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Article ; Online: Blood-Brain Barrier Permeability to Water Measured Using Multiple Echo Time Arterial Spin Labeling MRI in the Aging Human Brain.

Mahroo, Amnah / Konstandin, Simon / Günther, Matthias

Journal of magnetic resonance imaging : JMRI

2023 Volume 59, Issue 4, Page(s) 1269–1282

Abstract: Background: The blood-brain barrier (BBB) plays a vital role in maintaining brain homeostasis, but the integrity of this barrier deteriorates slowly with aging. Noninvasive water exchange magnetic resonance imaging (MRI) methods may identify changes in ... ...

Abstract	Background: The blood-brain barrier (BBB) plays a vital role in maintaining brain homeostasis, but the integrity of this barrier deteriorates slowly with aging. Noninvasive water exchange magnetic resonance imaging (MRI) methods may identify changes in the BBB occurring with healthy aging. Purpose: To investigate age-related changes in the BBB permeability to water using multiple-echo-time (multi-TE) arterial spin labeling (ASL) MRI. Study type: Prospective, cohort. Population: Two groups of healthy humans-older group (≥50 years, mean age = 56 ± 4 years, N = 13, females = 5) and younger group (≤20 years, mean age = 18 ± 1, N = 13, females = 7). Field strength/sequence: A 3T, multi-TE Hadamard pCASL with 3D Gradient and Spin Echo (GRASE) readout. Assessment: Two different approaches of variable complexity were applied. A physiologically informed biophysical model with a higher complexity estimating time ( Statistics: Two-tailed unpaired Student t-test, Pearson's correlation coefficient and effect size. P < 0.05 was considered significant. Results: Older volunteers showed significant differences of 36% lower Data conclusions: Both approaches of Multi-TE ASL imaging showed sensitivity to detect age-related changes in the BBB permeability. High tissue fractions at the earliest TI and short Evidence level: 2 TECHNICAL EFFICACY: Stage 1.
MeSH term(s)	Female ; Humans ; Middle Aged ; Adolescent ; Young Adult ; Adult ; Blood-Brain Barrier/diagnostic imaging ; Water ; Prospective Studies ; Brain/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Permeability ; Spin Labels ; Cerebrovascular Circulation/physiology
Chemical Substances	Water (059QF0KO0R) ; Spin Labels
Language	English
Publishing date	2023-06-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1146614-5
ISSN	1522-2586 ; 1053-1807
ISSN (online)	1522-2586
ISSN	1053-1807
DOI	10.1002/jmri.28874
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Article ; Online: Blood-Brain Barrier Permeability to Water Measured Using Multiple Echo Time Arterial Spin Labeling MRI in the Aging Human Brain

Mahroo, Amnah / Konstandin, Simon / Günther, Matthias

2024

Abstract: 1269 ... 1282 ... Background: The blood–brain barrier (BBB) plays a vital role in maintaining brain homeostasis, but the integrity of this barrier deteriorates slowly with aging. Noninvasive water exchange magnetic resonance imaging (MRI) methods may ... ...

Abstract	1269 1282 Background: The blood–brain barrier (BBB) plays a vital role in maintaining brain homeostasis, but the integrity of this barrier deteriorates slowly with aging. Noninvasive water exchange magnetic resonance imaging (MRI) methods may identify changes in the BBB occurring with healthy aging. Purpose: To investigate age-related changes in the BBB permeability to water using multiple-echo-time (multi-TE) arterial spin labeling (ASL) MRI. Study Type: Prospective, cohort. Population: Two groups of healthy humans - older group (≥50 years, mean age = 56 ± 4 years, N = 13, females = 5) and younger group (≤20 years, mean age = 18 ± 1, N = 13, females = 7). Field Strength/Sequence: A 3T, multi-TE Hadamard pCASL with 3D Gradient and Spin Echo (GRASE) readout. Assessment: Two different approaches of variable complexity were applied. A physiologically informed biophysical model with a higher complexity estimating time ((Formula presented.)) taken by the labeled water to move across the BBB and a simpler model of triexponential decay measuring tissue transition rate ((Formula presented.). Statistics: Two-tailed unpaired Student t-test, Pearson's correlation coefficient and effect size. P < 0.05 was considered significant. Results: Older volunteers showed significant differences of 36% lower (Formula presented.), 29% lower cerebral perfusion, 17% pronged arterial transit time and 22% shorter intra-voxel transit time compared to the younger volunteers. Tissue fraction ((Formula presented.)) at the earliest TI = 1600 msec was significantly higher in the older group, which contributed to a significantly lower (Formula presented.) compared to the younger group. (Formula presented.) at TI = 1600 msec showed significant negative correlation with (Formula presented.) (r = -0.80), and (Formula presented.) and (Formula presented.) showed significant positive correlation (r = 0.73). Data Conclusions: Both approaches of Multi-TE ASL imaging showed sensitivity to detect age-related changes in the BBB permeability. High ...
Keywords	aging ; arterial spin labeling ; blood–brain barrier ; MRI ; multi-TE ; permeability
Subject code	610
Language	English
Publishing country	de
Document type	Article ; Online
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Article ; Online: Subject-specific timing adaption in time-encoded arterial spin labeling imaging.

Breutigam, Nora-Josefin / Hoinkiss, Daniel Christopher / Konstandin, Simon / Buck, Mareike Alicja / Mahroo, Amnah / Eickel, Klaus / von Samson-Himmelstjerna, Federico / Günther, Matthias

Magma (New York, N.Y.)

2023 Volume 37, Issue 1, Page(s) 53–68

Abstract: Objectives: One challenge in arterial spin labeling (ASL) is the high variability of arterial transit times (ATT), which causes associated arterial transit delay (ATD) artifacts. In patients with pathological changes, these artifacts occur when post- ... ...

Abstract	Objectives: One challenge in arterial spin labeling (ASL) is the high variability of arterial transit times (ATT), which causes associated arterial transit delay (ATD) artifacts. In patients with pathological changes, these artifacts occur when post-labeling delay (PLD) and bolus durations are not optimally matched to the subject, resulting in difficult quantification of cerebral blood flow (CBF) and ATT. This is also true for the free lunch approach in Hadamard-encoded pseudocontinuous ASL (H-pCASL). Material and methods: Five healthy volunteers were scanned with a 3 T MR-system. pCASL-subbolus timing was adjusted individually by the developed adaptive Walsh-ordered pCASL sequence and an automatic feedback algorithm. The quantification results for CBF and ATT and the respective standard deviations were compared with results obtained using recommended timings and intentionally suboptimal timings. Results: The algorithm individually adjusted the pCASL-subbolus PLD for each subject within the range of recommended timing for healthy subjects, with a mean intra-subject adjustment deviation of 47.15 ms for single-shot and 44.5 ms for segmented acquisition in three repetitions. Discussion: A first positive assessment of the results was performed on healthy volunteers. The extent to which the results can be transferred to patients and are of benefit must be investigated in follow-up studies.
MeSH term(s)	Humans ; Magnetic Resonance Imaging/methods ; Spin Labels ; Reproducibility of Results ; Arteries/diagnostic imaging ; Cerebrovascular Circulation/physiology
Chemical Substances	Spin Labels
Language	English
Publishing date	2023-09-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1160826-2
ISSN	1352-8661 ; 0968-5243
ISSN (online)	1352-8661
ISSN	0968-5243
DOI	10.1007/s10334-023-01121-y
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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Robust Multi-TE ASL-Based Blood-Brain Barrier Integrity Measurements.

Mahroo, Amnah / Buck, Mareike Alicja / Huber, Jörn / Breutigam, Nora-Josefin / Mutsaerts, Henk J M M / Craig, Martin / Chappell, Michael / Günther, Matthias

Frontiers in neuroscience

2021 Volume 15, Page(s) 719676

Abstract: Multiple echo-time arterial spin labelling (multi-TE ASL) offers estimation of blood-tissue exchange dynamics by probing the T2 relaxation of the labelled spins. In this study, we provide a recipe for robust assessment of exchange time (Texch) as a proxy ...

Abstract	Multiple echo-time arterial spin labelling (multi-TE ASL) offers estimation of blood-tissue exchange dynamics by probing the T2 relaxation of the labelled spins. In this study, we provide a recipe for robust assessment of exchange time (Texch) as a proxy measure of blood-brain barrier (BBB) integrity based on a test-retest analysis. This includes a novel scan protocol and an extension of the two-compartment model with an "intra-voxel transit time" (ITT) to address tissue transit effects. With the extended model, we intend to separate the underlying two distinct mechanisms of tissue transit and exchange. The performance of the extended model in comparison with the two-compartment model was evaluated in simulations. Multi-TE ASL sequence with two different bolus durations was used to acquire
Language	English
Publishing date	2021-12-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2021.719676
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Article ; Online: Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer's disease (DEBBIE-AD): a prospective observational multicohort study protocol.

Padrela, Beatriz / Mahroo, Amnah / Tee, Mervin / Sneve, Markus H / Moyaert, Paulien / Geier, Oliver / Kuijer, Joost P A / Beun, Soetkin / Nordhøy, Wibeke / Zhu, Yufei David / Buck, Mareike A / Hoinkiss, Daniel C / Konstandin, Simon / Huber, Jörn / Wiersinga, Julia / Rikken, Roos / de Leeuw, Diederick / Grydeland, Håkon / Tippett, Lynette /

BMJ open

2024 Volume 14, Issue 3, Page(s) e081635

Abstract: Introduction: Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer's disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose ... ...

Abstract	Introduction: Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer's disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). Methods and analysis: DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies. Ethics and dissemination: Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.
MeSH term(s)	Humans ; Blood-Brain Barrier/diagnostic imaging ; Blood-Brain Barrier/pathology ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Spin Labels ; Magnetic Resonance Imaging/methods ; Cognitive Dysfunction/diagnostic imaging ; Biomarkers ; Observational Studies as Topic
Chemical Substances	Spin Labels ; Biomarkers
Language	English
Publishing date	2024-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-081635
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Article: Nanomedicine and cancer immunotherapy: focus on indoleamine 2,3-dioxygenase inhibitors.

Zulfiqar, Bilal / Mahroo, Amnah / Nasir, Kaenat / Farooq, Rai Khalid / Jalal, Nasir / Rashid, Muhammad Usman / Asghar, Kashif

OncoTargets and therapy

2017 Volume 10, Page(s) 463–476

Abstract: Nanomedicine application in cancer immunotherapy is currently one of the most challenging areas in cancer therapeutic intervention. Innovative solutions have been provided by nanotechnology to deliver cytotoxic agents to the cancer cells partially ... ...

Abstract	Nanomedicine application in cancer immunotherapy is currently one of the most challenging areas in cancer therapeutic intervention. Innovative solutions have been provided by nanotechnology to deliver cytotoxic agents to the cancer cells partially affecting the healthy cells of the body during the process. Nanoparticle-based drug delivery is an emerging approach to stimulate the immune responses against cancer. The inhibition of indoleamine 2,3-dioxygenase (IDO) is a pivotal area of research in cancer immunotherapy. IDO is a heme-containing immunosuppressive enzyme, which is responsible for the degradation of tryptophan while increasing the concentration of kynurenine metabolites. Various preclinical studies showed that IDO inhibition in certain diseases may result in significant therapeutic effects. Here, we provide a review of the natural and synthetic inhibitors of IDO. These inhibitors are classified according to their source, inhibitory concentrations, the chemical structure, and the mechanism of action. Tumor-targeted chemotherapy is an advanced technique and has more advantages as compared to the conventional chemotherapy. Search for more efficient and less toxic nanoparticles in conjunction with compounds to inhibit IDO is still an area of interest for several research groups worldwide, especially revealing to be an extensive and a promising area in cancer therapeutic innovations.
Language	English
Publishing date	2017-01-21
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2495130-4
ISSN	1178-6930
ISSN	1178-6930
DOI	10.2147/OTT.S119362
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Article: Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis.

Asghar, Kashif / Ashiq, M Taimour / Zulfiqar, Bilal / Mahroo, Amnah / Nasir, Kaenat / Murad, Sheeba

Experimental and therapeutic medicine

2014 Volume 9, Issue 3, Page(s) 901–904

Abstract: Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. It plays a key role in various malignancies, infection and autoimmune diseases. IDO induces immunosuppression through the depletion of tryptophan and its downstream metabolites. Hepatitis C ...

Abstract	Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. It plays a key role in various malignancies, infection and autoimmune diseases. IDO induces immunosuppression through the depletion of tryptophan and its downstream metabolites. Hepatitis C virus (HCV) has infected more than 12 million individuals in Pakistan. The aim of the present study was to assess the expression and activity of IDO in HCV-infected patients. The functional enzymatic activity of IDO was measured by colorimetric assay. Serum samples from 100 HCV-infected patients were taken to examine IDO activity and samples from 100 healthy volunteers were used as controls. Liver sections from patients with HCV (n=35) and healthy controls (n=5) were used for immunohistochemical studies. Immunohistochemical analysis revealed that IDO was overexpressed in 28 of 35 (80%) cirrhotic liver samples, whereas 5 of 35 (14.2%) cases presented moderate and 2 of 35 (5.7%) cases presented mild expression of IDO. The enzymatic activity of IDO was significantly higher in the serum samples of HCV-infected patients as compared with those in the control. These data indicate that the expression of IDO correlated with the pathogenesis of disease. In summary, it is suggested that the high expression of IDO in the progressively cirrhotic livers of HCV-infected patients might contribute to the development of hepatocellular carcinoma. IDO may characterize a novel therapeutic target against HCV.
Language	English
Publishing date	2014-12-18
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2683844-8
ISSN	1792-1015 ; 1792-0981
ISSN (online)	1792-1015
ISSN	1792-0981
DOI	10.3892/etm.2014.2146
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Article ; Online: Nanomedicine and cancer immunotherapy

Zulfiqar B / Mahroo A / Nasir K / Farooq RK / Jalal N / Rashid MU / Asghar K

OncoTargets and Therapy, Vol Volume 10, Pp 463-

focus on indoleamine 2,3-dioxygenase inhibitors

2017 Volume 476

Abstract: Bilal Zulfiqar,1 Amnah Mahroo,1 Kaenat Nasir,1 Rai Khalid Farooq,2 Nasir Jalal,3 Muhammad Usman ...

Abstract	Bilal Zulfiqar,1 Amnah Mahroo,1 Kaenat Nasir,1 Rai Khalid Farooq,2 Nasir Jalal,3 Muhammad Usman Rashid,4 Kashif Asghar1,4 1Healthcare Biotechnology Department, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 2Department of Physiology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan; 3Department of Molecular and Cellular Pharmacology, Health Sciences Platform, Tianjin University, Tianjin, People’s Republic of China; 4Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), Lahore, Pakistan Abstract: Nanomedicine application in cancer immunotherapy is currently one of the most challenging areas in cancer therapeutic intervention. Innovative solutions have been provided by nanotechnology to deliver cytotoxic agents to the cancer cells partially affecting the healthy cells of the body during the process. Nanoparticle-based drug delivery is an emerging approach to stimulate the immune responses against cancer. The inhibition of indoleamine 2,3-dioxygenase (IDO) is a pivotal area of research in cancer immunotherapy. IDO is a heme-containing immunosuppressive enzyme, which is responsible for the degradation of tryptophan while increasing the concentration of kynurenine metabolites. Various preclinical studies showed that IDO inhibition in certain diseases may result in significant therapeutic effects. Here, we provide a review of the natural and synthetic inhibitors of IDO. These inhibitors are classified according to their source, inhibitory concentrations, the chemical structure, and the mechanism of action. Tumor-targeted chemotherapy is an advanced technique and has more advantages as compared to the conventional chemotherapy. Search for more efficient and less toxic nanoparticles in conjunction with compounds to inhibit IDO is still an area of interest for several research groups worldwide, especially revealing to be an extensive and a promising area in cancer therapeutic innovations. Keywords: indoleamine 2,3-dioxygenase, natural inhibitors of IDO, synthetic inhibitors of IDO, nanomedicine, cancer therapeutics
Keywords	Indoleamine 2 ; 3-dioxygenase (IDO) ; Natural inhibitors of IDO ; Synthetic inhibitors of IDO ; Nanomedicine ; Cancer therapeutics. ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Dove Medical Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Blood-Brain Barrier Permeability to Water Measured Using Multiple Echo Time Arterial Spin Labeling MRI in the Aging Human Brain.

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Article ; Online: Blood-Brain Barrier Permeability to Water Measured Using Multiple Echo Time Arterial Spin Labeling MRI in the Aging Human Brain

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Article ; Online: Subject-specific timing adaption in time-encoded arterial spin labeling imaging.

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Article: Robust Multi-TE ASL-Based Blood-Brain Barrier Integrity Measurements.

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Article ; Online: Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer's disease (DEBBIE-AD): a prospective observational multicohort study protocol.

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Article: Nanomedicine and cancer immunotherapy: focus on indoleamine 2,3-dioxygenase inhibitors.

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Article: Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis.

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Article ; Online: Nanomedicine and cancer immunotherapy

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