Magnetization-prepared Rapid Acquisition Gradient Echo Research Articles

MRI-Derived AD Signature of Cortical Thinning and Plasma P-Tau217 for Predicting Alzheimer Dementia Among Community-Dwelling Older Adults.

Structural brain MRI and blood-based phosphorylated tau (p-tau) measures are among the least invasive and least expensive Alzheimer's disease (AD) biomarkers to date. The extent to which these biomarkers may outperform one another in predicting future Alzheimer dementia diagnosis is poorly understood, however. This study investigated 2 specific AD biomarkers, i.e., a cortical thickness signature of AD (AD-CT) and plasma p-tau217, for predicting Alzheimer dementia. Data came from community-dwelling older participants of the Religious Orders Study or the Rush Memory and Aging Project. AD-CT was obtained from 3T MRI scans using a magnetization-prepared rapid acquisition gradient echo sequence and by averaging thickness from previously identified cortical regions implicated in AD. Plasma p-tau217 was quantified using an immunoassay developed by Lilly Research Laboratories on the MSD platform. Both MRI scans and blood specimens were collected at the same visits, and subsequent diagnoses of Alzheimer dementia were determined through annual detailed clinical evaluations. Cox proportional hazards models examined the associations of the 2 biomarkers with incident Alzheimer dementia, and prediction accuracy was assessed using c-statistics. A total of 198 older adults, on average 84 years of age, were included. Over a mean follow-up of 4 years, 60 (30%) individuals developed Alzheimer dementia. AD-CT (hazard ratio: 1.71, 95% CI 1.26-2.31) and separately plasma p-tau217 (hazard ratio: 2.57, 95% CI 1.83-3.61) were associated with incident Alzheimer dementia. The c-statistic for prediction accuracy was consistently higher for plasma p-tau217 (between 0.74 and 0.81) than AD-CT (between 0.70 and 0.75) across a range of time horizons. Furthermore, with both biomarkers included in the same model, there was only modest improvement in the c-statistic due to AD-CT. Plasma p-tau217 outperforms an imaging-based cortical thickness signature of AD in predicting future Alzheimer dementia diagnosis. Furthermore, the AD cortical thickness signature adds little to the prediction accuracy above and beyond plasma p-tau217.

Structural changes in spinal cord following optic neuritis: Insights from quantitative spinal MRI

ObjectivesPrevious studies have demonstrated that optic neuritis (ON) affects brain plasticity. However, whether ON affects the spinal cord remains unclear. We aimed to investigate the spinal cord changes in ON and their associations with disability. MethodsA total of 101 ON patients, and 41 healthy controls (HC) were retrospectively recruited. High-resolution imaging was conducted using a Magnetization Prepared Rapid Acquisition Gradient-Echo (MP-RAGE) sequence for T1-weighted images and an echo planar imaging (EPI) sequence for Diffusion Tensor Imaging (DTI) data collection. Additionally, patients' disability and cognitive impairment were evaluated using the Expanded Disability Status Scale (EDSS) and the Paced Auditory Serial Addition Test (PASAT), respectively. The quantitative spinal MRI was employed to examine the cross-sectional area (CSA) and diffusion indicators, with a specific focus on calculating the average values across the C2-C7 cervical spinal cord segments. CSA, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between groups. Correlation analyses were performed between CSA, diffusion indicators, and clinical variables. ResultsNo significant differences were found in CSA between ON patients and HCs. MD (p = 0.007) and RD (p = 0.018) were increased in ON patients compared with HCs, and AD was decreased in ON (p = 0.013). The AD values of the ON patients were significantly positively correlated with PASAT scores (r = 0.37, p < 0.001). ConclusionsThis study provided imaging evidence for DTI abnormalities in patients with ON. Spinal cord DTI can improve our knowledge of the path physiology of ON, and clinical progression.

Pseudo-Label Assisted nnU-Net enables automatic segmentation of 7T MRI from a single acquisition.

Automatic whole brain and lesion segmentation at 7T presents challenges, primarily from bias fields, susceptibility artifacts including distortions, and registration errors. Here, we sought to use deep learning algorithms (D/L) to do both skull stripping and whole brain segmentation on multiple imaging contrasts generated in a single Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) acquisition on participants clinically diagnosed with multiple sclerosis (MS), bypassing registration errors. Brain scans Segmentation from 3T and 7T scanners were analyzed with software packages such as FreeSurfer, Classification using Derivative-based Features (C-DEF), nnU-net, and a novel 3T-to-7T transfer learning method, Pseudo-Label Assisted nnU-Net (PLAn). 3T and 7T MRIs acquired within 9 months from 25 study participants with MS (Cohort 1) were used for training and optimizing. Eight MS patients (Cohort 2) scanned only at 7T, but with expert annotated lesion segmentation, was used to further validate the algorithm on a completely unseen dataset. Segmentation results were rated visually by experts in a blinded fashion and quantitatively using Dice Similarity Coefficient (DSC). Of the methods explored here, nnU-Net and PLAn produced the best tissue segmentation at 7T for all tissue classes. In both quantitative and qualitative analysis, PLAn significantly outperformed nnU-Net (and other methods) in lesion detection in both cohorts. PLAn's lesion DSC improved by 16% compared to nnU-Net. Limited availability of labeled data makes transfer learning an attractive option, and pre-training a nnUNet model using readily obtained 3T pseudo-labels was shown to boost lesion detection capabilities at 7T.

Gray Matter Thickness and Subcortical Nuclear Volume in Men After SARS-CoV-2 Omicron Infection

The clinical manifestations and effects on the brain of the SARS-CoV-2 Omicron variant in the acute postinfection phase remain unclear. To investigate the pathophysiological mechanisms underlying clinical symptoms and changes to gray matter and subcortical nuclei among male patients after Omicron infection and to provide an imaging basis for early detection and intervention. In this cohort study, a total of 207 men underwent health screening magnetic resonance imaging scans between August 28 and September 18, 2022; among them, 98 provided complete imaging and neuropsychiatric data. Sixty-one participants with Omicron infection were reevaluated after infection (January 6 to 14, 2023). Neuropsychiatric data, clinical symptoms, and magnetic resonance imaging data were collected in the acute post-Omicron period, and their clinical symptoms were followed up after 3 months. Gray matter indexes and subcortical nuclear volumes were analyzed. Associations between changes in gray matter and neuropsychiatric data were evaluated with correlation analyses. Gray matter thickness and subcortical nuclear volume change data were compared before and after Omicron infection. The gray matter indexes and subcutaneous nuclear volume were generated from the 3-dimensional magnetization-prepared rapid acquisition gradient echo and were calculated with imaging software. Ninety-eight men underwent complete baseline data collection; of these, 61 (mean [SD] age, 43.1 [9.9] years) voluntarily enrolled in post-Omicron follow-up and 17 (mean [SD] age, 43.5 [10.0] years) voluntarily enrolled in 3-month follow-up. Compared with pre-Omicron measures, Beck Anxiety Inventory scores were significantly increased (median, 4.50 [IQR, 1.00-7.00] to 4.00 [IQR, 2.00-9.75]; P = .006) and depressive distress scores were significantly decreased (median, 18.00 [IQR, 16.00-20.22] to 16.00 [IQR, 15.00-19.00]; P = .003) at the acute post-Omicron follow-up. Fever, headache, fatigue, myalgia, cough, and dyspnea were the main symptoms during the post-Omicron follow-up; among the participants in the 3-month follow-up, fever (11 [64.7%] vs 2 [11.8%]; P = .01), myalgia (10 [58.8%] vs 3 (17.6%]; P = .04), and cough (12 [70.6%] vs 4 [23.5%]; P = .02) were significantly improved. The gray matter thickness in the left precuneus (mean [SD], 2.7 [0.3] to 2.6 [0.2] mm; P < .001) and right lateral occipital region (mean [SD], 2.8 [0.2] to 2.7 [0.2] and 2.5 [0.2] to 2.5 [0.2] mm; P < .001 for both) and the ratio of the right hippocampus volume to the total intracranial volume (mean [SD]. 0.003 [0.0003] to 0.003 [0.0002]; P = .04) were significantly reduced in the post-Omicron follow-up. The febrile group had reduced sulcus depth of the right inferior parietal region compared with the nonfebrile group (mean [SD], 3.9 [2.3] to 4.8 [1.1]; P = .048. In the post-Omicron period, the thickness of the left precuneus was negatively correlated with the Beck Anxiety Inventory scores (r = -0.39; P = .002; false discovery rate P = .02), and the ratio of the right hippocampus to the total intracranial volume was positively correlated with the Word Fluency Test scores (r = 0.34; P = .007). In this cohort study of male patients infected with the Omicron variant, the duration of symptoms in multiple systems after infection was short. Changes in gray matter thickness and subcortical nuclear volume injury were observed in the post-Omicron period. These findings provide new insights into the emotional and cognitive mechanisms of an Omicron infection, demonstrate its association with alterations to the nervous system, and verify an imaging basis for early detection and intervention of neurological sequelae.

Black-Blood Magnetization Prepared 2 Rapid Acquisition Gradient Echoes: A Fast and Three-Dimensional MR Black-Blood T1 Mapping Technique for Quantitative Assessment of Atherosclerosis and Venous Thrombosis.

Blood flow signals may be a confounder in quantifying T1 values of plaque or thrombus and how to realize black-blood T1 mapping remains a challenge task. To develop a fast and three-dimensional black-blood T1 mapping technique for quantitative assessment of atherosclerosis and venous thrombosis. Sequence development and optimization via phantoms and volunteers as well as pilot prospective. Numerical simulations, a standard phantom, 8 healthy volunteers (mean age, 22 ± 1 years; 5 males), and 19 patients (mean age, 57 ± 14 years; 13 males) with atherosclerosis or venous thrombosis. 3T/inversion recovery spin-echo sequence (IR-SE), magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE), and black-blood prepared MP2RAGE (BB-MP2RAGE). The black-blood preparation (i.e., delay alternating with nutation for tailored excitation, DANTE) was incorporated into MP2RAGE for black-blood T1 mapping. The BB-MP2RAGE was optimized numerically based on the Bloch equation, and then the phantom study was performed to verify the accuracy of T1 mapping by BB-MP2RAGE against IR-SE and MP2RAGE. Preliminary clinical validation was prospectively performed to assess the flow suppression effect and its potential application in plaque and thrombosis identification. Pearson correlation test, Bland-Altman analysis, paired t-test, and intraclass correlation coefficient. A P value <0.05 indicates a statistically significant difference. Phantom experiments showed comparable accuracy of T1 maps by BB-MP2RAGE with IR-SE and MP2RAGE (all r2 > 0.99); Compared to MP2RAGE, BB-MP2RAGE effectively nulled the blood flow signals, and had a significant improvement in contrast-to-noise ratio between static tissue and blood (250.5 ± 66.6 vs. 91.9 ± 35.9). BB-MP2RAGE can quantify plaque or thrombus T1 relaxation time with blood flow signal suppression. Accurate T1 mapping with sufficient blood flow suppression was achieved by BB-MP2RAGE. BB-MP2RAGE has the potential to quantitatively characterize atherosclerosis and venous thrombosis. 1 TECHNICAL EFFICACY: Stage 1.

MRI motion artifact reduction using a conditional diffusion probabilistic model (MAR-CDPM).

High-resolution magnetic resonance imaging (MRI) with excellent soft-tissue contrast is a valuable tool utilized for diagnosis and prognosis. However, MRI sequences with long acquisition time are susceptible to motion artifacts, which can adversely affect the accuracy of post-processingalgorithms. This study proposes a novel retrospective motion correction method named "motion artifact reduction using conditional diffusion probabilistic model" (MAR-CDPM). The MAR-CDPM aimed to remove motion artifacts from multicenter three-dimensional contrast-enhanced T1 magnetization-prepared rapid acquisition gradient echo (3D ceT1 MPRAGE) brain dataset with different brain tumor types. This study employed two publicly accessible MRI datasets: one containing 3D ceT1 MPRAGE and 2D T2-fluid attenuated inversion recovery (FLAIR) images from 230 patients with diverse brain tumors, and the other comprising 3D T1-weighted (T1W) MRI images of 148 healthy volunteers, which included real motion artifacts. The former was used to train and evaluate the model using the in silico data, and the latter was used to evaluate the model performance to remove real motion artifacts. A motion simulation was performed in k-space domain to generate an in silico dataset with minor, moderate, and heavy distortion levels. The diffusion process of the MAR-CDPM was then implemented in k-space to convert structure data into Gaussian noise by gradually increasing motion artifact levels. A conditional network with a Unet backbone was trained to reverse the diffusion process to convert the distorted images to structured data. The MAR-CDPM was trained in two scenarios: one conditioning on the time step of the diffusion process, and the other conditioning on both and T2-FLAIR images. The MAR-CDPM was quantitatively and qualitatively compared with supervised Unet, Unet conditioned on T2-FLAIR, CycleGAN, Pix2pix, and Pix2pix conditioned on T2-FLAIR models. To quantify the spatial distortions and the level of remaining motion artifacts after applying the models, quantitative metrics were reported including normalized mean squared error (NMSE), structural similarity index (SSIM), multiscale structural similarity index (MS-SSIM), peak signal-to-noise ratio (PSNR), visual information fidelity (VIF), and multiscale gradient magnitude similarity deviation (MS-GMSD). Tukey's Honestly Significant Difference multiple comparison test was employed to quantify the difference between the models where p-value was considered statisticallysignificant. Qualitatively, MAR-CDPM outperformed these methods in preserving soft-tissue contrast and different brain regions. It also successfully preserved tumor boundaries for heavy motion artifacts, like the supervised method. Our MAR-CDPM recovered motion-free in silico images with the highest PSNR and VIF for all distortion levels where the differences were statistically significant (p-values ). In addition, our method conditioned on t and T2-FLAIR outperformed (p-values ) other methods to remove motion artifacts from the in silico dataset in terms of NMSE, MS-SSIM, SSIM, and MS-GMSD. Moreover, our method conditioned on only t outperformed generative models (p-values ) and had comparable performances compared with the supervised model (p-values ) to remove real motionartifacts. The MAR-CDPM could successfully remove motion artifacts from 3D ceT1 MPRAGE. It is particularly beneficial for elderly who may experience involuntary movements during high-resolution MRI imaging with long acquisitiontimes.

Targeted magnetic resonance imaging (tMRI) of small changes in the T1 and spatial properties of normal or near normal appearing white and gray matter in disease of the brain using divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences.

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T1 by up to 15 times compared to conventional T1-weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T2-weighted spin echo (T2-wSE) and/or fluid attenuated inversion recovery (T2-FLAIR) images. The small changes in T1 or T2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T1 maps. There is a nearly linear relationship between signal and T1 in the middle domain (mD) of the two sequences which includes T1s between the nulling T1s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T2-wSE and T2-FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T1-bipolar filters; to explain their targeting, signal, contrast, boundaries, T1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences.

Radiomics features from 3D-MPRAGE imaging can differentiate temporal-plus epilepsy from temporal lobe epilepsy.

This study aimed to differentiate temporal-plus epilepsy (TPE) from temporal lobe epilepsy (TLE) using extraction of radiomics features from three-dimensional magnetization-prepared rapid acquisition gradient echo (3D-MPRAGE) imaging data. Data from patients with TLE or TPE who underwent epilepsy surgery between January 2019 and January 2021 were retrospectively analyzed. Thirty-three regions of interest in the affected hemisphere of each patient were defined on 3D-MPRAGE images. A total of 3531 image features were extracted from each patient. Four feature selection methods and 10 machine learning algorithms were used to build 40 differentiation models. Model performance was evaluated using receiver operating characteristic analysis. Eighty-two patients were included for analysis, 47 with TLE and 35 with TPE. The model combining logistic regression and the relief selection method had the best performance (area under the receiver operating characteristic curve, .779; accuracy, .875; sensitivity, .800; specificity, .929; positive predictive value, .889; negative predictive value, .867). Radiomics analysis can differentiate TPE from TLE. The logistic regression classifier trained with radiomics features extracted from 3D-MPRAGE images had the highest accuracy and best performance.

Utility of 3D T1-weighted turbo spin echo black blood sequence for the diagnosis of cerebral venous thrombosis.

Accurate assessment of dural sinus, deep and cortical venous thrombosis on MR imaging is challenging. The aim of this study is to evaluate the accuracy of 3D-T1 turbo spin echo (T1S), sequences in detecting venous thrombosis and comparing it with susceptibility-weighted imaging (SWI), magnetic resonance venography (MRV) and post contrast T1 magnetization-prepared rapid acquisition gradient echo (T1C). A blinded retrospective observational analysis of 71 consecutive patients evaluated for cerebral venous thrombosis (CVT) and 30 control patients was performed. Multimodality reference standard adopted included T1C, SWI with MRV. Sub-analyses in superficial, deep and cortical venous segments were performed in addition to correlation of signal intensity of thrombus with the clinical stage. A total of 2222 segments in 101 complete MRI examinations were evaluated. Sensitivity/specificity/positive predictive value/negative predictive value/accuracy and precision of T1S for detection of cortical vein thrombosis was 0.994/1/1/0.967/0.995/1, 1/0.874/0.949/1/0.963/0.950 for detection of superficial venous sinus thrombosis and 1/1/1/1/1/1 for deep venous thrombosis. The AUC yield for T1S was 0.997 for cortical, 1 for deep and 0.988 for superficial venous segments. T1S paralleled the accuracy of conventional sequences in the overall detection of CVT but showed superior accuracy in the detection of cortical venous thrombosis. It makes a fitting addition to the CVT MRI protocol in scenarios demanding negation of gadolinium administration.

Clinical feasibility of CS-VIBE accelerates MRI techniques in diagnosing intracranial metastasis

Our objective was to evaluate and compare the diagnostic performance of post-contrast 3D compressed-sensing volume-interpolated breath-hold examination (CS-VIBE) and 3D T1 magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) in detecting intracranial metastasis. Additionally, we analyzed and compared the image quality between the two. We enrolled 164 cancer patients who underwent contrast-enhanced brain MRI. Two neuroradiologists independently reviewed all the images. The signal-to-noise ratio (SNR), contrast-to noise ratio (CNR) were compared between two sequences. For patients with intracranial metastasis, we measured enhancement degree and CNRlesion/parenchyma of the lesion. The overall image quality, motion artifact, gray-white matter discrimination and enhancing lesion conspicuity were analyzed. Both MPRAGE and CS-VIBE showed similar performance in diagnosing intracranial metastasis. Overall image quality of CS-VIBE was better with less motion artifact; however conventional MPRAGE was superior in enhancing lesion conspicuity. Overall, the SNR and CNR of conventional MPRAGE were higher than those of CS-VIBE. For 30 enhancing intracranial metastatic lesions, MPRAGE showed a lower CNR (p = 0.02) and contrast ratio (p = 0.03). MPRAGE and CS-VIBE were preferred in 11.6 and 13.4% of cases, respectively. In comparison with conventional MPRAGE, CS-VIBE achieved comparable image quality and visualization, with the scan time being half of that of MPRAGE.

Hippocampal Volume And Type 2 Diabetes Mellitus Without Comorbid Malady.

Evidence of type 2 diabetes mellitus (T2DM) associated with hippocampal atrophy is reported by researchers all around the globe. The majority of such studies were conducted among the geriatric and elderly populations with other substantial co-morbid diseases. Hence, the present study aims to evaluate the hippocampal volume of T2DM subjects below 60 years without any concomitant disorders and assess the declarative memory. The cross-sectional observational study was conducted among the ethnic population of Manipur. A total of 17 T2DM subjects and 17 healthy controls, who are apparently healthy, matched by age, sex, and comparable education, were enrolled in the study. Magnetic Resonance Imaging (MRI) of high-resolution sagittal structural T1-weighted anatomical sequence was acquired using a three-dimension magnetization-prepared rapid-acquisition gradient echo (MPRAGE). The hippocampus volume was measured using the volBrain Automated MRI Brain Volumetry System. Declarative memory was estimated by the Rey Auditory Verbal Learning Test (RAVLT). No statistically significant differences were found in hippocampal volume, and RAVLT scores between T2DM subjects, and healthy controls group (P > 0.05). The study data indicates that there is no particular hippocampal volume vulnerability in T2DM participants within the ethnic population of Manipur.

Reliability of spinal cord measures based on synthetic T1-weighted MRI derived from multiparametric mapping (MPM)

Short MRI acquisition time, high signal-to-noise ratio, and high reliability are crucial for image quality when scanning healthy volunteers and patients. Cross-sectional cervical cord area (CSA) has been suggested as a marker of neurodegeneration and potential outcome measure in clinical trials and is conventionally measured on T1-weigthed 3D Magnetization Prepared Rapid Acquisition Gradient-Echo (MPRAGE) images. This study aims to reduce the acquisition time for the comprehensive assessment of the spinal cord, which is typically based on MPRAGE for morphometry and multi-parameter mapping (MPM) for microstructure. The MPRAGE is replaced by a synthetic T1-w MRI (synT1-w) estimated from the MPM, in order to measure CSA. SynT1-w images were reconstructed using the MPRAGE signal equation based on quantitative maps of proton density (PD), longitudinal (R1) and effective transverse (R2*) relaxation rates. The reliability of CSA measurements from synT1-w images was determined within a multi-center test-retest study format and validated against acquired MPRAGE scans by assessing the agreement between both methods. The response to pathological changes was tested by longitudinally measuring spinal cord atrophy following spinal cord injury (SCI) for synT1-w and MPRAGE using linear mixed effect models. CSA measurements based on the synT1-w MRI showed high intra-site (Coefficient of variation [CoV]: 1.43% to 2.71%) and inter-site repeatability (CoV: 2.90% to 5.76%), and only a minor deviation of -1.65 mm2 compared to MPRAGE. Crucially, by assessing atrophy rates and by comparing SCI patients with healthy controls longitudinally, differences between synT1-w and MPRAGE were negligible. These results demonstrate that reliable estimates of CSA can be obtained from synT1-w images, thereby reducing scan time significantly.

Personalized maps of T1 relaxometry abnormalities provide correlates of disability in multiple sclerosis patients

Objectives and aimsQuantitative MRI (qMRI) has greatly improved the sensitivity and specificity of microstructural brain pathology in multiple sclerosis (MS) when compared to conventional MRI (cMRI). More than cMRI, qMRI also provides means to assess pathology within the normal-appearing and lesion tissue. In this work, we further developed a method providing personalized quantitative T1 (qT1) abnormality maps in individual MS patients by modeling the age dependence of qT1 alterations. In addition, we assessed the relationship between qT1 abnormality maps and patients’ disability, in order to evaluate the potential value of this measurement in clinical practice. MethodsWe included 119 MS patients (64 relapsing-remitting MS (RRMS), 34 secondary progressive MS (SPMS), 21 primary progressive MS (PPMS)), and 98 Healthy Controls (HC). All individuals underwent 3T MRI examinations, including Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) for qT1 maps and High-Resolution 3D Fluid Attenuated Inversion Recovery (FLAIR) imaging. To calculate personalized qT1 abnormality maps, we compared qT1 in each brain voxel in MS patients to the average qT1 obtained in the same tissue (grey/white matter) and region of interest (ROI) in healthy controls, hereby providing individual voxel-based Z-score maps. The age dependence of qT1 in HC was modeled using linear polynomial regression. We computed the average qT1 Z-scores in white matter lesions (WMLs), normal-appearing white matter (NAWM), cortical grey matter lesions (GMcLs) and normal-appearing cortical grey matter (NAcGM). Lastly, a multiple linear regression (MLR) model with the backward selection including age, sex, disease duration, phenotype, lesion number, lesion volume and average Z-score (NAWM/NAcGM/WMLs/GMcLs) was used to assess the relationship between qT1 measures and clinical disability (evaluated with EDSS). ResultsThe average qT1 Z-score was higher in WMLs than in NAWM. (WMLs: 1.366 ± 0.409, NAWM: −0.133 ± 0.288, [mean ± SD], p < 0.001). The average Z-score in NAWM in RRMS patients was significantly lower than in PPMS patients (p = 0.010). The MLR model showed a strong association between average qT1 Z-scores in white matter lesions (WMLs) and EDSS (R2 = 0.549, β = 0.178, 97.5 % CI = 0.030 to 0.326, p = 0.019). Specifically, we measured a 26.9 % increase in EDSS per unit of qT1 Z-score in WMLs in RRMS patients (R2 = 0.099, β = 0.269, 97.5 % CI = 0.078 to 0.461, p = 0.007). ConclusionsWe showed that personalized qT1 abnormality maps in MS patients provide measures related to clinical disability, supporting the use of those maps in clinical practice.

Cerebrospinal fluid neurofilament light and cerebral atrophy in younger-onset dementia and primary psychiatric disorders.

Neurodegeneration underpins the pathological processes of younger-onset dementia (YOD) and has been implicated in primary psychiatric disorders (PSYs). Cerebrospinal fluid (CSF) neurofilament light (NfL) has been used to investigate neurodegeneration severity through correlation with structural brain changes in various conditions, but has seldom been evaluated in YOD and PSYs. This retrospective study included patients with YOD or PSYs with magnetic resonance imaging (MRI) of the brain and CSF NfL analysis. Findings from brain MRI were analysed using automated volumetry (volBrain) to measure white matter (WM), grey matter (GM) and whole brain (WB) volumes expressed as percentages of total intracranial volume. Correlations between NfL and brain volume measurements were computed whilst adjusting for age. Seventy patients (47 with YOD and 23 with PSY) were identified. YOD types included Alzheimer disease and behavioural variant frontotemporal dementia. PSY included schizophrenia and major depressive disorder. MRI brain sequences were either fast spoiler gradient-echo (FSPGR) or magnetization-prepared rapid acquisition gradient-echo (MPRAGE). In the total cohort, higher NfL was associated with reduced WB in the FSPGR and MPRAGE sequences (r=-0.402 [95% confidence interval (CI), -0.593 to -0.147], P=0.008 and r=-0.625 [95% CI, -0.828 to -0.395], P < 0.001, respectively). Higher NfL was related to reduced GM in FSPGR (r=0.385 [95% CI, -0.649 to -0.014], P=0.017) and reduced WM in MPRAGE (r=-0.650 [95% CI, -0.777 to -0.307], P < 0.001). Similar relationships were seen in YOD, but not in PSY. Higher CSF NfL is related to brain atrophy in YOD, further supporting its use as a nonspecific marker of neurodegeneration severity.

Alterations of gray and white matter volumes and cortical thickness in treated HIV-positive patients

Brain structural changes in HIV identified by voxel-based morphometry (VBM) alone could arise from a variety of causes that are difficult to distinguish without further information, such as cortical thickness (CT), gyrification index (GI) or sulcal depth (SD). Hence, our goal was to assess these additional metrics in HIV using high-resolution 3D T1-weighted images and investigate if surface-based morphometric (SBM) analysis would reveal significant changes in the gray matter (GM) and white matter (WM) volumes combined with alterations in cortical thickness (CT), gyrification index (GI), sulcal depth (SD). T1-w magnetization-prepared-rapid-acquisition gradient-echo (MP-RAGE) scans were acquired in 27 HIV-infected individuals on antiretroviral therapy (ART) and 15 HIV-uninfected healthy controls using a 3T MRI scanner equipped with a 16-channel head “receive” and a quadrature body “transmit” coil. Voxel-based and surface-based morphometric analyses were performed using the MATLAB based SPM Computational Anatomy Toolbox (CAT12.7(1700)). HIV-infected patients showed significantly altered GM and WM volumes, CT, GI, and SD, in multiple brain regions. This study showed the association of altered GM and WM volumes in local brain regions with the changes in region-wise CT, GI and SD measures of HIV-infected patients, especially in the parahippocampal and middle frontal regions as compared to uninfected healthy controls. The outcome of this study suggests that the findings of VBM may not necessarily indicate the volumetric shrinkage or increase alone, but might also be due to altered CT, GI, or SD. Correlation analysis showed a significantly accelerated gray matter loss with age in HIV-infected individuals compared to uninfected healthy controls.

Fabrication of Customizable Intraplaque Hemorrhage Phantoms for Magnetic Resonance Imaging

PurposeMagnetic resonance (MR) imaging detection of methemoglobin, a molecular marker of intraplaque hemorrhage (IPH), in atherosclerotic plaque is a promising method of assessing stroke risk. However, the multicenter imaging studies required to further validate this technique necessitate the development of IPH phantoms to standardize images acquired across different scanners. This study developed a set of phantoms that modeled methemoglobin-laden IPH for use in MR image standardization.ProceduresA time-stable material mimicking the MR properties of methemoglobin in IPH was created by doping agarose hydrogel with gadolinium and sodium alginate. This material was used to create a phantom that consisted of 9 cylindrical IPH sites (with sizes from 1 to 8 mm). Anatomical replicas of IPH-positive atherosclerosis were also created using 3D printed molds. These plaque replicas also modeled other common plaque components including a lipid core and atheroma cap. T1 mapping and a magnetization-prepared rapid acquisition gradient echo (MPRAGE) carotid imaging protocol were used to assess phantom realism and long-term stability.ResultsCylindrical phantom IPH sites possessed a T1 time of 335 ± 51 ms and exhibited little change in size or MPRAGE signal intensity over 31 days; the mean (SD) magnitude of changes in size and signal were 6.4 % (2.7 %) and 7.3 % (6.7 %), respectively. IPH sites incorporated into complex anatomical plaque phantoms exhibited contrast comparable to clinical images.ConclusionsThe cylindrical IPH phantom accurately modeled the short T1 time characteristic of methemoglobin-laden IPH, with the IPH sites exhibiting little variation in imaging properties over 31 days. Furthermore, MPRAGE images of the anatomical atherosclerosis replicas closely matched those of clinical plaques. In combination, these phantoms will allow for IPH imaging protocol standardization and thus facilitate future multicenter IPH imaging.

Loss of hippocampal dentation in hippocampal sclerosis and its relationship to memory dysfunction.

Hippocampal dentation (HD) is a "toothlike" morphological feature observed on the inferior aspect of the human hippocampus. It has been found that HD varies dramatically in healthy adults and is positively associated with verbal and visual memory. In this work, we evaluate the loss of HD and its association with memory dysfunction in patients with temporal lobe epilepsy (TLE) who have hippocampal sclerosis (HS). Fifty-eight unilateral HS patients with neuropsychological data were identified from a retrospective database. T1-weighted magnetization-prepared rapid acquisition gradient echo images (~1mm resolution) were upsampled to .25mm and were processed using ASHS software to obtain ultra-high-resolution segmentations and three-dimensional renderings. Dentes were counted on the epileptic and contralateral sides, and associations were tested between dentation on the epileptic versus contralateral sides and measures of verbal and visuospatial memory with respect to the dominant versus nondominant hemisphere. The median number of dentes in epileptic hippocampi was significantly lower than in contralateral hippocampi (p<.0001). Among cases with HS in the dominant hemisphere, verbal memory was significantly correlated with contralateral nondominant hemisphere dentation (r=.43, p=.04). Similarly, among cases of HS in the nondominant hemisphere, visual memory was significantly correlated with contralateral dominant hemisphere dentation (r=.48, p=.04). All other analyses were not significant. This is the first study characterizing dentation in TLE patients with HS and its memory correlates. There is marked loss of dentation in sclerotic hippocampi compared to the unaffected contralateral hippocampi. Material-specific measures of memory performance are paradoxically correlated with dentation contralateral to the side with HS, suggesting that contralateral functional capacity explains some of the variation in memory across TLE patients. HD is an important variable to consider in understanding memory loss in TLE.

Longitudinal Changes in Global Cerebral Blood Flow in Cognitively Normal Older Adults: A Phase-Contrast MRI Study.

Characterization of blood supply changes in older individuals is important in understanding brain aging and diseases. However, prior studies largely focused on cross-sectional design, thus change in cerebral blood flow (CBF) could not be assessed on an individual level. To evaluate longitudinal short-term changes in global CBF in cognitively normal older adults. Prospective, longitudinal, and cohort. One-hundred twenty-seven cognitive-normal participants (mean age 69 ± 7 years, 47 males) underwent serial MRI with an average follow-up time of 2.1 years. 3 T phase-contrast (PC), three-dimensional magnetization-prepared-rapid-acquisition-of-gradient-echo (MPRAGE) and fluid-attenuated inversion recovery (FLAIR) MRI. Total CBF was measured with PC MRI allowing assessment of quantitative flow in four major feeding arteries by a trained radiologist with >3 years' experience (O.K.). Brain volume was obtained from MPRAGE MRI and measured by T1-MultiAtlas MRICloud tool. The ratio between total CBF and brain volume yielded global CBF in mL/100 g/min. White matter hyperintensity (WMH) was measured automatically using a Bayesian probability approach on FLAIR. Linear mixed effect model was used to simultaneously assess cross-sectional age-differences and longitudinal age-changes in CBF. Spearman rank correlation was used to evaluate the relationship between CBF change and WMH progression. A P-value of <0.05 (two-tailed) was considered significant. Global CBF decreased with age at a longitudinal rate of -0.56 mL/100 g/min/year (95% confidence interval [CI]: -1.09, -0.03), compared to a cross-sectional rate of -0.26 mL/100 g/min/year (95% CI: -0.41, -0.11). Changes in CBF were significantly associated with progression of WMH (Spearman rank correlation r=-0.25), as those participants who had a more rapid CBF reduction had greater increases in WMH volumes and the relationship remained significant when adjusting for baseline vascular risk scores. Additionally, age-related changes in whole-brain volume were found to be -0.151%/year (95% CI: -0.186, -0.116). These findings suggest that brain aging in older adults is accompanied by a rapid longitudinal reduction in CBF, the rate of which is associated with white matter damage. 1 TECHNICAL EFFICACY STAGE: 2.

Correlation Between Thrombus Signal Intensity and Aneurysm Wall Thickness in Partially Thrombosed Intracranial Aneurysms Using 7T Magnetization-Prepared Rapid Acquisition Gradient Echo Magnetic Resonance Imaging.

ObjectiveThe objective of this study is to investigate the relationship between the thrombus signal intensity and aneurysm wall thickness in partially thrombosed intracranial aneurysms in vivo with magnetization-prepared rapid acquisition gradient echo (MPRAGE) taken using 7T magnetic resonance imaging (MRI) and correlate the findings to wall instability.MethodsSixteen partially thrombosed intracranial aneurysms were evaluated using a 7T whole-body MR system with nonenhanced MPRAGE. To normalize the thrombus signal intensity, its highest signal intensity was compared to that of the anterior corpus callosum of the same subject, and the signal intensity ratio was calculated. The correlation between the thrombus signal intensity ratio and the thickness of the aneurysm wall was analyzed. Furthermore, aneurysmal histopathological specimens from six tissue samples were compared with radiological findings to detect any correlation.ResultsThe mean thrombus signal intensity ratio was 0.57 (standard error of the mean [SEM] 0.06, range 0.25–1.01). The mean thickness of the aneurysm wall was 1.25 (SEM 0.08, range 0.84–1.55) mm. The thrombus signal intensity ratio significantly correlated with the aneurysm wall thickness (p < 0.01). The aneurysm walls with the high thrombus signal intensity ratio were significantly thicker. In histopathological examinations, three patients with a hypointense thrombus had fewer macrophages infiltrating the thrombus and a thin degenerated aneurysmal wall. In contrast, three patients with a hyperintense thrombus had abundant macrophages infiltrating the thrombus.ConclusionThe thrombus signal intensity ratio in partially thrombosed intracranial aneurysms correlated with aneurysm wall thickness and histologic features, indicating wall instability.

Brain iron deposits are associated with apathy in cognitively normal and impaired adults

AbstractBackgroundApathy is a common symptom in older cognitively normal and impaired individuals and can be distinguished from depression. Apathy is characterized by loss of interest and motivation, emotional unresponsiveness, executive deficits, and diminished dopaminergic and noradrenergic neurotransmission. Apathy is linked to vascular risk and fronto‐striatal deficits [(volume‐loss &amp; white‐matter‐hyperintensities(WMH)], but mechanisms still relatively unknown. Prior studies link brain‐iron deposition to oxidative‐stress, vascular‐diseases, neurodegeneration, disrupted striatal‐dopamine neurotransmission, and report equivocal associations between depression and peripheral iron‐levels, which might not reflect cerebral iron‐deposits.Quantitative‐Susceptibility‐Mapping(QSM)‐MRI quantifies bulk tissue‐magnetic‐susceptibility from gradient‐echo(GRE) signal‐phase, successfully providing an estimate for iron‐content in gray‐matter tissue in neurodegenerative disorders, and major‐depressive‐disorder. This study probes a possible mechanistic connection between apathy‐symptoms and cerebral iron‐deposits.MethodA cross‐sectional study was conducted in 73 participants (71.7±7.13 years; 24‐normal, 38‐MCI,11‐mild‐dementia)(Table‐1). Geriatric Depression Scale: (GDS,15‐items), assesses constellation of depressive symptoms including apathy. 3Tesla‐Philips scanner acquired MRI‐images using a 3D T1‐weighted Magnetization‐Prepared‐Rapid‐Acquisition‐of‐Gradient‐Echo(MPRAGE) sequence(1×1×1mm3) for anatomic reference and a 3Dmulti‐echo gradient‐echo sequence(0.8×0.8×1.6 mm, TE1/TE/TR=6/6/30, 5‐unipolar‐echoes) for QSM, which were reconstructed using JHU/KKI QSM‐Toolbox(version3.0; http://godzilla.kennedykrieger.org/QSM/). Phase‐processing, QSM‐dipole‐inversion and brain‐segmentation was performed. Twelve regions‐of‐interest(ROI) were quantified for volume and tissue‐magnetic‐susceptibility(reference,CSF). Fluid‐Attenuated‐Inversion‐Recovery(FLAIR) images were rated and assigned a Fazekas‐score by neuroradiologist to quantify WMH. Vascular Risk Score(VRS), a composite of dichotomous(yes/no) 5‐clinical history‐items: hypertension, hypercholesterolemia, diabetes, smoking, and body‐mass‐index(≥ 30), was used.ResultHigher gray‐matter tissue‐magnetic‐susceptibilities (indicating iron‐concentrations) in12‐ROIs were associated with higher GDS(Fig1). These patterns of associations remained after adjusting age, sex, diagnosis, and structural‐volume in regression analysis(Table‐2). Next, total‐iron‐content (susceptibility x regional‐volume) was estimated for ROIs. Principal Component analysis removed multicollinearity among 12‐ROIs, and only 1of the 3‐components obtained(Fig‐3a), was associated with GDS(Table‐3b). Regression using these independent component residuals showed the same ROIs remained associated with GDS(Table‐3c). Finally, Partial Least Squares Regression was done to determine the GDS‐items contributing to the associations, after adjusting age, sex, structural‐volume, Fazekas‐score and VRS(Fig‐4). Mostly the same ROIs were associated with apathy‐related symptoms(3 GDS‐items), but not depression symptoms(12‐items)(Table‐4).ConclusionIron‐deposits(QSM) in several brain‐regions were associated with apathy‐symptoms, after adjusting WMH, VRS and structural‐volume in 73 normal and impaired older‐individuals. Findings indicate possible mechanistic associations between brain iron‐deposition and apathy, distinct from depression.