Theoretical Compartment Modeling of DCE-MRI Data Based on the Transport across Physiological Barriers in the Brain

Neurological disorders represent major causes of lost years of healthy life and mortality worldwide. Development of their quantitative interdisciplinary in vivo evaluation is required. Compartment modeling (CM) of brain data acquired in vivo using magnetic resonance imaging techniques with clinically available contrast agents can be performed to quantitatively assess brain perfusion. Transport of 1H spins in water molecules across physiological compartmental brain barriers in three different pools was mathematically modeled and theoretically evaluated in this paper and the corresponding theoretical compartment modeling of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data was analyzed. The pools considered were blood, tissue, and cerebrospinal fluid (CSF). The blood and CSF data were mathematically modeled assuming continuous flow of the 1H spins in these pools. Tissue data was modeled using three CMs. Results in this paper show that transport across physiological brain barriers such as the blood to brain barrier, the extracellular space to the intracellular space barrier, or the blood to CSF barrier can be evaluated quantitatively. Statistical evaluations of this quantitative information may be performed to assess tissue perfusion, barriers' integrity, and CSF flow in vivo in the normal or disease-affected brain or to assess response to therapy

Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe

MRI techniques for detection of developing inflammatory response

Since at least 1552 BC, inflammatory eye disease have been acknowledged as a major threat to sight. There have been a limited number of studies of in vivo inflammatory eye disease in humans and more information is required to improve image interpretation. The aim of this study was to develop and evaluate MRI techniques for the in vivo investigation of retinal damage and macrophage activity in the rat eye affected by experimental autoimmune uveitis (EAU), an inflammatory and autoimmune mediated eye disease. Rat eye structures affected by EAU were visualised in vivo in MR images acquired using figure-of-eight or single loop copper surface coils. Retinal damage in EAU was detected in vivo by MRI at the early stages of EAU. Retinal thickening and detachment in the moderate and severe forms of EAU were monitored in vivo using the same MRI technique. Unlabelled macrophages infiltrating eye structures such as the retina, iris and ciliary body of the rat eye at peak of EAU were visualised in vivo by MRI using a newly-developed single loop, 2-turn surface coil. This study demonstrated that MRI, using specially designed surface coils, can be used for non-invasive in vivo monitoring and also for the in vivo investigation of macrophage activity during development of EAU and of eye disease involving retinal thickening and detachment. The MRI techniques investigated in this study have also demonstrated their potential for the evaluation of new therapies in inflammatory and autoimmune mediated eye disease. All these are non invasive and hence have potential for future possible clinical investigation of inflammatory and autoimmune mediated eye disease or in eye disease involving retinal thickening and detachment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Magnetic Resonance Imaging in Ophthamology

Imaging the eye with magnetic resonance imaging (MRI) has proved difficult due to the eye?s propensity to move involuntarily over typical imaging timescales, obscuring the fine structure in the eye due to the resulting motion artifacts. However, advances in MRI technology help to mitigate such drawbacks, enabling the acquisition of high spatiotemporal resolution images with a variety of contrast mechanisms. This review aims to classify the MRI techniques used to date in clinical and preclinical ophthalmologic studies, describing the qualitative and quantitative information that may be extracted and how this may inform on ocular pathophysiology