Nathalie Just - Academia.edu (original) (raw)
Papers by Nathalie Just
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 1999
MeV ions passing through polymer ®lms modify their electrical and optical properties and these ch... more MeV ions passing through polymer ®lms modify their electrical and optical properties and these changes are related to changes in the chemical structures of the polymers. The eects of certain cross linking enhancers, such as sulfur and other pendant molecules, on the ion beam modi®cation process were investigated. Stacked, thin ®lms of polyethersulfone, polyvinyl chloride and polystyrene were bombarded with MeV helium ions and the induced changes in the chemical structure of the polymers were studied with Raman microprobe analysis and RBS combined with in situ residual gas analysis. FTIR spectroscopy was used to categorize the changes in the optical properties. The results were then compared with those from previously studied polyethylene and polyvinylidene chloride polymers.
ISMRM Annual Meeting
A processing and fitting challenge was initiated for the “Best practices & Tools for Diffusion MR... more A processing and fitting challenge was initiated for the “Best practices & Tools for Diffusion MR Spectroscopy” workshop held at the Lorentz Center (Leiden, NL) in September 2021. Our goal was to assess variabilities in processing and fitting pipelines and possibly identify the most robust steps to analyze diffusion-weighted MRS data. A “brain-like” dataset of diffusion-weighted spectra was simulated and participants were asked to analyze the data with their routinely used pipelines. Results showed that variabilities between participants (n=8) particularly increased at higher b-values and for J-coupled metabolites (Ins, Glu) as a result of lower SNR and higher CRLB values.
ISMRM Annual Meeting
Metabolite diffusion provide the unique ability to study the intracellular environment of specifi... more Metabolite diffusion provide the unique ability to study the intracellular environment of specific cell types of the brain. Multiple studies suggest that the diffusivity along dendrites and axons is time dependent due to variations in diameter. We explore the signal due to such effects in Monte Carlo simulations in settings feasible for preclinical PGSE measurements and find that time dependent kurtosis, but not diffusivity provide the most potent source of contrast to this effect. We observe similar effects of intraneuronal NAA diffusion in rat.
Médecine du Sommeil, 2021
ISMRM Annual Meeting
In-vivo Manganese-Enhanced MRI (MEMRI) studies have shown important potential in rodents for the ... more In-vivo Manganese-Enhanced MRI (MEMRI) studies have shown important potential in rodents for the delineation of cytoarchitectural brain features and of functional details. Ex-vivo MEMRI on the other hand offers the possibility to investigate brain microstructure and function with improved spatial resolution and no motion artefacts. Here, ex-vivo lamb brains were immersed in a highly concentrated MnCl2 solution for a month and revealed interesting cytoarchitectural features already 24 hours after immersion and up to 3 months after the end of immersion on MPRAGE images at 3T. A novel ex-vivo MEMRI approach is proposed, which could benefit MEMRI translation to human studies.
ISMRM Annual Meeting
Tensor-valued diffusion encoding can be confounded by time-dependent diffusion (TDD). Matching se... more Tensor-valued diffusion encoding can be confounded by time-dependent diffusion (TDD). Matching sensitivity to TDD or tuning of b-tensors with different shapes is needed for unbiased microstructure assessment. We present a method for tuning linear tensor encoding (LTE) to spherical tensor encoding (STE), which could be optimized for different hardware constraints. Furthermore, we introduce the spectral principle axes system (SPAS), representing spectral anisotropy of STE. The SPAS LTEs could provide an alternative to tuning and enable disentangling effects of microscopic anisotropy and TDD, useful to correlate cell shape and size.
NeuroImage, 2019
Most studies involving BOLD fMRI in basic neuroscience research are conducted with anesthetized a... more Most studies involving BOLD fMRI in basic neuroscience research are conducted with anesthetized animals. This study investigates neural and hemodynamic activity through a combination of experiments comprising BOLD fMRI, optical calcium recordings and ASL in vivo. Patch clamp experiments of neurons were conducted to evaluate electrophysiological correlates of neural activity in vitro. Various anesthetic conditions embracing numerous anesthetic depths evoked by different concentrations of isoflurane (ISO) and different degrees of hypercapnia under a constant stimulus were investigated. We observed that different anesthetic conditions had major impact on the results obtained, particularly that anesthesia could cause a massive divergence of different experimental modalities. In ventilated animals, robust BOLD responses were detectable even with relatively deep anesthesia, while in non-ventilated animals, BOLD responses were not detectable under these conditions. This was most likely due to hypercapnia caused by respiratory depression, as in ventilated animals administered CO 2 had the same effect. This observation agreed with measurements of perfusion, which showed that inhaled CO 2 increased perfusion significantly, while ISO did not. In optical calcium measurements, higher concentrations of ISO decreased spontaneous neural activity, but not stimulus-evoked responses. This observation was explained by a generally lower excitability of neurons under ISO, which suppressed spontaneous activity, and consequently left more neurons available to fire synchronously in response to a stimulus. Interpreting this phenomenon as an integrated signal of independent single neurons was supported by patch clamp experiments as the number of action potentials (APs) per stimulus was decreased by addition of CO 2. Addition of ISO on the other hand had no significant effect. Our results provide an explanation on the cellular level for anesthesia-dependent observations in previous studies of task-induced BOLD and resting state connectivity. They further inform selection of the adequate anesthetic regimen for a given combination of modalities.
![Research paper thumbnail of {"__content__"=>"Thymidine Metabolism as Confounding Factor of 3'-Deoxy-3'-[F]Fluorothymidine Uptake after Therapy in a Colorectal Cancer Model.", "sup"=>{"__content__"=>"18"}}](https://attachments.academia-assets.com/95889790/thumbnails/1.jpg)
](Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 23, 2018
Non-invasive monitoring of tumor therapy response helps in developing personalized treatment stra... more Non-invasive monitoring of tumor therapy response helps in developing personalized treatment strategies. Here, we performed sequential positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) to evaluate changes induced by a FOLFOX-like combination chemotherapy in colorectal cancer (CRC) xenografts, to identify the cellular and molecular determinants of these imaging biomarkers. Tumor bearing CD1 nude mice, engrafted with FOLFOX-sensitive Colo205 CRC xenografts, were treated with FOLFOX (5 fluorouracil, leucovorin and oxaliplatin) in weekly intervals. On d1, d2, d6, d9 and d13 of therapy, tumors were assessed by in vivo imaging and ex vivo analyses. In addition, HCT116 xenografts, which did not respond to the FOLFOX treatment, were imaged on d1 of therapy. In Colo205 xenografts, FOLFOX induced a profound increase in uptake of the proliferation PET tracer 3'-deoxy-3'-[F]fluorothymidine ([F]FLT), which was accompanied by increases in marker...
Glia, Mar 9, 2017
Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic... more Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate-glutamine cycle (VNT ) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation. After identifying the activated cortical volume by blood oxygenation level-dependent functional magnetic resonance imaging, 1 H MRS was performed to measure stimulation-induced variations in metabolite concentrations. Relative to baseline, stimulation of cortical activity for 20 min caused a...
Frontiers in physiology, 2017
The Excitatory-Inhibitory balance (EIB) between glutamatergic and GABAergic neurons is known to r... more The Excitatory-Inhibitory balance (EIB) between glutamatergic and GABAergic neurons is known to regulate the function of thalamocortical neurocircuits. The thalamus is known as an important relay for glutamatergic and GABAergic signals ascending/descending to/from the somatosensory cortex in rodents. However, new investigations attribute a larger role to thalamic nuclei as modulators of information processing within the cortex. In this study, functional Magnetic Resonance Spectroscopy (fMRS) was used to measure glutamate (Glu) and GABA associations with BOLD responses during activation of the thalamus to barrel cortex (S1BF) pathway at 9.4T. In line with previous studies in humans, resting GABA and Glu correlated negatively and positively respectively with BOLD responses in S1BF. Moreover, a significant negative correlation (R = -0.68, p = 0.0024) between BOLD responses in the thalamus and the barrel cortex was found. Rats with low Glu levels and high resting GABA levels in S1BF dem...
Journal of neuroscience research, Nov 19, 2017
Barbiturates, commonly used as general anaesthetics, depress neuronal activity and thus cerebral ... more Barbiturates, commonly used as general anaesthetics, depress neuronal activity and thus cerebral metabolism. Moreover, they are likely to disrupt the metabolic support of astrocytes to neurons, as well as the uptake of nutrients from circulation. By employing (13) C magnetic resonance spectroscopy (MRS) in vivo at high magnetic field, we characterized neuronal and astrocytic pathways of energy metabolism in the rat cortex under thiopental anaesthesia. The neuronal tricarboxylic acid (TCA) cycle rate was 0.46 ± 0.02 µmol/g/min, and the rate of the glutamate-glutamine cycle was 0.09 ± 0.02 µmol/g/min. In astrocytes, the TCA cycle rate was 0.16 ± 0.02 µmol/g/min, accounting for a quarter of whole brain glucose oxidation, pyruvate carboxylase rate was 0.02 ± 0.01 µmol/g/min, and glutamine synthetase was 0.12 ± 0.01 µmol/g/min. Relative to previous experiments under light α-chloralose anaesthesia, thiopental reduced oxidative metabolism in neurons and even more so in astrocytes. Interest...
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, May 28, 2016
Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the imp... more Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the importance of functional compartmentation between neurons and glial cells, there is still debate on the specific regulation of pathways of energy metabolism at different activity levels. Using (13)C magnetic resonance spectroscopy (MRS) in vivo, we determined fluxes of energy metabolism in the rat cortex under α-chloralose anaesthesia at rest and during electrical stimulation of the paws. Compared to resting metabolism, the stimulated rat cortex exhibited increased glutamate-glutamine cycle (+67 nmol/g/min, +95%, P < 0.001) and tricarboxylic (TCA) cycle rate in both neurons (+62 nmol/g/min, +12%, P < 0.001) and astrocytes (+68 nmol/g/min, +22%, P = 0.072). A minor, non-significant modification of the flux through pyruvate carboxylase was observed during stimulation (+5 nmol/g/min, +8%). Altogether, this increase in metabolism amounted to a 15% (67 nmol/g/min, P < 0.001) increase in...
British journal of cancer, Jan 9, 2014
By definition, tumours are heterogeneous. They are defined by marked differences in cells, microe... more By definition, tumours are heterogeneous. They are defined by marked differences in cells, microenvironmental factors (oxygenation levels, pH, VEGF, VPF and TGF-α) metabolism, vasculature, structure and function that in turn translate into heterogeneous drug delivery and therapeutic outcome. Ways to estimate quantitatively tumour heterogeneity can improve drug discovery, treatment planning and therapeutic responses. It is therefore of paramount importance to have reliable and reproducible biomarkers of cancerous lesions' heterogeneity. During the past decade, the number of studies using histogram approaches increased drastically with various magnetic resonance imaging (MRI) techniques (DCE-MRI, DWI, SWI etc.) although information on tumour heterogeneity remains poorly exploited. This fact can be attributed to a poor knowledge of the available metrics and of their specific meaning as well as to the lack of literature references to standardised histogram methods with which surroga...
NMR in Biomedicine, 2015
Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in exper... more Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience, although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods, it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long-term modifications induced by these functional challenges. While different types of sustained stimulation paradigm have been explored in human studies, the BOLD response is typically limited to a few minutes in animal models, due to fatigue, anesthesia effects and physiological instability. In the present study, the rat forepaw was electrically stimulated for 2 h, which resulted in a prolonged and localized cortical BOLD response over that period. The stimulation paradigm, including an inter-stimulus interval (ISI) of 10 s, that is 25% of the total time, was applied at constant or variable frequency over 2 h. The steady-state level of the BOLD response was reached after 15-20 min of stimulation and was maintained until the end of the stimulation. On average, no substantial loss in activated volume was observed at the end of the stimulation, but less variability in the fraction of remaining activated volume and higher steady-state BOLD amplitude were observed when stimulation frequency was varied between 2 and 3 Hz every 5 min. We conclude that the combination of ISI and variable stimulus frequency reproducibly results in robust, prolonged and localized BOLD activation.
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 1999
MeV ions passing through polymer ®lms modify their electrical and optical properties and these ch... more MeV ions passing through polymer ®lms modify their electrical and optical properties and these changes are related to changes in the chemical structures of the polymers. The eects of certain cross linking enhancers, such as sulfur and other pendant molecules, on the ion beam modi®cation process were investigated. Stacked, thin ®lms of polyethersulfone, polyvinyl chloride and polystyrene were bombarded with MeV helium ions and the induced changes in the chemical structure of the polymers were studied with Raman microprobe analysis and RBS combined with in situ residual gas analysis. FTIR spectroscopy was used to categorize the changes in the optical properties. The results were then compared with those from previously studied polyethylene and polyvinylidene chloride polymers.
ISMRM Annual Meeting
A processing and fitting challenge was initiated for the “Best practices & Tools for Diffusion MR... more A processing and fitting challenge was initiated for the “Best practices & Tools for Diffusion MR Spectroscopy” workshop held at the Lorentz Center (Leiden, NL) in September 2021. Our goal was to assess variabilities in processing and fitting pipelines and possibly identify the most robust steps to analyze diffusion-weighted MRS data. A “brain-like” dataset of diffusion-weighted spectra was simulated and participants were asked to analyze the data with their routinely used pipelines. Results showed that variabilities between participants (n=8) particularly increased at higher b-values and for J-coupled metabolites (Ins, Glu) as a result of lower SNR and higher CRLB values.
ISMRM Annual Meeting
Metabolite diffusion provide the unique ability to study the intracellular environment of specifi... more Metabolite diffusion provide the unique ability to study the intracellular environment of specific cell types of the brain. Multiple studies suggest that the diffusivity along dendrites and axons is time dependent due to variations in diameter. We explore the signal due to such effects in Monte Carlo simulations in settings feasible for preclinical PGSE measurements and find that time dependent kurtosis, but not diffusivity provide the most potent source of contrast to this effect. We observe similar effects of intraneuronal NAA diffusion in rat.
Médecine du Sommeil, 2021
ISMRM Annual Meeting
In-vivo Manganese-Enhanced MRI (MEMRI) studies have shown important potential in rodents for the ... more In-vivo Manganese-Enhanced MRI (MEMRI) studies have shown important potential in rodents for the delineation of cytoarchitectural brain features and of functional details. Ex-vivo MEMRI on the other hand offers the possibility to investigate brain microstructure and function with improved spatial resolution and no motion artefacts. Here, ex-vivo lamb brains were immersed in a highly concentrated MnCl2 solution for a month and revealed interesting cytoarchitectural features already 24 hours after immersion and up to 3 months after the end of immersion on MPRAGE images at 3T. A novel ex-vivo MEMRI approach is proposed, which could benefit MEMRI translation to human studies.
ISMRM Annual Meeting
Tensor-valued diffusion encoding can be confounded by time-dependent diffusion (TDD). Matching se... more Tensor-valued diffusion encoding can be confounded by time-dependent diffusion (TDD). Matching sensitivity to TDD or tuning of b-tensors with different shapes is needed for unbiased microstructure assessment. We present a method for tuning linear tensor encoding (LTE) to spherical tensor encoding (STE), which could be optimized for different hardware constraints. Furthermore, we introduce the spectral principle axes system (SPAS), representing spectral anisotropy of STE. The SPAS LTEs could provide an alternative to tuning and enable disentangling effects of microscopic anisotropy and TDD, useful to correlate cell shape and size.
NeuroImage, 2019
Most studies involving BOLD fMRI in basic neuroscience research are conducted with anesthetized a... more Most studies involving BOLD fMRI in basic neuroscience research are conducted with anesthetized animals. This study investigates neural and hemodynamic activity through a combination of experiments comprising BOLD fMRI, optical calcium recordings and ASL in vivo. Patch clamp experiments of neurons were conducted to evaluate electrophysiological correlates of neural activity in vitro. Various anesthetic conditions embracing numerous anesthetic depths evoked by different concentrations of isoflurane (ISO) and different degrees of hypercapnia under a constant stimulus were investigated. We observed that different anesthetic conditions had major impact on the results obtained, particularly that anesthesia could cause a massive divergence of different experimental modalities. In ventilated animals, robust BOLD responses were detectable even with relatively deep anesthesia, while in non-ventilated animals, BOLD responses were not detectable under these conditions. This was most likely due to hypercapnia caused by respiratory depression, as in ventilated animals administered CO 2 had the same effect. This observation agreed with measurements of perfusion, which showed that inhaled CO 2 increased perfusion significantly, while ISO did not. In optical calcium measurements, higher concentrations of ISO decreased spontaneous neural activity, but not stimulus-evoked responses. This observation was explained by a generally lower excitability of neurons under ISO, which suppressed spontaneous activity, and consequently left more neurons available to fire synchronously in response to a stimulus. Interpreting this phenomenon as an integrated signal of independent single neurons was supported by patch clamp experiments as the number of action potentials (APs) per stimulus was decreased by addition of CO 2. Addition of ISO on the other hand had no significant effect. Our results provide an explanation on the cellular level for anesthesia-dependent observations in previous studies of task-induced BOLD and resting state connectivity. They further inform selection of the adequate anesthetic regimen for a given combination of modalities.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 23, 2018
Non-invasive monitoring of tumor therapy response helps in developing personalized treatment stra... more Non-invasive monitoring of tumor therapy response helps in developing personalized treatment strategies. Here, we performed sequential positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) to evaluate changes induced by a FOLFOX-like combination chemotherapy in colorectal cancer (CRC) xenografts, to identify the cellular and molecular determinants of these imaging biomarkers. Tumor bearing CD1 nude mice, engrafted with FOLFOX-sensitive Colo205 CRC xenografts, were treated with FOLFOX (5 fluorouracil, leucovorin and oxaliplatin) in weekly intervals. On d1, d2, d6, d9 and d13 of therapy, tumors were assessed by in vivo imaging and ex vivo analyses. In addition, HCT116 xenografts, which did not respond to the FOLFOX treatment, were imaged on d1 of therapy. In Colo205 xenografts, FOLFOX induced a profound increase in uptake of the proliferation PET tracer 3'-deoxy-3'-[F]fluorothymidine ([F]FLT), which was accompanied by increases in marker...
Glia, Mar 9, 2017
Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic... more Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate-glutamine cycle (VNT ) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation. After identifying the activated cortical volume by blood oxygenation level-dependent functional magnetic resonance imaging, 1 H MRS was performed to measure stimulation-induced variations in metabolite concentrations. Relative to baseline, stimulation of cortical activity for 20 min caused a...
Frontiers in physiology, 2017
The Excitatory-Inhibitory balance (EIB) between glutamatergic and GABAergic neurons is known to r... more The Excitatory-Inhibitory balance (EIB) between glutamatergic and GABAergic neurons is known to regulate the function of thalamocortical neurocircuits. The thalamus is known as an important relay for glutamatergic and GABAergic signals ascending/descending to/from the somatosensory cortex in rodents. However, new investigations attribute a larger role to thalamic nuclei as modulators of information processing within the cortex. In this study, functional Magnetic Resonance Spectroscopy (fMRS) was used to measure glutamate (Glu) and GABA associations with BOLD responses during activation of the thalamus to barrel cortex (S1BF) pathway at 9.4T. In line with previous studies in humans, resting GABA and Glu correlated negatively and positively respectively with BOLD responses in S1BF. Moreover, a significant negative correlation (R = -0.68, p = 0.0024) between BOLD responses in the thalamus and the barrel cortex was found. Rats with low Glu levels and high resting GABA levels in S1BF dem...
Journal of neuroscience research, Nov 19, 2017
Barbiturates, commonly used as general anaesthetics, depress neuronal activity and thus cerebral ... more Barbiturates, commonly used as general anaesthetics, depress neuronal activity and thus cerebral metabolism. Moreover, they are likely to disrupt the metabolic support of astrocytes to neurons, as well as the uptake of nutrients from circulation. By employing (13) C magnetic resonance spectroscopy (MRS) in vivo at high magnetic field, we characterized neuronal and astrocytic pathways of energy metabolism in the rat cortex under thiopental anaesthesia. The neuronal tricarboxylic acid (TCA) cycle rate was 0.46 ± 0.02 µmol/g/min, and the rate of the glutamate-glutamine cycle was 0.09 ± 0.02 µmol/g/min. In astrocytes, the TCA cycle rate was 0.16 ± 0.02 µmol/g/min, accounting for a quarter of whole brain glucose oxidation, pyruvate carboxylase rate was 0.02 ± 0.01 µmol/g/min, and glutamine synthetase was 0.12 ± 0.01 µmol/g/min. Relative to previous experiments under light α-chloralose anaesthesia, thiopental reduced oxidative metabolism in neurons and even more so in astrocytes. Interest...
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, May 28, 2016
Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the imp... more Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the importance of functional compartmentation between neurons and glial cells, there is still debate on the specific regulation of pathways of energy metabolism at different activity levels. Using (13)C magnetic resonance spectroscopy (MRS) in vivo, we determined fluxes of energy metabolism in the rat cortex under α-chloralose anaesthesia at rest and during electrical stimulation of the paws. Compared to resting metabolism, the stimulated rat cortex exhibited increased glutamate-glutamine cycle (+67 nmol/g/min, +95%, P < 0.001) and tricarboxylic (TCA) cycle rate in both neurons (+62 nmol/g/min, +12%, P < 0.001) and astrocytes (+68 nmol/g/min, +22%, P = 0.072). A minor, non-significant modification of the flux through pyruvate carboxylase was observed during stimulation (+5 nmol/g/min, +8%). Altogether, this increase in metabolism amounted to a 15% (67 nmol/g/min, P < 0.001) increase in...
British journal of cancer, Jan 9, 2014
By definition, tumours are heterogeneous. They are defined by marked differences in cells, microe... more By definition, tumours are heterogeneous. They are defined by marked differences in cells, microenvironmental factors (oxygenation levels, pH, VEGF, VPF and TGF-α) metabolism, vasculature, structure and function that in turn translate into heterogeneous drug delivery and therapeutic outcome. Ways to estimate quantitatively tumour heterogeneity can improve drug discovery, treatment planning and therapeutic responses. It is therefore of paramount importance to have reliable and reproducible biomarkers of cancerous lesions' heterogeneity. During the past decade, the number of studies using histogram approaches increased drastically with various magnetic resonance imaging (MRI) techniques (DCE-MRI, DWI, SWI etc.) although information on tumour heterogeneity remains poorly exploited. This fact can be attributed to a poor knowledge of the available metrics and of their specific meaning as well as to the lack of literature references to standardised histogram methods with which surroga...
NMR in Biomedicine, 2015
Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in exper... more Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience, although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods, it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long-term modifications induced by these functional challenges. While different types of sustained stimulation paradigm have been explored in human studies, the BOLD response is typically limited to a few minutes in animal models, due to fatigue, anesthesia effects and physiological instability. In the present study, the rat forepaw was electrically stimulated for 2 h, which resulted in a prolonged and localized cortical BOLD response over that period. The stimulation paradigm, including an inter-stimulus interval (ISI) of 10 s, that is 25% of the total time, was applied at constant or variable frequency over 2 h. The steady-state level of the BOLD response was reached after 15-20 min of stimulation and was maintained until the end of the stimulation. On average, no substantial loss in activated volume was observed at the end of the stimulation, but less variability in the fraction of remaining activated volume and higher steady-state BOLD amplitude were observed when stimulation frequency was varied between 2 and 3 Hz every 5 min. We conclude that the combination of ISI and variable stimulus frequency reproducibly results in robust, prolonged and localized BOLD activation.