RESUMO
Chemical exchange saturation transfer (CEST) is a magnetic resonance (MR) imaging method providing molecular image contrasts based on indirect detection of low concentrated solutes. Previous CEST studies focused predominantly on the imaging of single CEST exchange regimes (e.g., slow, intermediate or fast exchanging groups). In this work, we aim to establish a so-called comprehensive CEST protocol for 7 T, covering the different exchange regimes by three saturation B1 amplitude regimes: low, intermediate and high. We used the results of previous publications and our own simulations in pulseq-CEST to produce a 7 T CEST protocol that has sensitivity to these three B1 regimes. With postprocessing optimization (simultaneous mapping of water shift and B1, B0-fitting, multiple interleaved mode saturation B1 correction, neural network employment (deepCEST) and analytical input feature reduction), we are able to shorten our initially 40 min protocol to 15 min and generate six CEST contrast maps simultaneously. With this protocol, we measured four healthy subjects and one patient with a brain tumor. We established a comprehensive CEST protocol for clinical 7 T MRI, covering three different B1 amplitude regimes. We were able to reduce the acquisition time significantly by more than 50%, while still maintaining decent image quality and contrast in healthy subjects and one patient with a tumor. Our protocol paves the way to perform comprehensive CEST studies in clinical scan times for hypothesis generation regarding molecular properties of certain pathologies, for example, ischemic stroke or high-grade brain tumours.
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Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Redes Neurais de Computação , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagemRESUMO
PURPOSE: To evaluate the classifiability of small multiple sclerosis (MS)-like lesions in simulated sodium (23 Na) MRI for different 23 Na MRI contrasts and reconstruction methods. METHODS: 23 Na MRI and 23 Na inversion recovery (IR) MRI of a phantom and simulated brain with and without lesions of different volumes (V = 1.3-38.2 nominal voxels) were simulated 100 times by adding Gaussian noise matching the SNR of real 3T measurements. Each simulation was reconstructed with four different reconstruction methods (Gridding without and with Hamming filter, Compressed sensing (CS) reconstruction without and with anatomical 1 H prior information). Based on the mean signals within the lesion volumes of simulations with and without lesions, receiver operating characteristics (ROC) were determined and the area under the curve (AUC) was calculated to assess the classifiability for each lesion volume. RESULTS: Lesions show higher classifiability in 23 Na MRI than in 23 Na IR MRI. For typical parameters and SNR of a 3T scan, the voxel normed minimal classifiable lesion volume (AUC > 0.9) is 2.8 voxels for 23 Na MRI and 19 voxels for 23 Na IR MRI, respectively. In terms of classifiability, Gridding with Hamming filter and CS without anatomical 1 H prior outperform CS reconstruction with anatomical 1 H prior. CONCLUSION: Reliability of lesion classifiability strongly depends on the lesion volume and the 23 Na MRI contrast. Additional incorporation of 1 H prior information in the CS reconstruction was not beneficial for the classification of small MS-like lesions in 23 Na MRI.
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Esclerose Múltipla , Sódio , Humanos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Processamento de Imagem Assistida por Computador/métodosRESUMO
PURPOSE: In this work, we investigated the ability of neural networks to rapidly and robustly predict Lorentzian parameters of multi-pool CEST MRI spectra at 7 T with corresponding uncertainty maps to make them quickly and easily available for routine clinical use. METHODS: We developed a deepCEST 7 T approach that generates CEST contrasts from just 1 scan with robustness against B1 inhomogeneities. The input data for a neural feed-forward network consisted of 7 T in vivo uncorrected Z-spectra of a single B1 level, and a B1 map. The 7 T raw data were acquired using a 3D snapshot gradient echo multiple interleaved mode saturation CEST sequence. These inputs were mapped voxel-wise to target data consisting of Lorentzian amplitudes generated conventionally by 5-pool Lorentzian fitting of normalized, denoised, B0 - and B1 -corrected Z-spectra. The deepCEST network was trained with Gaussian negative log-likelihood loss, providing an uncertainty quantification in addition to the Lorentzian amplitudes. RESULTS: The deepCEST 7 T network provides fast and accurate prediction of all Lorentzian parameters also when only a single B1 level is used. The prediction was highly accurate with respect to the Lorentzian fit amplitudes, and both healthy tissues and hyperintensities in tumor areas are predicted with a low uncertainty. In corrupted cases, high uncertainty indicated wrong predictions reliably. CONCLUSION: The proposed deepCEST 7 T approach reduces scan time by 50% to now 6:42 min, but still delivers both B0 - and B1 -corrected homogeneous CEST contrasts along with an uncertainty map, which can increase diagnostic confidence. Multiple accurate 7 T CEST contrasts are delivered within seconds.
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Imageamento por Ressonância Magnética , Neoplasias , Humanos , Incerteza , Imageamento por Ressonância Magnética/métodos , Redes Neurais de Computação , Meios de ContrasteRESUMO
APTw CEST MRI suffers from long preparation times and consequently long acquisition times (~5 min). Recently, a consensus on the preparation module for clinical APTw CEST at 3 T was found in the community, and we present a fast whole-brain APTw CEST MRI sequence following this consensus preparation of pulsed RF irradiation of 2 s duration at 90% RF duty-cycle and a B1,rms of 2 µT. After optimization of the snapshot CEST approach for APTw imaging regarding flip angle, voxel size and frequency offset sampling, we extend it by undersampled GRE acquisition and compressed sensing reconstruction. This allows 2 mm isotropic whole-brain APTw imaging for clinical research at 3 T below 2 min. With this sequence, a fast snapshot APTw imaging method is now available for larger clinical studies of brain tumors.
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Neoplasias Encefálicas , Encéfalo , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Imagens de Fantasmas , AmidasRESUMO
The objective of the current study was to optimize the postprocessing pipeline of 7 T chemical exchange saturation transfer (CEST) imaging for reproducibility and to prove this optimization for the detection of age differences and differences between patients with Parkinson's disease versus normal subjects. The following 7 T CEST MRI experiments were analyzed: repeated measurements of a healthy subject, subjects of two age cohorts (14 older, seven younger subjects), and measurements of 12 patients with Parkinson's disease. A slab-selective, B 1 + -homogeneous parallel transmit protocol was used. The postprocessing, consisting of motion correction, smoothing, B 0 -correction, normalization, denoising, B 1 + -correction and Lorentzian fitting, was optimized regarding the intrasubject and intersubject coefficient of variation (CoV) of the amplitudes of the amide pool and the aliphatic relayed nuclear Overhauser effect (rNOE) pool within the brain. Seven "tricks" for postprocessing accomplished an improvement of the mean voxel CoV of the amide pool and the aliphatic rNOE pool amplitudes of less than 5% and 3%, respectively. These postprocessing steps are: motion correction with interpolation of the motion of low-signal offsets (1) using the amide pool frequency offset image as reference (2), normalization of the Z-spectrum using the outermost saturated measurements (3), B 0 correction of the Z-spectrum with moderate spline smoothing (4), denoising using principal component analysis preserving the 11 highest intensity components (5), B 1 + correction using a linear fit (6) and Lorentzian fitting using the five-pool fit model (7). With the optimized postprocessing pipeline, a significant age effect in the amide pool can be detected. Additionally, for the first time, an aliphatic rNOE contrast between subjects with Parkinson's disease and age-matched healthy controls in the substantia nigra is detected. We propose an optimized postprocessing pipeline for CEST multipool evaluation. It is shown that by the use of these seven "tricks", the reproducibility and, thus, the statistical power of a CEST measurement, can be greatly improved and subtle changes can be detected.
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Doença de Parkinson , Humanos , Reprodutibilidade dos Testes , Doença de Parkinson/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo , AmidasRESUMO
Isolated evaluation of multiparametric in vivo chemical exchange saturation transfer (CEST) MRI often requires complex computational processing for both correction of B0 and B1 inhomogeneity and contrast generation. For that, sufficiently densely sampled Z-spectra need to be acquired. The list of acquired frequency offsets largely determines the total CEST acquisition time, while potentially representing redundant information. In this work, a linear projection-based multiparametric CEST evaluation method is introduced that offers fast B0 and B1 inhomogeneity correction, contrast generation and feature selection for CEST data, enabling reduction of the overall measurement time. To that end, CEST data acquired at 7 T in six healthy subjects and in one brain tumor patient were conventionally evaluated by interpolation-based inhomogeneity correction and Lorentzian curve fitting. Linear regression was used to obtain coefficient vectors that directly map uncorrected data to corrected Lorentzian target parameters. L1-regularization was applied to find subsets of the originally acquired CEST measurements that still allow for such a linear projection mapping. The linear projection method allows fast and interpretable mapping from acquired raw data to contrast parameters of interest, generalizing from healthy subject training data to unseen healthy test data and to the tumor patient dataset. The L1-regularization method shows that a fraction of the acquired CEST measurements is sufficient to preserve tissue contrasts, offering up to a 2.8-fold reduction of scan time. Similar observations as for the 7-T data can be made for data from a clinical 3-T scanner. Being a fast and interpretable computation step, the proposed method is complementary to neural networks that have recently been employed for similar purposes. The scan time acceleration offered by the L1-regularization ("CEST-LASSO") constitutes a step towards better applicability of multiparametric CEST protocols in a clinical context.
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Encéfalo , Imageamento por Ressonância Magnética Multiparamétrica , Humanos , Redes Neurais de Computação , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagemRESUMO
Apparent tissue sodium concentrations (aTSCs) determined by 23 Na brain magnetic resonance imaging (MRI) have the potential to serve as a biomarker in pathologies such as multiple sclerosis (MS). However, the quantification is hindered by the intrinsically low signal-to-noise ratio of 23 Na MRI. The purpose of this study was to improve the accuracy and reliability of quantitative 23 Na brain MRI by implementing a dedicated postprocessing pipeline and to evaluate the applicability of the developed approach for the examination of MS patients. 23 Na brain MRI measurements of 13 healthy volunteers and 17 patients with secondary progressive multiple sclerosis (SPMS) were performed at 7 T using a dual-tuned 23 Na/1 H birdcage coil with a receive-only 32-channel phased array. The aTSC values were determined for normal appearing white matter (NAWM) and normal appearing gray matter (NAGM) in healthy subjects and SPMS patients. Signal intensities were normalized using the mean cerebrospinal fluid (CSF) sodium concentration determined in 37 separate patients receiving a spinal tap for routine diagnostic purposes. Five volunteers underwent MRI examinations three times in a row to assess repeatability. Coefficients of variation (CoVs) were used to quantify the repeatability of the proposed method. aTSC values were compared regarding brain regions and subject cohort using the paired-samples Wilcoxon rank-sum test. Laboratory CSF sodium concentration did not differ significantly between patients without and with MS (p = 0.42). The proposed quantification workflow for 23 Na MRI was highly repeatable with CoVs averaged over all five volunteers of 1.9% ± 0.9% for NAWM and 2.2% ± 1.6% for NAGM. Average NAWM aTSC was significantly higher in patients with SPMS compared with the control group (p = 0.009). Average NAGM aTSC did not differ significantly between healthy volunteers and MS patients (p = 0.98). The proposed postprocessing pipeline shows high repeatability and the results can serve as a baseline for further studies establishing 23 Na brain MRI as a biomarker in diseases such as MS.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Humanos , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/patologia , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Sódio , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , BiomarcadoresRESUMO
BACKGROUND: Sodium enhancement has been demonstrated in multiple sclerosis (MS) lesions. PURPOSE: To investigate sodium MRI with and without an inversion recovery pulse in acute MS lesions in an MS relapse and during recovery. STUDY TYPE: Prospective. SUBJECTS: Twenty-nine relapsing-remitting MS patients with an acute relapse were included. FIELD STRENGTH/SEQUENCE: A 3D density-adapted radial sodium sequence at 3 T using a dual-tuned (23 Na/1 H) head coil. ASSESSMENT: Full-brain images of the tissue sodium concentration (TSC1, n = 29) and a sodium inversion recovery sequence (SIR1, n = 20) at the beginning of the anti-inflammatory therapy and on medium-term follow-up visits (days 27-99, n = 12 [TSC], n = 5 [SIR]) were measured. Regions of interest (RoIs) with contrast enhancement (T1 CE+) and without change in T1-weighted imaging (FL + T1n) were normalized (nTSC and nSIR). To gain insight on the origin of the TSC enhancement at time point 1, it is investigated whether the nTSC enhancement of the lesions is accompanied by a change of the respective nSIR. Potential prognostic value of nSIR1 is examined referring to the nTSC progression. STATISTICAL TESTS: nTSC and nSIR were compared regarding the type of lesion and the time point using a one-way ANOVA. Pearson's correlation coefficient was calculated for nTSC over nSIR and for nTSC1-nTSC2 over nSIR1. A P-value <0.05 was considered statistically significant. RESULTS: At the first measurement, all lesion types showed increased nTSC, while nSIR was decreased in the FL + T1 n and the T1 CE+ lesions in comparison to the normal-appearing white matter. For acute lesions, the difference between nTSC at baseline and nTSC at time point 2 showed a significant correlation with the baseline nSIR. DATA CONCLUSION: At time point 1, nTSC is increased, while nSIR is unchanged or decreased in the lesions. The mean sodium IR signal at baseline correlates with recovery or progression of an acute lesion. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 4.
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Esclerose Múltipla , Sódio , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Estudos ProspectivosRESUMO
Since the seminal works by Brodmann and contemporaries, it is well-known that different brain regions exhibit unique cytoarchitectonic and myeloarchitectonic features. Transferring the approach of classifying brain tissues - and other tissues - based on their intrinsic features to the realm of magnetic resonance (MR) is a longstanding endeavor. In the 1990s, atlas-based segmentation replaced earlier multi-spectral classification approaches because of the large overlap between the class distributions. Here, we explored the feasibility of performing global brain classification based on intrinsic MR features, and used several technological advances: ultra-high field MRI, q-space trajectory diffusion imaging revealing voxel-intrinsic diffusion properties, chemical exchange saturation transfer and semi-solid magnetization transfer imaging as a marker of myelination and neurochemistry, and current neural network architectures to analyze the data. In particular, we used the raw image data as well to increase the number of input features. We found that a global brain classification of roughly 97 brain regions was feasible with gross classification accuracy of 60%; and that mapping from voxel-intrinsic MR data to the brain region to which the data belongs is possible. This indicates the presence of unique MR signals of different brain regions, similar to their cytoarchitectonic and myeloarchitectonic fingerprints.
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Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Análise de Dados , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Adulto , Idoso , Mapeamento Encefálico/classificação , Feminino , Humanos , Aprendizado de Máquina/classificação , Imageamento por Ressonância Magnética/classificação , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: To enable whole-brain quantitative CEST MRI at ultra-high magnetic field strengths (B0 ≥ 7T) within short acquisition times. METHODS: Multiple interleaved mode saturation (MIMOSA) was combined with fast online-customized (FOCUS) parallel transmission (pTx) excitation pulses and B1+ correction to achieve homogenous whole-brain coverage. Examinations of 13 volunteers were performed on a 7T MRI system with 3 different types of pulse sequences: (1) saturation in circular polarized (CP) mode and CP mode readout, (2) MIMOSA and CP readout, and (3) MIMOSA and FOCUS readout. For comparison, the inverse magnetic transfer ratio metric for relayed nuclear Overhauser effect and amide proton transfer were calculated. To investigate the number of required acquisitions for a good B1+ correction, 4 volunteers were measured with 6 different B1 amplitudes. Finally, time point repeatability was investigated for 6 volunteers. RESULTS: MIMOSA FOCUS sequence using B1+ correction, with both single and multiple points, reduced inhomogeneity of the CEST contrasts around the occipital lobe and cerebellum. Results indicate that the most stable inter-subject coefficient of variation was achieved using the MIMOSA FOCUS sequence. Time point repeatability of MIMOSA FOCUS with single-point B1+ correction showed a maximum coefficient of variation below 8% for 3 measurements in a single volunteer. CONCLUSION: A combination of MIMOSA FOCUS with a single-point B1+ correction can be used to achieve quantitative CEST measurements at ultra-high magnetic field strengths. Compared to previous B1+ correction methods, acquisition time can be reduced as additional scans required for B1+ correction can be omitted.
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Algoritmos , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Meios de Contraste , Humanos , PrótonsRESUMO
OBJECTIVES: Metal artefacts can impair accurate diagnosis of haemorrhage using flat detector CT (FD-CT), especially after aneurysm coiling. Within this work we evaluate a prototype metal artefact reduction algorithm by comparison of the artefact-reduced and the non-artefact-reduced FD-CT images to pre-treatment FD-CT and multi-slice CT images. METHODS: Twenty-five patients with acute aneurysmal subarachnoid haemorrhage (SAH) were selected retrospectively. FD-CT and multi-slice CT before endovascular treatment as well as FD-CT data sets after treatment were available for all patients. The algorithm was applied to post-treatment FD-CT. The effect of the algorithm was evaluated utilizing the pre-post concordance of a modified Fisher score, a subjective image quality assessment, the range of the Hounsfield units within three ROIs, and the pre-post slice-wise Pearson correlation. RESULTS: The pre-post concordance of the modified Fisher score, the subjective image quality, and the pre-post correlation of the ranges of the Hounsfield units were significantly higher for artefact-reduced than for non-artefact-reduced images. Within the metal-affected slices, the pre-post slice-wise Pearson correlation coefficient was higher for artefact-reduced than for non-artefact-reduced images. CONCLUSION: The overall diagnostic quality of the artefact-reduced images was improved and reached the level of the pre-interventional FD-CT images. The metal-unaffected parts of the image were not modified. KEY POINTS: ⢠After coiling subarachnoid haemorrhage, metal artefacts seriously reduce FD-CT image quality. ⢠This new metal artefact reduction algorithm is feasible for flat-detector CT. ⢠After coiling, MAR is necessary for diagnostic quality of affected slices. ⢠Slice-wise Pearson correlation is introduced to evaluate improvement of MAR in future studies. ⢠Metal-unaffected parts of image are not modified by this MAR algorithm.
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Algoritmos , Artefatos , Hemorragia Subaracnóidea/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Doença Aguda , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Several studies and recent models of effects of nicotine, the main addictive and psychoactive component in tobacco, point to action of the drug on the limbic system during maintenance of addiction, either direct or indirect via projections from the ventral tegmental area. The objective of this study was to demonstrate physiological effects of cigarette smoking on the hippocampus and the grey matter of the dorsal anterior cingulate cortex in the human brain with regard to addiction and withdrawal. This aim was achieved by group comparisons of results of magnetic resonance spectroscopy between non-smokers, smokers and smokers during withdrawal. 12 smokers and 12 non-smokers were measured with single voxel proton magnetic resonance spectroscopy for total N-acetyl aspartate, glutamate and glutamine, choline-containing compounds, myo-inositol and total creatine in the right and the left hippocampus and in the right and the left dorsal anterior cingulate cortex. Smokers were examined twice, first during regular cigarette smoking and second on the third day of nicotine withdrawal. The ratios to total creatine were used for better reliability. In our study, Glx/tCr was significantly increased and tCho/tCr was significantly decreased in the left cingulate cortex in smokers compared to non-smokers (p = 0.01, both). Six out of seven smokers showed normalization of the Glx/tCr in the left cingulate cortex during withdrawal. Although these results are preliminary due to the small sample size, our results confirm the assumption that cigarette smoking interferes directly or indirectly with the glutamate circuit in the dorsal anterior cingulate cortex.
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Giro do Cíngulo/metabolismo , Hipocampo/metabolismo , Fumar/metabolismo , Adulto , Feminino , Humanos , Masculino , Espectroscopia de Prótons por Ressonância Magnética , Processamento de Sinais Assistido por Computador , Síndrome de Abstinência a Substâncias/metabolismo , Adulto JovemRESUMO
OBJECTIVES: The purpose of this work was to evaluate the influence of residual quadrupolar interaction on the determination of human brain apparent tissue sodium concentrations (aTSCs) using quantitative sodium magnetic resonance imaging ( 23 Na MRI) in healthy controls (HCs) and patients with multiple sclerosis (MS). Especially, it was investigated if the more detailed examination of residual quadrupolar interaction effects enables further analysis of the observed 23 Na MRI signal increase in MS patients. MATERIALS AND METHODS: 23 Na MRI with a 7 T MR system was performed on 21 HC and 50 MS patients covering all MS subtypes (25 patients with relapsing-remitting MS, 14 patients with secondary progressive MS, and 11 patients with primary progressive MS) using 2 different 23 Na pulse sequences for quantification: a commonly used standard sequence (aTSC Std ) as well as a sequence with shorter excitation pulse length and lower flip angle for minimizing signal loss resulting from residual quadrupolar interactions (aTSC SP ). Apparent tissue sodium concentration was determined using the same postprocessing pipeline including correction of the receive profile of the radiofrequency coil, partial volume correction, and relaxation correction. Spin dynamic simulations of spin-3/2 nuclei were performed to aid in the understanding of the measurement results and to get deeper insight in the underlying mechanisms. RESULTS: In normal-appearing white matter (NAWM) of HC and all MS subtypes, the aTSC SP values were approximately 20% higher than the aTSC Std values ( P < 0.001). In addition, the ratio aTSC SP /aTSC Std was significantly higher in NAWM than in normal-appearing gray matter (NAGM) for all subject cohorts ( P < 0.002). In NAWM, aTSC Std values were significantly higher in primary progressive MS compared with HC ( P = 0.01) as well as relapsing-remitting MS ( P = 0.03). However, in contrast, no significant differences between the subject cohorts were found for aTSC SP . Spin simulations assuming the occurrence of residual quadrupolar interaction in NAWM were in good accordance with the measurement results, in particular, the ratio aTSC SP /aTSC Std in NAWM and NAGM. CONCLUSIONS: Our results showed that residual quadrupolar interactions in white matter regions of the human brain have an influence on aTSC quantification and therefore must be considered, especially in pathologies with expected microstructural changes such as loss of myelin in MS. Furthermore, the more detailed examination of residual quadrupolar interactions may lead to a better understanding of the pathologies themselves.
Assuntos
Esclerose Múltipla , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Sódio/análise , Química EncefálicaRESUMO
Objective: Functional magnetic resonance imaging (fMRI) visualizes brain structures at increasingly higher resolution and better signal-to-noise ratio (SNR) as field strength increases. Yet, mapping the blood oxygen level dependent (BOLD) response to distinct neuronal processes continues to be challenging. Here, we investigated the characteristics of 7 T-fMRI compared to 3 T-fMRI in the human brain beyond the effect of increased SNR and verified the benefits of 7 T-fMRI in the detection of tiny, highly specific modulations of functional connectivity in the resting state following a motor task. Methods: 18 healthy volunteers underwent two resting state and a stimulus driven measurement using a finger tapping motor task at 3 and 7 T, respectively. The SNR for each field strength was adjusted by targeted voxel size variation to minimize the effect of SNR on the field strength specific outcome. Spatial and temporal characteristics of resting state ICA, network graphs, and motor task related activated areas were compared. Finally, a graph theoretical approach was used to detect resting state modulation subsequent to a simple motor task. Results: Spatial extensions of resting state ICA and motor task related activated areas were consistent between field strengths, but temporal characteristics varied, indicating that 7 T achieved a higher functional specificity of the BOLD response than 3 T-fMRI. Following the motor task, only 7 T-fMRI enabled the detection of highly specific connectivity modulations representing an "offline replay" of previous motor activation. Modulated connections of the motor cortex were directly linked to brain regions associated with memory consolidation. Conclusion: These findings reveal how memory processing is initiated even after simple motor tasks, and that it begins earlier than previously shown. Thus, the superior capability of 7 T-fMRI to detect subtle functional dynamics promises to improve diagnostics and therapeutic assessment of neurological diseases.
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This study compares the diagnostic performance and image quality of single-shot turbo spin-echo DWI (tseDWI), standard readout-segmented DWI (rsDWI), and a modified rsDWI version (topupDWI) for cholesteatoma diagnostics. Thirty-four patients with newly suspected unilateral cholesteatoma were examined on a 1.5 Tesla MRI scanner. Diagnostic performance was evaluated by calculating and comparing the sensitivity and specificity using histopathological results as the standard of reference. Image quality was independently reviewed by two readers using a 5-point Likert scale evaluating image distortions, susceptibility artifacts, image resolution, lesion conspicuity, and diagnostic confidence. Twenty-five cholesteatomas were histologically confirmed after surgery and originated in the study group. TseDWI showed the highest sensitivity with 96% (95% confidence interval (CI): 88-100%), followed by topupDWI with 92% (95% CI: 81-100%) for both readers. The sensitivity for rsDWI was 76% (95% CI: 59-93%) for reader 1 and 84% (95% CI: 70-98%) for reader 2, respectively. Both tseDWI and topupDWI revealed a specificity of 100% (95% CI: 66-100%) and rsDWI of 89% (95% CI: 52-100%). Both tseDWI and topupDWI showed fewer image distortions and susceptibility artifacts compared to rsDWI. Image resolution was consistently rated best for topupDWI, followed by rsDWI, which both outperformed tseDWI. TopupDWI and tseDWI showed comparable results for lesions' conspicuity and diagnostic confidence, both outperforming rsDWI. Modified readout-segmented DWI using the topup-correction method is preferable to standard rsDWI and may be regarded as an accurate alternative to single-shot turbo spin-echo DWI in cholesteatoma diagnostics.
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Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel FA2H variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15. Additional symptoms included exotropia, dystonia, and limb ataxia. Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the FA2H gene, which was located in the cytochrome b5 heme-binding domain. Evolutionary conservation, prediction models, and structural protein modeling indicated a pathogenic loss of function. Brain imaging showed characteristic features, thus fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35. In summary, we here present a novel FA2H variant and provide prototypical clinical findings and structural analyses underpinning its pathogenicity.
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Transtornos Heredodegenerativos do Sistema Nervoso , Oxigenases de Função Mista , Paraplegia Espástica Hereditária , Masculino , Humanos , Adolescente , Oxigenases de Função Mista/genética , Imageamento por Ressonância Magnética , Mutação , Transtornos Heredodegenerativos do Sistema Nervoso/genéticaRESUMO
Background: Due to the absence of robust biomarkers, and the low sensitivity and specificity of routine imaging techniques, the differential diagnosis between Parkinson's disease (PD) and multiple system atrophy (MSA) is challenging. High-field magnetic resonance imaging (MRI) opened up new possibilities regarding the analysis of pathological alterations associated with neurodegenerative processes. Recently, we have shown that quantitative susceptibility mapping (QSM) enables visualization and quantification of two major histopathologic hallmarks observed in MSA: reduced myelin density and iron accumulation in the basal ganglia of a transgenic murine model of MSA. It is therefore emerging as a promising imaging modality on the differential diagnosis of Parkinsonian syndromes. Objectives: To assess QSM on high-field MRI for the differential diagnosis of PD and MSA. Methods: We assessed 23 patients (nine PDs and 14 MSAs) and nine controls using QSM on 3T and 7T MRI scanners at two academic centers. Results: We observed increased susceptibility in MSA at 3T in prototypical subcortical and brainstem regions. Susceptibility measures of putamen, pallidum, and substantia nigra reached excellent diagnostic accuracy to separate both synucleinopathies. Increase toward 100% sensitivity and specificity was achieved using 7T MRI in a subset of patients. Magnetic susceptibility correlated with age in all groups, but not with disease duration in MSA. Sensitivity and specificity were particularly high for possible MSA, and reached 100% in the putamen. Conclusion: Putaminal susceptibility measures, in particular on ultra-high-field MRI, may distinguish MSA patients from both, PD and controls, allowing an early and sensitive diagnosis of MSA.
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Hippocampal-sparing radiotherapy (HSR) is a promising approach to alleviate cognitive side effects following cranial radiotherapy. Microstructural brain changes after irradiation have been demonstrated using Diffusion Tensor Imaging (DTI). However, evidence is conflicting for certain parameters and anatomic structures. This study examines the effects of radiation on white matter and hippocampal microstructure using DTI and evaluates whether these may be mitigated using HSR. A total of 35 tumor patients undergoing a prospective randomized controlled trial receiving either conventional or HSR underwent DTI before as well as 6, 12, 18, 24, and 30 (±3) months after radiotherapy. Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD) were measured in the hippocampus (CA), temporal, and frontal lobe white matter (TL, FL), and corpus callosum (CC). Longitudinal analysis was performed using linear mixed models. Analysis of the entire patient collective demonstrated an overall FACC decrease and RDCC increase compared to baseline in all follow-ups; ADCC decreased after 6 months, and MDCC increased after 12 months (p ≤ 0.001, 0.001, 0.007, 0.018). ADTL decreased after 24 and 30 months (p ≤ 0.004, 0.009). Hippocampal FA increased after 6 and 12 months, driven by a distinct increase in ADCA and MDCA, with RDCA not increasing until 30 months after radiotherapy (p ≤ 0.011, 0.039, 0.005, 0.040, 0.019). Mean radiation dose correlated positively with hippocampal FA (p < 0.001). These findings may indicate complex pathophysiological changes in cerebral microstructures after radiation, insufficiently explained by conventional DTI models. Hippocampal microstructure differed between patients undergoing HSR and conventional cranial radiotherapy after 6 months with a higher ADCA in the HSR subgroup (p ≤ 0.034).
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PURPOSE: To demonstrate direct imaging of the white matter ultrashort T2∗ components at 7 Tesla using inversion recovery (IR)-enhanced ultrashort echo time (UTE) MRI. To investigate its characteristics, potentials and limitations, and to establish a clinical protocol. MATERIAL AND METHODS: The IR UTE technique suppresses long T2∗ signals within white matter by using adiabatic inversion in combination with dual-echo difference imaging. Artifacts arising at 7 T from long T2∗ scalp fat components were reduced by frequency shifting the IR pulse such that those frequencies were inverted likewise. For 8 healthy volunteers, the T2∗ relaxation times of white matter were then quantified. In 20 healthy volunteers, the UTE difference and fraction contrast were evaluated. Finally, in 6 patients with multiple sclerosis (MS), the performance of the technique was assessed. RESULTS: A frequency shift of -1.2 ppm of the IR pulse (i.e. towards the fat frequency) provided a good suppression of artifacts. With this, an ultrashort compartment of (68 ± 6) % with a T2∗ time of (147 ± 58) µs was quantified with a chemical shift of (-3.6 ± 0.5) ppm from water. Within healthy volunteers' white matter, a stable ultrashort T2∗ fraction contrast was calculated. For the MS patients, a significant fraction reduction in the identified lesions as well as in the normal-appearing white matter was observed. CONCLUSIONS: The quantification results indicate that the observed ultrashort components arise primarily from myelin tissue. Direct IR UTE imaging of the white matter ultrashort T2∗ components is thus feasible at 7 T with high quantitative inter-subject repeatability and good detection of signal loss in MS.