pinecone/core-2020-05-10-deduplication huggingface dataset:
Single-shot single-voxel lactate measurements using FOCI-LASER and a multiple-quantum filter

Measurement of tissue lactate using H-1 MRS is often confounded by overlap with intense lipid signals at 1.3 ppm. Single-voxel localization using PRESS is also compromised by the large chemical shift displacement between voxels for the 4.1 ppm (-CH) resonance and the 1.3 ppm -CH3 resonance, leading to subvoxels with signals of opposite phase and hence partial signal cancellation. To reduce the chemical shift displacement to negligible proportions, a modified semi-LASER sequence was written ("FOCI-LASER", abbreviated as fLASER) using FOCI pulses to permit high RF bandwidth even with the limited RF amplitude characteristic of clinical MRI scanners. A further modification, MQF-fLASER, includes a selective multiple-quantum filter to detect lactate and reject lipid signals. The sequences were implemented on a Philips 3 T Achieva TX system. In a solution of brain metabolites fLASER lactate signals were 2.7 times those of PRESS. MQF-fLASER lactate was 47% of fLASER (the theoretical maximum is 50%) but still larger than PRESS lactate. In oil, the main 1.3 ppm lipid peak was suppressed to less than 1%. Enhanced suppression was possible using increased gradient durations. The minimum detectable lactate concentration was approximately 0.5 mM. Coherence selection gradients needed to be at the magic angle to avoid large water signals derived from intermolecular multiple-quantum coherences. In pilot patient measurements, lactate peaks were often observed in brain tumours, but not in cervix tumours; lipids were effectively suppressed. In summary, compared with PRESS, the fLASER sequence yields greatly superior sensitivity for direct detection of lactate (and equivalent sensitivity for other metabolites), while the single-voxel single-shot MQF-fLASER sequence surpasses PRESS for lactate detection while eliminating substantial signals from lipids. This sequence will increase the potential for in vivo lactate measurement as a biomarker in targeted anti-cancer treatments as well as in measurements of tissue hypoxia. Copyright (C) 2015 John Wiley & Sons, Ltd. 49
Parallel transmission for ultrahigh-field imaging

The development of MRI systems operating at or above 7 T has provided researchers with a new window into the human body, yielding improved imaging speed, resolution and signal-to-noise ratio. In order to fully realise the potential of ultrahigh-field MRI, a range of technical hurdles must be overcome. The non-uniformity of the transmit field is one of such issues, as it leads to non-uniform images with spatially varying contrast. Parallel transmission (i.e. the use of multiple independent transmission channels) provides previously unavailable degrees of freedom that allow full spatial and temporal control of the radiofrequency (RF) fields. This review discusses the many ways in which these degrees of freedom can be used, ranging from making more uniform transmit fields to the design of subject-tailored RF pulses for both uniform excitation and spatial selection, and also the control of the specific absorption rate. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd
Reproducibility and effect of tissue composition on cerebellar GABA MRS in an elderly population.

Magnetic resonance spectroscopy (MRS) provides a valuable tool to non-invasively  detect brain gamma-amino butyric acid (GABA) in vivo. GABAergic dysfunction has been observed in the aging cerebellum. Studying cerebellar GABA changes is of considerable interest in understanding certain age-related motor disorders. However, little is known about the reproducibility of GABA MRS in an aged population. Therefore, this study aimed to explore the feasibility and reproducibility of GABA MRS in the aged cerebellum at 3.0 Tesla and to examine the effect of differing tissue composition on GABA measurements. MRI and 1H MRS exams were performed on 10 healthy elderly volunteers (mean age 75.2 years ± 6.5  years) using a 3.0 Tesla Siemens Tim Trio scanner. Among them, 5 subjects were scanned twice to assess short-term reproducibility. The MEGA-PRESS J-editing sequence was used for GABA detection in two volumes of interest (VOIs) in left and right cerebellar dentate. MRS data processing and quantification were performed with LCModel 6.3-0L using two separate basis sets, generated from density matrix simulations using published values for chemical shifts an
Classification of Brain Tumours from MR Spectra: The INTERPRET Collaboration and its Outcomes

The INTERPRET project was a multicentre European collaboration, carried out from 2000 to 2002, which developed a decision-support system (DSS) for helping neuroradiologists with no experience of MRS to utilise spectroscopic data for the diagnosis and grading of human brain tumours. Its development involved gathering a large collection of MR spectra of brain tumours and pseudo-tumoural lesions from seven centres. Consensus acquisition protocols, a standard processing pipeline and strict methods for quality control of the aquired data were put in place. Particular emphasis was put on ensuring diagnostic certainty of each case, for which all cases were evaluated by a clinical data validation committee. One outcome of the project is a database of 304 fully-validated spectra from brain tumours, pseudotumoural lesions and normal brains, along with their associated images and clinical data, which is available to the scientific and medical community and has been the basis of twenty-one papers. The second is the INTERPRET DSS, which has continued to be developed and clinically evaluated after the project ended.   
We also review here the results of the post-INTERPRET period. We evaluate the results of the studies that have been performed with the INTERPRET database after sharing its data with other consortia or research groups. A summary of the clinical evaluations that have been performed on the post-INTERPRET DSS versions is also presented. Several have shown that diagnostic certainty can be improved for certain tumour types when the INTERPRET DSS is used in conjunction with conventional radiological image interpretation.  About 30 papers concerned with the INTERPRET single voxel dataset have so far been published.Funding from project MARESCAN (SAF2011-23870) from Ministerio de Economia y Competitividad in Spain. This work was also partially funded by CIBER-BBN, which is an initiative of the VI National R&D&i Plan 2008-2011, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.  JRG acknowledges support from Cancer Research UK, the University of Cambridge and Hutchison Whampoa Ltd.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/nbm.343
Modeling non-linear kinetics of hyperpolarized 1-C-13 pyruvate in the crystalloid-perfused rat heart

Hyperpolarized C-13 MR measurements have the potential to display non-linear kinetics. We have developed an approach to describe possible non-first-order kinetics of hyperpolarized [1-C-13] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second-order model for conversion of [1-C-13] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second-order modeling yielded significantly improved fits of pyruvate-bicarbonate kinetics compared with the more traditionally used first-order model and suggested time-dependent decreases in pyruvate-bicarbonate flux. Second-order modeling gave time-dependent changes in forward and reverse reaction kinetics of pyruvate-lactate exchange and pyruvate-alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first-order model. The mechanism giving rise to second-order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD(+) (the cofactor for PDH), consistent with the non-linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect. (c) 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd
A comparison of quantitative methods for clinical imaging with hyperpolarized 13C-pyruvate

Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized 13C-labelled molecules, such as the conversion of [1-13C]pyruvate to [1-13C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumor grade. The first human DNP study has recently been completed, and for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumors in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside-step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches which accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region-of-interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized 13C data.CJD is jointly funded by the National Institute for Health Research (NIHR), Cambridge Biomedical Research Centre and GlaxoSmithKline (GSK). Additional funding for this study was provided by Cancer Research UK (CRUK, C19212/A16628; C19212/A911376), The Wellcome Trust, Cambridge Experimental Cancer Medicine Centre, Cambridge Cancer Centre, the School of Clinical Medicine at the University of Cambridge and the CRUK and Engineering and Physical Sciences Research Council (EPSRC) Cancer Imaging Centre in Cambridge and Manchester.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/nbm.346
Structural and resting-state MRI detects regional brain differences in young and mid-age healthy APOE-e4 carriers compared with non-APOE-e4 carriers

The presence of the e4 allele of the apolipoprotein E (APOE) gene is the best-known genetic risk factor for Alzheimer's disease. In this study, we investigated the link between functional and behavioural differences and regional brain volume and cortical thickness differences in those who carry the e4 allele (e4+) and those who only carry the e3 allele (e3/e3). We studied these genotype populations in two age groups: a young group (average age, 21 years) and a mid-age group (average age, 50 years). High-resolution T1 -weighted MRI scans were analysed with Freesurfer to measure regional white matter brain volume and cortical thickness differences between genotype groups at each age. These data were correlated with behavioural findings in the same cohort. Resting-state MRI was also conducted to identify differences in underlying brain functional connectivity. We found that there was a positive correlation between the thickness of the parahippocampal cortex in young e4+ individuals and performance on an episodic memory task. Young e4+ individuals also showed a positive correlation between white matter volume in the left anterior cingulate and performance on a covert attention task. At mid-age, e4+ individuals had structural differences relative to e3/e3 individuals in these areas: the parahippocampal cortex was thicker and white matter volume in the left anterior cingulate was greater than in e3/e3 individuals. We discuss the possibility that an over-engagement with these regions by e4+ individuals in youth may have a neurogenic effect that is observable later in life. The cuneus appears to be an important region for APOE-driven differences in the brain, with greater functional connectivity among young e3/e3 individuals and greater white matter volume in young e4+ individuals. Copyright © 2016 John Wiley & Sons, Ltd
Spatio-spectral regularization to improve magnetic resonance spectroscopic imaging quantification

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive technique able to provide the spatial distribu- tion of relevant biochemical compounds commonly used as biomarkers of disease. Information provided by MRSI can be used as a valuable insight for the diagnosis, treatment and follow-up of several diseases such as cancer or neurological disorders. Obtaining accurate metabolite concentrations from in vivo MRSI signals is a crucial require- ment for the clinical utility of this technique. Despite the numerous publications on the topic, accurate quantification is still a challenging problem due to the low signal-to-noise ratio of the data, overlap of spectral lines and the pres- ence of nuisance components. We propose a novel quantification method, which alleviates these limitations by exploiting a spatio-spectral regularization scheme. In contrast to previous methods, the regularization terms are not expressed directly on the parameters being sought, but on appropriate transformed domains. In order to quan- tify all signals simultaneously in the MRSI grid, while introducing prior information, a fast proximal optimization al- gorithm is proposed. Experiments on synthetic MRSI data demonstrate that the error in the estimated metabolite concentrations is reduced by a mean of 41% with the proposed scheme. Results on in vivo brain MRSI data show the benefit of the proposed approach, which is able to fit overlapping peaks correctly and to capture metabolites that are missed by single-voxel methods due to their lower concentrations
Characterization of a novel MR-detectable nanoantioxidant that mitigates the recall immune response

In many human diseases, the presence of inflammation is associated with an increase in the level of reactive oxygen species (ROS). The resulting state of oxidative stress is highly detrimental and can initiate a cascade of events that ultimately lead to cell death. Thus, many therapeutic attempts have been focused on either modulating the immune system to lower inflammation or reducing the damaging caused by ROS. Berlin et al. reported the development of a novel nanoantioxidant known as poly(ethylene glycol)-functionalized-hydrophilic carbon clusters (PEG-HCCs). They showed that PEG-HCCs could be targeted to cancer cells, utilized as a drug delivery vector, and can even be visualized ex vivo. Our work here furthers this work and characterizes Gd-DTPA conjugated PEG-HCCs and explores the potential for in vivo tracking of T cells in live mice. We utilized a mouse model of delayed-type hypersensitivity (DTH) to assess the immunomodulatory effects of PEG-HCCs. The T1-agent Gd-DTPA was then conjugated to the PEG-HCCs and T1 measurements, and T1-weighted MRI of the modified PEG-HCCs was done to assess their relaxivity. We then assessed if PEG-HCCs could be visualized both ex vivo and in vivo within the mouse lymph node and spleen. Mice treated with PEG-HCCs showed significant improvements in the DTH assay as compared to the vehicle (saline)-treated control. Flow cytometry demonstrated that splenic T cells are capable of internalizing PEG-HCCs whereas fluorescent immunohistochemistry showed that PEG-HCCs are detectable within the cortex of lymph nodes. Finally, our nanoantioxidants can be visualized in vivo within the lymph nodes and spleen of a mouse after addition of the Gd-DTPA. PEG-HCCs are internalized by T cells in the spleen and can reduce inflammation by suppression of a recall immune response. PEG-HCCs can be modified to allow for both in vitro and in vivo visualization using MRI
Validating a robust double-quantum-filtered H-1 MRS lactate measurement method in high-grade brain tumours

H-1 MRS measurements of lactate are often confounded by overlapping lipid signals. Double-quantum (DQ) filtering eliminates lipid signals and permits single-shot measurements, which avoid subtraction artefacts in moving tissues. This study evaluated a single-voxel-localized DQ filtering method qualitatively and quantitatively for measuring lactate concentrations in the presence of lipid, using high-grade brain tumours in which the results could be compared with standard acquisition as a reference. Paired standard acquisition and DQ-filtered H-1 MR spectra were acquired at 3T from patients receiving treatment for glioblastoma, using fLASER (localization by adiabatic selective refocusing using frequency offset corrected inversion pulses) single-voxel localization. Data were acquired from 2 x 2 x 2 cm(3) voxels, with a repetition time of 1 s and 128 averages (standard acquisition) or 256 averages (DQ-filtered acquisition), requiring 2.15 and 4.3 min respectively. Of 37 evaluated data pairs, 20 cases (54%) had measureable lactate (fitted Cramer-Rao lower bounds <= 20%) in either the DQ-filtered or the standard acquisition spectra. The measured DQ-filtered lactate signal was consistently downfield of lipid (1.33 +/- 0.03 ppm vs 1.22 +/- 0.08 ppm; p = 0.002), showing that it was not caused by lipid breakthrough, and that it matched the lactate signal seen in standard measurements (1.36 +/- 0.02 ppm). In the absence of lipid, similar lactate concentrations were measured by the two methods (mean ratio DQ filtered/standard acquisition = 1.10 +/- 0.21). In 7/20 cases with measurable lactate, signal was not measureable in the standard acquisition owing to lipid overlap but was quantified in the DQ-filtered acquisition. Conversely, lactate was undetected in seven DQ-filtered acquisitions but visible using the standard acquisition. In conclusion, the DQ filtering method has proven robust in eliminating lipid and permits uncontaminated measurement of lactate. This is important validation prior to use in tissues outside the brain, which contain large amounts of lipid and which are often susceptible to motion
Investigating intracranial tumour growth patterns with multiparametric MRI incorporating Gd-DTPA and USPIO-enhanced imaging

High grade and metastatic brain tumours exhibit considerable spatial variations in proliferation, angiogenesis, invasion, necrosis and oedema. Vascular heterogeneity arising from vascular co-option in regions of invasive growth (in which the blood-brain barrier remains intact) and neoangiogenesis is a major challenge faced in the assessment of brain tumours by conventional MRI. A multiparametric MRI approach, incorporating native measurements and both Gd-DTPA (Magnevist) and ultrasmall superparamagnetic iron oxide (P904)-enhanced imaging, was used in combination with histogram and unsupervised cluster analysis using a k-means algorithm to examine the spatial distribution of vascular parameters, water diffusion characteristics and invasion in intracranially propagated rat RG2 gliomas and human MDA-MB-231 LM2-4 breast adenocarcinomas in mice. Both tumour models presented with higher R-1 (the change in transverse relaxation rate R-1 induced by Gd-DTPA), fractional blood volume (fBV) and apparent diffusion coefficient than uninvolved regions of the brain. MDA-MB-231 LM2-4 tumours were less densely cellular than RG2 tumours and exhibited substantial local invasion, associated with oedema, whereas invasion in RG2 tumours was minimal. These additional features were reflected in the more heterogeneous appearance of MDA-MB-231 LM2-4 tumours on T-2-weighted images and maps of functional MRI parameters. Unsupervised cluster analysis separated subregions with distinct functional properties; areas with a low fBV and relatively impermeable blood vessels (low R-1) were predominantly located at the tumour margins, regions of MDA-MB-231 LM2-4 tumours with relatively high levels of water diffusion and low vascular permeability and/or fBV corresponded to histologically identified regions of invasion and oedema, and areas of mismatch between vascular permeability and blood volume were identified. We demonstrate that dual contrast MRI and evaluation of tissue diffusion properties, coupled with cluster analysis, allows for the assessment of heterogeneity within invasive brain tumours and the designation of functionally diverse subregions that may provide more informative predictive biomarkers
Early detection of human glioma sphere xenografts in mouse brain using diffusion MRI at 14.1 T.

Glioma models have provided important insights into human brain cancers. Among the investigative tools, MRI has allowed their characterization and diagnosis. In this study, we investigated whether diffusion MRI might be a useful technique for early detection and characterization of slow-growing and diffuse infiltrative gliomas, such as the proposed new models, LN-2669GS and LN-2540GS glioma sphere xenografts. Tumours grown in these models are not visible in conventional T2 -weighted or contrast-enhanced T1 -weighted MRI at 14.1 T. Diffusion-weighted imaging and diffusion tensor imaging protocols were optimized for contrast by exploring long diffusion times sensitive for probing the microstructural alterations induced in the normal brain by the slow infiltration of glioma sphere cells. Compared with T2 -weighted images, tumours were properly identified in their early stage of growth using diffusion MRI, and confirmed by localized proton MR spectroscopy as well as immunohistochemistry. The first evidence of tumour presence was revealed for both glioma sphere xenograft models three months after tumour implantation, while no necrosis, oedema or haemorrhage were detected either by MRI or by histology. Moreover, different values of diffusion indices, such as mean diffusivity and fractional anisotropy, were obtained in tumours grown from LN-2669GS and LN-2540GS glioma sphere lines. These observations highlighted diverse tumour microstructures for both xenograft models, which were reflected in histology. This study demonstrates the ability of diffusion MRI techniques to identify and investigate early stages of slow-growing, invasive tumours in the mouse brain, thus providing a potential imaging biomarker for early detection of tumours in humans