This dissertation describes the development, implementation, validation, optimization, and application, of a noninvasive and quantitative method for measuring cerebral blood volume changes with functional magnetic resonance imaging (fMRI) for mapping of neural activity changes. Since its inception over twenty years ago, the field of fMRI has grown in usage, sophistication, range of applications, and impact. Nevertheless it has yet to exploit its full potential regarding, spatiotemporal resolution, signal specificity, and quantifiability of hemodynamic changes. By utilization of a new MR pulse sequence, new concepts of radio frequency pulses, and high magnetic fields (7 T), a novel fMRI method named SS-SI VASO is presented here that overcomes sensitivity limitations of other noninvasive quantitative imaging methods. In order to validate that its signal represents changes in cerebral blood volume without other contaminations, SS-SI VASO is implemented in animal models for a close comparison with established, but invasive methods. A good agreement of blood volume sensitivity has been found with the new method compared to the established ones. After its validation, the SS-SI VASO method and its unprecedented sensitivity was used to localize and quantify hemodynamic changes in applications where conventional oxygenation based fMRI methods are limited. (A) SS-SI VASO was used to investigate biophysical aspects of actively controlled arteries and passive balloon-like veins during activity induced hemodynamic changes. (B) SS-SI VASO was used to provide insights whether the interplay of neural activity and resultant vascular response are the same for tasks that increase neural activity compared to tasks that suppress neural activity. (C) SS-SI VASO was used to calibrate conventional oxygenation based fMRI to quantify local changes in oxygen metabolism. (D) The high sensitivity of SS-SI VASO was further used to obtain sub-millimeter resolutions and estimate activity changes between cortical layers. This enables to address questions not only where the brain is activated but also how and whereby this activity is evoked. The implementation and application of this new SS-SI VASO fMRI method is a major step forward for the field of imaging neuroscience; it demonstrates that the current limitations of fMRI can be even overcome with respect to quantifiability, spatial specificity and distinguishing between vascular and neuronal phenomena.

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Introduction- Exercise-induced plasma volume (PV) expansion is typically associated with an increase in plasma albumin content. Increased hepatic albumin synthesis, a transcriptionally regulated process, is thought to contribute to the increase in albumin content. Objective- We tested the hypothesis that exercise training induces an increase in albumin gene expression in relationship to the increase in PV. Methods and Results- 40 adult male Sprague-Dawley rats weighing between 245-350 grams were randomly assigned to one of four groups: cage control (CC); sham exercise 10 min/day at 48% VO2max (NE); continuous exercise training, 60 min /day at 72% VO2max (LI); and high intensity, intermittent exercise training, 8 bouts of 4 min at 98% VO2max followed by 5 min at 48% VO2max (HI). The training period lasted for two weeks with 12 training sessions with equalized training volumes in the exercise groups. 24 hours after the last training session the rats were anesthetized and a jugular catheter was placed for collecting blood samples during PV determination by a dilution of a labeled-albumin molecule (Texas Red albumin). The liver and red quadriceps (RQ) muscle tissue was then removed, flash frozen, and stored for later analysis. The training protocol produced a significant increase in RQ citrate synthase activity (p < 0.05). PV increased in proportion to the exercise intensity (p < 0.05) averaging 23.6 ± 2.7 ml•kg-1 body weight in the CC group and 26.6 ± 1.3 ml•kg-1 body weight in the HI group. Albumin mRNA expression determined by real time polymerase chain reaction (PCR) increased 2.2 ± 0.1 and 2.9 ± 0.2 fold following LI and HI exercise training, respectively. Conclusion- These data support the hypothesis that, during exercise-induced PV expansion, albumin gene expression is increased and contributes to an increase in plasma albumin content and PV.

Background: Intradialytic hypotension is a potential complication experienced by patients with end-stage renal disease who receive hemodialysis. This complication occurs during the dialysis treatment in 15-30% of all treatments. The multiple comorbidities that exist in hemodialysis patients predispose them to recurrent intradialytic hypotension episodes. Recurrent intradialytic hypotensive episodes can result in negative short-term and long-term clinical consequences. Short-term consequences include complications such as ischemic events (e.g., heart attacks, strokes), clotting of patient dialysis access, or heart rhythm abnormalities. Long-term consequences include end-organ damage, increased cardiovascular morbidity, and a higher mortality rate. Problem Statement: Available nursing interventions used to treat intradialytic hypotension such as decreased dialysis fluid temperature, changes in the calcium and sodium concentrations in the dialysis fluid and oral medication have limited success. Another existing technological intervention called blood volume monitoring shows greater potential success but is currently underutilized. Purpose: The purpose of this literature review is to synthesize current literature on blood volume monitoring technology used to prevent intradialytic hypotension in hemodialysis patients. Methods: A literature review was conducted analyzing pertinent research articles published in the last ten years, in addition to seminal articles. Seventeen articles were retrieved and analyzed that met criteria. Results: Fourteen of the seventeen research studies reached a consensus on the successful use of blood volume monitoring to decrease intradialytic hypotension and the related symptoms. Conclusion: Results of the literature review support the use of blood volume monitoring technology as an effective nursing intervention to prevent intradialytic hypotension in hemodialysis patients.

When performing sepsis diagnosis, the most important preanalytical variable is blood volume. Too little blood increases the risk for false negatives whereas overfilling causes increased risk for false positives. Even though this fact is known, there are case studies showing that in a majority of tests, the taken blood sample volume is not the recommended amount. As previously tried methods have been limited in their ability to tackle the problem this study aimed at creating a technical device to aid healthcare providers with blood volume sample collection. As a base, the double diamond approach by the Design Council was used. This design approach splits up the design process in four distinctly different phases (discover, define, develop, and deliver) all using their own methods to aid the creative process. After completing the discover and define phase it was determined that a non-contact capacitance liquid level sensor could operate as an ideal blood volume sample device. During the development and delivery phase prototypes were created and evaluated. The final results of this work could not give conclusive evidence concerning if a non-contact liquid level sensor could operate as an ideal blood volume collection device. The methodological approach used in this thesis can be used as inspiration for a designer to create a device for a similar or different purpose. Moreover, information from this thesis can also work as reference material to develop a device to perform ideal blood volume sample collection. Such a device would have the potential to be an essential part of the everyday workflow in sample collection from patients with sepsis worldwide and would aid in ensures effective and fast diagnostics.

The historical development, current practice, and the future of interventional neuroradiology are intricately linked to the advancements in the imaging and devices used for neuroendovascular treatments. This thesis explores the advanced imaging potential of the C-arm imaging systems used in the neurointerventional suite and investigates the initial clinical experience with a new flow diverter device to treat the intracranial aneurysms. A cohort of aneurysmal SAH patients who developed delayed cerebral ischaemia (DCI) were prospectively studied with a new parenchymal blood volume (PBV) research protocol C-arm CT examination concurrent with a magnetic resonance (MR) imaging examination that included perfusion and diffusion weighted sequences. Using a robust quantitative volume-of-interest analysis, it was demonstrated that C-arm CT PBV measurements are in agreement with MR-PWI CBV and CBF, and the PBV represents a composite perfusion parameter with both blood-flow (&asymp;60&percnt;) and blood-volume (&asymp;40&percnt;) weightings. Subsequently, using a voxel-wise ROC curve analysis and MR-DWI, it was shown that using optimal thresholds, C-arm CT PBV measurements allow reliable demarcation of the irreversibly infarcted parenchyma. For evaluation of ischaemic parenchyma, the PBV measurements were reliable for moderate-to-severe ischaemia but were prone to underestimate the mild-to-moderate ischaemia. A catalogue of reference mean PBV measurements was then created for various anatomical regions encompassing the whole brain after excluding any locations with ongoing ischaemia or infarction. Next, using an ROI-based analysis of the C-arm CT projection data, steady-state contrast concentration assumption underlying the PBV calculations was investigated. It was demonstrated that for clinical scans, the ideal steady-state assumption is not fully met, however, for a large majority of C-arm CT examinations the temporal characteristics of TDCs closely approximate the expected ideal steady-state. The degree to which the TDC of a C-arm CT scan approximates the ideal steady-state was found to influence the resulting PBV measurements and their agreement to MR-CBV. Moreover, the temporal characteristics of TDCs showed inter-subject variation. Finally, the C-arm CT cross-sectional soft tissue images were demonstrated to be of adequate quality for the assessment of ventricles and for the detection of procedural vessel rupture. These findings advance the understanding of the nature of PBV parameter, establish the optimal PBV thresholds for infarction, provide reference PBV measurements, and highlight the limitations of C-arm CT PBV imaging. The work is of considerable clinical significance and has implications for implementation of C-arm CT PBV imaging in the interventional suite for management of patients with acute brain ischaemia. In regards to the initial clinical experience with the flow diversion treatment of intracranial aneurysms, the procedural, angiographic, and clinical outcomes were studied. Several pertinent technical and clinical issues were highlighted for this new treatment approach. Based on the observations made during this work, a new grading schema was then developed to monitor the angiographic outcomes after flow diversion treatment. Using the angiographic data for patients treated with FD, the new grading schema was demonstrated to be sufficiently sensitive to register gradual aneurysm occlusion and evaluate parent artery patency, with an excellent inter-rater reliability and applicability to various aneurysm morphologies. This work (largest multi-centre series at the time of its publication) informed the interventional neuroradiology community about the safety, efficacy, and outcomes of flow diversion treatment. Additionally, it provided a sensitive and reliable scale to evaluate the angiographic outcomes after flow diversion treatment, in both research and clinical practice.

No description available.

Microvascular lesions of the brain are observed in numerous pathological conditions including Alzheimer's disease (AD). Regional patterns of microvascular abnormality can be characterized using current neuroimaging technologies. When applied to mouse models of human disease, these technologies reveal cerebral vascular patterns and help uncover genotype-to-phenotype relationships. This thesis focuses on the development and testing of techniques for measuring two perfusion-related metrics in mouse brain regions, namely, cerebral blood volume (CBV) and cerebral blood flow (CBF) using micro-computed tomography (micro-CT) and arterial spin labeling (ASL), respectively. The main developments for measurement of CBV have included: refinements to micro-CT specimen preparation; registration of micro-CT images to an MRI anatomical brain atlas; and masking of major vessels to calculate small-vessel CBV (sv-CBV). The development of this micro-CT technique provided reference values of CBV over neuroanatomical brain regions in wildtype mice. A separate study was conducted to assess regional sv-CBV in a mouse model of AD; this study was motivated by the prevalence of microvascular lesions in patients who suffer from AD. Significant regional differences in sv-CBV were found between AD-afflicted mice and controls. The main developments for measurement of CBF have included: design and implementation of accurate ASL slice positioning and optimization of inversion efficiency parameters. The development of this ASL technique provided reference values of CBF over neuroanatomical brain regions in wildtype mice. These techniques for measuring CBV and CBF over mouse brain regions could lead to improved characterization of vascularity in models of neurological diseases.

Microvascular lesions of the brain are observed in numerous pathological conditions including Alzheimer's disease (AD). Regional patterns of microvascular abnormality can be characterized using current neuroimaging technologies. When applied to mouse models of human disease, these technologies reveal cerebral vascular patterns and help uncover genotype-to-phenotype relationships. This thesis focuses on the development and testing of techniques for measuring two perfusion-related metrics in mouse brain regions, namely, cerebral blood volume (CBV) and cerebral blood flow (CBF) using micro-computed tomography (micro-CT) and arterial spin labeling (ASL), respectively. The main developments for measurement of CBV have included: refinements to micro-CT specimen preparation; registration of micro-CT images to an MRI anatomical brain atlas; and masking of major vessels to calculate small-vessel CBV (sv-CBV). The development of this micro-CT technique provided reference values of CBV over neuroanatomical brain regions in wildtype mice. A separate study was conducted to assess regional sv-CBV in a mouse model of AD; this study was motivated by the prevalence of microvascular lesions in patients who suffer from AD. Significant regional differences in sv-CBV were found between AD-afflicted mice and controls. The main developments for measurement of CBF have included: design and implementation of accurate ASL slice positioning and optimization of inversion efficiency parameters. The development of this ASL technique provided reference values of CBF over neuroanatomical brain regions in wildtype mice. These techniques for measuring CBV and CBF over mouse brain regions could lead to improved characterization of vascularity in models of neurological diseases.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.