Strategically Acquired Gradient Echo Research Articles

Strategically Acquired Gradient Echo (STAGE) Imaging, part IV: Constrained Reconstruction of White Noise (CROWN) Processing as a Means to Improve Signal-to-Noise in STAGE Imaging at 3 Tesla

Increasing the signal-to-noise ratio (SNR) has always been of critical importance for magnetic resonance imaging. Although increasing field strength provides a linear increase in SNR, it is more and more costly as field strength increases. Therefore, there is a major effort today to use signal processing methods to improve SNR since it is more efficient and economical. There are a variety of methods to improve SNR such as averaging the data at the expense of imaging time, or collecting the data with a lower resolution, all of these methods, including imaging processing methods, usually come at the expense of loss of image detail or image blurring. Therefore, we developed a new mathematical approach called CROWN (Constrained Reconstruction of White Noise) to enhance SNR without loss of structural detail and without affecting scanning time. In this study, we introduced and tested the concept behind CROWN specifically for STAGE (strategically acquired gradient echo) imaging. The concept itself is presented first, followed by simulations to demonstrate its theoretical effectiveness. Then the SNR improvement on proton spin density (PSD) and R2⁎ maps was investigated using brain STAGE data acquired from 10 healthy controls (HCs) and 10 patients with Parkinson's disease (PD). For the PSD and R2* maps, the SNR and CNR between white matter and gray matter were improved by a factor of 1.87 ± 0.50 and 1.72 ± 0.88, respectively. The white matter hyperintensity lesions in PD patients were more clearly defined after CROWN processing. Using these improved maps, simulated images for any repeat time, echo time or flip angle can be created with improved SNR. The potential applications of this technology are to trade off the increased SNR for higher resolution images and/or faster imaging.

Characterization of white matter lesions in multiple sclerosis using proton density and T1-relaxation measures

PurposeAlthough lesion dissemination in time is a defining characteristic of multiple sclerosis (MS), there is a limited understanding of lesion heterogeneity. Currently, conventional sequences such as fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W) data are used to assess MS lesions qualitatively. Estimating water content could provide a measure of local tissue rarefaction, or reduced tissue density, resulting from chronic inflammation. Our goal was to utilize the proton spin density (PD), derived from a rapid, multi-contrast STAGE (strategically acquired gradient echo) protocol to characterize white matter (WM) lesions seen on T2W, FLAIR and T1W data. Materials and methodsTwenty (20) subjects with relapsing-remitting MS were scanned at 3 T using T1W, T2-weighted, FLAIR and strategically acquired gradient echo (STAGE) sequences. PD and T1 maps were derived from the STAGE data. Disease severity scores, including Extended Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC), were correlated with total, high PD and high T1 lesion volumes. A probability map of high PD regions and all lesions across all subjects was generated. Five perilesional normal appearing WM (NAWM) bands surrounding the lesions were generated to compare the median PD and T1 values in each band with the lesional values and the global WM. ResultsT1W intensity was negatively correlated with PD as expected (R = −0.87, p < 0.01, R2 = 0.756) and the FLAIR signal was suppressed for high PD volumes within the lesions, roughly for PD ≥ 0.85. The threshold for high PD and T1 regions was set to 0.909 and 1953.6 ms, respectively. High PD regions showed a high probability of occurrence near the boundary of the lateral ventricles. EDSS score and nine-hole peg test (dominant and non-dominant hand) were significantly correlated with the total lesion volume and the volumes of high PD and T1 regions (p < 0.05). There was a significant difference in PD/T1 values between the high PD/T1 regions within the lesions and the remaining lesional tissue (p < 0.001). In addition, the PD values of the first NAWM perilesional band directly adjacent to the lesional boundary displayed a significant difference (p < 0.05) compared to the global WM. ConclusionLesions with high PD and T1s had the highest probability of occurrence at the boundary of the lateral ventricles and likely represent chronic lesions with significant local tissue rarefaction. Moreover, the perilesional NAWM exhibited subtly increasing PD and T1 values from the NAWM up to the lesion boundary. Unlike on the T1 maps, the perilesional band adjacent to the lesion boundary possessed a significantly higher PD value than the global WM PD values. This shows that PD maps were sensitive to the subtle changes in NAWM surrounding the lesions.

Impaired T1 mapping and Tmax during the first 7 days after ischemic stroke. A retrospective observational study

ObjectiveTo measure the relative T1 (rT1) value in different hypo-perfused regions after ischemic stroke using T1 mapping derived by Strategically Acquired Gradient Echo (STAGE) and assess its relationship with onset time and severity of ischemia. Materials and MethodsSixty-three patients with acute anterior circulation ischemic stroke from 2017 to 2022 who underwent STAGE, diffusion weighted imaging (DWI) and dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) within 7 days were retrospectively enrolled. The areas with reduced diffusion and hypo-perfusion were segmented based on apparent diffusion coefficient (ADC) value < 0.62 × 10−3mm2/s and time-to-maximum (Tmax) thresholds (4, 6, 8, and 10 seconds). We measured the T1 value in the diffusion reduced and every 2 s Tmax strata regions and calculated rT1 (T1ipsi/T1contra) to explore the relationship between rT1 value, Tmax, and onset time. ResultsrT1 value was increased in diffusion reduced (1.42) and hypo-perfused regions (1.02, 1.06, 1.12, 1.27, Tmax 4–6 s, 6–8 s, 8–10 s, > 10 s, respectively; all different from 1, P < 0.001). rT1 value was positively correlated with Tmax (rs = 0.61, P < 0.001) and onset time in area with reduced diffusion (rs = 0.39, P = 0.014). ConclusionsIncreased rT1 value in different hypo-perfused brain regions using T1 mapping derived by STAGE may reflect the edema; it was associated with the severity of Tmax and showed a weak correlation with the onset time in diffusion reduced areas.

Deep gray matters iron deposition is positively associated with white matter hyperintensity in hypertension.

The association and underlying mechanisms between iron deposition and white matter hyperintensity (WMH) remain unclear. In this study, quantitative susceptibility mapping (QSM) was used to quantify deep gray matters iron deposition and to explore the association from both global and regional perspectives. A total of 84 patients with hypertension and 26 healthy controls underwent a strategically acquired gradient echo (STAGE) protocol, and the multi-echo data were used to reconstruct QSM images. The susceptibilities were used to describe iron content. Global region (RI) susceptibilities were measured in regions of interest, and age-related thresholds were used to determine high-iron content region (RII) susceptibilities. Compared with healthy controls, hypertension had higher total WMH scores and regional scores (all p=.001) and higher susceptibilities using the RI or RII analysis (all p<.05). In healthy controls, there was no significant association between susceptibilities and WMH scores. In hypertension, the susceptibilities of deep gray matters were positively correlated with WMH scores (RI analysis: right putamen; RII analysis: bilateral caudate nucleus head, putamen, red nucleus, substantia nigra, and dentate nucleus; age and education corrected p<.05). These findings suggest that iron deposition in deep gray matters was positively associated with WMH in hypertension, especially using the RII analysis.

Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus.

To quantitatively evaluate the iron deposition and volume changes in deep gray nuclei according to threshold-method of quantitative susceptibility mapping (QSM) acquired by strategically acquired gradient echo (STAGE) sequence, and to analyze the correlation between the magnetic susceptibility values (MSV) and cognitive scores in type 2 diabetes mellitus (T2DM) patients. Twenty-nine patients with T2DM and 24 healthy controls (HC) matched by age and gender were recruited in this prospective study. QSM images were used to evaluate whole-structural volumes (Vwh), regional magnetic susceptibility values (MSVRII), and volumes (VRII) in high-iron regions in nine gray nuclei. All QSM data were compared between groups. Receiver operating characteristic (ROC) analysis was used to assess the discriminating ability between groups. The predictive model from single and combined QSM parameters was also established using logistic regression analysis. The correlation between MSVRII and cognitive scores was further analyzed. Multiple comparisons of all statistical values were corrected by false discovery rate (FDR). A statistically significant P-value was set at 0.05. Compared with HC group, the MSVRII of all gray matter nuclei in T2DM were increased by 5.1-14.8%, with significant differences found in bilateral head of caudate nucleus (HCN), right putamen (PUT), right globus pallidus (GP), and left dentate nucleus (DN) (P < 0.05). The Vwh of most gray nucleus in T2DM group were decreased by 1.5-16.9% except bilateral subthalamic nucleus (STN). Significant differences were found in bilateral HCN, bilateral red nucleus (RN), and bilateral substantia nigra (SN) (P < 0.05). VRII was increased in bilateral GP, bilateral PUT (P < 0.05). VRII/Vwh was also increased in bilateral GP, bilateral PUT, bilateral SN, left HCN and right STN (P < 0.05). Compared with the single QSM parameter, the combined parameter showed the largest area under curve (AUC) of 0.86, with a sensitivity of 87.5% and specificity of 75.9%. The MSVRII in the right GP was strongly associated with List A Long-delay free recall (List A LDFR) scores (r = -0.590, P = 0.009). In T2DM patients, excessive and heterogeneous iron deposition as well as volume loss occurs in deep gray nuclei. The MSV in high iron regions can better evaluate the distribution of iron, which is related to the decline of cognitive function.

Applications of strategically acquired gradient echo imaging to neurodegenerative diseases

Background: One major thrust in radiology today is image standardization with a focus on rapid, quantitative, multi-contrast data collection and processing.&#x0D; Methods: Strategically acquired gradient echo (STAGE) imaging1-4 is one such method that uses multiple flip angles and multiple echo times. It can provide 8 qualitative and 7 quantitative images as well as transmit field B1 transmit field and B1 receive field maps in 4-6 minutes or less on a 3T magnetic resonance (MR) scanner. STAGE provides qualitative images in the form of proton density-weighted images, T1 weighted images and T2* weighted images. STAGE provides quantitative data in the form of proton spin density (PSD), T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid via simulated double inversion recovery (sDIR) images. STAGE has been tested using the NIST phantom and yields intrasubject errors of only 1-2% and intrasubject variation of 2 to 5%. Contrast-to-noise ratio (CNR) measurements show that the T1WE images are comparable to the conventional T1W MP-RAGE images. Today these quantitative measures are providing new biomarkers for imaging a variety of neurodegenerative diseases (Figure 1).&#x0D; Results: During the last few years, we have focused on measuring iron content and neuromelanin (NM) in the substantia nigra (SN) for comparing idiopathic Parkinson’s disease (PD) with healthy controls and patients with other movement disorders. We have found that the volume of NM, the iron content of the SN, the volume of the SN and the N1 sign all together can provide an area under the curve of 95% in distinguishing PD from healthy controls.5 We have developed a template of the midbrain to allow for automatic detection and quantification of these properties. We use tSWI to enhance the N1 sign visibility. We have also used STAGE to study multiple sclerosis (MS) lesions. QSM can be used to map changes in white matter susceptibility and potentially correlated with demyelination. We provide a composite image using tSWI combined with fluid-attenuated inversion recovery (FLAIR) to highlight those lesions that are purely inflammatory from inflammatory demyelinating lesions. Recently we have begun to study the use of absolute water content as a measure of lesion atrophy. Higher water content means a higher likelihood of tissue damage. This also explains why the presence of “black holes” seen in T1W images of MS patients tends to correlate with the expanded disability status score.&#x0D; Conclusions: In summary, STAGE provides a comprehensive clinical imaging protocol that, combined with diffusion-weighted imaging (DWI) and FLAIR, can yield a standardized 10-minute (3T) o 15-minute (1.5T) imaging protocol of the entire brain across all manufacturers.

Glioblastoma Response during Chemoradiation by Daily Quantitative Multiparametric MRI

<h3>Purpose/Objective(s)</h3> Quantitative Multiparametric MRI (qMP-MRI) is a fast and robust technique for providing relaxometry information such as T1, R2 and R2* maps. This information is correlated to glioblastoma (GBM) cellular density and may be useful to predict sites of tumor progression. For example, T1 has longer and R2 and R2* have shorter relaxation times for voxels adjacent to gadolinium enhancing tumor. The availability of MRI-Linac systems provides the opportunity to detect qMP-MRI changes daily through the course of radiation therapy (RT) and to adapt plans during RT. We hypothesize that qMP-MRI can detect tumor changes during a course of MRI-Linac treatment and correlates with patient outcomes. <h3>Materials/Methods</h3> We analyzed an IRB-approved prospective cohort of 21 consecutive GBM patients treated on a 0.35T MRI-Linac system with 30 fractions to 60 Gy and temozolomide. Daily qMP-MRI data were obtained with multi-TE and the Strategically Acquired Gradient Echo (STAGE) on alternating treatment days (15 qMP-MRI acquisitions during RT). For STAGE, 36 slices of 1.5 × 1.5 × 5 mm³ resolution were acquired using varying TEs and flip angles. A multi-TE sequence with 18 slices of 1.6 × 1.6 × 6 mm³ were also acquired. Quantitative T1 and R2* (1/T2*) maps were obtained from STAGE acquisitions and R2 (1/T2) maps from the multi-TE acquisition. Image changes related to tumor area and resection cavity were contoured on the T2 weighted images from daily patient setup using a standard contouring software. A ROI (Peri-tumor) was created based on a 10 mm expansion around the tumor or resection cavity. Changes of T1, R2* and R2 from each voxel within the Peri-tumor were analyzed by parametric response mapping comparing the images from each fraction to those obtained during pre-RT simulation. <h3>Results</h3> Of the 21 GBM patients, 10 had no tumor growth on first post-RT diagnostic MRI (48%), 4 (19%) were determined to have pseudoprogression based on regression or long-term stability of findings, and 7 (33%) had true progression due to continued progression of disease past 6 months, rapid patient death from disease, or tissue sampling showing active malignancy. The analysis of qMP-MRI obtained during RT showed that true progressors presented increases of T1 and decreases of R2* and R2 values for at least 10, 20 and 15%, respectively, of the voxels within the Peri-tumor when compared to patients with no change (Fisher's exact test, p<0.05 for each metric). All true progressors showed such changes before the 15^th fraction (3^rd week) of treatment. <h3>Conclusion</h3> Changes of qMP-MRI based parameters obtained during RT, such as increases in T1 and decreases in R2 and R2* within the Peri-tumor, were found to correlate with true progression. These changes were observed in images obtained before the third week of treatment, suggesting that adaptive RT or other therapies may be useful to intervene early for patients with GBM unresponsive to conventional therapy.

Quantifying calcium changes in the fetal spine using quantitative susceptibility mapping as extracted from STAGE imaging.

To evaluate calcium deposition in the fetal spine in vivo during the second and third trimesters using quantitative susceptibility mapping (QSM). Fifty-four pregnant women in their second and third trimesters underwent a 2D multi-echo STrategically Acquired Gradient Echo (STAGE) MR imaging protocol at 3T covering the fetal spine. The first echo data was used for QSM processing. A linear regression model was used to assess the correlation between magnetic susceptibility and gestational age (GA). A paired sample t-test was used to compare the consistency of QSM measurements from each sequence. The magnetic susceptibility of the fetal spine decreased linearly with advancing GA, with a slope of -52.3 parts per billion (ppb)/week and a Pearson correlation coefficient (r) of 0.83 (p < 0.001). In 37 subjects for whom the STAGE local QSM data were available from both flip angles, the average magnetic susceptibility values were -1111 ± 278 ppb and -1081 ± 262 ppb for FA = 8° and FA = 40°, respectively. These means were not statistically different according to a paired sample t-test (p = 0.156). QSM is a reliable technique for evaluating calcium deposition and bone mineral density of fetal vertebrae. Our results demonstrate an increase in fetal calcium levels as a function of GA. These measures might be able to provide reference values for calcium content in the fetal spine during the second and third trimesters. • Calcium deposition and mineralization in the fetal spine, evaluated by vertebral magnetic susceptibility, increased with advancing gestational age. • Our results provide reference values for calcium content in the fetal spine during the second and third trimesters.

Quantitative Susceptibility Mapping of Brain Iron Relating to Cognitive Impairment in Hypertension.

Hypertension (HTN) might impair cognition. Brain iron deposition correlates with cognitive impairment. The relationship between brain iron and cognition in HTN patients is less clear. To measure brain susceptibility in HTN patients using quantitative susceptibility mapping (QSM) and to explore the relationship between brain iron and cognition. Retrospective cross-sectional study. Sixty HTN patients (35 with mild cognitive impairment [MCI] and 25 without MCI) and 24 age, gender, and education matched controls. 3 T; strategically acquired gradient echo (STAGE) imaging protocol for QSM analysis. All subjects underwent Montreal Cognitive Assessment (MoCA) scoring of visuospatial/executive, naming, attention, abstraction, language, delayed memory, and orientation functions. HTN patients were divided into two groups (with and without MCI) depending on the MoCA score. Regions of interest (ROIs) were manually demarcated on the STAGE images by three independent radiologists and susceptibility were determined for bilateral frontal white matter, parietal white matter, occipital white matter, caudate nucleus (CN), putamen (PU), globus pallidus (GP), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). Analysis of variance with post-hoc least significant difference (LSD) tests and Pearson correlation coefficients (r). A P-value <0.05 was considered to be statistically significant. The susceptibility was significantly different in CN, PU, and DN among the three groups. The susceptibility of right CN and left PU were correlated with MoCA scores (r=-0.429 and r=-0.389, respectively). The susceptibility of left PU was also correlated with delayed memory scores (r=-0.664). The susceptibility of left and right GP were correlated with naming scores (r=-0.494 and r=-0.446, respectively) and the susceptibility of left DN were correlated with visuospatial/executive scores (r=0.479). QSM measured brain iron was significantly higher in CN, PU, and DN in HTN patients. Cognitive impairment was correlated with regional brain iron deposition. 2 TECHNICAL EFFICACY: Stage 3.

Fetal brain tissue characterization at 1.5 T using STrategically Acquired Gradient Echo (STAGE) imaging

To estimate human fetal brain MRI tissue properties including apparent T1 (T1app) and apparent proton density (PDapp) by using a rapid multi-contrast acquisition protocol called STrategically Acquired Gradient Echo (STAGE) imaging. STAGE data were collected using two flip angles (15° and 60°, with a TR = 600 ms) for 30 pregnant women at 1.5 T (15 healthy controls: gestational age (GA) range 19 + 1/7 weeks to 34 + 5/7 weeks; 11 abnormal subjects with ventriculomegaly: GA range 21 + 5/7 weeks to 31 + 5/7 weeks; 4 subjects with other abnormalities). Both T1app and PDapp maps of the fetal brain were calculated from the STAGE data. A region-of-interest-based approach was used to measure T1app and PDapp in the subplate/intermediate zone (SP/IZ), cortical plate (CP), and cerebrospinal fluid (CSF) in the fetal brain. The ratios of T1appSP/IZ/T1appCP and PDappSP/IZ/PDappCP were larger than unity while T1appSP/IZ/T1appCSF and PDappSP/IZ/PDappCSF were both less than unity. STAGE imaging provides a potential practical approach to estimate multi-parametric properties of the human fetal brain. • STAGE is feasible in measuring fetal brain tissue properties. • Water content in cortical plate and subplate/intermediate zone approaches that of cerebrospinal fluid in early gestational ages.

Quantitative MRI using STrategically Acquired Gradient Echo (STAGE): optimization for 1.5 T scanners and T1 relaxation map validation.

The strategically acquired gradient echo (STAGE) protocol, developed for 3T scanners, allows one to derive quantitative maps such as T1, T2*, proton density, and quantitative susceptibility mapping in about 5 min. Our aim was to adapt the STAGE sequences for 1.5T scanners which are still commonly used in clinical practice. Furthermore, the accuracy and repeatability of the STAGE-derived T1 estimate were tested. Flip angle (FA) optimization was performed using a theoretical simulation by maximizing signal-to-noise ratio, contrast-to-noise ratio, and T1 precision. The FA choice was further refined with the ISMRM/NIST phantom and in vivo acquisitions. The accuracy of the T1 estimate was assessed by comparing STAGE-derived T1 values with T1 maps obtained with an inversion recovery sequence. T1 accuracy was investigated for both the phantom and in vivo data. Finally, one subject was acquired 10 times once a week and a group of 27 subjects was scanned once. The T1 coefficient of variation (COV) was computed to assess scan-rescan and physiological variability, respectively. The FA1,2 = 7°,38° were identified as the optimal FA pair at 1.5T. The T1 estimate errors were below 3% and 5% for phantom and in vivo measurements, respectively. COV for different tissues ranged from 1.8 to 4.8% for physiological variability, and between 0.8 and 2% for scan-rescan repeatability. The optimized STAGE protocol can provide accurate and repeatable T1 mapping along with other qualitative images and quantitative maps in about 7 min on 1.5T scanners. This study provides the groundwork to assess the role of STAGE in clinical settings. • The STAGE imaging protocol was optimized for use on 1.5T field strength scanners. • A practical STAGE protocol makes it possible to derive quantitative maps (i.e., T1, T2*, PD, and QSM) in about 7 min at 1.5T. • The T1 estimate derived from the STAGE protocol showed good accuracy and repeatability.

Multi-Echo Quantitative Susceptibility Mapping for Strategically Acquired Gradient Echo (STAGE) Imaging.

PurposeTo develop a method to reconstruct quantitative susceptibility mapping (QSM) from multi-echo, multi-flip angle data collected using strategically acquired gradient echo (STAGE) imaging.MethodsThe proposed QSM reconstruction algorithm, referred to as “structurally constrained Susceptibility Weighted Imaging and Mapping” scSWIM, performs an ℓ1 and ℓ2 regularization-based reconstruction in a single step. The unique contrast of the T1 weighted enhanced (T1WE) image derived from STAGE imaging was used to extract reliable geometry constraints to protect the basal ganglia from over-smoothing. The multi-echo multi-flip angle data were used for improving the contrast-to-noise ratio in QSM through a weighted averaging scheme. The measured susceptibility values from scSWIM for both simulated and in vivo data were compared to the: original susceptibility model (for simulated data only), the multi orientation COSMOS (for in vivo data only), truncated k-space division (TKD), iterative susceptibility weighted imaging and mapping (iSWIM), and morphology enabled dipole inversion (MEDI) algorithms. Goodness of fit was quantified by measuring the root mean squared error (RMSE) and structural similarity index (SSIM). Additionally, scSWIM was assessed in ten healthy subjects.ResultsThe unique contrast and tissue boundaries from T1WE and iSWIM enable the accurate definition of edges of high susceptibility regions. For the simulated brain model without the addition of microbleeds and calcium, the RMSE was best at 5.21ppb for scSWIM and 8.74ppb for MEDI thanks to the reduced streaking artifacts. However, by adding the microbleeds and calcium, MEDI’s performance dropped to 47.53ppb while scSWIM performance remained the same. The SSIM was highest for scSWIM (0.90) and then MEDI (0.80). The deviation from the expected susceptibility in deep gray matter structures for simulated data relative to the model (and for the in vivo data relative to COSMOS) as measured by the slope was lowest for scSWIM + 1%(−1%); MEDI + 2%(−11%) and then iSWIM −5%(−10%). Finally, scSWIM measurements in the basal ganglia of healthy subjects were in agreement with literature.ConclusionThis study shows that using a data fidelity term and structural constraints results in reduced noise and streaking artifacts while preserving structural details. Furthermore, the use of STAGE imaging with multi-echo and multi-flip data helps to improve the signal-to-noise ratio in QSM data and yields less artifacts.

Plaque characteristics of middle cerebral artery assessed using strategically acquired gradient echo (STAGE) and vessel wall MR contribute to misery downstream perfusion in patients with intracranial atherosclerosis.

To assess plaque vulnerability of the middle cerebral artery (MCA) using strategically acquired gradient echo (STAGE) versus high-resolution vessel wall MRI (hr-vwMRI), and explore the relationship between plaque characteristics and misery downstream perfusion. Ninety-one patients with single MCA atherosclerotic plaques underwent STAGE and hr-vwMRI were categorized into a group with misery perfusion and a group without based on the Alberta Stroke Program Early CT score (MTT-ASPECTS) with a threshold of 6. Plaque characteristics including inner lumen area (IWA), susceptibility, presence of hyperintensity within plaque (HIP), surface irregularity, stenosis degree, remodeling index, lipid ratio, and enhancement grade were compared between the two groups. The vulnerability of each plaque was retrospectively assessed on both STAGE and hr-vwMRI according to the combination of plaque features. Logistic regression analysis and ROC curve were performed to evaluate the effect of plaque characteristics on the presence of misery perfusion. Taking hr-vwMRI as the reference, STAGE showed good efficiency in detecting vulnerable plaques. Patients with misery perfusion had less IWA, higher stenosis degree, more irregular surface and HIP, higher enhancement grade, and susceptibility (p < 0.01 for all). Higher susceptibility and stenosis degree were independent predictors for the occurrence of misery perfusion (p = 0.025, p = 0.048). The AUC was 0.900 for the combination of the two variables. STAGE shows good efficiency to assess MCA plaque vulnerability versus hr-vwMRI. Plaque susceptibility evaluated using STAGE provides incremental value to predict misery perfusion combined with hr-vwMRI plaque features. • STAGE has good efficiency in evaluating MCA plaque vulnerability versus hr-vwMRI. • Higher plaque susceptibility assessed using STAGE and higher grade luminal stenosis based on hr-vwMRI attribute to misery downstream perfusion. • STAGE provides incremental value on the understanding of plaque vulnerability in addition to conventional hr-vwMRI.

Rapid multicontrast brain imaging on a 0.35T MR-linac.

Magnetic resonance-guided radiation therapy (MRgRT) has shown great promise for localization and real-time tumor monitoring. However, to date, quantitative imaging has been limited for low field MRgRT. This work benchmarks quantitative T1, R2*, and Proton Density (PD)mapping in a phantom on a 0.35T MR-linac and implements a novel acquisition method, STrategically Acquired Gradient Echo (STAGE). To further validate STAGE in a clinical setting, a pilot study was undertaken in a cohort of brain tumor patients to elucidate opportunities for longitudinal functional imaging with an MR-linac in the brain. STAGE (two triple-echo gradient echo (GRE) acquisitions) was optimized for a 0.35T low-field MR-linac. Simulations were performed to choose two flip angles to optimize signal-to-noise ratio (SNR) and T1-mapping precision. Tradeoffs between SNR, scan time, and spatial resolution for whole-brain coverage were evaluated in healthy volunteers. Data were inputted into a STAGE processing pipeline to yield four qualitative images (T1-weighted, enhanced T1-weighted, proton-density (PD) weighted, and simulated FLuid-Attenuated Inversion Recovery (sFLAIR)), and three quantitative datasets (T1, PD, and R2*). A benchmarking ISMRM/NIST phantom consisting of vials with variable NiCl2 and MnCl2 concentrations was scanned using variable flip angles (VFA) (2-60degrees) and inversion recovery (IR) methods at 0.35T. STAGE and VFA T1 values of vials were compared to IR T1 values. As measures of agreement with reference values and repeatability, relative error (RE) and coefficient of variability (CV) were calculated, respectively, for quantitative MR values within the phantom vials (spheres). To demonstrate feasibility, longitudinal STAGE data (pretreatment, weekly, and~2months post-treatment) were acquired in an IRB-approved pilot study of brain tumor cases via the generation of temporal and differential quantitative MRI maps. In the phantom, RE of measured VFA T1 and STAGE relative to IR reference values were 7.0±2.5% and 9.5±2.2% respectively. RE for the PD vials was 8.1±6.8% and CV for phantom R2* measurements was 10.1±9.9%. Simulations and volunteer experiments yielded final STAGE parameters of FA=50°/10°, 1×1×3mm3 resolution, TR=40ms, TE=5/20/34ms in 10min (64 slices). In the pilot study of brain tumor patients, differential maps for R2* and T1 maps were sensitive to local tumor changes and appeared similar to 3T follow-up MRI datasets. Quantitative T1, R2*, and PD mapping are promising at 0.35T agreeing well with reference data. STAGE phantom data offer quantitative representations comparable to traditional methods in a fraction of the acquisition time. Initial feasibility of implementing STAGE at 0.35T in a patient brain tumor cohort suggests that detectable changes can be observed over time. With confirmation in a larger cohort, results may be implemented to identify areas of recurrence and facilitate adaptive radiation therapy.

Optimizing neuromelanin contrast in the substantia nigra and locus coeruleus using a magnetization transfer contrast prepared 3D gradient recalled echo sequence

Neuromelanin (NM) loss in the substantia nigra (SN) and locus coeruleus (LC) is being investigated as an imaging biomarker for Parkinson’s disease (PD) using magnetization transfer contrast (MTC) magnetic resonance imaging. The MTC pulse operates in a way to suppress tissue with high macromolecular content thereby highlighting the presence of NM in the LC and the SN. The MTC pulse also leads to a reduction in the effective T1 of the tissue. In the past, a 3D gradient echo (GRE) sequence has usually been run with a single flip angle (FA) generally to highlight the T1 shortening effect when trying to visualize NM. We contend that the NM will be best seen with a low FA (relative to the Ernst angle) because the NM has high water content relative to the surrounding tissues. Therefore, the goal of this paper was to optimize the NM contrast in the SN and LC as a function of flip angle using a 3D GRE MTC strategically acquired gradient echo (STAGE) imaging approach. In order to accomplish this, short repeat time (62 ​ms), 3D GRE imaging data were collected for 7 different flip angles ranging from 5° to 40° for 14 healthy volunteers (age range 24–43 years, mean ​± ​SD ​= ​34.8 ​± ​6.0 years, 6 males). By measuring the contrast-to-noise ratio between these structures and the surrounding tissues, we found that the FA showing the best NM contrast was 15° - 20° for the SN and 20° - 25° for the LC. Using STAGE imaging with just two flip angles (15° and 30°) made it possible to quantify not only tissue properties such as T1 and proton density but also to generate synthetic MTC images at an arbitrary FA. These synthetic images make it possible to optimize the contrast for any changes in tissue property that might occur in the LC or SN as a function of age or disease. In conclusion, practically, two scans could be collected in roughly 7 ​min each for both FAs in a standard clinical imaging setting to evaluate the signal intensity and volume of the NM in the LC and SN.

Strategically acquired gradient echo (STAGE)-derived MR angiography might be a superior alternative method to time-of-flight MR angiography in visualization of leptomeningeal collaterals.

This study aimed to compare the performance of strategically acquired gradient echo (STAGE)-derived MR angiography and time-of-flight MR angiography (TOF-MRA) in visualization of leptomeningeal collaterals (LMCs). Between May 2018 and January 2020, 75 participants (47 healthy volunteers and 28 intracranial atherosclerotic disease [ICAD] patients) undergoing TOF-MRA and STAGE-MRA were prospectively included. Image quality was scored at the internal carotid artery (ICA) terminus, proximal middle cerebral artery (MCA), and LMCs. Quantitative analysis included calculation of contrast-to-noise ratios (CNRs) in the M1-4 segments and number of LMCs counted in the line signal intensity profiles. Comparisons of image qualitative scores, CNRs, and number of LMCs were calculated using the Wilcoxon rank-sum test. Image qualitative scores were significantly higher in STAGE-MRA than in TOF-MRA for the ICA terminus, proximal MCA, and LMCs (ps < 0.05) in 75 participants. When referred to digital subtraction angiography (DSA) in 25 ICAD patients, STAGE-MRA showed higher qualitative scores only at LMCs. CNRs in the M1-4 segments were significantly higher in STAGE-MRA than in TOF-MRA (218.7 ± 90.7 vs 176.2 ± 72.6, 195.7 ± 86.0 vs 146.6 ± 71.7, 176.4 ± 71.6 vs 125.8 ± 61.1, 126.2 ± 62.9 vs 78.8 ± 43.6; all ps < 0.001). STAGE-MRA showed more LMCs (11.4 ± 3.4) than TOF-MRA (8.4 ± 3.3) with p < 0.05. STAGE-MRA might be superior to TOF-MRA in qualitative and quantitative assessment of LMCs in both healthy volunteers and ICAD patients; thus, it may serve as an alternative method in evaluating LMC. • Strategically acquired gradient echo (STAGE)-derived magnetic resonance angiography is a newly developed sequence with a pair of rephasing/dephasing gradient echoes. • STAGE-MRA enables higher image qualitative score, improves contrast-to-noise ratio, and shows greater number of leptomeningeal collaterals (LMCs) in healthy volunteers and patients with intracranial atherosclerotic disease. • LMC visualization by STAGE-MRA shows good to excellent inter-observer agreement.

Intracranial iron distribution and quantification in aceruloplasminemia: A case study

ObjectivesAceruloplasminemia (ACP) is a rare autosomal recessive disorder characterized by intracranial and visceral iron overload. With R2*-based imaging or quantitative susceptibility mapping (QSM), it is feasible to measure iron in the brain quantitatively, although to date this has not yet been done for patients with ACP. The aim of this study was to provide quantitative iron measurements for each affected brain region in an ACP patient with the potential to do so in all future ACP patients. This may shed light on the link between brain iron metabolism and the territories affected by ceruloplasmin function. MethodsWe imaged a patient with ACP using a 3T magnetic resonance imaging scanner with a fifteen-channel head coil. We manually demarcated gray matter and white matter on the Strategically Acquired Gradient Echo (STAGE) images, and calculated values for susceptibility and R2* in these regions. Correlation analysis was performed between the R2* values and the susceptibility values. ResultsBesides the usual territories affected in ACP, we also discovered that the mammillary bodies and the lateral habenulae had significant increases in iron, and the hippocampus was severely affected both in terms of iron content and abnormal tissue signal. We also noted that the iron in the cortical gray matter appeared to be deposited in the inner layers. Moreover, several pathways between the superior colliculus and the pulvinar thalamus, between the caudate and putamen anteriorly and between the caudate and pulvinar thalamus posteriorly were also evident. Finally, R2* correlated strongly with the QSM data (R2 = 0.67, t = 6.78, p < 0.001). ConclusionQSM and R2* have proven to be sensitive and quantitative means by which to measure iron content in the brain. Our findings included several newly noted affected brain regions of iron overload and provided some new aspects of iron metabolism in ACP that may be further applicable to other pathologic conditions. Furthermore, our study may pave the way for assessing efficacy of iron chelation therapy in these patients and for other common iron related neurodegenerative disorders.

STrategically Acquired Gradient Echo (STAGE) imaging, part III: Technical advances and clinical applications of a rapid multi-contrast multi-parametric brain imaging method

One major thrust in radiology today is image standardization with a focus on rapidly acquired quantitative multi-contrast information. This is critical for multi-center trials, for the collection of big data and for the use of artificial intelligence in evaluating the data. Strategically acquired gradient echo (STAGE) imaging is one such method that can provide 8 qualitative and 7 quantitative pieces of information in 5 min or less at 3 T. STAGE provides qualitative images in the form of proton density weighted images, T1 weighted images, T2* weighted images and simulated double inversion recovery (DIR) images. STAGE also provides quantitative data in the form of proton spin density, T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid. STAGE uses vendors' product gradient echo sequences. It can be applied from 0.35 T to 7 T across all manufacturers producing similar results in contrast and quantification of the data. In this paper, we discuss the strengths and weaknesses of STAGE, demonstrate its contrast-to-noise (CNR) behavior relative to a large clinical data set and introduce a few new image contrasts derived from STAGE, including DIR images and a new concept referred to as true susceptibility weighted imaging (tSWI) linked to fluid attenuated inversion recovery (FLAIR) or tSWI-FLAIR for the evaluation of multiple sclerosis lesions. The robustness of STAGE T1 mapping was tested using the NIST/NIH phantom, while the reproducibility was tested by scanning a given individual ten times in one session and the same subject scanned once a week over a 12-week period. Assessment of the CNR for the enhanced T1W image (T1WE) showed a significantly better contrast between gray matter and white matter than conventional T1W images in both patients with Parkinson's disease and healthy controls. We also present some clinical cases using STAGE imaging in patients with stroke, metastasis, multiple sclerosis and a fetus with ventriculomegaly. Overall, STAGE is a comprehensive protocol that provides the clinician with numerous qualitative and quantitative images.

STrategically Acquired Gradient Echo (STAGE) imaging, part II: Correcting for RF inhomogeneities in estimating T1 and proton density

PurposeTo develop a method for mapping the B1 transmit (B1t) and B1 receive (B1r) fields from two gradient echo datasets each with a different flip angle and from these two images obtain accurate T1 and proton density (PD) maps of the brain. MethodsA strategically acquired gradient echo (STAGE) data set is collected using two flip angles each with multiple echoes. The B1t field extraction was based on forcing cortical gray matter and white matter to have specific T1 values and fitting the resulting B1t field to a quadratic function. The B1r field extraction was based on synthesizing isointense images despite there being two or three tissue types present in the brain. This method was tested on 10 healthy volunteers and 20 stroke patients from data acquired at 3.0Tesla. ResultsWith the knowledge of the B1t and B1r fields, the uniformity of tissue T1 and PD maps was considerably improved. T1 values were measured for both the midbrain and basal ganglia and found to be in good agreement with the literature. Discussion and ConclusionsSTAGE provides a practical way to assess the B1t and the B1r fields which can then be used to correct for spatial variations in the images.

STrategically Acquired Gradient Echo (STAGE) imaging, part I: Creating enhanced T1 contrast and standardized susceptibility weighted imaging and quantitative susceptibility mapping

PurposeTo provide whole brain grey matter (GM) to white matter (WM) contrast enhanced T1W (T1WE) images, multi-echo quantitative susceptibility mapping (QSM), proton density (PD) weighted images, T1 maps, PD maps, susceptibility weighted imaging (SWI), and R2* maps with minimal misregistration in scanning times <5min. MethodsStrategically acquired gradient echo (STAGE) imaging includes two fully flow compensated double echo gradient echo acquisitions with a resolution of 0.67×1.33×2.0mm3 acquired in 5min for 64 slices. Ten subjects were recruited and scanned at 3 Tesla. The optimum pair of flip angles (6° and 24° with TR=25ms at 3T) were used for both T1 mapping with radio frequency (RF) transmit field correction and creating enhanced GM/WM contrast (the T1WE). The proposed T1WE image was created from a combination of the proton density weighted (6°, PDW) and T1W (24°) images and corrected for RF transmit field variations. Prior to the QSM calculation, a multi-echo phase unwrapping strategy was implemented using the unwrapped short echo to unwrap the longer echo to speed up computation. R2* maps were used to mask deep grey matter and veins during the iterative QSM calculation. A weighted-average sum of susceptibility maps was generated to increase the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR). ResultsThe proposed T1WE image has a significantly improved CNR both for WM to deep GM and WM to cortical GM compared to the acquired T1W image (the first echo of 24° scan) and the T1MPRAGE image. The weighted-average susceptibility maps have 80±26%, 55±22%, 108±33% SNR increases across the ten subjects compared to the single echo result of 17.5ms for the putamen, caudate nucleus, and globus pallidus, respectively. ConclusionsSTAGE imaging offers the potential to create a standardized brain imaging protocol providing four pieces of quantitative tissue property information and multiple types of qualitative information in just 5min.