Leif Østergaard

Dynamic bolus tracking MRI has been used to calculate maps of cerebral blood volume (1, 2) and, more recently, cerebral blood flow (3, 4). It has been predicted that a shorter contrast agent bolus may be advantageous for the quality of the perfusion maps (3-5). Gadobutrol, a neutral macrocyclic contrast agent, allows concentrations of 0.5 mol/l and 1.0 mol/l and therefore allows halved injection volumes at the same dose. Animal experiments showed that the arterial concentration following intravenous bolus injection of gadobutrol at the same dose was about 30% higher for the 1.0 molar concentration than for the 0.5 molar concentration (6). This supported further animal experiments which showed improved contrast between ischemic and non-ischemic brain tissue at the same dose for the 1.0 molar concentration (7).

Post-stroke cognitive impairment (PSCI) is common. However, the underlying pathophysiology remains largely unknown. Understanding the role of microvascular changes and finding markers that can predict PSCI, could be a first step towards better screening and management of PSCI. Capillary dysfunction is a pathological feature of cerebral small vessel disease and may play a role in the mechanisms underlying PSCI. Extracellular vesicles (EVs) are secreted from cells and may act as disease biomarkers. We aim to investigate the role of capillary dysfunction in PSCI and the associations between EV characteristics and cognitive function one year after acute ischemic stroke (AIS) and transient ischemic attack (TIA). The ENIGMA study is a single-centre prospective clinical observational study conducted at Aarhus University Hospital, Denmark. Consecutive patients with AIS and TIA are included and followed for …

Hypoparathyroidism (HypoPT) is a disease with no/or inadequate production/secretion of parathyroid hormone (PTH) from the parathyroid glands. Low levels of PTH result in hypocalcemia, which is often treated with calcium supplementation and active vitamin-D analogs. However, increasing evidence suggests that HypoPT has a profound impact on several organ systems. Quality of life (QOL) is reduced in patients with HypoPT, partly due to symptoms related to the central nervous system—including subjective feelings of confusion, a reduced ability to focus and think clearly(i.e., “brain fog”). However, the extent to which these complex symptoms relate to quantifiable changes in patients’ cognitive performance as determined by neuropsychological tests remains unclear. The brains of HypoPT patients may reveal tissue calcifications, but the extent to which long-term brain exposure to low PTH levels and/or …

Mitochondria are the main suppliers of energy for cells and their bioenergetic function is regulated by mitochondrial dynamics: the constant changes in mitochondria size, shape, and cristae morphology to secure cell homeostasis. Although changes in mitochondrial function are implicated in a wide range of diseases, our understanding is challenged by a lack of reliable ways to extract spatial features from the cristae, the detailed visualization of which requires electron microscopy (EM). Here, we present a semi-automatic method for the segmentation, 3D reconstruction, and shape analysis of mitochondria, cristae, and intracristal spaces based on 2D EM images of the murine hippocampus. We show that our method provides a more accurate characterization of mitochondrial ultrastructure in 3D than common 2D approaches and propose an operational index of mitochondria’s internal organization. With an improved …

The pathophysiological development of Alzheimer's disease (AD) begins in the brain years before the onset of clinical symptoms. The accumulation of beta‐amyloid (Aβ) is thought to be the first cortical pathology to occur. Carrying one apolipoprotein E (APOE) ε4 allele increases the risk of developing AD at least 2–3 times and is associated with earlier Aβ accumulation. Although it is difficult to identify Aβ‐related cognitive impairment in early AD with standard cognitive tests, more sensitive memory tests may be able to do this. We sought to examine associations between Aβ and performance on three tests within three subdomains of memory, verbal, visual, and associative memory, to elucidate which of these tests were sensitive to Aβ‐related cognitive impairment in at‐risk subjects. 55 APOE ε4 carriers underwent MRI, 11C‐Pittsburgh Compound B (PiB) PET, and cognitive testing. A composite cortical PiB SUVR cut …

INTRODUCTION Capillary dysfunction, characterized by disturbances in capillary blood flow distribution, might be an overlooked factor in the development of Alzheimer's disease (AD). This study investigated microvascular blood flow in preclinical and prodromal AD individuals. METHODS Using dynamic susceptibility contrast magnetic resonance imaging and positron emission tomography, we examined alterations in microvascular circulation and levels of Aβ deposition in two independent cohorts of APOE ε4 carriers. RESULTS Capillary dysfunction was elevated in both prodromal and preclinical AD individuals compared to age‐matched controls. Additionally, the prodromal group exhibited higher levels of capillary dysfunction compared to the preclinical group. DISCUSSION These findings suggest that capillary dysfunction can be detected at the preclinical stage of AD and indicates a worsening of capillary …

Alterations in cerebral perfusion is increasingly considered to play a crucial role in Alzheimer's disease (AD) and together with accumulated amyloid-β, deficiencies in the brain microvascular circulation may result in local hypoxia. Here, we studied alterations in cerebral circulation and the correlation between amyloid-β load and cerebral perfusion in prodromal AD (pAD). Using dynamic susceptibility contrast MRI and PET, we evaluated cerebral perfusion and amyloid-β levels in 19 individuals with mild cognitive impairment (MCI) and high amyloid-β load (pAD-MCI), 13 MCI individuals without AD pathology and 21 healthy controls. The pAD-MCI group showed significantly lower microvascular blood flow and significantly higher heterogeneity of microvascular blood transit times (p < 0.01) compared with the other 2 groups. Additionally, in the pAD-MCI group raised amyloid-β levels correlated with decreased …

3D mitochondrial ultrastructure using volume electron microscopy — Aarhus University Skip to main navigation Skip to search Skip to main content Aarhus University Home Aarhus University Logo Help & FAQ English Dansk Home Profiles Research units Projects Research output Prizes Activities Courses Press/Media Search by expertise, name or affiliation 3D mitochondrial ultrastructure using volume electron microscopy Chenhao Wang, Leif Østergaard, Stine Hasselholt, Jon Sporring Department of Clinical Medicine - Center of Functionally Integrative Neuroscience Research output: Contribution to conference › Conference abstract for conference › Research › peer-review Overview Original language English Publication date 31 Oct 2023 Publication status Published - 31 Oct 2023 Event 6th Annual Research Meeting at the Department of Clinical Medicine - Aarhus Universitetshospital, Aarhus N, Denmark Duration: …