Application of resting-state fMRI methods to acute ischemic stroke

Diffusion weighted imaging (DWI) and dynamic susceptibility contrast-enhanced (DSC) perfusion-weighted imaging (PWI) are commonly employed in clinical practice and in research to give pathophysiological information for patients with acute ischemic stroke. DWI is thought to roughly reflect the severely damaged infarct core, while DSC-PWI reflects the area of hypoperfusion. The volumetric difference between DWI and DSC-PWI is termed the PWI/DWI-mismatch, and has been suggested as an MRI surrogate of the ischemic penumbra. However, due to the application of a contrast agent, which has potentially severe side-effects (e.g., nephrogenic systemic fibrosis), the DSC-PWI precludes repetitive examinations for monitoring purposes. New approaches are being sought to overcome this shortcoming. BOLD (blood oxygen-level dependent) signal can reflect the metabolism of blood oxygen in the brain and hemodynamics can be assessed with resting-state fMRI. The aim of this thesis was to use resting-state fMRI as a new approach to give similar information as DSC-PWI. This thesis comprises two studies: In the first study (see Chapter 2), two resting-state fMRI methods, local methods which compare low frequency amplitudes between two hemispheres and a k-means clustering approach, were applied to investigate the functional damage of patients with acute ischemic stroke both in the time domain and frequency domain. We found that the lesion areas had lower amplitudes than contralateral homotopic healthy tissues. We also differentiated the lesion areas from healthy tissues using a k-means clustering approach. In the second study (see Chapter 3), time-shift analysis (TSA), which assesses time delays of the spontaneous low frequency fluctuations of the resting-state BOLD signal, was applied to give similar pathophysiological information as DSC-PWI in the acute phase of stroke. We found that areas which showed a pronounced time delay to the respective mean time course were very similar to the hypoperfusion area. In summary, we suggest that the resting-state fMRI methods, especially the time-shift analysis (TSA), may provide comparable information to DSC-PWI and thus serve as a useful diagnostic tool for stroke MRI without the need for the application of a contrast agent

Functional Imaging of Malignant Gliomas with CT Perfusion

The overall survival of patients with malignant gliomas remains dismal despite multimodality treatments. Computed tomography (CT) perfusion is a functional imaging tool for assessing tumour hemodynamics. The goals of this thesis are to 1) improve measurements of various CT perfusion parameters and 2) assess treatment outcomes in a rat glioma model and in patients with malignant gliomas. Chapter 2 addressed the effect of scan duration on the measurements of blood flow (BF), blood volume (BV), and permeability-surface area product (PS). Measurement errors of these parameters increased with shorter scan duration. A minimum scan duration of 90 s is recommended. Chapter 3 evaluated the improvement in the measurements of these parameters by filtering the CT perfusion images with principal component analysis (PCA). From computer simulation, measurement errors of BF, BV, and PS were found to be reduced. Experiments showed that CT perfusion image contrast-to-noise ratio was improved. Chapter 4 investigated the efficacy of CT perfusion as an early imaging biomarker of response to stereotactic radiosurgery (SRS). Using the C6 glioma model, we showed that responders to SRS (surviving \u3e 15 days) had lower relative BV and PS on day 7 post-SRS when compared to controls and non-responders (P \u3c 0.05). Relative BV and PS on day 7 post-SRS were predictive of survival with 92% accuracy. Chapter 5 examined the use of multiparametric imaging with CT perfusion and 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) to identify tumour sites that are likely to correlate with the eventual location of tumour progression. We developed a method to generate probability maps of tumour progression based on these imaging data. Chapter 6 investigated serial changes in tumour volumetric and CT perfusion parameters and their predictive ability in stratifying patients by overall survival. Pre-surgery BF in the non-enhancing lesion and BV in the contrast-enhancing lesion three months after radiotherapy had the highest combination of sensitivities and specificities of ≥ 80% in predicting 24 months overall survival. iv Optimization and standardization of CT perfusion scans were proposed. This thesis also provided corroborating evidence to support the use of CT perfusion as a biomarker of outcomes in patients with malignant gliomas

Respiratory challenge MRI: practical aspects

Respiratory challenge MRI is the modification of arterial oxygen (PaO2) and/or carbon dioxide (PaCO2) concentration to induce a change in cerebral function or metabolism which is then measured by MRI. Alterations in arterial gas concentrations can lead to profound changes in cerebral haemodynamics which can be studied using a variety of MRI sequences. Whilst such experiments may provide a wealth of information, conducting them can be complex and challenging. In this paper we review the rationale for respiratory challenge MRI including the effects of oxygen and carbon dioxide on the cerebral circulation. We also discuss the planning, equipment, monitoring and techniques that have been used to undertake these experiments. We finally propose some recommendations in this evolving area for conducting these experiments to enhance data quality and comparison between techniques

Arterial Spin Labeling Perfusion of the Brain: Emerging Clinical Applications

Arterial spin labeling (ASL) is a magnetic resonance (MR) imaging technique used to assess cerebral blood flow noninvasively by magnetically labeling inflowing blood. In this article, the main labeling techniques, notably pulsed and pseudocontinuous ASL, as well as emerging clinical applications will be reviewed. In dementia, the pattern of hypoperfusion on ASL images closely matches the established patterns of hypometabolism on fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) images due to the close coupling of perfusion and metabolism in the brain. This suggests that ASL might be considered as an alternative for FDG, reserving PET to be used for the molecular disease-specific amyloid and tau tracers. In stroke, ASL can be used to assess perfusion alterations both in the acute and the chronic phase. In arteriovenous malformations and dural arteriovenous fistulas, ASL is very sensitive to detect even small degrees of shunting. In epilepsy, ASL can be used to assess the epileptogenic focus, both in peri- and interictal period. In neoplasms, ASL is of particular interest in cases in which gadolinium-based perfusion is contraindicated (eg, allergy, renal impairment) and holds promise in differentiating tumor progression from benign causes of enhancement. Finally, various neurologic and psychiatric diseases including mild traumatic brain injury or posttraumatic stress disorder display alterations on ASL images in the absence of visualized structural changes. In the final part, current limitations and future developments of ASL techniques to improve clinical applicability, such as multiple inversion time ASL sequences to assess alterations of transit time, reproducibility and quantification of cerebral blood flow, and to measure cerebrovascular reserve, will be reviewed

Multiparametric Imaging and MR Image Texture Analysis in Brain Tumors

Discrimination of tumor from radiation injured (RI) tissues and differentiation of tumor types using noninvasive imaging is essential for guiding surgical and radiotherapy treatments are some of the challenges that clinicians face in the course of treatment of brain tumors. The first objective in this thesis was to develop a method to discriminate between glioblastoma tumor recurrences and radiation injury using multiparametric characterization of the tissue incorporating conventional magnetic resonance imaging signal intensities and diffusion tensor imaging parameters. Our results show significant correlations in the RI that was missing in the tumor regions. These correlations may aid in differentiating between tumor recurrence and RI. The second objective of was to investigate whether texture based image analysis of routine MR images would provide quantitative information that could be used to differentiate between glioblastoma and metastasis. Our results demonstrate that first-order texture feature of standard deviation and second-order texture features of entropy, inertia, homogeneity, and energy show significant differences between the two groups. The third objective was to investigate whether quantitative measurements of tumor size and appearance on MRI scans acquired prior to helical tomotherapy (HT) type whole brain radiotherapy with simultaneous infield boost treatment could be used to differentiate responder and non-responder patient groups. Our results demonstrated that smaller size lesions may respond better to this type of radiation therapy. Measures of appearance provided limited added value over measures of size for response prediction. Quantitative measurements of rim enhancement and core necrosis performed separately did not provide additional predictive value

The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

A number of laboratories and companies are currently exploring the development of integrated imaging systems for magnetic resonance imaging (MRI) and positron emission tomography (PET). Scanners for both preclinical and human research applications are being pursued. In contrast to the widely distributed and now quite mature PET/computed tomography technology, most PET/MRI designs allow for simultaneous rather than sequential acquisition of PET and MRI data. While this offers the possibility of novel imaging strategies, it also creates considerable challenges for acquiring artifact-free images from both modalities. This paper discusses the motivation for developing combined PET/MRI technology, outlines the obstacles in realizing such an integrated instrument, and presents recent progress in the development of both the instrumentation and of novel imaging agents for combined PET/MRI studies. The performance of the first-generation PET/MRI systems is described. Finally, a range of possible biomedical applications for PET/MRI are outlined