ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Magnetic Resonance Imaging , Radio Waves , Equipment Design , Magnetic Resonance Imaging/methods , Phantoms, ImagingABSTRACT
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).
Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , Metabolome , Early Diagnosis , Biomarkers, Tumor/metabolismABSTRACT
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.