Cerebral Blood Flow in Relation to Contralateral Carotid Disease an MRA and TCD Study

AbstractObjective: to describe redistribution of cerebral blood flow in patients with severe internal carotid artery (ICA) stenoses in relation to contralateral ICA disease. Methods: sixty-six patients scheduled for carotid endarterectomy (CEA) were grouped according to severity of contralateral stenosis (<30% [group I]; 30–69% [group II]; 70–99% [group III]; occlusion [group IV]. Transcranial Doppler (TCD) and magnetic resonance angiography (MRA) investigations were performed preoperatively. Results: TCD demonstrated a reversed flow in the contralateral anterior cerebral artery (A1segment) and ophthalmic artery in three-quarters of group IV patients (p <0.0001). Group IV patients also exhibited decreased blood flow velocity in the contralateral middle cerebral artery (p =0.001). MRA showed increased ipsilateral ICA and basilar artery (BA) blood flow volumes (Q-flows) in group IV patients when compared to the other groups (p <0.001). No changes in total Q-flow (ICAs+BA) were found. Conclusions: in patients considered for CEA, the severity of the contralateral ICA disease is an important determinant of the pattern of blood flow redistribution through the anterior communicating pathway and ophthalmic artery. Significant flow redistribution through the posterior communicating pathway occurs especially in patients with contralateral ICA occlusion

Improving Acute Stroke Management with CT Perfusion Imaging: Approaches to Treatment Guidance and Brain Tissue Salvage

CT Perfusion (CTP) provides measurement of perfusion at the capillary level which can be used to characterize tissue viability, and blood-brain-barrier (BBB) compromise. Using CTP, the goals of this research are to: 1) select patients that will benefit from acute stroke treatment, and 2) determine if pre-stroke neuroprotection reduces stroke severity. Chapter two investigates the cerebral blood volume (CBV) parameter in a small acute ischemic stroke (AIS) patient set. Overestimation of the acute CBV defect is caused by incomplete wash-out of the CT contrast due to a shortened CTP acquisition time (“truncation artifact”). In chapter three we examine the prognostic reliability of the acute CBV defect to predict infarct core and penumbra in AIS. We determine that hypervolemia, the “truncation artifact” and recanalization are all important variables which affect the relationship between the acute CBV defect volume and the final infarct volume. Chapter four implements a novel porcine model of ischemic stroke using the transient vasoconstrictor, endothelin-1. Using this model, we show that the CTP-cerebral blood flow (CBF) parameter is as good as MR-DWI for acute infarct core delineation, and the CBF/CBV mismatch may not indicate penumbral tissue in the acute stroke setting. In Chapter five, it we show that vascular integrity measured with the CTP-BBB permeability surface area product (PS) is a strong predictor of sub-acute bleeding in the brain (hemorrhagic transformation). Chapter six shows that different rates of CT contrast extravasation exist for primary intracerebral hemorrhage (ICH) patients with/without the CTA-Spot Sign and/or post-contrast leakage. Furthermore, early rates of extravasation are correlated with sub-acute hematoma expansion. Chapter seven describes the development of an improved, reproducible and survivable rabbit large clot embolic model (RLCEM) of cerebral ischemia for testing treatment options for AIS. We demonstrate that pre-stroke treatment with dipyridamole provides a neurovascular advantage post stroke onset. In summary, the current uses of CTP imaging in acute stroke include: 1) quantifying ischemia to define infarct core and penumbra in AIS, 2) predicting hemorrhagic transformation of AIS, 3) predicting hematoma expansion in primary ICH, and 4) assessing treatment response in animal models of stroke to facilitate new drug development

Clinical advances in cardiovascular magnetic resonace imaging and angiography

Cardiovascular magnetic resonance imaging is an important noninvasive imaging modality for the diagnosis, clinical work‐up and treatment planning in patients suspected for a wide range of cardiovascular pathology. CMR imaging is accurate and reliable, and provides invaluable information to evaluate the cardiovascular system without the need of ionizing radiation. The studies described in this thesis evaluate new CMR imaging techniques in clinical practice and explore the prognostic value of new CMR imaging biomarkers in patients with symptomatic peripheral arterial occlusive disease. New advances and innovations in MR imaging technology improve and further expand the clinical applications of cardiovascular imaging in daily clinical practice. In this thesis, a new, fast free‐breathing 2D delayed‐enhancement MRI sequence is validated and demonstrated to be a reliable tool for detecting myocardial infarction. Furthermore, new technical developments allow single‐injection, three‐station, moving‐table MRA protocol at 3Tesla with similar diagnostic performance when compared to 1.5Tesla. Additionally, submillimeter isotropic voxel acquisition in the lower legs at 1.5Tesla improves the diagnostic accuracy and depicts more open infragenual arterial segments.Additionally, it is demonstrated that new MRI biomarkers as distal aortic pulse wave velocity statistically significantly correlate with stenosis severity in symptomatic patients with peripheral arterial occlusive disease. Finally, we showed that CMR derived biomarkers relating to stenosis severity, aortic stiffness and left ventricular function play a role in prognosis of outcome in patients with symptomatic PAOD. In the future, incorporation of the described new MRI biomarkers in the clinical workup of peripheral arterial occlusive disease may play an important role for full vascular risk assessment and ultimately, patients may benefit in clinical practice.LUMC / Geneeskunde Repositoriu

New Insight into Cerebrovascular Diseases

“Brain circulation is a true road map that consists of large extended navigation territories and a number of unimagined and undiscovered routes.” Dr. Patricia Bozzetto Ambrosi This book combines an update on the review of cerebrovascular diseases in the form of textbook chapters, which has been carefully reviewed by Dr. Patricia Bozzetto Ambrosi, Drs. Rufai Ahmad and Auwal Abdullahi and Dr. Amit Agrawal, high-performance academic editors with extensive experience in neurodisciplines, including neurology, neurosurgery, neuroscience, and neuroradiology, covering the best standards of neurological practice involving basic and clinical aspects of cerebrovascular diseases. Each topic was carefully revised and prepared using smooth, structured vocabulary, plus superb graphics and scientific illustrations. In emphasizing the most common aspects of cerebrovascular diseases: stroke burden, pathophysiology, hemodynamics, diagnosis, management, repair, and healing, the book is comprehensive but concise and should become the standard reference guide for this neurological approach

Analysis of contrast-enhanced medical images.

Early detection of human organ diseases is of great importance for the accurate diagnosis and institution of appropriate therapies. This can potentially prevent progression to end-stage disease by detecting precursors that evaluate organ functionality. In addition, it also assists the clinicians for therapy evaluation, tracking diseases progression, and surgery operations. Advances in functional and contrast-enhanced (CE) medical images enabled accurate noninvasive evaluation of organ functionality due to their ability to provide superior anatomical and functional information about the tissue-of-interest. The main objective of this dissertation is to develop a computer-aided diagnostic (CAD) system for analyzing complex data from CE magnetic resonance imaging (MRI). The developed CAD system has been tested in three case studies: (i) early detection of acute renal transplant rejection, (ii) evaluation of myocardial perfusion in patients with ischemic heart disease after heart attack; and (iii), early detection of prostate cancer. However, developing a noninvasive CAD system for the analysis of CE medical images is subject to multiple challenges, including, but are not limited to, image noise and inhomogeneity, nonlinear signal intensity changes of the images over the time course of data acquisition, appearances and shape changes (deformations) of the organ-of-interest during data acquisition, determination of the best features (indexes) that describe the perfusion of a contrast agent (CA) into the tissue. To address these challenges, this dissertation focuses on building new mathematical models and learning techniques that facilitate accurate analysis of CAs perfusion in living organs and include: (i) accurate mathematical models for the segmentation of the object-of-interest, which integrate object shape and appearance features in terms of pixel/voxel-wise image intensities and their spatial interactions; (ii) motion correction techniques that combine both global and local models, which exploit geometric features, rather than image intensities to avoid problems associated with nonlinear intensity variations of the CE images; (iii) fusion of multiple features using the genetic algorithm. The proposed techniques have been integrated into CAD systems that have been tested in, but not limited to, three clinical studies. First, a noninvasive CAD system is proposed for the early and accurate diagnosis of acute renal transplant rejection using dynamic contrast-enhanced MRI (DCE-MRI). Acute rejection–the immunological response of the human immune system to a foreign kidney–is the most sever cause of renal dysfunction among other diagnostic possibilities, including acute tubular necrosis and immune drug toxicity. In the U.S., approximately 17,736 renal transplants are performed annually, and given the limited number of donors, transplanted kidney salvage is an important medical concern. Thus far, biopsy remains the gold standard for the assessment of renal transplant dysfunction, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The diagnostic results of the proposed CAD system, based on the analysis of 50 independent in-vivo cases were 96% with a 95% confidence interval. These results clearly demonstrate the promise of the proposed image-based diagnostic CAD system as a supplement to the current technologies, such as nuclear imaging and ultrasonography, to determine the type of kidney dysfunction. Second, a comprehensive CAD system is developed for the characterization of myocardial perfusion and clinical status in heart failure and novel myoregeneration therapy using cardiac first-pass MRI (FP-MRI). Heart failure is considered the most important cause of morbidity and mortality in cardiovascular disease, which affects approximately 6 million U.S. patients annually. Ischemic heart disease is considered the most common underlying cause of heart failure. Therefore, the detection of the heart failure in its earliest forms is essential to prevent its relentless progression to premature death. While current medical studies focus on detecting pathological tissue and assessing contractile function of the diseased heart, this dissertation address the key issue of the effects of the myoregeneration therapy on the associated blood nutrient supply. Quantitative and qualitative assessment in a cohort of 24 perfusion data sets demonstrated the ability of the proposed framework to reveal regional perfusion improvements with therapy, and transmural perfusion differences across the myocardial wall; thus, it can aid in follow-up on treatment for patients undergoing the myoregeneration therapy. Finally, an image-based CAD system for early detection of prostate cancer using DCE-MRI is introduced. Prostate cancer is the most frequently diagnosed malignancy among men and remains the second leading cause of cancer-related death in the USA with more than 238,000 new cases and a mortality rate of about 30,000 in 2013. Therefore, early diagnosis of prostate cancer can improve the effectiveness of treatment and increase the patient’s chance of survival. Currently, needle biopsy is the gold standard for the diagnosis of prostate cancer. However, it is an invasive procedure with high costs and potential morbidity rates. Additionally, it has a higher possibility of producing false positive diagnosis due to relatively small needle biopsy samples. Application of the proposed CAD yield promising results in a cohort of 30 patients that would, in the near future, represent a supplement of the current technologies to determine prostate cancer type. The developed techniques have been compared to the state-of-the-art methods and demonstrated higher accuracy as shown in this dissertation. The proposed models (higher-order spatial interaction models, shape models, motion correction models, and perfusion analysis models) can be used in many of today’s CAD applications for early detection of a variety of diseases and medical conditions, and are expected to notably amplify the accuracy of CAD decisions based on the automated analysis of CE images

Diseases of the Brain, Head and Neck, Spine 2020–2023

This open access book offers an essential overview of brain, head and neck, and spine imaging. Over the last few years, there have been considerable advances in this area, driven by both clinical and technological developments. Written by leading international experts and teachers, the chapters are disease-oriented and cover all relevant imaging modalities, with a focus on magnetic resonance imaging and computed tomography. The book also includes a synopsis of pediatric imaging. IDKD books are rewritten (not merely updated) every four years, which means they offer a comprehensive review of the state-of-the-art in imaging. The book is clearly structured and features learning objectives, abstracts, subheadings, tables and take-home points, supported by design elements to help readers navigate the text. It will particularly appeal to general radiologists, radiology residents, and interventional radiologists who want to update their diagnostic expertise, as well as clinicians from other specialties who are interested in imaging for their patient care

Added value of acute multimodal CT-based imaging (MCTI) : a comprehensive analysis

Introduction: MCTI is used to assess acute ischemic stroke (AIS) patients.We postulated that use of MCTI improves patient outcome regardingindependence and mortality.Methods: From the ASTRAL registry, all patients with an AIS and a non-contrast-CT (NCCT), angio-CT (CTA) or perfusion-CT (CTP) within24 h from onset were included. Demographic, clinical, biological, radio-logical, and follow-up caracteristics were collected. Significant predictorsof MCTI use were fitted in a multivariate analysis. Patients undergoingCTA or CTA&amp;CTP were compared with NCCT patients with regards tofavourable outcome (mRS ≤ 2) at 3 months, 12 months mortality, strokemechanism, short-term renal function, use of ancillary diagnostic tests,duration of hospitalization and 12 months stroke recurrence

Oxygen challenge MRI: development of a novel technique and application to acute stroke patients

The treatment of hyperacute ischaemic stroke has been revolutionised by the concept of potentially salvageable tissue – the ‘ischaemic penumbra’. However, current therapeutic practice is to administer thrombolytic therapy with recombinant tissue plasminogen activator after exclusion of intra-cerebral haemorrhage, with ‘time since onset’ used as a surrogate marker for the presence or absence of the ischaemic penumbra. The ability to identify the penumbra on an individual basis would enable bespoke treatment plans on the basis of underlying pathophysiology. The most commonly employed penumbral image technique is multi-modal magnetic resonance imaging (MRI) to identify a region of perfusion-diffusion mismatch. However, this approach remains to be validated. Moreover, a systematic review presented as an appendix to this thesis highlights the marked heterogeneity for its application. This thesis focusses on the development of a novel MRI technique (Oxygen Challenge) and is the first to report findings from human acute ischaemic stroke. The rationale for this technique is that it is sensitive to deoxyhaemoglobin, which is produced as a consequence of oxidative metabolism. It therefore has the potential to discriminate tissue compartments based on metabolic activity. For this study, 35 subjects with acute ischaemic stroke were imaged with transient hyperoxia (Oxygen Challenge) applied during continuous T2*-weighted MRI. Exploratory analyses suggested the following; •Oxygen Challenge precipitates a T2*-weighted signal increase in healthy tissue •This signal increase is partly dependent on the underlying cerebral blood volume, as suggested by univariate and multivariate analyses •In general, higher concentrations of oxygen precipitate greater T2*-weighted signal increases, but oxygen may influence T2*-weighted signal intensity in a bi-modal manner •The signal changes in operationally defined infarct core are attenuated, suggesting a metabolic influence on Oxygen Challenge results •Signal increases in the hyperacute perfusion-diffusion mismatch region were sometimes exaggerated, consistent with increased oxygen extraction fraction. However, small volumes of tissue acquired from only a few subjects limited definitive conclusions in this study •Oxygen Challenge may detect regions of crossed cerebellar diaschsis, although further confirmation is required •Maps of ‘percentage signal change’ allowed rapid evaluation of whole brain Oxygen Challenge data •Improvements in signal-to-noise ratio are required before this technique can be applied in clinical practice. On the basis of these data it is concluded that the technique is encouraging and further validation is warranted

Microvasculature, the Trigeminal System and Migraine

Aims of this thesis In Part I the focus is on experimental models of migraine, that are applied in pharmacological as well as in pathophysiological studies. Calcitonin gene-related peptide is the key neuropeptide in migraine pathophysiology. CGRP is being extensively researched, especially as a novel anti-migraine drug target. In Chapter 3 we review existing experimental models that can be applied to study the effects of the novel CGRP receptor antagonists and the recently developed antibodies directed against CGRP and its receptor. In Chapter 4 we comment on an existing experimental model to demonstrate its limitations with regard to distinguishing between structures important to migraine, like the intracranial part of the middle meningeal artery. In Chapter 5 we describe our experimental trigeminal nerve-mediated vasodilatation model. We developed this model to study trigeminovascular pathophysiological and pharmacological mechanisms of migraine. In Chapter 6 we investigate the effects of the anti-migraine drug sumatriptan with this model, to validate it as a biomarker for studies on future anti-migraine drugs. Besides its direct burden, migraine has recently also been identified as a major independent risk factor for cardiovascular disease. Yet, cross-sectional studies investigating the vascular dysfunction in migraine patients have reported conflicting results. This may relate to the fact that the experimental models used to identify vascular dysfunction were diverse and often limited. Therefore, in Chapter 7 we compared different measures of vascular function to assess their reproducibility and their usefulness to identify endothelial dysfunction. In Chapter 8 we applied one of these measures, the post-occlusive reactive hyperemia (PORH), to characterize the microvascular function in a knock-in mouse (V235fs KI mice) model of migraine. In Part II we evaluate the role of female sex hormones in migraine. The prevalence of migraine is much higher in women than in men. Hormonal milestones in women are