In vivo mapping of hippocampal venous vasculature and oxygenation using susceptibility imaging at 7T.

Mapping the small venous vasculature of the hippocampus in vivo is crucial for understanding how functional changes of hippocampus evolve with age. Oxygen utilization in the hippocampus could serve as a sensitive biomarker for early degenerative changes, surpassing hippocampal tissue atrophy as the main source of information regarding tissue degeneration. Using an ultrahigh field (7T) susceptibility-weighted imaging (SWI) sequence, it is possible to capture oxygen-level dependent contrast of submillimeter-sized vessels. Moreover, the quantitative susceptibility mapping (QSM) results derived from SWI data allow for the simultaneous estimation of venous oxygenation levels, thereby enhancing the understanding of hippocampal function. In this study, we proposed two potential imaging markers in a cohort of 19 healthy volunteers aged between 20 and 74 years. These markers were: 1) hippocampal venous density on SWI images and 2) venous susceptibility (Δχvein) in the hippocampus-associated draining veins (the inferior ventricular veins (IVV) and the basal veins of Rosenthal (BVR) using QSM images). They were chosen specifically to help characterize the oxygen utilization of the human hippocampus and medial temporal lobe (MTL). As part of the analysis, we demonstrated the feasibility of measuring hippocampal venous density and Δχvein in the IVV and BVR at 7T with high spatial resolution (0.25 × 0.25 × 1 mm3). Our results demonstrated the in vivo reconstruction of the hippocampal venous system, providing initial evidence regarding the presence of the venous arch structure within the hippocampus. Furthermore, we evaluated the age effect of the two quantitative estimates and observed a significant increase in Δχvein for the IVV with age (p=0.006, r2 = 0.369). This may suggest the potential application of Δχvein in IVV as a marker for assessing changes in atrophy-related hippocampal oxygen utilization in normal aging and neurodegenerative diseases such as AD and dementia.

PENCIL imaging: A novel approach for neuromelanin sensitive MRI in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is associated with the loss of neuromelanin (NM) and increased iron in the substantia nigra (SN). Magnetization transfer contrast (MTC) is widely used for NM visualization but has limitations in brain coverage and scan time. This study aimed to develop a new approach called Proton-density Enhanced Neuromelanin Contrast in Low flip angle gradient echo (PENCIL) imaging to visualize NM in the SN. METHODS: This study included 30 PD subjects and 50 healthy controls (HCs) scanned at 3T. PENCIL and MTC images were acquired. NM volume in the SN pars compacta (SNpc), normalized image contrast (Cnorm), and contrast-to-noise ratio (CNR) were calculated. The change of NM volume in the SNpc with age was analyzed using the HC data. A group analysis compared differences between PD subjects and HCs. Receiver operating characteristic (ROC) analysis and area under the curve (AUC) calculations were used to evaluate the diagnostic performance of NM volume and CNR in the SNpc. RESULTS: PENCIL provided similar visualization and structural information of NM compared to MTC. In HCs, PENCIL showed higher NM volume in the SNpc than MTC, but this difference was not observed in PD subjects. PENCIL had higher CNR, while MTC had higher Cnorm. Both methods revealed a similar pattern of NM volume in SNpc changes with age. There were no significant differences in AUCs between NM volume in SNpc measured by PENCIL and MTC. Both methods exhibited comparable diagnostic performance in this regard. CONCLUSIONS: PENCIL imaging provided improved CNR compared to MTC and showed similar diagnostic performance for differentiating PD subjects from HCs. The major advantage is PENCIL has rapid whole-brain coverage and, when using STAGE imaging, offers a one-stop quantitative assessment of tissue properties.

Vascular Aging in the Choroid Plexus: A 7T Ultrasmall Superparamagnetic Iron Oxide (USPIO)-MRI Study.

BACKGROUND: The choroid plexus (ChP), a densely vascularized structure, has drawn increasing attention for its involvement in brain homeostasis and waste clearance. While the volumetric changes have been explored in many imaging studies, few studies have investigated the vascular degeneration associated with aging in the ChP. PURPOSE: To investigate the sub-structural characteristics of the ChP, particularly the vascular compartment using high-resolution 7T imaging enhanced with Ferumoxytol, an ultrasmall super-paramagnetic iron oxide, which greatly increase the susceptibility contrast for vessels. STUDY TYPE: Prospective. SUBJECTS: Forty-nine subjects without neurological disorders (age: 21-80 years; 42 ± 17 years; 20 females). FIELD STRENGTH/SEQUENCE: 7-T with 2D and 3D T2* GRE, 3D MPRAGE T1, 2D TSE T2, and 2D FLAIR. ASSESSMENT: The vascular and stromal compartments of the ChP were segmented using K-means clustering on post-contrast 2D GRE images. Visual and qualitative assessment of ChP vascular characteristics were conducted independently by three observers. Vascular density (Volvessel/VolChP ratio) and susceptibility change (Δχ) induced by Ferumoxytol were analyzed on 3D GRE-derived susceptibility-weighted imaging and quantitative susceptibility mapping, respectively. STATISTICAL TESTS: Independent t-test, Mann-Whitney U test, and Chi-square test were utilized for group comparisons. The relationship between age and ChP's vascular alterations was examined using Pearson's correlation. Intra-class coefficient was calculated for inter-observer agreement. A P value <0.05 was considered statistically significant. RESULTS: 2D GRE images demonstrated superior contrast and accurate delineation of ChP substructures (ICC = 0.86). Older subjects exhibited a significantly smaller vascular density (16.5 ± 4.34%) and lower Δχ (22.10 ± 12.82 ppb) compared to younger subjects (24.85 ± 6.84% and 34.64 ± 12.69 ppb). Vascular density and mean Δχ within the ChP negatively correlated with age (r = -0.48, and r = -0.45). DATA CONCLUSION: Ferumoxytol-enhanced 7T images can demonstrate ChP alterations in elderly with decreased vascular density and expansion of nonvascular compartment. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Enhancing Nigrosome-1 Sign Identification via Interpretable AI using True Susceptibility Weighted Imaging.

BACKGROUND: Nigrosome 1 (N1), the largest nigrosome region in the ventrolateral area of the substantia nigra pars compacta, is identifiable by the "N1 sign" in long echo time gradient echo MRI. The N1 sign's absence is a vital Parkinson's disease (PD) diagnostic marker. However, it is challenging to visualize and assess the N1 sign in clinical practice. PURPOSE: To automatically detect the presence or absence of the N1 sign from true susceptibility weighted imaging by using deep-learning method. STUDY TYPE: Prospective. POPULATION/SUBJECTS: 453 subjects, including 225 PD patients, 120 healthy controls (HCs), and 108 patients with other movement disorders, were prospectively recruited including 227 males and 226 females. They were divided into training, validation, and test cohorts of 289, 73, and 91 cases, respectively. FIELD STRENGTH/SEQUENCE: 3D gradient echo SWI sequence at 3T; 3D multiecho strategically acquired gradient echo imaging at 3T; NM-sensitive 3D gradient echo sequence with MTC pulse at 3T. ASSESSMENT: A neuroradiologist with 5 years of experience manually delineated substantia nigra regions. Two raters with 2 and 36 years of experience assessed the N1 sign on true susceptibility weighted imaging (tSWI), QSM with high-pass filter, and magnitude data combined with MTC data. We proposed NINet, a neural model, for automatic N1 sign identification in tSWI images. STATISTICAL TESTS: We compared the performance of NINet to the subjective reference standard using Receiver Operating Characteristic analyses, and a decision curve analysis assessed identification accuracy. RESULTS: NINet achieved an area under the curve (AUC) of 0.87 (CI: 0.76-0.89) in N1 sign identification, surpassing other models and neuroradiologists. NINet localized the putative N1 sign within tSWI images with 67.3% accuracy. DATA CONCLUSION: Our proposed NINet model's capability to determine the presence or absence of the N1 sign, along with its localization, holds promise for enhancing diagnostic accuracy when evaluating PD using MR images. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Diagnosing Parkinson's disease by combining neuromelanin and iron imaging features using an automated midbrain template approach.

BACKGROUND AND PURPOSE: Early diagnosis of Parkinson's disease (PD) is still a clinical challenge. Most previous studies using manual or semi-automated methods for segmenting the substantia nigra (SN) are time-consuming and, despite raters being well-trained, individual variation can be significant. In this study, we used a template-based, automatic, SN subregion segmentation pipeline to detect the neuromelanin (NM) and iron features in the SN and SN pars compacta (SNpc) derived from a single 3D magnetization transfer contrast (MTC) gradient echo (GRE) sequence in an attempt to develop a comprehensive imaging biomarker that could be used to diagnose PD. MATERIALS AND METHODS: A total of 100 PD patients and 100 age- and sex-matched healthy controls (HCs) were imaged on a 3T scanner. NM-based SN (SNNM) boundaries and iron-based SN (SNQSM) boundaries and their overlap region (representing the SNpc) were delineated automatically using a template-based SN subregion segmentation approach based on quantitative susceptibility mapping (QSM) and NM images derived from the same MTC-GRE sequence. All PD and HC subjects were evaluated for the nigrosome-1 (N1) sign by two raters independently. Receiver Operating Characteristic (ROC) analyses were performed to evaluate the utility of SNNM volume, SNQSM volume, SNpc volume and iron content with a variety of thresholds as well as the N1 sign in diagnosing PD. Correlation analyses were performed to study the relationship between these imaging measures and the clinical scales in PD. RESULTS: In this study, we verified the value of the fully automatic template based midbrain deep gray matter mapping approach in differentiating PD patients from HCs. The automatic segmentation of the SN in PD patients led to satisfactory DICE similarity coefficients and volume ratio (VR) values of 0.81 and 1.17 for the SNNM, and 0.87 and 1.05 for the SNQSM, respectively. For the HC group, the average DICE similarity coefficients and VR values were 0.85 and 0.94 for the SNNM, and 0.87 and 0.96 for the SNQSM, respectively. The SNQSM volume tended to decrease with age for both the PD and HC groups but was more severe for the PD group. For diagnosing PD, the N1 sign performed reasonably well by itself (Area Under the Curve (AUC) = 0.783). However, combining the N1 sign with the other quantitative measures (SNNM volume, SNQSM volume, SNpc volume and iron content) resulted in an improved diagnosis of PD with an AUC as high as 0.947 (using an SN threshold of 50ppb and an NM threshold of 0.15). Finally, the SNQSM volume showed a negative correlation with the MDS-UPDRS III (R2 = 0.1, p = 0.036) and the Hoehn and Yahr scale (R2 = 0.04, p = 0.013) in PD patients. CONCLUSION: In summary, this fully automatic template based deep gray matter mapping approach performs well in the segmentation of the SN and its subregions for not only HCs but also PD patients with SN degeneration. The combination of the N1 sign with other quantitative measures (SNNM volume, SNQSM volume, SNpc volume and iron content) resulted in an AUC of 0.947 and provided a comprehensive set of imaging biomarkers that, potentially, could be used to diagnose PD clinically.

The iron burden of cerebral microbleeds contributes to brain atrophy through the mediating effect of white matter hyperintensity.

The goal of this work was to explore the total iron burden of cerebral microbleeds (CMBs) using a semi-automatic quantitative susceptibility mapping and to establish its effect on brain atrophy through the mediating effect of white matter hyperintensities (WMH). A total of 95 community-dwelling people were enrolled. Quantitative susceptibility mapping (QSM) combined with a dynamic programming algorithm (DPA) was used to measure the characteristics of 1309 CMBs. WMH were evaluated according to the Fazekas scale, and brain atrophy was assessed using a 2D linear measurement method. Histogram analysis was used to explore the distribution of CMBs susceptibility, volume, and total iron burden, while a correlation analysis was used to explore the relationship between volume and susceptibility. Stepwise regression analysis was used to analyze the risk factors for CMBs and their contribution to brain atrophy. Mediation analysis was used to explore the interrelationship between CMBs and brain atrophy. We found that the frequency distribution of susceptibility of the CMBs was Gaussian in nature with a mean of 201 ppb and a standard deviation of 84 ppb; however, the volume and total iron burden of CMBs were more Rician in nature. A weak but significant correlation between the susceptibility and volume of CMBs was found (r = -0.113, P < 0.001). The periventricular WMH (PVWMH) was a risk factor for the presence of CMBs (number: ß = 0.251, P = 0.014; volume: ß = 0.237, P = 0.042; total iron burden: ß = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: ß = 0.325, P = 0.001; Evans's index: ß = 0.323, P = 0.001). PVWMH had a significant mediating effect on the correlation between CMBs and brain atrophy. In conclusion, QSM along with the DPA can measure the total iron burden of CMBs. PVWMH might be a risk factor for CMBs and may mediate the effect of CMBs on brain atrophy.

Visualizing the deep cerebellar nuclei using quantitative susceptibility mapping: An application in healthy controls, Parkinson's disease patients and essential tremor patients.

The visualization and identification of the deep cerebellar nuclei (DCN) (dentate [DN], interposed [IN] and fastigial nuclei [FN]) are particularly challenging. We aimed to visualize the DCN using quantitative susceptibility mapping (QSM), predict the contrast differences between QSM and T2* weighted imaging, and compare the DCN volume and susceptibility in movement disorder populations and healthy controls (HCs). Seventy-one Parkinson's disease (PD) patients, 39 essential tremor patients, and 80 HCs were enrolled. The PD patients were subdivided into tremor dominant (TD) and postural instability/gait difficulty (PIGD) groups. A 3D strategically acquired gradient echo MR imaging protocol was used for each subject to obtain the QSM data. Regions of interest were drawn manually on the QSM data to calculate the volume and susceptibility. Correlation analysis between the susceptibility and either age or volume was performed and the intergroup differences of the volume and magnetic susceptibility in all the DCN structures were evaluated. For the most part, all the DCN structures were clearly visualized on the QSM data. The susceptibility increased as a function of volume for both the HC group and disease groups in the DN and IN (p < .001) but not the FN (p = .74). Only the volume of the FN in the TD-PD group was higher than that in the HCs (p = .012), otherwise, the volume and susceptibility among these four groups did not differ significantly. In conclusion, QSM provides clear visualization of the DCN structures. The results for the volume and susceptibility of the DCN can be used as baseline references in future studies of movement disorders.

Application of Neuromelanin MR Imaging in Parkinson Disease.

MRI has been used to develop biomarkers for movement disorders such as Parkinson disease (PD) and other neurodegenerative disorders with parkinsonism such as progressive supranuclear palsy and multiple system atrophy. One of these imaging biomarkers is neuromelanin (NM), whose integrity can be assessed from its contrast and volume. NM is found mainly in certain brain stem structures, namely, the substantia nigra pars compacta (SNpc), the ventral tegmental area, and the locus coeruleus. Another major biomarker is brain iron, which often increases in concert with NM degeneration. These biomarkers have the potential to improve diagnostic certainty in differentiating between PD and other neurodegenerative disorders similar to PD, as well as provide a better understanding of pathophysiology. Mapping NM in vivo has clinical importance for gauging the premotor phase of PD when there is a greater than 50% loss of dopaminergic SNpc melanized neurons. As a metal ion chelator, NM can absorb iron. When NM is released from neurons, it deposits iron into the intracellular tissues of the SNpc; the result is iron that can be imaged and measured using quantitative susceptibility mapping. An increase of iron also leads to the disappearance of the nigrosome-1 sign, another neuroimage biomarker for PD. Therefore, mapping NM and iron changes in the SNpc are a practical means for improving early diagnosis of PD and in monitoring disease progression. In this review, we discuss the functions and location of NM, how NM-MRI is performed, the automatic mapping of NM and iron content, how NM-related imaging biomarkers can be used to enhance PD diagnosis and differentiate it from other neurodegenerative disorders, and potential advances in NM imaging methods. With major advances currently evolving for rapid imaging and artificial intelligence, NM-related biomarkers are likely to have increasingly important roles for enhancing diagnostic capabilities in PD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

The role of the parenchymal vascular system in cerebrospinal fluid tracer clearance.

OBJECTIVES: The current understanding of cerebral waste clearance (CWC) involves cerebrospinal fluid (CSF) participation but lacks convincing evidence for the direct participation of the parenchymal vascular system. The objective of this study was to evaluate the role of the parenchymal vascular system in CSF tracer clearance in rats. METHODS: We used superparamagnetic iron oxide-enhanced susceptibility-weighted imaging (SPIO-SWI) and quantitative susceptibility mapping (QSM) methods to simultaneously study 7 T MRI signal changes in parenchymal veins, arteries, and their corresponding para-vascular spaces in 26 rats, following intra-cisterna magna (ICM) infusion of different CSF tracers (FeREX, Ferumoxytol, Fe-Dextran) to determine the amount of tracer in the artery and vein quantitatively. RESULTS: We observed that the parenchymal venous system participated in CSF tracer clearance following ICM infusion of different MRI tracers with different concentrations of iron. Parenchymal venous participation was more obvious when 75 µg iron was injected. In the parenchymal veins, the relative mean (± SE) value of the susceptibility increased by 13.5 (± 1.0)% at 15 min post-tracer infusion (p < 0.01), and 33.6 (± 6.7)% at 45 min post-tracer infusion (p = 0.01), compared to baseline. In contrast to the parenchymal veins, a negligible amount of CSF tracer entered the parenchymal arteries: 1.3 (± 2.6)% at 15 min post-tracer infusion (p = 0.6), and 12 (± 19)% at 45 min post-tracer infusion (p = 0.5), compared to baseline. CONCLUSIONS: MRI tracers can enter the parenchymal vascular system and more MRI tracers were observed in the cerebral venous than arterial vessels, suggesting the direct participation of parenchymal vascular system in CWC. KEY POINTS: • MRI results revealed that the parenchymal venous system directly participates in cerebrospinal fluid tracer clearance following ICM infusion of MRI tracer. • Different sizes of MRI tracers can enter the parenchymal venous system.

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

OBJECTIVES: To evaluate calcium deposition in the fetal spine in vivo during the second and third trimesters using quantitative susceptibility mapping (QSM). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. KEY POINTS: • 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.

Vascular mapping of the human hippocampus using Ferumoxytol-enhanced MRI.

The hippocampus is a small but complex grey matter structure that plays an important role in spatial and episodic memory and can be affected by a wide range of pathologies including vascular abnormalities. In this work, we introduce the use of Ferumoxytol, an ultra-small superparamagnetic iron oxide (USPIO) agent, to induce susceptibility in the arteries (as well as increase the susceptibility in the veins) to map the hippocampal micro-vasculature and to evaluate the quantitative change in tissue fractional vascular density (FVD), in each of its subfields. A total of 39 healthy subjects (aged 35.4 ± 14.2 years, from 18 to 81 years old) were scanned with a high-resolution (0.22×0.44×1 mm3) dual-echo SWI sequence acquired at four time points during a gradual increase in Ferumoxytol dose (final dose = 4 mg/kg). The volumes of each subfield were obtained automatically from the pre-contrast T1-weighted data. The dynamically acquired SWI data were co-registered and adaptively combined to reduce the blooming artifacts from large vessels, preserving the contrast from smaller vessels. The resultant SWI data were used to segment the hippocampal vasculature and to measure the FVD ((volume occupied by vessels)/(total volume)) for each subfield. The hippocampal fissure, along with the fimbria, granular cell layer of the dentate gyrus and cornu ammonis layers (except for CA1), showed higher micro-vascular FVD than the other parts of hippocampus. The CA1 region exhibited a significant correlation with age (R = -0.37, p < 0.05). demonstrating an overall loss of hippocampal vascularity in the normal aging process. Moreover, the vascular density reduction was more prominent than the age correlation with the volume reduction (R = -0.1, p > 0.05) of the CA1 subfield, which would suggest that vascular degeneration may precede tissue atrophy.

Three-dimensional simultaneous brain mapping of T1, T2, T2∗ and magnetic susceptibility with MR Multitasking.

PURPOSE: To develop a new technique that enables simultaneous quantification of whole-brain T1 , T2 , T2∗ , as well as susceptibility and synthesis of six contrast-weighted images in a single 9.1-minute scan. METHODS: The technique uses hybrid T2 -prepared inversion-recovery pulse modules and multi-echo gradient-echo readouts to collect k-space data with various T1, T2, and T2∗ weightings. The underlying image is represented as a six-dimensional low-rank tensor consisting of three spatial dimensions and three temporal dimensions corresponding to T1 recovery, T2 decay, and multi-echo behaviors, respectively. Multiparametric maps were fitted from reconstructed image series. The proposed method was validated on phantoms and healthy volunteers, by comparing quantitative measurements against corresponding reference methods. The feasibility of generating six contrast-weighted images was also examined. RESULTS: High quality, co-registered T1 , T2 , and T2∗ susceptibility maps were generated that closely resembled the reference maps. Phantom measurements showed substantial consistency (R2 > 0.98) with the reference measurements. Despite the significant differences of T1 (p < .001), T2 (p = .002), and T2∗ (p = 0.008) between our method and the references for in vivo studies, excellent agreement was achieved with all intraclass correlation coefficients greater than 0.75. No significant difference was found for susceptibility (p = .900). The framework is also capable of synthesizing six contrast-weighted images. CONCLUSION: The MR Multitasking-based 3D brain mapping of T1 , T2 , T2∗ , and susceptibility agrees well with the reference and is a promising technique for multicontrast and quantitative imaging.

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

BACKGROUND: 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. PURPOSE: To measure brain susceptibility in HTN patients using quantitative susceptibility mapping (QSM) and to explore the relationship between brain iron and cognition. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: Sixty HTN patients (35 with mild cognitive impairment [MCI] and 25 without MCI) and 24 age, gender, and education matched controls. FIELD STRENGTH/SEQUENCE: 3 T; strategically acquired gradient echo (STAGE) imaging protocol for QSM analysis. ASSESSMENT: 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). STATISTICAL TESTS: 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. RESULTS: 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). DATA CONCLUSION: QSM measured brain iron was significantly higher in CN, PU, and DN in HTN patients. Cognitive impairment was correlated with regional brain iron deposition. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Brain iron deposition and movement disorders in hereditary haemochromatosis without liver failure: A cross-sectional study.

BACKGROUND AND PURPOSE: Hereditary haemochromatosis (HH) is the most common inherited disorder of systemic iron excess in Northern Europeans. Emerging evidence indicates that brain iron overload occurs in HH. Despite this observation, there is a paucity of literature regarding central neurological manifestations, in particular movement disorders, in HH. The current study documents deep gray matter (DGM) nuclei iron deposition, movement disorders, and clinicoradiological correlations in HH without liver failure. METHODS: This is a cross-sectional study. Consecutive subjects with HFE-haemochromatosis without liver disease were recruited from an outpatient gastroenterology clinic. Age- and sex-matched healthy controls (HCs) were enrolled. Iron content in individual DGM nuclei was measured as mean susceptibility on magnetic resonance imaging using quantitative susceptibility mapping-based regions of interest analysis. Occurrence and phenotype of movement disorders were documented and correlated with patterns of DGM nuclei iron deposition in subjects with HH. RESULTS: Fifty-two subjects with HH and 47 HCs were recruited. High magnetic susceptibility was demonstrated in several DGM nuclei in all HH subjects compared to HCs. Thirty-five subjects with HH had movement disorders. Magnetic susceptibility in specific DGM nuclei correlated with individual movement disorder phenotypes. Serum ferritin, phlebotomy frequency, and duration were poor predictors of brain iron deposition. CONCLUSIONS: Abnormal brain iron deposition can be demonstrated on imaging in all subjects with HH without liver failure. A significant proportion of these subjects manifest movement disorders. Peripheral iron measurements appear not to correlate with brain iron deposition. Therefore, routine neurological examination and quantitative brain iron imaging are recommended in all subjects with HH.

Susceptibility-weighted imaging to evaluate normal and abnormal vertebrae in fetuses: A preliminary study.

OBJECTIVE: To evaluate the performance of susceptibility-weighted imaging (SWI) in visualizing normal and abnormal fetal vertebrae in vivo and in utero. METHODS: Ninety-seven women with normal fetal vertebrae and 127 women suspected fetal vertebral anomalies on ultrasound were included in our study. SWI, true fast imaging with steady state precession (TrueFISP), and half-Fourier acquisition single-shot turbo spin-echo (HASTE) of the fetal spine were performed on 1.5-T magnetic resonance imaging. The image quality and diagnostic performance between HASTE/TrueFISP and SWI were compared. Pearson correlations to correlate the L1 centrum ossification center (COC) measurements with gestational age (GA) were performed. RESULTS: The visibility of the fetal vertebral structures on the SWI images (3.58 ± 0.69) was significantly greater than those on the HASTE (1.98 ± 0.51, p < 0.001) and TrueFISP (2.63 ± 0.52, p < 0.001). The diagnostic accuracy of SWI (89.0%) was superior to HASTE/TrueFISP (48.0%) (p < 0.001) and the area under the curve for SWI was 0.909 (p < 0.001). The height, transverse, sagittal diameter, and area of L1 COC were linearly correlated with GA (all p < 0.001). CONCLUSION: SWI proved to be a reliable method for depicting fetal vertebral structure and growth, which can significantly improve the diagnostic performance of vertebral anomalies in fetuses.

Imaging iron and neuromelanin simultaneously using a single 3D gradient echo magnetization transfer sequence: Combining neuromelanin, iron and the nigrosome-1 sign as complementary imaging biomarkers in early stage Parkinson's disease.

Diagnosing early stage Parkinson's disease (PD) is still a clinical challenge. Previous studies using iron, neuromelanin (NM) or the Nigrosome-1 (N1) sign in the substantia nigra (SN) by themselves have been unable to provide sufficiently high diagnostic performance for these methods to be adopted clinically. Our goal in this study was to extract the NM complex volume, iron content and volume representing the entire SN, and the N1 sign as potential complementary imaging biomarkers using a single 3D magnetization transfer contrast (MTC) gradient echo sequence and to evaluate their diagnostic performance and clinical correlations in early stage PD. A total of 40 early stage idiopathic PD subjects and 40 age- and sex-matched healthy controls (HCs) were imaged at 3T. NM boundaries (representing the SN pars compacta (SNpc) and parabrachial pigmented nucleus) and iron boundaries representing the total SN (SNpc and SN pars reticulata) were determined semi-automatically using a dynamic programming (DP) boundary detection algorithm. Receiver operating characteristic analyses were performed to evaluate the utility of these imaging biomarkers in diagnosing early stage PD. A correlation analysis was used to study the relationship between these imaging measures and the clinical scales. We also introduced the concept of NM and total iron overlap volumes to demonstrate the loss of NM relative to the iron containing SN. Furthermore, all 80 cases were evaluated for the N1 sign independently. The NM and SN volumes were lower while the iron content was higher in the SN for PD subjects compared to HCs. Interestingly, the PD subjects with bilateral loss of the N1 sign had the highest iron content. The area under the curve (AUC) values for the average of both hemispheres for single measures were: .960 for NM complex volume; .788 for total SN volume; .740 for SN iron content and .891 for the N1 sign. Combining NM complex volume with each of the following measures through binary logistic regression led to AUC values for the averaged right and left sides of: .976 for total iron content; .969 for total SN volume, .965 for overlap volume and .983 for the N1 sign. We found a negative correlation between SN volume and UPDRS-III (R2 = .22, p = .002). While the N1 sign performed well, it does not contain any information about iron content or NM quantitatively, therefore, marrying this sign with the NM and iron measures provides a better physiological explanation of what is happening when the N1 sign disappears in PD subjects. In summary, the combination of NM complex volume, SN volume, iron content and the N1 sign as derived from a single MTC sequence provides complementary information for understanding and diagnosing early stage PD.

Susceptibility-weighted Imaging: Technical Essentials and Clinical Neurologic Applications.

Susceptibility-weighted imaging (SWI) evolved from simple two-dimensional T2*-weighted sequences to three-dimensional sequences with improved spatial resolution and enhanced susceptibility contrast. SWI is an MRI sequence sensitive to compounds that distort the local magnetic field (eg, calcium and iron), in which the phase information can differentiate. But the term SWI is colloquially used to denote high-spatial-resolution susceptibility-enhanced sequences across different MRI vendors and sequences even when phase information is not used. The imaging appearance of SWI and related sequences strongly depends on the acquisition technique. Initially, SWI and related sequences were mostly used to improve the depiction of findings already known from standard two-dimensional T2*-weighted neuroimaging: more microbleeds in patients who are aging or with dementia or mild brain trauma; increased conspicuity of superficial siderosis in Alzheimer disease and amyloid angiopathy; and iron deposition in neurodegenerative diseases or abnormal vascular structures, such as capillary telangiectasia. But SWI also helps to identify findings not visible on standard T2*-weighted images: the nigrosome 1 in Parkinson disease and dementia with Lewy bodies, the central vein and peripheral rim signs in multiple sclerosis, the peripheral rim sign in abscesses, arterial signal loss related to thrombus, asymmetrically prominent cortical veins in stroke, and intratumoral susceptibility signals in brain neoplasms.

Dynamic Changes of Asymmetric Cortical Veins Relate to Neurologic Prognosis in Acute Ischemic Stroke.

Background Cerebral oxygenation is closely related to neural function in acute ischemic stroke (AIS) and can be measured noninvasively from asymmetrically prominent cortical veins (APCVs) using quantitative susceptibility mapping (QSM). Purpose To quantify venous oxygen saturation (SvO2) using brain MRI with QSM in patients with AIS, to analyze its change at 2-week follow-up, and to assess the influence of SvO2 in clinical prognosis. Materials and Methods Between 2016 and 2020, consecutive patients with AIS who underwent brain MRI within 24 hours from symptom onset and 2 weeks after treatment were retrospectively enrolled. The SvO2 of APCVs was quantified using QSM. The independent sample t test was used to compare the SvO2 between patients with and patients without APCVs. The paired sample t test was used to assess the dynamic change in SvO2. Pearson and Spearman correlation analysis was used to explore the relationship among dynamic change in SvO2 and hypoperfusion, National Institutes of Health Stroke Scale (NIHSS) score change, and 90-day modified Rankin Scale (mRS) score. The independent sample t test was used to compare the dynamic change in SvO2 between different clinical prognoses and outcome subgroups. Results APCVs were detected in 39 of 73 patients (mean age, 70 years ± 10 [standard deviation]; 49 men) at admission and disappeared in 35 patients at 2-week follow-up MRI. The mean SvO2 increased from 35.0% ± 5.8 to 64.5% ± 10.0 (P < .001) in 39 patients. For the 35 patients with APCVs that disappeared, the dynamic change in SvO2 negatively correlated with change in NIHSS score (r = -0.37, R2 = 0.19, P = .03) and 90-day mRS score (r = -0.54, R2 = 0.27, P = .001), and the dynamic change in SvO2 in the subgroup with good 90-day outcomes (n = 19) was greater than that in the subgroup with poor 90-day outcomes (n = 16) (mean, 34.5% ± 5.8 vs 29.7% ± 6.3; 95% CI: 0.6, 8.9; P = .03). Conclusion Improved oxygen saturation of asymmetric cortical veins detected using brain MRI with quantitative susceptibility mapping corresponded with better acute ischemic stroke outcomes for patients with asymmetrically prominent cortical veins that disappeared at 2-week follow-up MRI. © RSNA, 2021 Online supplemental material is available for this article.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. KEY POINTS: • 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.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: STAGE imaging provides a potential practical approach to estimate multi-parametric properties of the human fetal brain. KEY POINTS: • 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.