Purpose
Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange ...saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations.
Methods
Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (
B
1rms
= 2μT,
T
sat
= 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3–4 ppm, amines: 1.5–2.5 ppm, amide/amine ratio) were calculated with two models: ‘asymmetry-based’ (AB) and ‘fluid-suppressed’ (FS). The presence of T2/FLAIR mismatch was noted.
Results
IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19q
codel
(
p
< 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (
p
< 0.0045) and from IDH-mutant_1p/19q
ret
(
p
< 0.021). IDH-mutant_1p/19q
ret
had higher amides and amines than IDH-mutant_1p/19q
codel
(
p
< 0.035). IDH-mutant_1p/19q
ret
with AB/FS mismatch had higher amines than IDH-mutant_1p/19q
ret
without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19q
ret
, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (
p
= 0.014).
Conclusions
CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance.
The pulsatility of blood flow through cerebral arteries is clinically important, as it is intrinsically associated with cerebrovascular health. In this study we outline a new MRI approach to ...measuring the real-time pulsatile flow in cerebral arteries, which is based on the inflow phenomenon associated with fast gradient-recalled-echo acquisitions. Unlike traditional phase-contrast techniques, this new method, which we dub dynamic inflow magnitude contrast (DIMAC), does not require velocity-encoding gradients as sensitivity to flow velocity is derived purely from the inflow effect. We achieved this using a highly accelerated single slice EPI acquisition with a very short TR (15 ms) and a 90° flip angle, thus maximizing inflow contrast. We simulate the spoiled GRE signal in the presence of large arteries and perform a sensitivity analysis. The sensitivity analysis demonstrates that in the regime of high inflow contrast, DIMAC shows much greater sensitivity to flow velocity over blood volume changes. We support this theoretical prediction with
data collected in two separate experiments designed to demonstrate the utility of the DIMAC signal contrast. We perform a hypercapnia challenge experiment in order to experimentally modulate arterial tone within subjects, and thus modulate the arterial pulsatile flow waveform. We also perform a thigh-cuff release challenge, designed to induce a transient drop in blood pressure, and demonstrate that the continuous DIMAC signal captures the complex transient change in the pulsatile and non-pulsatile components of flow. In summary, this study proposes a new role for a well-established source of MR image contrast and demonstrates its potential for measuring both steady-state and dynamic changes in arterial tone.
Purpose:
Parallel transmit technology for MRI at 7 tesla will significantly benefit from high performance transmit arrays that offer high transmit efficiency and low mutual coupling between the ...individual array elements. A novel dual-mode transmit array with nested array elements has been developed to support imaging the human brain in both the single-channel (sTx) and parallel-transmit (pTx) excitation modes of a 7 tesla MRI scanner. In this work, the design, implementation, validation, specific absorption rate (SAR) management, and performance of the head coil is presented.
Methods:
The transmit array consisted of a nested arrangement to improve decoupling between the second-neighboring elements. Two large cut-outs were introduced in the RF shield for an open-face design to reduce claustrophobia and to allow patient monitoring. A hardware interface allows the coil to be used in both the sTx and pTx modes. SAR monitoring is done with virtual observation points (VOP) derived from human body models. The transmit efficiency and coverage is compared with the commercial single-channel and parallel-transmit head coils.
Results:
Decoupling inductors between the second-neighboring coil elements reduced the coupling to less than −20 dB. Local SAR estimates from the electromagnetic (EM) simulations were always less than the EM-based VOPs, which in turn were always less than scanner predictions and measurements for static and dynamic pTx waveforms. In sTx mode, we demonstrate improved coverage of the brain compared to the commercial sTx coil. The transmit efficiency is within 10% of the commercial pTx coil despite the two large cut-outs in the RF shield. In pTx mode, improved signal homogeneity was shown when the Universal Pulse was used for acquisition
in vivo
.
Conclusion:
A novel head coil which includes a nested eight-channel transmit array has been presented. The large cut-outs improve patient monitoring and reduce claustrophobia. For pTx mode, the EM simulation and VOP-based SAR management provided greater flexibility to apply pTx methods without the limitations of SAR constraints. For scanning
in vivo
, the coil was shown to provide an improved coverage in sTx mode compared to a standard commercial head coil.
With fast-growing evidence in literature for clinical applications of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI), this prospective study aimed at applying amide ...proton transfer-weighted (APTw) CEST imaging in a clinical setting to assess its diagnostic potential in differentiation of intracranial tumors at 3 tesla (T).
Using the asymmetry magnetization transfer ratio (MTRasym) analysis, CEST signals were quantitatively investigated in the tumor areas and in a similar sized region of the normal-appearing white matter (NAWM) on the contralateral hemisphere of 27 patients with intracranial tumors. Area under curve (AUC) analyses were used and results were compared to perfusion-weighted imaging (PWI).
Using APTw CEST, contrast-enhancing tumor areas showed significantly higher APTw CEST metrics than contralateral NAWM (AUC = 0.82;
< 0.01). In subgroup analyses of each tumor entity vs. NAWM, statistically significant effects were yielded for glioblastomas (AUC = 0.96;
< 0.01) and for meningiomas (AUC = 1.0;
< 0.01) but not for lymphomas as well as metastases (
> 0.05). PWI showed results comparable to APTw CEST in glioblastoma (
< 0.01).
This prospective study confirmed the high diagnostic potential of APTw CEST imaging in a routine clinical setting to differentiate brain tumors.
Based on in silico, in vitro, in situ, and in vivo evaluations, this study aims to establish and optimize the chemical exchange saturation transfer (CEST) imaging of lactate (Lactate-CEST—LATEST). To ...this end, we optimized LATEST sequences using Bloch−McConnell simulations for optimal detection of lactate with a clinical 3 T MRI scanner. The optimized sequences were used to image variable lactate concentrations in vitro (using phantom measurements), in situ (using nine human cadaveric lower leg specimens), and in vivo (using four healthy volunteers after exertional exercise) that were then statistically analyzed using the non-parametric Friedman test and Kendall Tau-b rank correlation. Within the simulated Bloch−McConnell equations framework, the magnetization transfer ratio asymmetry (MTRasym) value was quantified as 0.4% in the lactate-specific range of 0.5−1 ppm, both in vitro and in situ, and served as the imaging surrogate of the lactate level. In situ, significant differences (p < 0.001) and strong correlations (τ = 0.67) were observed between the MTRasym values and standardized intra-muscular lactate concentrations. In vivo, a temporary increase in the MTRasym values was detected after exertional exercise. In this bench-to-bedside comprehensive feasibility study, different lactate concentrations were detected using an optimized LATEST imaging protocol in vitro, in situ, and in vivo at 3 T, which prospectively paves the way towards non-invasive quantification and monitoring of lactate levels across a broad spectrum of diseases.
Noninvasive prediction of isocitrate dehydrogenase (IDH) mutation status in glioma guides surgical strategies and individualized management. We explored the capability on preoperatively identifying ...IDH status of combining a convolutional neural network (CNN) and a novel imaging modality, ultra-high field 7.0 Tesla (T) chemical exchange saturation transfer (CEST) imaging.
We enrolled 84 glioma patients of different tumor grades in this retrospective study. Amide proton transfer CEST and structural Magnetic Resonance (MR) imaging at 7T were performed preoperatively, and the tumor regions are manually segmented, leading to the "annotation" maps that offers the location and shape information of the tumors. The tumor region slices in CEST and T1 images were further cropped out as samples and combined with the annotation maps, which were inputted to a 2D CNN model for generating IDH predictions. Further comparison analysis to radiomics-based prediction methods was performed to demonstrate the crucial role of CNN for predicting IDH based on CEST and T1 images.
A fivefold cross-validation was performed on the 84 patients and 4090 slices. We observed a model based on only CEST achieved accuracy of 74.01% ± 1.15%, and the area under the curve (AUC) of 0.8022 ± 0.0147. When using T1 image only, the prediction performances dropped to accuracy of 72.52% ± 1.12% and AUC of 0.7904 ± 0.0214, which indicates no superiority of CEST over T1. However, when we combined CEST and T1 together with the annotation maps, the performances of the CNN model were further boosted to accuracy of 82.94% ± 1.23% and AUC of 0.8868 ± 0.0055, suggesting the importance of a joint analysis of CEST and T1. Finally, using the same inputs, the CNN-based predictions achieved significantly improved performances above those from radiomics-based predictions (logistic regression and support vector machine) by 10% to 20% in all metrics.
7T CEST and structural MRI jointly offer improved sensitivity and specificity of preoperative non-invasive imaging for the diagnosis of IDH mutation status. As the first study of CNN model on imaging acquired at ultra-high field MR, our results could demonstrate the potential of combining ultra-high-field CEST and CNN for facilitating decision-making in clinical practice. However, due to the limited cases and B1 inhomogeneities, the accuracy of this model will be improved in our further study.
For precise delineation of glioma extent, amino acid PET is superior to conventional MR imaging. Since metabolic MR sequences such as chemical exchange saturation transfer (CEST) imaging and MR ...spectroscopy (MRS) were developed, we aimed to evaluate the diagnostic accuracy of combined CEST and MRS to predict glioma infiltration. Eighteen glioma patients of different tumor grades were enrolled in this study; 18F-fluoroethyltyrosine (FET)-PET, amide proton transfer CEST at 7 Tesla(T), MRS and conventional MR at 3T were conducted preoperatively. Multi modalities and their association were evaluated using Pearson correlation analysis patient-wise and voxel-wise. Both CEST (R = 0.736, p < 0.001) and MRS (R = 0.495, p = 0.037) correlated with FET-PET, while the correlation between CEST and MRS was weaker. In subgroup analysis, APT values were significantly higher in high grade glioma (3.923 ± 1.239) and IDH wildtype group (3.932 ± 1.264) than low grade glioma (3.317 ± 0.868, p < 0.001) or IDH mutant group (3.358 ± 0.847, p < 0.001). Using high FET uptake as the standard, the CEST/MRS combination (AUC, 95% CI: 0.910, 0.907−0.913) predicted tumor infiltration better than CEST (0.812, 0.808−0.815) or MRS (0.888, 0.885−0.891) alone, consistent with contrast-enhancing and T2-hyperintense areas. Probability maps of tumor presence constructed from the CEST/MRS combination were preliminarily verified by multi-region biopsies. The combination of 7T CEST/MRS might serve as a promising non-radioactive alternative to delineate glioma infiltration, thus reshaping the guidance for tumor resection and irradiation.
Introduction
Chronic cerebral hypoperfusion has been considered the etiology for sporadic Alzheimer's disease (AD). However, no valid clinical evidence exists due to the similar risk factors between ...cerebrovascular disease and AD.
Methods
We used moyamoya disease (MMD) as a model of chronic hypoperfusion and cognitive impairment, without other etiology interference.
Results
Based on the previous reports and preliminary findings, we hypothesized that chronic cerebral hypoperfusion could be an independent upstream crucial variable, resulting in AD, and induce pathological hallmarks such as amyloid beta peptide and hyperphosphorylated tau accumulation.
Discussion
Timely intervention with revascularisation would help reverse the brain damage with AD hallmarks and lead to cognitive improvement.
Purpose
Tailored parallel‐transmit (pTx) pulses produce uniform excitation profiles at 7 T, but are sensitive to head motion. A potential solution is real‐time pulse redesign. A deep learning ...framework is proposed to estimate pTx B1+ distributions following within‐slice motion, which can then be used for tailored pTx pulse redesign.
Methods
Using simulated data, conditional generative adversarial networks were trained to predict B1+ distributions in the head following a displacement. Predictions were made for two virtual body models that were not included in training. Predicted maps were compared with ground‐truth (simulated, following motion) B1 maps. Tailored pTx pulses were designed using B1 maps at the original position (simulated, no motion) and evaluated using simulated B1 maps at displaced position (ground‐truth maps) to quantify motion‐related excitation error. A second pulse was designed using predicted maps (also evaluated on ground‐truth maps) to investigate improvement offered by the proposed method.
Results
Predicted B1+ maps corresponded well with ground‐truth maps. Error in predicted maps was lower than motion‐related error in 99% and 67% of magnitude and phase evaluations, respectively. Worst‐case flip‐angle normalized RMS error due to motion (76% of target flip angle) was reduced by 59% when pulses were redesigned using predicted maps.
Conclusion
We propose a framework for predicting B1+ maps online with deep neural networks. Predicted maps can then be used for real‐time tailored pulse redesign, helping to overcome head motion–related error in pTx.
Diffusion MRI (dMRI) is inherently limited by SNR. Scanning at 7 T increases intrinsic SNR but 7 T MRI scans suffer from regions of signal dropout, especially in the temporal lobes and cerebellum. We ...applied dynamic parallel transmit (pTx) to allow whole-brain 7 T dMRI and compared with circularly polarized (CP) pulses in 6 subjects.
Subject-specific 2-spoke dynamic pTx pulses were designed offline for 8 slabs covering the brain. We used vendor-provided B0 and B1+ mapping. Spokes positions were set using the Fourier difference approach, and RF coefficients optimized with a Jacobi-matrix high-flip-angle optimizer. Diffusion data were analyzed with FSL.
Comparing whole-brain averages for pTx against CP scans: mean flip angle error improved by 15% for excitation (2-spoke-VERSE 15.7° vs CP 18.4°, P = 0.012) and improved by 14% for refocusing (2-spoke-VERSE 39.7° vs CP 46.2°, P = 0.008). Computed spin-echo signal standard deviation improved by 14% (2-spoke-VERSE 0.185 vs 0.214 CP, P = 0.025). Temporal SNR increased by 5.4% (2-spoke-VERSE 8.47 vs CP 8.04, P = 0.004) especially in the inferior temporal lobes. Diffusion fitting uncertainty decreased by 6.2% for first fibers (2-spoke VERSE 0.0655 vs CP 0.0703, P < 0.001) and 1.3% for second fibers (2-spoke VERSE 0.139 vs CP 0.141, P = 0.01).
In conclusion, dynamic parallel transmit improves the uniformity of 7 T diffusion-weighted imaging. In future, less restrictive SAR limits for parallel transmit scans are expected to allow further improvements.
•We implemented dynamic parallel transmit whole brain diffusion MRI.•Our protocols are based on the Human Connectome Project 7T study.•Parallel transmit improves uniformity of diffusion MRI, especially in temporal lobe.•Fiber fitting performance improves especially at the edges of the brain.•Forthcoming less restrictive SAR limits should further improve uniformity.