Article
Multidisciplinary Sciences
Samantha Paterson, Antoine Vallatos, Jean Rodgers, William M. Holmes
Summary: This study is the first to use diffusion weighted ASL (DWASL) to examine changes in the blood brain barrier (BBB) during Human African Trypanosomiasis (HAT) infection. The study found no significant changes in water exchange across the BBB, even when a loss of barrier integrity was observed during the late stage of the disease using Contrast Enhanced MRI (Gd-DTPA). Furthermore, using multiple boli ASL (mbASL), changes in cerebral blood flow (CBF) were identified during HAT infection. Overall, this study highlights the importance of further investigating the BBB during HAT infection to understand the complex mechanisms involved.
SCIENTIFIC REPORTS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Stig P. Cramer, Henrik B. W. Larsson, Maria H. Knudsen, Helle J. Simonsen, Mark B. Vestergaard, Ulrich Lindberg
Summary: This study investigates the reproducibility of DCE-MRI in healthy controls and evaluates the impact of arterial input function selection and manual region of interests delineation versus automated global segmentation. The results show excellent reproducibility of pharmacokinetic variables derived from DCE-MRI in healthy controls.
JOURNAL OF MAGNETIC RESONANCE IMAGING
(2023)
Review
Biochemistry & Molecular Biology
Carla Rodriguez-Mogeda, Sabela Rodriguez-Lorenzo, Jiji Attia, Jack van Horssen, Maarten E. Witte, Helga E. de Vries
Summary: Multiple sclerosis is an inflammatory disease where B cells play a crucial role in the pathogenesis, migrating into the central nervous system through various routes. Understanding the routes of B cell entry into the inflamed CNS is essential for comprehending the disease.
Article
Endocrinology & Metabolism
Isabel N. Christie, Rowan Windsor, Henk J. M. M. Mutsaerts, Therese Tillin, Carole H. Sudre, Alun D. Hughes, Xavier Golay, Alexander Gourine, Patrick S. Hosford
Summary: This study examined the link between systemic arterial blood pressure and cerebral perfusion in a tri-ethnic study in the UK. Results showed a significant negative correlation between blood pressure, age, and cerebral blood flow. The group of hypertensive patients prescribed with anti-hypertensive drugs but with uncontrolled blood pressure recorded the lowest cerebral blood flow values. These findings highlight the importance of blood pressure control for maintaining brain blood flow.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Clinical Neurology
Sebok K. Halder, Richard Milner
Summary: Fifty years of research on multiple sclerosis have provided significant insights into this neurological disease, revealing its characteristics and raising questions about the initial trigger of the inflammatory demyelinating process. Recent studies suggest that hypoxia, in addition to the immune system, may play a role in disease progression, leading researchers to investigate the impact of manipulating inspired oxygen levels.
Article
Clinical Neurology
Sebok K. Halder, Richard Milner
Summary: Multiple sclerosis is an autoimmune disease that may be affected by hypoxia as a new potential trigger for the inflammatory demyelinating process. Studies have shown the presence of hypoxia in early demyelinating lesions, prompting researchers to investigate how oxygen levels impact disease progression.
Article
Biochemistry & Molecular Biology
Jayanarayanan Sadanandan, Monica Sathyanesan, Yutong Liu, Neeraj K. Tiwari, Samuel S. Newton
Summary: Cerebral hypoperfusion has negative effects on cognitive function and increases the risk of neuropsychiatric disorders. Erythropoietin (EPO) has been shown to improve cognitive function, but its use is limited due to its erythropoietic activity. However, carbamoylated erythropoietin (CEPO), a non-erythropoietic derivative of EPO, has similar neurotrophic and behavioral effects without affecting hematocrit levels. Our study reveals that CEPO can increase blood perfusion through neurotransmission and vasodilation, without affecting tight junction integrity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Ian J. Tagge, Valerie C. Anderson, Charles S. Springer, Manoj K. Sammi, Dennis M. Bourdette, Rebecca Spain, William D. Rooney
Summary: Transcapillary water exchange is reduced in the normal-appearing gray matter of individuals with progressive multiple sclerosis compared to healthy controls, and is further decreased in white matter lesions, indicating impaired brain metabolism. The k(po) parameter provides a sensitive measure of cerebral metabolic activity and can be mapped at higher spatial resolution than conventional imaging techniques.
JOURNAL OF NEUROIMAGING
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Dejan Jakimovski, Niels Bergsland, Michael G. Dwyer, Kunsang Choedun, Karen Marr, Bianca Weinstock-Guttman, Robert Zivadinov
Summary: This study aimed to investigate the relationship between systemic arterial blood flow (SABF) and cerebral perfusion in patients with multiple sclerosis (MS). The results showed that higher SABF was associated with shorter mean transit time (MTT) and time-to-peak (TTP) in the whole brain and gray matter, primarily in progressive MS patients. SABF remained a significant predictor of normal-appearing whole brain (NAWB) and gray matter (GM) TTP in progressive MS patients. Patients with lower SABF had significantly lower MTT and TTP.
EUROPEAN RADIOLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Elles P. Elschot, Walter H. Backes, Joost J. A. de Jong, Gerhard S. Drenthen, Sau May Wong, Julie Staals, Alida A. Postma, Rob P. W. Rouhl, Robert J. van Oostenbrugge, Jacobus F. A. Jansen
Summary: This study investigated the ability of dynamic susceptibility contrast (DSC) MRI to measure subtle blood-brain barrier (BBB) leakage in cerebral small vessel disease (cSVD) in a clinical feasibility setting. The results showed that DSC-MRI is capable of detecting subtle BBB leakage differences between white matter hyperintensities (WMH) and normal-appearing brain tissue. However, further research is needed to better differentiate perfusion from leakage effects due to signal uncertainties.
MAGNETIC RESONANCE IMAGING
(2023)
Review
Biochemistry & Molecular Biology
Thomas Gabriel Schreiner, Constantin Romanescu, Bogdan Ovidiu Popescu
Summary: This article reviews the role of the blood-brain barrier (BBB) in multiple sclerosis (MS) pathology, emphasizing the importance of neurovascular unit damage in MS onset and progression, as well as the impact of BBB cell alterations and immune cell penetration into the central nervous system on MS pathology.
Review
Biochemistry & Molecular Biology
Rodica Balasa, Laura Barcutean, Oana Mosora, Doina Manu
Summary: This review discusses the disruption of the blood-brain barrier (BBB) in multiple sclerosis (MS) pathogenesis, focusing on the impairment of the neurovascular unit (NVU) and metabolic and mitochondrial dysfunctions of BBB’s endothelial cells. It highlights the hypoxic hypothesis in MS, potential mechanisms of neurodegeneration in progressive forms of MS, and the possibility of BBB as a therapeutic target for delivering neuroprotective molecules into the central nervous system. Additionally, it explores the beneficial effects of disease-modifying therapies (DMTs) that can cross the BBB and act directly in the CNS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Wafae Labriji, Julien Clauzel, Jean-Louis Mestas, Maxime Lafond, Cyril Lafon, Anne-Sophie Salabert, Lydiane Hirschler, Jan M. Warnking, Emmanuel L. Barbier, Isabelle Loubinoux, Franck Desmoulin
Summary: The purpose of this study was to investigate the effect of Blood Brain Barrier (BBB) opening using ultrasound combined with microbubbles injection on cerebral blood flow in rats. The results showed that BBB opening induced by microbubble intravenous injection led to transient hypoperfusion, which shared some similarities with cortical spreading depression phenomenon.
MAGNETIC RESONANCE IN MEDICINE
(2023)
Article
Multidisciplinary Sciences
Antonio Maria Chiarelli, Alessandro Villani, Daniele Mascali, Nikolaos Petsas, Emma Biondetti, Alessandra Caporale, Anna Digiovanni, Eleonora Agata Grasso, Paola Ajdinaj, Maria D'Apolito, Marianna Gabriella Rispoli, Stefano Sensi, Kevin Murphy, Carlo Pozzilli, Richard G. Wise, Valentina Tomassini
Summary: This study investigated the relationship between cerebrovascular reactivity (CVR) and neuroinflammation in patients with multiple sclerosis (MS). The findings showed lower CVR in patients before treatment compared to healthy controls and a negative correlation between pre-treatment CVR and grey matter volume. During treatment, CVR increased and was negatively correlated with pre-treatment CVR. Reduction in enhancing lesions was associated with increased CVR. The resolution of inflammation may restore altered cerebrovascular function in MS.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
S. M. Lunin, E. G. Novoselova, O. V. Glushkova, S. B. Parfenyuk, A. A. Kuzekova, T. V. Novoselova, M. G. Sharapov, E. K. Mubarakshina, R. G. Goncharov, M. O. Khrenov
Summary: This study showed that the immunomodulator thymulin and the antioxidant enzyme Prdx6 can improve the condition of blood-brain barrier (BBB) and alleviate symptoms of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Thymulin decreased immune cell activation, while Prdx6 reduced NOX1 and NOX4 gene expression in brain tissue, contributing to the improvements in BBB condition and health status. Simultaneous administration of thymulin and Prdx6 resulted in complete symptomatic restoration of mice with EAE.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Endocrinology & Metabolism
Samaira Younis, Casper E. Christensen, Mark B. Vestergaard, Ulrich Lindberg, Daniel Tolnai, Olaf B. Paulson, Henrik B. W. Larsson, Anders Hougaard, Messoud Ashina
Summary: Migraine is a complex disorder involving both peripheral and central brain structures, with the exact mechanisms of attack initiation remaining unknown. Research indicates that dorsolateral pontine activation during migraine is not linked to increased glutamate levels, but the simultaneous increase in total creatine levels may suggest altered energy metabolism. This finding highlights the need for further investigation into the role of the pons in acute migraine.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Clinical Neurology
Amalie Monberg Hindsholm, Stig Praestekjaer Cramer, Helle Juhl Simonsen, Jette Lautrup Frederiksen, Flemming Andersen, Liselotte Hojgaard, Claes Nohr Ladefoged, Ulrich Lindberg
Summary: This study implemented and validated an algorithm for automatic delineation of white matter lesions on MRI in MS patients, achieving promising results after adaptation to a local dataset.
CLINICAL NEURORADIOLOGY
(2022)
Article
Clinical Neurology
Massimo Filippi, Paolo Preziosa, Alessandro Meani, Gloria Dalla Costa, Sarlota Mesaros, Jelena Drulovic, Jovana Ivanovic, Alex Rovira, Mar Tintore, Xavier Montalban, Olga Ciccarelli, Wallace Brownlee, Katherine Miszkiel, Christian Enzinger, Michael Khalil, Frederik Barkhof, Eva M. M. Strijbis, Jette L. Frederiksen, Stig P. Cramer, Enrico Fainardi, Maria Pia Amato, Claudio Gasperini, Serena Ruggieri, Vittorio Martinelli, Giancarlo Comi, Maria A. Rocca
Summary: This study compares the performance of the 2017 revisions to the McDonald criteria with the 2010 criteria in diagnosing and predicting prognosis of multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS). The results show that the 2017 criteria have higher sensitivity, lower specificity, and shorter time to MS diagnosis compared to the 2010 criteria.
Review
Clinical Neurology
Mark B. Vestergaard, Jette L. Frederiksen, Henrik B. W. Larsson, Stig P. Cramer
Summary: Inflammatory processes in the central nervous system could potentially impair cerebrovascular function in multiple sclerosis patients. However, studies on cerebrovascular reactivity and neurovascular coupling in MS patients have produced diverse results, indicating the need for further research to understand the discrepancies.
FRONTIERS IN NEUROLOGY
(2022)
Article
Urology & Nephrology
Jens Christian Laursen, Niels Sondergaard-Heinrich, Bryan Haddock, Ida Kirstine Bull Rasmussen, Christian Stevns Hansen, Henrik Bo Wiberg Larsson, Per-Henrik Groop, Petter Bjornstad, Marie Frimodt-Moller, Ulrik Bjorn Andersen, Peter Rossing
Summary: In individuals with T1D and albuminuria, higher medullary oxygenation was observed despite lower cortical perfusion and renal artery blood flow. Lower cortical oxygenation and renal artery blood flow were associated with higher UACR and lower eGFR in T1D participants.
CLINICAL KIDNEY JOURNAL
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Otto M. Henriksen, Adam E. Hansen, Aida Muhic, Lisbeth Marner, Karine Madsen, Soren Moller, Benedikte Hasselbalch, Michael J. Lundemann, David Scheie, Jane Skjoth-Rasmussen, Hans S. Poulsen, Vibeke A. Larsen, Henrik B. W. Larsson, Ian Law
Summary: This study compared the diagnostic yield of dynamic contrast-enhanced (DCE) perfusion MRI and O-(2-[F-18]-fluoroethyl)-L-tyrosine ([F-18]FET) PET in patients with recurrent high-grade gliomas. The results showed that DCE BV imaging had good overall diagnostic accuracy, but lower than [F-18]FET PET. Combining both techniques can improve specificity and risk stratification of the lesions.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Clinical Neurology
Maria Hojberg Knudsen, Ulrich Lindberg, Jette Lautrup Frederiksen, Mark Bitsch Vestergaard, Helle Juhl Simonsen, Aravinthan Varatharaj, Ian Galea, Morten Blinkenberg, Finn Sellebjerg, Henrik Bo Wiberg Larsson, Stig Praestekjaer Cramer
Summary: The study found that BBB permeability measured by MRI can serve as a biomarker to assess the efficacy of alemtuzumab treatment. Patients who maintained NEDA-3 status had a greater decrease in BBB permeability at 6 and 12 months after treatment compared to those who experienced disease activity.ROC curve analysis showed that changes in BBB permeability predicted the loss of NEDA status with high sensitivity and specificity.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Oncology
Charlotte M. Stuart, Aravinthan Varatharaj, Martin E. Winberg, Pascale Galea, Henrik B. W. Larsson, Stig P. Cramer, Alessio Fasano, Zaynah Maherally, Geoffrey J. Pilkington, Asa V. Keita, Ian Galea
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Stig P. Cramer, Henrik B. W. Larsson, Maria H. Knudsen, Helle J. Simonsen, Mark B. Vestergaard, Ulrich Lindberg
Summary: This study investigates the reproducibility of DCE-MRI in healthy controls and evaluates the impact of arterial input function selection and manual region of interests delineation versus automated global segmentation. The results show excellent reproducibility of pharmacokinetic variables derived from DCE-MRI in healthy controls.
JOURNAL OF MAGNETIC RESONANCE IMAGING
(2023)
Article
Endocrinology & Metabolism
Mark B. Vestergaard, Helle K. Iversen, Sofie Amalie Simonsen, Ulrich Lindberg, Stig P. Cramer, Ulrik B. Andersen, Henrik B. W. Larsson
Summary: Healthy cerebral perfusion is characterized by a homogeneous distribution of capillary transit times, but disruption of this homogeneity may hinder oxygen extraction. Capillary transit time heterogeneity (CTH) refers to some capillaries having excessively low blood flows, while others have excessively high blood flows, resulting in short transit times. CTH is often seen in cerebral vessel disease. This study aimed to investigate the relationship between CTH and cerebral steno-occlusive vessel disease. Results showed that patients with impaired cerebrovascular reserve capacity had elevated CTH and a significant reduction in cerebral metabolic rate of oxygen (CMRO2) after administration of acetazolamide (ACZ), indicating the potential negative impact of CTH on oxygen extraction. This highlights the importance of addressing CTH in patients with cerebral vessel disease.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Henrik Bo Wiberg Larsson, Ian Law, Thomas L. Andersen, Flemming L. Andersen, Barbara M. Fischer, Mark B. Vestergaard, Tanne S. W. Larsson, Ulrich Lindberg
Summary: New total-body PET scanners with a long axial field of view allow for noninvasive perfusion estimation of multiple tracers, providing detailed physiological insight into normal and pathologic tissue. This study investigates the use of a model-free Tikhonov generalized deconvolution method to estimate brain perfusion using five different PET tracers. The results demonstrate the feasibility of this approach and provide information about the fate of the tracers and their extraction fractions.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Physiology
Signe Sloth Madsen, Ulrich Lindberg, Sohail Asghar, Karsten Skovgaard Olsen, Kirsten Moller, Henrik Bo Wiberg Larsson, Mark Bitsch Vestergaard
Summary: This study investigated the reproducibility of cerebral physiology measurements in young healthy adults using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques. The results showed significant correlations between baseline and subsequent measurements for cerebral blood flow (CBF), global cerebral metabolic rate of oxygen (CMRO2), global arteriovenous oxygen saturation difference (A-V.O2), and cerebral lactate and N-acetyl-aspartate (NAA) concentrations. The reproducibility was highest for within-day measurements and declined over time.
FRONTIERS IN PHYSIOLOGY
(2023)