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Radiology Apr 2018Cerebral microbleeds (CMBs), also referred to as microhemorrhages, appear on magnetic resonance (MR) images as hypointense foci notably at T2*-weighted or... (Review)
Review
Cerebral microbleeds (CMBs), also referred to as microhemorrhages, appear on magnetic resonance (MR) images as hypointense foci notably at T2*-weighted or susceptibility-weighted (SW) imaging. CMBs are detected with increasing frequency because of the more widespread use of high magnetic field strength and of newer dedicated MR imaging techniques such as three-dimensional gradient-echo T2*-weighted and SW imaging. The imaging appearance of CMBs is mainly because of changes in local magnetic susceptibility and reflects the pathologic iron accumulation, most often in perivascular macrophages, because of vasculopathy. CMBs are depicted with a true-positive rate of 48%-89% at 1.5 T or 3.0 T and T2*-weighted or SW imaging across a wide range of diseases. False-positive "mimics" of CMBs occur at a rate of 11%-24% and include microdissections, microaneurysms, and microcalcifications; the latter can be differentiated by using phase images. Compared with postmortem histopathologic analysis, at least half of CMBs are missed with premortem clinical MR imaging. In general, CMB detection rate increases with field strength, with the use of three-dimensional sequences, and with postprocessing methods that use local perturbations of the MR phase to enhance T2* contrast. Because of the more widespread availability of high-field-strength MR imaging systems and growing use of SW imaging, CMBs are increasingly recognized in normal aging, and are even more common in various disorders such as Alzheimer dementia, cerebral amyloid angiopathy, stroke, and trauma. Rare causes include endocarditis, cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and radiation therapy. The presence of CMBs in patients with stroke is increasingly recognized as a marker of worse outcome. Finally, guidelines for adjustment of anticoagulant therapy in patients with CMBs are under development. RSNA, 2018.
Topics: Cerebral Hemorrhage; Humans; Magnetic Resonance Imaging
PubMed: 29558307
DOI: 10.1148/radiol.2018170803 -
Eye (London, England) Jan 2021Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Optical coherence tomography angiography (OCTA) has been developed to visualize... (Review)
Review
Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Optical coherence tomography angiography (OCTA) has been developed to visualize the retinal microvasculature and choriocapillaris based on the motion contrast of circulating blood cells. Depth-resolved ability and non-invasive nature of OCTA allow for repeated examinations and visualization of microvasculature at the retinal capillary plexuses and choriocapillaris. OCTA enables quantification of microvascular alterations in the retinal capillary network, in addition to the detection of classical features associated with DR, including microaneurysms, intraretinal microvascular abnormalities, and neovascularization. OCTA has a promising role as an objective tool for quantifying extent of microvascular damage and identify eyes with diabetic macular ischaemia contributed to visual loss. Furthermore, OCTA can identify preclinical microvascular abnormalities preceding the onset of clinically detectable DR. In this review, we focused on the applications of OCTA derived quantitative metrics that are relevant to early detection, staging and progression of DR. Advancement of OCTA technology in clinical research will ultimately lead to enhancement of individualised management of DR and prevention of visual impairment in patients with diabetes.
Topics: Diabetes Mellitus; Diabetic Retinopathy; Fluorescein Angiography; Humans; Microaneurysm; Retinal Vessels; Tomography, Optical Coherence
PubMed: 33099579
DOI: 10.1038/s41433-020-01233-y -
Cells Jun 2022Diabetic macular edema (DME) is a major ocular complication of diabetes mellitus (DM), leading to significant visual impairment. DME's pathogenesis is multifactorial.... (Review)
Review
Diabetic macular edema (DME) is a major ocular complication of diabetes mellitus (DM), leading to significant visual impairment. DME's pathogenesis is multifactorial. Focal edema tends to occur when primary metabolic abnormalities lead to a persistent hyperglycemic state, causing the development of microaneurysms, often with extravascular lipoprotein in a circinate pattern around the focal leakage. On the other hand, diffusion edema is due to a generalized breakdown of the inner blood-retinal barrier, leading to profuse early leakage from the entire capillary bed of the posterior pole with the subsequent extravasation of fluid into the extracellular space. The pathogenesis of DME occurs through the interaction of multiple molecular mediators, including the overexpression of several growth factors, including vascular endothelial growth factor (VEGF), insulin-like growth factor-1, angiopoietin-1, and -2, stromal-derived factor-1, fibroblast growth factor-2, and tumor necrosis factor. Synergistically, these growth factors mediate angiogenesis, protease production, endothelial cell proliferation, and migration. Treatment for DME generally involves primary management of DM, laser photocoagulation, and pharmacotherapeutics targeting mediators, namely, the anti-VEGF pathway. The emergence of anti-VEGF therapies has resulted in significant clinical improvements compared to laser therapy alone. However, multiple factors influencing the visual outcome after anti-VEGF treatment and the presence of anti-VEGF non-responders have necessitated the development of new pharmacotherapies. In this review, we explore the pathophysiology of DME and current management strategies. In addition, we provide a comprehensive analysis of emerging therapeutic approaches to the treatment of DME.
Topics: Angiogenesis Inhibitors; Blood-Retinal Barrier; Diabetes Mellitus; Diabetic Retinopathy; Humans; Macular Edema; Vascular Endothelial Growth Factor A
PubMed: 35741079
DOI: 10.3390/cells11121950 -
Progress in Retinal and Eye Research Sep 2017OCT has revolutionized the practice of ophthalmology over the past 10-20 years. Advances in OCT technology have allowed for the creation of novel OCT-based methods.... (Review)
Review
OCT has revolutionized the practice of ophthalmology over the past 10-20 years. Advances in OCT technology have allowed for the creation of novel OCT-based methods. OCT-Angiography (OCTA) is one such method that has rapidly gained clinical acceptance since it was approved by the FDA in late 2016. OCTA images are based on the variable backscattering of light from the vascular and neurosensory tissue in the retina. Since the intensity and phase of backscattered light from retinal tissue varies based on the intrinsic movement of the tissue (e.g. red blood cells are moving, but neurosensory tissue is static), OCTA images are essentially motion-contrast images. This motion-contrast imaging provides reliable, high resolution, and non-invasive images of the retinal vasculature in an efficient manner. In many cases, these images are approaching histology level resolution. This unprecedented resolution coupled with the simple, fast and non-invasive imaging platform have allowed a host of basic and clinical research applications. OCTA demonstrates many important clinical findings including areas of macular telangiectasia, impaired perfusion, microaneurysms, capillary remodeling, some types of intraretinal fluid, and neovascularization among many others. More importantly, OCTA provides depth-resolved information that has never before been available. Correspondingly, OCTA has been used to evaluate a spectrum of retinal vascular diseases including diabetic retinopathy (DR), retinal venous occlusion (RVO), uveitis, retinal arterial occlusion, and age-related macular degeneration among others. In this review, we will discuss the methods used to create OCTA images, the practical applications of OCTA in light of invasive dye-imaging studies (e.g. fluorescein angiography) and review clinical studies demonstrating the utility of OCTA for research and clinical practice.
Topics: Angiography; Humans; Retina; Retinal Diseases; Retinal Vessels; Tomography, Optical Coherence
PubMed: 28760677
DOI: 10.1016/j.preteyeres.2017.07.002 -
Investigative Ophthalmology & Visual... Oct 2023Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF)...
PURPOSE
Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF) therapy. This study aimed to investigate the effect of faricimab, a bispecific antibody against angiopoietin-2 and VEGF, on the number of MAs and their turnover in the treatment of DME.
METHODS
We included that patients with DME who underwent three monthly injections of faricimab in one eye, with the other eye as control. We examined central retinal thickness (CRT) based on optical coherence tomography (OCT) and best-corrected visual acuity. Turnover, including loss and newly formed MAs, and the total number of MAs were counted based on merged images of the OCT map and fluorescein angiography.
RESULTS
We enrolled 28 patients with DME. After 3 monthly injections of faricimab, CRT significantly improved, 66.0 ± 16.2% of MAs disappeared, and 6.71 ± 5.6% of new MAs were generated, resulting in total reduction to 40.7 ± 15.2%. In the treated eyes, MA disappearance (P < 0.0001) and turnover (P = 0.007) were significantly greater, and new formation was smaller (P < 0.0001) than in non-treated eyes. The size of the retained MAs decreased after treatment. Microaneurysm turnover was not significantly different between areas with and without edema before treatment.
CONCLUSIONS
In the process of improving edema in DME with faricimab, MAs shrink and disappear, and formation of MAs are inhibited, resulting in decreased total number of MAs. Intravitreal administration of faricimab suppresses vascular permeability and improves vascular structure.
Topics: Humans; Macular Edema; Diabetic Retinopathy; Vascular Endothelial Growth Factor A; Angiogenesis Inhibitors; Microaneurysm; Intravitreal Injections; Edema; Tomography, Optical Coherence; Diabetes Mellitus
PubMed: 37856112
DOI: 10.1167/iovs.64.13.31 -
Vision Research Oct 2017Early histopathological studies of diabetic choroids demonstrated loss of choriocapillaris (CC), tortuous blood vessels, microaneurysms, drusenoid deposits on Bruchs... (Review)
Review
Early histopathological studies of diabetic choroids demonstrated loss of choriocapillaris (CC), tortuous blood vessels, microaneurysms, drusenoid deposits on Bruchs membrane, and choroidal neovascularization. The preponderance of histopathological changes were at and beyond equator. Studies from my lab suggest that diabetic choroidopathy is an inflammatory disease in that leukocyte adhesion molecules are elevated in the choroidal vasculature and polymorphonuclear neutrophils are often associated with sites of vascular loss. Modern imaging techniques demonstrate that blood flow is reduced in subfoveal choroidal vasculature. Angiography has shown areas of hypofluorescence and late filling that probably represent areas of vascular loss and/or compromise. Perhaps, as a result of vascular insufficiency, the choroid appears to thin in DC unless macular edema is present. Enhanced depth imaging (EDI-SD) OCT and swept source (SS) OCT have documented the tortuosity and loss in intermediate and large blood vessels in Sattler's and Haller's layer seen previously with histological techniques. The risk factors for DC include diabetic retinopathy, degree of diabetic control, and the treatment regimen. In the future, OCT angiography could be used to document loss of CC. Because most of the measurement and imaging are in the posterior pole, the severity of DC may be underappreciated in the published accounts of DC assessed with imaging techniques. However, it is now possible to document DC and quantify these changes clinically. This suggests that DC should be evaluated in future clinical trials of drugs targeting DR because vascular changes similar to those in DR are occurring in DC.
Topics: Choroid; Choroid Diseases; Diabetes Complications; Humans; Neutrophils; Tomography, Optical Coherence
PubMed: 28535994
DOI: 10.1016/j.visres.2017.04.011 -
Nature Communications Dec 2023We report the case of a 79-year-old woman with Alzheimer's disease who participated in a Phase III randomized controlled trial called CLARITY-AD testing the experimental...
We report the case of a 79-year-old woman with Alzheimer's disease who participated in a Phase III randomized controlled trial called CLARITY-AD testing the experimental drug lecanemab. She was randomized to the placebo group and subsequently enrolled in an open-label extension which guaranteed she received the active drug. After the third biweekly infusion, she suffered a seizure characterized by speech arrest and a generalized convulsion. Magnetic resonance imaging revealed she had multifocal swelling and a marked increase in the number of cerebral microhemorrhages. She was treated with an antiepileptic regimen and high-dose intravenous corticosteroids but continued to worsen and died after 5 days. Post-mortem MRI confirmed extensive microhemorrhages in the temporal, parietal and occipital lobes. The autopsy confirmed the presence of two copies of APOE4, a gene associated with a higher risk of Alzheimer's disease, and neuropathological features of moderate severity Alzheimer's disease and severe cerebral amyloid angiopathy with perivascular lymphocytic infiltrates, reactive macrophages and fibrinoid degeneration of vessel walls. There were deposits of β-amyloid in meningeal vessels and penetrating arterioles with numerous microaneurysms. We conclude that the patient likely died as a result of severe cerebral amyloid-related inflammation.
Topics: Aged; Female; Humans; Alzheimer Disease; Amyloid beta-Peptides; Arteritis; Brain; Cerebral Amyloid Angiopathy; Iatrogenic Disease; Vasculitis, Central Nervous System; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 38086820
DOI: 10.1038/s41467-023-43933-5