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PURPOSE: The pathological hallmarks of Alzheimer's disease (AD), amyloid, tau, and associated neurodegeneration, are present in the cortical gray matter (GM) years before symptom onset, and at significantly greater levels in carriers of the apolipoprotein E4 (APOE4) allele. Their respective biomarkers, A/T/N, have been found to correlate with aspects of brain biochemistry, measured with magnetic resonance spectroscopy (MRS), indicating a potential for MRS to augment the A/T/N framework for staging and prediction of AD. Unfortunately, the relationships between MRS and A/T/N biomarkers are unclear, largely due to a lack of studies examining them in the context of the spatial and temporal model of T/N progression. Advanced MRS acquisition and post-processing approaches have enabled us to address this knowledge gap and test the hypotheses, that glutamate-plus-glutamine (Glx) and N-acetyl-aspartate (NAA), metabolites reflecting synaptic and neuronal health, respectively, measured from regions on the Braak stage continuum, correlate with: (i) cerebrospinal fluid (CSF) p-tau181 level (T), and (ii) hippocampal volume or cortical thickness of parietal lobe GM (N). We hypothesized that these correlations will be moderated by Braak stage and APOE4 genotype. METHODS: We conducted a retrospective imaging study of 34 cognitively unimpaired elderly individuals who received APOE4 genotyping and lumbar puncture from pre-existing prospective studies at the NYU Grossman School of Medicine between October 2014 and January 2019. Subjects returned for their imaging exam between April 2018 and February 2020. Metabolites were measured from the left hippocampus (Braak II) using a single-voxel semi-adiabatic localization by adiabatic selective refocusing sequence; and from the bilateral posterior cingulate cortex (PCC; Braak IV), bilateral precuneus (Braak V), and bilateral precentral gyrus (Braak VI) using a multi-voxel echo-planar spectroscopic imaging sequence. Pearson and Spearman correlations were used to examine the relationships between absolute levels of choline, creatine, myo-inositol, Glx, and NAA and CSF p-tau181, and between these metabolites and hippocampal volume or parietal cortical thicknesses. Covariates included age, sex, years of education, Fazekas score, and months between CSF collection and MRI exam. RESULTS: There was a direct correlation between hippocampal Glx and CSF p-tau181 in APOE4 carriers (Pearson's r = 0.76, p = 0.02), but not after adjusting for covariates. In the entire cohort, there was a direct correlation between hippocampal NAA and hippocampal volume (Spearman's r = 0.55, p = 0.001), even after adjusting for age and Fazekas score (Spearman's r = 0.48, p = 0.006). This relationship was observed only in APOE4 carriers (Pearson's r = 0.66, p = 0.017), and was also retained after adjustment (Pearson's r = 0.76, p = 0.008; metabolite-by-carrier interaction p = 0.03). There were no findings in the PCC, nor in the negative control (late Braak stage) regions of the precuneus and precentral gyrus. CONCLUSIONS: Our findings are in line with the spatially- and temporally-resolved Braak staging model of pathological severity in which the hippocampus is affected earlier than the PCC. The correlations, between MRS markers of synaptic and neuronal health and, respectively, T and N pathology, were found exclusively within APOE4 carriers, suggesting a connection with AD pathological change, rather than with normal aging. We therefore conclude that MRS has the potential to augment early A/T/N staging, with the hippocampus serving as a more sensitive MRS target compared to the PCC.
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Enfermedad de Alzheimer , Apolipoproteína E4 , Biomarcadores , Espectroscopía de Resonancia Magnética , Proteínas tau , Humanos , Apolipoproteína E4/genética , Anciano , Femenino , Masculino , Proteínas tau/líquido cefalorraquídeo , Proteínas tau/genética , Proteínas tau/metabolismo , Estudios Retrospectivos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Anciano de 80 o más Años , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Alelos , Persona de Mediana Edad , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Hipocampo/metabolismoRESUMEN
OBJECTIVE: To investigate the relationship of followings for patients with moyamoya disease (MMD): arterial wall enhancement on vessel wall MRI (VW-MRI), cross-sectional area (CSA), time-of-flight MR angiography (MRA), age, locations from intracranial internal carotid artery (ICA) to proximal middle cerebral artery (MCA), disease progression, and transient ischemic attack (TIA). METHODS: Patients who underwent VW-MRI between October 2018 and December 2020 were enrolled in this retrospective study. We measured arterial wall enhancement (enhancement ratio, ER) and CSA at five sections of ICA and MCA. Also, we scored MRA findings. Multiple linear regression (MLR) analysis was performed to explore the associations between ER, age, MRA score, CSA, history of TIA, and surgical revascularization. RESULTS: We investigated 102 sides of 51 patients with MMD (35 women, 16 men, mean age 31 years ± 18 [standard deviation]). ER for MRA score 2 (signal discontinuity) was higher than ER for other scores in sections D (end of ICA) and E (proximal MCA) on MLR analysis. ER in section E was significantly higher in patients for MRA score 2 with TIA history than without. ER significantly increased as CSA increased in section E, which suggests ER becomes less in decreased CSA due to negative remodeling. CONCLUSION: Arterial wall enhancement in MMD varies by age, location, and disease progression. Arterial wall enhancement may be stronger in the progressive stage of MMD. Arterial wall enhancement increases with history of TIA at proximal MCA, which may indicate the progression of the disease. CLINICAL RELEVANCE STATEMENT: Arterial wall enhancement in moyamoya disease varies by age, location of arteries, and disease progression, and arterial wall enhancement may be used as an imaging biomarker of moyamoya disease. KEY POINTS: It has not been clarified what arterial wall enhancement in moyamoya disease represents. Arterial wall enhancement in moyamoya disease varies by age, location of arteries, and disease progression. Arterial wall enhancement in moyamoya disease increases as the disease progresses.
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Ataque Isquémico Transitorio , Enfermedad de Moyamoya , Masculino , Humanos , Femenino , Adulto , Enfermedad de Moyamoya/diagnóstico por imagen , Estudios Retrospectivos , Ataque Isquémico Transitorio/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Arteria Cerebral Media , Progresión de la EnfermedadRESUMEN
BACKGROUND: Sensitive detection and quantification of cerebral glucose is desired. PURPOSE: To quantify cerebral glucose by detecting the H1-α-glucose peak at 5.23 ppm in 1 H magnetic resonance spectroscopy at 7 T. STUDY TYPE: Prospective. SUBJECTS: Twenty-eight non-fasted healthy subjects (aged 20-28 years). FIELD STRENGTH/SEQUENCE: Short echo time stimulated echo acquisition mode (short-TE STEAM) and semi-localized by adiabatic selective refocusing (semi-LASER) at 7 T. ASSESSMENT: Single voxel spectra were obtained from the posterior cingulate cortex (27-mL) using a 32-channel head coil. The H1-α-glucose peak in the spectrum with retrospective removal of the residual water peak was fitted using LCModel with a glucose basis set of only the H1-α-glucose peak. Conventional spectral analysis was performed with a glucose basis set of a full spectral pattern of glucose, also. Fitting precision was evaluated with Cramér-Rao lower bounds (CRLBs). The repeatability of glucose quantification via the semi-LASER sequence was tested. STATISTICAL TESTS: Paired or Welch's t-test were used for normally distributed values. A P value of <0.05 was considered significant. The repeatability of measures was analyzed using coefficient of variation (CV). RESULTS: Removal of the residual water peak improved the flatness and stability of baselines around the H1-α-glucose peak and reduced CRLBs for fitting the H1-α-glucose peak. The semi-LASER sequence was superior to the short-TE STEAM in the higher signal-to-noise ratio of the H1-α-glucose peak (mean ± SD 7.9 ± 2.5, P < 0.001). The conventional analysis overfitted the H1-α-glucose peak. The individual CVs of glucose quantification by detecting the H1-α-glucose peak were smaller than the corresponding CRLBs. DATA CONCLUSION: Cerebral glucose concentration is quantitated to be 1.07 mM by detecting the H1-α-glucose peak in the semi-LASER spectra. Despite requiring long scan times, detecting the H1-α-glucose peak allows true glucose quantification free from the influence of overlapping taurine and macromolecule signals. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.
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Encéfalo , Agua , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Espectroscopía de Resonancia Magnética/métodos , Relación Señal-Ruido , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismoRESUMEN
To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.
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Encéfalo , Imagen por Resonancia Magnética , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Cabeza , Neuroimagen , Relación Señal-RuidoRESUMEN
Rationale and objectives: Macromolecules (MMs) affect the precision and accuracy of neurochemical quantification in magnetic resonance spectroscopy. A measured MM basis is increasingly used in LCModel analysis combined with a spline baseline, whose stiffness is controlled by a parameter named DKNTMN. The effects of measured MM basis and DKNTMN were investigated. Materials and methods: Twenty-six healthy subjects were prospectively enrolled and scanned twice using a short echo-time Stimulated Echo Acquisition Mode (STEAM) at 7-T. Using LCModel, analyses were conducted using the simulated MM basis (MMsim) with DKNTMN 0.15 and an MM basis measured inhouse (MMmeas) with DKNTMN of 0.15, 0.30, 0.60 and 1.00. Cramér-Rao lower bound (CRLB) and the concentrations of gamma-aminobutyric acid (GABA), glutamate and excitatory-inhibitory ratio (EIR), in addition to MMs were statistically analyzed. Measurement stability was evaluated using coefficient of variation (CV). Results: CRLBs of GABA were significantly lower when using MMsim than MMmeas; those of glutamate were 2-3. GABA concentrations were significantly higher in the analysis using MMsim than MMmeas where concentrations were significantly higher with DKNTMN of 0.15 or 0.30 than 0.60 or 1.00. Difference in glutamate concentration was not significant. EIRs showed the same difference as in GABA depending on the DKNTMN values. CVs between test-retest scans were relatively stable for glutamate but became larger as DKNTMN increased for GABA and EIR. Conclusion: Neurochemical quantification depends on the parameters of the basis sets used for fitting. Analysis using MMmeas with DKNTMN of 0.30 conformed best to previous studies and is recommended.
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PURPOSE: CEST MRI has been used to probe changes in cardiac metabolism via assessment of CEST contrast from Cr. However, B1 variation across the myocardium leads to spatially variable Cr CEST contrast in healthy myocardium. METHODS: We developed a spatial-spectral (SPSP) saturation pulsed CEST protocol to compensate for B1 variation. Flip angle maps were used to individually tailor SPSP pulses comprised of a train of one-dimensional spatially selective subpulses selective along the principal B1 gradient dimension. Complete Z-spectra in the hearts of (n = 10) healthy individuals were acquired using conventional Gaussian saturation and SPSP schemes and supported by phantom studies. RESULTS: In simulations, the use of SPSP pulses reduced the average SD of the effective saturation B1 values within the myocardium (n = 10) from 0.12 ± 0.02 µT to 0.05 ± 0.01 µT (p < 0.01) and reduced the average SD of Cr CEST contrast in vivo from 10.0 ± 4.3% to 6.1 ± 3.5% (p < 0.05). Results from the hearts of human subjects showed a significant reduction of CEST contrast distribution at 2 ppm, as well as amplitude, when using SPSP saturation. Corresponding phantom experiments revealed PCr-specific contrast generation at body temperature when SPSP saturation was used but combined PCr and Cr contrast generation when Gaussian saturation was used. CONCLUSION: The use of SPSP saturation pulsed CEST resulted in PCr-specific contrast generation and enabled ratiometric mapping of PCr to total Cr CEST contrast in the human heart at 3T.
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PURPOSE: Proton magnetic resonance spectroscopy (1H MRS) offers biomarkers of metabolic damage after mild traumatic brain injury (mTBI), but a lack of replicability studies hampers clinical translation. In a conceptual replication study design, the results reported in four previous publications were used as the hypotheses (H1-H7), specifically: abnormalities in patients are diffuse (H1), confined to white matter (WM) (H2), comprise low N-acetyl-aspartate (NAA) levels and normal choline (Cho), creatine (Cr) and myo-inositol (mI) (H3), and correlate with clinical outcome (H4); additionally, a lack of findings in regional subcortical WM (H5) and deep gray matter (GM) structures (H6), except for higher mI in patients' putamen (H7). METHODS: 26 mTBI patients (20 female, age 36.5 ± 12.5 [mean ± standard deviation] years), within two months from injury and 21 age-, sex-, and education-matched healthy controls were scanned at 3 Tesla with 3D echo-planar spectroscopic imaging. To test H1-H3, global analysis using linear regression was used to obtain metabolite levels of GM and WM in each brain lobe. For H4, patients were stratified into non-recovered and recovered subgroups using the Glasgow Outcome Scale Extended. To test H5-H7, regional analysis using spectral averaging estimated metabolite levels in four GM and six WM structures segmented from T1-weighted MRI. The Mann-Whitney U test and weighted least squares analysis of covariance were used to examine mean group differences in metabolite levels between all patients and all controls (H1-H3, H5-H7), and between recovered and non-recovered patients and their respectively matched controls (H4). Replicability was defined as the support or failure to support the null hypotheses in accordance with the content of H1-H7, and was further evaluated using percent differences, coefficients of variation, and effect size (Cohen's d). RESULTS: Patients' occipital lobe WM Cho and Cr levels were 6.0% and 4.6% higher than controls', respectively (Cho, d = 0.37, p = 0.04; Cr, d = 0.63, p = 0.03). The same findings, i.e., higher patients' occipital lobe WM Cho and Cr (both p = 0.01), but with larger percent differences (Cho, 8.6%; Cr, 6.3%) and effect sizes (Cho, d = 0.52; Cr, d = 0.88) were found in the comparison of non-recovered patients to their matched controls. For the lobar WM Cho and Cr comparisons without statistical significance (frontal, parietal, temporal), unidirectional effect sizes were observed (Cho, d = 0.07 - 0.37; Cr, d = 0.27 - 0.63). No differences were found in any metabolite in any lobe in the comparison between recovered patients and their matched controls. In the regional analyses, no differences in metabolite levels were found in any GM or WM region, but all WM regions (posterior, frontal, corona radiata, and the genu, body, and splenium of the corpus callosum) exhibited unidirectional effect sizes for Cho and Cr (Cho, d = 0.03 - 0.34; Cr, d = 0.16 - 0.51). CONCLUSIONS: We replicated findings of diffuse WM injury, which correlated with clinical outcome (supporting H1-H2, H4). These findings, however, were among the glial markers Cho and Cr, not the neuronal marker NAA (not supporting H3). No differences were found in regional GM and WM metabolite levels (supporting H5-H6), nor in putaminal mI (not supporting H7). Unidirectional effect sizes of higher patients' Cho and Cr within all WM analyses suggest widespread injury, and are in line with the conclusion from the previous publications, i.e., that detection of WM injury may be more dependent upon sensitivity of the 1H MRS technique than on the selection of specific regions. The findings lend further support to the corollary that clinic-ready 1H MRS biomarkers for mTBI may best be achieved by using high signal-to-noise-ratio single-voxels placed anywhere within WM. The biochemical signature of the injury, however, may differ and therefore absolute levels, rather than ratios may be preferred. Future replication efforts should further test the generalizability of these findings.
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Conmoción Encefálica , Lesiones Encefálicas , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Espectroscopía de Protones por Resonancia Magnética , Conmoción Encefálica/patología , Espectroscopía de Resonancia Magnética/métodos , Protones , Lesiones Encefálicas/patología , Encéfalo/patología , Ácido Aspártico , Creatina/metabolismo , Colina/metabolismoRESUMEN
Hepatic encephalopathy (HE) is a common neurological manifestation of liver cirrhosis and is characterized by an increase of ammonia in the brain accompanied by a disrupted neurotransmitter balance, including the GABAergic and glutamatergic systems. The aim of this study is to investigate metabolic abnormalities in the cerebello-thalamo-cortical system of HE patients using GABA-edited MRS and links between metabolite levels, disease severity, critical flicker frequency (CFF), motor performance scores, and blood ammonia levels. GABA-edited MRS was performed in 35 participants (16 controls, 19 HE patients) on a clinical 3 T MRI system. MRS voxels were placed in the right cerebellum, left thalamus, and left motor cortex. Levels of GABA+ and of other metabolites of interest (glutamine, glutamate, myo-inositol, glutathione, total choline, total NAA, and total creatine) were assessed. Group differences in metabolite levels and associations with clinical metrics were tested. GABA+ levels were significantly increased in the cerebellum of patients with HE. GABA+ levels in the motor cortex were significantly decreased in HE patients, and correlated with the CFF (r = 0.73; p < .05) and motor performance scores (r = -0.65; p < .05). Well-established HE-typical metabolite patterns (increased glutamine, decreased myo-inositol and total choline) were confirmed in all three regions and were closely linked to clinical metrics. In summary, our findings provide further evidence for alterations in the GABAergic system in the cerebellum and motor cortex in HE. These changes were accompanied by characteristic patterns of osmolytes and oxidative stress markers in the cerebello-thalamo-cortical system. These metabolic disturbances are a likely contributor to HE motor symptoms in HE. In patients with hepatic encephalopathy, GABA+ levels in the cerebello-thalamo-cortical loop are significantly increased in the cerebellum and significantly decreased in the motor cortex. GABA+ levels in the motor cortex strongly correlate with critical flicker frequency (CFF) and motor performance score (pegboard test tPEG), but not blood ammonia levels (NH3).
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Encefalopatía Hepática , Humanos , Encefalopatía Hepática/metabolismo , Glutamina/metabolismo , Amoníaco , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Inositol , Ácido gamma-Aminobutírico/metabolismo , Colina/metabolismoRESUMEN
Whether brain temperature noninvasively extracted by magnetic resonance imaging has a role in identifying brain changes in the later phases of mild to moderate traumatic brain injury (TBI) is not known. This prospective study aimed to evaluate if TBI patients in subacute and chronic phases had altered brain temperature measured by whole-brain magnetic resonance spectroscopic imaging (WB-MRSI) and if the measurable brain temperature had any relationship with cognitive function scores. WB-MRSI was performed on eight TBI patients and fifteen age- and sex-matched control subjects. Brain temperature (T) was extracted from the brain's major metabolites and compared between the two groups. The T of the patients was tested for correlation with cognitive function test scores. The results showed significantly lower brain temperature in the TBI patients (p < 0.05). Brain temperature derived from N-acetylaspartate (TNAA) strongly correlated with the 2 s paced auditory serial addition test (PASAT-2s) score (p < 0.05). The observation of lower brain temperature in TBI patients may be due to decreased metabolic activity resulting from glucose and oxygen depletion. The correlation of brain temperature with PASAT-2s may imply that noninvasive brain temperature may become a noninvasive index reflecting cognitive performance.
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PURPOSE: Severe geometric distortions induced by tissue susceptibility, water-fat chemical shift, and eddy currents pose a substantial obstacle in single-shot EPI, especially for high-resolution imaging at ultrahigh field. View angle tilting (VAT)-EPI can mitigate in-plane distortion. However, the accompanied strong image blurring prevented its widespread applications. On the other hand, point-spread function mapping (PSF)-EPI can correct distortion and blurring accurately but requires prolonged scan time. We present fused VAT-PSF-EPI and possibilities for acceleration. METHODS: MR signal equations were explicitly derived to quantify image blurring in VAT-EPI and the maximum acceleration capacity in VAT-PSF-EPI. To validate the theoretical prediction, phantom measurements with varying in-plane parallel imaging factors, slice thicknesses, and RF pulses were conducted at 7 Tesla. In addition, in vivo human brain scans were acquired with T2 and diffusion weighting to assess distortion and blurring correction. RESULTS: VAT can effectively suppress distortion, and the introduced image blurring is corrected through PSF encoding. Up to fourfold acceleration (only 5 shots) in VAT-PSF-EPI was achieved compared with standard PSF-EPI without VAT. VAT-induced signal loss was mitigated by adjusting the sequence parameters and EPI resolution. In vivo T2 -weighted EPI data with 1.4 mm3 resolution demonstrate immunity to water-fat chemical shift-induced distortion. Very high-spatial resolution diffusion-weighted EPI (0.7 × 0.7 × 2.8 mm3 and 1.2 mm3 ) demonstrates the immunity to eddy current-induced distortion. CONCLUSION: VAT-PSF-EPI is a novel spin-echo EPI-based sequence for fast high-resolution diffusion imaging at ultrahigh field.
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Algoritmos , Imagen Eco-Planar , Artefactos , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Eco-Planar/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , AguaRESUMEN
This prospective study aimed to evaluate the variation in magnetic resonance spectroscopic imaging (MRSI)-observed brain metabolite concentrations according to anatomical location, sex, and age, and the relationships among regional metabolite distributions, using short echo time (TE) whole-brain MRSI (WB-MRSI). Thirty-eight healthy participants underwent short TE WB-MRSI. The major metabolite ratios, i.e., N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myoinositol (mI)/Cr, were calculated voxel-by-voxel. Their variations according to anatomical regions, sex, and age, and their relationship to each other were evaluated by using repeated-measures analysis of variance, t-tests, and Pearson's product-moment correlation analyses. All four metabolite ratios exhibited widespread regional variation across the cerebral hemispheres (corrected p < 0.05). Laterality between the two sides and sex-related variation were also shown (p < 0.05). In several regions, NAA/Cr and Glx/Cr decreased and mI/Cr increased with age (corrected p < 0.05). There was a moderate positive correlation between NAA/Cr and mI/Cr in the insular lobe and thalamus and between Glx/Cr and mI/Cr in the parietal lobe (r ≥ 0.348, corrected p ≤ 0.025). These observations demand age- and sex- specific regional reference values in interpreting these metabolites, and they may facilitate the understanding of glial-neuronal interactions in maintaining homeostasis.
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Prior studies indicate a pathogenic role of neuroinflammation in psychiatric disorders; however, there are no accepted methods that can reliably measure low-level neuroinflammation non-invasively in these individuals. Magnetic resonance spectroscopic imaging (MRSI) is a versatile, non-invasive neuroimaging technique that demonstrates sensitivity to brain inflammation. MRSI in conjunction with echo-planar spectroscopic imaging (EPSI) measures brain metabolites to derive whole-brain and regional brain temperatures, which may increase in neuroinflammation. The validity of MRSI/EPSI for measurement of low level neuroinflammation was tested using a safe experimental model of human brain inflammation - intramuscular administration of typhoid vaccine. Twenty healthy volunteers participated in a double-blind, placebo-controlled crossover study including MRSI/EPSI scans before and 3 h after vaccine/placebo administration. Body temperature and mood, assessed using the Profile of Mood States, were measured every hour up to four hours post-treatment administration. A mixed model analysis of variance was used to test for treatment effects. A significant proportion of brain regions (44/47) increased in temperature post-vaccine compared to post-placebo (p < 0.0001). For temperature change in the brain as a whole, there was no significant treatment effect. Significant associations were seen between mood scores assessed at 4 h and whole brain and regional temperatures post-treatment. Findings indicate that regional brain temperature may be a more sensitive measure of low-level neuroinflammation than whole-brain temperature. Future work where these measurement techniques are applied to populations with psychiatric disorders would be of clinical interest.
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Encefalitis , Vacunas Tifoides-Paratifoides , Encéfalo/patología , Estudios Cruzados , Encefalitis/metabolismo , Encefalitis/patología , Humanos , Espectroscopía de Resonancia Magnética/métodos , Enfermedades Neuroinflamatorias , Temperatura , Vacunas Tifoides-Paratifoides/metabolismoRESUMEN
Attending to a stimulus enhances the neuronal responses to it, while responses to nonattended stimuli are not enhanced and may even be suppressed. Although the neural mechanisms of response enhancement for attended stimuli have been intensely studied, the neural mechanisms underlying attentional suppression remain largely unknown. It is uncertain whether attention acts to suppress the processing in sensory cortical areas that would otherwise process the nonattended stimulus or the subcortical input to these cortical areas. Moreover, the neurochemical mechanisms inducing a reduction or suppression of neuronal responses to nonattended stimuli are as yet unknown. Here, we investigated how attention directed toward visual processing cross-modally acts to suppress vestibular responses in the human brain. By using functional magnetic resonance spectroscopy in a group of female and male subjects, we find that attention to visual motion downregulates in a load-dependent manner the concentration of excitatory neurotransmitter (glutamate and its precursor glutamine, referred to together as Glx) within the parietoinsular vestibular cortex (PIVC), a core cortical area of the vestibular system, while leaving the concentration of inhibitory neurotransmitter (GABA) in PIVC unchanged. This makes PIVC less responsive to excitatory thalamic vestibular input, as corroborated by functional magnetic resonance imaging. Together, our results suggest that attention acts to suppress the processing of nonattended sensory cues cortically by neurochemically rendering the core cortical area of the nonattended sensory modality less responsive to excitatory thalamic input.SIGNIFICANCE STATEMENT Here, we address a fundamental problem that has eluded attention research for decades, namely, how the brain ignores irrelevant stimuli. To date, three classes of solutions to this problem have been proposed: (1) enhancement of GABAergic interneuron activity in cortex, (2) downregulation of glutamatergic cell activity in cortex; and (3) downregulation of neural activity in thalamic projection areas, which would then provide the cortex with less input. Here, we use magnetic resonance spectroscopy in humans and find support for the second hypothesis, implying that attention to one sensory modality involves the suppression of irrelevant stimuli of another sensory modality by downregulating glutamate in the cortex.
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Atención/fisiología , Corteza Cerebral/fisiología , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Adulto , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Estimulación Luminosa , Percepción Visual/fisiología , Adulto JovenRESUMEN
BACKGROUND: Proton magnetic resonance spectroscopy (MRS) provides a unique opportunity for in vivo measurements of the brain's metabolic profile. Two methods of mainstream data acquisition are compared at 7 T, which provides certain advantages as well as challenges. The two representative methods have seldom been compared in terms of measured metabolite concentrations and different scan times. The current study investigated proton MRS of the posterior cingulate cortex using a semi-localized by adiabatic selective refocusing (sLASER) sequence and a short echo time (TE) stimulated echo acquisition mode (sSTEAM) sequence, and it compared their reliability and repeatability at 7 T using a 32-channel head coil. METHODS: Sixteen healthy subjects were prospectively enrolled and scanned twice with an off-bed interval between scans. The scan parameters for sLASER were a TR/TE of 6.5 s/32 ms and 32 and 48 averages (sLASER×32 and sLASER×48, respectively). The scan parameters for sSTEAM were a TR/TE of 4 s/5 ms and 32, 48, and 64 averages (sSTEAM4×32, sSTEAM4×48, and sSTEAM4×64, respectively) in addition to that with a TR/TE of 8 s/5 ms and 32 averages (sSTEAM8×32). Data were analyzed using LCModel. Metabolites quantified with Cramér-Rao lower bounds (CRLBs) >50% were classified as not detected, and metabolites quantified with mean or median CRLBs ≤20% were included for further analysis. The SNR, CRLBs, coefficient of variation (CV), and metabolite concentrations were statistically compared using the Shapiro-Wilk test, one-way ANOVA, or the Friedman test. RESULTS: The sLASER spectra for N-acetylaspartate + N-acetylaspartylglutamate (tNAA) and glutamate (Glu) had a comparable or higher SNR than sSTEAM spectra. Ten metabolites had lower CRLBs than prefixed thresholds: aspartate (Asp), γ-aminobutyric acid (GABA), glutamine (Gln), Glu, glutathione (GSH), myo-inositol (Ins), taurine (Tau), the total amount of phosphocholine + glycerophosphocholine (tCho), creatine + phosphocreatine (tCr), and tNAA. Performance of the two sequences was satisfactory except for GABA, for which sLASER yielded higher CRLBs (≥18%) than sSTEAM. Some significant differences in CRLBs were noted, but they were ≤2% except for GABA and Gln. Signal averaging significantly lowered CRLBs for some metabolites but only by a small amount. Measurement repeatability as indicated by median CVs was ≤10% for Gln, Glu, Ins, tCho, tCr, and tNAA in all scans, and that for Asp, GABA, GSH, and Tau was ≥10% under some scanning conditions. The CV for GABA according to sLASER was significantly higher than that according to sSTEAM, whereas the CV for Ins was higher according to sSTEAM. An increase in signal averaging contribute little to lower CVs except for Ins. CONCLUSIONS: Both sequences quantified brain metabolites with a high degree of precision and repeatability. They are comparable except for GABA, for which sSTEAM would be a better choice.
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BACKGROUND: Neuromelanin-sensitive magnetic resonance imaging techniques have been developed but currently require relatively long scan times. The aim of this study was to assess the ability of black-blood delay alternating with nutation for tailored excitation-prepared T1-weighted variable flip angle turbo spin echo (DANTE T1-SPACE), which provides relatively high resolution with a short scan time, to visualize neuromelanin in the substantia nigra pars compacta (SNpc). METHODS: Participants comprised 49 healthy controls and 25 patients with Parkinson's disease (PD). Contrast ratios of SNpc and hyperintense SNpc areas, which show pixels brighter than thresholds, were assessed between DANTE T1-SPACE and T1-SPACE in healthy controls. To evaluate the diagnostic ability of DANTE T1-SPACE, the contrast ratios and hyperintense areas were compared between healthy and PD groups, and receiver operating characteristic analyses were performed. We also compared areas under the curve (AUCs) between DANTE T1-SPACE and the previously reported gradient echo neuromelanin (GRE-NM) imaging. Each analysis was performed using original images in native space and images transformed into Montreal Neurological Institute space. Values of P < 0.05 were considered significant. RESULTS: DANTE T1-SPACE showed significantly higher contrast ratios and larger hyperintense areas than T1-SPACE. On DANTE T1-SPACE, healthy controls showed significantly higher contrast ratios and larger hyperintense areas than patients with PD. Hyperintense areas in native space analysis achieved the best AUC (0.94). DANTE T1-SPACE showed AUCs as high as those of GRE-NM. CONCLUSIONS: DANTE T1-SPACE successfully visualized neuromelanin of the SNpc and showed potential for evaluating PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Melaninas , Enfermedad de Parkinson , Humanos , Imagen por Resonancia Magnética , Enfermedad de Parkinson/diagnóstico por imagen , Porción Compacta de la Sustancia Negra , Sustancia NegraRESUMEN
BACKGROUND: 3D non-contrast high-resolution black-blood cardiovascular magnetic resonance (CMR) (DANTE-SPACE) has been used for surveillance of abdominal aortic aneurysm (AAA) and validated against computed tomography (CT) angiography. However, it requires a long scan time of more than 7 min. We sought to develop an accelerated sequence applying compressed sensing (CS-DANTE-SPACE) and validate it in AAA patients undergoing surveillance. METHODS: Thirty-eight AAA patients (all males, 73 ± 6 years) under clinical surveillance were recruited for this study. All patients were scanned with DANTE-SPACE (scan time 7:10 min) and CS-DANTE-SPACE (scan time 4:12 min, a reduction of 41.4%). Nine 9 patients were scanned more than 2 times. In total, 50 pairs of images were available for comparison. Two radiologists independently evaluated the image quality on a 1-4 scale, and measured the maximal diameter of AAA, the intra-luminal thrombus (ILT) and lumen area, ILT-to-muscle signal intensity ratio, and the ILT-to-lumen contrast ratio. The sharpness of the aneurysm inner/outer boundaries was quantified. RESULTS: CS-DANTE-SPACE achieved comparable image quality compared with DANTE-SPACE (3.15 ± 0.67 vs. 3.03 ± 0.64, p = 0.06). There was excellent agreement between results from the two sequences for diameter/area and ILT ratio measurements (ICCs> 0.85), and for quantifying growth rate (3.3 ± 3.1 vs. 3.3 ± 3.4 mm/year, ICC = 0.95.) CS-DANTE-SPACE showed a higher ILT-to-lumen contrast ratio (p = 0.01) and higher sharpness than DANTE-SPACE (p = 0.002). Both sequences had excellent inter-reader reproducibility for quantitative measurements (ICC > 0.88). CONCLUSION: CS-DANTE-SPACE can reduce scan time while maintaining image quality for AAA imaging. It is a promising tool for the surveillance of patients with AAA disease in the clinical setting.
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Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Imagenología Tridimensional , Angiografía por Resonancia Magnética , Anciano , Aorta Abdominal/fisiopatología , Aneurisma de la Aorta Abdominal/fisiopatología , Humanos , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Factores de Tiempo , Flujo de TrabajoRESUMEN
BACKGROUND: MRI is the imaging modality of choice for diagnosis and intervention assessment in neurological disease. Its full potential has not been realized due in part to challenges in harmonizing advanced techniques across multiple sites. PURPOSE: To develop a method for the assessment of reliability and repeatability of advanced multisite-multisession neuroimaging studies and specifically to assess the reliability of an advanced MRI protocol, including multiband fMRI and diffusion tensor MRI, in a multisite setting. STUDY TYPE: Prospective. POPULATION: Twice repeated measurement of a single subject with stable relapsing-remitting multiple sclerosis (MS) at seven institutions. FIELD STRENGTH/SEQUENCE: A 3 T MRI protocol included higher spatial resolution anatomical scans, a variable flip-angle longitudinal relaxation rate constant (R1 ≡ 1/T1 ) measurement, quantitative magnetization transfer imaging, diffusion tensor imaging, and a resting-state fMRI (rsFMRI) series. ASSESSMENT: Multiple methods of assessing intrasite repeatability and intersite reliability were evaluated for imaging metrics derived from each sequence. STATISTICAL TESTS: Student's t-test, Pearson's r, and intraclass correlation coefficient (ICC) (2,1) were employed to assess repeatability and reliability. Two new statistical metrics are introduced that frame reliability and repeatability in the respective units of the measurements themselves. RESULTS: Intrasite repeatability was excellent for quantitative R1 , magnetization transfer ratio (MTR), and diffusion-weighted imaging (DWI) based metrics (r > 0.95). rsFMRI metrics were less repeatable (r = 0.8). Intersite reliability was excellent for R1 , MTR, and DWI (ICC >0.9), and moderate for rsFMRI metrics (ICCâ¼0.4). DATA CONCLUSION: From most reliable to least, using a new reliability metric introduced here, MTR > R1 > DWI > rsFMRI; for repeatability, MTR > DWI > R1 > rsFMRI. A graphical method for at-a-glance assessment of reliability and repeatability, effect sizes, and outlier identification in multisite-multisession neuroimaging studies is introduced. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:878-888.
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Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Encéfalo/patología , Protocolos Clínicos , Imagen de Difusión Tensora/métodos , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/patología , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
Spectral editing allows direct measurement of low-concentration metabolites, such as GABA, glutathione (GSH) and lactate (Lac), relevant for understanding brain (patho)physiology. The most widely used spectral editing technique is MEGA-PRESS, which has been diversely implemented across research sites and vendors, resulting in variations in the final resolved edited signal. In this paper, we describe an effort to develop a new universal MEGA-PRESS sequence with HERMES functionality for the major MR vendor platforms with standardized RF pulse shapes, durations, amplitudes and timings. New RF pulses were generated for the universal sequence. Phantom experiments were conducted on Philips, Siemens, GE and Canon 3â¯T MRI scanners using 32-channel head coils. In vivo experiments were performed on the same six subjects on Philips and Siemens scanners, and on two additional subjects, one on GE and one on Canon scanners. On each platform, edited MRS experiments were conducted with the vendor-native and universal MEGA-PRESS sequences for GABA (TEâ¯=â¯68â¯ms) and Lac editing (TEâ¯=â¯140â¯ms). Additionally, HERMES for GABA and GSH was performed using the universal sequence at TEâ¯=â¯80â¯ms. The universal sequence improves inter-vendor similarity of GABA-edited and Lac-edited MEGA-PRESS spectra. The universal HERMES sequence yields both GABA- and GSH-edited spectra with negligible levels of crosstalk on all four platforms, and with strong agreement among vendors for both edited spectra. In vivo GABA+/Cr, Lac/Cr and GSH/Cr ratios showed relatively low variation between scanners using the universal sequence. In conclusion, phantom and in vivo experiments demonstrate successful implementation of the universal sequence across all four major vendors, allowing editing of several metabolites across a range of TEs.
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Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/normas , Adulto , Femenino , Glutatión/metabolismo , Humanos , Ácido Láctico/metabolismo , Espectroscopía de Resonancia Magnética/instrumentación , Masculino , Ácido gamma-Aminobutírico/metabolismoRESUMEN
BACKGROUND: Few studies directed at assessing the visualization of the walls of unruptured aneurysms have used higher-resolution 3D MRI vessel wall imaging. Prospective longitudinal studies are also needed to screen vessel wall changes in unruptured aneurysms. PURPOSE: To compare the aneurysm wall visualization on pre- and post-3D isotropic T1 -weighted Sampling Perfection with Application-optimized Contrasts by using different flip angle Evolutions (SPACE) images and to explore whether there is a change in wall enhancement at follow up. STUDY TYPE: Prospective. POPULATION: Twenty-nine patients with a total of 35 unruptured intracranial aneurysms. SEQUENCE: 3D T1 -weighted pre- and postcontrast SPACE (0.5 mm isotropic) at 3.0T. ASSESSMENT: The aneurysm wall visibility (0-5 scale) between pre- and postcontrast images as well as the wall enhancement (0-5 scale) between follow-up and baseline studies (6-30 months, average 12.7 months) were compared. Differences in wall visibility and enhancement were also investigated as a function of aneurysm diameter and location. STATISTICAL TEST: The Wilcoxon signed rank paired test was used to compare the wall visibility score between pre- and postcontrast SPACE images, as well as wall enhancement between follow-up and baseline. The Mann-Whitney and Kruskal-Wallis tests were used to investigate the enhancement difference between different diameters and locations. RESULTS: Postcontrast images had significantly higher wall visibility (P = 0.01). A wall enhancement score ≥2 was found in 71% of the aneurysms. Changes in levels of wall enhancement were found in 17% of the aneurysms at follow-up studies, but those changes were small. Wall visibility and enhancement scores of large aneurysms were significantly higher than small ones (P < 0.001). DATA CONCLUSION: 3D T1 -weighted higher resolution SPACE can be used to assess changes in enhancement at follow-up studies. Contrast SPACE image provides better aneurysm wall visibility and improves visualization of the aneurysm wall. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:193-200.
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Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Aneurisma Intracraneal/diagnóstico por imagen , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
This case report describes the usefulness of delay alternating with nutation for tailored excitation (DANTE)-prepared, contrast-enhanced magnetic resonance imaging (CE-MRI) for detecting the rupture site of an arteriovenous malformation (AVM). A ruptured intranidal aneurysm was confirmed histopathologically. Accurate non-invasive information about the possible rupture site of an AVM is critical for optimal treatment and evaluation. Vessel wall enhancement visualized by DANTE-prepared CE-MRI may be a useful tool for providing information about changes in inflammatory status and vulnerability to further developments.