Abstract Magnetic resonance imaging (MRI) provides important information about structural and biochemical changes in organs. MRI is also an effective imaging method for the evaluation of spinal disorders. However, many of its potential applications - particularly diffusion imaging - have not yet been thoroughly explored. The purpose of this study was to determine the MRI-detectable changes in the intervertebral disc after trauma and to test the feasibility of diffusion-weighted MR imaging of the intervertebral discs. A minipig model was used in the experimental study to determine the MRI changes in the intervertebral disc after peripheral annular lesions in different time frames. Three of eight discs with experimental annular lesions had a normal annular appearance in MRI. Annular lesions, when detectable, were manifested as a bulging of the disc or as a high-intensity zone (HIZ) inside the annulus. Either the signal intensity or the area of bright signal intensity in the nucleus had nearly always decreased after one month, but they were still detectable even in cases where no signs of annular trauma could be seen in the MR images. The histology of HIZ is presented for the first time: clusters of nuclear cells and disorganized granulation tissue with capillaries were detected in the HIZ area. Fourteen patients 8 to 21 years of age with histories of vertebral fracture at least one year previously and 14 asymptomatic healthy control subjects 8 to 22 years of age were studied by MRI. In these young people a vertebral fracture, especially with end-plate injury, proved to be a notable risk factor for initiating disc degeneration. The apparent diffusion coefficients (ADCs) of the thoracolumbar intervertebral discs were determined in three orthogonal directions in 18 healthy young volunteers aged 8-22 years. The ADCs were also determined in 10 young patients with previous vertebral fractures, and clear decreases were found in the ADCx and ADCy directions, but in the ADCz direction values had not changed significantly as compared to the values in the controls. The most marked changes were observed in the degenerated discs, followed by those in the discs with a normal signal intensity adjacent to the primary trauma area. Diffusion-weighted MR imaging affords a useful tool for evaluating disc diseases in the early phases. Additionally, 37 adult volunteers without back symptoms were studied by MRI and by magnetic resonance angiography (MRA) and it was found that the status of the lumbar arteries significantly explained the diffusion values in the lumbar intervertebral discs. The correlation between disc degeneration and diffusion was mostly linear, but not significant.

By sensitising the magnetic resonance signal to the diffusion of water molecules in tissue, diffusion-weighted magnetic resonance imaging provides a means of assessing tumour microstructure non-invasively. Such measurements have the potential to provide important information about tumour development and the response of tumours to treatment, but the way in which different tissue properties affect the diffusion-weighted signal remains unclear. Through simulations, in vivo studies and phantom experiments, this thesis investigates the relationship between the diffusion-weighted signal, the pulse sequence parameters used for acquisition, and microstructural properties of tumours. The use of oscillating gradient pulse sequences on a clinical scanner was investigated initially, with theoretical and practical considerations leading subsequent work to focus on pulsed gradient sequences. The forward problem of predicting the diffusion-weighted signal for given combinations of tissue properties and sequence parameters was addressed numerically through Monte Carlo simulations, focussing on how tumour cell size, intracellular volume fraction and membrane permeability affect the signal. These simulations allowed the sensitivity of the signal to changes in these tissue properties to be investigated, revealing how sensitivity depends on sequence parameters as well as the specific microstructural configuration. By repeating the simulations using the specific sequence parameters used in a clinical and preclinical study, the sensitivity of the implemented protocols was assessed, and linked to the experimental findings. The preclinical study illustrated the importance of the diffusion time in determining the sensitivity to treatment-induced changes in tumours, with larger post-treatment signal changes observed at longer diffusion times. These trends were qualitatively reflected in the sensitivity analysis derived from the simulations. Finally, the inverse problem of estimating microstructural properties from the diffusion-weighted signal was addressed using a physical phantom designed as a simple mimic of tumour tissue. By fitting a biophysical model to the diffusion data, the size and volume fraction of the approximately spherical 'cells' were estimated. The radius was slightly underestimated compared with that determined from independent measurements, the fitted volume fraction was plausible, and parameters were found to be estimated with reasonably good precision.

In dogs with large primary tumors, regional lymph node involvement or evidence of distant metastasis can have worse prognoses and significantly decreased survival. Lymph node size alone has been shown to be insufficient as a predictor for the accurate clinical staging of some canine neoplasia, including oral malignant melanoma. However, regional lymph nodes of the oral cavity, such as the medial retropharyngeal lymph nodes, are difficult to access for routine sampling. Diffusion weighted magnetic resonance imaging (DWI) has demonstrated the ability to differentiate metastatic from inflammatory/benign lymph nodes in clinical studies with human cancer patients through the calculation of quantitative values of diffusion termed apparent diffusion coefficients (ADC). The objective of this exploratory study was to evaluate DWI and ADC as potential future methods for detecting malignant lymph nodes in dogs with naturally occurring disease. We hypothesized that DWI would identify significantly different ADC values between benign and metastatic lymph nodes in a group of canine patients with head or neck disease. Our results demonstrated that two of four observers identified a significant difference between the mean ADC values of the benign and metastatic lymph nodes. When data from all four observers were pooled, the difference between the mean ADC values of the benign and metastatic lymph nodes approached but did not reach significance (P-value: 0.0566). Therefore, our hypothesis was not supported. However, DWI does show promise in its ability to differentiate benign from metastatic lymph nodes, and further studies with increased patient numbers are warranted / Master of Science

The possibility to perform virtual, non-invasive, quantitative, in vivo histological assessments might revolutionize entire fields, among which clinical and cognitive neurosciences. Magnetic Resonance Imaging (MRI) is an ideal non-invasive imaging technique to achieve these goals. Tremendous advancements in the last decades have favored the transition of MRI scanners from “imaging devices” to “measurement devices” (Novikov, 2021), thus capable to yield measurements in physical units, which might be further combined to provide quantities describing histological properties of substrates. A central role in this community endeavor has been played by diffusion-weighted MRI (dMRI), which by measuring the dynamics of spin diffusion, allows inferences on geometrical properties of tissues. Yet, conventional dMRI methodologies suffer from poor specificity. In this thesis, techniques aiming at improving the specificity of microstructural descriptions have been explored in dMRI datasets supporting an increasing level of complexity of the dMRI signal representations. Applications in individuals with different age range, in different populations, and for different MRI scanner fields, have been considered. Firstly, tractography has been combined with Diffusion Tensor Imaging (DTI), an along-tract framework, and morphometry, in the study of the microstructure of the optic radiations in different groups of blind individuals. Secondly, DTI has been combined with Free-Water Imaging (FWI) to monitor the effect of proton-irradiation in a pediatric brain tumor case study. Thirdly, FWI and Diffusion Kurtosis Imaging (DKI) have been combined with an advanced thalamic segmentation framework to study the associations between motor performance and thalamic microstructure in a cohort of individuals affected by Parkinson’s disease. Finally, the largest contribution of this thesis is represented by the adaptation of the Correlation Tensor Imaging - a technique increasing the specificity of DKI harnessing Double Diffusion Encoding previously applied only in preclinical settings - for a clinical 3 T scanner. The ensuing investigation revealed new important insights on the sources of diffusional kurtosis, in particular of the microscopic kurtosis (μK), a component so far neglected by contemporary neuroimaging techniques, which might carry an important clinical role (Alves et al., 2022), and can now be accessed by clinical scanners. In conclusion, strategies to increase the specificity of microstructural descriptions in the brain are presented for different datasets, and their strength and limitations are discussed.

Abstract Magnetic resonance imaging (MRI) provides methods to study the microstructure and functional properties of tissues that can be utilized to acquire information about the degenerative processes in the spine. The purpose of the current study was to evaluate the value of diffusion-weighted MRI and quantification of delayed gadolinium enhancement in assessing intervertebral disc degeneration. An experimental degeneration model was used to evaluate the sensitivity of diffusion-weighted MRI and T2 relaxation time measurements in detecting early degenerative changes in the disc. In six pigs, an annular disc lesion was induced surgically, after which the discs were repeatedly MR imaged for up to eight weeks. T2 relaxation time of the lesioned discs decreased postoperatively, whereas apparent diffusion coefficient (ADC) initially increased, but at eight weeks decreased when compared to the control discs. The value of ADC in degeneration of human discs was evaluated by imaging 228 voluntary middle-aged men. ADC values of the three lowest lumbar intervertebral discs were measured and disc degeneration was visually graded. The reduction in ADC between visually normal and moderately degenerated discs was 4%, whereas severely degenerated discs showed 5% higher ADC values than normal discs. T2 signal intensity of the discs was significantly correlated with the ADC values. Because of a considerable overlap between ADC values of normal and degenerated discs the clinical relevance of the ADC measurements of lumbar intervertebral discs remains questionable. A method to quantify delayed enhancement of the nucleus pulposus after intravenous gadolinium contrast agent injection was developed to evaluate the diffusion of small solutes into the disc. Twenty male volunteers were imaged in order to correlate the measured change in the T1 relaxation rate with visually evaluated degenerative changes. The percentual change of T1 relaxation rate for individual discs was up to 126%, and a positive trend was observed between the delayed enhancement and the disc degeneration grades. In order to study the factors that determine the intensity of delayed enhancement, T1 relaxation rate measurements were further correlated with lumbar artery stenosis, bone marrow changes adjacent to endplates, endplate defects, and ADC of the disc. Lumbar artery stenosis and ADC values of the discs were not correlated with enhancement, while disc space narrowing and the presence of degenerative endplate changes had a strong correlation, suggesting an important role for the endplate in maintaining the integrity of the disc.

Abstract The purpose of this study was to evaluate the role of diminished arterial blood flow in painful disc degeneration. Diffusion in intervertebral discs of 37 asymptomatic adults measured by magnetic resonance imaging (MRI) and their lumbar arterial blood supply measured by magnetic resonance angiography (MRA) correlated significantly. End plate degeneration in intervertebral discs evaluated with MRI was analysed with reference to disc distress evaluated with computed tomography (CT) discography, and a significant correlation between end plate degeneration and disc degeneration was found among 36 low back pain patients. Intradiscal pain caused by discography did not correlate with end plate degeneration. There were significantly more atheromatous plaques in the abdominal aorta among 29 chronic low back pain patients compared to 52 asymptomatic people, especially in the age group under 50 years. Occlusion of lumbar arteries in MRA correlated significantly with disc degeneration in MRI among 113 sciatica patients. Furthermore, the disc degeneration and the occlusion of lumbar arteries were severe among 41 sciatica patients and 41 asymptomatic people. During a three-year follow-up, the occlusion of lumbar arteries in MRA correlated significantly with physical and mental ability measured by a self-efficacy questionnaire at every assessment point (1,2,3 years). Furthermore, the intensity of back pain at 1 year and leg pain at 2 years correlated with the occlusion of lumbar arteries. Re-stenosis of lumbar arteries within 3 years correlated significantly with medical consultations for low back pain, prolonged low back pain and prolonged sciatica during one year before the baseline assessment.

Abstract The goal of this study was to explore preoperative evaluation of patients with intracranial tumours using magnetic resonance imaging (MRI) methods: oedema-attenuated inversion recovery (EDAIR) sequence in low-field MRI, and diffusion-weighted imaging (DWI) and resting-state functional MRI (fMRI) in high-field MRI. The aim was also to increase our knowledge about the effects of brain surgery on eloquent brain cortices using new MRI techniques. The total number of patients in these studies was 50 (24 women). Enhancement of the tumour in ten patients after intravenous administration of gadolinium-based contrast agent in low-field MRI was examined with a new sequence, EDAIR, and compared with more conventionally used partial saturation spin echo sequences. EDAIR may facilitate the perception of small enhancing lesions and is valuable in low-field imaging, where T1-based contrast is inferior to high-field imaging. DWI was performed on 25 patients in order to evaluate the potential of this imaging method to assist in differential diagnosis of intracranial tumours. It was shown that apparent diffusion coefficient values of the tumour and peritumoural oedema produced by DWI were different in benign and malignant tumours. Resting-state blood oxygen level-dependent (BOLD) fMRI was performed on eight patients and ten healthy volunteers to examine if functional sensorimotor areas in the brain could be determined without any task-related activations. It was shown that intracranial tumours do not appear to hamper visualization of the sensorimotor area in resting-state BOLD fMRI when independent component analysis is performed, and this method may be used in preoperative imaging when activation studies cannot be performed. Conventional BOLD fMRI with motor and auditory stimuli was used with seven patients as the effect of brain surgery was studied. The results suggest that resection of a tumour with preoperative oedema probably decreases pressure on the brain and makes the functional cortex transiently more easily detectable in BOLD fMRI. In conclusion, the MRI imaging methods used in this study can give valuable additional information about the tumour, specifically for preoperative imaging and planning for surgery.

No description available.

Introdução: O Stent Carotídeo (SC) surgiu como uma alternativa à cirurgia de endarterectomia para o tratamento de estenose carotídea extracraniana com o objetivo de prevenir o acidente vascular encefálico (AVE). O sucesso do SC depende de estratégias que minimizem o risco de AVE. No início do estudo não existiam estudos randomizados comparando o implante de stent carotídeo com diferentes tipos de proteção cerebral. Objetivos: Testar de forma aleatória a eficácia de dois diferentes princípios de proteção embólica no território carotídeo (Angioguard®) e Mo.Ma), utilizando a ressonância magnética ponderada em Difusão (RM-PD) para detectar novas lesões isquêmicas no encéfalo analisando número, tamanho e localização. Métodos: Sessenta pacientes submetidos ao implante do stent carotídeo (SC), foram alocados aleatoriamente para utilizar filtro distal Angioguard® (30 pacientes) e balão de oclusão proximal Mo.Ma (30 pacientes) desde julho de 2008 a 2011. Todos os pacientes realizaram RM-PD pré e 48 horas pós o SC. Os resultados foram avaliados por neurologista independente e cego ao tipo de proteção cerebral utilizada. Foram acompanhados por um período de pelo menos um ano. Os dados qualitativos foram resumidos em frequências absolutas e relativas (porcentagens) e comparados utilizando o teste quiquadrado com correção de continuidade de Yates ou o teste exato de Fisher. Os dados quantitativos foram expressos em médias e desvio-padrão, e/ou medianas e intervalos interquartis e foram comparadas utilizando o teste t de Student ou não paramétrico de Mann-Whitney. Resultados: Não houve diferença estatisticamente significativa em quanto a antecedentes clínicos ou características das lesões carotídeas entre os grupos, apenas as lesões eram mais calcificadas no grupo Angioguard® (p < 0,01). Não houve diferença entre os grupos quanto a incidência de novas lesões isquêmicas (63,3% do Angioguard® vs 66,7% do Mo.Ma, p = 0,787). Quando presentes, as lesões isquêmicas por pacientes o fizeram em número significativamente menor no grupo Mo.Ma, entre 1 e 43 lesões (mediana = 6), comparado ao grupo AngioguardÒ, entre 1 e 76 lesões (mediana = 10) com p < 0,001. Três pacientes (5%) apresentaram eventos neurológicos em até 30 dias e no seguimento de um ano, 1 paciente teve um infarto agudo do miocárdio. Conclusão: Foram observadas novas lesões isquêmicas cerebrais em mais de 60% dos pacientes que utilizaram os dois dispositivos de proteção cerebral, entretanto houve significativamente menos lesões por paciente no grupo Mo.Ma, com significância estatística p = < 0,001. A maioria das lesões foi pequena < 0,5 mm, e encontradas em território ipsilateral. Não foi observado óbito ou AVE maior no seguimento de pelo menos um ano. / Background: Carotid Stent (CAS) has emerged as an alternative to surgical carotid endarterectomy for the treatment of extracranial carotid stenosis in order to prevent stroke. The success of the CAS depends on estrategies that minimize the risk of stroke. When this study began there were no randomized trial comparing different types of cerebral protection during carotid stenting. Objectives: Randomly test the effectiveness of two different embolic protection principles in carotid artery (Angioguard®) vs Mo.Ma) using diffusion-weighted magnetic resonance imaging (DWI) to detect new ischemic lesions in the brain, analyzing the number, size and location of this new ischemic lesions between groups. Methods: Sixty patients undergoing CAS, were randomly assigned to use distal filter AngioguardÒ (30p) and proximal balloon occlusion Mo.Ma (30p) from July 2008 to July 2011. All patients underwent DWI before and 48 hours after the CAS. The results were evaluated by an independent neuroradiologist blind to the type of cerebral protection used. The patients were followed during at least year. Qualitative data were summarized as absolute and relative frequencies (percentages) and compared using chisquare test with Yates continuity correction or Fisher\'s exact test. Quantitative data were expressed as means and standard deviations, and / or medians and interquartile ranges and were compared using the Student t test or nonparametric Mann-Whitney test. Results: Demographic, clinical and lesion characteristics were not different between the two groups, there were more calcified lesion in the Angioguard® group (p < 0.001). There was no difference between groups regarding the incidence of new ischemic lesions in the Angioguard® group compared to the Mo.Ma group (63.3% vs 66.7% p = 0.787). When present, the number of ischemic cerebral lesions per pacient were in fewer number in the Mo.Ma group (1 to 43 lesions; median = 6) compared to the Angioguard® group (1 to 76 lesions; median = 10) p < 0.001 and this difference was significant. Three patients (5%) had neurological events within 30 days with complete regression of symptoms, and one patient develop an infarction during the first year of follow-up. Conclusions: There were new cerebral ischemic lesions detected by DWI in more than 60% of the patients in both groups, on the other hand there were significantly fewer lesions per patient in those allocated to Mo.Ma as compared to Angioguard® with statistical significance p = 0.001. Most lesions were small < 0.5mm, and localized in ipsilateral territory. There was no death or disabling stroke in at least one year of follow-up.

Introdução: O Stent Carotídeo (SC) surgiu como uma alternativa à cirurgia de endarterectomia para o tratamento de estenose carotídea extracraniana com o objetivo de prevenir o acidente vascular encefálico (AVE). O sucesso do SC depende de estratégias que minimizem o risco de AVE. No início do estudo não existiam estudos randomizados comparando o implante de stent carotídeo com diferentes tipos de proteção cerebral. Objetivos: Testar de forma aleatória a eficácia de dois diferentes princípios de proteção embólica no território carotídeo (Angioguard®) e Mo.Ma), utilizando a ressonância magnética ponderada em Difusão (RM-PD) para detectar novas lesões isquêmicas no encéfalo analisando número, tamanho e localização. Métodos: Sessenta pacientes submetidos ao implante do stent carotídeo (SC), foram alocados aleatoriamente para utilizar filtro distal Angioguard® (30 pacientes) e balão de oclusão proximal Mo.Ma (30 pacientes) desde julho de 2008 a 2011. Todos os pacientes realizaram RM-PD pré e 48 horas pós o SC. Os resultados foram avaliados por neurologista independente e cego ao tipo de proteção cerebral utilizada. Foram acompanhados por um período de pelo menos um ano. Os dados qualitativos foram resumidos em frequências absolutas e relativas (porcentagens) e comparados utilizando o teste quiquadrado com correção de continuidade de Yates ou o teste exato de Fisher. Os dados quantitativos foram expressos em médias e desvio-padrão, e/ou medianas e intervalos interquartis e foram comparadas utilizando o teste t de Student ou não paramétrico de Mann-Whitney. Resultados: Não houve diferença estatisticamente significativa em quanto a antecedentes clínicos ou características das lesões carotídeas entre os grupos, apenas as lesões eram mais calcificadas no grupo Angioguard® (p < 0,01). Não houve diferença entre os grupos quanto a incidência de novas lesões isquêmicas (63,3% do Angioguard® vs 66,7% do Mo.Ma, p = 0,787). Quando presentes, as lesões isquêmicas por pacientes o fizeram em número significativamente menor no grupo Mo.Ma, entre 1 e 43 lesões (mediana = 6), comparado ao grupo AngioguardÒ, entre 1 e 76 lesões (mediana = 10) com p < 0,001. Três pacientes (5%) apresentaram eventos neurológicos em até 30 dias e no seguimento de um ano, 1 paciente teve um infarto agudo do miocárdio. Conclusão: Foram observadas novas lesões isquêmicas cerebrais em mais de 60% dos pacientes que utilizaram os dois dispositivos de proteção cerebral, entretanto houve significativamente menos lesões por paciente no grupo Mo.Ma, com significância estatística p = < 0,001. A maioria das lesões foi pequena < 0,5 mm, e encontradas em território ipsilateral. Não foi observado óbito ou AVE maior no seguimento de pelo menos um ano. / Background: Carotid Stent (CAS) has emerged as an alternative to surgical carotid endarterectomy for the treatment of extracranial carotid stenosis in order to prevent stroke. The success of the CAS depends on estrategies that minimize the risk of stroke. When this study began there were no randomized trial comparing different types of cerebral protection during carotid stenting. Objectives: Randomly test the effectiveness of two different embolic protection principles in carotid artery (Angioguard®) vs Mo.Ma) using diffusion-weighted magnetic resonance imaging (DWI) to detect new ischemic lesions in the brain, analyzing the number, size and location of this new ischemic lesions between groups. Methods: Sixty patients undergoing CAS, were randomly assigned to use distal filter AngioguardÒ (30p) and proximal balloon occlusion Mo.Ma (30p) from July 2008 to July 2011. All patients underwent DWI before and 48 hours after the CAS. The results were evaluated by an independent neuroradiologist blind to the type of cerebral protection used. The patients were followed during at least year. Qualitative data were summarized as absolute and relative frequencies (percentages) and compared using chisquare test with Yates continuity correction or Fisher\'s exact test. Quantitative data were expressed as means and standard deviations, and / or medians and interquartile ranges and were compared using the Student t test or nonparametric Mann-Whitney test. Results: Demographic, clinical and lesion characteristics were not different between the two groups, there were more calcified lesion in the Angioguard® group (p < 0.001). There was no difference between groups regarding the incidence of new ischemic lesions in the Angioguard® group compared to the Mo.Ma group (63.3% vs 66.7% p = 0.787). When present, the number of ischemic cerebral lesions per pacient were in fewer number in the Mo.Ma group (1 to 43 lesions; median = 6) compared to the Angioguard® group (1 to 76 lesions; median = 10) p < 0.001 and this difference was significant. Three patients (5%) had neurological events within 30 days with complete regression of symptoms, and one patient develop an infarction during the first year of follow-up. Conclusions: There were new cerebral ischemic lesions detected by DWI in more than 60% of the patients in both groups, on the other hand there were significantly fewer lesions per patient in those allocated to Mo.Ma as compared to Angioguard® with statistical significance p = 0.001. Most lesions were small < 0.5mm, and localized in ipsilateral territory. There was no death or disabling stroke in at least one year of follow-up.