Arterial pulsation dependence of perivascular cerebrospinal fluid flow measured by dynamic diffusion tensor imaging in the human brain.

Perivascular cerebrospinal fluid (pCSF) flow is a key component of the glymphatic system. Arterial pulsation has been proposed as the main driving force of pCSF influx along the superficial and penetrating arteries; however, evidence of this mechanism in humans is limited. We proposed an experimental framework of dynamic diffusion tensor imaging with low b-values and ultra-long echo time (dynDTIlow-b) to capture pCSF flow properties during the cardiac cycle in human brains. Healthy adult volunteers (aged 17-28 years; seven men, one woman) underwent dynDTIlow-b using a clinical 3T scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) with simultaneously recorded cardiac output. The results showed that diffusion tensors reconstructed from pCSF were mainly oriented in the direction of the neighboring arterial flow. When switching from vasoconstriction to vasodilation, the axial and radial diffusivities of the pCSF increased by 5.7% and 4.94%, respectively, suggesting that arterial pulsation alters the pCSF flow both parallel and perpendicular to the arterial wall. DynDTIlow-b signal intensity at b=0 s/mm2 (i.e., T2-weighted, [S(b=0 s/mm2)]) decreased in systole, but this change was ∼7.5% of a cardiac cycle slower than the changes in apparent diffusivity, suggesting that changes in S(b=0 s/mm2) and apparent diffusivity arise from distinct physiological processes and potential biomarkers associated with perivascular space volume and pCSF flow, respectively. Additionally, the mean diffusivities of white matter showed cardiac-cycle dependencies similar to pCSF, although a delay relative to the peak time of S(b=0 s/mm2) was present, suggesting that dynDTIlow-b could potentially reveal the dynamics of magnetic resonance imaging-invisible pCSF surrounding small arteries and arterioles in white matter; this delay may result from pulse wave propagation along penetrating arteries. In conclusion, the vasodilation-induced increases in axial and radial diffusivities of pCSF and mean diffusivities of white matter are consistent with the notion that arterial pulsation can accelerate pCSF flow in human brain. Furthermore, the proposed dynDTIlow-b technique can capture various pCSF dynamics in artery pulsation.

Vessel-specific quantification of cerebral venous oxygenation with velocity-encoding preparation and rapid acquisition.

PURPOSE: Non-invasive measurement of cerebral venous oxygenation (Yv) is of critical importance in brain diseases. The present work proposed a fast method to quantify regional Yv map for both large and small veins. METHODS: A new sequence was developed, referred to as TRU-VERA (T2 relaxation under velocity encoding and rapid acquisition, which isolates blood spins from static tissue with velocity-encoding preparation, modulates the T2 weighting of venous signal with T2-preparation and utilizes a bSSFP readout to achieve fast acquisition with high resolution. The sequence was first optimized to achieve best sensitivity for both large and small veins, and then validated with TRUST (T2 relaxation under spin tagging), TRUPC (T2 relaxation under phase contrast), and accelerated TRUPC MRI. Regional difference of Yv was evaluated, and test-retest reproducibility was examined. RESULTS: Optimal Venc was determined to be 3 cm/s, while recovery time and balanced SSFP flip angle within reasonable range had minimal effect on SNR efficiency. Venous T2 measured with TRU-VERA was highly correlated with T2 from TRUST (R2 = 0.90), and a conversion equation was established for further calibration to Yv. TRU-VERA sequences showed consistent Yv estimation with TRUPC (R2 = 0.64) and accelerated TRUPC (R2 = 0.79). Coefficient of variation was 0.84% for large veins and 2.49% for small veins, suggesting an excellent test-retest reproducibility. CONCLUSION: The proposed TRU-VERA sequence is a promising method for vessel-specific oxygenation assessment.

An improved attention module based on nnU-Net for segmenting primary central nervous system lymphoma (PCNSL) in MRI images1.

BACKGROUND: Accurate volumetric segmentation of primary central nervous system lymphoma (PCNSL) is essential for assessing and monitoring the tumor before radiotherapy and the treatment planning. The tedious manual segmentation leads to interindividual and intraindividual differences, while existing automatic segmentation methods cause under-segmentation of PCNSL due to the complex and multifaceted nature of the tumor. OBJECTIVE: To address the challenges of small size, diffused distribution, poor inter-layer continuity on the same axis, and tendency for over-segmentation in brain MRI PCNSL segmentation, we propose an improved attention module based on nnUNet for automated segmentation. METHODS: We collected 114 T1 MRI images of patients in the Huashan Hospital, Shanghai. Then randomly split the total of 114 cases into 5 distinct training and test sets for a 5-fold cross-validation. To efficiently and accurately delineate the PCNSL, we proposed an improved attention module based on nnU-Net with 3D convolutions, batch normalization, and residual attention (res-attention) to learn the tumor region information. Additionally, multi-scale dilated convolution kernels with different dilation rates were integrated to broaden the receptive field. We further used attentional feature fusion with 3D convolutions (AFF3D) to fuse the feature maps generated by multi-scale dilated convolution kernels to reduce under-segmentation. RESULTS: Compared to existing methods, our attention module improves the ability to distinguish diffuse and edge enhanced types of tumors; and the broadened receptive field captures tumor features of various scales and shapes more effectively, achieving a 0.9349 Dice Similarity Coefficient (DSC). CONCLUSIONS: Quantitative results demonstrate the effectiveness of the proposed method in segmenting the PCNSL. To our knowledge, this is the first study to introduce attention modules into deep learning for segmenting PCNSL based on brain magnetic resonance imaging (MRI), promoting the localization of PCNSL before radiotherapy.

Vascular-water-exchange MRI (VEXI) enables the detection of subtle AXR alterations in Alzheimer's disease without MRI contrast agent, which may relate to BBB integrity.

Blood-brain barrier (BBB) impairment is an important pathophysiological process in Alzheimer's disease (AD) and a potential biomarker for early diagnosis of AD. However, most current neuroimaging methods assessing BBB function need the injection of exogenous contrast agents (or tracers), which limits the application of these methods in a large population. In this study, we aim to explore the feasibility of vascular water exchange MRI (VEXI), a diffusion-MRI-based method proposed to assess the BBB permeability to water molecules without using a contrast agent, in the detection of the BBB breakdown in AD. We tested VEXI on a 3T MRI scanner on three groups: AD patients (AD group), mild cognitive impairment (MCI) patients due to AD (MCI group), and the age-matched normal cognition subjects (NC group). Interestingly, we find that the apparent water exchange across the BBB (AXRBBB) measured by VEXI shows higher values in MCI compared with NC, and this higher AXRBBB happens specifically in the hippocampus. This increase in AXRBBB value gets larger and extends to more brain regions (medial orbital frontal cortex and thalamus) from MCI group to the AD group. Furthermore, we find that the AXRBBB values of these three regions is correlated significantly with the impairment of respective cognitive domains independent of age, sex and education. These results suggest VEXI is a promising method to assess the BBB breakdown in AD.

Numerical fitting of Extrapolated semisolid Magnetization transfer Reference (NEMR) signals: Improved detection of ischemic stroke.

PURPOSE: To propose a novel Numerical fitting method of the Extrapolated semisolid Magnetization transfer Reference (NEMR) signal for quantifying the CEST effect. THEORY AND METHODS: Modified two-pool Bloch-McConnell equations were used to numerically fit the magnetization transfer (MT) and direct water saturation (DS) signals at far off-resonance frequencies, which was subsequently extrapolated into the frequency range of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) pools. Then the subtraction of the fitted two-pool z-spectrum and the experimentally acquired z-spectrum yielded APT# and NOE# signals mostly free of MT and DS contamination. Several strategies were used to accelerate the NEMR fitting. Furthermore, the proposed NEMR method was compared with the conventional extrapolated semisolid magnetization transfer reference (EMR) and magnetization transfer ratio asymmetry (MTRasym ) methods in simulations and stroke patients. RESULTS: The combination of RF downsampling, MT lineshape look-up table, and conversion of MATLAB code to C code accelerated the NEMR fitting by over 2700-fold. Monte-Carlo simulations showed that NEMR had higher accuracy than EMR and eliminated the requirement of the steady-state condition. In ischemic stroke patients, the NEMR maps at 1 µT removed hypointense artifacts seen on EMR and MTRasym images, and better depicted stroke lesions than EMR. For NEMR, NOE# yielded significantly (p < 0.05) stronger signal contrast between stroke and normal tissues than APT# at 1 µT. CONCLUSION: The proposed NEMR method is suitable for arbitrary saturation settings and can remove MT and DS contamination from the CEST signal for improved detection of ischemic stroke.

3D diffusion MRI with twin navigator-based GRASE and comparison with 2D EPI for tractography in the human brain.

PURPOSE: 3D pulse sequences enable high-resolution acquisition with a high SNR and ideal slice profiles, which, however, is particularly difficult for diffusion MRI (dMRI) due to the additional phase errors from diffusion encoding. METHODS: We proposed a twin navigator-based 3D diffusion-weighted gradient spin-echo (GRASE) sequence to correct the phase errors between shots and between odd and even spin echoes for human whole-brain acquisition. We then compared the SNR of 3D GRASE and 2D simultaneous multi-slice EPI within the same acquisition time. We further tested the performance of 2D versus 3D acquisition at equivalent SNR on fiber tracking and microstructural mapping, using the diffusion tensor and high-order fiber orientation density-based metrics. RESULTS: The proposed twin navigator approach removed multi-shot phase errors to some extent in the whole brain dMRI, and the 2D navigator performed better than the 1D navigator. Comparisons of SNR between the 2D simultaneous multi-slice EPI and 3D GRASE sequences demonstrated that the SNR of the GRASE sequence was 1.4-1.5-fold higher than the EPI sequence at an equivalent scan time. More importantly, we found a significantly higher fiber cross-section in the cerebrospinal tract, as well as richer subcortical fibers (U-fibers) using the 3D GRASE sequence compared to 2D EPI. CONCLUSION: The twin navigator-based 3D diffusion-weighted-GRASE sequence minimized the multishot phase error and effectively improved the SNR for whole-brain dMRI acquisition. We found differences in fiber tracking and microstructural mapping between 2D and 3D acquisitions, possibly due to the different slice profiles.

Echo time optimization for in-vivo measurement of unsaturated lipid resonances using J-difference-edited MRS.

PURPOSE: Measuring lipid composition provides more information than just total lipid content. Hence, the non-invasive measurement of unsaturated lipid protons with both high efficiency and precision is of pressing need. This study was to optimize echo time (TE) for the best resolving of J-difference editing of unsaturated lipid resonances. METHODS: The TE dependence of J-difference-edited (JDE) MRS was verified in the density-matrix simulation, soybean oil phantom, in-vivo experiments of white adipose tissue (WAT), and skeletal muscles using single-voxel MEGA-PRESS sequence at 3T. The peak SNRs and Cramér-Rao lower bounds (CRLBs) acquired at the proposed TE of 45 ms and previously published TE of 70 ms were compared (eight pairs) in WAT, extramyocelluar lipids (EMCLs), and intramyocellular lipids (IMCLs). The lipid composition in skeletal muscles was compared between healthy males (n = 7) and females (n = 7). RESULTS: The optimal TE was suggested as 45 ms. Compared to 70 ms, the mean signal gains at TE of 45 ms were 151% in WAT, 168% in EMCL, 204% in IMCL for allylic resonance, and 52% in EMCL for diallylic resonance. CRLBs were significantly reduced at TE of 45 ms in WAT, EMCL, IMCL for allylic resonance and in EMCL for diallylic resonance. With TE of 45 ms, significant gender differences were found in the lipid composition in EMCL pools, while no difference in IMCL pools. CONCLUSION: The JDE-MRS protocol with TE of 45 ms allows improved quantification of unsaturated lipid resonances in vivo and future lipid metabolism investigations.

Saturation-prolongated and inhomogeneity-mitigated chemical exchange saturation transfer imaging with parallel transmission.

Chemical exchange saturation transfer (CEST) imaging benefits from a longer saturation duration and a higher saturation duty cycle. Dielectric shading effects occur when the radiofrequency (RF) wavelength approaches the object size. Here, we proposed a simultaneous parallel transmission-based CEST (pTx-CEST) sequence to prolongate the saturation duration at a 100% duty cycle and improve the RF saturation homogeneity in CEST imaging. The simultaneous pTx-CEST sequence was implemented by switching the CEST saturation module from the non-pTx to pTx mode, using the pTx functionality with both transmit channels being driven simultaneously (instead of time-interleaved). The optimization of amplitude ratio and phase difference settings between RF channels for best B1 homogeneity was performed in phantoms of two different sizes mimicking the human brain and abdomen. The optimal amplitude and phase settings generating the best B1 homogeneity in the phantoms were used in pTx-CEST scans of the human study. The comparison of the maximum achievable saturation duration between the non-pTx-CEST and pTx-CEST sequences was performed in a protein phantom, healthy volunteers, and a metastatic brain tumor patient. The optimal amplitude ratio and phase difference setting between transmit channels manifested circular and elliptical polarization in the head-sized and abdomen-sized phantoms. In the brain, the maximum saturation durations achieved at a 100% duty cycle using the simultaneous pTx-CEST sequence were prolonged to 2240, 3220, and 4200 ms compared with 980 ms using the non-pTx-CEST sequence at repetition times of 3, 4, and 5 s, respectively. The longer saturation duration helped improve the image contrast between the tumor and the normal tissue in the patient. The optimized elliptical polarization mode saturation pulses yielded improved uniformity of CEST signals acquired from the human abdomen. The proposed simultaneous pTx-CEST sequence enabled essentially arbitrarily long saturation duration at a 100% duty cycle and helped reduce the dielectric shading effects with the optimized RF setting.

The Consistence of Dynamic Contrast-Enhanced MRI and Filter-Exchange Imaging in Measuring Water Exchange Across the Blood-Brain Barrier in High-Grade Glioma.

BACKGROUND: Water exchange across blood-brain barrier (BBB) (WEXBBB ) is an emerging biomarker of BBB dysfunction with potential applications in many brain diseases. Several MRI methods have been proposed to measure WEXBBB , but evidence remains scarce whether different methods can produce comparable WEXBBB . PURPOSE: To explore whether dynamic contrast-enhanced (DCE)-MRI and vascular water exchange imaging (VEXI) could produce comparable WEXBBB in high-grade glioma (HGG) patients. STUDY TYPE: Prospective cross-sectional. SUBJECTS: 13 HGG patients (58.4 ± 9.4 years, 9 females, 4 WHO III and 9 WHO IV). FIELD STRENGTH/SEQUENCE: A 3 T, spoiled gradient-recalled-echo DCE-MRI and VEXI containing two pulsed-gradient spin-echo blocks separated by a mixing block. ASSESSMENTS: The enhanced tumor and contralateral normal-appearing white matter (cNAWM) volume-of-interests (VOIs) were drew by two neuroradiologists. And whole-brain NAWM and normal-appearing gray matter (NAGM) without tumor-affected regions were segmented by automated segmentation algorithm in FSL. STATISTICAL TESTS: Student's t-test was used to evaluate parameters difference between cNAWM and tumor, NAGM and NAWM, respectively. The correlation between vascular water efflux rate constant (kbo ) from DCE-MRI and apparent exchange rate across BBB (AXRBBB ) from VEXI was evaluated by Pearson correlation. P < 0.05 was considered statistically significant. RESULTS: Compared with cNAWM, both kbo and AXRBBB were significantly reduced in tumor (kbo = 3.50 ± 1.18 sec-1 vs. 1.03 ± 0.75 sec-1 ; AXRBBB = 3.54 ± 1.11 sec-1 vs. 1.94 ± 1.04 sec-1 ). Both kbo and AXRBBB showed significantly higher values in NAWM than NAGM (kbo = 3.50 ± 0.59 sec-1 vs. 2.10 ± 0.56 sec-1 ; AXRBBB = 3.35 ± 0.77 sec-1 vs. 2.07 ± 0.52 sec-1 ). The VOI-averaged kbo and AXRBBB were also linearly correlated in tumor, NAWM, and NAGM (r = 0.59). DATA CONCLUSION: DCE-MRI and VEXI showed comparable and correlated WEXBBB in HGG patients, suggesting that the consistence and reliability of these two MRI methods in measuring WEXBBB . EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 1.

Inversion-Recovery-Prepared Oscillating Gradient Sequence Improves Diffusion-Time Dependency Measurements in the Human Brain.

BACKGROUND: Oscillating gradient diffusion MRI (dMRI) enables measurements at a short diffusion-time (td ), but it is challenging for clinical systems. Particularly, the low b-value and low resolution may give rise to cerebrospinal fluid (CSF) contamination. PURPOSE: To assess the effect of CSF partial volume on td -dMRI measurements and efficacy of inversion-recovery (IR) prepared oscillating and pulsed gradient dMRI sequence to improve td -dMRI measurements in the human brain. STUDY TYPE: Prospective. SUBJECTS: Ten normal volunteers and six glioma patients. FIELD STRENGTH/SEQUENCE: A 3 T; three-dimensional (3D) IR-prepared oscillating gradient-prepared gradient spin-echo (GRASE) and two-dimensional (2D) IR-prepared oscillating gradient echo-planar imaging (EPI) sequences. ASSESSMENT: We assessed the td -dependent patterns of apparent diffusion coefficient (ADC) in several gray and white matter structures, including the hippocampal subfields (head, body, and tail), cortical gray matter, thalamus, and posterior white matter in normal volunteers. Pulsed gradient (0 Hz) and oscillating gradients at frequencies of 20 Hz, 40 Hz, and 60 Hz dMRI were acquired with GRASE and EPI sequences with or without the IR module. We also tested the td -dependency patterns in glioma patients using the EPI sequence with or without the IR module. STATISTICAL TESTS: The differences in ADC across the different td s were compared by one-way ANOVA followed by post hoc pairwise t-tests with Bonferroni correction. RESULTS: In the healthy subjects, brain regions that were possibly contaminated by CSF signals, such as the hippocampus (head, body, and tail) and cortical gray matter, td -dependent ADC changes were only significant with the IR-prepared 2D and 3D sequences but not with the non-IR sequences. In brain glioblastomas patients, significantly higher td -dependence was observed in the tumor region with the IR module than that without IR (slope = 0.0196 µm2 /msec2 vs. 0.0034 µm2 /msec2 ). CONCLUSION: The IR-prepared sequence effectively suppressed the CSF partial volume effect and significantly improved the td -dependent measurements in the human brain. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

The direction-dependence of apparent water exchange rate in human white matter.

Transmembrane water exchange is a potential biomarker in the diagnosis and understanding of cancers, brain disorders, and other diseases. Filter-exchange imaging (FEXI), a special case of diffusion exchange spectroscopy adapted for clinical applications, has the potential to reveal different physiological water exchange processes. However, it is still controversial whether modulating the diffusion encoding gradient direction can affect the apparent exchange rate (AXR) measurements of FEXI in white matter (WM) where water diffusion shows strong anisotropy. In this study, we explored the diffusion-encoding direction dependence of FEXI in human brain white matter by performing FEXI with 20 diffusion-encoding directions on a clinical 3T scanner in-vivo. The results show that the AXR values measured when the gradients are perpendicular to the fiber orientation (0.77 ± 0.13 s - 1, mean ± standard deviation of all the subjects) are significantly larger than the AXR estimates when the gradients are parallel to the fiber orientation (0.33 ± 0.14 s - 1, p < 0.001) in WM voxels with coherently-orientated fibers. In addition, no significant correlation is found between AXRs measured along these two directions, indicating that they are measuring different water exchange processes. What's more, only the perpendicular AXR rather than the parallel AXR shows dependence on axonal diameter, indicating that the perpendicular AXR might reflect transmembrane water exchange between intra-axonal and extra-cellular spaces. Further finite difference (FD) simulations having three water compartments (intra-axonal, intra-glial, and extra-cellular spaces) to mimic WM micro-environments also suggest that the perpendicular AXR is more sensitive to the axonal water transmembrane exchange than parallel AXR. Taken together, our results show that AXR measured along different directions could be utilized to probe different water exchange processes in WM.

Time-Dependent Diffusion MRI for Quantitative Microstructural Mapping of Prostate Cancer.

Background Recently developed time-dependent diffusion MRI has potential in characterizing cellular tissue microstructures; however, its value in imaging prostate cancer (PCa) remains unknown. Purpose To investigate the feasibility of time-dependent diffusion MRI-based microstructural mapping for noninvasively characterizing cellular properties of PCa and for discriminating between clinically significant PCa and clinically insignificant disease. Materials and Methods Men with a clinical suspicion of PCa were enrolled prospectively between October 2019 and August 2020. Time-dependent diffusion MRI data were acquired with pulsed and oscillating gradient diffusion MRI sequences at an equivalent diffusion time of 7.5-30 msec on a 3.0-T scanner. Time-dependent diffusion MRI-based microstructural parameters, including cell diameter, intracellular volume fraction, cellularity, and diffusivities, were estimated with a two-compartment model. These were compared for different International Society of Urological Pathology grade groups (GGs), and their performance in discriminating clinically significant PCa (GG >1) from clinically insignificant disease (benign and GG 1) was determined with a linear discriminant analysis. The fitted microstructural parameters were validated by means of correlation with histopathologic measurements. Results In the 48 enrolled men, the time-dependent diffusion MRI measurements showed that higher GG was correlated with higher intracellular volume fraction and higher cellularity (intracellular volume fraction = 0.22, 0.36, 0.34, 0.37, and 0.40 in GGs 1-5, respectively; P < .001 at one-way analysis of variance), while lower cell diameter was found at higher GGs (diameter = 23.4, 18.3, 19.2, 17.9, and 18.5 µm in GGs 1-5, respectively; P = .002). Among all measurements derived from time-dependent diffusion MRI, cellularity achieved the highest diagnostic performance, with an accuracy of 92% (44 of 48 participants) and area under the receiver operating characteristic curve of 0.96 (95% CI: 0.87, 0.99) in discriminating clinically significant PCa from clinically insignificant disease. Microstructural mapping was supported by positive correlations between time-dependent diffusion MRI-based and pathologic examination-based intracellular volume fraction (r = 0.83; P < .001). Conclusion Time-dependent diffusion MRI-based microstructural mapping correlates with pathologic findings and demonstrates promise for characterizing prostate cancer. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chatterjee and Oto in this issue.

Diffusion-prepared 3D gradient spin-echo sequence for improved oscillating gradient diffusion MRI.

PURPOSE: Oscillating gradient (OG) enables the access of short diffusion times for time-dependent diffusion MRI (dMRI); however, it poses several technical challenges for clinical use. This study proposes a 3D oscillating gradient-prepared gradient spin-echo (OGprep-GRASE) sequence to improve SNR and shorten acquisition time for OG dMRI on clinical scanners. METHODS: The 3D OGprep-GRASE sequence consisted of global saturation, diffusion encoding, fat saturation, and GRASE readout modules. Multiplexed sensitivity-encoding reconstruction was used to correct the phase errors between multiple shots. We compared the scan time and SNR of the proposed sequence and the conventional 2D-EPI sequence for OG dMRI at 30-90-mm slice coverage. We also examined the time-dependent diffusivity changes with OG dMRI acquired at frequencies of 50 Hz and 25 Hz and pulsed-gradient dMRI at diffusion times of 30 ms and 60 ms. RESULTS: The OGprep-GRASE sequence reduced the scan time by a factor of 1.38, and increased the SNR by 1.74-2.27 times compared with 2D EPI for relatively thick slice coverage (60-90 mm). The SNR gain led to improved diffusion-tensor reconstruction in the multishot protocols. Image distortion in 2D-EPI images was also reduced in GRASE images. Diffusivity measurements from the pulsed-gradient dMRI and OG dMRI showed clear diffusion-time dependency in the white matter and gray matter of the human brain, using both the GRASE and EPI sequences. CONCLUSION: The 3D OGprep-GRASE sequence improved scan time and SNR and reduced image distortion compared with the 2D multislice acquisition for OG dMRI on a 3T clinical system, which may facilitate the clinical translation of time-dependent dMRI.

Frequency-stabilized chemical exchange saturation transfer imaging with real-time free-induction-decay readout.

PURPOSE: To correct the temporal B0 drift in chemical exchange saturation transfer (CEST) imaging in real-time with extra free-induction-decay (FID) readout. THEORY AND METHODS: The frequency stabilization module of the recently proposed frequency-stabilized CEST (FS-CEST) sequence was further simplified by replacing the original three k-space lines of gradient-echo (GRE) readout with a single k-space line of FID readout. The B0 drift was quantified using the phase difference between the odd and even parts of the FID signal in the frequency stabilization module and then used to update the B0 frequency in the succeeding modules. The proposed FS-CEST sequence with FID readout (FID FS-CEST) was validated in phantoms and 16 human subjects on cross-vendor scanners. RESULTS: In the Siemens experiments, the FID FS-CEST sequence successfully corrected the user-induced B0 drift, generating consistent amide proton transfer-weighted (APTw) images and magnetization transfer ratio asymmetry (MTRasym ) spectra with those from the non-frequency-stabilized CEST (NFS-CEST) sequence without B0 drift. In the Philips experiments, the FID FS-CEST sequence produced more stable APTw images and MTRasym spectra than the NFS-CEST sequence in the presence of practical B0 drift. Quantitatively, the SD of the APTw signal values in the deep gray matter from 15 subjects was 0.26% for the FID FS-CEST sequence compared to 1.03% for the NFS-CEST sequences, with the fluctuations reduced by nearly three-quarters. CONCLUSIONS: The proposed FS-CEST sequence with FID readout can effectively correct the temporal B0 drift on cross-vendor scanners.

Chemical exchange saturation transfer imaging for epilepsy secondary to tuberous sclerosis complex at 3 T: Optimization and analysis.

The homeostasis of various metabolites is impaired in epilepsy secondary to the tuberous sclerosis complex (TSC). Chemical exchange saturation transfer (CEST) imaging is an emerging molecular MRI technique that can detect various metabolites and proteins in vivo. However, the role of CEST imaging for TSC-associated epilepsy has not been assessed. Here, we aim to investigate the feasibility of applying CEST imaging to TSC-associated epilepsy, optimize the CEST acquisition parameters, and provide an analysis method for exploring the dominant molecular contributors to the CEST signal measured. Nine TSC epilepsy patients were scanned on a 3-T MRI system. The CEST saturation frequencies were swept from -6 to 6 ppm with 12 different combinations of saturation power (4, 3, 2 and 1 µT) and duration (1000, 700 and 400 ms). Furthermore, a two-stage simulation method based on the seven-pool Bloch-McConnell model was proposed to assess the contribution of each exchangeable pool to the CEST signal in normal-appearing white matter and cortical tubers, which avoided the complexity and uncertainty of full Bloch-McConnell fitting. The results showed that under the optimal saturation duration of 1000 ms, the greatest contrast between tubers and normal tissues occurred around 3, 2.5, 1.75 and 3.5 ppm for B1 of 4, 3, 2 and 1 µT, respectively. At the optimal frequency offsets, the CEST values of tubers were significantly higher than those in the normal brain tissues (P < 0.01). Furthermore, the two-stage analysis suggested that the amine pool played a dominant role in yielding the contrast between cortical tubers and normal tissues. These results indicate that CEST MRI may serve as a potentially useful tool for identifying tubers in TSC, and the two-stage analysis method may provide a route for investigating the molecular contributions to the CEST contrast in biological tissues.

Hyperperfusion on Arterial Spin Labeling MRI Predicts the 90-Day Functional Outcome After Mechanical Thrombectomy in Ischemic Stroke.

BACKGROUND: The prognostic significance of hyperperfusion after reperfusion therapy in patients with acute ischemic stroke (AIS) remains controversial. PURPOSE: To investigate the clinical factors associated with hyperperfusion, and the 90-day prognostic value of hyperperfusion after mechanical thrombectomy in AIS patients. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: Fifty-four AIS patients who underwent mechanical thrombectomy. FIELD STRENGTH/SEQUENCE: Time-of-flight MR angiography, pulsed arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and susceptibility-weighted imaging were performed at 3.0T within 1 week after thrombectomy. ASSESSMENT: Clinical factors including demographics, risk factors, stroke and treatment characteristics were collected and assessed. Hyperperfusion on ASL was defined as a focal increased cerebral blood flow on the affected side ≥130% of its mirror counterpart. Good clinical outcome at 90 days was defined as modified Rankin Scale score of 0-2. STATISTICAL TESTS: The interrater agreement was assessed using Cohen's kappa or the intraclass correlation coefficient. The relationship between hyperperfusion and clinical factors were analyzed by appropriate univariate statistics. Predictors of 90-day functional outcome were assessed by univariate analyses followed by multivariate logistic regression analysis and receiver-operating-characteristic curves. RESULTS: Thirty-six (66.7%) patients developed hyperperfusion on ASL after thrombectomy. Hyperperfusion was significantly correlated with successful recanalization (P < 0.05) and improvement of National Institutes of Health Stroke Scale scores at 24 hours (NIHSS24h ) (P < 0.05). A higher incidence of hemorrhage transformation was observed in patients with hyperperfusion than those without (63.9% vs. 50.0%), but no significant difference was found (P = 0.327). NIHSS24h (odds ratio [OR], 0.75, [95% confidence interval [CI] 0.62-0.91], P < 0.05), lesion volume on diffusion-weighted imaging (OR, 0.97, [95% CI 0.95-1.00], P < 0.05), and hyperperfusion on ASL (OR, 9.8, [95% CI 1.7-55.3], P < 0.05) were independent variables for predicting good functional outcomes. DATA CONCLUSION: Hyperperfusion on ASL correlated with successful recanalization and may be an independent prognostic marker for good neurological outcomes at 90 days in AIS patients after mechanical thrombectomy. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Feasibility of filter-exchange imaging (FEXI) in measuring different exchange processes in human brain.

Transmembrane water exchange, including intra-to-extravascular and intra-to-extracellular ones, are potential biomarkers in the diagnosis and understanding of cancers, brain disorders, and other diseases. Filter-exchange imaging (FEXI), a special case of diffusion exchange spectroscopy (DEXSY) adapted for clinical applications, has the potential to reveal different physiological water exchange processes using the same MRI sequence. In this study, we aim to explore the feasibility of FEXI in measuring different water exchange processes by modulating the diffusion filter (bf) and detection blocks in FEXI. Two FEXI protocols were implemented on a 3T MRI clinical scanner and reveal distinct apparent exchange rate (AXR) contrast in brain tissues in seven healthy volunteers. AXR estimated from a FEXI protocol with bf â€‹= â€‹250 â€‹s/mm2, which is expected to filter out the vascular water specifically, are significantly larger than those of a FEXI protocol with bf â€‹= â€‹900 â€‹s/mm2. Besides, the filter efficiency of FEXI with bf â€‹= â€‹250 â€‹s/mm2 shows a strong correlation with vascular density, a metric estimated as the fraction of water exhibiting intravoxel incoherent motion (IVIM). AXR of FEXI with bf â€‹= â€‹250 â€‹s/mm2 agrees with the vascular water efflux rate constants reported by other independent measurements, although the physiological basis of the AXR of FEXI with bf â€‹= â€‹900 â€‹s/mm2 is not clear yet. Collectively, our current results demonstrate the feasibility of FEXI in measuring different water exchange processes in vivo, and that FEXI targeting the vascular water could help characterize the intra-to-extravascular water exchange process.

Whole-brain chemical exchange saturation transfer imaging with optimized turbo spin echo readout.

PURPOSE: To achieve fast whole-brain chemical exchange saturation transfer (CEST) imaging with negligible susceptibility artifact. METHODS: An optimized turbo spin echo readout module, also known as sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE), was deployed in the CEST sequence. The SPACE-CEST sequence was tested in a phantom, 6 healthy volunteers, and 3 brain tumor patients on a 3T human scanner. A dual-echo gradient echo sequence was used for B0 inhomogeneity mapping. In addition, the proposed SPACE-CEST sequence was compared with the widely used turbo spin echo-CEST sequence for amide proton transfer-weighted (APTw) images. RESULTS: The SPACE-CEST sequence generated highly consistent APTw maps to those of the turbo spin echo-CEST sequence in the phantom. In healthy volunteers, the SPACE-CEST sequence yielded whole-brain 2.8-mm isotropic APTw source images within 5 minutes, with no discernible susceptibility artifact. As for the B0 maps in the whole brain, its mean, median, and standard deviation B0 offset values were 5.0 Hz, 5.6 Hz, and 16 Hz, respectively. Regarding the APTw map throughout the whole brain, its mean, median, and standard deviation values were 0.78%, 0.56%, and 1.74%, respectively. The SPACE-CEST sequence was also successfully applied to a postsurgery brain tumor patient, suggesting no disease progression. In addition, on the newly diagnosed brain tumor patients, the SPACE-CEST and turbo spin echo-CEST sequences yielded essentially identical APTw values. CONCLUSION: The proposed SPACE-CEST technique can rapidly generate whole-brain CEST source images with negligible susceptibility artifact.

Design of a shim coil array matched to the human brain anatomy.

PURPOSE: The purpose of this study is to introduce a novel design method of a shim coil array specifically optimized for whole brain shimming and to compare the performance of the resulting coils to conventional spherical harmonic shimming. METHODS: The proposed design approach is based on the stream function method and singular value decomposition. Eighty-four field maps from 12 volunteers measured in seven different head positions were used during the design process. The cross validation technique was applied to find an optimal number of coil elements in the array. Additional 42 field maps from 6 further volunteers were used for an independent validation. A bootstrapping technique was used to estimate the required population size to achieve a stable coil design. RESULTS: Shimming using 12 and 24 coil elements outperforms fourth- and fifth-order spherical harmonic shimming for all measured field maps, respectively. Coil elements show novel coil layouts compared to the conventional spherical harmonic coils and existing multi-coils. Both leave-one-out and independent validation demonstrate the generalization ability of the designed arrays. The bootstrapping analysis predicts that field maps from approximately 140 subjects need to be acquired to arrive at a stable design. CONCLUSIONS: The results demonstrate the validity of the proposed method to design a shim coil array matched to the human brain anatomy, which naturally satisfies the laws of electrodynamics. The design method may also be applied to develop new shim coil arrays matched to other human organs.

Audio enhancement and intelligent classification of household sound events using a sparsely deployed array.

A household sound event classification system consisting of an audio localization and enhancement front-end cascaded with an intelligent classification back-end is presented. The front-end is composed of a sparsely deployed microphone array and a preprocessing unit to localize the source and extract the associated signal. In the front-end, a two-stage method and a direct method are compared for localization. The two-stage method introduces a subspace algorithm to estimate the time difference of arrival, followed by a constrained least squares algorithm to determine the source location. The direct localization methods, the delay-and-sum beamformer, the minimum power distortionless response beamformer, and the multiple signal classification algorithm are compared in terms of localization performance for sparse array configuration. A modified particle swarm optimization algorithm enabled an efficient grid-search. A minimum variance distortionless response beamformer in conjunction with a minimum-mean-square-error postfilter is exploited to extract the source signals for sound event classification tasks that follow. The back-end of the system is a sound event classifier that is based on convolutional neural networks (CNNs), and convolutional long short-term memory networks Mel-spectrograms are used as the input features to the CNNs. Simulations and experiments conducted in a live room have demonstrated the strength and weakness of the direct and two-stage methods. Signal quality enhancement using the array-based front-end proves beneficial for improved classification accuracy over a single microphone.