Background: White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease.
Methods: Structural T-weighted imaging, multishell diffusion imaging, and dynamic contrast-enhanced magnetic resonance imaging were performed at 3T in 44 participants with sporadic cerebral small vessel disease and 32 participants with monogenic cerebral small vessel disease (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; 59±12 years, 41 males) between June 2017 and May 2020 as part of the prospective, multicenter (Edinburgh, the United Kingdom; Maastricht, the Netherlands; and Munich, Germany), observational INVESTIGATE-SVDs study (Imaging Neurovascular, Endothelial and Structural Integrity in Preparation to Treat Small Vessel Diseases). The mean diffusivity, free water content, and perfusion (all derived from multishell diffusion imaging), as well as the blood-brain barrier leakage and plasma volume fraction (derived from dynamic contrast-enhanced magnetic resonance imaging), were compared between deep and periventricular WMH types using paired tests. Additional spatial analyses were performed inside and outside the WMH types to determine the internal heterogeneity and the extent of the penumbras, that is, adjacent white matter at risk for conversion to WMH.
Results: Periventricular WMH had higher mean diffusivity, higher free water content, and more plasma volume compared with deep WMH (<0.001, =0.01, and <0.001, respectively). No differences were observed in perfusion (=0.94) and blood-brain barrier leakage (=0.65) between periventricular and deep WMHs. The spatial analyses inside WMH and the adjacent white matter revealed a gradual gradient in white matter microstructure, free water content, perfusion, and plasma volume but not in blood-brain barrier leakage.
Conclusions: We showed different pathophysiological heterogeneity of the 2 WMH types. Periventricular WMHs display more severe damage and fluid accumulation compared with deep WMH, whereas deep WMHs reflect stronger hypoperfusion in the lesion's core.
Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN10514229.
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http://dx.doi.org/10.1161/STROKEAHA.124.047910 | DOI Listing |
Am J Cardiol
December 2024
Jinan Hospital, 63-1 Lishan Road, Jinan City 250013.
Individual cerebral small vessel disease (SVD) markers independently predict poor prognosis following stroke. However, the impact of a single SVD, especially cumulative SVD burden on outcomes in acute ischemic stroke (AIS) after intravenous thrombolysis remains unclear. This work evaluated the occurrence of small vessel disease (SVD) in AIS patients who were treated with intravenous thrombolytic therapy by using multimodal MRI imaging.
View Article and Find Full Text PDFComput Biol Med
December 2024
Escuela Técnica Superior de Ingeniería, Universidad de Sevilla, Spain. Electronic address:
Background: Organoids are 3D in vitro models that fulfill a hierarchical function, representing a small version of living tissues and, therefore, a good approximation of cellular mechanisms. However, one of the main disadvantages of these models is the appearance of a necrotic core due to poor vascularization. The aim of this work is the development of a numerical framework that incorporates the mechanical stimulation as a key factor in organoid vascularization.
View Article and Find Full Text PDFCancer Gene Ther
December 2024
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Angiosarcomas are a group of vascular cancers that form malignant blood vessels. These malignancies are seemingly inflamed primarily due to their pathognomonic nature, which consists of irregular endothelium and tortuous blood channels. PIK3CA mutations are oncogenic and disrupt the PI3K pathway.
View Article and Find Full Text PDFNeurotherapeutics
December 2024
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Neurocritical Care Division, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, MD, United States; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address:
Brain ischemia is a major cause of neurological dysfunction and mortality worldwide. It occurs not only acutely, such as in acute ischemic stroke (AIS), but also in chronic conditions like cerebral small vessel disease (cSVD). Any other conditions resulting in brain hypoperfusion can also lead to ischemia.
View Article and Find Full Text PDFEBioMedicine
December 2024
Department of Engineering Physics, Polytechnique Montréal, Montreal, Canada; Montreal Heart Institute, Montreal, Canada. Electronic address:
Background: Haemodynamic changes occur in stroke and neurodegenerative diseases. Developing imaging techniques allowing the in vivo visualisation and quantification of cerebral blood flow would help better understand the underlying mechanism of these cerebrovascular diseases.
Methods: 3D ultrasound localization microscopy (ULM) is a recently developed technology that can map the microvasculature of the brain at large depth and has been mainly used until now in rodents.
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