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Purpose: Phosphorus Magnetic Resonance Spectroscopy (31P MRS) enables non-invasive assessment of energy metabolism, yet its application is hindered by sensitivity limitations. To overcome this, often high magnetic fields are used, leading to challenges such as spatial B 1 + inhomogeneity and therefore the need for accurate flip angle determination in accelerated acquisitions with short repetition times T R ) . In response to these challenges, we propose a novel short T R and look-up table-based Double-Angle Method for fast 3D 31P B 1 + mapping (fDAM). Methods: Our method incorporates 3D weighted stack of spiral gradient echo acquisitions and a frequency-selective pulse to enable efficient B 1 + mapping based on the phosphocreatine signal at 7T. Protocols were optimised using simulations and validated through phantom experiments. The method was validated in phantom experiments and skeletal muscle applications using a birdcage 1H/31P volume coil. Results: The results of fDAM were compared to the classical DAM (cDAM). A good correlation (r=0.94) was obtained between the two B 1 + maps. A 3D 31P B 1 + mapping in the human calf muscle was achieved in about 10 min using a birdcage volume coil, with a 20% extended coverage relative to that of the cDAM (24 min). fDAM also enabled the first full brain coverage 31P 3D B 1 + mapping in approx. 10 min using a 1 Tx/ 32 Rx coil. Conclusion: fDAM is an efficient method for 31P 3D B 1 + mapping, showing promise for future applications in rapid 31P MRSI.
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This study aims to determine whether 1) individuals with treatment-resistant schizophrenia display early cognitive impairment compared to treatment-responders and healthy controls and 2) N-methyl-D-aspartate-receptor hypofunction is an underlying mechanism of cognitive deficits in treatment-resistance. In this caseâcontrol 3-year-follow-up longitudinal study, n = 697 patients with first-episode psychosis, aged 18 to 35, were screened for Treatment Response and Resistance in Psychosis criteria through an algorithm that assigns patients to responder, limited-response or treatment-resistant category (respectively resistant to 0, 1 or 2 antipsychotics). Assessments at baseline: MATRICS Consensus Cognitive Battery; N-methyl-D-aspartate-receptor co-agonists biomarkers in brain by MRS (prefrontal glutamate levels) and plasma (D-serine and glutamate pathways key markers). Patients were compared to age- and sex-matched healthy controls (n = 114). Results: patient mean age 23, 27% female. Treatment-resistant (n = 51) showed lower scores than responders (n = 183) in processing speed, attention/vigilance, working memory, verbal learning and visual learning. Limited responders (n = 59) displayed an intermediary phenotype. Treatment-resistant and limited responders were merged in one group for the subsequent D-serine and glutamate pathway analyses. This group showed D-serine pathway dysregulation, with lower levels of the enzymes serine racemase and serine-hydroxymethyltransferase 1, and higher levels of the glutamate-cysteine transporter 3 than in responders. Better cognition was associated with higher D-serine and lower glutamate-cysteine transporter 3 levels only in responders; this association was disrupted in the treatment resistant group. Treatment resistant patients and limited responders displayed early cognitive and persistent functioning impairment. The dysregulation of NMDAR co-agonist pathways provides underlying molecular mechanisms for cognitive deficits in treatment-resistant first-episode psychosis. If replicated, our findings would open ways to mechanistic biomarkers guiding response-based patient stratification and targeting cognitive improvement in clinical trials.
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Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. Here, we conduct NMR- and MS-based metabolomics on 1,153 matched ESCC tissues, normal mucosae, pre- and one-week post-operative sera and urines from 560 participants across three hospitals, with machine learning and WGCNA. Aberrations in 'alanine, aspartate and glutamate metabolism' proved to be prevalent throughout the ESCC evolution, consistently identified by NMR and MS, and reflected in 16 serum and 10 urine metabolic signatures in both discovery and validation sets. NMR-based simplified panels of any five serum or urine metabolites outperform clinical serological tumor markers (AUC = 0.984 and 0.930, respectively), and are effective in distinguishing early-stage ESCC in test set (serum accuracy = 0.994, urine accuracy = 0.879). Collectively, NMR-based biofluid screening can reveal characteristic metabolic events of ESCC and be feasible for early detection (ChiCTR2300073613).
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Metaboloma , Diagnóstico Precoz , Biomarcadores de Tumor/metabolismoRESUMEN
OBJECTIVE: This study evaluates the performance of a twisted pair transmission line coil as a transceive element for 7 T MRI in terms of physical flexibility, robustness to shape deformations, and interelement decoupling. METHODS: Each coil element was created by shaping a twisted pair of wires into a circle. One wire was interrupted at the top, while the other was interrupted at the bottom, and connected to the matching circuit. Electromagnetic simulations were conducted to determine the optimal number of twists per length (in terms of B1+ field efficiency, SAR efficiency, sensitivity to elongation, and interelement decoupling properties) and for investigating the fundamental operational principle of the coil through fields streamline visualisation. A comparison between the twisted pair coil and a conventional loop coil in terms of B1+ fields, maxSAR10g, and stability of S11 when the coil was deformed was performed. Experimentally measured interelement coupling between individual elements of multichannel arrays was also investigated. RESULTS: Increasing the number of twists per length resulted in a more physically robust coil. Poynting vector streamline visualisation showed that the twisted pair coil concentrated most of the energy in the near field. The twisted pair coil exhibited comparable B1+ fields and improved maxSAR10g to the conventional coil but demonstrated exceptional stability with respect to coil deformation and a strong self-decoupling nature when placed in an array configuration. DISCUSSION: The findings highlight the robustness of the twisted pair coil, showcasing its stability under shape variations. This coil holds great potential as a flexible RF coil for various imaging applications using multiple-element arrays, benefiting from its inherent decoupling.
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Imagen por Resonancia Magnética , Ondas de Radio , Diseño de Equipo , Imagen por Resonancia Magnética/métodos , Fantasmas de ImagenRESUMEN
In acute ischemic stroke, the composition of the occlusive clot can be associated with the underlying pathophysiology and the response to treatment. For these reasons, it is important to characterize the clot composition from clinical scans. We examine the ability of 3T and 7T MRI to distinguish the composition of in vitro clots, using quantitative T1 and T2*, alternatively R2*, mapping. When comparing the two field strengths, we found a tradeoff between sensitivity for clot composition and confidence in the clot depiction associated with spatial resolution. The loss of sensitivity at 7T can be mitigated by combining the T1 and T2* signals.
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Accidente Cerebrovascular Isquémico , Trombosis , Humanos , Imagen por Resonancia Magnética , Trombosis/diagnóstico por imagenRESUMEN
γ-Aminobutyric acid (GABA), as the primary inhibitory neurotransmitter, is extremely important for maintaining healthy brain function, and deviations from GABA homeostasis are related to various brain diseases. Short-echo-time (short-TE) proton MR spectroscopy (1 H-MRS) has been employed to measure GABA concentration from various human brain regions at high magnetic fields. The aim of this study was to investigate the effect of spectral linewidth on GABA quantification and explore the application of an optimized basis-set preparation approach using a spectral-linewidth-matched (LM) basis set in LCModel to improve the reproducibility of GABA quantification from short-TE 1 H-MRS. In contrast to the fixed-linewidth basis-set approach, the LM basis-set preparation approach, where all metabolite basis spectra were simulated with a linewidth 4 Hz narrower than that of water, showed a smaller standard deviation of estimated GABA concentration from synthetic spectra with varying linewidths and lineshapes. The test-retest reproducibility was assessed by the mean within-subject coefficient of variation, which improved from 19.2% to 12.0% in the thalamus, from 27.9% to 14.9% in the motor cortex, and from 9.7% to 2.8% in the medial prefrontal cortex using LM basis sets at 7 T. We conclude that spectral linewidth has a large effect on GABA quantification from short-TE 1 H-MRS data and that using LM basis sets in LCModel can improve the reproducibility of GABA quantification.
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Encéfalo , Protones , Humanos , Reproducibilidad de los Resultados , Espectroscopía de Protones por Resonancia Magnética/métodos , Encéfalo/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Nicotinamide Adenine Dinucleotide (NAD) plays a central role in the master circadian clock of the brain (the suprachiasmatic nuclei, SCN) as demonstrated in many model organisms. NAD acts as an enzyme co-factor and substrate and its modulation was found to be tightly regulated to the periodicity of the cycles. However, in human brain, the effect of the circadian rhythm (CR) on the metabolism of the SCN and other brain regions is poorly understood. We conducted a magnetic resonance spectroscopy (MRS) study at a high magnetic field, measuring the occipital brain NAD levels and other metabolites in two different morning and afternoon diurnal states in 25 healthy participants. Salivary cortisol levels were determined to confirm that the experiment was done in two chronologically different physiological conditions, and a behavioral test of risk-taking propensity was administered. Overall, we found that the CR did not significantly affect NAD levels in the occipital brain region. The other brain metabolites measured, including lactate, were not significantly affected by the CR either, except for taurine. The CR did impact risk-taking behavior and salivary cortisol level, confirming that the participants were in two circadian different behavioral and physiological states in the morning and in the afternoon. Measurement of the CR effect on NAD and taurine levels in other brain regions might provide stronger effects.
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Defects in essential metabolic regulation for energy supply, increased oxidative stress promoting excitatory/inhibitory imbalance and phospholipid membrane dysfunction have been implicated in the pathophysiology of schizophrenia (SZ). The knowledge about the developmental trajectory of these key pathophysiological components and their interplay is important to develop new preventive and treatment strategies. However, this assertion is so far limited. To investigate the developmental regulations of these key components in the brain, we assessed, for the first time, in vivo redox state from the oxidized (NAD+) and reduced (NADH) form of Nicotinamide Adenine Dinucleotide (NAD), energy and membrane metabolites, inhibitory and excitatory neurotransmitters by 31P and 1H MRS during the neurodevelopment of an SZ animal model with genetically compromised glutathione synthesis (gclm-KO mice). When compared to age-matched wild type (WT), an increase in NAD+/NADH redox ratio was found in gclm-KO mice until early adulthood, followed by a decrease in full adults as observed in patients. Especially, in early postnatal life (P20, corresponding to childhood), levels of several metabolites were altered in gclm-KO mice, including NAD+, NAD+/NADH, ATP, and glutamine + glutamate, suggesting an interactive compensation for redox dysregulation between NAD, energy metabolism, and neurotransmission. The identified temporal neurometabolic regulations under deficits in redox regulation provide insights into preventive treatment targets for at-risk individuals, and other neurodevelopmental disorders involving oxidative stress and energetic dysfunction.
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Antioxidantes , Esquizofrenia , Ratones , Animales , NAD/metabolismo , Esquizofrenia/metabolismo , Oxidación-Reducción , Metabolismo Energético , Modelos Animales de EnfermedadRESUMEN
A new and efficient magnetisation transfer 31 P magnetic resonance fingerprinting (MT-31 P-MRF) approach is introduced to measure the creatine kinase metabolic rate k CK between phosphocreatine (PCr) and adenosine triphosphate (ATP) in human brain. The MRF framework is extended to overcome challenges in conventional 31 P measurement methods in the human brain, enabling reduced acquisition time and specific absorption rate (SAR). To address the challenge of creating and matching large multiparametric dictionaries in an MRF scheme, a nested iteration interpolation method (NIIM) is introduced. As the number of parameters to estimate increases, the size of the dictionary grows exponentially. NIIM can reduce the computational load by breaking dictionary matching into subsolutions of linear computational order. MT-31 P-MRF combined with NIIM provides T 1 PCr , T 1 ATP and k CK estimates in good agreement with those obtained by the exchange kinetics by band inversion transfer (EBIT) method and literature values. Furthermore, the test-retest reproducibility results showed that MT-31 P-MRF achieves a similar or better coefficient of variation (<12%) for T 1 ATP and k CK measurements in 4 min 15 s, than EBIT with 17 min 4 s scan time, enabling a fourfold reduction in scan time. We conclude that MT-31 P-MRF in combination with NIIM is a fast, accurate, and reproducible approach for in vivo k CK assays in the human brain, which enables the potential to investigate energy metabolism in a clinical setting.
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BACKGROUND: There is increasing evidence that children or young adults having acquired liver disease in childhood display neurocognitive impairment which may become more apparent as they grow older. The molecular, cellular and morphological underpinnings of this clinical problem are incompletely understood. AIM: Therefore, we used the advantages of highly-resolved proton magnetic resonance spectroscopy at ultra-high magnetic field to analyze the neurometabolic profile and brain morphometry of children with chronic, compensated liver disease, hypothesizing that with high field spectroscopy we would identify early evidence of rising brain glutamine and decreased myoinositol, such as has been described both in animals and humans with more significant liver disease. METHODS: Patients (n = 5) and age-matched controls (n = 19) underwent 7T MR scans and short echo time 1H MR spectra were acquired using the semi-adiabatic SPECIAL sequence in two voxels located in gray and white matter dominated prefrontal cortex, respectively. A 3D MP2RAGE sequence was also acquired for brain volumetry and T1 mapping. Liver disease had to have developed at least 6 months before entering the study. Subjects underwent routine blood analysis and neurocognitive testing using validated methods within 3 months of MRI and MRS. RESULTS: Five children aged 8-16 years with liver disease acquired in childhood were included. Baseline biological characteristics were similar among patients. There were no statistically significant differences between subjects and controls in brain metabolite levels or brain volumetry. Finally, there were minor neurocognitive fluctuations including attention deficit in one child, but none fell in the statistically significant range. CONCLUSION: Children with chronic, compensated liver disease did not display an abnormal neurometabolic profile, neurocognitive abnormalities, or signal intensity changes in the globus pallidus. Despite the absence of neurometabolic changes, it is an opportunity to emphasize that it is only by developing the use of 1H MRS at high field in the clinical arena that we will understand the significance and generalizability of these findings in children with CLD. Healthy children displayed neurometabolic regional differences as previously reported in adult subjects.
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Hepatopatías , Protones , Animales , Adulto Joven , Humanos , Niño , Espectroscopía de Protones por Resonancia Magnética/métodos , Proyectos Piloto , Encéfalo/metabolismo , Hepatopatías/metabolismo , Imagen por Resonancia MagnéticaRESUMEN
PURPOSE: To introduce the dipolectric antenna: a novel RF coil design for high-field MRI using a combination of a dipole antenna with a loop-coupled dielectric resonator antenna. METHODS: Simulations in human voxel model Duke involving 8-, 16-, and 38-channel dipolectric antenna arrays for brain MRI were conducted. An 8-channel dipolectric antenna for occipital lobe MRI at 7 T was designed and constructed. The array was built of four dielectric resonator antennas (dielectric constant = 1070) and four segmented dipole antennas. In vivo MRI experiments were conducted in one subject, and the SNR performance was benchmarked against a commercial 32-channel head coil. RESULTS: A 38-channel dipolectric antenna array provided the highest whole-brain SNR (up to a 2.3-fold SNR gain in the center of the Duke's head vs. an 8-channel dipolectric antenna array). Dipolectric antenna arrays driven in dipole-only mode (with dielectric resonators used as receive-only) yielded the highest transmit performance. The constructed 8-channel dipolectric antenna array provided up to threefold higher in vivo peripheral SNR when compared with a 32-channel commercial head coil. CONCLUSION: Dipolectric antenna can be considered a promising approach to enhance SNR in human brain MRI at 7 T. This strategy can be used to develop novel multi-channel arrays for different high-field MRI applications.
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Encéfalo , Imagen por Resonancia Magnética , Humanos , Diseño de Equipo , Fantasmas de Imagen , Encéfalo/diagnóstico por imagen , Lóbulo Occipital , Relación Señal-RuidoRESUMEN
Redox biology and immune signaling play major roles in the body, including in brain function. A rapidly growing literature also suggests that redox and immune abnormalities are implicated in neuropsychiatric conditions such as schizophrenia (SZ), bipolar disorder, autism, and epilepsy. In this article we review this literature, its implications for the pathophysiology of SZ, and the potential for development of novel treatment interventions targeting redox and immune signaling. Redox biology and immune signaling in the brain are complex and not fully understood; in addition, there are discrepancies in the literature, especially in patient-oriented studies. Nevertheless, it is clear that abnormalities arise in SZ from an interaction between genetic and environmental factors during sensitive periods of brain development, and these abnormalities disrupt local circuits and long-range connectivity. Interventions that correct these abnormalities may be effective in normalizing brain function in psychotic disorders, especially in early phases of illness.
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Trastorno Bipolar , Trastornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Estrés Oxidativo/fisiología , Oxidación-ReducciónRESUMEN
PURPOSE: In this study, we aimed to measure the apparent diffusion coefficients (ADCs) of major phosphorous metabolites in the human calf muscle at 7 T with a diffusion-weighted (DW)-STEAM sequence. METHODS: A DW-STEAM sequence with bipolar gradients was implemented at 7 T, and DW MR spectra were acquired in three orthogonal directions in the human calf muscle of six healthy volunteers (TE/TM/TR = 15 ms/750 ms/5 s) at three b-values (0, 800, and 1200 s/mm2). Frequency and phase alignments were applied prior to spectral averaging. Averaged DW MR spectra were analyzed with LCModel, and ADCs of 31P metabolites were estimated. RESULTS: Four metabolites (phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and glycerol phosphorylcholine (GPC)) were quantified at all b-values with mean CRLBs below 10%. The ADC values of PCr, ATP, Pi, and GPC were (0.24 ± 0.02, 0.15 ± 0.04, 0.43 ± 0.14, 0.40 ± 0.09) × 10-3 mm2/s, respectively. CONCLUSION: The ADCs of four 31P metabolites were successfully measured in the human calf muscle at 7 T, among which those of ATP, Pi and GPC were reported for the first time in humans. This study paves the way to investigate 31P metabolite diffusion properties in health and disease on the clinical MR scanner.
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Imagen de Difusión por Resonancia Magnética , Músculo Esquelético , Humanos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/metabolismo , Fósforo , Adenosina Trifosfato/metabolismo , FosfatosRESUMEN
PURPOSE: We have introduced an artificial intelligence framework, 31P-SPAWNN, in order to fully analyze phosphorus-31 ( 31 $$ {}^{31} $$ P) magnetic resonance spectra. The flexibility and speed of the technique rival traditional least-square fitting methods, with the performance of the two approaches, are compared in this work. THEORY AND METHODS: Convolutional neural network architectures have been proposed for the analysis and quantification of 31 $$ {}^{31} $$ P-spectroscopy. The generation of training and test data using a fully parameterized model is presented herein. In vivo unlocalized free induction decay and three-dimensional 31 $$ {}^{31} $$ P-magnetic resonance spectroscopy imaging data were acquired from healthy volunteers before being quantified using either 31P-SPAWNN or traditional least-square fitting techniques. RESULTS: The presented experiment has demonstrated both the reliability and accuracy of 31P-SPAWNN for estimating metabolite concentrations and spectral parameters. Simulated test data showed improved quantification using 31P-SPAWNN compared with LCModel. In vivo data analysis revealed higher accuracy at low signal-to-noise ratio using 31P-SPAWNN, yet with equivalent precision. Processing time using 31P-SPAWNN can be further shortened up to two orders of magnitude. CONCLUSION: The accuracy, reliability, and computational speed of the method open new perspectives for integrating these applications in a clinical setting.
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Inteligencia Artificial , Fósforo , Humanos , Reproducibilidad de los Resultados , Espectroscopía de Resonancia Magnética/métodos , Redes Neurales de la ComputaciónRESUMEN
Emerging evidence is implicating mitochondrial function and metabolism in the nucleus accumbens in motivated performance. However, the brain is vulnerable to excessive oxidative insults resulting from neurometabolic processes, and whether antioxidant levels in the nucleus accumbens contribute to motivated performance is not known. Here, we identify a critical role for glutathione (GSH), the most important endogenous antioxidant in the brain, in motivation. Using proton magnetic resonance spectroscopy at ultra-high field in both male humans and rodent populations, we establish that higher accumbal GSH levels are highly predictive of better, and particularly, steady performance over time in effort-related tasks. Causality was established in in vivo experiments in rats that, first, showed that downregulating GSH levels through micro-injections of the GSH synthesis inhibitor buthionine sulfoximine in the nucleus accumbens impaired effort-based reward-incentivized performance. In addition, systemic treatment with the GSH precursor N-acetyl-cysteine increased accumbal GSH levels in rats and led to improved performance, potentially mediated by a cell-type-specific shift in glutamatergic inputs to accumbal medium spiny neurons. Our data indicate a close association between accumbal GSH levels and an individual's capacity to exert reward-incentivized effort over time. They also suggest that improvement of accumbal antioxidant function may be a feasible approach to boost motivation.
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Motivación , Núcleo Accumbens , Humanos , Masculino , Ratas , Animales , Núcleo Accumbens/fisiología , Antioxidantes/metabolismo , Recompensa , Glutatión/metabolismoRESUMEN
The purposes of the current study were to introduce a Mescher-Garwood (MEGA) semi-adiabatic spin-echo full-intensity localization (MEGA-sSPECIAL) sequence with macromolecule (MM) subtraction and to compare the test-retest reproducibility of γ-aminobutyric acid (GABA) measurements at 7 T using the sSPECIAL and MEGA-sSPECIAL sequences. The MEGA-sSPECIAL editing scheme using asymmetric adiabatic and highly selective Gaussian pulses was used to compare its GABA measurement reproducibility with that of short echo-time (TE) sSPECIAL. Proton magnetic resonance spectra were acquired in the motor cortex (M1) and medial prefrontal cortex (mPFC) using the sSPECIAL (TR/TE = 4000/16 ms) and MEGA-sSPECIAL sequences (TR/TE = 4000/80 ms). The metabolites were quantified using LCModel with unsuppressed water spectra. The concentrations are reported in institutional units. The test-retest reproducibility was evaluated by scanning each subject twice. Between-session reproducibility was assessed using coefficients of variation (CVs), Pearson's r correlation coefficients, and intraclass correlation coefficients (ICCs). Intersequence agreement was evaluated using Pearson's r correlation coefficients and Bland-Altman plots. Regarding GABA measurements by sSPECIAL, the GABA concentrations were 0.92 ± 0.31 (IU) in the M1 and 1.56 ± 0.49 (IU) in the mPFC. This demonstrated strong between-session correlation across both regions (r = 0.81, p < 0.01; ICC = 0.82). The CVs between the two scans were 21.8% in the M1 and 10.2% in the mPFC. On the other hand, the GABA measurements by MEGA-sSPECIAL were 0.52 ± 0.04 (IU) in the M1 and 1.04 ± 0.24 (IU) in the mPFC. MEGA-sSPECIAL demonstrated strong between-session correlation across the two regions (r = 0.98, p < 0.001; ICC = 0.98) and lower CVs than sSPECIAL, providing 4.1% in the M1 and 5.8% in the mPFC. The MEGA-editing method showed better reproducibility of GABA measurements in both brain regions compared with the short-TE sSPECIAL method. Thus it is a more sensitive method with which to detect small changes in areas with low GABA concentrations. In GABA-rich brain regions, GABA measurements can be achieved reproducibly using both methods.
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Encéfalo , Ácido gamma-Aminobutírico , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Humanos , Sustancias Macromoleculares/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Introduction: Recent efforts have been made to apply machine learning and deep learning approaches to the automated classification of schizophrenia using structural magnetic resonance imaging (sMRI) at the individual level. However, these approaches are less accurate on early psychosis (EP) since there are mild structural brain changes at early stage. As cognitive impairments is one main feature in psychosis, in this study we apply a multi-task deep learning framework using sMRI with inclusion of cognitive assessment to facilitate the classification of patients with EP from healthy individuals. Method: Unlike previous studies, we used sMRI as the direct input to perform EP classifications and cognitive estimations. The proposed deep learning model does not require time-consuming volumetric or surface based analysis and can provide additionally cognition predictions. Experiments were conducted on an in-house data set with 77 subjects and a public ABCD HCP-EP data set with 164 subjects. Results: We achieved 74.9 ± 4.3% five-fold cross-validated accuracy and an area under the curve of 71.1 ± 4.1% on EP classification with the inclusion of cognitive estimations. Discussion: We reveal the feasibility of automated cognitive estimation using sMRI by deep learning models, and also demonstrate the implicit adoption of cognitive measures as additional information to facilitate EP classifications from healthy controls.
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The invasive behavior of glioblastoma, the most aggressive primary brain tumor, is considered highly relevant for tumor recurrence. However, the invasion zone is difficult to visualize by Magnetic Resonance Imaging (MRI) and is protected by the blood brain barrier, posing a particular challenge for treatment. We report biological features of invasive growth accompanying tumor progression and invasion based on associated metabolic and transcriptomic changes observed in patient derived orthotopic xenografts (PDOX) in the mouse and the corresponding patients' tumors. The evolution of metabolic changes, followed in vivo longitudinally by 1H Magnetic Resonance Spectroscopy (1H MRS) at ultra-high field, reflected growth and the invasive properties of the human glioblastoma transplanted into the brains of mice (PDOX). Comparison of MRS derived metabolite signatures, reflecting temporal changes of tumor development and invasion in PDOX, revealed high similarity to spatial metabolite signatures of combined multi-voxel MRS analyses sampled across different areas of the patients' tumors. Pathway analyses of the transcriptome associated with the metabolite profiles of the PDOX, identified molecular signatures of invasion, comprising extracellular matrix degradation and reorganization, growth factor binding, and vascular remodeling. Specific analysis of expression signatures from the invaded mouse brain, revealed extent of invasion dependent induction of immune response, recapitulating respective signatures observed in glioblastoma. Integrating metabolic profiles and gene expression of highly invasive PDOX provided insights into progression and invasion associated mechanisms of extracellular matrix remodeling that is essential for cell-cell communication and regulation of cellular processes. Structural changes and biochemical properties of the extracellular matrix are of importance for the biological behavior of tumors and may be druggable. Ultra-high field MRS reveals to be suitable for in vivo monitoring of progression in the non-enhancing infiltration zone of glioblastoma.
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Neoplasias Encefálicas/genética , Glioblastoma/genética , Adulto , Anciano , Animales , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Femenino , Glioblastoma/diagnóstico por imagen , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Metaboloma , Ratones , Persona de Mediana Edad , Invasividad Neoplásica , Trasplante de Neoplasias , Espectroscopía de Protones por Resonancia Magnética , TranscriptomaRESUMEN
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.