the mathematical complexity of current musculoskeletal spine models, there is a need for computationally-efficient models of the intervertebral disc (IVD). The aim of this study is to develop a mathematical model that will adequately describe the motion of the IVD under axial cyclic loading and three-dimensional quasi-static loading as well as maintain computational efficiency for use in future musculoskeletal spine models. A viscoelastic standard nonlinear solid (SNS) model is introduced within this study. It was developed to predict the axial response of the human lumbar IVD subjected to low-frequency vibration. Nonlinear axial behavior of the SNS model was simulated by a strain-dependent elastic modulus on the standard linear solid (SLS) model. The SNS model was able to predict the dynamic modulus of the IVD for frequencies of 0.01, 0.1, and 1 Hz. Furthermore, the model was able to quantitatively predict the load relaxation at a frequency of 0.01 Hz. However, model performance was unsatisfactory when predicting load relaxation and hysteresis at higher frequencies (0.1 Hz and 1 Hz). Results suggest that the standard solid model may require strain-dependent elastic and viscous behavior to represent the dynamic response to compressive strain. The SNS model was expanded to a three-dimensional elastic model by adding a matrix of spring elements in parallel with the SNS model. The geometry and orientation of the added elements represent the regional variations in stiffness and physiologic fiber angle. Results suggest that lordotic posture may be advantageous when modeling the intervertebral joint (IVJ) behavior. / Master of Science

Previous studies have reported that combination of electroacupuncture (EA) and mesenchymal stem/stromal cells (MSC) promoted survival, differentiation and functional recovery in spinal cord-transected rats. In this study, it was examined the therapeutic effects of stem cells from canine exfoliated dental pulp (SCED) combined with EA treatment in dogs with chronic naturally occurred spinal cord injury due to intervertebral disc herniation (IVDH). Dogs were randomly assigned to four experimental groups (n=4 for each group; total of 16 animals): SCED, EA, SCED + EA) and control. Mild increase in the neurological scoring was found in one animal from SCED group (1/4; 2 points gained), one from EA group (1/4; 8 points gained), three from SCED+EA group (3/4; 16 points gained) and one from control group (1/4; 2 points gained). Functional outcome improvements were observed two animals from SCED group (2/4; 3 points gained), two from EA group (2/4; 4 points gained), one from SCED+EA group (1/4; 1 point gained) and two were from control group (2/4; 6 points gained). However no statistical differences were observed. Magnetic resonance imaging (MRI) findings did not suggest improvement comparing pre- and post-treatment within groups, excepted from one animal from SCED group (1/4), and 10 animals from all groups (10/16) presented signs of injury progression in the SCI in post-treatment exam, which could not be associated to the procedures from study, but could be related to the natural evolution of the disease. Limitation such as number of transplanted stem cells, delivery route, injury chronicity and intrinsic variation among naturally spinal cord injured dogs could have influence outcomes negatively. Moreover, canine deciduous exfoliated teeth were easily obtained and SCED were simply isolated, and no mortality followed up 7 month from procedure were observed. / Estudos anteriores demonstraram que a associação da eletroacupuntura e células-tronco mesenquimais/estromais (CTMs) pode promover a sobrevivência e diferenciação das CTMs, assim como recuperação funcional em ratos com transecção da medula espinal. Neste estudo, foram avaliados os efeitos terapêuticos da associação de células-tronco derivadas de polpa de dente decíduo esfoliado de cães (CPDEc) e eletroacupuntura (EAP) em cães com lesão de medula espinhal crônica causada de forma natural por herniação do disco interververtebral. Os cães foram divididos aleatoriamente em quatro grupos experimentais (n=4 para cada grupo; total de 16 animais): CPDEc, EAP, CPDEc+EAP e grupo controle. Foram encontradas pequenas melhoras na pontuação do exame neurológico em um animal do grupo CPDEc (1/4; 2 pontos ganhos), um do grupo EAP (1/4; 8 pontos ganhos), três do grupo CPDEc+EAP (3/4; 16 pontos ganhos) e um do grupo controle (1/4; 2 pontos ganhos). Na avaliação funcional, pequenas melhoras também foram observadas em dois animais do grupo CPDEc (2/4; 3 pontos ganhos), dois do grupo EAP (2/3; 4 pontos ganhos), um do grupo CPDEc+EAP (1/4; 1 ponto ganho) e dois do grupo controle (2/4; 6 pontos ganhos). No entanto, não foram encontradas diferenças estatísticas entre os grupos. Os achados ressonância magnética não sugeriram melhoras comparando os exames pré e pós tratamento entre os grupos, com exceção de um animal do grupo CPDEc (1/4), e 10 animais dentre todos os grupos (10/16) apresentaram sinais de progressão na lesão da medula espinhal, que não puderam ser associados com os procedimentos do estudo, mas podem estar relacionados à progressão natural da doença. Além disso, os dentes decíduos esfoliados foram obtidos facilmente e as CPDEc foram isoladas de forma simples, ademais, não foi observada nenhuma mortalidade foi observada até 7 meses após o procedimento.

INTRODUÇÃO: A hérnia de disco lombar (HDL) acomete cerca de 5% dos pacientes com de dor lombar e o tratamento cirúrgico nestes casos é cada vez menos indicado, optando-se, na maior parte dos casos, pelo conservador. Embora o método estabilização lombar (EL) e a estimulação elétrica nervosa transcutânea (TENS) tenham mostrado bons resultados em indivíduos portadores de dor lombar inespecífica, há escassa literatura que tenha verificado a eficácia destes tratamentos isoladamente em sujeitos acometidos por hérnia de disco lombar. OBJETIVO: Comparar a eficácia dos exercícios de estabilização lombar e da TENS na dor, incapacidade funcional, e capacidade de ativação do músculo transverso do abdome (TrA) de indivíduos com hérnia de disco lombar. METODOLOGIA: Participaram da pesquisa 40 indivíduos com idade variando de 25 a 58 anos com dor lombar e hérnia de disco, e foram randomizados em dois grupos: Grupo estabilização lombar (EL) (exercícios específicos para os músculos TrA e multífido lombar(ML)) (n=20) e Grupo TENS (GT) (n=20) que receberam atendimento com corrente de estimulação elétrica nervosa transcutânea. Foram avaliados quanto à dor (Escala Visual Analógica e Questionário McGill de Dor), incapacidade funcional (Índice de Incapacidade de Oswestry), e capacidade de recrutamento do TrA (Unidade de Biofeedback Pressórico-UBP). Os grupos foram tratados em duas sessões semanais com duração de 60 minutos por oito semanas. Cada indivíduo foi avaliado antes e após o tratamento. O nível de significância estabelecido foi de alfa=0,05. RESULTADOS: Após oito semanas, o grupo estabilização lombar mostrou melhora significativa na dor (p < 0,001), incapacidade funcional (p < 0,001), e capacidade de ativação do TrA (p < 0,001). O grupo TENS apresentou diferença estatisticamente significante apenas na dor (p < 0,012). A estabilização foi superior à TENS na melhora na dor (p < 0,001), incapacidade funcional (p < 0,001), e capacidade de ativação do TrA (p < 0,001). CONCLUSÃO: Os resultados indicam que a estabilização é efetiva na melhora da dor, incapacidade funcional, e capacidade da ativação do TrA, e a TENS apenas na dor. A estabilização foi superior à TENS em todas as variáveis / INTRODUCTION: Lumbar disc herniation (LDH) affects about 5% of low back pain (LBP) patients. Surgical treatment in these cases is increasingly less suitable, opting, in most cases, for the conservative. Although lumbar stabilization method and transcutaneous electric nerve stimulation (TENS) have shown good results in patients with nonspecific low back pain, there is scarce literature that has verified the effectiveness of these treatments alone in subjects suffering from lumbar disc herniation.OBJECTIVE: To compare the effectiveness of lumbar stabilization exercises and transcutaneous electrical nerve stimulation (TENS), on pain, functional disability and activation of the transversus abdominis muscle (TrA), in individuals with lumbar disc herniation (LDH). METHODS: This study involved 40 patients (age range 25-58 years) with lumbar disc herniation randomized into two groups: Stabilization group (SG: n=20); which received of stabilization exercises (transversus abdominis and lumbar multifidus muscles) and TENS group (TG: n=20), which received electrotherapy. The following instruments were used: visual analogue pain scale and McGill Pain Questionnaire for pain, Oswestry Disability Index for functional disability, and pressure biofeedback unit (PBU) for ability to contract the TrA. Analyses within and between groups were performed after treatment. Groups underwent 16 sessions, for 60 minutes, twice a week and they were evaluated before and after eight weeks. Significance level was set at alfa= 0.05. RESULTS: After eight weeks, lumbar stabilization group showed significant improvements in pain (p < 0.001), functional disability (p < 0.001), and the ability to contract the TrA (p < 0.001). There were no significant differences in TENS group in terms of disability (p < 0.264) or ability to contract the TrA muscle (p < 0.181), however, improvement in pain was demonstrated (p < 0.012). The stabilization was superior to TENS in terms of improvements in pain (p < 0.001), functional disability (p < 0.001), and ability to contract the TrA (p < 0.001). CONCLUSION: The results indicate that stabilization is effective in improving pain, functional disability, and the ability to contract the TrA in individuals with LDH. In the TENS group, the only improvement after treatment was in terms of pain. Stabilization was superior to TENS in all outcomes

T1rho弛豫是旋轉坐標系中的自旋晶格弛豫，它決定橫向磁化向量在存有自旋鎖定射頻脈衝情況下的衰減，自旋鎖定脈衝與橫向磁化向量同向。T1rho磁共振成像對於低頻運動過程敏感，故可研究水與其周大分子物質環境間的交互作用，有鑒別組織內早期生化改變的潛力。 / 衰老與慢性高血壓是常見腦退行性疾病的兩個主要危險因素。但是正常腦衰老過程及慢性高血壓兩個因素與腦組織T1rho是否有相關性，尚缺乏研究。序貫性測量SD老鼠自5至15月齡、WKY（血壓正常）和SHR（患有自發性高血壓）老鼠自6至12月齡的雙側丘腦、海馬、和皮質的腦組織T1rho值。發現三組老鼠的丘腦、海馬及皮質的T1rho均隨年齡增長而增高；且SHR的顯著高於WKY老鼠。 / T1rho值與椎間盤退變等級的相關性已有報導。但相比T2值，T1rho在評價椎間盤退變方面是否優於或如何優於T2值尚缺乏研究。將椎間盤髓核及纖維環的T1rho和T2值與5級和8級椎間盤退變等級系統做比較；發現髓核的T1rho及T2與椎間盤退變等級的相關性均呈二次函數降低，且無顯著差別(P=0.40)。纖維環的T1rho及T2與椎間盤退變等級的相關性呈線性函數降低，T2降低的斜率明顯比T1rho降低的斜率要平坦(P<0.001)。故T1rho值比T2值更加適合評價纖維環退變，而兩者在評價髓核時相似。 / 肝纖維化是幾乎所有慢性肝病的常見特徵，包括大分子物質在細胞外基質的沉積。選用四氯化碳CCl4腹腔注射6周來製造肝纖維化模型。肝臟T1rho在注射後的第二天輕度上升，然後持續上升，直到注射六周後T1rho達最高值，此後T1rho隨CCl4注射停止而降低。顯示T1rho磁共振成像對於監測慢性注射CCl4誘導的肝纖維化及肝損傷有價值。當沒有明顯肝纖維化時，肝T1rho輕微受水腫及急性炎症的影響。 / 為將肝臟T1rho磁共振成像轉化到臨床使用，我們研究了其可行性，以及正常志願者肝臟T1rho值分佈範圍。發現採用六個自旋鎖定時間來測量健康志願者肝T1rho，結果有較高的可重複性和一致性，肝T1rho平均值為42.5ms，分佈範圍為38.8到46.5ms。採用三個自鎖鎖定時間點掃描，可以減少一半掃描時間，且可以得到可信的肝T1rho值，但採用兩個自旋鎖定時間點則不行。 / T1rho relaxation is spin-lattice relaxation in the rotating frame. It determines the decay of the transverse magnetization in the presence of a spin-lock radiofrequency pulse, which applied along the transverse magnetization. T1rho MRI is sensitive to low frequency motional processes, so it can be used to investigate the interaction between water molecules and their macromolecular environment. T1rho imaging is suggested to have the potential to identify early biochemical changes in tissues. / Aging and chronic hypertension are two major risk factors for common neurodegenerative disease. However, whether normal brain aging and chronic spontaneous hypertensive are associated with brain T1rho values changes were not reported. We longitudinally measured the T1rho value in rat brain of Sprague-Dawley (SD) rats from 5-month to 15-month, and spontaneous hypertensive rats (SHR) with Wistar Kyoto (WKY) rats from 6-month to 12-month. The T1rho values in three brain regions of thalamus, hippocampus, and cortices increased with aging process, and were significantly higher in SHR than WKY rats. / For intervertebral disc, the correlation between T1rho and degenerative grade has been reported. However, whether and how T1rho specifically offer better evaluation of disc degeneration compared with T2 was not studied previously. T1rho and T2 value of nucleus pulposus (NP) and annulus fibrosus (AF) was compared with reference to the five-level and eight-level semi-quantitative disc degeneration grading systems. For NP, T1rho and T2 decreased quadratically with disc degeneration grades and had no significant trend difference (P=0.40). In NP, T1rho and T2 decrease in a similar pattern following disc degeneration. For AF, T1rho and T2 decreased linearly and the slopes of T2 were significantly flatter than those of T1rho (P<0.001). Therefore, the T1rho is better suited for evaluating AF in degenerated disc than T2. / Liver fibrosis, a common feature of almost all causes of chronic liver disease, involves macromolecules accumulated within the extracellular matrix. Male Sprague-Dawley rats received intraperitoneal injection of 2 ml/kg CCl4 twice weekly for up to 6 weeks. Then CCl4 was withdrawn for recovery. The liver T1rho values increased slightly on day 2, then increased further and were highest at week 6 post CCl4 insults, and decreased upon the withdrawal of the CCl4 insult. This study demonstrated that T1rho MRI is a valuable imaging biomarker for liver injury and fibrosis induced by CCl4. Liver T1rho value was only mildly affected by edema and acute inflammation when there was no apparent fibrosis. / To translate liver T1rho MRI to clinical application, the technical feasibility of T1rho MRI in human liver was explored and the normal range of T1rho values in healthy volunteers was determined. We found it is feasible to obtain consistent liver T1rho measurement for healthy human liver with six spin-lock time (SLT) points of 1, 10, 20, 30, 40, and 50ms; the mean liver T1rho value of the healthy subjects was 42.5ms, with a range of 38.8-46.5ms. Adopting 3-SLT points of 1, 20, and 50ms for T1rho measurement could provide reliable measurement and reduce the scanning time, while 2-SLT points of 1 and 50ms do not provide reliable measurement. / 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. / Zhao, Feng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 119-143). / Abstracts also in Chinese. / ABSTRACT --- p.i / ACKNOWLEDGEMENTS --- p.vi / LIST OF FIGURES --- p.viii / LIST OF TABLES --- p.xvi / LIST OF ABBREVIATIONS --- p.xvii / CONTENTS --- p.xxi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Conventional Magnetic Resonance Imaging --- p.1 / Chapter 1.1.1 --- Basic Principle of Conventional Magnetic Resonance Imaging --- p.1 / Chapter 1.1.2 --- T1 Relaxation --- p.2 / Chapter 1.1.3 --- T2 Relaxation --- p.3 / Chapter 1.2 --- T1rho Magnetic Resonance Imaging --- p.3 / Chapter 1.2.1 --- T1rho Relaxation --- p.3 / Chapter 1.2.2 --- Principle of T1rho Magnetic Resonance Imaging --- p.4 / Chapter 1.2.3 --- Radiofrequency Pulse for T1rho Magnetic Resonance Imaging --- p.5 / Chapter 1.2.4 --- T1rho-weighted Contrast Imaging and Application --- p.10 / Chapter 1.2.5 --- Quantitative T1rho Mapping and Application --- p.11 / Chapter 1.2.6 --- T1rho Dispersion and Application --- p.13 / Chapter 1.3 --- Thesis Overview --- p.14 / Chapter Chapter 2 --- T1rho MRI in brain aging of animal model --- p.19 / Chapter 2.1 --- Introduction --- p.19 / Chapter 2.2 --- Materials and Methods --- p.20 / Chapter 2.2.1 --- Animal Model of Brain Aging --- p.20 / Chapter 2.2.2 --- T1rho Data Acquisition --- p.21 / Chapter 2.2.3 --- T1rho Data Processing --- p.23 / Chapter 2.2.4 --- T1rho Measurement and Statistical Analysis --- p.24 / Chapter 2.3 --- Results --- p.27 / Chapter 2.4 --- Discussion --- p.38 / Chapter 2.5 --- Summary --- p.42 / Chapter Chapter 3 --- T1rho MRI in lumbar disc degeneration of human subjects --- p.43 / Chapter 3.1 --- Introduction --- p.43 / Chapter 3.2 --- Methods --- p.45 / Chapter 3.2.1 --- Subjects --- p.45 / Chapter 3.2.2 --- MR Image Acquisition --- p.46 / Chapter 3.2.2.1 --- T2-weighted MRI --- p.46 / Chapter 3.2.2.2 --- T2 Mapping Imaging --- p.47 / Chapter 3.2.2.3 --- T1rho MRI --- p.47 / Chapter 3.2.3 --- Data Processing --- p.49 / Chapter 3.2.4 --- Data Measurement and Statistical Analysis --- p.49 / Chapter 3.3 --- Results --- p.52 / Chapter 3.3.1 --- Range of T1rho/T2 Values for Discs --- p.52 / Chapter 3.3.2 --- The Relationship between NP T1rho/T2 Values and 8-level Degeneration Grading of Discs --- p.52 / Chapter 3.3.3 --- The Relationship between NP T1rho/T2 Values and 5-level Degeneration Grading of Discs --- p.55 / Chapter 3.3.4 --- The Relationship between AF T1rho/T2 Values and 8-level Degeneration Grading of Discs --- p.58 / Chapter 3.3.5 --- The Relationship between AF T1rho/T2 Values and 8-level Degeneration Grading of Discs --- p.61 / Chapter 3.4 --- Discussion --- p.64 / Chapter 3.5 --- Summary --- p.69 / Chapter Chapter 4 --- T1rho MRI in rat liver fibrosis model induced by CCl4 insult --- p.71 / Chapter 4.1 --- Introduction --- p.71 / Chapter 4.2 --- Materials and Methods --- p.73 / Chapter 4.2.1 --- Animal Preparation --- p.73 / Chapter 4.2.2 --- MR Image Acquisition --- p.74 / Chapter 4.2.2.1 --- T2-weighted MRI --- p.75 / Chapter 4.2.2.2 --- T1rho MRI --- p.75 / Chapter 4.2.3 --- Data Processing --- p.76 / Chapter 4.2.4 --- Data Measurement and Statistical Analysis --- p.78 / Chapter 4.2.5 --- Histology Analysis --- p.79 / Chapter 4.3 --- Results --- p.80 / Chapter 4.3.1 --- T1rho Measurement Reproducibility --- p.80 / Chapter 4.3.2 --- Rat Liver T1rho Values at Different Time Phase --- p.81 / Chapter 4.3.3 --- Relative Rat Liver Signal Intensity on T2WI at Different Time Phase --- p.83 / Chapter 4.3.4 --- Histology Results --- p.84 / Chapter 4.4 --- Discussion --- p.86 / Chapter 4.5 --- Summary --- p.91 / Chapter Chapter 5 --- T1rho MRI in liver of healthy human subjects --- p.93 / Chapter 5.1 --- Introduction --- p.93 / Chapter 5.2 --- Methods --- p.95 / Chapter 5.2.1 --- Subjects --- p.95 / Chapter 5.2.2 --- MR Image Acquisition --- p.96 / Chapter 5.2.2.1 --- T2-weighted MRI --- p.96 / Chapter 5.2.2.2 --- T1rho MRI --- p.97 / Chapter 5.2.3 --- T1rho Data Processing --- p.99 / Chapter 5.2.4 --- T1rho Measurement --- p.100 / Chapter 5.3 --- Results --- p.102 / Chapter 5.3.1 --- T1rho Measurement Reproducibility --- p.105 / Chapter 5.3.2 --- T1rho Value Agreement of the Fasting Status with Post Meal Status --- p.105 / Chapter 5.3.3 --- T1rho Value Agreement for T1rho Maps Constructed by Different Spin-lock Time Points --- p.106 / Chapter 5.3.4 --- T1rho Value Range of Healthy Human Subjects --- p.108 / Chapter 5.4 --- Discussion --- p.108 / Chapter 5.5 --- Summary --- p.113 / Chapter Chapter 6 --- General discussion and further work --- p.115 / References: --- p.119 / LIST OF PUBLICATIONS --- p.138

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.

INTRODUÇÃO: A hérnia de disco lombar (HDL) acomete cerca de 5% dos pacientes com de dor lombar e o tratamento cirúrgico nestes casos é cada vez menos indicado, optando-se, na maior parte dos casos, pelo conservador. Embora o método estabilização lombar (EL) e a estimulação elétrica nervosa transcutânea (TENS) tenham mostrado bons resultados em indivíduos portadores de dor lombar inespecífica, há escassa literatura que tenha verificado a eficácia destes tratamentos isoladamente em sujeitos acometidos por hérnia de disco lombar. OBJETIVO: Comparar a eficácia dos exercícios de estabilização lombar e da TENS na dor, incapacidade funcional, e capacidade de ativação do músculo transverso do abdome (TrA) de indivíduos com hérnia de disco lombar. METODOLOGIA: Participaram da pesquisa 40 indivíduos com idade variando de 25 a 58 anos com dor lombar e hérnia de disco, e foram randomizados em dois grupos: Grupo estabilização lombar (EL) (exercícios específicos para os músculos TrA e multífido lombar(ML)) (n=20) e Grupo TENS (GT) (n=20) que receberam atendimento com corrente de estimulação elétrica nervosa transcutânea. Foram avaliados quanto à dor (Escala Visual Analógica e Questionário McGill de Dor), incapacidade funcional (Índice de Incapacidade de Oswestry), e capacidade de recrutamento do TrA (Unidade de Biofeedback Pressórico-UBP). Os grupos foram tratados em duas sessões semanais com duração de 60 minutos por oito semanas. Cada indivíduo foi avaliado antes e após o tratamento. O nível de significância estabelecido foi de alfa=0,05. RESULTADOS: Após oito semanas, o grupo estabilização lombar mostrou melhora significativa na dor (p < 0,001), incapacidade funcional (p < 0,001), e capacidade de ativação do TrA (p < 0,001). O grupo TENS apresentou diferença estatisticamente significante apenas na dor (p < 0,012). A estabilização foi superior à TENS na melhora na dor (p < 0,001), incapacidade funcional (p < 0,001), e capacidade de ativação do TrA (p < 0,001). CONCLUSÃO: Os resultados indicam que a estabilização é efetiva na melhora da dor, incapacidade funcional, e capacidade da ativação do TrA, e a TENS apenas na dor. A estabilização foi superior à TENS em todas as variáveis / INTRODUCTION: Lumbar disc herniation (LDH) affects about 5% of low back pain (LBP) patients. Surgical treatment in these cases is increasingly less suitable, opting, in most cases, for the conservative. Although lumbar stabilization method and transcutaneous electric nerve stimulation (TENS) have shown good results in patients with nonspecific low back pain, there is scarce literature that has verified the effectiveness of these treatments alone in subjects suffering from lumbar disc herniation.OBJECTIVE: To compare the effectiveness of lumbar stabilization exercises and transcutaneous electrical nerve stimulation (TENS), on pain, functional disability and activation of the transversus abdominis muscle (TrA), in individuals with lumbar disc herniation (LDH). METHODS: This study involved 40 patients (age range 25-58 years) with lumbar disc herniation randomized into two groups: Stabilization group (SG: n=20); which received of stabilization exercises (transversus abdominis and lumbar multifidus muscles) and TENS group (TG: n=20), which received electrotherapy. The following instruments were used: visual analogue pain scale and McGill Pain Questionnaire for pain, Oswestry Disability Index for functional disability, and pressure biofeedback unit (PBU) for ability to contract the TrA. Analyses within and between groups were performed after treatment. Groups underwent 16 sessions, for 60 minutes, twice a week and they were evaluated before and after eight weeks. Significance level was set at alfa= 0.05. RESULTS: After eight weeks, lumbar stabilization group showed significant improvements in pain (p < 0.001), functional disability (p < 0.001), and the ability to contract the TrA (p < 0.001). There were no significant differences in TENS group in terms of disability (p < 0.264) or ability to contract the TrA muscle (p < 0.181), however, improvement in pain was demonstrated (p < 0.012). The stabilization was superior to TENS in terms of improvements in pain (p < 0.001), functional disability (p < 0.001), and ability to contract the TrA (p < 0.001). CONCLUSION: The results indicate that stabilization is effective in improving pain, functional disability, and the ability to contract the TrA in individuals with LDH. In the TENS group, the only improvement after treatment was in terms of pain. Stabilization was superior to TENS in all outcomes

Previous studies have reported that combination of electroacupuncture (EA) and mesenchymal stem/stromal cells (MSC) promoted survival, differentiation and functional recovery in spinal cord-transected rats. In this study, it was examined the therapeutic effects of stem cells from canine exfoliated dental pulp (SCED) combined with EA treatment in dogs with chronic naturally occurred spinal cord injury due to intervertebral disc herniation (IVDH). Dogs were randomly assigned to four experimental groups (n=4 for each group; total of 16 animals): SCED, EA, SCED + EA) and control. Mild increase in the neurological scoring was found in one animal from SCED group (1/4; 2 points gained), one from EA group (1/4; 8 points gained), three from SCED+EA group (3/4; 16 points gained) and one from control group (1/4; 2 points gained). Functional outcome improvements were observed two animals from SCED group (2/4; 3 points gained), two from EA group (2/4; 4 points gained), one from SCED+EA group (1/4; 1 point gained) and two were from control group (2/4; 6 points gained). However no statistical differences were observed. Magnetic resonance imaging (MRI) findings did not suggest improvement comparing pre- and post-treatment within groups, excepted from one animal from SCED group (1/4), and 10 animals from all groups (10/16) presented signs of injury progression in the SCI in post-treatment exam, which could not be associated to the procedures from study, but could be related to the natural evolution of the disease. Limitation such as number of transplanted stem cells, delivery route, injury chronicity and intrinsic variation among naturally spinal cord injured dogs could have influence outcomes negatively. Moreover, canine deciduous exfoliated teeth were easily obtained and SCED were simply isolated, and no mortality followed up 7 month from procedure were observed. / Estudos anteriores demonstraram que a associação da eletroacupuntura e células-tronco mesenquimais/estromais (CTMs) pode promover a sobrevivência e diferenciação das CTMs, assim como recuperação funcional em ratos com transecção da medula espinal. Neste estudo, foram avaliados os efeitos terapêuticos da associação de células-tronco derivadas de polpa de dente decíduo esfoliado de cães (CPDEc) e eletroacupuntura (EAP) em cães com lesão de medula espinhal crônica causada de forma natural por herniação do disco interververtebral. Os cães foram divididos aleatoriamente em quatro grupos experimentais (n=4 para cada grupo; total de 16 animais): CPDEc, EAP, CPDEc+EAP e grupo controle. Foram encontradas pequenas melhoras na pontuação do exame neurológico em um animal do grupo CPDEc (1/4; 2 pontos ganhos), um do grupo EAP (1/4; 8 pontos ganhos), três do grupo CPDEc+EAP (3/4; 16 pontos ganhos) e um do grupo controle (1/4; 2 pontos ganhos). Na avaliação funcional, pequenas melhoras também foram observadas em dois animais do grupo CPDEc (2/4; 3 pontos ganhos), dois do grupo EAP (2/3; 4 pontos ganhos), um do grupo CPDEc+EAP (1/4; 1 ponto ganho) e dois do grupo controle (2/4; 6 pontos ganhos). No entanto, não foram encontradas diferenças estatísticas entre os grupos. Os achados ressonância magnética não sugeriram melhoras comparando os exames pré e pós tratamento entre os grupos, com exceção de um animal do grupo CPDEc (1/4), e 10 animais dentre todos os grupos (10/16) apresentaram sinais de progressão na lesão da medula espinhal, que não puderam ser associados com os procedimentos do estudo, mas podem estar relacionados à progressão natural da doença. Além disso, os dentes decíduos esfoliados foram obtidos facilmente e as CPDEc foram isoladas de forma simples, ademais, não foi observada nenhuma mortalidade foi observada até 7 meses após o procedimento.

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.