Over more than 30 years in vivo MR spectroscopic imaging (MRSI) has undergone an enormous evolution from theoretical concepts in the early 1980s to the robust imaging technique that it is today. The ...development of both fast and efficient sampling and reconstruction techniques has played a fundamental role in this process. State‐of‐the‐art MRSI has grown from a slow purely phase‐encoded acquisition technique to a method that today combines the benefits of different acceleration techniques. These include shortening of repetition times, spatial‐spectral encoding, undersampling of k‐space and time domain, and use of spatial‐spectral prior knowledge in the reconstruction. In this way in vivo MRSI has considerably advanced in terms of spatial coverage, spatial resolution, acquisition speed, artifact suppression, number of detectable metabolites and quantification precision. Acceleration not only has been the enabling factor in high‐resolution whole‐brain 1H‐MRSI, but today is also common in non‐proton MRSI (31P, 2H and 13C) and applied in many different organs. In this process, MRSI techniques had to constantly adapt, but have also benefitted from the significant increase of magnetic field strength boosting the signal‐to‐noise ratio along with high gradient fidelity and high‐density receive arrays. In combination with recent trends in image reconstruction and much improved computation power, these advances led to a number of novel developments with respect to MRSI acceleration. Today MRSI allows for non‐invasive and non‐ionizing mapping of the spatial distribution of various metabolites’ tissue concentrations in animals or humans, is applied for clinical diagnostics and has been established as an important tool for neuro‐scientific and metabolism research. This review highlights the developments of the last five years and puts them into the context of earlier MRSI acceleration techniques. In addition to 1H‐MRSI it also includes other relevant nuclei and is not limited to certain body regions or specific applications.
This review summarizes the progress in fast MR spectroscopic imaging (MRSI) of the last five years and puts it into the context of earlier MRSI acceleration techniques. It highlights emerging techniques for time‐efficient sampling of MRSI data including repetition time reduction, spatial‐spectral encoding, k‐space undersampling, and use of spatial‐spectral prior knowledge. In addition to 1H‐MRSI it also includes other relevant nuclei and is not limited to certain body regions or specific applications.
•Labeling effects in metabolites after oral intake of 1-13CGlc in human brain.•High temporal and spatial resolution could be achieved using 1H-FID-MRSI at 9.4 t.•Determination of spatial dependence ...of glutamatergic metabolism.•enrichment curves of GluC4, GlxC3, GlxC2, GlnC4, AspC2,3, and NAAC6.•enrichment maps of GluC4.
Glutamate is the major excitatory transmitter in the brain and malfunction of the related metabolism is associated with various neurological diseases and disorders. The observation of labeling changes in the spectra after the administration of a 13C labelled tracer is a common tool to gain better insights into the function of the metabolic system. But so far, only a very few studies presenting the labeling effects in more than two voxels to show the spatial dependence of metabolism.
In the present work, the labeling effects were measured in a transversal plane in the human brain using ultra-short TE and TR 1H FID-MRSI. The measurement set-up was most simple: The 1-13CGlc was administered orally instead of intravenous and the spectra were measured with a pure 1H technique without the need of a 13C channel (as Boumezbeur et al. demonstrated in 2004). Thus, metabolic maps and enrichment curves could be obtained for more metabolites and in more voxels than ever before in human brain. Labeling changes could be observed in 4–13Cglutamate, 3–13Cglutamate+glutamine, 2–13Cglutamate+glutamine, 4–13Cglutamine, and 3–13Caspartate with a high temporal (3.6 min) and spatial resolution (32 × 32 grid with nominal voxel size of 0.33 µL) in five volunteers.
•Quantitative metabolite maps of 12 metabolites in the human brain acquired at 9.4 T.•Voxel-specific T1-weighting corrections for water and metabolites.•Comparisons of T1-weighted and T1-corrected ...metabolite maps.
Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive imaging modality that enables observation of metabolites. Applications of MRSI for neuroimaging have shown promise for monitoring and detecting various diseases. This study builds off previously developed techniques of short TR, 1H FID MRSI by correcting for T1-weighting of the metabolites and utilizing an internal water reference to produce quantitative (mmol kg−1) metabolite maps. This work reports and shows quantitative metabolite maps for 12 metabolites for a single slice. Voxel-specific T1-corrections for water are common in MRSI studies; however, most studies use either averaged T1-relaxation times to correct for T1-weighting of metabolites or omit this correction step entirely. This work employs the use of voxel-specific T1-corrections for metabolites in addition to water. Utilizing averaged T1-relaxation times for metabolites can bias metabolite maps for metabolites that have strong differences between T1-relaxation for GM and WM (i.e. Glu). This work systematically compares quantitative metabolite maps to single voxel quantitative results and qualitatively compares metabolite maps to previous works.
Takotsubo cardiomyopathy is an increasingly recognized acute heart failure syndrome precipitated by intense emotional stress. Although there is an apparent rapid and spontaneous recovery of left ...ventricular ejection fraction, the long-term clinical and functional consequences of takotsubo cardiomyopathy are ill-defined.
In an observational case-control study, we recruited 37 patients with prior (>12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and comorbidity-matched control subjects. Patients completed the Minnesota Living with Heart Failure Questionnaire. All participants underwent detailed clinical phenotypic characterization, including serum biomarker analysis, cardiopulmonary exercise testing, echocardiography, and cardiac magnetic resonance including cardiac
P-spectroscopy.
Participants were predominantly middle-age (64±11 years) women (97%). Although takotsubo cardiomyopathy occurred 20 (range 13-39) months before the study, the majority (88%) of patients had persisting symptoms compatible with heart failure (median of 13 range 0-76 in the Minnesota Living with Heart Failure Questionnaire) and cardiac limitation on exercise testing (reduced peak oxygen consumption, 24±1.3 versus 31±1.3 mL/kg/min,
<0.001; increased VE/Vco
slope, 31±1 versus 26±1,
=0.002). Despite normal left ventricular ejection fraction and serum biomarkers, patients with prior takotsubo cardiomyopathy had impaired cardiac deformation indices (reduced apical circumferential strain, -16±1.0 versus -23±1.5%,
<0.001; global longitudinal strain, -17±1 versus -20±1%,
=0.006), increased native T1 mapping values (1264±10 versus 1184±10 ms,
<0.001), and impaired cardiac energetic status (phosphocreatine/γ-adenosine triphosphate ratio, 1.3±0.1 versus 1.9±0.1,
<0.001).
In contrast to previous perceptions, takotsubo cardiomyopathy has long-lasting clinical consequences, including demonstrable symptomatic and functional impairment associated with persistent subclinical cardiac dysfunction. Taken together our findings demonstrate that after takotsubo cardiomyopathy, patients develop a persistent, long-term heart failure phenotype.
URL: https://clinicaltrials.gov. Unique identifier: NCT02989454.
Acute stress-induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable with that of myocardial infarction. In this study, we hypothesized that ...inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy.
In a multicenter study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age-, sex-, and comorbidity-matched control subjects. During the index event and at the 5-month follow-up, patients with takotsubo cardiomyopathy underwent multiparametric cardiac magnetic resonance imaging, including ultrasmall superparamagnetic particles of iron oxide (USPIO) enhancement for detection of inflammatory macrophages in the myocardium. Blood monocyte subpopulations and serum cytokines were assessed as measures of systemic inflammation. Matched control subjects underwent investigation at a single time point.
Subjects were predominantly middle-aged (64±14 years) women (90%). Compared with control subjects, patients with takotsubo cardiomyopathy had greater USPIO enhancement (expressed as the difference between pre-USPIO and post-USPIO T2*) in both ballooning (14.3±0.6 milliseconds versus 10.5±0.9 milliseconds; P<0.001) and nonballooning (12.9±0.6 milliseconds versus 10.5±0.9 milliseconds; P=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 pg/mL versus 6.5±5.8 pg/mL; P<0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 pg/mL versus 1272±177 pg/mL; P=0.01) concentrations and classic CD14
CD16
monocytes (90±0.5% versus 87±0.9%; P=0.01) were also increased whereas intermediate CD14
CD16
(5.4±0.3% versus 6.9±0.6%; P=0.01) and nonclassic CD14
CD16
(2.7±0.3% versus 4.2±0.5%; P=0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium, although persistent elevations in serum interleukin-6 concentrations ( P=0.009) and reductions in intermediate CD14
CD16
monocytes (5.6±0.4% versus 6.9±0.6%; P=0.01) remained.
We demonstrate for the first time that takotsubo cardiomyopathy is characterized by a myocardial macrophage inflammatory infiltrate, changes in the distribution of monocyte subsets, and an increase in systemic proinflammatory cytokines. Many of these changes persisted for at least 5 months, suggesting a low-grade chronic inflammatory state.
URL: https://www.clinicaltrials.gov . Unique identifier: NCT02897739.
Magnetic Resonance Spectroscopy (MRS) allows for a non-invasive and non-ionizing determination of in vivo tissue concentrations and metabolic turn-over rates of more than 20 metabolites and compounds ...in the central nervous system of humans. The aim of this review is to give a comprehensive overview about the advantages, challenges and advances of ultra-high field MRS with regard to methodological development, discoveries and applications from its beginnings around 15 years ago up to the current state. The review is limited to human brain and spinal cord application at field strength of 7T and 9.4T and includes all relevant nuclei (1H, 31P, 13C).
This study presents a method to directly link metabolite concentration changes and BOLD response in the human brain during visual stimulation by measuring the water and metabolite signals ...simultaneously. Therefore, the metabolite-cycling (MC) non-water suppressed semiLASER localization technique was optimized for functional 1H MRS in the human brain at 9.4 T. Data of 13 volunteers were acquired during a 26:40 min visual stimulation block-design paradigm. Activation-induced BOLD signal was observed in the MC water signal as well as in the NAA-CH3 and tCr-CH3 singlets. During stimulation, glutamate concentration increased 2.3 ± 2.0% to a new steady-state, while a continuous increase over the whole stimulation period could be observed in lactate with a mean increase of 35.6 ± 23.1%. These increases of Lac and Glu during brain activation confirm previous findings reported in literature. A positive correlation of the MC water BOLD signal with glutamate and lactate concentration changes was found. In addition, a pH decrease calculated from a change in the ratio of PCr to Cr was observed during brain activation, particularly at the onset of the stimulation.
Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic ...system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder. Using resting state functional magnetic resonance imaging (rsfMRI), the "dorsal nexus "(DN) was recently identified as a bilateral dorsal medial prefrontal cortex region showing dramatically increased depression-associated functional connectivity with large portions of a cognitive control network (CCN), the default mode network (DMN), and a rostral affective network (AN). Hence, Sheline and colleagues (2010) proposed that reducing increased connectivity of the DN might play a critical role in reducing depression symptomatology and thus represent a potential therapy target for affective disorders. Here, using a randomized, placebo-controlled, double-blind, crossover rsfMRI challenge in healthy subjects we demonstrate that ketamine decreases functional connectivity of the DMN to the DN and to the pregenual anterior cingulate (PACC) and medioprefrontal cortex (MPFC) via its representative hub, the posterior cingulate cortex (PCC). These findings in healthy subjects may serve as a model to elucidate potential biomechanisms that are addressed by successful treatment of major depression. This notion is further supported by the temporal overlap of our observation of subacute functional network modulation after 24 hours with the peak of efficacy following an intravenous ketamine administration in treatment-resistant depression.
Magnetic resonance spectroscopic imaging (MRSI) offers considerable promise for monitoring metabolic alterations associated with disease or injury; however, to date, these methods have not had a ...significant impact on clinical care, and their use remains largely confined to the research community and a limited number of clinical sites. The MRSI methods currently implemented on clinical MRI instruments have remained essentially unchanged for two decades, with only incremental improvements in sequence implementation. During this time, a number of technological developments have taken place that have already greatly benefited the quality of MRSI measurements within the research community and which promise to bring advanced MRSI studies to the point where the technique becomes a true imaging modality, while making the traditional review of individual spectra a secondary requirement. Furthermore, the increasing use of biomedical MR spectroscopy studies has indicated clinical areas where advanced MRSI methods can provide valuable information for clinical care. In light of this rapidly changing technological environment and growing understanding of the value of MRSI studies for biomedical studies, this article presents a consensus from a group of experts in the field that reviews the state‐of‐the‐art for clinical proton MRSI studies of the human brain, recommends minimal standards for further development of vendor‐provided MRSI implementations, and identifies areas which need further technical development.
MR spectroscopic imaging enables noninvasive mapping of metabolites within the body and offers considerable potential for clinical and biomedical research studies. Recent technological advances, in high‐field MRI instrumentation, spatial‐spectral sampling and image reconstruction methods, and data analysis, have greatly improved spatial resolution and the extent of the brain over which metabolites can be mapped. This consensus statement summarizes the state‐of‐the‐art for clinical MRSI studies of the brain and provides a set of implementation standards matched to different clinical applications.
Purpose
Accurate and precise MRS fitting is crucial for metabolite concentration quantification of 1H‐MRS spectra. LCModel, a spectral fitting software, has shown to have certain limitations to ...perform advanced spectral fitting by previous literature. Herein, we propose an open‐source spectral fitting algorithm with adaptive spectral baseline determination and more complex cost functions.
Theory
The MRS spectra are characterized by several parameters, which reflect the environment of the contributing metabolites, properties of the acquisition sequence, or additional disturbances. Fitting parameters should accurately describe these parameters. Baselines are also a major contributor to MRS spectra, in which smoothness of the spline baselines used for fitting can be adjusted based on the properties of the spectra. Three different cost functions used for the minimization problem were also investigated.
Methods
The newly developed ProFit‐1D fitting algorithm is systematically evaluated for simulations of several types of possible in vivo parameter variations. Although accuracy and precision are tested with simulated spectra, spectra measured in vivo at 9.4 T are used for testing precision using subsets of averages. ProFit‐1D fitting results are also compared with LCModel.
Results
Both ProFit‐1D and LCModel fitted the spectra well with induced parameter and baseline variations. ProFit‐1D proved to be more accurate than LCModel for simulated spectra. However, LCModel showed a somewhat increased precision for some spectral simulations and for in vivo data.
Conclusion
The open‐source ProFit‐1D fitting algorithm demonstrated high accuracy while maintaining precise metabolite concentration quantification. Finally, through the newly proposed cost functions, new ways to improve fitting were shown.
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