O processo de envelhecimento é acompanhado por um declínio nas funções cognitivas, principalmente, de funções fluidas ou de processamento. Essas diminuições são pelo menos, em parte, devido a alterações estruturais e funcionais do sistema nervoso central. Uma abordagem para estudar as mudanças funcionais é a medição da utilização metabólica regional da glicose, ou, alternativamente, um parâmetro físico correlacionado ao metabolismo cerebral e à atividade funcional local, como o fluxo sanguíneo cerebral (CBF). Neste contexto, em Imagens por Ressonância Magnética (IRM), a técnica de Marcação dos Spins Arteriais (ASL) surge como uma importante ferramenta não invasiva para análises perfusionais. Seu uso não só permite avaliar a perfusão sanguínea cerebral, gerando mapas quantitativos de CBF, mas também fornecer uma alternativa para estudar a conectividade funcional (FC), um parâmetro importante para descrição da topologia e funcionalidade cerebral. Sessenta e três indivíduos saudáveis, na faixa etária entre dezoito à setenta e dois anos, foram recrutados para participar deste estudo. Análises estatísticas mostram uma diminuição de CBF em várias regiões cerebrais, especialmente nos lobos frontal e temporal, que acompanham o processo de envelhecimento. As medidas de FC foram obtidas em análises por regiões de interesse e teoria de grafos; estas também demostraram uma diminuição, com o avanço da idade, em regiões presentes nos lobos frontal e temporal, mas também relataram um maior número de regiões prejudicadas no lobo parietal. Portanto, usando uma técnica de imagem não invasiva, foi possível observar déficits de CBF além de alterações de aspectos da organização funcional, oferecendo valores quantitativos que podem ajudar na melhor descrição dos efeitos do envelhecimento na hemodinâmica cerebral. / Aging process is accompanied by a decline in cognitive functions foremost comprise fluid or processing-based functions. These decreases are at least partly due to structural and functional deteriorating changes of the central nervous system. One approach to study these functional changes is the measurement of the regional metabolic utilization of glucose, or, alternatively, a physical quantity correlated to cerebral metabolism and local functional activity, such as the cerebral blood flow (CBF). In this context, Arterial spin labeling (ASL) emerges as a noninvasive Magnetic Resonance Imaging (MRI) perfusion technique. Its use not only allows assessing cerebral perfusion, by generating CBF values, but also can provide an alternative to study functional connectivity (FC), which is an important parameter that describes the brain topology and functionality. Sixty-three healthy subjects, from age eighteen to seventy-two years, were recruited to participate in this study. ASL-CBF maps showed a decrease in several brain regions, especially in frontal and temporal lobes that follows aging process. FC measures were assessed with regions of interest (ROI-to-ROI) and graph theory analysis, also showing a decrease in regions present in frontal and temporal lobes, and also more impaired regions in the parietal lobe. Therefore, using a noninvasive imaging technique it was possible to observe CBF deficits besides alteration in aspects on functional organization, offering quantitative values that can help to describe better the aging effects on cerebral hemodynamics.

A presença de redes cerebrais funcionais ativadas durante o repouso é bem conhecida e verificada por diferentes técnicas de imagens, como as Imagens por Ressonância Magnética funcionais (IRMf) baseadas no contraste dependente do nível de oxigenação do sangue (BOLD, Blood Oxygenation Level Dependent). Entretanto, apesar de ser atualmente o método não invasivo convencional para tais estudos, o contraste BOLD é sensível a diferentes parâmetros hemodinâmicos (fluxo sanguíneo cerebral, CBF; volume sanguíneo cerebral e extração de oxigênio), cuja relação não é completamente conhecida em diversas patologias. Por outro lado, o método de Marcação dos Spins Arteriais (ASL) é uma técnica de IRM não invasiva que fornece mapas quantitativos de CBF e pode ser usada para avaliar as redes de repouso. Portanto, o objetivo do presente estudo foi investigar a viabilidade de usar sequências de ASL (pulsada e pseudocontínua), disponíveis para o uso na rotina clínica, para o estudo da conectividade funcional do cérebro em estado de repouso. Imagens de ASL e BOLD, de 23 indivíduos jovens e saudáveis, foram adquiridas em um equipamento de 3T. Após o pré-processamento usual das imagens e cálculos dos mapas de perfusão, CBF e pseudo-BOLD (pBOLD), a partir das imagens de ASL, as redes cerebrais de repouso foram obtidas pela Análise de Componentes Independentes (ICA) e pelo método baseado em semente. Utilizando ICA, a análise em grupo conjunta de pBOLD e BOLD identificou cinco redes: rede de modo padrão (DMN), visual, auditiva, saliência e motora. Quando analisados separadamente, os dados de pBOLD mostraram apenas as redes DMN e visual, enquanto os dados de BOLD mostraram também as redes auditiva, saliência, motora, atentiva e frontoparietais direita e esquerda. Para ambas as análises, comparações entre as redes de pBOLD e BOLD apresentaram similaridades de moderadas a altas. Entretanto, nenhuma rede foi observada utilizando os dados de perfusão e CBF. Já as análises baseadas em sementes mostraram correlações significativas, para as séries temporais de pBOLD e CBF, entre regiões que constituem algumas redes de repouso conhecidas (DMN, visual, sensorial-motora, atentiva e frontoparietal). Os valores obtidos para a força das conectividades nas redes de pBOLD e CBF se correlacionaram com aqueles obtidos nas redes de BOLD. As diferenças no desempenho de ASL e BOLD devem-se a uma combinação de fatores, como relação sinal ruído e resolução temporal. Além disso, a natureza dos sinais não é a mesma. O sinal BOLD é influenciado por diferentes parâmetros fisiológicos e é proveniente principalmente de grandes veias; enquanto o sinal de ASL é proveniente da rede de capilares, fornecendo especificidade espacial mais alta para a atividade neuronal, além de permitir a quantificação do CBF, que está relacionado mais diretamente ao metabolismo cerebral. Portanto, o presente estudo mostrou ser possível investigar a conectividade funcional do cérebro no estado de repouso com uma sequência comercial, apesar das limitações técnicas da ASL. Além disso, as séries temporais de CBF e BOLD refletem diferentes aspectos do cérebro em repouso, fornecendo informações complementares dos seus processos fisiológicos / The presence of functional brain networks activated during resting state is well known and has been verified by different imaging techniques, such as the functional Magnetic Resonance Imaging (fMRI) based on the Blood Oxygenation Level-Dependent (BOLD) contrast. Although BOLD-fMRI is currently the conventional non invasive method for such studies, BOLD contrast is sensitive to different hemodynamic parameters (Cerebral Blood Flow, CBF; cerebral blood volume and oxygen extraction fraction), whose relationship is not fully understood in several pathologies. In contrast, the Arterial Spin Labeling (ASL) MRI technique is a non invasive tool for CBF quantification and can be used to investigate resting-state networks. Therefore, the goal of the present study was to investigate the feasibility of using ASL sequences (pulsed and pseudocontinuous), available for clinical routine use, for the study of functional connectivity of the brain at rest. ASL and BOLD images of 23 healthy young subjects were acquired in a 3T machine. After the usual image pre-processing and quantification of perfusion, CBF and pseudo-BOLD (pBOLD) maps, from ASL images, resting-state brain networks were obtained by Independent Component Analysis (ICA) and a seed-based method. Five networks were identified in a joint analysis of pBOLD and BOLD: Default Mode Network (DMN), visual, auditory, salience, and motor. When analyzed separately, pBOLD showed only the DMN and visual networks, while BOLD also showed auditory, salience, motor, attentive, right and left frontoparietal networks. For both analyses, comparisons between pBOLD and BOLD networks showed from moderate to high similarities. However, no network was obtained from perfusion and CBF time series. Seed-based analysis showed significant correlations, for pBOLD e CBF time series, between regions that integrate some known networks (DMN, visual, sensorial-motor, attentive and frontoparietal). Functional connectivity strength obtained from pBOLD and CBF networks correlated with the ones from BOLD data. Differences in performance with ASL and BOLD are due to a combination of factors, such as SNR and temporal resolution. Moreover, the nature of the signals is not the same. BOLD signal is influenced by different physiologic parameters and comes mainly from large veins; while ASL signal comes from small capillaries, providing higher spatial specificity regarding neural activity, in addition to allow the quantification of CBF, which is closer related to the cerebral metabolism. In conclusion, the present study showed the feasibility of investigating functional connectivity of the brain at rest using a commercial ASL sequence, even with its technical limitations. Moreover, CBF and BOLD time series reflect different aspects of the resting-state brain and provide complementary information on its physiological processes

A esquizofrenia é um transtorno psiquiátrico incapacitante que afeta estimadamente 1% da população mundial. Delírios, alucinações, desorganização de pensamento e prejuízo cognitivo são as principais marcas da Esquizofrenia. Fisiologicamente, além de anormalidades funcionais e estruturais, alterações na atividade neuronal são reportadas. Como a atividade neuronal possui uma relação direta com o fluxo sanguíneo cerebral (CBF, Cerebral Blood Flow), a técnica de Imagens por Ressonância Magnética, denominada Marcação dos Spins Arteriais (ASL, Arterial Spin Labeling), que permite a obtenção de mapa quantitativo de CBF, é uma ferramenta útil na avaliação funcional cerebral. Além disso, a ASL pode ser usada na avaliação da conectividade funcional, que é eficiente na investigação de rupturas funcionais entre as regiões do cérebro. Comparando com um grupo de sujeitos saudáveis, os pacientes com esquizofrenia, recrutados no Hospital das Clínicas de Ribeirão Preto (HCFMRP), apresentaram redução de CBF em regiões bilaterais do polo frontal e giro frontal superior, giro frontal medial direito, partes triangular e opercular do giro frontal inferior direito, divisão posterior do giro supramarginal esquerdo, divisão superior e inferior do córtex occipital lateral esquerdo e polo occipital. A conectividade funcional, avaliada por três diferentes métodos (baseado em semente, análise de componentes independentes e teoria dos grafos), se apresentou prejudicada em regiões envolvendo funções motoras, sensoriais e cognitivas dos pacientes. Portanto, utilizando uma técnica de imagem completamente não invasiva, foi possível observar déficits de CBF e alterações na organização funcional do cérebro de pacientes com esquizofrenia, relacionados com os sintomas e características da psicopatologia. / Schizophrenia is a disabling psychiatric disorder that affects around 1% of the population worldwide. Delusions, hallucinations, disorganized thought, and cognitive deficits are the main features of schizophrenia. Physiologically, in addition to functional and structural abnormalities, changes in neuronal activity are reported. Since the Cerebral Blood Flow (CBF) is directly related with neuronal activity, the Magnetic Resonance Imaging (MRI) technique called Arterial Spin Labeling (ASL), which allows the quantification of CBF, is a useful tool in brain functional evaluation. In addition, ASL can be used to assess functional connectivity, which is efficient in investigating functional impairment between regions of the brain. Patients with Schizophrenia, recruited at the Clinical Hospital (HCFMRP), presented a reduction of CBF in bilateral regions of the frontal pole and superior frontal gyrus, right medial frontal gyrus, triangular and opercular parts of the right inferior frontal gyrus, posterior division of left supramarginal gyrus, superior and inferior division of left lateral occipital cortex and occipital pole. Functional connectivity, assessed by three different methods (seed-based, independent component analysis and graph theory), was impaired in regions involving patients\' motor, sensory and cognitive functions. Therefore, using a noninvasive imaging technique, it was possible to observe CBF deficits and alterations in the functional organization of the brain of schizophrenia patients, related to the symptoms and characteristics of the psychopathology.

The high prevalence and mortality of cerebrovascular disease has led to the development of several methods to measure cerebral blood flow (CBF) in vivo. One of these, arterial spin labeling (ASL), is a quantitative magnetic resonance imaging (MRI) technique with the advantage that it is completely non-invasive. The quantification of CBF using ASL requires correction for a tissue specific parameter called the brain-blood partition coefficient (BBPC). Despite regional and inter-subject variability in BBPC, the current recommended implementation of ASL uses a constant assumed value of 0.9 mL/g for all regions of the brain, all subjects, and even all species. The purpose of this dissertation is 1) to apply ASL to a novel population to answer an important clinical question in the setting of Down syndrome, 2) to demonstrate proof of concept of a rapid technique to measure BBPC in mice to improve CBF quantification, and 3) to translate the correction method by applying it to a population of healthy canines using equipment and parameters suitable for use with humans. Chapter 2 reports the results of an ASL study of adults with Down syndrome (DS). This population is unique for their extremely high prevalence of Alzheimer’s disease (AD) and very low prevalence of systemic cardiovascular risk factors like atherosclerosis and hypertension. This prompted the hypothesis that AD pathology would lead to the development of perfusion deficits in people with DS despite their healthy cardiovascular profile. The results demonstrate that perfusion is not compromised in DS participants until the middle of the 6th decade of life after which measured global CBF was reduced by 31% (p=0.029). There was also significantly higher prevalence of residual arterial signal in older participants with DS (60%) than younger DS participants (7%, p = 0.005) or non-DS controls (0%, p < 0.001). This delayed pattern of perfusion deficits in people with DS differs from observations in studies of sporadic AD suggesting that adults with DS benefit from an improved cardiovascular risk profile early in life. Chapter 3 introduces calibrated short TR recovery (CaSTRR) imaging as a rapid method to measure BBPC and its development in mice. This was prompted by the inability to account for potential changes in BBPC due to age, brain atrophy, or the accumulation of hydrophobic A-β plaques in the ASL study of people with DS in Chapter 2. The CaSTRR method reduces acquisition time of BBPC maps by 87% and measures a significantly higher BBPC in cortical gray matter (0.99±0.04 mL/g,) than white matter in the corpus callosum (0.93±0.05 mL/g, p=0.03). Furthermore, when CBF maps are corrected for BBPC, the contrast between gray and white matter regions of interest is improved by 14%. This demonstrates proof of concept for the CaSTRR technique. Chapter 4 describes the application of CaSTRR on healthy canines (age 5-8 years) using a 3T human MRI scanner. This represents a translation of the technique to a setting suitable for use with a human subject. Both CaSTRR and pCASL acquisitions were performed and further optimization brought the acquisition time of CaSTRR down to 4 minutes which is comparable to pCASL. Results again show higher BBPC in gray matter (0.83 ± 0.05 mL/g) than white matter (0.78 ± 0.04 mL/g, p = 0.007) with both values unaffected by age over the range studied. Also, gray matter CBF is negatively correlated with age (p = 0.003) and BBPC correction improved the contrast to noise ratio by 3.6% (95% confidence interval = 0.6 – 6.5%). In summary, the quantification of ASL can be improved using BBPC maps derived from the novel, rapid CaSTRR technique.

Arterial spin labeling is a completely non-invasive method for blood-flow measurement techniques. Alzheimer's disease pathology includes microvascular abnormalities in addition to practically all risk factors having a vascular component that reduces cerebral perfusion. Hemodynamic parameters of cerebral blood flow and arterial transit time were estimated via single-compartment modeling of pseudo continuous arterial spin labeling data and neurocognitive test scores (Alzheimer's disease assessment scale and mini-mental state examination) were compared between a group of healthy (N=20) and early Alzheimer's disease (N=25) subjects before and six months after the Alzheimer's subjects began treatment with cholinesterase inhibitors. The early Alzheimer's group showed improved CBF after 6 months' treatment in every Alzheimer's-prone region except the medial and lateral temporal lobes. No difference in arterial transit time was found between groups, indicating that the pathophysiological process causing hypoperfusion in Alzheimer's disease may differ from vascular dementia.

Arterial spin labeling is a completely non-invasive method for blood-flow measurement techniques. Alzheimer's disease pathology includes microvascular abnormalities in addition to practically all risk factors having a vascular component that reduces cerebral perfusion. Hemodynamic parameters of cerebral blood flow and arterial transit time were estimated via single-compartment modeling of pseudo continuous arterial spin labeling data and neurocognitive test scores (Alzheimer's disease assessment scale and mini-mental state examination) were compared between a group of healthy (N=20) and early Alzheimer's disease (N=25) subjects before and six months after the Alzheimer's subjects began treatment with cholinesterase inhibitors. The early Alzheimer's group showed improved CBF after 6 months' treatment in every Alzheimer's-prone region except the medial and lateral temporal lobes. No difference in arterial transit time was found between groups, indicating that the pathophysiological process causing hypoperfusion in Alzheimer's disease may differ from vascular dementia.

A presença de redes cerebrais funcionais ativadas durante o repouso é bem conhecida e verificada por diferentes técnicas de imagens, como as Imagens por Ressonância Magnética funcionais (IRMf) baseadas no contraste dependente do nível de oxigenação do sangue (BOLD, Blood Oxygenation Level Dependent). Entretanto, apesar de ser atualmente o método não invasivo convencional para tais estudos, o contraste BOLD é sensível a diferentes parâmetros hemodinâmicos (fluxo sanguíneo cerebral, CBF; volume sanguíneo cerebral e extração de oxigênio), cuja relação não é completamente conhecida em diversas patologias. Por outro lado, o método de Marcação dos Spins Arteriais (ASL) é uma técnica de IRM não invasiva que fornece mapas quantitativos de CBF e pode ser usada para avaliar as redes de repouso. Portanto, o objetivo do presente estudo foi investigar a viabilidade de usar sequências de ASL (pulsada e pseudocontínua), disponíveis para o uso na rotina clínica, para o estudo da conectividade funcional do cérebro em estado de repouso. Imagens de ASL e BOLD, de 23 indivíduos jovens e saudáveis, foram adquiridas em um equipamento de 3T. Após o pré-processamento usual das imagens e cálculos dos mapas de perfusão, CBF e pseudo-BOLD (pBOLD), a partir das imagens de ASL, as redes cerebrais de repouso foram obtidas pela Análise de Componentes Independentes (ICA) e pelo método baseado em semente. Utilizando ICA, a análise em grupo conjunta de pBOLD e BOLD identificou cinco redes: rede de modo padrão (DMN), visual, auditiva, saliência e motora. Quando analisados separadamente, os dados de pBOLD mostraram apenas as redes DMN e visual, enquanto os dados de BOLD mostraram também as redes auditiva, saliência, motora, atentiva e frontoparietais direita e esquerda. Para ambas as análises, comparações entre as redes de pBOLD e BOLD apresentaram similaridades de moderadas a altas. Entretanto, nenhuma rede foi observada utilizando os dados de perfusão e CBF. Já as análises baseadas em sementes mostraram correlações significativas, para as séries temporais de pBOLD e CBF, entre regiões que constituem algumas redes de repouso conhecidas (DMN, visual, sensorial-motora, atentiva e frontoparietal). Os valores obtidos para a força das conectividades nas redes de pBOLD e CBF se correlacionaram com aqueles obtidos nas redes de BOLD. As diferenças no desempenho de ASL e BOLD devem-se a uma combinação de fatores, como relação sinal ruído e resolução temporal. Além disso, a natureza dos sinais não é a mesma. O sinal BOLD é influenciado por diferentes parâmetros fisiológicos e é proveniente principalmente de grandes veias; enquanto o sinal de ASL é proveniente da rede de capilares, fornecendo especificidade espacial mais alta para a atividade neuronal, além de permitir a quantificação do CBF, que está relacionado mais diretamente ao metabolismo cerebral. Portanto, o presente estudo mostrou ser possível investigar a conectividade funcional do cérebro no estado de repouso com uma sequência comercial, apesar das limitações técnicas da ASL. Além disso, as séries temporais de CBF e BOLD refletem diferentes aspectos do cérebro em repouso, fornecendo informações complementares dos seus processos fisiológicos / The presence of functional brain networks activated during resting state is well known and has been verified by different imaging techniques, such as the functional Magnetic Resonance Imaging (fMRI) based on the Blood Oxygenation Level-Dependent (BOLD) contrast. Although BOLD-fMRI is currently the conventional non invasive method for such studies, BOLD contrast is sensitive to different hemodynamic parameters (Cerebral Blood Flow, CBF; cerebral blood volume and oxygen extraction fraction), whose relationship is not fully understood in several pathologies. In contrast, the Arterial Spin Labeling (ASL) MRI technique is a non invasive tool for CBF quantification and can be used to investigate resting-state networks. Therefore, the goal of the present study was to investigate the feasibility of using ASL sequences (pulsed and pseudocontinuous), available for clinical routine use, for the study of functional connectivity of the brain at rest. ASL and BOLD images of 23 healthy young subjects were acquired in a 3T machine. After the usual image pre-processing and quantification of perfusion, CBF and pseudo-BOLD (pBOLD) maps, from ASL images, resting-state brain networks were obtained by Independent Component Analysis (ICA) and a seed-based method. Five networks were identified in a joint analysis of pBOLD and BOLD: Default Mode Network (DMN), visual, auditory, salience, and motor. When analyzed separately, pBOLD showed only the DMN and visual networks, while BOLD also showed auditory, salience, motor, attentive, right and left frontoparietal networks. For both analyses, comparisons between pBOLD and BOLD networks showed from moderate to high similarities. However, no network was obtained from perfusion and CBF time series. Seed-based analysis showed significant correlations, for pBOLD e CBF time series, between regions that integrate some known networks (DMN, visual, sensorial-motor, attentive and frontoparietal). Functional connectivity strength obtained from pBOLD and CBF networks correlated with the ones from BOLD data. Differences in performance with ASL and BOLD are due to a combination of factors, such as SNR and temporal resolution. Moreover, the nature of the signals is not the same. BOLD signal is influenced by different physiologic parameters and comes mainly from large veins; while ASL signal comes from small capillaries, providing higher spatial specificity regarding neural activity, in addition to allow the quantification of CBF, which is closer related to the cerebral metabolism. In conclusion, the present study showed the feasibility of investigating functional connectivity of the brain at rest using a commercial ASL sequence, even with its technical limitations. Moreover, CBF and BOLD time series reflect different aspects of the resting-state brain and provide complementary information on its physiological processes

O processo de envelhecimento é acompanhado por um declínio nas funções cognitivas, principalmente, de funções fluidas ou de processamento. Essas diminuições são pelo menos, em parte, devido a alterações estruturais e funcionais do sistema nervoso central. Uma abordagem para estudar as mudanças funcionais é a medição da utilização metabólica regional da glicose, ou, alternativamente, um parâmetro físico correlacionado ao metabolismo cerebral e à atividade funcional local, como o fluxo sanguíneo cerebral (CBF). Neste contexto, em Imagens por Ressonância Magnética (IRM), a técnica de Marcação dos Spins Arteriais (ASL) surge como uma importante ferramenta não invasiva para análises perfusionais. Seu uso não só permite avaliar a perfusão sanguínea cerebral, gerando mapas quantitativos de CBF, mas também fornecer uma alternativa para estudar a conectividade funcional (FC), um parâmetro importante para descrição da topologia e funcionalidade cerebral. Sessenta e três indivíduos saudáveis, na faixa etária entre dezoito à setenta e dois anos, foram recrutados para participar deste estudo. Análises estatísticas mostram uma diminuição de CBF em várias regiões cerebrais, especialmente nos lobos frontal e temporal, que acompanham o processo de envelhecimento. As medidas de FC foram obtidas em análises por regiões de interesse e teoria de grafos; estas também demostraram uma diminuição, com o avanço da idade, em regiões presentes nos lobos frontal e temporal, mas também relataram um maior número de regiões prejudicadas no lobo parietal. Portanto, usando uma técnica de imagem não invasiva, foi possível observar déficits de CBF além de alterações de aspectos da organização funcional, oferecendo valores quantitativos que podem ajudar na melhor descrição dos efeitos do envelhecimento na hemodinâmica cerebral. / Aging process is accompanied by a decline in cognitive functions foremost comprise fluid or processing-based functions. These decreases are at least partly due to structural and functional deteriorating changes of the central nervous system. One approach to study these functional changes is the measurement of the regional metabolic utilization of glucose, or, alternatively, a physical quantity correlated to cerebral metabolism and local functional activity, such as the cerebral blood flow (CBF). In this context, Arterial spin labeling (ASL) emerges as a noninvasive Magnetic Resonance Imaging (MRI) perfusion technique. Its use not only allows assessing cerebral perfusion, by generating CBF values, but also can provide an alternative to study functional connectivity (FC), which is an important parameter that describes the brain topology and functionality. Sixty-three healthy subjects, from age eighteen to seventy-two years, were recruited to participate in this study. ASL-CBF maps showed a decrease in several brain regions, especially in frontal and temporal lobes that follows aging process. FC measures were assessed with regions of interest (ROI-to-ROI) and graph theory analysis, also showing a decrease in regions present in frontal and temporal lobes, and also more impaired regions in the parietal lobe. Therefore, using a noninvasive imaging technique it was possible to observe CBF deficits besides alteration in aspects on functional organization, offering quantitative values that can help to describe better the aging effects on cerebral hemodynamics.

A novel non-invasive imaging method of unique k-space trajectory named “3D center-out EPI with cylindrical encoding” was developed and implemented for fast imaging of the human brain. The method based on a variant of 3D hybrid EPI combines advantages of the Cartesian and the radial encoding to achieve ultra-short echo time independent of spatial resolution and reasonably short echo train length yielding a quality image of high signal-to-noise ratio. Unlike rectilinear sampling, the method offers not only less motion and flow artifacts but enables also the undersampling capability. As a result, the method improves temporal resolution by shortening the measurement time. Nonetheless, artifacts induced from long-term drifts of the magnetic field as well as geometrical distortions caused by B0 inhomogeneity were removed with the average phase of the k-space center lines and an additional field map scan. Compared to other cylindrical k-space trajectories based on echo-planar imaging, which lead to progressively increasing echo time upon increasing the spatial resolution, the proposed method offers more benefits. As a significant application, imaging readout of the novel technique was applied to true 3D cine imaging which was later used in the combination of pseudo-continuous arterial spin labeling module in order to track a short arterial spin labeling (ASL) bolus of well-defined length along the fast passage through the large vessel compartment of the brain. Parametric maps of ASL signal change, estimated time-to-peak and ASL bolus width were extracted in order to characterize the macrovascular compartments of the brain-feeding arteries. Consequently, bolus dispersion within a single arterial branch was also assessed.

Die magnetische Blutbolusmarkierung (Spin-Labeling) ermöglicht die nichtinvasive quantitative Messung des Blutflusses im Gewebe. Beim Spin-Labeling wird arterielles Blut durch Radiofrequenzpulse magnetisch markiert und der Transport der Markierung MR-tomographisch gemessen. Am Modell einer unter physiologischen Bedingungen perfundierten extrakorporalen Schweineniere konnte die Quantifizierbarkeit der Messmethode nachgewiesen werden. In einer Studie an 36 Hirntumorpatienten wurde das Verfahren mit der kontrastmittelbasierten First-Pass-Bolus-Methode zur nicht-quantitativen Perfusionsmessung verglichen. Es zeigte sich eine sehr gute Übereinstimmung zwischen beiden Methoden, der lineare Korrelationskoeffizient des relativen Blutflusses in der Tumorregion lag bei R=0,83. Die mittels Spin-Labeling ermittelten Absolutwerte des Blutflusses spielen bei der Beurteilung des Tumorgrades eine untergeordnete Rolle, da die mittlere Perfusion individuell sehr verschieden ist. Ein zweiter Anwendungsbereich für das Spin-Labeling ist die Darstellung großer Arterien. Spin-Labeling ermöglicht die nichtinvasive dynamische Angiographie (Dynamische Spin-Labeling-Angiographie - DSLA). Analog zur digitalen Subtraktionsangiographie kann damit der Einstromvorgang des Blutes in den Gefäßbaum zeitaufgelöst gemessen werden, jedoch mit wesentlich höherer zeitlicher Auflösung und frei wählbarer Projektionsrichtung. In einer Studie an 18 Patienten mit einseitigen Carotisstenosen wurden die Zeitdifferenzen der Anflutung der zerebralen Gefäße zwischen der betroffenen und der nicht stenosierten Seite bestimmt. Die im Carotis-Siphon gemessenen Zeitdifferenzen korrelieren signifikant mit dem Stenosegrad, steigen aber erst ab einer Lumeneinengung oberhalb von 80 Prozent deutlich an. Im Vergleich zu den etablierten Methoden werden die Möglichkeiten und Grenzen der DSLA dargestellt. / Arterial spin labeling methods allow to determine quantitative tissue blood flow values noninvasively. Arterial blood is labelled by an inversion pulse and the distribution of this intrinsic tracer is measured using magnetic resonance imaging. Experiments using an extra corporal in-vitro porcine kidney in a MR compatible set-up were carried out to determine the accuracy of blood flow values calculated from arterial spin labeling measurements. In a study of 36 brain tumor patients, spin labeling was compared to non-quantitative contrast-enhanced dynamic susceptibility-weighted perfusion imaging. Relative blood flow values determined with both methods were in good agreement, the linear regression coefficient in the tumor region was R=0.83. Due to the variable individual perfusion state, quantitative blood flow values determined using spin labeling play a minor role in the assessment of tumor grade. Application of spin labeling to angiography of major arteries was investigated. Dynamic spin labeling angiography (DSLA) sequences were implemented and tested on a clinical scanner. This technique allows time-resolved depiction of blood flow in large vessels with very high temporal resolution. As opposed to digital subtraction angiography, the method allows arbitrary projection directions. In a study, 18 patients with one-sided carotid stenoses were examined. In these patients the time differences of blood bolus arrival at both hemispheres were determined. Time differences measured in the carotid siphon show a significant correlation with the degree of stenosis. However, a clear increase is not seen until 80% narrowing of a carotid. Possibilities and limitations of the DSLA method are discussed in comparison to established techniques.