Gradient-recalled Echo Images Research Articles

Prospective 3D Fat Navigator (FatNav) motion correction for 7T Terra MRI.

Ultra-high field (7T) MRI allows scans at sub-millimetre resolution with exquisite signal-to-noise ratio (SNR). As 7T MRI becomes more widely used clinically, the challenge of patient motion must be overcome. Retrospective motion correction is used successfully for some protocols, but for acquisitions such as slice-by-slice scans only prospective motion correction can deliver the full potential of 7T MRI. We report the first implementation of prospective 3D Fat Navigator ("FatNav") motion correction for the Siemens 7T Terra MRI. We implemented a modular Sequence Building Block for FatNav and embedded it into the vendor's gradient-recalled echo (GRE) sequence. We modified the reconstruction pipeline to reconstruct FatNav images online, coregistering them and sending motion updates to the host sequence online. We tested five registration algorithms for performance and accuracy on synthetic FatNav data. We implemented the best three of these in our sequence and tested them online. We acquired T1 and T2* weighted brain images of healthy volunteers correcting every other image for motion to visualise the effectiveness of online motion correction. Data were acquired with and without head immobilisation. We also tested performance while correcting every measurement for motion. Our implementation uses a 1.23 s 3D FatNav acquisition module and delivers motion updates in less than 3s, which is sufficient for motion updates every few k-space lines in typical scans. Corrected images are crisper with fewer visible motion artefacts. This improved sharpness is reflected quantitatively by an increase in the variance of the image Laplacian which is 1.59 x better for corrected vs uncorrected images. Profiles across the cerebral falx are 33% steeper for corrected vs uncorrected images. Prospective FatNav improves GRE image quality in the brain. Our modular Sequence Building Block provides a simple method to integrate motion correction in 7T MRI pulse sequences.

Role of Magnetic Resonance Spectroscopy and Diffusion-weighted Imaging in the Evaluation of Supratentorial Brain Tumours with Histopathology Correlation at a Tertiary Care Hospital: An Observational Study

Abstract Background: Traditional magnetic resonance imaging (MRI) may face challenges in accurately discerning supratentorial malignancies. However, advanced techniques such as diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) have significantly enhanced diagnostic accuracy. Thus, the study aimed to evaluate the effectiveness of these non-invasive diagnostic methods in patients with suspected intracranial lesions. Materials and Methods: In this prospective observational study at Osmania General and Allied Hospitals, 40 eligible patients were enrolled. After applying the inclusion and exclusion criteria, MRI examinations were conducted at two hospitals utilising GE 1.5T and PHILIPS 1.5T 32-channel machines. Standardised brain sequences, encompassing T1- and T2-weighted scans, DWI, gradient-recalled echo and fluid-attenuated inversion recovery imaging, were systematically performed. In addition, post-contrast administration and contrast-enhanced MRS were employed. Results: In this study, a higher tumour incidence was observed in males (52%) compared to females (48%). The choline/creatine (CHO/Cr) ratio revealed more cases below 1.5 and fewer at the 3.1–3.5 level. Perilesional CHO/Cr ratio had the highest cases (21) at 1.1–2.0 and the lowest (2) at 3.1–4.0. Further analysis revealed significant differences in the mean CHO/Cr ratio amongst primary low-grade (1.8), primary high-grade (3.91) and metastatic tumours (7.23). The mean choline/N-acetyl aspartate (NAA) ratio also differed significantly amongst these tumour types, with choline/NAA and CHO/Cr ratios indicating statistical significance in distinguishing primary low-grade tumours. In addition, mean apparent diffusion coefficient values showed significant differences between primary low-grade tumours (1.1), primary high-grade tumours (0.87) and metastasis (0.855). Conclusion: This study underscores gender-related differences in supratentorial tumour susceptibility and highlights distinct tumour distributions based on grades. These findings emphasise the significance of considering gender, age and histopathological attributes when evaluating supratentorial tumours.

Absence of the Susceptibility Vessel Sign with Cancer-Associated Hypercoagulability-Related Stroke.

The susceptibility vessel sign, a hypointense signal on MR T2-weighted gradient-recalled echo images, is associated with erythrocyte-predominant thrombi, which are often present in cardioembolism. In contrast, cancer-associated hypercoagulability (CAH)-related stroke, which is presumably caused by fibrin-predominant thrombi, is associated with the absence of the susceptibility vessel sign. We hypothesized that the prevalence of the susceptibility vessel sign may be helpful in distinguishing CAH-related stroke from cardioembolism. This study attempted to validate this hypothesis and investigated the usefulness of the susceptibility vessel sign in differentiating CAH-related stroke from cardioembolism. We retrospectively studied patients with both CAH-related stroke (CAH group) and cardioembolism (cardioembolism group) who had major cerebral artery occlusion on MRA that was performed within 6 hours of stroke onset. All patients visited our department from 2015 to 2021. CAH-related stroke was defined as the following: 1) complication of active cancer, 2) pretreatment D-dimer value of >3 μg/mL, 3) multiple vascular territory infarctions, and 4) lack of any other specifically identified causes of stroke. We compared susceptibility vessel sign positivity rates within each group. Multivariable logistic regression analysis was used to assess the association between the absence of the susceptibility vessel sign and CAH-related stroke. Of 691 patients with CAH-related stroke or cardioembolism, major cerebral artery occlusion was observed in 10 patients in the CAH group and 198 patients in the cardioembolism group. The absence of the susceptibility vessel sign was identified in 55 of 208 patients and was significantly more frequent in the CAH group versus the cardioembolism group (90% versus 24%, P < .05). For predicting CAH-related stroke, the absence of the susceptibility vessel sign demonstrated a sensitivity of 90% (95% CI, 59%-99%), specificity of 78% (95% CI, 71%-83%), a positive predictive value of 18% (95% CI, 10-31), a negative predictive value of 99% (95% CI, 96%-99%), and a likelihood ratio of 4.06. Multivariable logistic regression analysis revealed that the absence of the susceptibility vessel sign was independently associated with CAH-related stroke (OR, 43; 95% CI, 6.8-863; P < .01). The absence of the susceptibility vessel sign was more frequent in CAH-related stroke than in cardioembolism. These findings could potentially be helpful for clinical management and differentiating cardioembolism and CAH-related stroke.

T1 signal intensity ratio correlation with T1 mapping in pediatric pancreatitis.

Our primary purpose was to understand the correlation between pancreas T1-weighted signal intensity ratio (SIR) and T1 relaxation time in children. We also sought to characterize differences in T1 SIR between children without and with pancreatitis. Retrospective study of patients < 18-years-old. SIR-pancreas:spleen (SIR-PS) and SIR-pancreas:paraspinal muscle (SIR-PM) were generated from T1-weighted gradient recalled echo images. Subdivided by field strength, T1 SIR was correlated (Spearman's) with T1 relaxation time. 220 participants were included, 144 imaged at 1.5T (mean: 11.4 ± 4.2 years) and 76 imaged at 3T (mean: 10.9 ± 4.5 years). At 1.5T, SIR-PS (rho=-0.62, 95% CI: -0.71 to -0.51, p < 0.0001) and SIR-PM(rho=-0.57, 95% CI: -0.67 to -0.45, p < 0.0001) moderately negatively correlated with T1 relaxation time. At 3T, correlations between T1 SIR and T1 relaxation time were moderate (rho=-0.40 to -0.43, p ≤ 0.0003). SIR-PS was significantly different between patient groups at 1.5T (p < 0.0001) with pairwise differences between: normal vs. acute on chronic pancreatitis (1.52 vs. 1.13; p < 0.0001). SIR-PM was also significantly different between groups at 1.5T (p < 0.0001) with differences between: normal vs. acute pancreatitis (1.65 vs. 1.40; p = 0.0006), normal vs. acute on chronic pancreatitis (1.65 vs. 1.18; p < 0.0001), and normal vs. chronic pancreatitis (1.65 vs. 1.52; p = 0.0066). A SIR-PS cut-off of ≤ 1.31 had 44% sensitivity and 95% specificity and SIR-PM cut-off of ≤ 1.53 had 69% sensitivity and 70% specificity for pancreatitis. At 3T, SIR-PS was significantly different between groups (p = 0.033) but without significant pairwise differences. At 1.5T pancreas T1 SIR moderately to strongly correlates with estimated T1 relaxation time and is significantly lower in children with pancreatitis.

Cerebral microbleeds in acute ischemic stroke after intravenous thrombolysis and their impact on short term outcome of stroke

Objectives Strong evidence suggests the occurrence of cerebral microbleeds (CMBs) in 5–13% of stroke patients within the first week after stroke onset. The aim of this work was to study risk factors associated with occurrence of CMBs in patients with stroke who received intravenous thrombolysis, and to clarify their impact on the clinical outcome. Methods This prospective observational study was conducted on 61 acute ischemic stroke patients eligible for treatment with recombinant tissue plasminogen activator (rt-PA). Assessment of stroke-related neurologic deficit was done using National Institute of Health Stroke Scale (NIHSS). Assessment of stroke related disability after 3 months from stroke onset was done using Modified Rankin Scale (mRS). CMBs were detected by T2*-weighed gradient-recalled echo (T2*-GRE) and susceptibility-weighted imaging (SWI) magnetic resonance imaging (MRI) sequences. Results There was a statistically significant impact of age, mean arterial pressure (MAP) at stroke onset, history of hypertension (HTN), and white matter changes assessed by Fazekas scale on the occurrence of CMBs in the included stroke patients (P-value= 0.002, <0.001, <0.001, 0.008 respectively). There was no statistically significant difference between patients with favorable and those with unfavorable outcome regarding the total number of CMBs (P-value =0.542). There was also no statistically significant difference between patients who developed complications from rt-PA and those who didn’t develop regarding the total number of CMBs (P-value =0.186). Conclusion Cerebral microbleeds are more likely to occur in older stroke patients and in those who had high MAP at stroke onset, history of HTN, and white matter changes.

Exploring the cognitive assessment potential of MRI-based volumetric hippocampal segmentation in Parkinson's disease.

To investigate the potential of magnetic resonance imaging (MRI)-based total and segmental hippocampus volume analysis in the assessment of cognitive status in Parkinson's disease (PD). We divided participants into three groups Group A-Parkinson patients (Pp) with normal cognitive status (n=25), Group B-Pp with dementia (n=17), and Group C-healthy controls (n=37). Three-dimensional T1W Fast Spoiled Gradient Recalled Echo images were used for Volbrain hippocampus subfield segmentation. We used the "Winterburn" protocol, which divides the hippocampus into five segments, Cornu Ammonis (CA),CA2/CA3, CA4/dentate gyrus, stratum radiatum, lacunosum, and moleculare, and subiculum. A total of 79 participants were included in the study, consisting of 42 individuals with PD (64.2% male) and 37 healthy controls (54.1% male). The mean age of PD was 60.9±10.7 years and the mean age of control group was 59.27±12.3 years. Significant differences were found in total hippocampal volumes between Group A and B (p=.047. Statistically significant group differences were found in total, right, and left CA1 volumes (analysis of variance [ANOVA]: F(2,76)=8.098, p=.001; F(2,76)=7.628, p=.001; F(2,76)=5.084, p=.008, respectively), as well as in total subiculum volumes (ANOVA: F(2,76)=4.368, p=.016). Post hoc tests showed that total subiculum volume was significantly lower in individuals with normal cognitive status (0.474±0.116cm3) compared to healthy controls (0.578±0.151cm3, p=.013). Volumetric hippocampal MRI can be used to assess the cognitive status of Pp. Longitudinal studies that evaluate Pp who progress from normal cognition to dementia are required to establish a causal relationship.

Implementation of Oxygen Enhanced Magnetic Resonance Imaging (OE-MRI) and a Pilot Genomic Study of Hypoxia in Bladder Cancer Xenografts.

Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery. The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm3) or large (700 mm3) tumours were imaged, breathing air then 100% O2, 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N2, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays. Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour. OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.

Precision and Test-Retest Repeatability of Stiffness Measurement with MR Elastography: A Multicenter Phantom Study.

Background MR elastography (MRE) has been shown to have excellent performance for noninvasive liver fibrosis staging. However, there is limited knowledge regarding the precision and test-retest repeatability of stiffness measurement with MRE in the multicenter setting. Purpose To determine the precision and test-retest repeatability of stiffness measurement with MRE across multiple centers using the same phantoms. Materials and Methods In this study, three cylindrical phantoms made of polyvinyl chloride gel mimicking different degrees of liver stiffness in humans (phantoms 1-3: soft, medium, and hard stiffness, respectively) were evaluated. Between January 2021 and January 2022, phantoms were circulated between five different centers and scanned with 10 MRE-equipped clinical 1.5-T and 3-T systems from three major vendors, using two-dimensional (2D) gradient-recalled echo (GRE) imaging and/or 2D spin-echo (SE) echo-planar imaging (EPI). Similar MRE acquisition parameters, hardware, and reconstruction algorithms were used at each center. Mean stiffness was measured by a single observer for each phantom and acquisition on a single section. Stiffness measurement precision and same-session test-retest repeatability were assessed using the coefficient of variation (CV) and the repeatability coefficient (RC), respectively. Results The mean precision represented by the CV was 5.8% (95% CI: 3.8, 7.7) for all phantoms and both sequences combined. For all phantoms, 2D GRE achieved a CV of 4.5% (95% CI: 3.3, 5.7) whereas 2D SE EPI achieved a CV of 7.8% (95% CI: 3.1, 12.6). The mean RC of stiffness measurement was 5.8% (95% CI: 3.7, 7.8) for all phantoms and both sequences combined, 4.9% (95% CI: 2.7, 7.0) for 2D GRE, and 7.0% (95% CI: 2.9, 11.2) for 2D SE EPI (all phantoms). Conclusion MRE had excellent in vitro precision and same-session test-retest repeatability in the multicenter setting when similar imaging protocols, hardware, and reconstruction algorithms were used. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Tang in this issue.

Magnetic resonance imaging subtraction vs. pre- and post-contrast 3D gradient recalled echo fat suppressed imaging for evaluation of the canine and feline brain.

Subtraction magnetic resonance imaging (MRI) has been reported to increase accuracy in the diagnosis of meningeal and inflammatory brain diseases in small animals. 3D T1W gradient recalled echo (GRE) techniques have been proposed as a suitable alternative to conventional spin echo sequences in imaging the canine brain. The aim of this study was to compare subtraction images and paired pre- and post-contrast 3D T1W GRE fat suppressed (FS) images in canine and feline MRI studies using clinical diagnosis as the gold standard. Paired pre- and post-contrast T1W 3D FS GRE images and individual subtraction images of 100 small animal patients were randomized and independently evaluated by 2 blinded observers. Diagnosis categories were "normal," "inflammatory," "neoplastic," and "other." Clinical diagnosis was made in the same categories and served as the gold standard. Image interpretation results were compared to the clinical diagnosis. Interobserver agreement was determined. Clinically, 41 studies were categorized as "normal," 18 as "inflammatory," 28 as "neoplastic," and 13 as "other." The agreement of the pre- and post-contrast GRE images with the gold standard was significantly higher than that of the subtraction images (k = 0.7491 vs. k = 0.5924; p = 0.0075). The largest sources of error were misinterpretation of "other" as "normal" and "normal" as "inflammatory." There was no significant difference between the two observers (p = 0.8820). Based on this study, subtraction images do not provide an advantage to paired pre- and post-contrast FS GRE images when evaluating the canine and feline brain.

Enhancing the brain MRI at ultra-high field systems using a meta-array structure.

The main advantage of ultra-high field (UHF) magnetic resonance neuroimaging is theincreased signal-to-noise ratio (SNR) compared with lower field strength imaging. However, the wavelength effect associated with UHF MRI results in radiofrequency (RF) inhomogeneity, compromising whole brain coverage for many commercial coils. Approaches to resolving this issue of transmit field inhomogeneity include the design of parallel transmit systems (PTx), RF pulse design, and applying passive RF shimming such as high dielectric materials. However, these methods have some drawbacks such as unstable material parameters of dielectric pads, high-cost, and complexity of PTx systems. Metasurfaces are artificial structures with a unique platform that can control the propagation of the electromagnetic (EM) waves, and they are very promising for engineering EM device. Implementation of meta-arrays enhancing MRI has been explored previously in several studies. The aim of this study was to assess the effect of new meta-array technology on enhancing the brain MRI at 7T. A meta-array based on a hybrid structure consisting of an array of broadside-coupled split-ring resonators and high-permittivity materials was designed to work at the Larmor frequency of a 7 Tesla (7T) MRI scanner. When placed behind the head and neck, this construct improves the SNR in the region of the cerebellum,brainstem and the inferior aspect of the temporal lobes. Numerical electromagnetic simulations were performed to optimize the meta-array design parameters and determine the RF circuit configuration. The resultant transmit-efficiency and signal sensitivity improvements were experimentally analyzed in phantoms followed by healthy volunteers using a 7T whole-body MRI scanner equipped with a standard one-channel transmit, 32-channel receive head coil. Efficacy was evaluated through acquisition with and without the meta-array using two basic sequences: gradient-recalled-echo (GRE) and turbo-spin-echo (TSE). Experimental phantom analysis confirmed two-fold improvement in the transmit efficiency and 1.4-fold improvement in the signal sensitivity in the target region. In vivo GRE and TSE images with the meta-array in place showed enhanced visualization in inferior regions of the brain, especially of the cerebellum, brainstem, and cervical spinal cord. Addition of the meta-array to commonly used MRI coils can enhance SNR to extend the anatomical coverage of the coil and improve overall MRI coil performance. This enhancement in SNR can be leveraged to obtain a higher resolution image over the same time slot or faster acquisition can be achieved with same resolution. Using this technique could improve the performance of existing commercial coils at 7T for whole brain and other applications.

MRI-based quantification of whole-organ renal metabolic rate of oxygen.

During the early stages of diabetes, kidney oxygen utilization increases. The mismatch between oxygen demand and supply contributes to tissue hypoxia, a key driver of chronic kidney disease. Thus, whole-organ renal metabolic rate of oxygen (rMRO2 ) is a potentially valuable biomarkerof kidney function. The key parameters required to determine rMRO2 include the renal blood flow rate (RBF) in the feeding artery and oxygen saturation in the draining renal vein (SvO2 ). However, there is currently no noninvasive method to quantify rMRO2 in absolute physiologic units. Here, a new MRI pulse sequence, Kidney Metabolism of Oxygen via T2 and Interleaved Velocity Encoding (K-MOTIVE), is described, along with evaluation of its performance in the human kidney in vivo. K-MOTIVE interleaves a phase-contrast module before a background-suppressed T2 -prepared balanced steady-state-free-precession (bSSFP) readout to measure RBF and SvO2 in a single breath-hold period of 22 s, yielding rMRO2 via Fick's principle. Variants of K-MOTIVE to evaluate alternative bSSFP readout strategies were studied. Kidney mass was manually determined from multislice gradient recalled echo images. Healthy subjects were recruited to quantify rMRO2 of the left kidney at 3-T field strength (N= 15). Assessments of repeat reproducibility and comparisons with individual measurements of RBF and SvO2 were performed, and the method's sensitivity was evaluated with a high-protein meal challenge (N= 8). K-MOTIVE yielded the following metabolic parameters: T2 = 157 ± 19 ms; SvO2 = 92% ± 6%; RBF = 400 ± 110 mL/min; and rMRO2 = 114 ± 117(μmol O2 /min)/100 g tissue. Reproducibility studies of T2 and RBF (parameters directly measured by K-MOTIVE) resulted in coefficients of variation less than 10% and intraclass correlation coefficients more than 0.75. The high-protein meal elicited an increase in rMRO2 , which was corroborated by serum biomarkers. The K-MOTIVE sequence measures SvO2 and RBF, the parameters necessary to quantify whole-organ rMRO2 , in a single breath-hold. The present work demonstrates that rMRO2 quantification is feasible with good reproducibility. rMRO2 is a potentially valuable physiological biomarker.

Functional and Morphological Brain Alterations in Dysthyroid Optic Neuropathy: A Combined Resting-State fMRI and Voxel-Based Morphometry Study.

Increasing evidence has indicated that the entire visual pathway from retina to visual cortex may be involved in dysthyroid optic neuropathy (DON) pathological mechanisms. To explore the functional and morphological brain characteristics in DON and their relationship with ophthalmologic performance. Retrospective. A total of 30 DON patients, 40 thyroid-associated ophthalmopathy (TAO) without DON patients and 21 healthy-controls (HCs). A 3.0 T, 3D T1-weighted spoiled gradient-recalled echo and gradient-recalled echo-planar imaging. Functional and structural alterations in brain regions were evaluated with fractional amplitude of low-frequency fluctuations, degree centrality (DC), and gray matter volume (GMV). Clinical activity score (CAS) is assessed across patients. One-way analysis of variance with post hoc two sample t-tests (GRF-corrected, voxel level: P< 0.005, cluster level: P< 0.05) and correlation analysis (significance level: P< 0.05). Compared to HCs, DON patients had significantly decreased DC values in the bilateral BA17 and BA18 regions. Compared to the TAO group, DON patients had decreased GMV in the left anterior cingulate cortex, left middle frontal gyrus, left lingual gyrus, left parietal gyrus, right Rolandic operculum, left supplementary motor area, and right middle temporal gyrus. In addition, GMV in the right Rolandic operculum was significantly positively correlated with CAS (correlation coefficient: r= 0.448). This study showed significant morphological and functional alterations in visual cortex and morphological alterations in partial default mode network regions of DON patients, which may provide insights into the mechanism of vision loss and may facilitate the diagnosis and treatment of DON. 3. Stage 3.

Quantitative Susceptibility Mapping of Brain Iron Deposition in Patients With Recurrent Depression.

Objective Recurrence is the most significant feature of depression and the relationship between iron and recurrent depression is still lack of direct evidence in vivo. Methods Twenty-one patients with depression and twenty control subjects were included. Gradient-recalled echo, T1 and T2 images were acquired using a 3.0T MRI system. After quantitative susceptibility mapping were reconstructed and standardized, a whole-brain and the regions of interest were respectively analyzed. Results Significant increases in susceptibility were found in multiple recurrent depression patients, which involved several brain regions (frontal lobes, temporal lobe structures, occipital lobes hippocampal regions, putamen, thalamus, cingulum, and cerebellum). Interestingly, no susceptibility changes after treatment compared to pre-treatment (all p>0.05) and no significant correlation between susceptibility and Hamilton Depression Rating Scale were found. Besides, it was close to significance that those with a higher relapse frequency or a longer mean duration of single episode had a higher susceptibility in the putamen, thalamus, and hippocampus. Further studies showed susceptibility across the putamen (ρ2=0.27, p<0.001), thalamus (ρ2=0.21, p<0.001), and hippocampus (ρ2=0.19, p<0.001) were strongly correlated with total course of disease onset. Conclusion Brain iron deposition is related to the total course of disease onset, but not the severity of depression, which suggest that brain iron deposition may be a sign of brain damage in multiple recurrent depression.

Multi-echo quantitative susceptibility mapping: how to combine echoes for accuracy and precision at 3 Tesla.

PurposeTo compare different multi‐echo combination methods for MRI QSM. Given the current lack of consensus, we aimed to elucidate how to optimally combine multi‐echo gradient‐recalled echo signal phase information, either before or after applying Laplacian‐base methods (LBMs) for phase unwrapping or background field removal.MethodsMulti‐echo gradient‐recalled echo data were simulated in a numerical head phantom, and multi‐echo gradient‐recalled echo images were acquired at 3 Tesla in 10 healthy volunteers. To enable image‐based estimation of gradient‐recalled echo signal noise, 5 volunteers were scanned twice in the same session without repositioning. Five QSM processing pipelines were designed: 1 applied nonlinear phase fitting over TEs before LBMs; 2 applied LBMs to the TE‐dependent phase and then combined multiple TEs via either TE‐weighted or SNR‐weighted averaging; and 2 calculated TE‐dependent susceptibility maps via either multi‐step or single‐step QSM and then combined multiple TEs via magnitude‐weighted averaging. Results from different pipelines were compared using visual inspection; summary statistics of susceptibility in deep gray matter, white matter, and venous regions; phase noise maps (error propagation theory); and, in the healthy volunteers, regional fixed bias analysis (Bland–Altman) and regional differences between the means (nonparametric tests).ResultsNonlinearly fitting the multi‐echo phase over TEs before applying LBMs provided the highest regional accuracy of χ and the lowest phase noise propagation compared to averaging the LBM‐processed TE‐dependent phase. This result was especially pertinent in high‐susceptibility venous regions.ConclusionFor multi‐echo QSM, we recommend combining the signal phase by nonlinear fitting before applying LBMs.

A Multifunctional Contrast Agent for 19F-Based Magnetic Resonance Imaging.

Magnetic resonance imaging, MRI, relying on 19F nuclei has attracted much attention, because the isotopes exhibit a high gyromagnetic ratio (comparable to that of protons) and have 100% natural abundance. Furthermore, due to the very low traces of intrinsic fluorine in biological tissues, fluorine labeling allows easy visualization in vivo using 19F-based MRI. However, one of the drawbacks of the available fluorine tracers is their very limited solubility in water. Here, we detail the design and preparation of a set of water-compatible fluorine-rich polymers as contrast agents that can enhance the effectiveness of 19F-based MRI. The agents are synthesized using the nucleophilic addition reaction between poly(isobutylene-alt-maleic anhydride) copolymer and a mixture of amine-appended fluorine groups and polyethylene glycol (PEG) blocks. This allows control over the polymer architecture and stoichiometry, resulting in good affinity to water solutions. We further investigate the effects of introducing additional segmental mobility to the fluorine moieties in the polymer, by inserting a PEG linker between the moieties and the polymer backbone. We find that controlling the polymer stoichiometry and introducing additional segmental mobility enhance the NMR signals and narrow the peak profile. In particular, we assess the impact of the PEG linker on T2* and T1 relaxation times, using a series of gradient-recalled echo images with varying echo times, TE, or recovery time, TR, respectively. We find that for equivalent concentrations, the PEG linker greatly increases T2*, while maintaining high T1 values, as compared to polymers without this linker. Phantom images collected from these compounds show bright signals over a background with high intensities.

T1 mapping as a surrogate marker of chemotherapy response evaluation in patients with osteosarcoma

ObjectivesTo characterize baseline T1 values of tumors, measure changes after the course of chemotherapy, and evaluate its potential as a marker of response assessment in patients with osteosarcoma. Materials and MethodsA total of 35 patients (male:female = 27:8; age = 17.9 ± 6 years; metastatic:localized = 11:24) with biopsy-proven osteosarcoma were analyzed prospectively. All patients underwent magnetic resonance imaging before neoadjuvant chemotherapy (NACT) (baseline) and after NACT completion (follow-up), followed by surgery and histopathological evaluation. Histopathological necrosis served as the gold standard for assessing chemotherapy response (responder: ≥50% necrosis and non-responder: <50% necrosis). Three-dimensional spoiled gradient recalled echo images were acquired with varying flip angles (50, 100, 200, and 300) using a 1.5 Tesla scanner. T1 values were estimated in healthy muscle tissue and tumors at baseline and follow-up, and the relative percentage changes after NACT (ΔT1) were evaluated, and histogram analysis was performed to characterize the T1 value of the tumor and predict the NACT response using the Pearson correlation coefficient (r) and receiver operating characteristic curve analysis. ResultsAt baseline, a significantly higher T1-mean (830.96 ± 193.88 msec versus 683.29 ± 210.00 msec; p = 0.003) and lower T1-skewness (0.86 ± 1.66 versus 1.60 ± 1.55; p = 0.02) were observed in osteosarcoma than healthy tissue. Responder:non-responder ratio was 13:22. At baseline, a significantly higher T1-mean (936.14 ± 193.17 msec versus 768.82 ± 169.25 msec; p = 0.018) and lower T1-skewness (-0.17 ± 0.85 versus 1.47 ± 1.73; p = 0.003) were observed among responders, than non-responders. After NACT, ΔT1 in tumor was significantly higher among responders than non-responders (-27.22 ± 12.17% versus −15.70 ± 18.99%; p = 0.034). ΔT1-mean and ΔT1-skewness after NACT were moderately correlated (r = − 0.4, p = 0.030; r = 0.4, p = 0.011) with histopathological necrosis. For predicting NACT response, T1-mean and T1-skewness jointly produced an area under the curve (AUC) = 0.80 at baseline, and ΔT1-mean and ΔT1-skewness jointly produced AUC = 0.76 after NACT. ConclusionThe mean and skewness of T1 values in osteosarcoma are potential non-invasive imaging markers for chemotherapy response assessment.

Quantitative analysis of the ACL and PCL using T1rho and T2 relaxation time mapping: an exploratory, cross-sectional comparison between OA and healthy control knees

BackgroundQuantitative magnetic resonance imaging (MRI) methods such as T1rho and T2 mapping are sensitive to changes in tissue composition, however their use in cruciate ligament assessment has been limited to studies of asymptomatic populations or patients with posterior cruciate ligament tears only. The aim of this preliminary study was to compare T1rho and T2 relaxation times of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) between subjects with mild-to-moderate knee osteoarthritis (OA) and healthy controls.MethodsA single knee of 15 patients with mild-to-moderate knee OA (Kellgren-Lawrence grades 2–3) and of 6 age-matched controls was imaged using a 3.0 T MRI. Three-dimensional (3D) fat-saturated spoiled gradient recalled-echo images were acquired for morphological assessment and T1ρ- and T2-prepared pseudo-steady-state 3D fast spin echo images for compositional assessment of the cruciate ligaments. Manual segmentation of whole ACL and PCL, as well as proximal / middle / distal thirds of both ligaments was carried out by two readers using ITK-SNAP and mean relaxation times were recorded. Variation between thirds of the ligament were assessed using repeated measures ANOVAs and differences in these variations between groups using a Kruskal-Wallis test. Inter- and intra-rater reliability were assessed using intraclass correlation coefficients (ICCs).ResultsIn OA knees, both T1rho and T2 values were significantly higher in the distal ACL when compared to the rest of the ligament with the greatest differences in T1rho (e.g. distal mean = 54.5 ms, proximal = 47.0 ms, p < 0.001). The variation of T2 values within the PCL was lower in OA knees (OA: distal vs middle vs proximal mean = 28.5 ms vs 29.1 ms vs 28.7 ms, p = 0.748; Control: distal vs middle vs proximal mean = 26.4 ms vs 32.7 ms vs 33.3 ms, p = 0.009). ICCs were excellent for the majority of variables.ConclusionT1rho and T2 mapping of the cruciate ligaments is feasible and reliable. Changes within ligaments associated with OA may not be homogeneous. This study is an important step forward in developing a non-invasive, radiological biomarker to assess the ligaments in diseased human populations in-vivo.

MR elastography in patients with suspected diffuse liver disease at 1.5T: Intraindividual comparison of gradient-recalled echo versus spin-echo echo-planar imaging sequences and investigation of potential confounding factors

PurposeTo compare liver stiffness (LS) in patients with suspected diffuse liver disease between gradient-recalled-echo magnetic resonance elastography (GRE-MRE) and different spin-echo echo-planar imaging (SE-EPI-MRE) sequences and to investigate confounding factors including fat, iron, age, and sex. MethodLS was measured at 1.5T using GRE-MRE, SE-EPI-MRE and short-TE-SE-EPI-MRE (hiSE-EPI-MRE) sequences and compared using Bland-Altman-plots together with concordance correlation coefficients (CCC). Success gradings were evaluated considering possible confounding factors. Results305 patients (225 male, 80 females, mean age 51.12 years) were included. 109/305 showed hepatic iron overload, 183 hepatic steatosis. The mean difference (bias) in stiffness values between GRE-MRE and SE-EPI-MRE/hiSE-EPI-MRE was 0.15/0.2 kPa (LOA: −0.72,0.41 kPa/-0.94,0.55 kPa), between SE-EPI-MRE and hiSE-EPI-MRE 0.04 kPa (LOA: −0.62,0.53 kPa). The CCC for agreement between stiffness values for GRE-MRE and SE-EPI-MRE was 0.94 (0.92–0.95), 0.89 (0.86–0.91) for hiSE-EPI-MRE and GRE-MRE and 0.94 (0.92–0.95) for SE-EPI-MRE and hiSE-EPI-MRE. Using GRE-MRE, 72/305 showed unusable results whereby all these patients had high iron levels (mean R2*=209.7 1/s). For SE-EPI-MRE and hiSE-EPI-MRE only 10/305 and 8/305 were inconclusive respectively, corresponding to a significantly higher iron load (mean R2*= 549.2 1/s for SE-EPI-MRE and 570.7 1/s for hiSE-EPI-MRE). Concerning fat, age or sex no significant influence on success was observed for all sequences. ConclusionsGood agreement of LS values was observed between GRE-MRE and SE-EPI-MRE sequences. The number of successful exams, however, was considerably lower for GRE-MRE, mainly due to iron content.Study reference number: AN5093.

Reader Response: Critical Illness-Associated Cerebral Microbleeds in COVID-19 Acute Respiratory Distress Syndrome.

We read with great interest the report by Cannac et al.,1 which adds to a rapidly growing body of evidence that severe COVID-19 is associated with cerebral microvascular lesions.2 However, we caution against the assumption that the observed lesions solely represent microhemorrhages. Although lesions showing a susceptibility effect on T2*-weighted gradient-recalled echo imaging often indicate microhemorrhages,3 the differential diagnosis for these lesions also includes microthrombi and air emboli, the latter being common in patients treated with extracorporeal membrane oxygenation (ECMO), as in the patient reported here. Indeed, in a patient with similar susceptibility lesions in the setting of H1N1 influenza treated with ECMO, postmortem histopathologic analysis revealed that many lesions corresponded to microinfarcts, not microhemorrhages.4

Frequency, Determinants, and Outcomes of Emboli to Distal and New Territories Related to Mechanical Thrombectomy for Acute Ischemic Stroke.

Clot fragmentation and distal embolization during endovascular thrombectomy for acute ischemic stroke may produce emboli downstream of the target occlusion or in previously uninvolved territories. Susceptibility-weighted magnetic resonance imaging can identify both emboli to distal territories (EDT) and new territories (ENT) as new susceptibility vessel signs (SVS). Diffusion-weighted imaging (DWI) can identify infarcts in new territories (INT). We studied consecutive acute ischemic stroke patients undergoing magnetic resonance imaging before and after thrombectomy. Frequency, predictors, and outcomes of EDT and ENT detected on gradient-recalled echo imaging (EDT-SVS and ENT-SVS) and INT detected on DWI (INT-DWI) were analyzed. Among 50 thrombectomy-treated acute ischemic stroke patients meeting study criteria, mean age was 70 (±16) years, 44% were women, and presenting National Institutes of Health Stroke Scale score 15 (interquartile range, 8–19). Overall, 21 of 50 (42%) patients showed periprocedural embolic events, including 10 of 50 (20%) with new EDT-SVS, 10 of 50 (20%) with INT-DWI, and 1 of 50 (2%) with both. No patient showed ENT-SVS. On multivariate analysis, model-selected predictors of EDT-SVS were lower initial diastolic blood pressure (odds ratio, 1.09 [95% CI, 1.02–1.16]), alteplase pretreatment (odds ratio, 5.54 [95% CI, 0.94–32.49]), and atrial fibrillation (odds ratio, 7.38 [95% CI, 1.02–53.32]). Classification tree analysis identified pretreatment target occlusion SVS as an additional predictor. On univariate analysis, INT-DWI was less common with internal carotid artery (5%), intermediate with middle cerebral artery (25%), and highest with vertebrobasilar (57%) target occlusions (P=0.02). EDT-SVS was not associated with imaging/functional outcomes, but INT-DWI was associated with reduced radiological hemorrhagic transformation (0% versus 54%; P<0.01). Among acute ischemic stroke patients treated with thrombectomy, imaging evidence of distal emboli, including EDT-SVS beyond the target occlusion and INT-DWI in novel territories, occur in about 2 in every 5 cases. Predictors of EDT-SVS are pretreatment intravenous fibrinolysis, potentially disrupting thrombus structural integrity; atrial fibrillation, possibly reflecting larger target thrombus burden; lower diastolic blood pressure, suggestive of impaired embolic washout; and pretreatment target occlusion SVS sign, indicating erythrocyte-rich, friable target thrombus.