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Purpose Reliable detection and fitting of macromolecules (MM) are crucial for accurate quantification of brain short-echo time (TE) 1 H-MR spectra. An experimentally acquired single MM spectrum is commonly used. Higher spectral resolution at ultra-high field (UHF) led to increased interest in using a parametrized MM spectrum together with flexible spline baselines to address unpredicted spectroscopic components. Herein, we aimed to: (1) implement an advanced methodological approach for post-processing, fitting, and parametrization of 9.4T rat brain MM spectra; (2) assess the concomitant impact of the LCModel baseline and MM model (ie, single vs parametrized); and (3) estimate the apparent T2 relaxation times for seven MM components. Methods A single inversion recovery sequence combined with advanced AMARES prior knowledge was used to eliminate the metabolite residuals, fit, and parametrize 10 MM components directly from 9.4T rat brain in vivo 1 H-MR spectra at different TEs. Monte Carlo simulations were also used to assess the concomitant influence of parametrized MM and DKNTMN parameter in LCModel. Results A very stiff baseline (DKNTMN ≥ 1 ppm) in combination with a single MM spectrum led to deviations in metabolite concentrations. For some metabolites the parametrized MM showed deviations from the ground truth for all DKNTMN values. Adding prior knowledge on parametrized MM improved MM and metabolite quantification. The apparent T2 ranged between 12 and 24 ms for seven MM peaks. Conclusion Moderate flexibility in the spline baseline was required for reliable quantification of real/experimental spectra based on in vivo and Monte Carlo data. Prior knowledge on parametrized MM improved MM and metabolite quantification.

Fluorine-19 magnetic resonance imaging (19F MRI) enables detailed in vivo tracking of fluorine-containing tracers and is therefore becoming a particularly useful tool in noninvasive medical imaging. In previous studies, we introduced biocompatible polymers based on the hydrophilic monomer N-(2-hydroxypropyl)methacrylamide (HPMA) and the thermoresponsive monomer N-(2,2-difluoroethyl)acrylamide (DFEA). These polymers have abundant magnetically equivalent fluorine atoms and advantageous properties as 19F MRI tracers. Furthermore, in this pilot study, we modified these polymers by introducing a redox-responsive monomer. As a result, our polymers changed their physicochemical properties once exposed to an oxidative environment. Reactive oxygen species (ROS)-responsive polymers were prepared by incorporating small amounts (0.9-4.5 mol %) of the N-[2-(ferrocenylcarboxamido)ethyl]acrylamide (FcCEA) monomer, which is hydrophobic and diamagnetic in the reduced electroneutral (Fe(II), ferrocene) state but hydrophilic and paramagnetic in the oxidized (Fe(III), ferrocenium cation) state. This property can be useful for theranostic purposes (therapy and diagnostic purposes), especially, in terms of ROS-responsive drug-delivery systems. In the reduced state, these nanoparticles remain self-assembled with the encapsulated drug but release the drug upon oxidation in ROS-rich tumors or inflamed tissues.

Chemical Shift Encoded Magnetic Resonance Imaging (CSE-MRI)-based quantification of low-level ( 5% of proton density fat fraction-PDFF) fat infiltration requires highly accurate data reconstruction for the assessment of hepatic or pancreatic fat accumulation in diagnostics and biomedical research.We compare three software tools available for water/fat image reconstruction and PDFF quantification with MRS as the reference method. Based on the algorithm exploited in the tested software, the accuracy of fat fraction quantification varies. We evaluate them in phantom and in vivo MRS and MRI measurements.The signal model of Intralipid 20% emulsion used for phantoms was established for 3 T and 9.4 T fields. In all cases, we noticed a high coefficient of determination (R-squared) between MRS and MRI-PDFF measurements: in phantoms0.9924-0.9990; and in vivo0.8069-0.9552. Bland-Altman analysis was applied to phantom and in vivo measurements.Multi-echo MRI in combination with an advanced algorithm including multi-peak spectrum modeling appears as a valuable and accurate method for low-level PDFF quantification over large FOV in high resolution, and is much faster than MRS methods. The graph-cut algorithm (GC) showed the fewest water/fat swaps in the PDFF maps, and hence stands out as the most robust method of those tested.

Background Olanzapine is a frequently used atypical antipsychotic drug known to exert structural brain alterations in animals. This study investigated whether chronic olanzapine exposure alters regional blood brain perfusion assessed by Arterial Spin Labelling (ASL) magnetic resonance imaging (MRI) in a validated model of olanzapine-induced metabolic disturbances. An effect of acute olanzapine exposure on brain perfusion was also assessed for comparison. Methods Adult Sprague-Dawley female rats were treated by intramuscular depot olanzapine injections (100 mg/kg every 14 days) or vehicle for 8 weeks. ASL scanning was performed on a 9.4 T Bruker BioSpec 94/30USR scanner under isoflurane anesthesia. Serum samples were used to assay leptin and TNF-α level while brains were sliced for histology. Another group received only one non-depot intraperitoneal dose of olanzapine (7 mg/kg) during MRI scanning, thus exposing its acute effect on brain perfusion. Results Both acute and chronic dosing of olanzapine resulted in decreased perfusion in the sensorimotor cortex, while no effect was observed in the piriform cortex or hippocampus. Furthermore, in the chronically treated group decreased cortex volume was observed. Chronic olanzapine dosing led to increased body weight, adipose tissue mass and leptin level, confirming its expected metabolic effects. Conclusion This study demonstrates region-specific decreases in blood perfusion associated with olanzapine exposure present already after the first dose. These findings extend our understanding of olanzapine-induced functional and structural brain changes.

Methamphetamine (METH) abuse is known to increase the risk of Parkinson's disease (PD) due to its dopaminergic neurotoxicity. This is the rationale for the METH model of PD developed by toxic METH dosing (10 mg/kg four times every 2 h) which features robust neurodegeneration and typical motor impairment in mice. In this study, we used diffusion kurtosis imaging to reveal microstructural brain changes caused by METH-induced neurodegeneration. The METH-treated mice and saline-treated controls underwent diffusion kurtosis imaging scanning using the Bruker Avance 9.4 Tesla MRI system at two time-points: 5 days and 1 month to capture both early and late changes induced by METH. At 5 days, we found a decrease in kurtosis in substantia nigra, striatum and sensorimotor cortex, which is likely to indicate loss of DAergic neurons. At 1 month, we found an increase of kurtosis in striatum and sensorimotor cortex and hippocampus, which may reflect certain recovery processes. Furthermore, we performed tract-based spatial statistics analysis in the white matter and at 1 month, we observed increased kurtosis in ventral nucleus of the lateral lemniscus and some of the lateral thalamic nuclei. No changes were present at the early stage. This study confirms the ability of diffusion kurtosis imaging to detect microstructural pathological processes in both grey and white matter in the METH model of PD. The exact mechanisms underlying the kurtosis changes remain to be elucidated but kurtosis seems to be a valuable biomarker for tracking microstructural brain changes in PD and potentially other neurodegenerative disorders.

Clinical diagnosis of Parkinson's disease (PD) occurs typically when a substantial proportion of dopaminergic neurons in the substantia nigra (SN) already died, and the first motor symptoms appear. Therefore, tools enabling the early diagnosis of PD are essential to identify early-stage PD patients in which neuroprotective treatments could have a significant impact. Here, we test the utility and sensitivity of the diffusion kurtosis imaging (DKI) in detecting progressive microstructural changes in several brain regions of mice exposed to chronic intragastric administration of rotenone, a mouse model that mimics the spatiotemporal progression of PD-like pathology from the ENS to the SN as described by Braak's staging. Our results show that DKI, especially kurtosis, can detect the progression of pathology-associated changes throughout the CNS. Increases in mean kurtosis were first observed in the dorsal motor nucleus of the vagus (DMV) after 2 months of exposure to rotenone and before the loss of dopaminergic neurons in the SN occurred. Remarkably, we also show that limited exposure to rotenone for 2 months is enough to trigger the progression of the disease in the absence of the environmental toxin, thus suggesting that once the first pathological changes in one region appear, they can self-perpetuate and progress within the CNS. Overall, our results show that DKI can be a useful radiological marker for the early detection and monitoring of PD pathology progression in patients with the potential to improve the clinical diagnosis and the development of neuroprotective treatments. (Figure presented.). © 2021 International Society for Neurochemistry

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field, which are all summarized at the end of the paper.

Magnetic resonance spectroscopy (MRS) can provide quantitative information about local metabolite concentrations in living tissues, but in practice the quantification can be difficult. Recently deep learning (DL) has been used for quantification of MRS signals in the frequency domain, and DL combined with time-frequency analysis for artefact detection in MRS. The networks most widely used in previous studies were Convolutional Neural Networks (CNN). Nonetheless, the optimal architecture and hyper-parameters of the CNN for MRS are not well understood; CNN has no knowledge about the nature of the MRS signal and its training is computationally expensive. On the other hand, Wavelet Scattering Convolutional Network (WSCN) is well-understood and computationally cheap. In this study, we found that a wavelet scattering network could hopefully be also used for metabolite quantification.

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low-molecular-weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field which are all summarized at the end of the manuscript.

Gestational methylazoxymethanol acetate (MAM) treatment produces offspring with adult phenotype relevant to schizophrenia, including positive- and negative-like symptoms, cognitive deficits, dopaminergic dysfunction, structural and functional abnormalities. Here we show that adult rats prenatally treated with MAM at gestational day 17 display significant increase in dopamine D3 receptor (D3) mRNA expression in prefrontal cortex (PFC), hippocampus and nucleus accumbens, accompanied by increased expression of dopamine D2 receptor (D2) mRNA exclusively in the PFC. Furthermore, a significant change in the blood perfusion at the level of the circle of Willis and hippocampus, paralleled by the enlargement of lateral ventricles, was also detected by magnetic resonance imaging (MRI) techniques. Peripubertal treatment with the non-euphoric phytocannabinoid cannabidiol (30 mg/kg) from postnatal day (PND) 19 to PND 39 was able to reverse in MAM exposed rats: i) the up-regulation of the dopamine D3 receptor mRNA (only partially prevented by haloperidol 0.6 mg/kg/day); and ii) the regional blood flow changes in MAM exposed rats. Molecular modelling predicted that cannabidiol could bind preferentially to dopamine D3 receptor, where it may act as a partial agonist according to conformation of ionic-lock, which is highly conserved in GPCRs. In summary, our results demonstrate that the mRNA expression of both dopamine D2 and D3 receptors is altered in the MAM model; however only the transcript levels of D3 are affected by cannabidiol treatment, likely suggesting that this gene might not only contribute to the schizophrenia symptoms but also represent an unexplored target for the antipsychotic activity of cannabidiol.

Dynamic contrast enhanced MRI (DCE-MRI) and dynamic susceptibility contrast MRI (DSC-MRI) are perfusion imaging techniques used mainly for clinical and preclinical measurement of vessel permeability and capillary blood flow, respectively. It is advantageous to apply both methods to exploit their complementary information about the perfusion status of the tissue. We propose a novel acquisition method that combines advantages of the current simultaneous and sequential acquisition. The proposed method consists of a DCE-MRI acquisition interrupted by DSC-MRI acquisition. A new method for processing of the DCE-MRI data is proposed which takes the interleaved acquisition into account. Analysis of both the DCE- and DSC-MRI data is reformulated so that they are approximated by the same pharmacokinetic model (constrained distributed capillary adiabatic tissue homogeneity model). This provides a straightforward evaluation of the methodology as some of the estimated DCE- and DSC-MRI perfusion parameters should be identical. Evaluation on synthetic data showed an acceptable precision and no apparent bias introduced by the interleaved character of the DCE-MRI acquisition. Intravascular perfusion parameters obtained from clinical glioma data showed a fairly high correlation of blood flow estimates from DCE- and DSC-MRI, however, an unknown scaling factor was still present mainly because of the tissue-specific r 2 * $r_2^*$ relaxivity. The results show validity of the proposed acquisition method. They also indicate that simultaneous processing of both DCE- and DSC-MRI data with joint estimation of some perfusion parameters (included in both DCE- and DSC-MRI) might be possible to increase the reliability of the DCE- and DSC-MRI methods alone.

Purpose To evaluate the impact of MR gradient system imperfections and limitations for the quantitative mapping of short T2* signals performed by ultrashort echo time (UTE) acquisition approach. Materials and methods The measurement of short T2* signals from a phantom and a healthy volunteer study (8 subjects of average age 28 ± 4 years) were performed on a 3T scanner. The characteristics of the gradient system were obtained using calibration method performed directly on the measured subject or phantom. This information was used to calculate the actual sampling trajectory with the help of a parametric eddy current model. The actual sample positions were used to reconstruct corrected images and compared with uncorrected data. Results Comparison of both approaches, i.e., without and with correction of k-space sampling trajectories revealed substantial improvement when correction was applied. The phantom experiments demonstrate substantial in-plane signal intensity variations for uncorrected sampling trajectories. In the case of the volunteer study, this led to significant differences in relative proton density (RPD) estimation between the uncorrected and corrected data (P = 0.0117 by Wilcoxon matched-pairs test) and provides for about ~15% higher values for short T2* components of white matter (WM) in the case of uncorrected images. Conclusion The imperfection of the applied gradients could induce errors in k-space data sampling which further propagates into the fidelity of the UTE images and jeopardizes precision of quantification. However, the study proved that measurement of gradient errors together with correction of sample positions can contribute to increased accuracy and unbiased characterization of short T2* signals.

Current possibilities and limitations of the simulation of in vivo magnetic resonance spectroscopic signals are demonstrated from the point of view of a simulation software user as well as its programmer. A brief review of the quantum-mechanical background addresses the specific needs of simulation implementation and in vivo MR spectroscopy in general. Practical application examples demonstrate how flexible simulation software, such as NMRScopeB, can be utilized not only for the preparation of metabolite basis signals for quantification of metabolite concentrations, but also in pulse sequence development, assessment of artifacts and analyzing mechanism leading to unexpected signal phenomena.

A new non-optic method for the study of Liesegang patterns was tested. Liesegang patterns are periodically banded precipitates produced by the reaction–diffusion process, mostly occurring in geology. The Liesegang experiment (5.5 M NH4OH, gelatin matrix with 0.4 M MgSO4) was monitored using a 9.4 T magnetic resonance imaging (MRI) system, allowing the acquisition of sample images in any location and orientation without interfering with the process studied. The development of patterns in a gel matrix was observed for 7 days after starting the reaction. Qualitative data (T 2- and T 2*-weighted images) and quantitative T 2 maps were acquired. Preliminary experiments show that MRI is able to distinguish the regions between the precipitated bands and the structural changes in the gel matrix during the reaction. A damaged gel matrix was measured to reveal the effect of the initial reagent-gel contact area. MRI study of Liesegang patterns provides empirical data which can be used in theoretical model testing.

MR images are affected by system delays and gradient field imperfections which induce discrepancies between prescribed and actual k-space trajectories. This could be even more critical for non-Cartesian data acquisitions where even a small deviation from the assumed k-space trajectory results in severe image degradation and artifacts. Knowledge of the actual k-space trajectories is therefore crucial and can be incorporated in the reconstruction of high quality non-Cartesian images. A novel MR method for the calibration of actual gradient waveforms was developed using a combination of phase encoding increments and subsequent detection of the exact time point at which the corresponding trajectory is crossing the k-space origin. The measured sets of points were fitted to a parametrical model to calculate the complete actual acquisition trajectory. Measurements performed on phantoms and volunteers, positioned both in- and off-isocenter of the magnet, clearly demonstrate the improvement in reconstructed ultrashort echo time (UTE) images, when information from calibration of k-space sampling trajectories is employed in the MR image reconstruction procedure. The unique feature of the proposed method is its robustness and simple experimental setup, making it suitable for quick acquisition trajectory calibration procedures e.g. for non-Cartesian radial fast imaging.

The experimental setup for accurate T 2 * mapping of Achilles tendon and enthesis was developed. The setup consists of a specially designed MR compatible RF coil holder and custom-made ultrashort echo time (UTE) pulse sequence. The performance of the UTE sequence was tested and compared with data obtained by variable echo time (vTE) sequence. The results showed that T 2 * values calculated with vTE are overestimated in comparison to UTE, however, the clinical adaptation of vTE might be easier, since it provides more slices with reduced blurring and lower scan times.

Clinical studies consistently report structural impairments (i.e.: ventricular enlargement, decreased volume of anterior cingulate cortex or hippocampus) and functional abnormalities including changes in regional cerebral blood flow in individuals suffering from schizophrenia, which can be evaluated by magnetic resonance imaging (MRI) techniques. The aim of this study was to assess cerebral blood perfusion in several schizophrenia-related brain regions using Arterial Spin Labelling MRI (ASL MRI, 9.4 T Bruker BioSpec 94/30USR scanner) in rats. In this study, prenatal exposure to methylazoxymethanol acetate (MAM, 22 mg/kg) at gestational day (GD) 17 and the perinatal treatment with Δ-9-tetrahydrocannabinol (THC, 5 mg/kg) from GD15 to postnatal day 9 elicited behavioral deficits consistent with schizophrenia-like phenotype, which is in agreement with the neurodevelopmental hypothesis of schizophrenia. In MAM exposed rats a significant enlargement of lateral ventricles and perfusion changes (i.e.: increased blood perfusion in the circle of Willis and sensorimotor cortex and decreased perfusion in hippocampus) were detected. On the other hand, the THC perinatally exposed rats did not show differences in the cerebral blood perfusion in any region of interest. These results suggest that although both pre/perinatal insults showed some of the schizophrenia-like deficits, these are not strictly related to distinct hemodynamic features.

Purpose One of the main obstacles for reliable quantitative dynamic contrast-enhanced (DCE) MRI is the need for accurate knowledge of the arterial input function (AIF). This is a special challenge for preclinical small animal applications where it is very difficult to measure the AIF without partial volume and flow artifacts. Furthermore, using advanced pharmacokinetic models (allowing estimation of blood flow and permeability-surface area product in addition to the classical perfusion parameters) poses stricter requirements on the accuracy and precision of AIF estimation. This paper addresses small animal DCE-MRI with advanced pharmacokinetic models and presents a method for estimation of the AIF based on blind deconvolution. Methods A parametric AIF model designed for small animal physiology and use of advanced pharmacokinetic models is proposed. The parameters of the AIF are estimated using multichannel blind deconvolution. Results Evaluation on simulated data show that for realistic signal to noise ratios blind deconvolution AIF estimation leads to comparable results as the use of the true AIF. Evaluation on real data based on DCE-MRI with two contrast agents of different molecular weights showed a consistence with the known effects of the molecular weight. Conclusion Multi-channel blind deconvolution using the proposed AIF model specific for small animal DCE-MRI provides reliable perfusion parameter estimates under realistic signal to noise conditions.

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At the molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression, which might be due to reduction in DNA methylation at the gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both the schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day), but not with haloperidol (0.6 mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.

In the last few years, magnetically labeled cells have been intensively explored, and non-invasive cell tracking and magnetic manipulation methods have been tested in preclinical studies focused on cell transplantation. For clinical applications, it is desirable to know the intracellular pathway of nanoparticles, which can predict their biocompatibility with cells and the long-term imaging properties of labeled cells. Here, we quantified labeling efficiency, localization, and fluorescence properties of Rhodamine derivatized superparamagnetic maghemite nanoparticles (SAMN-R) in mesenchymal stromal cells (MSC). We investigated the stability of SAMN-R in the intracellular space during a long culture (20 days). Analyses were based on advanced confocal microscopy accompanied by atomic absorption spectroscopy (AAS) and magnetic resonance imaging. SAMN-R displayed excellent cellular uptake (24 h of labeling), and no toxicity of SAMN-R labeling was found. 83% of SAMN-R nanoparticles were localized in lysosomes, only 4.8% were found in mitochondria, and no particles were localized in the nucleus. On the basis of the MSC fluorescence measurement every 6 days, we also quantified the continual decrease of SAMN-R fluorescence in the average single MSC during 18 days. An additional set of analyses showed that the intracellular SAMN-R signal decrease was minimally caused by fluorophore degradation or nanoparticles extraction from the cells, main reason is a cell division. The fluorescence of SAMN-R nanoparticles within the cells was detectable minimally for 20 days. These observations indicate that SAMN-R nanoparticles have a potential for application in transplantation medicine.

The biomedically focused brain research is largely performed on laboratory mice considering a high homology between the human and mouse genomes. A brain has an intricate and highly complex geometrical structure that is hard to display and analyse using only 2D methods. Applying some fast and efficient methods of brain visualization in 3D will be crucial for the neurobiology in the future. A post-mortem analysis of experimental animals' brains usually involves techniques such as magnetic resonance and computed tomography. These techniques are employed to visualize abnormalities in the brains' morphology or reparation processes. The X-ray computed microtomography (micro CT) plays an important role in the 3D imaging of internal structures of a large variety of soft and hard tissues. This non-destructive technique is applied in biological studies because the lab-based CT devices enable to obtain a several-micrometer resolution. However, this technique is always used along with some visualization methods, which are based on the tissue staining and thus differentiate soft tissues in biological samples. Here, a modified chemical contrasting protocol of tissues for a micro CT usage is introduced as the best tool for ex vivo 3D imaging of a post-mortem mouse brain. This way, the micro CT provides a high spatial resolution of the brain microscopic anatomy together with a high tissue differentiation contrast enabling to identify more anatomical details in the brain. As the micro CT allows a consequent reconstruction of the brain structures into a coherent 3D model, some small morphological changes can be given into context of their mutual spatial relationships.

Background and purpose One of the hallmarks of schizophrenia is altered brain structure, potentially due to antipsychotic treatment, the disorder itself or both. It was proposed that functional changes may precede the structural ones. In order to understand and potentially prevent this unwanted process, brain function assessment should be validated as a diagnostic tool. Methods We used Arterial Spin Labelling MRI technique for the evaluation of brain perfusion in several brain regions in a neurodevelopmental poly(I:C) model of schizophrenia (8 mg/kg on a gestational day 15) in rats taking into account sex-dependent effects and chronic treatment with aripiprazole (30 days), an atypical antipsychotic acting as a partial agonist on dopaminergic receptors. Results We found the sex of the animal to have a highly significant effect in all regions of interest, with females showing lower blood perfusion than males. However, both males and females treated prenatally with poly(I:C) showed enlargement of the lateral ventricles. Furthermore, we detected increased perfusion in the circle of Willis, hippocampus, and sensorimotor cortex, which was not influenced by chronic atypical antipsychotic aripiprazole treatment in male poly(I:C) rats. Conclusion We hypothesize that perfusion alterations may be caused by the hyperdopaminergic activity in the poly(I:C) model, and the absence of aripiprazole effect on perfusion in brain regions related to schizophrenia may be due to its partial agonistic mechanism.

In this paper we propose a novel method for magnetic resonance spectroscopy (MRS) fitting quality assessment based on time domain resampling of acquired spectra and bootstrapping of the obtained results. The authors introduce two resampling strategies and example results are shown. The proposed method requires MRS data without averaging.

Background: Proton magnetic resonance spectroscopy is a non-invasive measurement technique which provides information about concentrations of up to 20 metabolites participating in intracellular biochemical processes. In order to obtain any metabolic information from measured spectra a processing should be done in specialized software, like jMRUI. The processing is interactive and complex and often requires many trials before obtaining a correct result. This paper proposes a jMRUI enhancement for efficient and unambiguous history tracking and file identification.Results: A database storing all processing steps, parameters and files used in processing was developed for jMRUI. The solution was developed in Java, authors used a SQL database for robust storage of parameters and SHA-256 hash code for unambiguous file identification. The developed system was integrated directly in jMRUI and it will be publically available. A graphical user interface was implemented in order to make the user experience more comfortable. The database operation is invisible from the point of view of the common user, all tracking operations are performed in the background.Conclusions: The implemented jMRUI database is a tool that can significantly help the user to track the processing history performed on data in jMRUI. The created tool is oriented to be user-friendly, robust and easy to use. The database GUI allows the user to browse the whole processing history of a selected file and learn e.g. what processing lead to the results, where the original data are stored, to obtain the list of all processing actions performed on spectra.

The present trend in dynamic contrast-enhanced MRI is to increase the number of estimated perfusion parameters using complex pharmacokinetic models. However, less attention is given to the precision analysis of the parameter estimates. In this paper, the distributed capillary adiabatic tissue homogeneity pharmacokinetic model is extended by the bolus arrival time formulated as a free continuous parameter. With the continuous formulation of all perfusion parameters, it is possible to use standard gradient-based optimization algorithms in the approximation of the tissue concentration time sequences. This new six-parameter model is investigated by comparing Monte-Carlo simulations with theoretically derived covariance matrices. The covariance-matrix approach is extended from the usual analysis of the primary perfusion parameters of the pharmacokinetic model to the analysis of the perfusion parameters derived from the primary ones. The results indicate that the precision of the estimated perfusion parameters can be described by the covariance matrix for signal-to-noise ratio higher than ~ 20 dB. The application of the new analysis model on a real DCE-MRI data set is also presented.

Diffusion kurtosis imaging (DKI) is sensitive in detecting α-Synuclein (α-Syn) accumulation-associated microstructural changes at late stages of the pathology in α-Syn overexpressing TNWT-61 mice. The aim of this study was to perform DKI in young TNWT-61 mice when α-Syn starts to accumulate and to compare the imaging results with an analysis of motor and memory impairment and α-Syn levels. Three-month-old (3mo) and six-month-old (6mo) mice underwent DKI scanning using the Bruker Avance 9.4T magnetic resonance imaging system. Region of interest (ROI) analyses were performed in the gray matter; tract-based spatial statistics (TBSS) analyses were performed in the white matter. In the same mice, α-Syn expression was evaluated using quantitative immunofluorescence. Mean kurtosis (MK) was the best differentiator between TNWT-61 mice and wildtype (WT) mice. We found increases in MK in 3mo TNWT-61 mice in the striatum and thalamus but not in the substantia nigra (SN), hippocampus, or sensorimotor cortex, even though the immunoreactivity of human α-Syn was similar or even higher in the latter regions. Increases in MK in the SN were detected in 6mo mice. These findings indicate that α-Syn accumulation-associated changes may start in areas with a high density of dopaminergic nerve terminals. We also found TBSS changes in white matter only at 6mo, suggesting α-Syn accumulation-associated changes start in the gray matter and later progress to the white matter. MK is able to detect microstructural changes induced by α-Syn overexpression in TNWT-61 mice and could be a useful clinical tool for detecting early-stage Parkinson's disease in human patients.

A number of ‘Dixon’ techniques based on fast spin echo (FSE) sequence have been proposed and successfully used in many branches of medicine. Some require only one scan, but most of them need multiple scans and long scan times. This article describes a new fast triple-spin-echo Dixon (FTSED) technique suitable for ultra-high field MRI, in which three specific time shifts are introduced in the echo train; thus, three images with defined water-fat phase-differences (0, π, 2π) are encoded in the phase of the acquired images without extreme restrictions upon the echo duration. The water and fat images are then calculated by iterative least-squares estimation method. The sequence was successfully implemented at a 9.4 T ultra-high field MRI system and tested on a phantom and a rat.

The aim was to determine whether diffusion kurtosis imaging (DKI-MRI) could detect changes in dorsal motor nucleus of vagus (DMV) in mice who received chronic administration of rotenone. This may help in early diagnosis of patients with Parkinson’s disease. Mice received vehicle (VEH) or rotenone (ROT) intragastrically for 4 months. DKI scanning was performed at 2, 3 and 4 months. ROI analysis was used to compare kurtosis and diffusivity parameters in GM regions. WM tracts were investigated using the tract-based spatial statistics. We found significant increase in mean kurtosis in DMV in the ROT group at 2 months. At 3 months we found increase in kurtosis and decrease in diffusivity in almost all regions of interest, showing once the pathology crosses the DMV it spreads throughout the brain. At 4 months all the changes vanished. ROT group showed significant motor impairment at 4 months. At 2 months the DKI parameters may improve the early diagnosis of PD by showing increase in mean kurtosis in the DMV. This may help in monitoring and developing neuroprotective therapy. On the other hand, the lack of the DKI signal changes between ROT and VEH groups at the 4 months probably reflects the brain atrophy.

Diffusion kurtosis imaging (DKI) by measuring non-Gaussian diffusion allows an accurate estimation of the distribution of water molecule displacement and may correctly characterize microstructural brain changes caused by neurodegeneration. The aim of this study was to evaluate the ability of DKI to detect changes induced by α-synuclein (α-syn) accumulation in α-syn over-expressing transgenic mice (TNWT-61) in both gray matter (GM) and white matter (WM) using region of interest (ROI) and tract-based spatial statistics analyses, respectively, and to explore the relationship between α-syn accumulation and DKI metrics in our regions of interest. Fourteen-month-old TNWT-61 mice and wild-type (WT) littermates underwent in vivo DKI scanning using the Bruker Avance 9.4 Tesla magnetic resonance imaging system. ROI analysis in the GM regions substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus and tract-based spatial statistics analysis in WM were performed. Immunohistochemistry for α-syn was performed in TNWT-61 mice and correlated with DKI findings. We found increased kurtosis and decreased diffusivity values in GM regions such as the thalamus and sensorimotor cortex, and in WM regions such as the external and internal capsule, mamillothalamic tract, anterior commissure, cingulum, and corpus callosum in TNWT-61 mice as compared to WT mice. Furthermore, we report for the first time that α-syn accumulation is positively correlated with kurtosis and negatively correlated with diffusivity in the thalamus. The study provides evidence of an association between the amount of α-syn and the magnitude of DKI metric changes in the ROIs, with the potential of improving the clinical diagnosis of Parkinson's disease. We propose diffusion kurtosis imaging as a sensitive method for detecting human α-synuclein accumulation-induced changes in brain tissue, which may be reflective of Parkinson disease stage. Boxplots show the averaged mean kurtosis (orange) and mean diffusivity (blue) under the results of the analysis (*p

This paper is focused on quantitative perfusion analysis using MRI and ultrasound. In both MRI and ultrasound, most approaches allow estimation of rate constants (Ktrans, kep for MRI) and indices (AUC, TTP) that are only related to the physiological perfusion parameters of a tissue (e.g. blood flow, vessel permeability) but do not allow their absolute quantification. Recent methods for quantification of these physiological perfusion parameters are shortly reviewed. The main problem of these methods is estimation of the arterial input function (AIF). This paper summarizes and extends the current blind-deconvolution approaches to AIF estimation. The feasibility of these methods is shown on a small preclinical study using both MRI and ultrasound.

Introduction DKI by measuring non-Gaussian diffusion may better characterize the microstructural brain changes as compared to traditional DTI. The aim was to evaluate the capability of DKI for detecting the microstructural changes induced by alpha-synuclein accumulation in TNWT-61 mice using the tract based spatial statistics (TBSS) and region of interest (ROI) analyses. Methods Fourteen month old TNWT-61 mice and wild-type (WT) littermates underwent DKI scanning using 9.4 Tesla MRI system in vivo. TBSS and ROI analysis was performed to detect the changes in white and gray matter in TNWT-61 and WT mice. Immunohistochemistry for alpha-synuclein was performed in 5 TNWT-61 mice and correlated with DKI findings. Results The principle findings of this study were increase in mean kurtosis and decrease in mean diffusivity in thalamus, sensorimotor cortex, hippocampus, external capsule and basolateral amygdaloid nucleus in 14 month TNWT-61 mice as compared to WT littermates. We also found significant correlations between alpha-synuclein accumulation and increase in kurtosis and decrease in diffusivity in the thalamus. Conclusion Our results reveal that DKI is sensitive in detecting microstructural changes due to alpha-synuclein accumulation in both GM and WM. These findings suggest that in PD patients DKI should be preferred to routine DTI despite a longer acquisition protocol.

Evidence suggests that accumulation and aggregation of α-synuclein contribute to the pathogenesis of Parkinson’s disease (PD). The aim of this study was to evaluate whether diffusion kurtosis imaging (DKI) will provide a sensitive tool for differentiating between α-synuclein-overexpressing transgenic mouse model of PD (TNWT-61) and wild-type (WT) littermates. This experiment was designed as a proof-of-concept study and forms a part of a complex protocol and ongoing translational research. Nine-month-old TNWT-61 mice and age-matched WT littermates underwent behavioral tests to monitor motor impairment and MRI scanning using 9.4 Tesla system in vivo. Tract-based spatial statistics (TBSS) and the DKI protocol were used to compare the whole brain white matter of TNWT-61 and WT mice. In addition, region of interest (ROI) analysis was performed in gray matter regions such as substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus known to show higher accumulation of α-synuclein. For the ROI analysis, both DKI (6 b-values) protocol and conventional (2 b-values) diffusion tensor imaging (cDTI) protocol were used. TNWT-61 mice showed significant impairment of motor coordination. With the DKI protocol, mean, axial, and radial kurtosis were found to be significantly elevated, whereas mean and radial diffusivity were decreased in the TNWT-61 group compared to that in the WT controls with both TBSS and ROI analysis. With the cDTI protocol, the ROI analysis showed decrease in all diffusivity parameters in TNWT-61 mice. The current study provides evidence that DKI by providing both kurtosis and diffusivity parameters gives unique information that is complementary to cDTI for in vivo detection of pathological changes that underlie PD-like symptomatology in TNWT-61 mouse model of PD. This result is a crucial step in search for a candidate diagnostic biomarker with translational potential and relevance for human studies.

Using optimized, asymmetric radiofrequency (RF) pulses for slice selection, the authors demonstrate that stimulated echo acquisition mode (STEAM) localization with ultra-short echo time (1 ms) is possible. Water suppression was designed to minimize sensitivity to B1 inhomogeneity using a combination of 7 variable power RF pulses with optimized relaxation delays (VAPOR). Residual water signal was well below the level of most observable metabolites. Contamination by the signals arising from outside the volume of interest was minimized by outer volume saturation using a series of hyperbolic secant RF pulses, resulting in a sharp volume definition. In conjunction with FASTMAP shimming (Gruetter Magn Reson Med 1993;29: 804-811), the short echo time of 1 msec resulted in highly resolved in vivo 1H nuclear magnetic resonance spectra. In rat brain the water linewidths of 11-13 Hz and metabolite singlet linewidths of 8-10 Hz were measured in 65 microl volumes. Very broad intense signals (delta v(1/2) > 1 kHz), as expected from membranes, for example, were not observed, suggesting that their proton T2 are well below 1 msec. The entire chemical shift range of 1H spectrum was observable, including resolved resonances from alanine, aspartate, choline group, creatine, GABA, glucose, glutamate, glutamine, myo-inositol, lactate, N-acetylaspartate, N-acetylaspartylglutamate, phosphocreatine, and taurine. At 9.4 T, peaks close to the water were observed, including the H-1 of alpha-D-glucose at 5.23 ppm and a tentative H-1 resonance of glycogen at 5.35 ppm.

Summarizing we like to make the following concluding remarks: • We have assembled a low-cost CUDA-capable desktop PC, reflecting the PC state-of-the-art of about 1 1 over 2 years ago. • Via the Ubuntu 9.10 Linux operating system we could enable CUDA by installing a recent Linux NVIDIA driver and the CUDA software (version 2.3). • By applying the Java-bindings based JCuda software package we could call CUFFT library functions from a Java environment. • We could easily perform batched (multiple) 1D-FFT in a parallel fashion by exploiting the batch facility of CUFFT 1D-FFT for a CUDA-enabled GPU device. In this way we could avoid for statement looping, needed for the (CPU-based) reference method. • We could speed up the batched 1D-FFT execution time by about a factor of 20 by applying the GPU-based rather than the CPU-based approach. • Easy comparison of Java-based and ‘C for CUDA’-based benchmarking appeared to be hindered by the choices made for the JCuda implementation. • The CUDA-based benchmark results, reported in this work, seemed to be limited by the data-transfer bandwidth of the computer PCI Express 2.0×16 bus. • If data-transfer speed indeed is the limiting factor, significant computational accelerations can only be achieved if major parts of the numerical calculations can be carried out in the CUDA GPUs. • In the context of the latter, enhanced double-precision and amount of local memory of recent/future CUDA devices will become important. • Using CUDA-based batched 1D-FFT, we could carry out a sample user-guided exhaustive-search in MRS parameter space.

The software package jMRUI with Java-based graphical user interface enables user-friendly time-domain analysis of magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI), and HRMAS-NMR signals. The version 3.x has been distributed in more than 1000 groups or hospitals world-wide. The new version 4.x is a plug-in platform enabling the users to add their own algorithms. Moreover, it offers new functionalities compared to the versions 3.x.

Steady state free precession (SSFP) is an acquisition mode that may be useful for fast magnetic resonance spectroscopic imaging in high field MR systems because of the high achievable SNR. In such systems, metabolites with coupled spin systems may be observed, but the knowledge of their behavior and the induced spectral changes is still limited. Such information is needed for both experiment design and spectrum quantification. This work presents computer simulations of model molecules and of myo-inositol, which is one of the clinically relevant target molecules and describes the algorithm used. It is shown that antiphase and multiple-quantum coherences may represent a considerable portion of the steady state. The effects in spectra are studied based on hypothesized relaxation parameters.

Lineshape distortions and baseline undulations are the well-known undesirable effects of the linear phase correction, when applied to signals the initial part of which is corrupted, either duplicated or missing. While the former imperfection can be cured easily by proper time setting, the latter is more principal. It is shown, however, that some general prior knowledge of spectra enables the reconstruction of the missing part of the signal with high fidelity and the removal of most of the distortions appearing in the absorption-mode spectra. For this purpose a simple procedure is proposed yielding good results even after a single iteration step. Simplicity, negligible computational requirements, and its efficacy are the main advantages of this method.

We present the experimental results of generation and of detection of hyperpolarized xenon obtained by 4.7 T, 200 MHz magnetic resonance (MR) system. Xenon 129 was hyperpolarized by the spin-exchange with Rubidium pumped first by Ti:Sa laser and also by extended cavity laser system based on a high-power laser diode optimized for maximum efficiency of the optical pumping process. The application of the arrangement with semiconductor laser system is oriented medicine, especially to continuous production of hyperpolarized Xenon (HpXe) which serves as an contrast media in MR imaging systems.

Objectives The aim of this study was to test the hypothesis that dental materials vary significantly in MR-relevant material parameters—magnetic susceptibility and electrical conductivity, and that knowledge of these parameters may be used to estimate the quality of MR imaging in the presence of devices made of such materials. Methods Magnetic susceptibility, electrical conductivity and artifacts were evaluated for 45 standardized cylindrical samples of dental alloys and amalgams. Magnetic susceptibility was determined by fitting the phase of gradient-echo MR images to numerically modeled data. Electrical conductivity was determined by standard electrotechnical measurements. Artifact sizes were measured in spin-echo (SE) and gradient-echo (GE) images at 1.5 T according to the standards of the American Society for Testing and Materials. Results It has been confirmed that dental materials differ considerably in their magnetic susceptibility, electrical conductivity and artifacts. For typical dental devices, magnetic susceptibility differences were found of little clinical importance for diagnostic SE/GE imaging of the neck and brain, but significant for orofacial imaging. Short-TE GE imaging has been found possible even in very close distances from dental devices made of amalgams, precious alloys and titanium alloys. Nickel–chromium and cobalt–chromium artifacts were found still acceptable, but large restorations of aluminum bronzes may preclude imaging of the orofacial region. The influence of electrical conductivity on the artifact size was found negligible. Significance MR imaging is possible even close to dental devices if they are made of dental materials with low magnetic susceptibility. Not all materials in current use meet this requirement.

The software package jMRUI with Java-based graphical user interface enables user-friendly time-domain analysis of magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) and HRMAS-NMR signals. Version 3.x has been distributed in more than 1200 groups or hospitals worldwide. The new version 4.x is a plug-in platform enabling the users to add their own algorithms. Moreover, it offers new functionalities compared to versions 3.x. The quantum-mechanical simulator based on NMR-SCOPE, the quantitation algorithm QUEST and the main MRSI functionalities are described. Quantitation results of signals obtained in vivo from a mouse and a human brain are given.

The steady-state free-precession (SSFP) acquisition mode may be found useful for fast in vivo proton magnetic resonance spectroscopic imaging in high-field MR systems because of the achievable signal-to-noise ratio and the avoidance of RF pulses with large flip angles. Detection of signals from metabolites with coupled-spin systems under SSFP has not yet been accomplished, but should be possible in high field, albeit with substantial signal truncation. It must be expected that the spin system evolution and the spectra will be affected by the steady-state conditions, which prevent the spin systems from returning to the Boltzmann equilibrium. Computer simulation is needed for the experiment design and spectrum quantification. This work outlines a suitable simulation method (QuaM-EPG), which combines and extends two pre-existing approaches: the density matrix calculation, used in high-resolution NMR, and the extended phase graph method, used to describe cyclic excitation in fast MRI of water protons. The method is illustrated by its application to model molecules and myo-inositol, which is one of the clinically relevant target molecules. It is shown that antiphase and multiple-quantum coherences may represent a considerable portion of the steady-state magnetization in a quantum-mechanical sense and that the spectral patterns are affected thereby.

A new technique for the solvent-peak suppression is presented which delivers pure absorption-mode spectra. A considerable improvement of the null excitation profile and of the degree of the solvent-signal suppression was reached by incorporating into the hard-pulse scheme the solvent presaturation period. With the use of a difference approach an efficient elimination of the broad solvent signals arising from inhomogeneous parts of the sample was made possible.

On montre quelques proprietes des impulsions composites d'inversion de spin deduites de la sequence de depart Ca=(4―a)(4―a) dans laquelle le parametre a peu varier de facon continue sur un certain domaine de valeurs tel que les elements de la sequence n'aient pas besoin d'etre des multiples d'impulsions de 90°

The influences of three different methods on the accuracy of aromaticity determination of coal asphaltenes by carbon-13 FT NMR were investigated. The results are compared on the basis of statistical evaluation by means of a variance analysis method. The influences of nuclear Overhauser enhancements and spin-lattice relaxation times upon the results of analysis and their values for measured samples are discussed. Some conclusions concerning the size of the particles in solution are presented.

The 13C NMR spectra of samples of heavy crude oil fractions were interpreted. The spectra of all samples were of the same character. In the region of the aliphatic carbon shifts, ten different carbon atom types were discerned; some possible structure types of hydrocarbons were attributed to them and the arrangement of the aromatic rings in a mean molecule of the samples examined was discussed.