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Abstract
Stroke is now the second leading cause of death worldwide, after heart disease, and about two thirds or more of stroke deaths occur in the developing world. Throughout the world, unfavorable trends in stroke risk factor profile, lack of prevention programs, lack of awareness of stroke risk factors and warning signs by the public, misapplication or underutilization of stroke preventatives, and lack of emphasis on preventive training in medical school and postgraduate programs portend high stroke rates and serve to widen the stroke prevention gap. This is unfortunate because stroke is well suited for prevention since it has a high prevalence, high burden of illness and economic cost, well-defined modifiable risk factors, and effective prevention measures.
The realization that atherosclerosis is an inflammatory disease has led to a search for new stroke risk factors and treatments. The atherosclerotic process consists of a highly specific cellular and molecular inflammatory response. The earliest atherosclerotic lesion, the fatty streak, consists of monocyte-derived macrophages and T lymphocytes. The development of atherosclerosis has advanced from the response-to-injury hypothesis of endothelial denudation to the hypothesis of endothelial dysfunction. The endothelium is an important regulatory barrier that is constantly being challenged by factors such as elevated and modified low-density lipoprotein cholesterol (LDL-C), free radicals generated by cigarette smoking, hypertension, diabetes mellitus, genetic modifiers, elevated homocysteine, and infectious microorganisms.
If the endothelial barrier succumbs to injury, important surface changes occur: increased adhesiveness to leukocytes or platelets, increased permeability, and procoagulant tendency with formation of vasoactive molecules, cytokines, and growth factors. These changes eventually lead to the full-blown atheromatous lesion. During the course of development of the atherosclerotic lesion, there is an intermediate stage characterized by smooth-muscle cell proliferation, thickening of the arterial wall, and gradual dilation of the wall so that the blood vessel lumen remains unaltered (remodeling). With continued inflammation and increase in the numbers of macrophages, lymphocytes, and lipids, the release of hydrolytic enzymes, cytokines, chemokines, and growth factors facilitates intraplaque necrosis and rupture of the lipid core beyond the surrounding fibrous tissue cap and smooth muscle cells.
Treatment of acute ischemic stroke has changed substantially over the last two decades. Previously, stroke treatment was limited to different supportive measures and secondary prevention. Experimental investigations established the use of intravenous rt-PA for acute ischemic stroke treatment, which was established within the first 3 hours after symptom onset in 1996 and is now approved within that time frame in several countries.
Neuroimaging technology has progressed considerably during recent decades. Neuroimaging studies can be an invaluable part of the diagnostic workup of psychiatric patients. However, it can be difficult to determine which clinical situations call for the use of neuroimaging studies and which do not. In addition, it is often unclear what type of neuroimaging study should be ordered. Should contrast be used during the study? Are there specific acquisition parameters that may be useful in a particular clinical situation?
Structural neuroimaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) have revolutionized the practice of medicine in recent decades. Functional neuroimaging techniques developed after the advent of structural neuroimaging and show great promise for both clinical use and neuroscience research. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) have demonstrated the greatest clinical utility of all functional neuroimaging methods to date. Magnetic resonance spectroscopy (MRS) is another technology that uses unique MRI acquisition parameters to assess in vivo brain neurochemistry.
Clinical outcome depends on fast and efficient intracranial vessel recanalization. Spontaneous recanalization of occluded intracerebral vessels occurs in 15-/20% of patients within the first 24 hours. This rate may be increased to 34-/47% by intravenous application and up to 90% by local intra-arterial application of thrombolytics. Although rt-PA was a breakthrough, the reported low rate of recanalization after systemic application of rt-PA may contribute to the comparably low rate of recovery. This situation stimulated additional investigations into methods to speed up clot lysis. There is good evidence that ultrasound (US) insonation with lower frequencies (between 20 and 1 MHz) and higher intensities (1-35 W/cm2) than those used for routine diagnostic purposes of intracranial vessels is thrombolytic. More recent studies have shown low intensity US (in the level of intensities used for diagnostic examinations) to enhance enzymatic rt-PA mediated thrombolysis in vitro as well as in vivo. The low recanalization rate after routine systemic application of rt-PA stimulates further investigations into the direct acceleration of thrombolysis. One way to accomplish this is the implementation of endovascular therapies, e.g. local application of thrombolytics. Although clinical results showed a significant benefit, its applicability is extremely limited in acute stroke needing to highly specialized stroke centers with interventional neuroradiology services. Transcranial application of US in combination with systemic administration of rt-PA overcomes these obstacles. This combined treatment is a promising strategy to optimize therapy in acute stroke patients within the first (0-6) hours after symptom onset. With faster recanalization, it may also be possible to extend the therapeutic window.
Ultrasound sharpens the clinician’s ear and provides a stethoscope, an observation tool. And, like a microscope, an ultrasound probe needs a scientist to point it in the right direction. However, to paint a global picture, a complex ultrasound system also needs an artist to bring the art and science of medicine together. Ultrasound enables us to monitor brain responses to treatment in real time, a handy tool to tailor treatment when the current evidence is meager and made us believe that stroke is treatable.
Ultrasound (US) has emerged as a promising tool to treat ischemic stroke. The potential advantage of US is decreased risk of systemic bleeding complications due to its site-specific effect. Moreover, it is a fast, portable, repeatable, inexpensive, externally applicable; noninvasive and readily available.
To the present day, the first and most widespread diagnostic approach in the assessment of acute stroke remains CT scan. Its sensitivity is very high (nearly 100%) in detecting intracerebral hemorrhage in the acute period, but its capability of revealing ischemic injury in the very first hours from symptom onset is relatively poor. Since the efficacy of thrombolytic treatment in acute stroke has been established, the main goal of stroke therapy is to save as much as potentially salvageable tissue in the hyperacute period. In this regard, we need functional data to distinguish irreversibly injured areas from the still viable ones. Functional neuroimaging able to distinguish potentially salvageable tissue from irreversibly injured areas. The possibility to correctly identify the tissue of the ischemic penumbra within the first hours from symptom onset is essential for correct patient selection for thrombolytic treatment. Different imaging strategies are available for the definition of perfusion deficits within the acute time window; among these are positron emission tomography (PET), single photon emission computed tomography (SPECT), diffusion weighted magnetic resonance imaging (DW-MRI), and perfusion weighted magnetic resonance imaging (PW-MRI). Though each technique has its advantages and limitations to present day functional MRI remains the most widespread imaging technique in the assessment of acute stroke being more accessible than both SPECT and PET, and capable of giving information on both perfusion and tissue functional status in a single imaging session.