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  • 1
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2022-2-28)
    Abstract: To summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and to highlight the latest bench-to-bedside developments. Methods The current evidence regarding the potential for monitoring biomarkers was reviewed and individual modalities of metabolism and/or chemical composition imaging discussed. Perfusion, permeability, and microstructure imaging were similarly analyzed in Part 1 of this two-part review article and are valuable reading as background to this article. We appraise the clinic readiness of all the individual modalities and consider methodologies involving machine learning (radiomics) and the combination of MRI approaches (multiparametric imaging). Results The biochemical composition of high-grade gliomas is markedly different from healthy brain tissue. Magnetic resonance spectroscopy allows the simultaneous acquisition of an array of metabolic alterations, with choline-based ratios appearing to be consistently discriminatory in treatment response assessment, although challenges remain despite this being a mature technique. Promising directions relate to ultra-high field strengths, 2-hydroxyglutarate analysis, and the use of non-proton nuclei. Labile protons on endogenous proteins can be selectively targeted with chemical exchange saturation transfer to give high resolution images. The body of evidence for clinical application of amide proton transfer imaging has been building for a decade, but more evidence is required to confirm chemical exchange saturation transfer use as a monitoring biomarker. Multiparametric methodologies, including the incorporation of nuclear medicine techniques, combine probes measuring different tumor properties. Although potentially synergistic, the limitations of each individual modality also can be compounded, particularly in the absence of standardization. Machine learning requires large datasets with high-quality annotation; there is currently low-level evidence for monitoring biomarker clinical application. Conclusion Advanced MRI techniques show huge promise in treatment response assessment. The clinical readiness analysis highlights that most monitoring biomarkers require standardized international consensus guidelines, with more facilitation regarding technique implementation and reporting in the clinic.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 2
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-3-3)
    Abstract: Summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and highlight the latest bench-to-bedside developments. Methods Experts in advanced MRI techniques applied to high-grade glioma treatment response assessment convened through a European framework. Current evidence regarding the potential for monitoring biomarkers in adult high-grade glioma is reviewed, and individual modalities of perfusion, permeability, and microstructure imaging are discussed (in Part 1 of two). In Part 2, we discuss modalities related to metabolism and/or chemical composition, appraise the clinic readiness of the individual modalities, and consider post-processing methodologies involving the combination of MRI approaches (multiparametric imaging) or machine learning (radiomics). Results High-grade glioma vasculature exhibits increased perfusion, blood volume, and permeability compared with normal brain tissue. Measures of cerebral blood volume derived from dynamic susceptibility contrast-enhanced MRI have consistently provided information about brain tumor growth and response to treatment; it is the most clinically validated advanced technique. Clinical studies have proven the potential of dynamic contrast-enhanced MRI for distinguishing post-treatment related effects from recurrence, but the optimal acquisition protocol, mode of analysis, parameter of highest diagnostic value, and optimal cut-off points remain to be established. Arterial spin labeling techniques do not require the injection of a contrast agent, and repeated measurements of cerebral blood flow can be performed. The absence of potential gadolinium deposition effects allows widespread use in pediatric patients and those with impaired renal function. More data are necessary to establish clinical validity as monitoring biomarkers. Diffusion-weighted imaging, apparent diffusion coefficient analysis, diffusion tensor or kurtosis imaging, intravoxel incoherent motion, and other microstructural modeling approaches also allow treatment response assessment; more robust data are required to validate these alone or when applied to post-processing methodologies. Conclusion Considerable progress has been made in the development of these monitoring biomarkers. Many techniques are in their infancy, whereas others have generated a larger body of evidence for clinical application.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 3
    In: European Child & Adolescent Psychiatry, Springer Science and Business Media LLC, Vol. 28, No. 7 ( 2019-7), p. 1011-1022
    Type of Medium: Online Resource
    ISSN: 1018-8827 , 1435-165X
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 1463026-6
    SSG: 5,2
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  • 4
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 37, No. 6 ( 2017-06), p. 1994-2001
    Abstract: It is unclear whether cerebral blood flow responses to hypoglycemia are altered in people with type 1 diabetes and impaired awareness of hypoglycemia. The aim of this study was to investigate the effect of hypoglycemia on both global and regional cerebral blood flow in type 1 diabetes patients with impaired awareness of hypoglycemia, type 1 diabetes patients with normal awareness of hypoglycemia and healthy controls ( n = 7 per group). The subjects underwent a hyperinsulinemic euglycemic–hypoglycemic glucose clamp in a 3 T MR system. Global and regional changes in cerebral blood flow were determined by arterial spin labeling magnetic resonance imaging, at the end of both glycemic phases. Hypoglycemia generated typical symptoms in patients with type 1 diabetes and normal awareness of hypoglycemia and healthy controls, but not in patients with impaired awareness of hypoglycemia. Conversely, hypoglycemia increased global cerebral blood flow in patients with impaired awareness of hypoglycemia, which was not observed in the other two groups. Regionally, hypoglycemia caused a redistribution of cerebral blood flow towards the thalamus of both patients with normal awareness of hypoglycemia and healthy controls, consistent with activation of brain regions associated with the autonomic response to hypoglycemia. No such redistribution was found in the patients with impaired awareness of hypoglycemia. An increase in global cerebral blood flow may enhance nutrient supply to the brain, hence suppressing symptomatic awareness of hypoglycemia. Altogether these results suggest that changes in cerebral blood flow during hypoglycemia contribute to impaired awareness of hypoglycemia.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2039456-1
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  • 5
    In: Magnetic Resonance in Medicine, Wiley, Vol. 87, No. 2 ( 2022-02), p. 872-883
    Abstract: Current challenges of in vivo CEST imaging include overlapping signals from different pools. The overlap arises from closely resonating pools and/or the broad magnetization transfer contrast (MTC) from macromolecules. This study aimed to evaluate the feasibility of variable delay multipulse (VDMP) CEST to separately assess solute pools with different chemical exchange rates in the human brain in vivo , while mitigating the MTC. Methods VDMP saturation buildup curves were simulated for amines, amides, and relayed nuclear Overhauser effect. VDMP data were acquired from glutamate and bovine serum albumin phantoms, and from six healthy volunteers at 7T. For the in vivo data, MTC removal was performed via a three‐pool Lorentzian fitting. Different B 1 amplitudes and mixing times were used to evaluate CEST pools with different exchange rates. Results The results show the importance of removing MTC when applying VDMP in vivo and the influence of B 1 for distinguishing different pools. Finally, the optimal B 1 and mixing times to effectively saturate slow‐ and fast‐exchanging components are also reported. Slow‐exchanging amides and rNOE components could be distinguished when using B 1 = 1 μT and t mix = 10 ms and 40 ms, respectively. Fast‐exchanging components reached the highest saturation when using a B 1 = 2.8 μT and t mix = 0 ms. Conclusion VDMP is a powerful CEST‐editing tool, exploiting chemical exchange‐rate differences. After MTC removal, it allows separate assessment of slow‐ and fast‐exchanging solute pools in in vivo human brain.
    Type of Medium: Online Resource
    ISSN: 0740-3194 , 1522-2594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1493786-4
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  • 6
    Online Resource
    Online Resource
    Wiley ; 2022
    In:  Magnetic Resonance in Medicine Vol. 88, No. 1 ( 2022-07), p. 71-82
    In: Magnetic Resonance in Medicine, Wiley, Vol. 88, No. 1 ( 2022-07), p. 71-82
    Abstract: Single‐voxel MRS (SV MRS) requires robust volume localization as well as optimized crusher and phase‐cycling schemes to reduce artifacts arising from signal outside the volume of interest. However, due to local magnetic field gradients (B 0 inhomogeneities), signal that was dephased by the crusher gradients during acquisition might rephase, leading to artifacts in the spectrum. Here, we analyzed this mechanism, aiming to identify the source of signals arising from unwanted coherence pathways (spurious signals) in SV MRS from a B 0 map. Methods We investigated all possible coherence pathways associated with imperfect localization in a semi‐localized by adiabatic selective refocusing (semi‐LASER) sequence for potential rephasing of signals arising from unwanted coherence pathways by a local magnetic field gradient. We searched for locations in the B 0 map where the signal dephasing due to external (crusher) and internal (B 0 ) field gradients canceled out. To confirm the mechanism, SV‐MR spectra (TE = 31 ms) and 3D‐CSI data with the same volume localization as the SV experiments were acquired from a phantom and 2 healthy volunteers. Results Our analysis revealed that potential sources of spurious signals were scattered over multiple locations throughout the brain. This was confirmed by 3D‐CSI data. Moreover, we showed that the number of potential locations where spurious signals could originate from monotonically decreases with crusher strength. Conclusion We proposed a method to identify the source of spurious signals in SV 1 H MRS using a B 0 map. This can facilitate MRS sequence design to be less sensitive to experimental artifacts.
    Type of Medium: Online Resource
    ISSN: 0740-3194 , 1522-2594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1493786-4
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  • 7
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2017
    In:  Magnetic Resonance Materials in Physics, Biology and Medicine Vol. 30, No. 6 ( 2017-12), p. 537-544
    In: Magnetic Resonance Materials in Physics, Biology and Medicine, Springer Science and Business Media LLC, Vol. 30, No. 6 ( 2017-12), p. 537-544
    Type of Medium: Online Resource
    ISSN: 0968-5243 , 1352-8661
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 1502491-X
    SSG: 11
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  • 8
    In: Journal of Neuroscience Methods, Elsevier BV, Vol. 253 ( 2015-09), p. 116-125
    Type of Medium: Online Resource
    ISSN: 0165-0270
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 1500499-5
    SSG: 12
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  • 9
    In: BMJ Open Diabetes Research & Care, BMJ, Vol. 10, No. 2 ( 2022-03), p. e002401-
    Abstract: Impaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased cerebral blood flow (CBF) during hypoglycemia appear to be involved in the pathogenesis of impaired awareness of hypoglycemia. Here we examine the effect of lactate on CBF during hypoglycemia. Research design and methods Nine people with type 1 diabetes and normal awareness of hypoglycemia underwent two hyperinsulinemic euglycemic-hypoglycemic (3.0 mmol/L) glucose clamps in a 3T MR system, once with sodium lactate infusion and once with sodium chloride infusion. Global and regional changes in CBF were determined using pseudocontinuous arterial spin labeling. Results Lactate (3.3±0.6 vs 0.9±0.2 mmol/L during lactate infusion vs placebo infusion, respectively) suppressed the counter-regulatory hormone responses to hypoglycemia. Global CBF increased considerably in response to intravenous lactate infusion but did not further increase during hypoglycemia. Lactate also blunted the hypoglycemia-induced regional redistribution of CBF towards the thalamus. Conclusions Elevated lactate levels enhance global CBF and blunt the thalamic CBF response during hypoglycemia in patients with type 1 diabetes, mimicking observations of impaired awareness of hypoglycemia. These findings suggest that alteration of CBF associated with lactate may play a role in some aspects of the development of impaired awareness of hypoglycemia. Trial registration number NCT03730909 .
    Type of Medium: Online Resource
    ISSN: 2052-4897
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2732918-5
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  • 10
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 39, No. 10 ( 2019-10), p. 1974-1982
    Abstract: Administration of lactate during hypoglycemia suppresses symptoms and counterregulatory responses, as seen in patients with type 1 diabetes and impaired awareness of hypoglycemia (IAH), presumably because lactate can substitute for glucose as a brain fuel. Here, we examined whether lactate administration, in a dose sufficient to impair awareness of hypoglycemia, affects brain lactate levels in patients with normal awareness of hypoglycemia (NAH). Patients with NAH ( n = 6) underwent two euglycemic-hypoglycemic clamps (2.8 mmol/L), once with sodium lactate infusion (NAH w|lac) and once with saline infusion (NAH w|placebo). Results were compared to those obtained during lactate administration in patients with IAH ( n = 7) (IAH w|lac). Brain lactate levels were determined continuously with J-difference editing 1 H-MRS. During lactate infusion, symptom and adrenaline responses to hypoglycemia were considerably suppressed in NAH. Infusion of lactate increased brain lactate levels modestly, but comparably, in both groups (mean increase in NAH w|lac: 0.12 ± 0.05 µmol/g and in IAH w|lac: 0.06 ± 0.04 µmol/g). The modest increase in brain lactate may suggest that the excess of lactate is immediately metabolized by the brain, which in turn may explain the suppressive effects of lactate on awareness of hypoglycemia observed in patients with NAH.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2039456-1
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